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Sample records for heme reversibly damps

  1. Reversible dissipative processes, conformal motions and Landau damping

    Energy Technology Data Exchange (ETDEWEB)

    Herrera, L., E-mail: laherrera@cantv.net.ve [Departamento de Física Teórica e Historia de la Ciencia, Universidad del País Vasco, Bilbao (Spain); Di Prisco, A., E-mail: adiprisc@fisica.ciens.ucv.ve [Departamento de Física Teórica e Historia de la Ciencia, Universidad del País Vasco, Bilbao (Spain); Ibáñez, J., E-mail: j.ibanez@ehu.es [Departamento de Física Teórica e Historia de la Ciencia, Universidad del País Vasco, Bilbao (Spain)

    2012-02-06

    The existence of a dissipative flux vector is known to be compatible with reversible processes, provided a timelike conformal Killing vector (CKV) χ{sup α}=(V{sup α})/T (where V{sup α} and T denote the four-velocity and temperature respectively) is admitted by the spacetime. Here we show that if a constitutive transport equation, either within the context of standard irreversible thermodynamics or the causal Israel–Stewart theory, is adopted, then such a compatibility also requires vanishing dissipative fluxes. Therefore, in this later case the vanishing of entropy production generated by the existence of such CKV is not actually associated to an imperfect fluid, but to a non-dissipative one. We discuss also about Landau damping. -- Highlights: ► We review the problem of compatibility of dissipation with reversibility. ► We show that the additional assumption of a transport equation renders such a compatibility trivial. ► We discuss about Landau damping.

  2. The reversible opening of water channels in cytochrome c modulates the heme iron reduction potential.

    Science.gov (United States)

    Bortolotti, Carlo Augusto; Amadei, Andrea; Aschi, Massimiliano; Borsari, Marco; Corni, Stefano; Sola, Marco; Daidone, Isabella

    2012-08-22

    Dynamic protein-solvent interactions are fundamental for life processes, but their investigation is still experimentally very demanding. Molecular dynamics simulations up to hundreds of nanoseconds can bring to light unexpected events even for extensively studied biomolecules. This paper reports a combined computational/experimental approach that reveals the reversible opening of two distinct fluctuating cavities in Saccharomyces cerevisiae iso-1-cytochrome c. Both channels allow water access to the heme center. By means of a mixed quantum mechanics/molecular dynamics (QM/MD) theoretical approach, the perturbed matrix method (PMM), that allows to reach long simulation times, changes in the reduction potential of the heme Fe(3+)/Fe(2+) couple induced by the opening of each cavity are calculated. Shifts of the reduction potential upon changes in the hydration of the heme propionates are observed. These variations are relatively small but significant and could therefore represent a tool developed by cytochrome c for the solvent driven, fine-tuning of its redox functionality.

  3. Kinetics of reversible reductive carbonylation of heme in human cystathionine β-synthase.

    Science.gov (United States)

    Carballal, Sebastián; Cuevasanta, Ernesto; Marmisolle, Inés; Kabil, Omer; Gherasim, Carmen; Ballou, David P; Banerjee, Ruma; Alvarez, Beatriz

    2013-07-02

    Cystathionine β-synthase (CBS) catalyzes the condensation of homocysteine with serine or cysteine to form cystathionine and water or hydrogen sulfide (H2S), respectively. In addition to pyridoxal phosphate, human CBS has a heme cofactor with cysteine and histidine as ligands. While Fe(III)-CBS is inert to exogenous ligands, Fe(II)-CBS can be reversibly inhibited by carbon monoxide (CO) and reoxidized by O2 to yield superoxide radical. In this study, we have examined the kinetics of Fe(II)CO-CBS formation and reoxidation. Reduction of Fe(III)-CBS by dithionite showed a square root dependence on concentration, indicating that the reductant species was the sulfur dioxide radical anion (SO2(•-)) that exists in rapid equilibrium with S2O4(2-). Formation of Fe(II)CO-CBS from Fe(II)-CBS and 1 mM CO occurred with a rate constant of (3.1 ± 0.4) × 10(-3) s(-1) (pH 7.4, 25 °C). The reaction of Fe(III)-CBS with the reduced form of the flavoprotein methionine synthase reductase in the presence of CO and NADPH resulted in its reduction and carbonylation to form Fe(II)CO-CBS. Fe(II)-CBS was formed as an intermediate with a rate constant of (9.3 ± 2.5) × 10(2) M(-1) s(-1). Reoxidation of Fe(II)CO-CBS by O2 was multiphasic. The major phase showed a hyperbolic dependence on O2 concentration. Although H2S is a product of the CBS reaction and a potential heme ligand, we did not find evidence of an effect of exogenous H2S on activity or heme binding. Reversible reduction of CBS by a physiologically relevant oxidoreductase is consistent with a regulatory role for the heme and could constitute a mechanism for cross talk among the CO, H2S, and superoxide signaling pathways.

  4. Damping Dependence of Reversal Magnetic Field on Co-based Nano-Ferromagnetic with Thermal Activation

    Directory of Open Access Journals (Sweden)

    Nadia Ananda Herianto

    2015-02-01

    Full Text Available Currently, hard disk development has used HAMR technology that applies heat to perpendicular media until near Curie temperature, then cools it down to room temperature. The use of HAMR technology is significantly influence by Gilbert damping constants. Damping affects the magnetization reversal and coercivity field. Simulation is used to evaluate magnetization reversal by completing Landau-Lifshitz-Gilbert explicit equation. A strong ferromagnetic cobalt based material with size 50×50×20 nm3 is used which parameters are anisotropy materials 3.51×106 erg/cm3, magnetic saturation 5697.5 G, exchange constant 1×10-7 erg/cm, and various Gilbert damping from 0.09 to 0.5. To observe the thermal effect, two schemes are used which are Reduced Barrier Writing and Curie Point Writing. As a result, materials with high damping is able to reverse the magnetizations faster and reduce the energy barrier. Moreover, it can lower the minimum field to start the magnetizations reversal, threshold field, and probability rate. The heating near Curie temperature has succeeded in reducing the reversal field to 1/10 compared to writing process in absence of thermal field.

  5. DAMPE

    CERN Multimedia

    Chen, D

    The $\\textbf{DA}$rk $\\textbf{M}$atter $\\textbf{P}$article $\\textbf{E}$xplorer (DAMPE) experiment is a high-energy astroparticle physics satellite mission to search for Dark Matter signatures in space, study the cosmic ray spectrum and composition up to 100 TeV, and perform high-energy gamma astronomy. The launch is planned for end 2015, initially for 3 years, to compliment existing space missions FERMI, AMS and CALET.

  6. PageRank and rank-reversal dependence on the damping factor

    Science.gov (United States)

    Son, S.-W.; Christensen, C.; Grassberger, P.; Paczuski, M.

    2012-12-01

    PageRank (PR) is an algorithm originally developed by Google to evaluate the importance of web pages. Considering how deeply rooted Google's PR algorithm is to gathering relevant information or to the success of modern businesses, the question of rank stability and choice of the damping factor (a parameter in the algorithm) is clearly important. We investigate PR as a function of the damping factor d on a network obtained from a domain of the World Wide Web, finding that rank reversal happens frequently over a broad range of PR (and of d). We use three different correlation measures, Pearson, Spearman, and Kendall, to study rank reversal as d changes, and we show that the correlation of PR vectors drops rapidly as d changes from its frequently cited value, d0=0.85. Rank reversal is also observed by measuring the Spearman and Kendall rank correlation, which evaluate relative ranks rather than absolute PR. Rank reversal happens not only in directed networks containing rank sinks but also in a single strongly connected component, which by definition does not contain any sinks. We relate rank reversals to rank pockets and bottlenecks in the directed network structure. For the network studied, the relative rank is more stable by our measures around d=0.65 than at d=d0.

  7. PageRank and rank-reversal dependence on the damping factor.

    Science.gov (United States)

    Son, S-W; Christensen, C; Grassberger, P; Paczuski, M

    2012-12-01

    PageRank (PR) is an algorithm originally developed by Google to evaluate the importance of web pages. Considering how deeply rooted Google's PR algorithm is to gathering relevant information or to the success of modern businesses, the question of rank stability and choice of the damping factor (a parameter in the algorithm) is clearly important. We investigate PR as a function of the damping factor d on a network obtained from a domain of the World Wide Web, finding that rank reversal happens frequently over a broad range of PR (and of d). We use three different correlation measures, Pearson, Spearman, and Kendall, to study rank reversal as d changes, and we show that the correlation of PR vectors drops rapidly as d changes from its frequently cited value, d_{0}=0.85. Rank reversal is also observed by measuring the Spearman and Kendall rank correlation, which evaluate relative ranks rather than absolute PR. Rank reversal happens not only in directed networks containing rank sinks but also in a single strongly connected component, which by definition does not contain any sinks. We relate rank reversals to rank pockets and bottlenecks in the directed network structure. For the network studied, the relative rank is more stable by our measures around d=0.65 than at d=d_{0}.

  8. Heme Gazing: Illuminating Eukaryotic Heme Trafficking, Dynamics, and Signaling with Fluorescent Heme Sensors.

    Science.gov (United States)

    Hanna, David A; Martinez-Guzman, Osiris; Reddi, Amit R

    2017-04-04

    Heme (iron protoporphyrin IX) is an essential protein prosthetic group and signaling molecule required for most life on Earth. All heme-dependent processes require the dynamic and rapid mobilization of heme from sites of synthesis or uptake to hemoproteins present in virtually every subcellular compartment. The cytotoxicity and hydrophobicity of heme necessitate that heme mobilization be carefully controlled to mitigate the deleterious effects of this essential toxin. Indeed, a number of disorders, including certain cancers, cardiovascular diseases, and aging and age-related neurodegenerative diseases, are tied to defects in heme homeostasis. However, the molecules and mechanisms that mediate heme transport and trafficking, and the dynamics of these processes, are poorly understood. This is in large part due to the lack of physical tools for probing cellular heme. Herein, we discuss the recent development of fluorescent probes that can monitor and image kinetically labile heme with respect to its mobilization and role in signaling. In particular, we will highlight how heme gazing with these tools can uncover new heme trafficking factors upon being integrated with genetic screens and illuminate the concentration, subcellular distribution, and dynamics of labile heme in various physiological contexts. Altogether, the monitoring of labile heme, along with recent biochemical and cell biological studies demonstrating the reversible regulation of certain cellular processes by heme, is challenging us to reconceptualize heme from being a static cofactor buried in protein active sites to a dynamic and mobile signaling molecule.

  9. Current reversals of coupled driven and damped particles evolving in a tilted potential landscape

    Science.gov (United States)

    Mulhern, C.; Hennig, D.

    2011-09-01

    We explore the driven and damped dynamics of two coupled particles evolving in a symmetric and periodic substrate potential that is subjected to a static bias force. In addition, each particle is time-periodically driven with the same magnitude as, but out of phase to, its counterpart. It is shown that, for a certain parameter regime, the coupled particles can become self-organized and go against the direction of the bias force. This self-organization involves the particles becoming frequency locked with the driving force, and thus periodic motion ensues. We employ numerical arguments to show that running periodic states provide solutions of the system. Further, heuristic evidence is provided explaining how the two particles can travel against the bias force. In an effort to unearth coupling phenomena within the system, a detailed analysis of how the coupling strength affects the nonlinear dynamics is carried out. We show that within a range of coupling strengths the existence of periodic running solutions associated with negative mobility. To examine the robustness of our results we compare the deterministic system with the corresponding Langevin system. It is shown that, below a critical temperature, the qualitative behavior of the system remains the same.

  10. Modeling of the attenuation of stress waves in concrete based on the Rayleigh damping model using time-reversal and PZT transducers

    Science.gov (United States)

    Tian, Zhen; Huo, Linsheng; Gao, Weihang; Li, Hongnan; Song, Gangbing

    2017-10-01

    Wave-based concrete structural health monitoring has attracted much attention. A stress wave experiences significant attenuation in concrete, however there is a lack of a unified method for predicting the attenuation coefficient of the stress wave. In this paper, a simple and effective absorption attenuation model of stress waves in concrete is developed based on the Rayleigh damping model, which indicates that the absorption attenuation coefficient of stress waves in concrete is directly proportional to the square of the stress wave frequency when the damping ratio is small. In order to verify the theoretical model, related experiments were carried out. During the experiments, a concrete beam was designed in which the d33-model piezoelectric smart aggregates were embedded to detect the propagation of stress waves. It is difficult to distinguish direct stress waves due to the complex propagation paths and the reflection and scattering of stress waves in concrete. Hence, as another innovation of this paper, a new method for computing the absorption attenuation coefficient based on the time-reversal method is developed. Due to the self-adaptive focusing properties of the time-reversal method, the time-reversed stress wave focuses and generates a peak value. The time-reversal method eliminates the adverse effects of multipaths, reflection, and scattering. The absorption attenuation coefficient is computed by analyzing the peak value changes of the time-reversal focused signal. Finally, the experimental results are found to be in good agreement with the theoretical model.

  11. Diabetes Impairs the Vascular Recruitment of Normal Stem Cells by Oxidant Damage, Reversed by Increases in pAMPK, Heme Oxygenase-1, and Adiponectin

    Science.gov (United States)

    Sambuceti, Gianmario; Morbelli, Silvia; Vanella, Luca; Kusmic, Claudia; Marini, Cecilia; Massollo, Michela; Augeri, Carla; Corselli, Mirko; Ghersi, Chiara; Chiavarina, Barbara; Rodella, Luigi F; L'Abbate, Antonio; Drummond, George; Abraham, Nader G; Frassoni, Francesco

    2009-01-01

    Background Atherosclerosis progression is accelerated in diabetes mellitus (DM) by either direct endothelial damage or reduced availability and function of endothelial progenitor cells (EPCs). Both alterations are related to increased oxidant damage. Aim We examined if DM specifically impairs vascular signaling, thereby reducing the recruitment of normal EPCs, and if increases in antioxidant levels by induction of heme oxygenase-1 (HO-1) can reverse this condition. Methods Control and diabetic rats were treated with the HO-1 inducer cobalt protoporphyrin (CoPP) once a week for 3 weeks. Eight weeks after the development of diabetes, EPCs harvested from the aorta of syngenic inbred normal rats and labeled with technetium-99m-exametazime were infused via the femoral vein to estimate their blood clearance and aortic recruitment. Circulating endothelial cells (CECs) and the aortic expression of thrombomodulin (TM), CD31, and endothelial nitric oxide synthase (eNOS) were used to measure endothelial damage. Results DM reduced blood clearance and aortic recruitment of EPCs. Both parameters were returned to control levels by CoPP treatment without affecting EPC kinetics in normal animals. These abnormalities of EPCs in DM were paralleled by reduced serum adiponectin levels, increased numbers of CECs, reduced endothelial expression of phosphorylated eNOS, and reduced levels of TM, CD31, and phosphorylated AMP-activated protein kinase (pAMPK). CoPP treatment restored all of these parameters to normal levels. Conclusion Type II DM and its related oxidant damage hamper the interaction between the vascular wall and normal EPCs by mechanisms that are, at least partially, reversed by the induction of HO-1 gene expression, adiponectin, and pAMPK levels. PMID:19038792

  12. Quadratic Damping

    Science.gov (United States)

    Fay, Temple H.

    2012-01-01

    Quadratic friction involves a discontinuous damping term in equations of motion in order that the frictional force always opposes the direction of the motion. Perhaps for this reason this topic is usually omitted from beginning texts in differential equations and physics. However, quadratic damping is more realistic than viscous damping in many…

  13. Coulomb Damping

    Science.gov (United States)

    Fay, Temple H.

    2012-01-01

    Viscous damping is commonly discussed in beginning differential equations and physics texts but dry friction or Coulomb friction is not despite dry friction being encountered in many physical applications. One reason for avoiding this topic is that the equations involve a jump discontinuity in the damping term. In this article, we adopt an energy…

  14. Environmental heme utilization by heme-auxotrophic bacteria.

    Science.gov (United States)

    Gruss, Alexandra; Borezée-Durant, Elise; Lechardeur, Delphine

    2012-01-01

    Heme, an iron-containing porphyrin, is the prosthetic group for numerous key cellular enzymatic and regulatory processes. Many bacteria encode the biosynthetic enzymes needed for autonomous heme production. Remarkably, however, numerous other bacteria lack a complete heme biosynthesis pathway, yet encode heme-requiring functions. For such heme-auxotrophic bacteria (HAB), heme or porphyrins must be captured from the environment. Functional studies, aided by genomic analyses, provide insight into the HAB lifestyle, how they acquire and manage heme, and the uses of heme that make it worthwhile, and sometimes necessary, to capture this bioactive molecule. Copyright © 2012 Elsevier Ltd. All rights reserved.

  15. Red cell DAMPs and inflammation.

    Science.gov (United States)

    Mendonça, Rafaela; Silveira, Angélica A A; Conran, Nicola

    2016-09-01

    Intravascular hemolysis, or the destruction of red blood cells in the circulation, can occur in numerous diseases, including the acquired hemolytic anemias, sickle cell disease and β-thalassemia, as well as during some transfusion reactions, preeclampsia and infections, such as those caused by malaria or Clostridium perfringens. Hemolysis results in the release of large quantities of red cell damage-associated molecular patterns (DAMPs) into the circulation, which, if not neutralized by innate protective mechanisms, have the potential to activate multiple inflammatory pathways. One of the major red cell DAMPs, heme, is able to activate converging inflammatory pathways, such as toll-like receptor signaling, neutrophil extracellular trap formation and inflammasome formation, suggesting that this DAMP both activates and amplifies inflammation. Other potent DAMPs that may be released by the erythrocytes upon their rupture include heat shock proteins (Hsp), such as Hsp70, interleukin-33 and Adenosine 5' triphosphate. As such, hemolysis represents a major inflammatory mechanism that potentially contributes to the clinical manifestations that have been associated with the hemolytic diseases, such as pulmonary hypertension and leg ulcers, and likely plays a role in specific complications of sickle cell disease such as endothelial activation, vaso-occlusive processes and tissue injury.

  16. Landau damping

    CERN Document Server

    Hofmann, A

    2006-01-01

    Abstract Landau damping is the suppression of an instability by a spread of frequencies in the beam. It is treated here from an experimental point of view. To introduce the concept we consider a set of oscillators having a spread in resonant frequencies !r and calculate the response of their there center-of-mass to an external driving force. A pulse excitation gives each oscillator the same initial velocity but, due to their different frequencies, the center-of-mass motion will decay with time. A harmonic excitation with a frequency ! being inside the distribution in !r results in oscillators responding with different phases and only a few of them having !r ! will grow to large amplitudes and absorb energy. The oscillator response to a pulse excitation, called Green function, and the one to a harmonic excitation, called transfer function, serve as a basis to calculate Landau damping which suppresses an instability at infinitesimal level before any large amplitudes are reached. This is illustrated by a negativ...

  17. Kinetics of heme transfer by the Shr NEAT domains of Group A Streptococcus.

    Science.gov (United States)

    Ouattara, Mahamoudou; Pennati, Andrea; Devlin, Darius J; Huang, Ya-Shu; Gadda, Giovanni; Eichenbaum, Zehava

    2013-10-15

    The hemolytic Group A Streptococcus (GAS) is a notorious human pathogen. Shr protein of GAS participates in iron acquisition by obtaining heme from host hemoglobin and delivering it to the adjacent receptor on the surface, Shp. Heme is then conveyed to the SiaABC proteins for transport across the membrane. Using rapid kinetic studies, we investigated the role of the two heme binding NEAT modules of Shr. Stopped-flow analysis showed that holoNEAT1 quickly delivered heme to apoShp. HoloNEAT2 did not exhibit such activity; only little and slow transfer of heme from NEAT2 to apoShp was seen, suggesting that Shr NEAT domains have distinctive roles in heme transport. HoloNEAT1 also provided heme to apoNEAT2, by a fast and reversible process. To the best of our knowledge this is the first transfer observed between isolated NEAT domains of the same receptor. Sequence alignment revealed that Shr NEAT domains belong to two families of NEAT domains that are conserved in Shr orthologs from several species. Based on the heme transfer kinetics, we propose that Shr proteins modulate heme uptake according to heme availability by a mechanism where NEAT1 facilitates fast heme delivery to Shp, whereas NEAT2 serves as a temporary storage for heme on the bacterial surface. Copyright © 2013. Published by Elsevier Inc.

  18. How Heme Oxygenase-1 Prevents Heme-Induced Cell Death.

    Directory of Open Access Journals (Sweden)

    Lilibeth Lanceta

    Full Text Available Earlier observations indicate that free heme is selectively toxic to cells lacking heme oxygenase-1 (HO-1 but how this enzyme prevents heme toxicity remains unexplained. Here, using A549 (human lung cancer and immortalized human bronchial epithelial cells incubated with exogenous heme, we find knock-down of HO-1 using siRNA does promote the accumulation of cell-associated heme and heme-induced cell death. However, it appears that the toxic effects of heme are exerted by "loose" (probably intralysosomal iron because cytotoxic effects of heme are lessened by pre-incubation of HO-1 deficient cells with desferrioxamine (which localizes preferentially in the lysosomal compartment. Desferrioxamine also decreases lysosomal rupture promoted by intracellularly generated hydrogen peroxide. Supporting the importance of endogenous oxidant production, both chemical and siRNA inhibition of catalase activity predisposes HO-1 deficient cells to heme-mediated killing. Importantly, it appears that HO-1 deficiency somehow blocks the induction of ferritin; control cells exposed to heme show ~10-fold increases in ferritin heavy chain expression whereas in heme-exposed HO-1 deficient cells ferritin expression is unchanged. Finally, overexpression of ferritin H chain in HO-1 deficient cells completely prevents heme-induced cytotoxicity. Although two other products of HO-1 activity--CO and bilirubin--have been invoked to explain HO-1-mediated cytoprotection, we conclude that, at least in this experimental system, HO-1 activity triggers the induction of ferritin and the latter is actually responsible for the cytoprotective effects of HO-1 activity.

  19. Acquisition of iron from transferrin regulates reticulocyte heme synthesis

    Energy Technology Data Exchange (ETDEWEB)

    Ponka, P.; Schulman, H.M.

    1985-11-25

    Fe-salicylaldehyde isonicotinoylhydrazone (SIH), which can donate iron to reticulocytes without transferrin as a mediator, has been utilized to test the hypothesis that the rate of iron uptake from transferrin limits the rate of heme synthesis in erythroid cells. Reticulocytes take up VZFe from (VZFe)SIH and incorporate it into heme to a much greater extent than from saturating concentrations of (VZFe)transferrin. Also, Fe-SIH stimulates (2- UC)glycine into heme when compared to the incorporation observed with saturating levels of Fe-transferrin. In addition, delta-aminolevulinic acid does not stimulate VZFe incorporation into heme from either (VZFe)transferrin or (VZFe)SIH but does reverse the inhibition of VZFe incorporation into heme caused by isoniazid, an inhibitor of delta-aminolevulinic acid synthase. Taken together, these results suggest the hypothesis that some step(s) in the pathway of iron from extracellular transferrin to intracellular protoporphyrin limits the overall rate of heme synthesis in reticulocytes.

  20. Increased Heme Levels in the Heart Lead to Exacerbated Ischemic Injury.

    Science.gov (United States)

    Sawicki, Konrad Teodor; Shang, Meng; Wu, Rongxue; Chang, Hsiang-Chun; Khechaduri, Arineh; Sato, Tatsuya; Kamide, Christine; Liu, Ting; Naga Prasad, Sathyamangla V; Ardehali, Hossein

    2015-07-31

    Heme is an essential iron-containing molecule for cardiovascular physiology, but in excess it may increase oxidative stress. Failing human hearts have increased heme levels, with upregulation of the rate-limiting enzyme in heme synthesis, δ-aminolevulinic acid synthase 2 (ALAS2), which is normally not expressed in cardiomyocytes. We hypothesized that increased heme accumulation (through cardiac overexpression of ALAS2) leads to increased oxidative stress and cell death in the heart. We first showed that ALAS2 and heme levels are increased in the hearts of mice subjected to coronary ligation. To determine the causative role of increased heme in the development of heart failure, we generated transgenic mice with cardiac-specific overexpression of ALAS2. While ALAS2 transgenic mice have normal cardiac function at baseline, their hearts display increased heme content, higher oxidative stress, exacerbated cell death, and worsened cardiac function after coronary ligation compared to nontransgenic littermates. We confirmed in cultured cardiomyoblasts that the increased oxidative stress and cell death observed with ALAS2 overexpression is mediated by increased heme accumulation. Furthermore, knockdown of ALAS2 in cultured cardiomyoblasts exposed to hypoxia reversed the increases in heme content and cell death. Administration of the mitochondrial antioxidant MitoTempo to ALAS2-overexpressing cardiomyoblasts normalized the elevated oxidative stress and cell death levels to baseline, indicating that the effects of increased ALAS2 and heme are through elevated mitochondrial oxidative stress. The clinical relevance of these findings was supported by the finding of increased ALAS2 induction and heme accumulation in failing human hearts from patients with ischemic cardiomyopathy compared to nonischemic cardiomyopathy. Heme accumulation is detrimental to cardiac function under ischemic conditions, and reducing heme in the heart may be a novel approach for protection against the

  1. Power oscillation damping controller

    DEFF Research Database (Denmark)

    2012-01-01

    A power oscillation damping controller is provided for a power generation device such as a wind turbine device. The power oscillation damping controller receives an oscillation indicating signal indicative of a power oscillation in an electricity network and provides an oscillation damping control...... signal in response to the oscillation indicating signal, by processing the oscillation damping control signal in a signal processing chain. The signal processing chain includes a filter configured for passing only signals within a predetermined frequency range....

  2. Spectroscopic Studies Reveal That the Heme Regulatory Motifs of Heme Oxygenase-2 Are Dynamically Disordered and Exhibit Redox-Dependent Interaction with Heme

    Science.gov (United States)

    2015-01-01

    Heme oxygenase (HO) catalyzes a key step in heme homeostasis: the O2- and NADPH-cytochrome P450 reductase-dependent conversion of heme to biliverdin, Fe, and CO through a process in which the heme participates both as a prosthetic group and as a substrate. Mammals contain two isoforms of this enzyme, HO2 and HO1, which share the same α-helical fold forming the catalytic core and heme binding site, as well as a membrane spanning helix at their C-termini. However, unlike HO1, HO2 has an additional 30-residue N-terminus as well as two cysteine-proline sequences near the C-terminus that reside in heme regulatory motifs (HRMs). While the role of the additional N-terminal residues of HO2 is not yet understood, the HRMs have been proposed to reversibly form a thiol/disulfide redox switch that modulates the affinity of HO2 for ferric heme as a function of cellular redox poise. To further define the roles of the N- and C-terminal regions unique to HO2, we used multiple spectroscopic techniques to characterize these regions of the human HO2. Nuclear magnetic resonance spectroscopic experiments with HO2 demonstrate that, when the HRMs are in the oxidized state (HO2O), both the extra N-terminal and the C-terminal HRM-containing regions are disordered. However, protein NMR experiments illustrate that, under reducing conditions, the C-terminal region gains some structure as the Cys residues in the HRMs undergo reduction (HO2R) and, in experiments employing a diamagnetic protoporphyrin, suggest a redox-dependent interaction between the core and the HRM domains. Further, electron nuclear double resonance and X-ray absorption spectroscopic studies demonstrate that, upon reduction of the HRMs to the sulfhydryl form, a cysteine residue from the HRM region ligates to a ferric heme. Taken together with EPR measurements, which show the appearance of a new low-spin heme signal in reduced HO2, it appears that a cysteine residue(s) in the HRMs directly interacts with a second bound heme

  3. Hemoglobin and heme scavenger receptors

    DEFF Research Database (Denmark)

    Nielsen, Marianne Jensby; Møller, Holger Jon; Moestrup, Søren Kragh

    2010-01-01

    Heme, the functional group of hemoglobin, myoglobin, and other hemoproteins, is a highly toxic substance when it appears in the extracellular milieu. To circumvent potential harmful effects of heme from hemoproteins released during physiological or pathological cell damage (such as hemolysis...

  4. Hepatic heme catabolism in cultured hepatocytes

    Energy Technology Data Exchange (ETDEWEB)

    Lincoln, B.C.; Bonkovsky, H.L.

    1987-05-01

    Uncertainty persists concerning the role and importance of heme oxygenase in the catabolism of heme by hepatocytes. The products of heme oxygenase catalyzed heme catabolism are equimolar amounts of biliverdin IX..cap alpha.., CO, and iron. Previous reports from studies with rodent hepatocyte cultures have suggested the possibility that non-heme oxygenase pathway(s) predominate in the breakdown of hepatic hemoprotein heme. The authors have studied this question in cultured chick embryo hepatocytes, which retain normal regulation of heme metabolism and levels of cytochromes P-450 as in intact animals. Exogenous heme added to the culture medium with control chick embryo hepatocyte cultures was quantitatively converted to biliverdin IX..cap alpha... To study endogenous heme breakdown, cellular heme was labelled by exposing cultured cells to (5-/sup 14/C) 5-aminolevulinic acid (ALA). The hepatocytes were also treated with mephenytoin that increases cytochrome P-450, total hepatic heme and heme oxygenase. At various times after labelling heme, biliverdin, and CO were isolated and counted. For at least 8 hrs, the increase in CO radioactivity corresponded to the loss of radioactivity in heme. Beyond 1 h biliverdin was unstable in culture medium, but for 1 h after labelling (dpm BVIX..cap alpha.. + dpm CO) ..delta..dpm heme. All BV detected was the ..cap alpha.. isomer. They conclude that heme oxygenase accounts for both endogenous and exogenous heme breakdown by hepatocytes.

  5. Heme isomers substantially affect heme's electronic structure and function

    DEFF Research Database (Denmark)

    Kepp, Kasper Planeta

    2017-01-01

    to similar energy of the isomers but with a sizable (25 kJ mol-1) barrier to interconversion arising from restricted rotation around the conjugated bonds. The four isomers, EE, EZ, ZE, and ZZ, were then investigated as 4-coordinate hemes, as 5-coordinate deoxyhemes, in 6-coordinate O2-adducts of globins.......e. the effects are not method-dependent. Thus, the nature of the isomer state is an important but overlooked feature of heme chemistry and function, and previous and future studies of hemes may be reconsidered in this new context....

  6. Heme synthase (ferrochelatase) catalyzes the removal of iron from heme and demetalation of metalloporphyrins.

    Science.gov (United States)

    Taketani, Shigeru; Ishigaki, Mutsumi; Mizutani, Atsushi; Uebayashi, Masashi; Numata, Masahiro; Ohgari, Yoshiko; Kitajima, Sakihito

    2007-12-25

    The red pigments in meat products, including cooked cured ham, arise from the reaction of myoglobin with nitric oxide generated from exogenous nitrite. Since carcinogenic nitrosoamines may be generated by the treatment of meats with nitrite, the production of nitrite-free meat products is an attractive alternative. Raw dry-cured (Parma) hams are produced by the treatment of meats with salts other than nitrite. Analysis of pigments in raw dry-cured hams reveals that the main pigment is zinc protoporphyrin, suggesting that the conversion of heme to zinc protoporphyrin occurs via an iron-removal reaction from myoglobin heme during the processing of raw hams. Purification of the iron-removal enzyme showed that it was identical to ferrochelatase. Recombinant ferrochelatase in combination with NADH-cytochrome b5 reductase catalyzed NADH-dependent iron-removal reaction from hemin and hemoproteins. Metal ions such as zinc and cobalt were also removed from the corresponding metalloporphyrins. The addition of zinc ions led to the formation of zinc protoporphyrin. In cultured cells, the conversion of zinc mesoporphyrin to mesoheme was observed to be dependent on ferrochelatase and could be markedly induced during erythroid differentiation. This is the first demonstration of a new enzyme reaction, the reverse reaction of ferrochelatase, which may contribute to a new route of the recycling of protoporphyrin and heme in cells.

  7. Dr. Dampe - Doctor Democracy

    DEFF Research Database (Denmark)

    Andreasen, John

    2009-01-01

    On Dr.phil. J.J.Dampe's fight for democracy in the first part of the 19th century in Denmark and his dramatic writings......On Dr.phil. J.J.Dampe's fight for democracy in the first part of the 19th century in Denmark and his dramatic writings...

  8. Turbojet engine blade damping

    Science.gov (United States)

    Srinivasan, A. V.; Cutts, D. G.; Sridhar, S.

    1981-01-01

    The potentials of various sources of nonaerodynamic damping in engine blading are evaluated through a combination of advanced analysis and testing. The sources studied include material hysteresis, dry friction at shroud and root disk interfaces as well as at platform type external dampers. A limited seris of tests was conducted to evaluate damping capacities of composite materials (B/AL, B/AL/Ti) and thermal barrier coatings. Further, basic experiments were performed on titanium specimens to establish the characteristics of sliding friction and to determine material damping constants J and n. All the tests were conducted on single blades. Mathematical models were develthe several mechanisms of damping. Procedures to apply this data to predict damping levels in an assembly of blades are developed and discussed.

  9. Heme on innate immunity and inflammation

    Directory of Open Access Journals (Sweden)

    Fabianno Ferreira Dutra

    2014-05-01

    Full Text Available Heme is an essential molecule expressed ubiquitously all through our tissues. Heme plays major functions in cellular physiology and metabolism as the prostetic group of diverse proteins. Once released from cells and from hemeproteins free heme causes oxidative damage and inflammation, thus acting as a prototypic damage-associated molecular pattern. In this context, free heme is a critical component of the pathological process of sterile and infectious hemolytic conditions including malaria, hemolytic anemias, ischemia-reperfusion and hemorrhage. The plasma scavanger proteins hemopexin and albumin reduce heme toxicity and are responsible for transporting free heme to intracellular compartments where it is catabolized by heme-oxygenase enzymes. Upon hemolysis or severe cellular damage the serum capacity to scavange heme may saturate and increase free heme to sufficient amounts to cause tissue damage in various organs. The mechanism by which heme causes reactive oxygen generation, activation of cells of the innate immune system and cell death are not fully understood. Although heme can directly promote lipid peroxidation by its iron atom, heme can also induce ROS generation and production of inflammatory mediators through the activation of selective signaling pathways. Heme activates innate immune cells such as macrophages and neutrophils through activation of innate immune receptors. The importance of these events has been demonstrated in infectious and non-infectious diseases models. In this review we will discuss the mechanisms behind heme-induced citotoxicity and inflammation and the consequences of these events on different tissues and diseases.

  10. Vibrational Damping of Composite Materials

    OpenAIRE

    Biggerstaff, Janet M.

    2006-01-01

    The purpose of this research was to develop new methods of vibrational damping in polymeric composite materials along with expanding the knowledge of currently used vibrational damping methods. A new barrier layer technique that dramatically increased damping in viscoelastic damping materials that interacted with the composite resin was created. A method for testing the shear strength of damping materials cocured in composites was developed. Directional damping materials, where the loss facto...

  11. Structural Characterization of Heme Environmental Mutants of CgHmuT that Shuttles Heme Molecules to Heme Transporters

    Directory of Open Access Journals (Sweden)

    Norifumi Muraki

    2016-05-01

    Full Text Available Corynebacteria contain a heme uptake system encoded in hmuTUV genes, in which HmuT protein acts as a heme binding protein to transport heme to the cognate transporter HmuUV. The crystal structure of HmuT from Corynebacterium glutamicum (CgHmuT reveals that heme is accommodated in the central cleft with His141 and Tyr240 as the axial ligands and that Tyr240 forms a hydrogen bond with Arg242. In this work, the crystal structures of H141A, Y240A, and R242A mutants were determined to understand the role of these residues for the heme binding of CgHmuT. Overall and heme environmental structures of these mutants were similar to those of the wild type, suggesting that there is little conformational change in the heme-binding cleft during heme transport reaction with binding and the dissociation of heme. A loss of one axial ligand or the hydrogen bonding interaction with Tyr240 resulted in an increase in the redox potential of the heme for CgHmuT to be reduced by dithionite, though the wild type was not reduced under physiological conditions. These results suggest that the heme environmental structure stabilizes the ferric heme binding in CgHmuT, which will be responsible for efficient heme uptake under aerobic conditions where Corynebacteria grow.

  12. Roll Damping By Rudder Control

    DEFF Research Database (Denmark)

    Stoustrup, Jakob; Niemann, H.H.; Blanke, M.

    1994-01-01

    Roll damping and simultaneous course steering by rudder control is a challenging problem where a key factor is roll damping performance in waves.......Roll damping and simultaneous course steering by rudder control is a challenging problem where a key factor is roll damping performance in waves....

  13. Structure and heme-binding properties of HemQ (chlorite dismutase-like protein) from Listeria monocytogenes

    Science.gov (United States)

    Hofbauer, Stefan; Hagmüller, Andreas; Schaffner, Irene; Mlynek, Georg; Krutzler, Michael; Stadlmayr, Gerhard; Pirker, Katharina F.; Obinger, Christian; Daims, Holger; Djinović-Carugo, Kristina; Furtmüller, Paul G.

    2015-01-01

    Chlorite dismutase-like proteins are structurally closely related to functional chlorite dismutases which are heme b-dependent oxidoreductases capable of reducing chlorite to chloride with simultaneous production of dioxygen. Chlorite dismutase-like proteins are incapable of performing this reaction and their biological role is still under discussion. Recently, members of this large protein family were shown to be involved in heme biosynthesis in Gram-positive bacteria, and thus the protein was renamed HemQ in these organisms. In the present work the structural and heme binding properties of the chlorite dismutase-like protein from the Gram-positive pathogen Listeria monocytogenes (LmCld) were analyzed in order to evaluate its potential role as a regulatory heme sensing protein. The homopentameric crystal structure (2.0 Å) shows high similarity to chlorite-degrading chlorite dismutases with an important difference in the structure of the putative substrate and heme entrance channel. In solution LmCld is a stable hexamer able to bind the low-spin ligand cyanide. Heme binding is reversible with KD-values determined to be 7.2 μM (circular dichroism spectroscopy) and 16.8 μM (isothermal titration calorimetry) at pH 7.0. Both acidic and alkaline conditions promote heme release. Presented biochemical and structural data reveal that the chlorite dismutase-like protein from L. monocytogenes could act as a potential regulatory heme sensing and storage protein within heme biosynthesis. PMID:25602700

  14. Resonance Raman and EPR spectroscopic studies on heme-heme oxygenase complexes.

    Science.gov (United States)

    Sun, J; Wilks, A; Ortiz de Montellano, P R; Loehr, T M

    1993-12-28

    The binding of ferrous and ferric hemes and manganese(II)- and manganese(III)-substituted hemes to heme oxygenase has been investigated by optical absorption, resonance Raman, and EPR spectroscopy. The results are consistent with the presence of a six-coordinate heme moiety ligated to an essential histidine ligand and a water molecule. The latter ionizes with a pKa approximately 8.0 to give a mixture of high-spin and low-spin six-coordinate hydroxo adducts. Addition of excess cyanide converts the heme to a hexacoordinate low-spin species. The resonance Raman spectrum of the ferrous heme-heme oxygenase complex and that of the Mn(II)protoporphyrin-heme oxygenase complex shows bands at 216 and 212 cm-1, respectively, that are assigned to the metal-histidine stretching mode. The EPR spectrum of the oxidized heme-heme oxygenase complex has a strongly axial signal with g parallel of approximately 6 and g perpendicular approximately 2. 14NO and 15NO adducts of ferrous heme-heme oxygenase exhibit EPR hyperfine splittings of approximately 20 and approximately 25 Gauss, respectively. In addition, both nitrosyl complexes show additional superhyperfine splittings of approximately 7 Gauss from spin-spin interaction with the proximal histidine nitrogen. The heme environment in the heme-heme oxygenase enzyme-substrate complex has spectroscopic properties similar to those of the heme in myoglobin. Hence, there is neither a strongly electron-donating fifth (proximal) ligand nor an electron-withdrawing network on the distal side of the heme moiety comparable to that for cytochromes P-450 and peroxidases. This observation has profound implications about the nature of the oxygen-activating process in the heme-->biliverdin reaction that are discussed in this paper.

  15. Isoporphyrin Intermediate in Heme Oxygenase Catalysis

    Science.gov (United States)

    Evans, John P.; Niemevz, Fernando; Buldain, Graciela; de Montellano, Paul Ortiz

    2008-01-01

    Human heme oxygenase-1 (hHO-1) catalyzes the O2- and NADPH-dependent oxidation of heme to biliverdin, CO, and free iron. The first step involves regiospecific insertion of an oxygen atom at the α-meso carbon by a ferric hydroperoxide and is predicted to proceed via an isoporphyrin π-cation intermediate. Here we report spectroscopic detection of a transient intermediate during oxidation by hHO-1 of α-meso-phenylheme-IX, α-meso-(p-methylphenyl)-mesoheme-III, and α-meso-(p-trifluoromethylphenyl)-mesoheme-III. In agreement with previous experiments (Wang, J., Niemevz, F., Lad, L., Huang, L., Alvarez, D. E., Buldain, G., Poulos, T. L., and Ortiz de Montellano, P. R. (2004) J. Biol. Chem. 279, 42593–42604), only the α-biliverdin isomer is produced with concomitant formation of the corresponding benzoic acid. The transient intermediate observed in the NADPH-P450 reductase-catalyzed reaction accumulated when the reaction was supported by H2O2 and exhibited the absorption maxima at 435 and 930 nm characteristic of an isoporphyrin. Product analysis by reversed phase high performance liquid chromatography and liquid chromatography electrospray ionization mass spectrometry of the product generated with H2O2 identified it as an isoporphyrin that, on quenching, decayed to benzoylbiliverdin. In the presence of H218O2, one labeled oxygen atom was incorporated into these products. The hHO-1-isoporphyrin complexes were found to have half-lives of 1.7 and 2.4 h for the p-trifluoromethyl- and p-methyl-substituted phenylhemes, respectively. The addition of NADPH-P450 reductase to the H2O2-generated hHO-1-isoporphyrin complex produced α-biliverdin, confirming its role as a reaction intermediate. Identification of an isoporphyrin intermediate in the catalytic sequence of hHO-1, the first such intermediate observed in hemoprotein catalysis, completes our understanding of the critical first step of heme oxidation. PMID:18487208

  16. Directional damping material for integrally damped composite plates

    Science.gov (United States)

    Biggerstaff, Janet M.; Kosmatka, John B.

    1999-06-01

    Current viscoelastic-damping materials behave isotopically so that their stiffness and damping properties are the same in all directions. There is a desire to develop viscoelastic- damping materials that behave orthotropically so that the stiffness and damping properties vary with material orientation. These damping materials can be made othrotropic by embedding rows of thin wires within the viscoelastic damping material. These wires add significant directional stiffness and strength to the damping materials, where the stiffness and strength variation with wire orientation follows classical lamination theory. The presence of these wires introduce different damping mechanisms (longitudinal, transverse, and longitudinal shear damping coefficients) that depend upon mode type and orientation angle. Results from experimental studies show that the magnitude of the loss factor and shear modulus depends upon the mode type and orientation angle of these wires within the damping material. The in-plane axial mode loss factor is highly dependent upon the longitudinal coefficient for (0 degrees) wire orientation, the transverse coefficient for (90 degree) wire orientation, and the longitudinal shear-damping coefficient for all other off-angle wire orientations. The loss factor for the out-of- plane bending and torsion modes is highly dependent upon all three damping coefficients.

  17. Chiral damping of magnetic domain walls

    KAUST Repository

    Jué, Emilie

    2015-12-21

    Structural symmetry breaking in magnetic materials is responsible for the existence of multiferroics1, current-induced spin–orbit torques2, 3, 4, 5, 6, 7 and some topological magnetic structures8, 9, 10, 11, 12. In this Letter we report that the structural inversion asymmetry (SIA) gives rise to a chiral damping mechanism, which is evidenced by measuring the field-driven domain-wall (DW) motion in perpendicularly magnetized asymmetric Pt/Co/Pt trilayers. The DW dynamics associated with the chiral damping and those with Dzyaloshinskii–Moriya interaction (DMI) exhibit identical spatial symmetry13, 14, 15, 16, 17, 18, 19. However, both scenarios are differentiated by their time reversal properties: whereas DMI is a conservative effect that can be modelled by an effective field, the chiral damping is purely dissipative and has no influence on the equilibrium magnetic texture. When the DW motion is modulated by an in-plane magnetic field, it reveals the structure of the internal fields experienced by the DWs, allowing one to distinguish the physical mechanism. The chiral damping enriches the spectrum of physical phenomena engendered by the SIA, and is essential for conceiving DW and skyrmion devices owing to its coexistence with DMI (ref. 20).

  18. Heme Oxygenase-1 and breast cancer resistance protein protect against heme-induced toxicity

    NARCIS (Netherlands)

    Wagener, Frank A D T G; Dankers, Anita C A; van Summeren, Frank; Scharstuhl, Alwin; van den Heuvel, Jeroen J M W; Koenderink, Jan B; Pennings, Sebastiaan W C; Russel, Frans G M; Masereeuw, R.

    2013-01-01

    Heme is the functional group of diverse hemoproteins and crucial for many cellular processes. However, heme is increasingly recognized as a culprit for a wide variety of pathologies, including sepsis, malaria, and kidney failure. Excess of free heme can be detrimental to tissues by mediating

  19. Heme Oxygenase-1 and Breast Cancer Resistance Protein Protect Against Heme-induced Toxicity

    NARCIS (Netherlands)

    Wagener, F.A.D.T.G.; Dankers, A.C.A.; Summeren, F. van; Scharstuhl, A.; Heuvel, J.J. van den; Koenderink, J.B.; Pennings, S.W.C.; Russel, F.G.M.; Masereeuw, R.

    2013-01-01

    Heme is the functional group of diverse hemoproteins and crucial for many cellular processes. However, heme is increasingly recognized as a culprit for a wide variety of pathologies, including sepsis, malaria, and kidney failure. Excess of free heme can be detrimental to tissues by mediating

  20. Vibrational damping of composite materials

    Science.gov (United States)

    Biggerstaff, Janet M.

    The purpose of this research was to develop new methods of vibrational damping in polymeric composite materials along with expanding the knowledge of currently used vibrational damping methods. A new barrier layer technique that dramatically increased damping in viscoelastic damping materials that interacted with the composite resin was created. A method for testing the shear strength of damping materials cocured in composites was developed. Directional damping materials, where the loss factor and modulus could be tailored by changing the angle, were produced and investigated. The addition of particles between composite prepreg layers to increase damping was studied. Electroviscoelastic materials that drastically changed properties such as loss factor and modulus with an applied voltage were manufactured and tested.

  1. On Landau damping

    KAUST Repository

    Mouhot, Clément

    2011-09-01

    Going beyond the linearized study has been a longstanding problem in the theory of Landau damping. In this paper we establish exponential Landau damping in analytic regularity. The damping phenomenon is reinterpreted in terms of transfer of regularity between kinetic and spatial variables, rather than exchanges of energy; phase mixing is the driving mechanism. The analysis involves new families of analytic norms, measuring regularity by comparison with solutions of the free transport equation; new functional inequalities; a control of non-linear echoes; sharp "deflection" estimates; and a Newton approximation scheme. Our results hold for any potential no more singular than Coulomb or Newton interaction; the limit cases are included with specific technical effort. As a side result, the stability of homogeneous equilibria of the non-linear Vlasov equation is established under sharp assumptions. We point out the strong analogy with the KAM theory, and discuss physical implications. Finally, we extend these results to some Gevrey (non-analytic) distribution functions. © 2011 Institut Mittag-Leffler.

  2. Interaction of nitric oxide with human heme oxygenase-1.

    Science.gov (United States)

    Wang, Jinling; Lu, Shen; Moënne-Loccoz, Pierre; Ortiz de Montellano, Paul R

    2003-01-24

    NO and CO may complement each other as signaling molecules in some physiological situations. We have examined the binding of NO to human heme oxygenase-1 (hHO-1), an enzyme that oxidizes heme to biliverdin, CO, and free iron, to determine whether inhibition of hHO-1 by NO can contribute to the signaling interplay of NO and CO. An Fe(3+)-NO hHO-1-heme complex is formed with NO or the NO donors NOC9 or 2-(N,N-diethylamino)-diazenolate-2-oxide.sodium salt. Resonance Raman spectroscopy shows that ferric hHO-1-heme forms a 6-coordinated, low spin complex with NO. The nu(N-O) vibration of this complex detected by Fourier transform IR is only 4 cm(-1) lower than that of the corresponding metmyoglobin (met-Mb) complex but is broader, suggesting a greater degree of ligand conformational freedom. The Fe(3+)-NO complex of hHO-1 is much more stable than that of met-Mb. Stopped-flow studies indicate that k(on) for formation of the hHO-1-heme Fe(3+)-NO complex is approximately 50-times faster, and k(off) 10 times slower, than for met-Mb, resulting in K(d) = 1.4 microm for NO. NO thus binds 500-fold more tightly to ferric hHO-1-heme than to met-Mb. The hHO-1 mutations E29A, G139A, D140A, S142A, G143A, G143F, and K179A/R183A do not significantly diminish the tight binding of NO, indicating that NO binding is not highly sensitive to mutations of residues that normally stabilize the distal water ligand. As expected from the K(d) value, the enzyme is reversibly inhibited upon exposure to pathologically, and possibly physiologically, relevant concentrations of NO. Inhibition of hHO-1 by NO may contribute to the pleiotropic responses to NO and CO.

  3. Nitric oxide heme interactions in nitrophorin from Cimex lectularius

    Energy Technology Data Exchange (ETDEWEB)

    Christmann, R.; Auerbach, H., E-mail: auerbach@physik.uni-kl.de [University of Kaiserslautern, Department of Physics (Germany); Berry, R. E.; Walker, F. A. [The University of Arizona, Department of Chemistry and Biochemistry (United States); Schünemann, V. [University of Kaiserslautern, Department of Physics (Germany)

    2016-12-15

    The nitrophorin from the bedbug Cimex lectularius (cNP) is a nitric oxide (NO) carrying protein. Like the nitrophorins (rNPs) from the kissing bug Rhodnius prolixus, cNP forms a stable heme Fe(III)-NO complex, where the NO can be stored reversibly for a long period of time. In both cases, the NPs are found in the salivary glands of blood-sucking bugs. The insects use the nitrophorins to transport the NO to the victim’s tissues, resulting in vasodilation and reduced blood coagulation. However, the structure of cNP is significantly different to those of the rNPs from Rhodnius prolixus. Furthermore, the cNP can bind a second NO molecule to the proximal heme cysteine when present at higher concentrations. High field Mössbauer spectroscopy on {sup 57}Fe enriched cNP complexed with NO shows reduction of the heme iron and formation of a ferrous nitric oxide (Fe(II)-NO) complex. Density functional theory calculations reproduce the experimental Mössbauer parameters and confirm this observation.

  4. The use and abuse of heme in apicomplexan parasites.

    Science.gov (United States)

    van Dooren, Giel G; Kennedy, Alexander T; McFadden, Geoffrey I

    2012-08-15

    Heme is an essential prosthetic group for most life on Earth. It functions in numerous cellular redox reactions, including in antioxidant defenses and at several stages of the electron transport chain in prokaryotes and eukaryotic mitochondria. Heme also functions as a sensor and transport molecule for gases such as oxygen. Heme is a complex organic molecule and can only be synthesized through a multienzyme pathway from simpler precursors. Most free-living organisms synthesize their own heme by a broadly conserved metabolic pathway. Parasites are adept at scavenging molecules from their hosts, and heme is no exception. In this review we examine recent advances in understanding heme usage and acquisition in Apicomplexa, a group of parasites that include the causative agents of malaria, toxoplasmosis, and several major parasites of livestock. Heme is critical to the survival of Apicomplexa, although the functions of heme in these organisms remain poorly understood. Some Apicomplexa likely scavenge heme from their host organisms, while others retain the ability to synthesize heme. Surprisingly, some Apicomplexa may be able to both synthesize and scavenge heme. Several Apicomplexa live in intracellular environments that contain high levels of heme. Since heme is toxic at high concentrations, parasites must carefully regulate intracellular heme levels and develop mechanisms to detoxify excess heme. Indeed, drugs interfering with heme detoxification serve as major antimalarials. Understanding heme requirements and regulation in apicomplexan parasites promises to reveal multiple targets for much-needed therapeutic intervention against these parasites.

  5. The Duffing oscillator with damping

    DEFF Research Database (Denmark)

    Johannessen, Kim

    2015-01-01

    An analytical solution to the differential equation describing the Duffing oscillator with damping is presented. The damping term of the differential equation and the initial conditions satisfy an algebraic equation, and thus the solution is specific for this type of damping. The nonlinear term....... It is established that the period of oscillation is shorter compared to that of a linearized model but increasing with time and asymptotically approaching the period of oscillation of the linear damped model. An explicit expression for the period of oscillation has been derived, and it is found to be very accurate....

  6. Prebiotics increase heme iron bioavailability and do not affect non-heme iron bioavailability in humans.

    Science.gov (United States)

    Weinborn, Valerie; Valenzuela, Carolina; Olivares, Manuel; Arredondo, Miguel; Weill, Ricardo; Pizarro, Fernando

    2017-05-24

    The aim of this study was to establish the effect of a prebiotic mix on heme and non-heme iron (Fe) bioavailability in humans. To this purpose, twenty-four healthy women were randomized into one of two study groups. One group ate one yogurt per day for 12 days with a prebiotic mix (prebiotic group) and the other group received the same yogurt but without the prebiotic mix (control group). Before and after the intake period, the subjects participated in Fe absorption studies. These studies used (55)Fe and (59)Fe radioactive isotopes as markers of heme Fe and non-heme Fe, respectively, and Fe absorption was measured by the incorporation of radioactive Fe into erythrocytes. The results showed that there were no significant differences in heme and non-heme Fe bioavailability in the control group. Heme Fe bioavailability of the prebiotic group increased significantly by 56% post-prebiotic intake. There were no significant differences in non-heme Fe bioavailability in this group. We concluded that daily consumption of a prebiotic mix increases heme Fe bioavailability and does not affect non-heme iron bioavailability.

  7. The surface protein Shr of Streptococcus pyogenes binds heme and transfers it to the streptococcal heme-binding protein Shp

    Directory of Open Access Journals (Sweden)

    Lei Benfang

    2008-01-01

    Full Text Available Abstract Background The heme acquisition machinery in Streptococcus pyogenes is believed to consist of the surface proteins, Shr and Shp, and heme-specific ATP-binding cassette transporter HtsABC. Shp has been shown to rapidly transfer its heme to the lipoprotein component, HtsA, of HtsABC. The function of Shr and the heme source of Shp have not been established. Results The objective of this study was to determine whether Shr binds heme and is a heme source of Shp. To achieve the objective, recombinant Shr protein was prepared. The purified Shr displays a spectrum typical of hemoproteins, indicating that Shr binds heme and acquires heme from Escherichia coli hemoproteins in vivo. Spectral analysis of Shr and Shp isolated from a mixture of Shr and heme-free Shp (apoShp indicates that Shr and apoShp lost and gained heme, respectively; whereas Shr did not efficiently lose its heme in incubation with apoHtsA under the identical conditions. These results suggest that Shr directly transfers its heme to Shp. In addition, the rates of heme transfer from human hemoglobin to apoShp are close to those of simple ferric heme dissociation from hemoglobin, suggesting that methemoglobin does not directly transfer its heme to apoShp. Conclusion We have demonstrated that recombinant Shr can acquire heme from E. coli hemoproteins in vivo and appears to directly transfer its heme to Shp and that Shp appears not to directly acquire heme from human methemoglobin. These results suggest the possibility that Shr is a source of heme for Shp and that the Shr-to-Shp heme transfer is a step of the heme acquisition process in S. pyogenes. Further characterization of the Shr/Shp/HtsA system would advance our understanding of the mechanism of heme acquisition in S. pyogenes.

  8. Characterization of Heme Proteins Involved in Microbial Exoelectric Activity and Small Molecule-Sensing

    KAUST Repository

    Vogler, Malvina M.

    2018-01-01

    Heme proteins, also termed cytochromes, are a widespread class of metalloproteins containing an Fe-protoporphyrin IX cofactor. They perform numerous functions in nature such as oxygen-transport by hemoglobin, monooxygenation reactions catalyzed by Cytochrome P-450, and electron transfer reactions during photosynthesis. The differences between proteincofactor binding characteristics and the cofactor environment greatly influence the extensive range of functions. In this dissertation, proteins from the Mtr pathway of Shewanella oneidensis are characterized. These c-type cytochromes contain multiple heme cofactors per protein molecule that covalently attach to the protein amino acid sequence and are involved in electron transfer to extracellular metal oxides during anaerobic conditions. Successful recombinant expression of pathway components MtrC and MtrA is achieved in Escherichia coli. Heme-dependent gel staining and UV/Vis spectroscopy show characteristic c-type cytochrome characteristics. Mass spectrometry confirms that the correct extensive post-translational modifications were performed and the ten heme groups were incorporated per protein of MtrC and MtrA and the correct lipid-anchor was attached to extracellular MtrC. Raman spectroscopy measurements of MtrA provide intriguing structural information and highlight the strong influence of the heme cofactors within the protein structure. Next, an Arabidopsis thaliana protein is analyzed. It was previously identified via a motif search of the plant genome, based on conserved residues in the H4 NOX pocket. Here, the incorporation of a heme b cofactor is confirmed. UV/Vis spectroscopy under anaerobic conditions demonstrates reversible binding of nitric oxide to the heme iron and depicts the previously published characteristic absorption maxima for other H-NOX proteins.

  9. Dioxygen reactivity of meso-hydroxylated hemes: intermediates in ...

    Indian Academy of Sciences (India)

    Keywords. Heme oxygenase; heme degradation; coupled oxidation; variable temperature paramagnetic NMR. Abstract. Heme oxygenase (HO) is the only enzyme in mammals known to catalyse the physiological degradation of unwanted heme into biliverdin, Fe ion and CO. The process involves introduction of the hydroxyl ...

  10. Porphyrin and heme metabolism and the porphyrias.

    Science.gov (United States)

    Bonkovsky, Herbert L; Guo, Jun-Tao; Hou, Weihong; Li, Ting; Narang, Tarun; Thapar, Manish

    2013-01-01

    Porphyrins and metalloporphyrins are the key pigments of life on earth as we know it, because they include chlorophyll (a magnesium-containing metalloporphyrin) and heme (iron protoporphyrin). In eukaryotes, porphyrins and heme are synthesized by a multistep pathway that involves eight enzymes. The first and rate-controlling step is the formation of delta-aminolevulinic acid (ALA) from glycine plus succinyl CoA, catalyzed by ALA synthase. Intermediate steps occur in the cytoplasm, with formation of the monopyrrole porphobilinogen and the tetrapyrroles hydroxymethylbilane and a series of porphyrinogens, which are serially decarboxylated. Heme is utilized chiefly for the formation of hemoglobin in erythrocytes, myoglobin in muscle cells, cytochromes P-450 and mitochondrial cytochromes, and other hemoproteins in hepatocytes. The rate-controlling step of heme breakdown is catalyzed by heme oxygenase (HMOX), of which there are two isoforms, called HMOX1 and HMOX2. HMOX breaks down heme to form biliverdin, carbon monoxide, and iron. The porphyrias are a group of disorders, mainly inherited, in which there are defects in normal porphyrin and heme synthesis. The cardinal clinical features are cutaneous (due to the skin-damaging effects of excess deposited porphyrins) or neurovisceral attacks of pain, sometimes with weakness, delirium, seizures, and the like (probably due mainly to neurotoxic effects of ALA). The treatment of choice for the acute hepatic porphyrias is intravenous heme therapy, which repletes a critical regulatory heme pool in hepatocytes and leads to downregulation of hepatic ALA synthase, which is a biochemical hallmark of all forms of acute porphyria in relapse.

  11. Heme environment in HmuY, the heme-binding protein of Porphyromonas gingivalis

    Energy Technology Data Exchange (ETDEWEB)

    Wojtowicz, Halina [Laboratory of Biochemistry, Faculty of Biotechnology, University of Wroclaw, Tamka 2, 50-137 Wroclaw (Poland); Wojaczynski, Jacek [Department of Chemistry, University of Wroclaw, 50-383 Wroclaw (Poland); Olczak, Mariusz [Laboratory of Biochemistry, Faculty of Biotechnology, University of Wroclaw, Tamka 2, 50-137 Wroclaw (Poland); Kroliczewski, Jaroslaw [Laboratory of Biophysics, Faculty of Biotechnology, University of Wroclaw, 50-148 Wroclaw (Poland); Latos-Grazynski, Lechoslaw [Department of Chemistry, University of Wroclaw, 50-383 Wroclaw (Poland); Olczak, Teresa, E-mail: Teresa.Olczak@biotech.uni.wroc.pl [Laboratory of Biochemistry, Faculty of Biotechnology, University of Wroclaw, Tamka 2, 50-137 Wroclaw (Poland)

    2009-05-29

    Porphyromonas gingivalis, a Gram-negative anaerobic bacterium implicated in the development and progression of chronic periodontitis, acquires heme for growth by a novel mechanism composed of HmuY and HmuR proteins. The aim of this study was to characterize the nature of heme binding to HmuY. The protein was expressed, purified and detailed investigations using UV-vis absorption, CD, MCD, and {sup 1}H NMR spectroscopy were carried out. Ferric heme bound to HmuY may be reduced by sodium dithionite and re-oxidized by potassium ferricyanide. Heme complexed to HmuY, with a midpoint potential of 136 mV, is in a low-spin Fe(III) hexa-coordinate environment. Analysis of heme binding to several single and double HmuY mutants with the methionine, histidine, cysteine, or tyrosine residues replaced by an alanine residue identified histidines 134 and 166 as potential heme ligands.

  12. Persistent Motor Deficits in DAMP

    OpenAIRE

    J Gordon Millichap

    2000-01-01

    Motor control in ability to perform everyday and spare-time activities was assessed at 11 to 12 years of age in 10 boys with deficits in attention, motor control and perception (DAMP) and compared with a group of 20 boys without DAMP.

  13. Heme Compounds in Dinosaur Trabecular Bone

    National Research Council Canada - National Science Library

    Mary H. Schweitzer; Mark Marshall; Keith Carron; D. Scott Bohle; Scott C. Busse; Ernst V. Arnold; Darlene Barnard; J. R. Horner; Jean R. Starkey

    1997-01-01

    Six independent lines of evidence point to the existence of heme-containing compounds and/or hemoglobin breakdown products in extracts of trabecular tissues of the large theropod dinosaur Tyrannosaurus rex...

  14. Structural mechanisms of nonplanar hemes in proteins

    Energy Technology Data Exchange (ETDEWEB)

    Shelnutt, J.A.

    1997-05-01

    The objective is to assess the occurrence of nonplanar distortions of hemes and other tetrapyrroles in proteins and to determine the biological function of these distortions. Recently, these distortions were found by us to be conserved among proteins belonging to a functional class. Conservation of the conformation of the heme indicates a possible functional role. Researchers have suggested possible mechanisms by which heme distortions might influence biological properties; however, no heme distortion has yet been shown conclusively to participate in a structural mechanism of hemoprotein function. The specific aims of the proposed work are: (1) to characterize and quantify the distortions of the hemes in all of the more than 300 hemoprotein X-ray crystal structures in terms of displacements along the lowest-frequency normal coordinates, (2) to determine the structural features of the protein component that generate and control these nonplanar distortions by using spectroscopic studies and molecular-mechanics calculations for the native proteins, their mutants and heme-peptide fragments, and model porphyrins, (3) to determine spectroscopic markers for the various types of distortion, and, finally, (4) to discover the functional significance of the nonplanar distortions by correlating function with porphyrin conformation for proteins and model porphyrins.

  15. Heme Oxygenases in Cardiovascular Health and Disease

    Science.gov (United States)

    Ayer, Anita; Zarjou, Abolfazl; Agarwal, Anupam; Stocker, Roland

    2016-01-01

    Heme oxygenases are composed of two isozymes, Hmox1 and Hmox2, that catalyze the degradation of heme to carbon monoxide (CO), ferrous iron, and biliverdin, the latter of which is subsequently converted to bilirubin. While initially considered to be waste products, CO and biliverdin/bilirubin have been shown over the last 20 years to modulate key cellular processes, such as inflammation, cell proliferation, and apoptosis, as well as antioxidant defense. This shift in paradigm has led to the importance of heme oxygenases and their products in cell physiology now being well accepted. The identification of the two human cases thus far of heme oxygenase deficiency and the generation of mice deficient in Hmox1 or Hmox2 have reiterated a role for these enzymes in both normal cell function and disease pathogenesis, especially in the context of cardiovascular disease. This review covers the current knowledge on the function of both Hmox1 and Hmox2 at both a cellular and tissue level in the cardiovascular system. Initially, the roles of heme oxygenases in vascular health and the regulation of processes central to vascular diseases are outlined, followed by an evaluation of the role(s) of Hmox1 and Hmox2 in various diseases such as atherosclerosis, intimal hyperplasia, myocardial infarction, and angiogenesis. Finally, the therapeutic potential of heme oxygenases and their products are examined in a cardiovascular disease context, with a focus on how the knowledge we have gained on these enzymes may be capitalized in future clinical studies. PMID:27604527

  16. Rates and Equilibrium of CuA to heme a electron transfer in Paracoccus denitrificans cytochrome c oxidase

    DEFF Research Database (Denmark)

    Farver, Ole; Grell, Ernst; Ludwig, Bernd

    2006-01-01

    were found to be 20,400 s(-1) and 10,030 s(-1), respectively, at 25 degrees C and pH 7.5, which corresponds to an equilibrium constant of 2.0. Thermodynamic and activation parameters of these intramolecular ET reactions were determined. The significance of the results, particularly the low activation...... by absorption changes at 825 nm, followed by partial restoration of the absorption and paralleled by an increase in the heme a absorption at 605 nm. The latter observations indicate partial reoxidation of the CuA center and the concomitant reduction of heme a. The rate constants for heme a reduction and Cu......A reoxidation were identical within experimental error and independent of the enzyme concentration and its degree of reduction, demonstrating that a fast intramolecular electron equilibration is taking place between CuA and heme a. The rate constants for CuA --> heme a ET and the reverse heme a --> CuA process...

  17. Amplitude damping of vortex modes

    CSIR Research Space (South Africa)

    Dudley, Angela L

    2010-09-01

    Full Text Available An interferometer, mimicking an amplitude damping channel for vortex modes, is presented. Experimentally the action of the channel is in good agreement with that predicted theoretically. Since we can characterize the action of the channel on orbital...

  18. Regiospecificity determinants of human heme oxygenase: differential NADPH- and ascorbate-dependent heme cleavage by the R183E mutant.

    Science.gov (United States)

    Wang, Jinling; Lad, Latesh; Poulos, Thomas L; Ortiz de Montellano, Paul R

    2005-01-28

    The ability of the human heme oxygenase-1 (hHO-1) R183E mutant to oxidize heme in reactions supported by either NADPH-cytochrome P450 reductase or ascorbic acid has been compared. The NADPH-dependent reaction, like that of wild-type hHO-1, yields exclusively biliverdin IXalpha. In contrast, the R183E mutant with ascorbic acid as the reductant produces biliverdin IXalpha (79 +/- 4%), IXdelta (19 +/- 3%), and a trace of IXbeta. In the presence of superoxide dismutase and catalase, the yield of biliverdin IXdelta is decreased to 8 +/- 1% with a corresponding increase in biliverdin IXalpha. Spectroscopic analysis of the NADPH-dependent reaction shows that the R183E ferric biliverdin complex accumulates, because reduction of the iron, which is required for sequential iron and biliverdin release, is impaired. Reversal of the charge at position 183 makes reduction of the iron more difficult. The crystal structure of the R183E mutant, determined in the ferric and ferrous-NO bound forms, shows that the heme primarily adopts the same orientation as in wild-type hHO-1. The structure of the Fe(II).NO complex suggests that an altered active site hydrogen bonding network supports catalysis in the R183E mutant. Furthermore, Arg-183 contributes to the regiospecificity of the wild-type enzyme, but its contribution is not critical. The results indicate that the ascorbate-dependent reaction is subject to a lower degree of regiochemical control than the NADPH-dependent reaction. Ascorbate may be able to reduce the R183E ferric and ferrous dioxygen complexes in active site conformations that cannot be reduced by NADPH-cytochrome P450 reductase.

  19. Spatial Damping of Linear Compressional Magnetoacoustic Waves ...

    Indian Academy of Sciences (India)

    shows greater wave damping at low values of radiative time and then attains some maximum value and then decreases. The slow mode wave has higher values of damping per wavelength, showing higher levels of damping due to radiation. For τR → ∞, the wave takes infinite time to damp and therefore travels very long ...

  20. Identification of Light Damping in Structures

    DEFF Research Database (Denmark)

    Jensen, J. L.; Brincker, Rune; Rytter, A.

    1990-01-01

    Different methods to identification of linear and nonlinear damping in lightly damped structures are discussed in this paper. The discussion is based on experiments with a 4 meter high monopile. Two alternative methods have been used for experimental cases of linear and nonlinear damping. Method 1...... case was a naturally damped monopile which was considered to be linear viscous damped. The second case was nonlinear viscous damping of the monopile due to a mounted damper on the monopile. The two cases illustrates identification of lightly damping in the linear and nonlinear case....

  1. Identification of Light Damping in Structures

    DEFF Research Database (Denmark)

    Jensen, Jacob Laigaard; Brincker, Rune; Rytter, Anders

    Different methods to identification of linear and nonlinear damping in lightly damped structures are discussed in this paper. The discussion is based on experiments with a 4 meter high monopile. Two alternative methods have been used for experimental cases of linear and nonlinear damping. Method 1...... case was a naturally damped monopile which was considered to be linear viscous damped. The second case was nonlinear viscous damping of the monopile due to a mounted damper on the monopile. The two cases illustrate identification of lightly damping in the linear and the nonlinear case....

  2. Biology of Heme in Mammalian Erythroid Cells and Related Disorders

    Directory of Open Access Journals (Sweden)

    Tohru Fujiwara

    2015-01-01

    Full Text Available Heme is a prosthetic group comprising ferrous iron (Fe2+ and protoporphyrin IX and is an essential cofactor in various biological processes such as oxygen transport (hemoglobin and storage (myoglobin and electron transfer (respiratory cytochromes in addition to its role as a structural component of hemoproteins. Heme biosynthesis is induced during erythroid differentiation and is coordinated with the expression of genes involved in globin formation and iron acquisition/transport. However, erythroid and nonerythroid cells exhibit distinct differences in the heme biosynthetic pathway regulation. Defects of heme biosynthesis in developing erythroblasts can have profound medical implications, as represented by sideroblastic anemia. This review will focus on the biology of heme in mammalian erythroid cells, including the heme biosynthetic pathway as well as the regulatory role of heme and human disorders that arise from defective heme synthesis.

  3. Biology of Heme in Mammalian Erythroid Cells and Related Disorders

    Science.gov (United States)

    Fujiwara, Tohru; Harigae, Hideo

    2015-01-01

    Heme is a prosthetic group comprising ferrous iron (Fe2+) and protoporphyrin IX and is an essential cofactor in various biological processes such as oxygen transport (hemoglobin) and storage (myoglobin) and electron transfer (respiratory cytochromes) in addition to its role as a structural component of hemoproteins. Heme biosynthesis is induced during erythroid differentiation and is coordinated with the expression of genes involved in globin formation and iron acquisition/transport. However, erythroid and nonerythroid cells exhibit distinct differences in the heme biosynthetic pathway regulation. Defects of heme biosynthesis in developing erythroblasts can have profound medical implications, as represented by sideroblastic anemia. This review will focus on the biology of heme in mammalian erythroid cells, including the heme biosynthetic pathway as well as the regulatory role of heme and human disorders that arise from defective heme synthesis. PMID:26557657

  4. Molecular hijacking of siroheme for the synthesis of heme and d1 heme

    Science.gov (United States)

    Bali, Shilpa; Lawrence, Andrew D.; Lobo, Susana A.; Saraiva, Lígia M.; Golding, Bernard T.; Palmer, David J.; Howard, Mark J.; Ferguson, Stuart J.; Warren, Martin J.

    2011-01-01

    Modified tetrapyrroles such as chlorophyll, heme, siroheme, vitamin B12, coenzyme F430, and heme d1 underpin a wide range of essential biological functions in all domains of life, and it is therefore surprising that the syntheses of many of these life pigments remain poorly understood. It is known that the construction of the central molecular framework of modified tetrapyrroles is mediated via a common, core pathway. Herein a further branch of the modified tetrapyrrole biosynthesis pathway is described in denitrifying and sulfate-reducing bacteria as well as the Archaea. This process entails the hijacking of siroheme, the prosthetic group of sulfite and nitrite reductase, and its processing into heme and d1 heme. The initial step in these transformations involves the decarboxylation of siroheme to give didecarboxysiroheme. For d1 heme synthesis this intermediate has to undergo the replacement of two propionate side chains with oxygen functionalities and the introduction of a double bond into a further peripheral side chain. For heme synthesis didecarboxysiroheme is converted into Fe-coproporphyrin by oxidative loss of two acetic acid side chains. Fe-coproporphyrin is then transformed into heme by the oxidative decarboxylation of two propionate side chains. The mechanisms of these reactions are discussed and the evolutionary significance of another role for siroheme is examined. PMID:21969545

  5. Supramolecular assembling systems formed by heme-heme pocket interactions in hemoproteins.

    Science.gov (United States)

    Oohora, Koji; Onoda, Akira; Hayashi, Takashi

    2012-12-14

    A native protein in a biological system spontaneously produces large and elegant assemblies via self-assembly or assembly with various biomolecules which provide non-covalent interactions. In this context, the protein plays a key role in construction of a unique supramolecular structure operating as a functional system. Our group has recently highlighted the structure and function of hemoproteins reconstituted with artificially created heme analogs. The heme molecule is a replaceable cofactor of several hemoproteins. Here, we focus on the successive supramolecular protein assemblies driven by heme-heme pocket interactions to afford various examples of protein fibers, networks and three-dimensional clusters in which an artificial heme moiety is introduced onto the surface of a hemoprotein via covalent linkage and the native heme cofactor is removed from the heme pocket. This strategy is found to be useful for constructing hybrid materials with an electrode or with nanoparticles. The new systems described herein are expected to lead to the generation of various biomaterials with functions and characteristic physicochemical properties similar to those of hemoproteins.

  6. Kidney injury and heme oxygenase-1

    Directory of Open Access Journals (Sweden)

    Hai-xing MAI

    2012-02-01

    Full Text Available     Heme oxygenase-1 (HO-1 is one of the main pathways to degrade heme in mammals, and the main degradation products are free iron (Fe2+, carbon monoxide (CO, and bilirubin. Heme plays an important role in promoting cell survival, circulation of intracellular substrates, and immune regulation. Previous studies suggest that HO-1 pathway is an important internal factor in determining the susceptibility and severity of acute kidney injury (AKI. The induction of HO-1 expression can attenuate the severity of renal ischemia-reperfusion injury (IRI, and the inhibition of HO-1 expression will aggravate IRI. The present article summarizes the latest advances in research abroad and at home on protective mechanism by which HO-1 prevents AKI to further deepen our understanding of the role of HO-1 in the treatment of AKI.   

  7. Dampness in buildings and health

    DEFF Research Database (Denmark)

    Bornehag, Carl-Gustaf; Blomquist, G.; Gyntelberg, F.

    2001-01-01

    Several epidemiological investigations concerning indoor environments have indicated that "dampness" in buildings is associated to health effects such as respiratory symptoms, asthma and allergy The aim of the present interdisciplinary review is to evaluate this association as shown in the epidem......Several epidemiological investigations concerning indoor environments have indicated that "dampness" in buildings is associated to health effects such as respiratory symptoms, asthma and allergy The aim of the present interdisciplinary review is to evaluate this association as shown...... in the epidemiological literature. A literature search identified 590 peer-reviewed articles of which 61 have been the foundation for this review. The review shows that "dampness" in buildings appears to increase the risk for health effects in the airways, such as cough, wheeze and asthma. Relative risks...... are in the range of OR 1.4-2.2. There also seems to be an association between "dampness" and other symptoms Such as tiredness, headache and airways infections. It is concluded that the evidence for a causal association between "dampness" and health effects is strong. However, the mechanisms are unknown. Several...

  8. Damping mechanisms of a pendulum

    Science.gov (United States)

    Dolfo, Gilles; Castex, Daniel; Vigué, Jacques

    2016-11-01

    In this paper, we study the damping mechanisms of a pendulum. The originality of our setup is the use of a metal strip suspension and the development of extremely sensitive electric measurements of the pendulum velocity and position. Their sensitivity is absolutely necessary for a reliable measurement of the pendulum damping time constant because this measurement is possible only for very low oscillation amplitudes, when air friction forces quadratic in velocity have a negligible contribution to the observed damping. We have thus carefully studied damping by air friction forces, which is the dominant mechanism for large values of the Reynolds number Re but which is negligible in the Stokes regime, {Re} ∼ 1. In this last case, we have found that the dominant damping is due to internal friction in the metal strip, a universal effect called anelasticity, and, for certain frequencies, to resonant coupling to the support of the pendulum. All our measurements are well explained by theory. We believe this paper would be of interest to students in an undergraduate classical mechanics course.

  9. Molecular Simulations of Porphyrins and Heme Proteins

    Energy Technology Data Exchange (ETDEWEB)

    SHELNUTT,JOHN A.

    2000-01-18

    An overview of the use of classical mechanical molecular simulations of porphyrins, hydroporphyrins, and heme proteins is given. The topics cover molecular mechanics calculations of structures and conformer energies of porphyrins, energies of barriers for interconversion between stable conformers, molecular dynamics of porphyrins and heme proteins, and normal-coordinate structural analysis of experimental and calculated porphyrin structures. Molecular mechanics and dynamics are currently a fertile area of research on porphyrins. In the future, other computational methods such as Monte Carlo simulations, which have yet to be applied to porphyrins, will come into use and open new avenues of research into molecular simulations of porphyrins.

  10. Identification of the receptor scavenging hemopexin-heme complexes

    DEFF Research Database (Denmark)

    Hvidberg, Vibeke; Maniecki, Maciej B; Jacobsen, Christian

    2005-01-01

    Heme released from heme-binding proteins on internal hemorrhage, hemolysis, myolysis, or other cell damage is highly toxic due to oxidative and proinflammatory effects. Complex formation with hemopexin, the high-affinity heme-binding protein in plasma and cerebrospinal fluid, dampens these effects...

  11. Red meat and colon cancer : how dietary heme initiates hyperproliferation

    NARCIS (Netherlands)

    IJssennagger, N.

    2012-01-01

    Colorectal cancer is a leading cause of cancer deaths in Western countries. The risk to develop colorectal cancer is associated with the intake of red meat. Red meat contains the porphyrin pigment heme. Heme is an irritant for the colonic wall and it is previously shown that the addition of heme to

  12. Relaxation damping in oscillating contacts.

    Science.gov (United States)

    Popov, M; Popov, V L; Pohrt, R

    2015-11-09

    If a contact of two purely elastic bodies with no sliding (infinite coefficient of friction) is subjected to superimposed oscillations in the normal and tangential directions, then a specific damping appears, that is not dependent on friction or dissipation in the material. We call this effect "relaxation damping". The rate of energy dissipation due to relaxation damping is calculated in a closed analytic form for arbitrary axially-symmetric contacts. In the case of equal frequency of normal and tangential oscillations, the dissipated energy per cycle is proportional to the square of the amplitude of tangential oscillation and to the absolute value of the amplitude of normal oscillation, and is dependent on the phase shift between both oscillations. In the case of low frequency tangential oscillations with superimposed high frequency normal oscillations, the dissipation is proportional to the ratio of the frequencies. Generalization of the results for macroscopically planar, randomly rough surfaces as well as for the case of finite friction is discussed.

  13. IMPACT GRINDING OF DAMP MATERIALS

    Directory of Open Access Journals (Sweden)

    Ladaev Nikolay Mikhaylovich

    2012-10-01

    Centrifugal grinders were used to analyze the grinding process. The experimental data have proven that the probability of destruction of damp samples is a lot higher than the one of dry samples, given the same initial dimensions of particles and the loading intensity. The rise in the probability of destruction is stipulated by the fact that that the grinder speed at which crushing is triggered is lower in case of damp samples than in case of dry ones. Expressions for speed that describes destruction initiation and the probability of destruction depending on the type of materials, the moisture content and the loading intensity have been derived.

  14. Inhibition of Heme Peroxidases by Melamine

    Directory of Open Access Journals (Sweden)

    Pattaraporn Vanachayangkul

    2012-01-01

    Full Text Available In 2008 melamine-contaminated infant formula and dairy products in China led to over 50,000 hospitalizations of children due to renal injuries. In North America during 2007 and in Asia during 2004, melamine-contaminated pet food products resulted in numerous pet deaths due to renal failure. Animal studies have confirmed the potent renal toxicity of melamine combined with cyanuric acid. We showed previously that the solubility of melamine cyanurate is low at physiologic pH and ionic strength, provoking us to speculate how toxic levels of these compounds could be transported through the circulation without crystallizing until passing into the renal filtrate. We hypothesized that melamine might be sequestered by heme proteins, which could interfere with heme enzyme activity. Four heme peroxidase enzymes were selected for study: horseradish peroxidase (HRP, lactoperoxidase (LPO, and cyclooxygenase-1 and -2 (COX-1 and -2. Melamine exhibited noncompetitive inhibition of HRP (9.5±0.7mM, and LPO showed a mixed model of inhibition (14.5±4.7mM. The inhibition of HRP and LPO was confirmed using a chemiluminescent peroxidase assay. Melamine also exhibited COX-1 inhibition, but inhibition of COX-2 was not detected. Thus, our results demonstrate that melamine inhibits the activity of three heme peroxidases.

  15. Immunogenicity of heme complexes of peptides designed to mimic the heme environment of myoglobin and hemoglobin.

    Science.gov (United States)

    Atassi, M Zouhair; Childress, Catherine

    2005-01-01

    In the preceding paper (Protein J. 25, pages 37-49, 2005), we reported the preparation and oxygen-binding properties of peptides that form stable complexes with heme mimic. The design of the peptides was based on the natural environment of the heme group in myoglobin (Mb) and in the alpha- and beta-subunits of human adult hemoglobin (Hb). In the present work, the heme-peptides were each administered into mice, either as emulsions in adjuvant (both for injections and boosters) or intravenously as solutions in phosphate-buffered saline. Antibody (Ab) responses, monitored up to 14 weeks after the first administration, showed that when the heme-peptides were injected with adjuvant they stimulated Ab responses against the immunizing peptide, which in most cases bound to the correlate protein (Mb or Hb). However these heme-peptides were non-immunogenic when administered in PBS intravenously. It is concluded that heme-peptides:(a) would not trigger an adverse immune response if used for transfusion purposes.

  16. Heme and erythropoieis: more than a structural role

    Science.gov (United States)

    Chiabrando, Deborah; Mercurio, Sonia; Tolosano, Emanuela

    2014-01-01

    Erythropoiesis is the biological process that consumes the highest amount of body iron for heme synthesis. Heme synthesis in erythroid cells is finely coordinated with that of alpha (α) and beta (β)-globin, resulting in the production of hemoglobin, a tetramer of 2α- and 2β-globin chains, and heme as the prosthetic group. Heme is not only the structural component of hemoglobin, but it plays multiple regulatory roles during the differentiation of erythroid precursors since it controls its own synthesis and regulates the expression of several erythroid-specific genes. Heme is synthesized in developing erythroid progenitors by the stage of proerythroblast, through a series of eight enzymatic reactions divided between mitochondria and cytosol. Defects of heme synthesis in the erythroid lineage result in sideroblastic anemias, characterized by microcytic anemia associated to mitochondrial iron overload, or in erythropoietic porphyrias, characterized by porphyrin deposition in erythroid cells. Here, we focus on the heme biosynthetic pathway and on human erythroid disorders due to defective heme synthesis. The regulatory role of heme during erythroid differentiation is discussed as well as the heme-mediated regulatory mechanisms that allow the orchestration of the adaptive cell response to heme deficiency. PMID:24881043

  17. Dampness in Buildings and Health

    DEFF Research Database (Denmark)

    Clausen, Geo; Rode, Carsten; Bornehag, Carl-Gustaf

    1999-01-01

    . The main themes are:· Continued research in human perception of indoor air quality, especially by identification of the factors that may cause annoyance to the occupants. Such annoyances may be emissions from materials or biological activity, and is often linked to the dampness of buildings.· Studies...

  18. Composite Struts Would Damp Vibrations

    Science.gov (United States)

    Dolgin, Benjamin P.

    1991-01-01

    New design of composite-material (fiber/matrix laminate) struts increases damping of longitudinal vibrations without decreasing longitudinal stiffness or increasing weight significantly. Plies with opposing chevron patterns of fibers convert longitudinal vibrational stresses into shear stresses in intermediate viscoelastic layer, which dissipate vibrational energy. Composite strut stronger than aluminum strut of same weight and stiffness.

  19. Vibration Damping Circuit Card Assembly

    Science.gov (United States)

    Hunt, Ronald Allen (Inventor)

    2016-01-01

    A vibration damping circuit card assembly includes a populated circuit card having a mass M. A closed metal container is coupled to a surface of the populated circuit card at approximately a geometric center of the populated circuit card. Tungsten balls fill approximately 90% of the metal container with a collective mass of the tungsten balls being approximately (0.07) M.

  20. Next generation HOM-damping

    Science.gov (United States)

    Marhauser, Frank

    2017-06-01

    Research and development for superconducting radio-frequency cavities has made enormous progress over the last decades from the understanding of theoretical limitations to the industrial mass fabrication of cavities for large-scale particle accelerators. Key technologies remain hot topics due to continuously growing demands on cavity performance, particularly when in pursuit of high quality beams at higher beam currents or higher luminosities than currently achievable. This relates to higher order mode (HOM) damping requirements. Meeting the desired beam properties implies avoiding coupled multi-bunch or beam break-up instabilities depending on the machine and beam parameters that will set the acceptable cavity impedance thresholds. The use of cavity HOM-dampers is crucial to absorb the wakefields, comprised by all beam-induced cavity Eigenmodes, to beam-dynamically safe levels and to reduce the heat load at cryogenic temperature. Cavity damping concepts may vary, but are principally based on coaxial and waveguide couplers as well as beam line absorbers or any combination. Next generation energy recovery linacs and circular colliders call for cavities with strong HOM-damping that can exceed the state-of-the-art, while the operating mode efficiency shall not be significantly compromised concurrently. This imposes major challenges given the rather limited damping concepts. A detailed survey of established cavities is provided scrutinizing the achieved damping performance, shortcomings, and potential improvements. The scaling of the highest passband mode impedances is numerically evaluated in dependence on the number of cells for a single-cell up to a nine-cell cavity, which reveals the increased probability of trapped modes. This is followed by simulations for single-cell and five-cell cavities, which incorporate multiple damping schemes to assess the most efficient concepts. The usage and viability of on-cell dampers is elucidated for the single-cell cavity since it

  1. Biglutaminyl-biliverdin IX alpha as a heme degradation product in the dengue fever insect-vector Aedes aegypti.

    Science.gov (United States)

    Pereira, Luiza O R; Oliveira, Pedro L; Almeida, Igor C; Paiva-Silva, Gabriela O

    2007-06-12

    Hemoglobin digestion in the midgut of hematophagous animals results in the release of its prosthetic group, heme, which is a pro-oxidant molecule. Heme enzymatic degradation is a protective mechanism that has been described in several organisms, including plants, bacteria, and mammals. This reaction is catalyzed by heme oxygenase and results in formation of carbon monoxide, ferrous ion, and biliverdin IXalpha. During digestion, a large amount of a green pigment is produced and secreted into the intestinal lumen of Aedes aegypti adult females. In the case of another blood-sucking insect, the kissing-bug Rhodnius prolixus, we have recently shown that heme degradation involves a complex pathway that generates dicysteinyl-biliverdin IX gamma. The light absorption spectrum of the Aedes purified pigment was similar to that of biliverdin, but its mobility on a reverse-phase chromatography column suggested a compound less hydrophobic than biliverdin IXalpha. Structural characterization by ESI-MS revealed that the mosquito pigment is the alpha isomer of biliverdin bound to two glutamine residues by an amide bond. This biglutaminyl-biliverdin is formed by oxidative cleavage of the heme porphyrin ring followed by two subsequent additions of glutamine residues to the biliverdin IXalpha. The role of this pathway in the adaptation of this insect vector to a blood-feeding habit is discussed.

  2. Damping of gravitational waves by matter

    Science.gov (United States)

    Baym, Gordon; Patil, Subodh P.; Pethick, C. J.

    2017-10-01

    We develop a unified description, via the Boltzmann equation, of damping of gravitational waves by matter, incorporating collisions. We identify two physically distinct damping mechanisms—collisional and Landau damping. We first consider damping in flat spacetime, and then generalize the results to allow for cosmological expansion. In the first regime, maximal collisional damping of a gravitational wave, independent of the details of the collisions in the matter is, as we show, significant only when its wavelength is comparable to the size of the horizon. Thus damping by intergalactic or interstellar matter for all but primordial gravitational radiation can be neglected. Although collisions in matter lead to a shear viscosity, they also act to erase anisotropic stresses, thus suppressing the damping of gravitational waves. Damping of primordial gravitational waves remains possible. We generalize Weinberg's calculation of gravitational wave damping, now including collisions and particles of finite mass, and interpret the collisionless limit in terms of Landau damping. While Landau damping of gravitational waves cannot occur in flat spacetime, the expansion of the universe allows such damping by spreading the frequency of a gravitational wave of given wave vector.

  3. Roll Damping Characterisation Program: User Guide

    Science.gov (United States)

    2014-06-01

    Cubic roll damping coefficient blin Linear roll damping coefficient bqua Quadratic roll damping coefficient Cxx Roll restoring moment coefficient g...testing conducted on a 32 bit Hewlett Packard desktop personal computer the RDCP was observed to function satisfactorily, however, the processing of

  4. Striplines for CLIC Pre-damping and Damping Rings

    CERN Document Server

    Belver-Aguilar, C; Barnes, M J; Rumolo, G; Zannini, C; Toral, F

    2011-01-01

    The Compact Linear Collider (CLIC) study explores the scheme for an electron-positron collider with high luminosity and a nominal centre-of-mass energy of 3 TeV: CLIC will complement LHC physics in the multi-TeV range. The CLIC design relies on the presence of Pre-Damping Rings (PDR) and Damping Rings (DR) to achieve, through synchrotron radiation, the very low emittance needed to fulfill the luminosity requirements. The specifications for the kicker systems are very challenging and include very low beam coupling impedance and excellent field homogeneity: striplines have been chosen for the kicker elements. Analytical calculations have been carried out to determine the effect of tapering upon the high frequency beam coupling impedance. In addition detailed numerical modeling of the field homogeneity has been performed and the sensitivity of the homogeneity to various parameters, including stripline cross-section, have been studied. This paper presents the main conclusions of the beam impedance calculations an...

  5. Robust Rudder Roll Damping Control

    DEFF Research Database (Denmark)

    Yang, C.

    -infinity theory is used to deal with the problem. The necessary mathematical tools and the H-Infinity theory as the basis of controller design are presented in Chapter 2 and 3. The mu synthesis and the D-K iteration are introduced in Chapter 3. The ship dynamics and modeling technology are discussed in Chapter 4......The results of a systematic research to solve a specific ship motion control problem, simultaneous roll damping and course keeping using the rudder are presented in this thesis. The fundamental knowledge a priori is that rudder roll damping is highly sensitive to the model uncertainty, therefore H......, two kinds of ship model have been obtained: linear ship model used for designing the controller and nonlinear model used for simulation. The ship model uncertainty is discussed in this chapter and so is a wave model because the ship's roll motion is caused by waves. Using an unstructured model...

  6. Damping Effects in Aerospace Structures

    Science.gov (United States)

    1979-10-01

    dapeadeat «a the applied damping values. Incorrect daoping values m^ lead to an inpropcr desigo. CoUeetioB and evaluation of available wmavanA...23) (24) Ref. [36] n b^ rr a Z , r rk (a Z ^ s rk arV < E rk u b r rr (25) where: y is the oodal daoping factor t> /2üI and e is a

  7. The DAMPE silicon tungsten tracker

    CERN Document Server

    Gallo, Valentina; Asfandiyarov, R; Azzarello, P; Bernardini, P; Bertucci, B; Bolognini, A; Cadoux, F; Caprai, M; Domenjoz, M; Dong, Y; Duranti, M; Fan, R; Franco, M; Fusco, P; Gargano, F; Gong, K; Guo, D; Husi, C; Ionica, M; Lacalamita, N; Loparco, F; Marsella, G; Mazziotta, M N; Mongelli, M; Nardinocchi, A; Nicola, L; Pelleriti, G; Peng, W; Pohl, M; Postolache, V; Qiao, R; Surdo, A; Tykhonov, A; Vitillo, S; Wang, H; Weber, M; Wu, D; Wu, X; Zhang, F; De Mitri, I; La Marra, D

    2017-01-01

    The DArk Matter Particle Explorer (DAMPE) satellite has been successfully launched on the 17th December 2015. It is a powerful space detector designed for the identification of possible Dark Matter signatures thanks to its capability to detect electrons and photons with an unprecedented energy resolution in an energy range going from few GeV up to 10 TeV. Moreover, the DAMPE satellite will contribute to a better understanding of the propagation mechanisms of high energy cosmic rays measuring the nuclei flux up to 100 TeV. DAMPE is composed of four sub-detectors: a plastic strip scintillator, a silicon-tungsten tracker-converter (STK), a BGO imaging calorimeter and a neutron detector. The STK is made of twelve layers of single-sided AC-coupled silicon micro-strip detectors for a total silicon area of about 7 $m^2$ . To promote the conversion of incident photons into electron-positron pairs, tungsten foils are inserted into the supporting structure. In this document, a detailed description of the STK constructi...

  8. Role of Heme and Heme-Proteins in Trypanosomatid Essential Metabolic Pathways

    Directory of Open Access Journals (Sweden)

    Karina E. J. Tripodi

    2011-01-01

    Full Text Available Around the world, trypanosomatids are known for being etiological agents of several highly disabling and often fatal diseases like Chagas disease (Trypanosoma cruzi, leishmaniasis (Leishmania spp., and African trypanosomiasis (Trypanosoma brucei. Throughout their life cycle, they must cope with diverse environmental conditions, and the mechanisms involved in these processes are crucial for their survival. In this review, we describe the role of heme in several essential metabolic pathways of these protozoans. Notwithstanding trypanosomatids lack of the complete heme biosynthetic pathway, we focus our discussion in the metabolic role played for important heme-proteins, like cytochromes. Although several genes for different types of cytochromes, involved in mitochondrial respiration, polyunsaturated fatty acid metabolism, and sterol biosynthesis, are annotated at the Tritryp Genome Project, the encoded proteins have not yet been deeply studied. We pointed our attention into relevant aspects of these protein functions that are amenable to be considered for rational design of trypanocidal agents.

  9. Mimicking Heme Enzymes in the Solid State: Metal-Organic Materials with Selectively Encapsulated Heme

    Energy Technology Data Exchange (ETDEWEB)

    Larsen, Randy W; Wojtas, Lukasz; Perman, Jason; Musselman, Ronald L; Zaworotko, Michael J; Vetromile, Carissa M [USF

    2011-06-13

    To carry out essential life processes, nature has had to evolve heme enzymes capable of synthesizing and manipulating complex molecules. These proteins perform a plethora of chemical reactions utilizing a single iron porphyrin active site embedded within an evolutionarily designed protein pocket. We herein report the first class of metal–organic materials (MOMs) that mimic heme enzymes in terms of both structure and reactivity. The MOMzyme-1 class is based upon a prototypal MOM, HKUST-1, into which catalytically active metalloporphyrins are selectively encapsulated in a “ship-in-a-bottle” fashion within one of the three nanoscale cages that exist in HKUST-1. MOMs offer unparalleled levels of permanent porosity and their modular nature affords enormous diversity of structures and properties. The MOMzyme-1 class could therefore represent a new paradigm for heme biomimetic catalysis since it combines the activity of a homogeneous catalyst with the stability and recyclability of heterogeneous catalytic systems within a single material.

  10. Mimicking heme enzymes in the solid state: metal-organic materials with selectively encapsulated heme.

    Science.gov (United States)

    Larsen, Randy W; Wojtas, Lukasz; Perman, Jason; Musselman, Ronald L; Zaworotko, Michael J; Vetromile, Carissa M

    2011-07-13

    To carry out essential life processes, nature has had to evolve heme enzymes capable of synthesizing and manipulating complex molecules. These proteins perform a plethora of chemical reactions utilizing a single iron porphyrin active site embedded within an evolutionarily designed protein pocket. We herein report the first class of metal-organic materials (MOMs) that mimic heme enzymes in terms of both structure and reactivity. The MOMzyme-1 class is based upon a prototypal MOM, HKUST-1, into which catalytically active metalloporphyrins are selectively encapsulated in a "ship-in-a-bottle" fashion within one of the three nanoscale cages that exist in HKUST-1. MOMs offer unparalleled levels of permanent porosity and their modular nature affords enormous diversity of structures and properties. The MOMzyme-1 class could therefore represent a new paradigm for heme biomimetic catalysis since it combines the activity of a homogeneous catalyst with the stability and recyclability of heterogeneous catalytic systems within a single material.

  11. Structural Damping with Friction Beams

    Directory of Open Access Journals (Sweden)

    L. Gaul

    2008-01-01

    Full Text Available In the last several years, there has been increasing interest in the use of friction joints for enhancing damping in structures. The joints themselves are responsible for the major part of the energy dissipation in assembled structures. The dissipated work in a joint depends on both the applied normal force and the excitation force. For the case of a constant amplitude excitation force, there is an optimal normal force which maximizes the damping. A ‘passive’ approach would be employed in this instance. In most cases however, the excitation force, as well as the interface parameters such as the friction coefficient, normal pressure distribution, etc., are not constant. In these cases, a ‘semi-active’ approach, which implements an active varying normal force, is necessary. For the ‘passive’ and ‘semi-active’ approaches, the normal force has to be measured. Interestingly, since the normal force in a friction joint influences the local stiffness, the natural frequencies of the assembled structure can be tuned by adjusting the normal force. Experiments and simulations are performed for a simple laboratory structure consisting of two superposed beams with friction in the interface. Numerical simulation of the friction interface requires non-linear models. The response of the double beam system is simulated using a numerical algorithm programmed in MATLAB which models point-to-point friction with the Masing friction model. Numerical predictions and measurements of the double beam free vibration response are compared. A practical application is then described, in which a friction beam is used to damp the vibrations of the work piece table on a milling machine. The increased damping of the table reduces vibration amplitudes, which in turn results in enhanced surface quality of the machined parts, reduction in machine tool wear, and potentially higher feed rates. Optimal positioning of the friction beams is based on knowledge of the mode

  12. Heme metabolism as an integral part of iron homeostasis

    Directory of Open Access Journals (Sweden)

    Paweł Lipiński

    2014-01-01

    Full Text Available Heme, a ferrous iron protoporphyrin IX complex, is employed as a prosthetic group in a number of diverse heme proteins that participate in important cellular and systemic physiological processes. Provision of an adequate amount of iron for heme biosynthesis is one of the elemental hallmarks of intracellular iron homeostasis. In the cell the bioavailability of iron for the two main iron biological pathways – heme synthesis and the biogenesis of iron-sulfur clusters ([Fe-S] – is mainly regulated by the IRP/IRE posttranscriptional system. The biogenesis of [Fe-S] centers is crucial for heme synthesis because these co-factors determine the activity of IRP1 and that of ferrochelatase, an enzyme responsible for the insertion of an iron into protoporphyrin IX to produce heme. On the other hand, delivery of iron for heme and hemoglobin synthesis in erythroblasts, precursors of erythrocytes in bone marrow, is an indispensable element of body iron homeostasis. This process relies on the recovery of iron from senescent red blood cells through the enzymatic degradation of heme molecules and recycling of iron to the circulation. Molecular coordination of these processes involves the activity of heme oxygenase 1, IRP1 and IRP2 as well as the functioning of the hepcidin-ferroportin regulatory axis. Recent studies show in mammals the existence of an expanded system of proteins involved in the transport of intact heme molecules at the cellular and systemic levels. The biological role of this system is of particular importance when the concentration of free heme reaches a toxic level in the body (intravascular hemolysis as well as locally in cells having intensive heme metabolism such as erythroblasts and macrophages.

  13. Holo- And Apo- Structures of Bacterial Periplasmic Heme Binding Proteins

    Energy Technology Data Exchange (ETDEWEB)

    Ho, W.W.; Li, H.; Eakanunkul, S.; Tong, Y.; Wilks, A.; Guo, M.; Poulos, T.L.

    2009-06-01

    An essential component of heme transport in Gram-negative bacterial pathogens is the periplasmic protein that shuttles heme between outer and inner membranes. We have solved the first crystal structures of two such proteins, ShuT from Shigella dysenteriae and PhuT from Pseudomonas aeruginosa. Both share a common architecture typical of Class III periplasmic binding proteins. The heme binds in a narrow cleft between the N- and C-terminal binding domains and is coordinated by a Tyr residue. A comparison of the heme-free (apo) and -bound (holo) structures indicates little change in structure other than minor alterations in the heme pocket and movement of the Tyr heme ligand from an 'in' position where it can coordinate the heme iron to an 'out' orientation where it points away from the heme pocket. The detailed architecture of the heme pocket is quite different in ShuT and PhuT. Although Arg{sup 228} in PhuT H-bonds with a heme propionate, in ShuT a peptide loop partially takes up the space occupied by Arg{sup 228}, and there is no Lys or Arg H-bonding with the heme propionates. A comparison of PhuT/ShuT with the vitamin B{sub 12}-binding protein BtuF and the hydroxamic-type siderophore-binding protein FhuD, the only two other structurally characterized Class III periplasmic binding proteins, demonstrates that PhuT/ShuT more closely resembles BtuF, which reflects the closer similarity in ligands, heme and B{sub 12}, compared with ligands for FhuD, a peptide siderophore.

  14. Protein oxidation mediated by heme-induced active site conversion specific for heme-regulated transcription factor, iron response regulator.

    Science.gov (United States)

    Kitatsuji, Chihiro; Izumi, Kozue; Nambu, Shusuke; Kurogochi, Masaki; Uchida, Takeshi; Nishimura, Shin-ichiro; Iwai, Kazuhiro; O'Brian, Mark R; Ikeda-Saito, Masao; Ishimori, Koichiro

    2016-01-05

    The Bradyrhizobium japonicum transcriptional regulator Irr (iron response regulator) is a key regulator of the iron homeostasis, which is degraded in response to heme binding via a mechanism that involves oxidative modification of the protein. Here, we show that heme-bound Irr activates O2 to form highly reactive oxygen species (ROS) with the "active site conversion" from heme iron to non-heme iron to degrade itself. In the presence of heme and reductant, the ROS scavenging experiments show that Irr generates H2O2 from O2 as found for other hemoproteins, but H2O2 is less effective in oxidizing the peptide, and further activation of H2O2 is suggested. Interestingly, we find a time-dependent decrease of the intensity of the Soret band and appearance of the characteristic EPR signal at g = 4.3 during the oxidation, showing the heme degradation and the successive formation of a non-heme iron site. Together with the mutational studies, we here propose a novel "two-step self-oxidative modification" mechanism, during which O2 is activated to form H2O2 at the heme regulatory motif (HRM) site and the generated H2O2 is further converted into more reactive species such as ·OH at the non-heme iron site in the His-cluster region formed by the active site conversion.

  15. ICAN/DAMP-integrated composite analyzer with damping analysis capabilities: User's manual

    Science.gov (United States)

    Saravanos, Dimitrious A.; Sanfeliz, Jose G.

    1992-01-01

    This manual describes the use of the computer code ICAN/DAMP (Integrated Composite Analyzer with Damping Analysis Capabilities) for the prediction of damping in polymer-matrix composites. The code is written in FORTRAN 77 and is a version of the ICAN (Integrated Composite ANalyzer) computer program. The code incorporates a new module for synthesizing the material damping from micromechanics to laminate level. Explicit micromechanics equations based on hysteretic damping are programmed relating the on-axis damping capacities to the fiber and matrix properties and fiber volume ratio. The damping capacities of unidirectional composites subjected to off-axis loading are synthesized from on-axis damping values. The hygrothermal effect on the damping performance of unidirectional composites caused by temperature and moisture variation is modeled along with the damping contributions from interfacial friction between broken fibers and matrix. The temperature rise is continuously vibrating composite plies and composite laminates is also estimated. The ICAN/DAMP user's manual provides descriptions of the damping analysis module's functions, structure, input requirements, output interpretation, and execution requirements. It only addresses the changes required to conduct the damping analysis and is used in conjunction with the 'Second Generation Integrated Composite Analyzer (ICAN) Computer Code' user's manual (NASA TP-3290).

  16. Modelling of Dampers and Damping in Structures

    DEFF Research Database (Denmark)

    Høgsberg, Jan Riess

    2006-01-01

    The present thesis consists of an extended summary and four papers concerning damping of structures and algorithmic damping in numerical analysis. The first part of the thesis deals with the efficiency and the tuning of external collocated dampers acting on flexible structures. The dynamics......, and thereby the damping, of flexible structures are generally described in terms of the dominant vibration modes. A system reduction technique, where the damped vibration mode is constructed as a linear combination of the undamped mode shape and the mode shape obtained by locking the damper, is applied....... This two-component representation leads to a simple solution for the modal damping representing the natural frequency and the associated damping ratio. It appears from numerical examples that this system reduction technique provides very accurate results. % Analytical expressions for the optimal tuning...

  17. Anisotropic damping of Timoshenko beam elements

    DEFF Research Database (Denmark)

    Hansen, M.H.

    2001-01-01

    This report contains a description of a structural damping model for Timoshenko beam elements used in the aeroelastic code HawC developed at Risø for modeling wind turbines. The model has been developed to enable modeling of turbine blades which oftenhave different damping characteristics...... for ¤flapwise¤, ¤edgewise¤ and ¤torsional¤ vibrations. The structural damping forces acting on the beam element are modeled by viscous damping described by an element damping matrix. The composition of this matrix is basedon the element mass and stiffness matrices. It is shown how the coefficients for the mass...... and stiffness contributions can be calibrated to give the desired modal damping in the complete model of a blade....

  18. Heme Recognition By a Staphylococcus Aureus IsdE

    Energy Technology Data Exchange (ETDEWEB)

    Grigg, J.C.; Vermeiren, C.L.; Heinrichs, D.E.; Murphy, M.E.P.

    2009-06-03

    Staphylococcus aureus is a Gram-positive bacterial pathogen and a leading cause of hospital acquired infections. Because the free iron concentration in the human body is too low to support growth, S. aureus must acquire iron from host sources. Heme iron is the most prevalent iron reservoir in the human body and a predominant source of iron for S. aureus. The iron-regulated surface determinant (Isd) system removes heme from host heme proteins and transfers it to IsdE, the cognate substrate-binding lipoprotein of an ATP-binding cassette transporter, for import and subsequent degradation. Herein, we report the crystal structure of the soluble portion of the IsdE lipoprotein in complex with heme. The structure reveals a bi-lobed topology formed by an N- and C-terminal domain bridged by a single {alpha}-helix. The structure places IsdE as a member of the helical backbone metal receptor superfamily. A six-coordinate heme molecule is bound in the groove established at the domain interface, and the heme iron is coordinated in a novel fashion for heme transporters by Met{sup 78} and His{sup 229}. Both heme propionate groups are secured by H-bonds to IsdE main chain and side chain groups. Of these residues, His{sup 299} is essential for IsdE-mediated heme uptake by S. aureus when growth on heme as a sole iron source is measured. Multiple sequence alignments of homologues from several other Gram-positive bacteria, including the human pathogens pyogenes, Bacillus anthracis, and Listeria monocytogenes, suggest that these other systems function equivalently to S. aureus IsdE with respect to heme binding and transport.

  19. Relationship between natural and heme-mediated antibody polyreactivity

    Energy Technology Data Exchange (ETDEWEB)

    Hadzhieva, Maya; Vassilev, Tchavdar [Stephan Angelov Institute of Microbiology, Bulgarian Academy of Sciences, Sofia 1113 (Bulgaria); Bayry, Jagadeesh; Kaveri, Srinivas; Lacroix-Desmazes, Sébastien [Sorbonne Universités, UPMC Univ Paris 06, UMR-S 1138, Centre de Recherche des Cordeliers, F-75006 Paris (France); INSERM, UMR-S 1138, F-75006 Paris (France); Université Paris Descartes, Sorbonne Paris Cité, UMR-S 1138, F-75006 Paris (France); Dimitrov, Jordan D., E-mail: jordan.dimitrov@crc.jussieu.fr [Sorbonne Universités, UPMC Univ Paris 06, UMR-S 1138, Centre de Recherche des Cordeliers, F-75006 Paris (France); INSERM, UMR-S 1138, F-75006 Paris (France); Université Paris Descartes, Sorbonne Paris Cité, UMR-S 1138, F-75006 Paris (France)

    2016-03-25

    Polyreactive antibodies represent a considerable fraction of the immune repertoires. Some antibodies acquire polyreactivity post-translationally after interaction with various redox-active substances, including heme. Recently we have demonstrated that heme binding to a naturally polyreactive antibody (SPE7) results in a considerable broadening of the repertoire of recognized antigens. A question remains whether the presence of certain level of natural polyreactivity of antibodies is a prerequisite for heme-induced further extension of antigen binding potential. Here we used a second monoclonal antibody (Hg32) with unknown specificity and absence of intrinsic polyreactivity as a model to study the potential of heme to induce polyreactivity of antibodies. We demonstrated that exposure to heme greatly extends the antigen binding potential of Hg32, suggesting that the intrinsic binding promiscuity is not a prerequisite for the induction of polyreactivity by heme. In addition we compared the kinetics and thermodynamics of the interaction of heme-exposed antibodies with a panel of unrelated antigens. These analyses revealed that the two heme-sensitive antibodies adopt different mechanisms of binding to the same set of antigens. This study contributes to understanding the phenomenon of induced antibody polyreactivity. The data may also be of importance for understanding of physiological and pathological roles of polyreactive antibodies. - Highlights: • Exposure of certain monoclonal IgE antibodies to heme results in gain of antigen binding polyreactivity. • Natural polyreactivity of antibodies is dispensable for acquisition of polyreactivity through interaction with heme. • Heme-induced monoclonal IgE antibodies differ in their thermodynamic mechanisms of antigen recognition.

  20. CHARACTERIZATION OF DAMPING IN BOLTED LAP JOINTS

    Energy Technology Data Exchange (ETDEWEB)

    C. MALONEY; D. PEAIRS; ET AL

    2000-08-01

    The dynamic response of a jointed beam was measured in laboratory experiments. The data were analyzed and the system was mathematically modeled to establish plausible representations of joint damping behavior. Damping is examined in an approximate, local linear framework using log decrement and half power bandwidth approaches. in addition, damping is modeled in a nonlinear framework using a hybrid surface irregularities model that employs a bristles-construct. Experimental and analytical results are presented.

  1. Phenomenology of chiral damping in noncentrosymmetric magnets

    KAUST Repository

    Akosa, Collins Ashu

    2016-06-21

    A phenomenology of magnetic chiral damping is proposed in the context of magnetic materials lacking inversion symmetry. We show that the magnetic damping tensor acquires a component linear in magnetization gradient in the form of Lifshitz invariants. We propose different microscopic mechanisms that can produce such a damping in ferromagnetic metals, among which local spin pumping in the presence of an anomalous Hall effect and an effective “s-d” Dzyaloshinskii-Moriya antisymmetric exchange. The implication of this chiral damping in terms of domain-wall motion is investigated in the flow and creep regimes.

  2. Parametric Landau damping of space charge modes

    Energy Technology Data Exchange (ETDEWEB)

    Macridin, Alexandru [Fermilab; Burov, Alexey [Fermilab; Stern, Eric [Fermilab; Amundson, James [Fermilab; Spentzouris, Panagiotis [Fermilab

    2016-09-23

    Landau damping is the mechanism of plasma and beam stabilization; it arises through energy transfer from collective modes to the incoherent motion of resonant particles. Normally this resonance requires the resonant particle's frequency to match the collective mode frequency. We have identified an important new damping mechanism, parametric Landau damping, which is driven by the modulation of the mode-particle interaction. This opens new possibilities for stability control through manipulation of both particle and mode-particle coupling spectra. We demonstrate the existence of parametric Landau damping in a simulation of transverse coherent modes of bunched accelerator beams with space charge.

  3. Heme oxygenase-1, oxidation, inflammation and atherosclerosis

    Directory of Open Access Journals (Sweden)

    Jesus A Araujo

    2012-07-01

    Full Text Available Atherosclerosis is an inflammatory process of the vascular wall characterized by the infiltration of lipids and inflammatory cells. Oxidative modifications of infiltrating low density lipoproteins and induction of oxidative stress play a major role in lipid retention in the vascular wall, uptake by macrophages and generation of foam cells, a hallmark of this disorder. The vasculature has a plethora of protective resources against oxidation and inflammation, many of them regulated by the Nrf2 transcription factor. Heme oxygenase-1 (HO-1 is a Nrf2-regulated gene that plays a critical role in the prevention of vascular inflammation. It is the inducible isoform of heme oxygenase, responsible for the oxidative cleavage of heme groups leading to the generation of biliverdin, carbon monoxide and release of ferrous iron. HO-1 has important antioxidant, antiinflammatory, antiapoptotic, antiproliferative and immunomodulatory effects in vascular cells, most of which play a significant role in the protection against atherogenesis. HO-1 may also be an important feature in macrophage differentiation and polarization to certain subtypes. The biological effects of HO-1 are largely attributable to its enzymatic activity, which can be conceived as a system with three arms of action, corresponding to its three enzymatic byproducts. HO-1 mediated vascular protection may be due to a combination of systemic and vascular local effects. It is usually expressed at low levels but can be highly upregulated in the presence of several proatherogenic stimuli. The HO-1 system is amenable for use in the development of new therapies, some of them currently under experimental and clinical trials. Interestingly, in contrast to the HO-1 antiatherogenic actions, the expression of its transcriptional regulator Nrf2 leads to proatherogenic effects instead. This article reviews the evidence that supports the antiatherogenic role of HO-1, potential pathways and mechanisms mediating

  4. Superconductive material and magnetic field for damping and levitation support and damping of cryogenic instruments

    Science.gov (United States)

    Dolgin, Benjamin P. (Inventor)

    1994-01-01

    A superconductive load bearing support without a mechanical contact and vibration damping for cryogenic instruments in space is presented. The levitation support and vibration damping is accomplished by the use of superconducting magnets and the 'Meissner' effect. The assembly allows for transfer of vibration energy away from the cryogenic instrument which then can be damped by the use of either an electronic circuit or conventional vibration damping mean.

  5. Heme Distortions in Sperm-Whale Carbonmonoxy Myoglobin: Correlations between Rotational Strengths and Heme Distortions in MD-Generated Structures

    Energy Technology Data Exchange (ETDEWEB)

    KIEFL,CHRISTOPH; SCREERAMA,NARASIMHA; LU,YI; QIU,YAN; SHELNUTT,JOHN A.; WOODY,ROBERT W.

    2000-07-13

    The authors have investigated the effects of heme rotational isomerism in sperm-whale carbonmonoxy myoglobin using computational techniques. Several molecular dynamics simulations have been performed for the two rotational isomers A and B, which are related by a 180{degree} rotation around the {alpha}-{gamma} axis of the heme, of sperm-whale carbonmonoxy myoglobin in water. Both neutron diffraction and NMR structures were used as starting structures. In the absence of an experimental structure, the structure of isomer B was generated by rotating the heme in the structure of isomer A. Distortions of the heme from planarity were characterized by normal coordinate structural decomposition and by the angle of twist of the pyrrole rings from the heme plane. The heme distortions of the neutron diffraction structure were conserved in the MD trajectories, but in the NMR-based trajectories, where the heme distortions are less well defined, they differ from the original heme deformations. The protein matrix induced similar distortions on the heroes in orientations A and B. The results suggest that the binding site prefers a particular macrocycle conformation, and a 180{degree} rotation of the heme does not significantly alter the protein's preference for this conformation. The intrinsic rotational strengths of the two Soret transitions, separated according to their polarization in the heme plane, show strong correlations with the ruf-deformation and the average twist angle of the pyrrole rings. The total rotational strength, which includes contributions from the chromophores in the protein, shows a weaker correlation with heme distortions.

  6. Heme acquisition mechanisms of Porphyromonas gingivalis - strategies used in a polymicrobial community in a heme-limited host environment.

    Science.gov (United States)

    Smalley, J W; Olczak, T

    2017-02-01

    Porphyromonas gingivalis, a main etiologic agent and key pathogen responsible for initiation and progression of chronic periodontitis requires heme as a source of iron and protoporphyrin IX for its survival and the ability to establish an infection. Porphyromonas gingivalis is able to accumulate a defensive cell-surface heme-containing pigment in the form of μ-oxo bisheme. The main sources of heme for P. gingivalis in vivo are hemoproteins present in saliva, gingival crevicular fluid, and erythrocytes. To acquire heme, P. gingivalis uses several mechanisms. Among them, the best characterized are those employing hemagglutinins, hemolysins, and gingipains (Kgp, RgpA, RgpB), TonB-dependent outer-membrane receptors (HmuR, HusB, IhtA), and hemophore-like proteins (HmuY, HusA). Proteins involved in intracellular heme transport, storage, and processing are less well characterized (e.g. PgDps). Importantly, P. gingivalis may also use the heme acquisition systems of other bacteria to fulfill its own heme requirements. Porphyromonas gingivalis displays a novel paradigm for heme acquisition from hemoglobin, whereby the Fe(II)-containing oxyhemoglobin molecule must first be oxidized to methemoglobin to facilitate heme release. This process not only involves P. gingivalis arginine- and lysine-specific gingipains, but other proteases (e.g. interpain A from Prevotella intermedia) or pyocyanin produced by Pseudomonas aeruginosa. Porphyromonas gingivalis is then able to fully proteolyze the more susceptible methemoglobin substrate to release free heme or to wrest heme from it directly through the use of the HmuY hemophore. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  7. Dietary heme-mediated PPARα activation does not affect the heme-induced epithelial hyperproliferation and hyperplasia in mouse colon.

    Directory of Open Access Journals (Sweden)

    Noortje Ijssennagger

    Full Text Available Red meat consumption is associated with an increased colon cancer risk. Heme, present in red meat, injures the colon surface epithelium by luminal cytotoxicity and reactive oxygen species. This surface injury is overcompensated by hyperproliferation and hyperplasia of crypt cells. Transcriptome analysis of mucosa of heme-fed mice showed, besides stress- and proliferation-related genes, many upregulated lipid metabolism-related PPARα target genes. The aim of this study was to investigate the role of PPARα in heme-induced hyperproliferation and hyperplasia. Male PPARα KO and WT mice received a purified diet with or without heme. As PPARα is proposed to protect against oxidative stress and lipid peroxidation, we hypothesized that the absence of PPARα leads to more surface injury and crypt hyperproliferation in the colon upon heme-feeding. Heme induced luminal cytotoxicity and lipid peroxidation and colonic hyperproliferation and hyperplasia to the same extent in WT and KO mice. Transcriptome analysis of colonic mucosa confirmed similar heme-induced hyperproliferation in WT and KO mice. Stainings for alkaline phosphatase activity and expression levels of Vanin-1 and Nrf2-targets indicated a compromised antioxidant defense in heme-fed KO mice. Our results suggest that the protective role of PPARα in antioxidant defense involves the Nrf2-inhibitor Fosl1, which is upregulated by heme in PPARα KO mice. We conclude that PPARα plays a protective role in colon against oxidative stress, but PPARα does not mediate heme-induced hyperproliferation. This implies that oxidative stress of surface cells is not the main determinant of heme-induced hyperproliferation and hyperplasia.

  8. Dioxygen reactivity of meso-hydroxylated hemes: intermediates in ...

    Indian Academy of Sciences (India)

    464. Scheme 2. in which the HO-bound heme could be converted to verdoheme and biliverdin by ascorbic acid or hydra- zine in the absence of NADPH and cytochrome. P450 reductase via the formation of similar interme- diates observed during the biological oxidation of heme by HO.2–7 The process involves initial meso.

  9. Heme oxygenase-1 and carbon monoxide in pulmonary medicine

    NARCIS (Netherlands)

    Slebos, DJ; Ryter, SW; Choi, AMK

    2003-01-01

    Heme oxygenase-1 (HO-1), an inducible stress protein, confers cytoprotection against oxidative stress in vitro and in vivo. In addition to its physiological role in heme degradation, HO-1 may influence a number of cellular processes, including growth, inflammation, and apoptosis. By virtue of

  10. Synthetic Heme/Copper Assemblies: Toward an Understanding of Cytochrome c Oxidase Interactions with Dioxygen and Nitrogen Oxides

    Science.gov (United States)

    Hematian, Shabnam; Garcia-Bosch, Isaac; Karlin, Kenneth D.

    2016-01-01

    Conspectus Our long-time niche in synthetic biological inorganic chemistry has been to design ligands and generate coordination complexes of copper and/or iron ions, those reacting with dioxygen (O2) and/or nitrogen oxides (e.g., nitric oxide (NO(g)) and nitrite (NO2−)). As inspiration for this work, we turn to mitochondrial cytochrome c oxidase which is responsible for dioxygen consumption and is also the predominant target for NO(g) and nitrite within mitochondria. In this Account, we highlight recent advances in studying synthetic heme/Cu complexes in two respects. First, there is the design, synthesis and characterization of new O2-adducts whose further study will add insights into O2-reductive cleavage chemistry. Second, we describe how related heme/Cu constructs reduce nitrite ion to NO(g) or the reverse, oxidize NO(g) to nitrite. The reactions of nitrogen oxides occur as part of CcO’s function, which is intimately tied to cellular O2-balance. We had first discovered that reduced heme/Cu compounds react with O2 giving μ-oxo heme-FeIII-O-CuII(L) products; their properties are discussed. The O-atom is derived from dioxygen and interrogations of these systems led to the construction and characterization of three distinctive classes of heme-peroxo-complexes, two high-spin and one low-spin species. Recent investigations include a new approach to the synthesis of low-spin heme-peroxo-Cu complexes, employing a “naked” synthon, where the copper ligand denticity and geometric types can be varied. The result is a collection of such complexes; spectroscopic and structural features (by DFT calculations) are described. Some of these compounds are reactive toward reductants/protons effecting subsequent O-O cleavage. This points to how subtle improvements in ligand environment lead to a desired local structure and resulting optimized reactivity, as known to occur at enzyme active-sites. The other sector of research is focused on heme/Cu assemblies mediating the

  11. Susceptibility for cigarette smoke-induced DAMP release and DAMP-induced inflammation in COPD.

    Science.gov (United States)

    Pouwels, Simon D; Hesse, Laura; Faiz, Alen; Lubbers, Jaap; Bodha, Priya K; Ten Hacken, Nick H T; van Oosterhout, Antoon J M; Nawijn, Martijn C; Heijink, Irene H

    2016-11-01

    Cigarette smoke (CS) exposure is a major risk factor for chronic obstructive pulmonary disease (COPD). We investigated whether CS-induced damage-associated molecular pattern (DAMP) release or DAMP-mediated inflammation contributes to susceptibility for COPD. Samples, including bronchial brushings, were collected from young and old individuals, susceptible and nonsusceptible for the development of COPD, before and after smoking, and used for gene profiling and airway epithelial cell (AEC) culture. AECs were exposed to CS extract (CSE) or specific DAMPs. BALB/cByJ and DBA/2J mice were intranasally exposed to LL-37 and mitochondrial (mt)DAMPs. Functional gene-set enrichment analysis showed that CS significantly increases the airway epithelial gene expression of DAMPs and DAMP receptors in COPD patients. In cultured AECs, we observed that CSE induces necrosis and DAMP release, with specifically higher galectin-3 release from COPD-derived compared with control-derived cells. Galectin-3, LL-37, and mtDAMPs increased CXCL8 secretion in AECs. LL-37 and mtDAMPs induced neutrophilic airway inflammation, exclusively in mice susceptible for CS-induced airway inflammation. Collectively, we show that in airway epithelium from COPD patients, the CS-induced expression of DAMPs and DAMP receptors in vivo and the release of galectin-3 in vitro is exaggerated. Furthermore, our studies indicate that a predisposition to release DAMPs and subsequent induction of inflammation may contribute to the development of COPD. Copyright © 2016 the American Physiological Society.

  12. Effect of damping on the time variation of fields produced by a small pole tip with a soft under layer

    OpenAIRE

    Gao, K.Z.; Chantrell, R.W.; Boerner, E.D.

    2004-01-01

    The time variation of magnetostatic fields generated by space and time varying magnetization configurations in small perpendicular pole tips is studied. The magnetization configurations are a response to external fields driving the pole tip and soft under layer (SUL). When the system damping is sufficiently small the magnetization excitations persist for a long time after reversal. The effects of damping parameter, position in the media, and discretization cell size on the magnitude of the ti...

  13. Functional characterization of the Shigella dysenteriae heme ABC transporter.

    Science.gov (United States)

    Burkhard, Kimberly A; Wilks, Angela

    2008-08-05

    The heme ATP binding cassette (ABC) transporter, ShuUV, of Shigella dysenteriae has been incorporated into proteoliposomes. Functional characterization of ShuUV revealed that ATP hydrolysis and transport of heme from the periplasmic binding protein, ShuT, to the cytoplasmic binding protein, ShuS, are coupled. Site-directed mutagenesis of ShuT residues proposed to be required for stabilization of the complex abolished heme transport. Furthermore, residues His-252 and His-262, located in the translocation channel of ShuU, were required for the release of heme from ShuT and translocation to ShuS. The initial functional characterization of an in vitro heme uptake system provides a platform for future spectroscopic studies.

  14. Covalent heme attachment to the protein in human heme oxygenase-1 with selenocysteine replacing the His25 proximal iron ligand.

    Science.gov (United States)

    Jiang, Yongying; Trnka, Michael J; Medzihradszky, Katalin F; Ouellet, Hugues; Wang, Yongqiang; Ortiz de Montellano, Paul R

    2009-03-01

    To characterize heme oxygenase with a selenocysteine (SeCys) as the proximal iron ligand, we have expressed truncated human heme oxygenase-1 (hHO-1) His25Cys, in which Cys-25 is the only cysteine, in the Escherichia coli cysteine auxotroph strain BL21(DE3)cys. Selenocysteine incorporation into the protein was demonstrated by both intact protein mass measurement and mass spectrometric identification of the selenocysteine-containing tryptic peptide. One selenocysteine was incorporated into approximately 95% of the expressed protein. Formation of an adduct with Ellman's reagent (DTNB) indicated that the selenocysteine in the expressed protein was in the reduced state. The heme-His25SeCys hHO-1 complex could be prepared by either (a) supplementing the overexpression medium with heme, or (b) reconstituting the purified apoprotein with heme. Under reducing conditions in the presence of imidazole, a covalent bond is formed by addition of the selenocysteine residue to one of the heme vinyl groups. No covalent bond is formed when the heme is replaced by mesoheme, in which the vinyls are replaced by ethyl groups. These results, together with our earlier demonstration that external selenolate ligands can transfer an electron to the iron [Y. Jiang, P.R. Ortiz de Montellano, Inorg. Chem. 47 (2008) 3480-3482 ], indicate that a selenyl radical is formed in the hHO-1 His25SeCys mutant that adds to a heme vinyl group.

  15. Gyroscopic Stabilization of Indefinite Damped Systems

    DEFF Research Database (Denmark)

    Kliem, Wolfhard; Müller, Peter C.

    1997-01-01

    Modelling of mechanical systems with sliding bearings, or with dry friction, can lead to linear systems with an indefinite damping matrix. We ask under what conditions such a system is unstable (the indefiniteness of the damping matrix is not enough) and under what conditions we can stabilize the...... the system by adding a gyroscopic term....

  16. Damping device for a stationary labyrinth seal

    Science.gov (United States)

    El-Aini, Yehia M. (Inventor); Mitchell, William S. (Inventor); Roberts, Lawrence P. (Inventor); Montgomery, Stuart K. (Inventor); Davis, Gary A. (Inventor)

    2010-01-01

    A stationary labyrinth seal system includes a seal housing having an annular cavity, a plurality of damping devices, and a retaining ring. The damping devices are positioned within the annular cavity and are maintained within the annular cavity by the retaining ring.

  17. DAMPs from death to new life

    Directory of Open Access Journals (Sweden)

    Emilie eVénéreau

    2015-08-01

    Full Text Available Our body handles tissue damage by activating the immune system in response to intracellularmolecules released by injured tissues (Damage-Associated Molecular Patterns, DAMPs, in a similar way as it detects molecular motifs conserved in pathogens (pathogen-associated molecular patterns, PAMPs. DAMPs are molecules that have a physiological role inside the cell, but acquire additional functions when they are released outside the cell: they alert the body about danger, stimulate an inflammatory response, and finally promote the regeneration process. Beside their passive release by dead cells, some DAMPs can be secreted or exposed by living cells undergoing a life-threatening stress. DAMPs have been linked to inflammation and related disorders: hence, inhibition of DAMP-mediated inflammatory responses is a promising strategy to improve the clinical management of infection- and injury-elicited inflammatory diseases. However, it is important to consider that DAMPs are not only danger signals but also central players in tissue repair. Indeed, some DAMPs have been studied for their role in tissue healing after sterile or infection-associated inflammation. This review is focused on two exemplary DAMPs, HMGB1 and ATP, and their contribution to both inflammation and tissue repair.

  18. Damping-off in forest nurseries

    Science.gov (United States)

    Carl Hartley

    1921-01-01

    Damping-off is the commonest English name for a symptomatic group of diseases affecting great numbers of plant species of widely separated phylogenetic groups. It is commonly used for any disease which results in the rapid decay of young succulent seedlings or soft cuttings. Young shoots from underground rootstocks may also be damped-off before they break through the...

  19. Modified Composite Struts Would Damp Vibrations

    Science.gov (United States)

    Chen, Gun-Shing; Dolgin, Benjamin P.

    1993-01-01

    Composite-material (fiber/matrix laminate) struts damping longitudinal vibrations fabricated more easily in proposed new design. Prior design described in "Composite Struts Would Damp Vibrations" (NPO-17914). New design similar except pattern of fibers includes rounded bends (instead of sharp bends) in fibers.

  20. On Collisionless Damping of Ion Acoustic Waves

    DEFF Research Database (Denmark)

    Jensen, Vagn Orla; Petersen, P.I.

    1973-01-01

    Exact theoretical treatments show that the damping of ion acoustic waves in collisionless plasmas does not vanish when the derivative of the undisturbed distribution function at the phase velocity equals zero.......Exact theoretical treatments show that the damping of ion acoustic waves in collisionless plasmas does not vanish when the derivative of the undisturbed distribution function at the phase velocity equals zero....

  1. Reverse Logistics

    OpenAIRE

    Kulikova, Olga

    2016-01-01

    This thesis was focused on the analysis of the concept of reverse logistics and actual reverse processes which are implemented in mining industry and finding solutions for the optimization of reverse logistics in this sphere. The objective of this paper was the assessment of the development of reverse logistics in mining industry on the example of potash production. The theoretical part was based on reverse logistics and mining waste related literature and provided foundations for further...

  2. Allergy and respiratory health effects of dampness and dampness-related agents in schools and homes

    DEFF Research Database (Denmark)

    Holst, G; Høst, Arne; Doekes, G

    2016-01-01

    Little is known about the health effects of school-related indoor dampness and microbial exposures. In this study we investigated dampness and dampness-related agents in both homes and schools and their association with allergy and respiratory health effects in 330 Danish pupils. Classroom dampness...... was identified based on technical inspection and bedroom dampness on parents' self-report. Classroom and bedroom dust was analysed for seven microbial components. Skin-prick-testing determined atopic sensitisation. Lung function was expressed as z-scores for forced expiratory volume in one second (zFEV1...... ), forced vital capacity (zFVC) and the ratio zFEV1 /zFVC using GLI-2012-prediction-equations. The parents reported children's allergies, airway symptoms and doctor-diagnosed asthma. High classroom dampness, but not bedroom dampness, was negatively associated with zFEV1 (β-coef. -0.71; 95%CI -1.17 - -0...

  3. The mitochondrial heme exporter FLVCR1b mediates erythroid differentiation.

    Science.gov (United States)

    Chiabrando, Deborah; Marro, Samuele; Mercurio, Sonia; Giorgi, Carlotta; Petrillo, Sara; Vinchi, Francesca; Fiorito, Veronica; Fagoonee, Sharmila; Camporeale, Annalisa; Turco, Emilia; Merlo, Giorgio R; Silengo, Lorenzo; Altruda, Fiorella; Pinton, Paolo; Tolosano, Emanuela

    2012-12-01

    Feline leukemia virus subgroup C receptor 1 (FLVCR1) is a cell membrane heme exporter that maintains the balance between heme levels and globin synthesis in erythroid precursors. It was previously shown that Flvcr1-null mice died in utero due to a failure of erythropoiesis. Here, we identify Flvcr1b, a mitochondrial Flvcr1 isoform that promotes heme efflux into the cytoplasm. Flvcr1b overexpression promoted heme synthesis and in vitro erythroid differentiation, whereas silencing of Flvcr1b caused mitochondrial heme accumulation and termination of erythroid differentiation. Furthermore, mice lacking the plasma membrane isoform (Flvcr1a) but expressing Flvcr1b had normal erythropoiesis, but exhibited hemorrhages, edema, and skeletal abnormalities. Thus, FLVCR1b regulates erythropoiesis by controlling mitochondrial heme efflux, whereas FLVCR1a expression is required to prevent hemorrhages and edema. The aberrant expression of Flvcr1 isoforms may play a role in the pathogenesis of disorders characterized by an imbalance between heme and globin synthesis.

  4. The effect of proteins from animal source foods on heme iron bioavailability in humans.

    Science.gov (United States)

    Pizarro, Fernando; Olivares, Manuel; Valenzuela, Carolina; Brito, Alex; Weinborn, Valerie; Flores, Sebastián; Arredondo, Miguel

    2016-04-01

    Forty-five women (35-45 year) were randomly assigned to three iron (Fe) absorption sub-studies, which measured the effects of dietary animal proteins on the absorption of heme Fe. Study 1 was focused on heme, red blood cell concentrate (RBCC), hemoglobin (Hb), RBCC+beef meat; study 2 on heme, heme+fish, chicken, and beef; and study 3 on heme and heme+purified animal protein (casein, collagen, albumin). Study 1: the bioavailability of heme Fe from Hb was similar to heme only (∼13.0%). RBCC (25.0%) and RBCC+beef (21.3%) were found to be increased 2- and 1.6-fold, respectively, when compared with heme alone (pProteins from animal source foods and their digestion products did not enhance heme Fe absorption. Copyright © 2015. Published by Elsevier Ltd.

  5. Absorption by Isolated Ferric Heme Nitrosyl Cations In Vacuo

    DEFF Research Database (Denmark)

    Wyer, Jean; Nielsen, Steen Brøndsted

    2012-01-01

    Keywords:biophysics;gas-phase spectroscopy;heme proteins;mass spectrometry;nitric oxide Almost innocent: In photobiophysical studies of ferric heme nitrosyl complexes, the absorption spectra of six-coordinate complexes with NO and Met or Cys are similar to that of the five-coordinate complex ion ......(heme)(NO)+. Since the absorption spectra of related proteins with histidine as the proximal ligand are similar to those of the gaseous complexes, the protein microenvironment has little effect on the lowest-energy transition of the porphyrin macrocycle....

  6. [Hereditary porphyrias and heme related disorders].

    Science.gov (United States)

    Puy, Hervé; Gouya, Laurent; Deybach, Jean-charles

    2014-06-01

    Hereditary porphyrias comprise a group of eight metabolic disorders of the haem biosynthesis pathway, characterised by acute neurovisceral symptoms and/or skin lesions. Each porphyria is caused by abnormal functioning of a particular enzymatic step, resulting in specific accumulation of heme precursors. Seven porphyrias are due to a partial enzyme deficiency, while a gain-of-function mechanism has recently been identify in a novel porphyria. Acute porphyrias present with severe abdominal pain, nausea, constipation and confusion, and are sometimes complicated by seizures and severe neurological disorders, which may be life-threatening. Cutaneous porphyrias can also be present, with either acute painful photosensitivity or skin fragility and blisters. Rare recessive porphyrias usually manifest in early childhood with either severe chronic neurological symptoms or chronic haemolysis and severe cutaneous photosensitivity. Porphyrias are still under-diagnosed, but recent advances in the pathogenesis and genetics of human porphyrias are leading to better care of these patients and their families.

  7. Discovery of Intracellular Heme-binding Protein HrtR, Which Controls Heme Efflux by the Conserved HrtB-HrtA Transporter in Lactococcus lactis*

    Science.gov (United States)

    Lechardeur, Delphine; Cesselin, Bénédicte; Liebl, Ursula; Vos, Marten H.; Fernandez, Annabelle; Brun, Célia; Gruss, Alexandra; Gaudu, Philippe

    2012-01-01

    Most commensal and food bacteria lack heme biosynthesis genes. For several of these, the capture of environmental heme is a means of activating aerobic respiration metabolism. Our previous studies in the Gram-positive bacterium Lactococcus lactis showed that heme exposure strongly induced expression of a single operon, called here hrtRBA, encoding an ortholog of the conserved membrane hrt (heme-regulated transporter) and a unique transcriptional regulator that we named HrtR. We show that HrtR expressed as a fusion protein is a heme-binding protein. Heme iron interaction with HrtR is non-covalent, hexacoordinated, and involves two histidines, His-72 and His-149. HrtR specifically binds a 15-nt palindromic sequence in the hrtRBA promoter region, which is needed for hrtRBA repression. HrtR-DNA binding is abolished by heme addition, which activates expression of the HrtB-HrtA (HrtBA) transporter in vitro and in vivo. The use of HrtR as an intracellular heme sensor appears to be conserved among numerous commensal bacteria, in contrast with numerous Gram-positive pathogens that use an extracellular heme-sensing system, HssRS, to regulate hrt. Finally, we show for the first time that HrtBA permease controls heme toxicity by its direct and specific efflux. The use of an intracellular heme sensor to control heme efflux constitutes a novel paradigm for bacterial heme homeostasis. PMID:22084241

  8. Discovery of intracellular heme-binding protein HrtR, which controls heme efflux by the conserved HrtB-HrtA transporter in Lactococcus lactis.

    Science.gov (United States)

    Lechardeur, Delphine; Cesselin, Bénédicte; Liebl, Ursula; Vos, Marten H; Fernandez, Annabelle; Brun, Célia; Gruss, Alexandra; Gaudu, Philippe

    2012-02-10

    Most commensal and food bacteria lack heme biosynthesis genes. For several of these, the capture of environmental heme is a means of activating aerobic respiration metabolism. Our previous studies in the Gram-positive bacterium Lactococcus lactis showed that heme exposure strongly induced expression of a single operon, called here hrtRBA, encoding an ortholog of the conserved membrane hrt (heme-regulated transporter) and a unique transcriptional regulator that we named HrtR. We show that HrtR expressed as a fusion protein is a heme-binding protein. Heme iron interaction with HrtR is non-covalent, hexacoordinated, and involves two histidines, His-72 and His-149. HrtR specifically binds a 15-nt palindromic sequence in the hrtRBA promoter region, which is needed for hrtRBA repression. HrtR-DNA binding is abolished by heme addition, which activates expression of the HrtB-HrtA (HrtBA) transporter in vitro and in vivo. The use of HrtR as an intracellular heme sensor appears to be conserved among numerous commensal bacteria, in contrast with numerous Gram-positive pathogens that use an extracellular heme-sensing system, HssRS, to regulate hrt. Finally, we show for the first time that HrtBA permease controls heme toxicity by its direct and specific efflux. The use of an intracellular heme sensor to control heme efflux constitutes a novel paradigm for bacterial heme homeostasis.

  9. YC-1 activation of human soluble guanylyl cyclase has both heme-dependent and heme-independent components

    Science.gov (United States)

    Martin, E.; Lee, Y. C.; Murad, F.

    2001-01-01

    YC-1 [3-(5'-hydroxymethyl-2'furyl)-1-benzyl indazole] is an allosteric activator of soluble guanylyl cyclase (sGC). YC-1 increases the catalytic rate of the enzyme and sensitizes the enzyme toward its gaseous activators nitric oxide or carbon monoxide. In other studies the administration of YC-1 to experimental animals resulted in the inhibition of the platelet-rich thrombosis and a decrease of the mean arterial pressure, which correlated with increased cGMP levels. However, details of YC-1 interaction with sGC and enzyme activation are incomplete. Although evidence in the literature indicates that YC-1 activation of sGC is strictly heme-dependent, this report presents evidence for both heme-dependent and heme-independent activation of sGC by YC-1. The oxidation of the sGC heme by 1H-(1,2,4)oxadiazole(4,3-a)quinoxalin-1-one completely inhibited the response to NO, but only partially attenuated activation by YC-1. We also observed activation by YC-1 of a mutant sGC, which lacks heme. These findings indicate that YC-1 activation of sGC can occur independently of heme, but that activation is substantially increased when the heme moiety is present in the enzyme.

  10. Introduction of a covalent histidine-heme linkage in a hemoglobin: a promising tool for heme protein engineering.

    Science.gov (United States)

    Rice, Selena L; Preimesberger, Matthew R; Johnson, Eric A; Lecomte, Juliette T J

    2014-12-01

    The hemoglobins of the cyanobacteria Synechococcus and Synechocystis (GlbNs) are capable of spontaneous and irreversible attachment of the b heme to the protein matrix. The reaction, which saturates the heme 2-vinyl by addition of a histidine residue, is reproduced in vitro by preparing the recombinant apoprotein, adding ferric heme, and reducing the iron to the ferrous state. Spontaneous covalent attachment of the heme is potentially useful for protein engineering purposes. Thus, to explore whether the histidine-heme linkage can serve in such applications, we attempted to introduce it in a test protein. We selected as our target the heme domain of Chlamydomonas eugametos LI637 (CtrHb), a eukaryotic globin that exhibits less than 50% sequence identity with the cyanobacterial GlbNs. We chose two positions, 75 in the FG corner and 111 in the H helix, to situate a histidine near a vinyl group. We characterized the proteins with gel electrophoresis, absorbance spectroscopy, and NMR analysis. Both T111H and L75H CtrHbs reacted upon reduction of the ferric starting material containing cyanide as the distal ligand to the iron. With L75H CtrHb, nearly complete (>90%) crosslinking was observed to the 4-vinyl as expected from the X-ray structure of wild-type CtrHb. Reaction of T111H CtrHb also occurred at the 4-vinyl, in a 60% yield indicating a preference for the flipped heme orientation in the starting material. The work suggests that the His-heme modification will be applicable to the design of proteins with a non-dissociable heme group. Copyright © 2014 Elsevier Inc. All rights reserved.

  11. Radiation damping of a polarizable particle

    Science.gov (United States)

    Novotny, Lukas

    2017-09-01

    A polarizable body moving in an external electromagnetic field will slow down. This effect is referred to as radiation damping and is analogous to Doppler cooling in atomic physics. Using the principles of special relativity we derive an expression for the radiation damping force and find that it solely depends on the scattered power. The cooling of the particle's center-of-mass motion is balanced by heating due to radiation pressure shot noise, giving rise to an equilibrium that depends on the ratio of the field's frequency and the particle's mass. While damping is of relativistic nature, heating has its roots in quantum mechanics.

  12. Lifetime measurement of ATF damping ring

    Energy Technology Data Exchange (ETDEWEB)

    Okugi, T. [Tokyo Metropolitan Univ. (Japan); Hayano, H.; Kubo, K.; Naito, T.; Terunuma, N.; Urakawa, J. [High Energy Accelerator Research Organization, Tsukuba (Japan); Zimmermann, F. [Stanford Univ., CA (US). Stanford Linear Accelerator Center

    1998-06-01

    The purpose of the ATF damping ring is the development of technologies for producing a low emittance beam required in future linear colliders such as JLC. The lifetime of the damping ring is very short (typically a few minutes). It is limited by elastic beam-gas scattering along with a small dynamic aperture, and by single intra-beam scattering (Touschek effect). The Touschek lifetime strongly depends upon the charge density of the beam, especially, the size of the vertical emittance. In this paper, the authors report the results of beam lifetime measurements in the ATF damping ring and the estimation of the vertical emittance from these measurements.

  13. A Resonant Damping Study Using Piezoelectric Materials

    Science.gov (United States)

    Min, J. B.; Duffy, K. P.; Choi, B. B.; Morrison, C. R.; Jansen, R. H.; Provenza, A. J.

    2008-01-01

    Excessive vibration of turbomachinery blades causes high cycle fatigue (HCF) problems requiring damping treatments to mitigate vibration levels. Based on the technical challenges and requirements learned from previous turbomachinery blade research, a feasibility study of resonant damping control using shunted piezoelectric patches with passive and active control techniques has been conducted on cantilever beam specimens. Test results for the passive damping circuit show that the optimum resistive shunt circuit reduces the third bending resonant vibration by almost 50%, and the optimum inductive circuit reduces the vibration by 90%. In a separate test, active control reduced vibration by approximately 98%.

  14. Implication for using heme methyl hyperfine shifts as indicators of heme seating as related to stereoselectivity in the catabolism of heme by heme oxygenase: in-plane heme versus axial his rotation.

    Science.gov (United States)

    Ogura, Hiroshi; Evans, John P; de Montellano, Paul R Ortiz; La Mar, Gerd N

    2008-01-08

    The triple mutant of the solubilized, 265-residue construct of human heme oxygenase, K18E/E29K/R183E-hHO, has been shown to redirect the exclusive alpha-regioselectivity of wild-type hHO to primarily beta,delta-selectivity in the cleavage of heme (Wang, J., Evans, J. P., Ogura, H., La Mar, G. N., and Ortiz de Montellano, P. R. (2006) Biochemistry 45, 61-73). The 1H NMR hyperfine shift pattern for the substrate and axial His CbetaH's and the substrate-protein contacts of the cyanide-inhibited protohemin and 2,4-dimethyldeuterohemin complexes of the triple mutant have been analyzed in detail and compared to data for the WT complex. It is shown that protein contacts for the major solution isomers for both substrates in the mutant dictate approximately 90 degrees in-plane clockwise rotation relative to that in the WT. The conventional interpretation of the pattern of substrate methyl hyperfine shifts, however, indicates substrate rotations of only approximately 50 degrees . This paradox is resolved by demonstrating that the axial His25 imidazole ring also rotates counterclockwise with respect to the protein matrix in the mutant relative to that in the WT. The axial His25 CbetaH hyperfine shifts are shown to serve as independent probes of the imidazole plane orientation relative to the protein matrix. The analysis indicates that the pattern of heme methyl hyperfine shifts cannot be used alone to determine the in-plane orientation of the substrate as it relates to the stereospecificity of heme cleavage, without explicit consideration of the orientation of the axial His imidazole plane relative to the protein matrix.

  15. Immunolocalization of heme oxygenase-1 in periodontal diseases

    Directory of Open Access Journals (Sweden)

    G Gayathri

    2014-01-01

    Conclusion: The results of our study is an increasing evidence of involvement of antioxidant enzymes like heme oxygenase-1 in periodontal inflammation and their implication for treatment of chronic periodontitis.

  16. Heme Deficiency in Alzheimer's Disease: A Possible Connection to Porphyria

    Science.gov (United States)

    Dwyer, Barney E.; Stone, Meghan L.; Zhu, Xiongwei; Perry, George; Smith, Mark A.

    2006-01-01

    Mechanisms that cause Alzheimer's disease (AD), an invariably fatal neurodegenerative disease, are unknown. Important recent data indicate that neuronal heme deficiency may contribute to AD pathogenesis. If true, factors that contribute to the intracellular heme deficiency could potentially alter the course of AD. The porphyrias are metabolic disorders characterized by enzyme deficiencies in the heme biosynthetic pathway. We hypothesize that AD may differ significantly in individuals possessing the genetic trait for an acute hepatic porphyria. We elaborate on this hypothesis and briefly review the characteristics of the acute hepatic porphyrias that may be relevant to AD. We note the proximity of genes encoding enzymes of the heme biosynthesis pathway to genetic loci linked to sporadic, late-onset AD. In addition, we suggest that identification of individuals carrying the genetic trait for acute porphyria may provide a unique resource for investigating AD pathogenesis and inform treatment and management decisions. PMID:17047301

  17. Gas-phase spectroscopy of ferric heme-NO complexes

    DEFF Research Database (Denmark)

    Wyer, J.A.; Jørgensen, Anders; Pedersen, Bjarke

    2013-01-01

    and significantly blue-shifted compared to ferric heme nitrosyl proteins (maxima between 408 and 422 nm). This is in stark contrast to the Q-band absorption where the protein microenvironment is nearly innocent in perturbing the electronic structure of the porphyrin macrocycle. Photodissociation is primarily...... through loss of NO. In contrast to the Q-band region, two-photon absorption was seen in the Soret band despite NO loss only requiring ∼1 eV. A model based on intersystem crossing to a long-lived triplet state where a barrier has to be surmounted is suggested. Finally, we summarise the measured absorption...... maxima of heme and its complexes with amino acids and NO. Not so innocent: Weakly bound complexes between ferric heme and NO were synthesised in the gas phase, and their absorption measured from photodissociation yields. Opposite absorption trends in the Soret-band are seen upon NO addition to heme ions...

  18. Structure of the Escherichia coli O157:H7 heme oxygenase ChuS in complex with heme and enzymatic inactivation by mutation of the heme coordinating residue His-193

    Energy Technology Data Exchange (ETDEWEB)

    Suits,M.; Jaffer, N.; Jia, Z.

    2006-01-01

    Heme oxygenases catalyze the oxidation of heme to biliverdin, CO, and free iron. For pathogenic microorganisms, heme uptake and degradation are critical mechanisms for iron acquisition that enable multiplication and survival within hosts they invade. Here we report the first crystal structure of the pathogenic Escherichia coli O157:H7 heme oxygenase ChuS in complex with heme at 1.45 {angstrom} resolution. When compared with other heme oxygenases, ChuS has a unique fold, including structural repeats and a {beta}-sheet core. Not surprisingly, the mode of heme coordination by ChuS is also distinct, whereby heme is largely stabilized by residues from the C-terminal domain, assisted by a distant arginine from the N-terminal domain. Upon heme binding, there is no large conformational change beyond the fine tuning of a key histidine (His-193) residue. Most intriguingly, in contrast to other heme oxygenases, the propionic side chains of heme are orientated toward the protein core, exposing the {alpha}-meso carbon position where O{sub 2} is added during heme degradation. This unique orientation may facilitate presentation to an electron donor, explaining the significantly reduced concentration of ascorbic acid needed for the reaction. Based on the ChuS-heme structure, we converted the histidine residue responsible for axial coordination of the heme group to an asparagine residue (H193N), as well as converting a second histidine to an alanine residue (H73A) for comparison purposes. We employed spectral analysis and CO measurement by gas chromatography to analyze catalysis by ChuS, H193N, and H73A, demonstrating that His-193 is the key residue for the heme-degrading activity of ChuS.

  19. Simplified Model of Nonlinear Landau Damping

    Energy Technology Data Exchange (ETDEWEB)

    N. A. Yampolsky and N. J. Fisch

    2009-07-16

    The nonlinear interaction of a plasma wave with resonant electrons results in a plateau in the electron distribution function close to the phase velocity of the plasma wave. As a result, Landau damping of the plasma wave vanishes and the resonant frequency of the plasma wave downshifts. However, this simple picture is invalid when the external driving force changes the plasma wave fast enough so that the plateau cannot be fully developed. A new model to describe amplification of the plasma wave including the saturation of Landau damping and the nonlinear frequency shift is proposed. The proposed model takes into account the change of the plasma wave amplitude and describes saturation of the Landau damping rate in terms of a single fluid equation, which simplifies the description of the inherently kinetic nature of Landau damping. A proposed fluid model, incorporating these simplifications, is verified numerically using a kinetic Vlasov code.

  20. Piezoelectric RL shunt damping of flexible structures

    DEFF Research Database (Denmark)

    Høgsberg, Jan Becker; Krenk, Steen

    2015-01-01

    Resonant RL shunt circuits represent a robust and effective approach to piezoelectric damping, provided that the individual shunt circuit components are calibrated accurately with respect to the dynamic properties of the corresponding flexible structure. The balanced calibration procedure applied...

  1. Damping of wind turbine tower vibrations

    DEFF Research Database (Denmark)

    Brodersen, Mark Laier; Pedersen, Mikkel Melters

    Damping of wind turbine vibrations by supplemental dampers is a key ingredient for the continuous use of monopiles as support for offshore wind turbines. The present thesis consists of an extended summary with four parts and appended papers [P1-P4] concerning novel strategies for damping of tower...... in a stroke amplifying brace, which amplifies the displacement across the damper and thus reduces the desired level of damper force. For optimal damping of the two lowest tower modes, a novel toggle-brace concept for amplifying the bending deformation of the tower is presented. Numerical examples illustrate...... that a minimum of three braces in a symmetric circumferential configuration are needed to introduce homogeneous damping in the two lowest vibration modes, independent of the rotor direction. A novel hybrid viscous damper concept is described in the second part. The hybriddamper consists of a viscous dash...

  2. Structural dynamic modification using additive damping

    Indian Academy of Sciences (India)

    Some current trends for vibration control are also discussed. Keywords. Structural modifications; viscoelastic damping; perturbation; sensitivity analysis; optimization; vibration control. 1. Introduction. Vibrations in machines and structures, if not properly controlled, may cause component fatigue and human discomfort.

  3. Offline software for the DAMPE experiment

    Science.gov (United States)

    Wang, Chi; Liu, Dong; Wei, Yifeng; Zhang, Zhiyong; Zhang, Yunlong; Wang, Xiaolian; Xu, Zizong; Huang, Guangshun; Tykhonov, Andrii; Wu, Xin; Zang, Jingjing; Liu, Yang; Jiang, Wei; Wen, Sicheng; Wu, Jian; Chang, Jin

    2017-10-01

    A software system has been developed for the DArk Matter Particle Explorer (DAMPE) mission, a satellite-based experiment. The DAMPE software is mainly written in C++ and steered using a Python script. This article presents an overview of the DAMPE offline software, including the major architecture design and specific implementation for simulation, calibration and reconstruction. The whole system has been successfully applied to DAMPE data analysis. Some results obtained using the system, from simulation and beam test experiments, are presented. Supported by Chinese 973 Program (2010CB833002), the Strategic Priority Research Program on Space Science of the Chinese Academy of Science (CAS) (XDA04040202-4), the Joint Research Fund in Astronomy under cooperative agreement between the National Natural Science Foundation of China (NSFC) and CAS (U1531126) and 100 Talents Program of the Chinese Academy of Science

  4. Center Impedance Method for Damping Measurement

    Directory of Open Access Journals (Sweden)

    D. Malogi

    2009-01-01

    Full Text Available Damping materials are used extensively for reduction of vibration and noise. These damping materials have viscoelastic characteristics and are used by automotive and other industries. Testing of these materials is important in order to predict their performance and traditionally the damping properties are measured by the Oberst method. This paper discusses an alternate method called the Center Impedance method where force and response are measured directly and the damping properties are obtained. The Center Impedance method is easy to use requiring only standard vibration equipment for excitation, namely, shaker, and is easy to control the experiment for repeatability. Results of beams tested by both Oberst and Center Impedance methods are presented in order to validate this test method.

  5. Resonant Electromagnetic Shunt Damping of Flexible Structures

    DEFF Research Database (Denmark)

    Høgsberg, Jan Becker

    2016-01-01

    Electromagnetic transducers convert mechanical energy to electrical energy and vice versa. Effective passive vibration damping of flexible structures can therefore be introduced by shunting with an accurately calibrated resonant electrical network thatcontains a capacitor to create the desired...

  6. FORUM: Bioinspired Heme, Heme/non-heme Diiron, Heme/copper and Inorganic NOx Chemistry: ·NO(g) Oxidation, Peroxynitrite-Metal Chemistry and ·NO(g) Reductive Coupling

    Science.gov (United States)

    Schopfer, Mark P.; Wang, Jun; Karlin, Kenneth D.

    2010-01-01

    The focus of this Forum review highlights work from our own laboratories and those of others in the area of biochemical and biologically inspired inorganic chemistry dealing with nitric oxide (nitrogen monoxide, ·NO(g)) and its biological roles and reactions. The latter focus is on (i) oxidation of ·NO(g) to nitrate by nitric oxide dioxygenases (NOD’s), and (ii) reductive coupling of two molecules of ·NO(g) to give N2O(g). In the former case, NOD’s are described and the highlighting of possible peroxynitrite-heme intermediates and consequences of this are given by discussion of recent works with myoglobin and a synthetic heme model system for NOD action. Summaries of recent copper complex chemistries with ·NO(g) and O2(g) leading to peroxynitrite species are given. The coverage of biological reductive coupling of ·NO(g) deals with bacterial nitric oxide reductases (NOR’s) with heme/non-heme diiron active sites, and on heme/Cu oxidases such as cytochrome c oxidase which can mediate the same chemistry. Recent designed protein and synthetic model compound (heme/non-heme diiron or heme/copper) as functional mimics are discussed in some detail. We also highlight examples from the chemical literature, not necessarily involving biologically relevant metal ions, which describe the oxidation of ·NO(g) to nitrate (or nitrite) and possible peroxynitrite intermediates, or reductive coupling of ·NO(g) to give nitrous oxide. PMID:20666386

  7. Isocyanides inhibit human heme oxygenases at the verdoheme stage.

    Science.gov (United States)

    Evans, John P; Kandel, Sylvie; Ortiz de Montellano, Paul R

    2009-09-22

    Heme oxygenases (HO) catalyze the oxidative cleavage of heme to generate biliverdin, CO, and free iron. In humans, heme oxygenase-1 (hHO-1) is overexpressed in tumor tissues, where it helps to protect cancer cells from anticancer agents, while HOs in fungal pathogens, such as Candida albicans, function as the primary means of iron acquisition. Thus, HO can be considered a potential therapeutic target for certain diseases. In this study, we have examined the equilibrium binding of three isocyanides, isopropyl, n-butyl, and benzyl, to the two major human HO isoforms (hHO-1 and hHO-2), Candida albicans HO (CaHmx1), and human cytochrome P450 CYP3A4 using electronic absorption spectroscopy. Isocyanides coordinate to both ferric and ferrous HO-bound heme, with tighter binding by the more hydrophobic isocyanides and 200-300-fold tighter binding to the ferrous form. Benzyl isocyanide was the strongest ligand to ferrous heme in all the enzymes. Because the dissociation constants (KD) of the ligands for ferrous heme-hHO-1 were below the limit of accuracy for equilibrium titrations, stopped-flow kinetic experiments were used to measure the binding parameters of the isocyanides to ferrous hHO-1. Steady-state activity assays showed that benzyl isocyanide was the most potent uncompetitive inhibitor with respect to heme with a KI = 0.15 microM for hHO-1. Importantly, single turnover assays revealed that the reaction was completely stopped by coordination of the isocyanide to the verdoheme intermediate rather than to the ferric heme complex. Much tighter binding of the inhibitor to the verdoheme intermediate differentiates it from inhibition of, for example, CYP3A4 and offers a possible route to more selective inhibitor design.

  8. Isocyanides Inhibit Human Heme Oxygenases at the Verdoheme Stage†

    Science.gov (United States)

    Evans, John P.; Kandel, Sylvie; Ortiz de Montellano, Paul R.

    2010-01-01

    Heme oxygenases (HO) catalyze the oxidative cleavage of heme to generate biliverdin, CO, and free iron. In humans, heme oxygenase-1 (hHO-1) is overexpressed in tumor tissues, where it helps to protect cancer cells from anticancer agents, while HOs in fungal pathogens, such as Candida albicans, function as the primary means of iron acquisition. Thus, HO can be considered a potential therapeutic target for certain diseases. In this study, we have examined the equilibrium binding of three isocyanides; isopropyl, n-butyl, and benzyl, to the two major human HO isoforms (hHO-1 and hHO-2), Candida albicans HO (CaHmx1), and human cytochrome P450 CYP3A4 using electronic absorption spectroscopy. Isocyanides coordinate to both ferric and ferrous HO-bound heme, with tighter binding by the more hydrophobic isocyanides, and 200-300-fold tighter binding to the ferrous form. Benzyl isocyanide was the strongest ligand to ferrous heme in all the enzymes. Because the dissociation constants (KD) of the ligands for ferrous heme-hHO-1 were below the limit of accuracy for equilibrium titrations, stopped-flow kinetic experiments were used to measure the binding parameters of the isocyanides to ferrous hHO-1. Steady-state activity assays showed that benzyl isocyanide was the most potent uncompetitive inhibitor with respect to heme with a KI = 0.15 μM for hHO-1. Importantly, single turnover assays revealed that the reaction was completely stopped by coordination of the isocyanide to the verdoheme intermediate rather than to the ferric heme complex. Much tighter binding of the inhibitor to the verdoheme intermediate differentiates it from inhibition of, for example, CYP3A4 and offers a possible route to more selective inhibitor design. PMID:19694439

  9. Genome-wide analysis reveals novel genes essential for heme homeostasis in Caenorhabditis elegans.

    Directory of Open Access Journals (Sweden)

    Scott Severance

    2010-07-01

    Full Text Available Heme is a cofactor in proteins that function in almost all sub-cellular compartments and in many diverse biological processes. Heme is produced by a conserved biosynthetic pathway that is highly regulated to prevent the accumulation of heme--a cytotoxic, hydrophobic tetrapyrrole. Caenorhabditis elegans and related parasitic nematodes do not synthesize heme, but instead require environmental heme to grow and develop. Heme homeostasis in these auxotrophs is, therefore, regulated in accordance with available dietary heme. We have capitalized on this auxotrophy in C. elegans to study gene expression changes associated with precisely controlled dietary heme concentrations. RNA was isolated from cultures containing 4, 20, or 500 microM heme; derived cDNA probes were hybridized to Affymetrix C. elegans expression arrays. We identified 288 heme-responsive genes (hrgs that were differentially expressed under these conditions. Of these genes, 42% had putative homologs in humans, while genomes of medically relevant heme auxotrophs revealed homologs for 12% in both Trypanosoma and Leishmania and 24% in parasitic nematodes. Depletion of each of the 288 hrgs by RNA-mediated interference (RNAi in a transgenic heme-sensor worm strain identified six genes that regulated heme homeostasis. In addition, seven membrane-spanning transporters involved in heme uptake were identified by RNAi knockdown studies using a toxic heme analog. Comparison of genes that were positive in both of the RNAi screens resulted in the identification of three genes in common that were vital for organismal heme homeostasis in C. elegans. Collectively, our results provide a catalog of genes that are essential for metazoan heme homeostasis and demonstrate the power of C. elegans as a genetic animal model to dissect the regulatory circuits which mediate heme trafficking in both vertebrate hosts and their parasites, which depend on environmental heme for survival.

  10. The Damping Tail of CMB Anisotropies

    OpenAIRE

    Hu, Wayne; White, Martin

    1996-01-01

    By decomposing the damping tail of CMB anisotropies into a series of transfer functions representing individual physical effects, we provide ingredients that will aid in the reconstruction of the cosmological model from small-scale CMB anisotropy data. We accurately calibrate the model-independent effects of diffusion and reionization damping which provide potentially the most robust information on the background cosmology. Removing these effects, we uncover model-dependent processes such as ...

  11. Nonlinear damping and quasi-linear modelling

    OpenAIRE

    Elliott, S J; Ghandchi Tehrani, Maryam; Langley, R.

    2015-01-01

    The mechanism of energy dissipation in mechanical systems is often nonlinear. Even though there may be other forms of nonlinearity in the dynamics, nonlinear damping is the dominant source of nonlinearity in a number of practical systems. The analysis of such systems is simplified by the fact that they show no jump or bifurcation behaviour, and indeed can often be well represented by an equivalent linear system, whose damping parameters depend on the form and amplitude of the excitation, in a...

  12. CLIC Waveguide Damped Accelerating Structure Studies

    CERN Document Server

    Dehler, M; Wuensch, Walter

    1996-01-01

    Studies of waveguide damped 30 GHz accelerating structures for multibunching in CLIC are described. Frequency discriminated damping using waveguides with a lowest cutoff frequency above the fundamental but below the higher order modes was considered. The wakefield behavior was investigated using time domain MAFIA computations over up to 20 cells and for frequencies up to 150 GHz. A configuration consisting of four T-cross-sectioned waveguides per cell reduces the transverse wake below 1% at typical CLIC bunch spacings.

  13. On a Nonlocal Damping Model in Ferromagnetism

    Directory of Open Access Journals (Sweden)

    M. Moumni

    2015-01-01

    Full Text Available We consider a mathematical model describing nonlocal damping in magnetization dynamics. The model consists of a modified form of the Landau-Lifshitz-Gilbert (LLG equation for the evolution of the magnetization vector in a rigid ferromagnet. We give a global existence result and characterize the long time behaviour of the obtained solutions. The sensitivity of the model with respect to large and small nonlocal damping parameters is also discussed.

  14. Resonant Electromagnetic Shunt Damping of Flexible Structures

    DEFF Research Database (Denmark)

    Høgsberg, Jan Becker

    2016-01-01

    Electromagnetic transducers convert mechanical energy to electrical energy and vice versa. Effective passive vibration damping of flexible structures can therefore be introduced by shunting with an accurately calibrated resonant electrical network thatcontains a capacitor to create the desired...... resonance and a resistor to dissipate the correct amount of vibration energy. The modal interaction with residual vibration forms not targeted by the resonant shunt is represented by supplemental flexibility and inertia terms. This leads to modified calibration formulae that maintain the desired damping...

  15. Chromosomal localization of the human heme oxygenase genes: Heme oxygenase-1 (HMOX1) maps to chromosome 22q12 and heme oxygenase-2 (HMOX2) maps to chromosome 16p13. 3

    Energy Technology Data Exchange (ETDEWEB)

    Kutty, R.K.; Kutty, G.; Rodriguez, I.R.; Chader, G.J.; Wiggert, B. (National Institutes of Health, Bethesda, MD (United States))

    1994-04-01

    Heme oxygenase catalyzes the oxidation of heme to biliverdin, the precursor of the bile pigment bilirubin, and carbon monoxide, a putative neurotransmitter. The authors have employed polymerase chain reaction and fluorescence in situ hybridization to determine the chromosome localization of the genes coding for the two known heme oxygenase isozymes. Heme oxygenase-1 (HMOX1), the inducible form, was localized to human chromosome 22q12, while heme oxygenase-2 (HMOX2), the constitutive form, was localized to chromosome 16p13.3. 14 refs., 3 figs.

  16. Linear control strategies for damping of flexible structures

    DEFF Research Database (Denmark)

    Høgsberg, Jan Riess; Krenk, Steen

    2006-01-01

    Starting from the two-component representation technique for damping of structures the possible increase in damping efficiency obtained by introducing collocated active damping is illustrated. The two-component representation of the damped vibration mode is constructed as a linear combination of ...

  17. Comparing Sources of Damping of Cross-Wind Motion

    DEFF Research Database (Denmark)

    Tarp-Johansen, Niels Jacob; Andersen, Lars; Christensen, Erik Damgaard

    2009-01-01

    importance of the sources of damping clearly depends on the damping forces caused, but equally important is the displacements at the point of attack of the forces which is decisive for the amount of mechanical work performed, i.e. damping acting at the tower base has less potential than damping acting...

  18. HemeBIND: a novel method for heme binding residue prediction by combining structural and sequence information

    Directory of Open Access Journals (Sweden)

    Hu Jianjun

    2011-05-01

    Full Text Available Abstract Background Accurate prediction of binding residues involved in the interactions between proteins and small ligands is one of the major challenges in structural bioinformatics. Heme is an essential and commonly used ligand that plays critical roles in electron transfer, catalysis, signal transduction and gene expression. Although much effort has been devoted to the development of various generic algorithms for ligand binding site prediction over the last decade, no algorithm has been specifically designed to complement experimental techniques for identification of heme binding residues. Consequently, an urgent need is to develop a computational method for recognizing these important residues. Results Here we introduced an efficient algorithm HemeBIND for predicting heme binding residues by integrating structural and sequence information. We systematically investigated the characteristics of binding interfaces based on a non-redundant dataset of heme-protein complexes. It was found that several sequence and structural attributes such as evolutionary conservation, solvent accessibility, depth and protrusion clearly illustrate the differences between heme binding and non-binding residues. These features can then be separately used or combined to build the structure-based classifiers using support vector machine (SVM. The results showed that the information contained in these features is largely complementary and their combination achieved the best performance. To further improve the performance, an attempt has been made to develop a post-processing procedure to reduce the number of false positives. In addition, we built a sequence-based classifier based on SVM and sequence profile as an alternative when only sequence information can be used. Finally, we employed a voting method to combine the outputs of structure-based and sequence-based classifiers, which demonstrated remarkably better performance than the individual classifier alone

  19. Heme Degradation by Heme Oxygenase Protects Mitochondria but Induces ER Stress via Formed Bilirubin

    Directory of Open Access Journals (Sweden)

    Andrea Müllebner

    2015-04-01

    Full Text Available Heme oxygenase (HO, in conjunction with biliverdin reductase, degrades heme to carbon monoxide, ferrous iron and bilirubin (BR; the latter is a potent antioxidant. The induced isoform HO-1 has evoked intense research interest, especially because it manifests anti-inflammatory and anti-apoptotic effects relieving acute cell stress. The mechanisms by which HO mediates the described effects are not completely clear. However, the degradation of heme, a strong pro-oxidant, and the generation of BR are considered to play key roles. The aim of this study was to determine the effects of BR on vital functions of hepatocytes focusing on mitochondria and the endoplasmic reticulum (ER. The affinity of BR to proteins is a known challenge for its exact quantification. We consider two major consequences of this affinity, namely possible analytical errors in the determination of HO activity, and biological effects of BR due to direct interaction with protein function. In order to overcome analytical bias we applied a polynomial correction accounting for the loss of BR due to its adsorption to proteins. To identify potential intracellular targets of BR we used an in vitro approach involving hepatocytes and isolated mitochondria. After verification that the hepatocytes possess HO activity at a similar level as liver tissue by using our improved post-extraction spectroscopic assay, we elucidated the effects of increased HO activity and the formed BR on mitochondrial function and the ER stress response. Our data show that BR may compromise cellular metabolism and proliferation via induction of ER stress. ER and mitochondria respond differently to elevated levels of BR and HO-activity. Mitochondria are susceptible to hemin, but active HO protects them against hemin-induced toxicity. BR at slightly elevated levels induces a stress response at the ER, resulting in a decreased proliferative and metabolic activity of hepatocytes. However, the proteins that are targeted

  20. HEME OXYGENASE-1 AND FATTY LIVER DISEASE.

    Directory of Open Access Journals (Sweden)

    Daniela Nicolosi

    2016-04-01

    Full Text Available Fatty liver diseases are a spectrum of liver pathologies characterized by abnormal hepatocellular accumulations of lipids. This condition may occur in both adults and children, particularly those who are obese or have insulin resistance or following abuse of alcohol consumption. They are classified in Non-Alcoholic Fatty Liver Disease (NAFLD and Alcoholic Fatty Liver Disease (AFLD. Steatohepatitis is a specific pattern of injury within the spectrum of NAFLD and this pattern is associated with fibrotic progression and cirrhosis. The role of oxidative stress in liver steatosis production and its progression to inflammation leading to steatohepatitis has been discussed in relation to alterations in metabolic and pro-inflammatory pathway. One of the main enzymes responsible for antioxidant activity in the presence of liver damage is the Heme Oxygenase-1(HO-1.The products of the HO-1-catalyzed reaction, particularly carbon monoxide (CO and biliverdin/bilirubin have been shown to exert protective effects in several organs against oxidative and other noxious stimuli. In this context, it is interesting to note that induction of HO-1 expression contributes to protection against liver damage in various experimental models. The focus of this review is on the significance of targeted induction of HO-1 as a potential therapeutic strategy to protect the liver against fatty liver diseases.

  1. Introduction to the scientific application system of DAMPE (On behalf of DAMPE collaboration)

    Science.gov (United States)

    Zang, Jingjing

    2016-07-01

    The Dark Matter Particle Explorer (DAMPE) is a high energy particle physics experiment satellite, launched on 17 Dec 2015. The science data processing and payload operation maintenance for DAMPE will be provided by the DAMPE Scientific Application System (SAS) at the Purple Mountain Observatory (PMO) of Chinese Academy of Sciences. SAS is consisted of three subsystems - scientific operation subsystem, science data and user management subsystem and science data processing subsystem. In cooperation with the Ground Support System (Beijing), the scientific operation subsystem is responsible for proposing observation plans, monitoring the health of satellite, generating payload control commands and participating in all activities related to payload operation. Several databases developed by the science data and user management subsystem of DAMPE methodically manage all collected and reconstructed science data, down linked housekeeping data, payload configuration and calibration data. Under the leadership of DAMPE Scientific Committee, this subsystem is also responsible for publication of high level science data and supporting all science activities of the DAMPE collaboration. The science data processing subsystem of DAMPE has already developed a series of physics analysis software to reconstruct basic information about detected cosmic ray particle. This subsystem also maintains the high performance computing system of SAS to processing all down linked science data and automatically monitors the qualities of all produced data. In this talk, we will describe all functionalities of whole DAMPE SAS system and show you main performances of data processing ability.

  2. Susceptibility for cigarette smoke-induced DAMP release and DAMP-induced inflammation in COPD

    NARCIS (Netherlands)

    Pouwels, Simon D.; Hesse, Laura; Faiz, Alen; Lubbers, Jaap; Bodha, Priya K.; ten Hacken, Nick H. T.; van Oosterhout, Antoon J. M.; Nawijn, Martijn C.; Heijink, Irene H.

    2016-01-01

    Cigarette smoke (CS) exposure is a major risk factor for chronic obstructive pulmonary disease (COPD). We investigated whether CS-induced damage-associated molecular pattern (DAMP) release or DAMP-mediated inflammation contributes to susceptibility for COPD. Samples, including bronchial brushings,

  3. Non-coding RNAs and heme oxygenase-1 in vaccinia virus infection

    Energy Technology Data Exchange (ETDEWEB)

    Meseda, Clement A. [Division of Viral Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD (United States); Srinivasan, Kumar [Division of Transfusion Transmitted Diseases, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD (United States); Wise, Jasen [Qiagen, Frederick, MD (United States); Catalano, Jennifer [Center for Tobacco Products, Food and Drug Administration, Bethesda, MD (United States); Yamada, Kenneth M. [National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD (United States); Dhawan, Subhash, E-mail: subhash.dhawan@fda.hhs.gov [Division of Transfusion Transmitted Diseases, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD (United States)

    2014-11-07

    Highlights: • Heme oxygenase-1 (HO-1) induction inhibited vaccinia virus infection of macrophages. • Reduced infectivity inversely correlated with increased expression of non-coding RNAs. • The regulation of HO-1 and ncRNAs suggests a novel host defense response against vaccinia virus infection. - Abstract: Small nuclear RNAs (snRNAs) are <200 nucleotide non-coding uridylate-rich RNAs. Although the functions of many snRNAs remain undetermined, a population of snRNAs is produced during the early phase of infection of cells by vaccinia virus. In the present study, we demonstrate a direct correlation between expression of the cytoprotective enzyme heme oxygenase-1 (HO-1), suppression of selective snRNA expression, and inhibition of vaccinia virus infection of macrophages. Hemin induced HO-1 expression, completely reversed virus-induced host snRNA expression, and suppressed vaccinia virus infection. This involvement of specific virus-induced snRNAs and associated gene clusters suggests a novel HO-1-dependent host-defense pathway in poxvirus infection.

  4. Human heme oxygenase-1 efficiently catabolizes heme in the absence of biliverdin reductase.

    Science.gov (United States)

    Reed, James R; Huber, Warren J; Backes, Wayne L

    2010-11-01

    Heme oxygenase 1 (HO-1) uses molecular oxygen and electrons from NADPH cytochrome P450 reductase to convert heme to CO, ferrous iron, and biliverdin (BV). Enzymatic studies with the purified 30-kDa form of HO-1 routinely use a coupled assay containing biliverdin reductase (BVR), which converts BV to bilirubin (BR). BVR is believed to be required for optimal HO-1 activity. The goal of this study was to determine whether HO-1 activity could be monitored directly by following BV generation or iron release (using the ferrous iron chelator, ferrozine) in the absence of BVR. Using assays for each of the three end products, we found that HO-1 activity was stimulated in the presence of catalase and comparable rates were measured with each assay. Absorbance scans revealed characteristic spectra for BR, BV, and/or the ferrozine-iron complex. The optimal conditions were slightly different for the direct and coupled assays. BSA activated the coupled but inhibited the direct assays, and the assays had different pH optima. By measuring the activity of BVR directly using BV as a substrate, these differences were attributed to different enzymatic properties of BVR and HO-1. Thus, BVR is not needed to measure the activity of HO-1 when catalase is present. In fact, the factors affecting catalysis by HO-1 are better understood using the direct assays because the coupled assay can be influenced by properties of BVR.

  5. Determination of heme in microorganisms using HPLC-MS/MS and cobalt(III) protoporphyrin IX inhibition of heme acquisition in Escherichia coli.

    Science.gov (United States)

    Fyrestam, Jonas; Östman, Conny

    2017-10-17

    One of the main threats to the achievements in modern medicine is antimicrobial resistance. Molecular targeting of bacterial acquisition mechanisms of heme has been suggested to be an alternative to antibiotics. In the present study, HPLC-MS/MS combined with a simple clean-up based on liquid-liquid extraction has been developed and evaluated for simultaneous determination of heme and porphyrin heme precursors in microorganisms. Experimental design was used to optimize the extraction parameters, to obtain a method with high recovery, low matrix effects, and high precision. The effects of additives in the culture medium on the biosynthesis of heme were studied using Escherichia coli as a model microorganism. 5-Aminolaevulinic acid and hemin increased the heme concentration in E. coli by a factor of 1.5 and 4.5, respectively. Addition of 5-aminolaevulinic acid bypassed the E. coli negative feedback control of heme biosynthesis, which led to high amounts of intracellular porphyrins. The high heme concentration obtained when hemin was used as a culture additive shows that E. coli has an uptake of heme from its surroundings. In contrast, addition of cobalt protoporphyrin IX to the growth medium reduced the amount of heme in E. coli, demonstrating this compound's ability to mimic real heme and inhibit the heme acquisition mechanisms.

  6. Notes on the nonlinear beam dynamics with strong damping in the CLIC Damping Ring

    CERN Document Server

    Levichev, Eugene; Shatilov, Dmitry

    2010-01-01

    The beam is injected into the CLIC damping ring with the relatively large emittance and energy spread and then is damped to the extremely low phase volume. During the damping process the betatron frequency of each particle changes due to the space charge tune shift and nonlinear dependence of the betatron tune on the amplitude. This nonlinearity is produced by the strong chromatic sextupoles, wiggler nonlinear field components and, again, by the space charge force. During the damping, the particle cross resonances, which can trap some fraction of the beam, cause the loss of intensity, the beam blow up and degrade the beam quality. In this paper we study the evolution of the beam distribution in time during the damping for the original lattice of the CLIC DR (May 2005). Geneva, Switzerland June 2010 CLIC – Note – 850

  7. Numerical studies of shear damped composite beams using a constrained damping layer

    DEFF Research Database (Denmark)

    Kristensen, R.F.; Nielsen, Kim Lau; Mikkelsen, Lars Pilgaard

    2008-01-01

    Composite beams containing one or more damping layers are studied numerically. The work is based on a semi-analytical model using a Timoshenko beam theory and a full 2D finite element model. The material system analysed, is inspired by a train wagon suspension system used in a EUREKA project Sigma......!1841. For the material system, the study shows that the effect of the damping layer is strongly influenced by the presence of a stiff constraining layer, that enforces large shear strain amplitudes. The thickness of the damping rubber layer itself has only a minor influence on the overall damping....... In addition, a large influence of ill positioned cuts in the damping layer is observed....

  8. Dampness in buildings and health. Building characteristics as predictors for dampness in 8681 Swedish dwellings

    DEFF Research Database (Denmark)

    Hagerhed, L.; Bornehag, Carl-Gustaf; Sundell, Jan

    2002-01-01

    Questionnaire data on 8681 dwellings included in the Swedish study "Dampness in Buildings and Health" have been analysed for associations between dampness indicators, perceptions of indoor air quality and building characteristics such as time of construction, type of ventilation and type...... of foundation. Visible mold or damp stains were reported in 1.3 and 1.6% of single-family and multi-family houses respectively, dampness connected to the floor in 6.5 and 13.9% and condensation on windows in 12.5 and 16.9%. "Stuffy air" was reported in 22.3 and 42.8%, "Moldy odor" in 3.9 and 5.8% and perception...... of "Dry air" in 17.3 and 33.7% respectively. Older buildings and the use of natural ventilation were associated with increased frequency of dampness indicators as well as to increased frequencies of complaints on bad indoor air quality....

  9. Unwrapped phase inversion with an exponential damping

    KAUST Repository

    Choi, Yun Seok

    2015-07-28

    Full-waveform inversion (FWI) suffers from the phase wrapping (cycle skipping) problem when the frequency of data is not low enough. Unless we obtain a good initial velocity model, the phase wrapping problem in FWI causes a result corresponding to a local minimum, usually far away from the true solution, especially at depth. Thus, we have developed an inversion algorithm based on a space-domain unwrapped phase, and we also used exponential damping to mitigate the nonlinearity associated with the reflections. We construct the 2D phase residual map, which usually contains the wrapping discontinuities, especially if the model is complex and the frequency is high. We then unwrap the phase map and remove these cycle-based jumps. However, if the phase map has several residues, the unwrapping process becomes very complicated. We apply a strong exponential damping to the wavefield to eliminate much of the residues in the phase map, thus making the unwrapping process simple. We finally invert the unwrapped phases using the back-propagation algorithm to calculate the gradient. We progressively reduce the damping factor to obtain a high-resolution image. Numerical examples determined that the unwrapped phase inversion with a strong exponential damping generated convergent long-wavelength updates without low-frequency information. This model can be used as a good starting model for a subsequent inversion with a reduced damping, eventually leading to conventional waveform inversion.

  10. Elementary damping properties in braided composite materials

    Science.gov (United States)

    Dion, Bernard L.; Sadler, Robert; Silverberg, Larry

    1994-05-01

    This paper investigates the damping level trends of three-dimensionally braided composites as a function of matrix material, fiber-matrix interface, fiber braid angle, fiber volume, and axial fiber tow size. With knowledge of such trends, designers may increase the structural damping in a 3-D braided composite component, thereby reducing component vibration, shock response, and fatigue. The logarithmic decrements of the fundamental mode response of cantilevered, 3-D braided composite beam specimens were calculated for comparison. Although the logarithmic decrements of two specimens, differing only in their matrix materials (Tactix 123 and Epon 828), were essentially identical, both were considerably larger than that for steel. The value for the decrement of these two composite specimens' response was taken as a reference. Altering the nature of the fiber-matrix interface by lubricating the fibers before specimen consolidation greatly increased the damping relative to the baseline. Trends of increasing damping were measured with both increasing fiber braid angle and fiber volume. Finally, increasing levels of damping are reported for decreases in axial fiber tow size. Explanations for these trends, based on the possible microscopic and macroscopic nature of the braided composites, are offered.

  11. Damping modification factors for acceleration response spectra

    Directory of Open Access Journals (Sweden)

    Heng Li

    2017-09-01

    Full Text Available DMF (Damping modification factors are used to modify elastic response spectral values corresponding to damping ratio 5% to other damping levels. The influence of seismological parameters (magnitude, epicentral distances and site conditions on DMF for acceleration spectra was analysed. The results show that for a given period as the magnitude or distance increase, the effect of damping on the seismic response will also increase, which indicates the response reduction from the structural damping will become more efficient. In the near-field of small earthquakes, the influence of site conditions on DMF is obvious, but it does not show a consistent rule. Furthermore, the DMF corresponding to different site conditions gradually close to unity with increasing magnitude and distance. The influence of the above mentioned parameters is related to the relative attenuation of the frequency components of the ground motion. The attenuation index alone is sufficient to take into account the influence. Based on these features, this paper proposes a formula of DMF for acceleration response spectra.

  12. A simple and reusable fluorescent sensor for heme proteins based on a conjugated polymer-doped electrospun nanofibrous membrane.

    Science.gov (United States)

    Wang, Huaming; Peng, Zhou; Long, Yuanyuan; Chen, Haibo; Yang, Yufei; Li, Na; Liu, Feng

    2012-05-30

    We reported a simple and reusable fluorescent sensor for heme proteins based on the electrospun nanofibrous membrane doped with a fluorescent conjugated polymer P. The sensor showed favorable fluorescence sensing performance towards the heme proteins, including hemoglobin (Hb), myoglobin (Mb) and cytochrome c (Cyt c). The surface wettability and sensing performance of the electrospun nanofibrous membrane were investigated in detail using Hb as the model. The nanofibrous sensor showed satisfactory reversibility with less than 10% signal loss after nine quenching-regeneration cycles, and good batch-to-batch reproducibility with a relative standard deviation of 3.4% (n=3). The linear range of the sensor for Hb determination was 2.0×10(-8) to 3.0×10(-6) M with a detection limit of 1.2×10(-8) M. The quenching process is mainly based on the fluorescence resonance energy transfer mechanism between the fluorescent conjugated polymer P and the heme prosthetic groups, therefore the sensor was selective against most of the common interferents. As an example to evaluate the feasibility of the sensor in practical application, Hb in human blood samples was determined and the results were in good agreement with the data provided by the hospital. To the best of our knowledge, this is the first work using fluorescent electrospun nanofibrous sensor for protein analysis in real biological sample. Copyright © 2012 Elsevier B.V. All rights reserved.

  13. Reverse logistics

    NARCIS (Netherlands)

    M.P. de Brito (Marisa); S.D.P. Flapper; R. Dekker (Rommert)

    2002-01-01

    textabstractThis paper gives an overview of scientific literature that describes and discusses cases of reverse logistics activities in practice. Over sixty case studies are considered. Based on these studies we are able to indicate critical factors for the practice of reverse logistics. In

  14. Passive damping concepts for slender columns in space structures

    Science.gov (United States)

    Razzaq, Z.; Ekhelikar, R. K.

    1985-01-01

    An experimental and theoretical study of three different passive damping concepts is conducted for a slender member with partial rotational end restraints. Over a hundred full-scale natural vibration experiments were conducted to evaluate the effectiveness of mass-string, polyethylene tubing, and chain damping concepts. The damping properties obtained from the experiments were used in the approximate analyses based on the partial differential equation of motion for the problem. The comparison of the experimental and the theoretical deflection-time relations shows that the velocity-dependent damping model used in the theory is adequate. From the experimental results, the effect of end connection friction and induced axial forces on damping is identified. The definition of an efficiency index is proposed based on the damping ratio and the mass of a given passive damping device. Using this definition, the efficiencies of the three damping devices are compared. The polyethylene tubing concept resulted into a low damping efficiency.

  15. Dietary iron controls circadian hepatic glucose metabolism through heme synthesis.

    Science.gov (United States)

    Simcox, Judith A; Mitchell, Thomas Creighton; Gao, Yan; Just, Steven F; Cooksey, Robert; Cox, James; Ajioka, Richard; Jones, Deborah; Lee, Soh-Hyun; King, Daniel; Huang, Jingyu; McClain, Donald A

    2015-04-01

    The circadian rhythm of the liver maintains glucose homeostasis, and disruption of this rhythm is associated with type 2 diabetes. Feeding is one factor that sets the circadian clock in peripheral tissues, but relatively little is known about the role of specific dietary components in that regard. We assessed the effects of dietary iron on circadian gluconeogenesis. Dietary iron affects circadian glucose metabolism through heme-mediated regulation of the interaction of nuclear receptor subfamily 1 group d member 1 (Rev-Erbα) with its cosuppressor nuclear receptor corepressor 1 (NCOR). Loss of regulated heme synthesis was achieved by aminolevulinic acid (ALA) treatment of mice or cultured cells to bypass the rate-limiting enzyme in hepatic heme synthesis, ALA synthase 1 (ALAS1). ALA treatment abolishes differences in hepatic glucose production and in the expression of gluconeogenic enzymes seen with variation of dietary iron. The differences among diets are also lost with inhibition of heme synthesis with isonicotinylhydrazine. Dietary iron modulates levels of peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α), a transcriptional activator of ALAS1, to affect hepatic heme. Treatment of mice with the antioxidant N-acetylcysteine diminishes PGC-1α variation observed among the iron diets, suggesting that iron is acting through reactive oxygen species signaling. © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

  16. Heme oxygenase-1 deletion affects stress erythropoiesis.

    Directory of Open Access Journals (Sweden)

    Yu-An Cao

    Full Text Available Homeostatic erythropoiesis leads to the formation of mature red blood cells under non-stress conditions, and the production of new erythrocytes occurs as the need arises. In response to environmental stimuli, such as bone marrow transplantation, myelosuppression, or anemia, erythroid progenitors proliferate rapidly in a process referred to as stress erythropoiesis. We have previously demonstrated that heme oxygenase-1 (HO-1 deficiency leads to disrupted stress hematopoiesis. Here, we describe the specific effects of HO-1 deficiency on stress erythropoiesis.We used a transplant model to induce stress conditions. In irradiated recipients that received hmox(+/- or hmox(+/+ bone marrow cells, we evaluated (i the erythrocyte parameters in the peripheral blood; (ii the staining intensity of CD71-, Ter119-, and CD49d-specific surface markers during erythroblast differentiation; (iii the patterns of histological iron staining; and (iv the number of Mac-1(+-cells expressing TNF-α. In the spleens of mice that received hmox(+/- cells, we show (i decreases in the proerythroblast, basophilic, and polychromatophilic erythroblast populations; (ii increases in the insoluble iron levels and decreases in the soluble iron levels; (iii increased numbers of Mac-1(+-cells expressing TNF-α; and (iv decreased levels of CD49d expression in the basophilic and polychromatophilic erythroblast populations.As reflected by effects on secreted and cell surface proteins, HO-1 deletion likely affects stress erythropoiesis through the retention of erythroblasts in the erythroblastic islands of the spleen. Thus, HO-1 may serve as a therapeutic target for controlling erythropoiesis, and the dysregulation of HO-1 may be a predisposing condition for hematologic diseases.

  17. Dynamics of damped oscillations: physical pendulum

    Science.gov (United States)

    Quiroga, G. D.; Ospina-Henao, P. A.

    2017-11-01

    The frictional force between a physical damped pendulum and the medium is usually assumed to be proportional to the pendulum velocity. In this work, we investigate how the pendulum motion will be affected when the drag force is modeled using power-laws bigger than the usual 1 or 2, and we will show that such assumption leads to contradictions with experimental observations. For this purpose, a more general model of a damped pendulum is introduced, assuming a power-law with integer exponents in the damping term of the equation of motion, and also in the non-harmonic regime. A Runge–Kutta solver is implemented to compute the numerical solutions for the first five powers, showing that the linear drag has the fastest decay to rest, and that bigger exponents have long-time fluctuation around the equilibrium position, which have no correlation (as is expected) with experimental results.

  18. Damping Estimation by Frequency Domain Decomposition

    DEFF Research Database (Denmark)

    Brincker, Rune; Ventura, C. E.; Andersen, P.

    2001-01-01

    In this paper it is explained how the damping can be estimated using the Frequency Domain Decomposition technique for output-only modal identification, i.e. in the case where the modal parameters is to be estimated without knowing the forces exciting the system. Also it is explained how the natural...... back to time domain to identify damping and frequency. The technique is illustrated on a simple simulation case with 2 closely spaced modes. On this example it is illustrated how the identification is influenced by very closely spacing, by non-orthogonal modes, and by correlated input. The technique...... is further illustrated on the output-only identification of the Great Belt Bridge. On this example it is shown how the damping is identified on a weakly exited mode and a closely spaced mode....

  19. Passively damped vibration welding system and method

    Science.gov (United States)

    Tan, Chin-An; Kang, Bongsu; Cai, Wayne W.; Wu, Tao

    2013-04-02

    A vibration welding system includes a controller, welding horn, an anvil, and a passive damping mechanism (PDM). The controller generates an input signal having a calibrated frequency. The horn vibrates in a desirable first direction at the calibrated frequency in response to the input signal to form a weld in a work piece. The PDM is positioned with respect to the system, and substantially damps or attenuates vibration in an undesirable second direction. A method includes connecting the PDM having calibrated properties and a natural frequency to an anvil of an ultrasonic welding system. Then, an input signal is generated using a weld controller. The method includes vibrating a welding horn in a desirable direction in response to the input signal, and passively damping vibration in an undesirable direction using the PDM.

  20. Damping in Materials for Spintronic Applications

    Science.gov (United States)

    Mewes, Claudia

    The next generation of spintronic devices relies strongly on the development of new materials with high spin polarization, optimized intrinsic damping and tunable magnetic anisotropy. Therefore, technological progress in this area depends heavily on the successful search for new materials as well as on a deeper understanding of the fundamental mechanisms of the spin polarization, the damping and the magnetic anisotropy. This talk will focus on different aspects of materials with a low intrinsic relaxation rate. Our results are based on first principles calculations in combination with a non-orthogonal tight-binding model to predict those material properties for complex materials which can be used for example in new spin based memory devices or logic devices. However, the intrinsic damping parameter predicted from first principle calculations does not take into account adjacent layers that are present in the final device. Spin pumping is a well-known contribution that has to be taken into account for practical applications using multilayer structures. More recently a strong unidirectional contribution to the relaxation in exchange bias systems has been observed experimentally. To describe this phenomenon theoretically we use the formalism of an anisotropic Gilbert damping tensor that takes the place of the (scalar) Gilbert damping parameter in the Landau-Lifshitz-Gilbert equation of motion. While for single crystals this anisotropy is expected to be small, making experimental confirmation difficult, the broken symmetry in exchange bias systems provides an excellent testing ground to study the modified magnetization dynamics under the influence of unidirectional damping. C.K.A. Mewes would like to thank her colleague T. Mewes and her students J.B. Mohammadi, A.E. Farrar. We acknowledge support by the NSF-CAREER Award No. 1452670, and NSF-CAREER Award No. 0952929.

  1. Assessing Equivalent Viscous Damping Using Piping System test Results

    Energy Technology Data Exchange (ETDEWEB)

    Nie, J.; Morante, R.

    2010-07-18

    The specification of damping for nuclear piping systems subject to seismic-induced motions has been the subject of many studies and much controversy. Damping estimation based on test data can be influenced by numerous factors, consequently leading to considerable scatter in damping estimates in the literature. At present, nuclear industry recommendations and nuclear regulatory guidance are not consistent on the treatment of damping for analysis of nuclear piping systems. Therefore, there is still a need to develop a more complete and consistent technical basis for specification of appropriate damping values for use in design and analysis. This paper summarizes the results of recent damping studies conducted at Brookhaven National Laboratory.

  2. Heme oxygenase activity correlates with serum indices of iron homeostasis in healthy nonsmokers

    Science.gov (United States)

    Heme oxygenase (HO) catalyzes the breakdown of heme to carbon monoxide, iron, and biliverdin. While the use of genetically altered animal models in investigation has established distinct associations between HO activity and systemic iron availability, studies have not yet confirm...

  3. Mode damping in a commensurate monolayer solid

    DEFF Research Database (Denmark)

    Bruch, Ludwig Walter; Hansen, Flemming Yssing

    1997-01-01

    The normal modes of a commensurate monolayer solid may be damped by mixing with elastic waves of the substrate. This was shown by Hall, Mills, and Black [Phys. Rev. B 32, 4932 (1985)], for perpendicular adsorbate vibrations in the presence of an isotropic elastic medium. That work is generalized...... anisotropy of the elastic behavior of the graphite leads to quite different wave-vector dependence of the damping for modes polarized perpendicular and parallel to the substrate. A phenomenological extension of the elasticity theory of the graphite to include bond-bending energies improves the description...

  4. Damping of Crank–Nicolson error oscillations

    DEFF Research Database (Denmark)

    Britz, Dieter; Østerby, Ole; Strutwolf, J.

    2003-01-01

    The Crank–Nicolson (CN) simulation method has an oscillatory response to sharp initial transients. The technique is convenient but the oscillations make it less popular. Several ways of damping the oscillations in two types of electrochemical computations are investigated. For a simple one...... be computationally more expensive with some systems. The simple device of starting with one backward implicit (BI, or Laasonen) step does damp the oscillations, but not always sufficiently. For electrochemical microdisk simulations which are two-dimensional in space and using CN, the use of a first BI step is much...

  5. Power Oscillations Damping in DC Microgrids

    DEFF Research Database (Denmark)

    Hamzeh, Mohsen; Ghafouri, Mohsen; Karimi, Houshang

    2016-01-01

    This paper proposes a new control strategy for damping of power oscillations in a multi-source dc microgrid. A parallel combination of a fuel cell (FC), a photovoltaic (PV) system and a supercapacitor (SC) are used as a hybrid power conversion system (HPCS). The SC compensates for the slow...... transient response of the FC stack. The HPCS controller comprises a multi-loop voltage controller and a virtual impedance loop for power management. The virtual impedance loop uses a dynamic droop gain to actively damp the low-frequency oscillations of the power sharing control unit. The gain of virtual...

  6. Wind turbine blade with viscoelastic damping

    Science.gov (United States)

    Sievers, Ryan A.; Mullings, Justin L.

    2017-01-10

    A wind turbine blade (60) damped by viscoelastic material (54, 54A-F) sandwiched between stiffer load-bearing sublayers (52A, 52B, 56A, 56B) in portions of the blade effective to damp oscillations (38) of the blade. The viscoelastic material may be located in one or more of: a forward portion (54A) of the shell, an aft portion (54D) of the shell, pressure and suction side end caps (54B) of an internal spar, internal webbing walls (54C, 54E), and a trailing edge core (54F).

  7. Nitric oxide is a potent inhibitor of the cbb(3)-type heme-copper oxidases.

    Science.gov (United States)

    Arjona, Davinia; Wikström, Mårten; Ädelroth, Pia

    2015-05-08

    C-type heme-copper oxidases terminate the respiratory chain in many pathogenic bacteria, and will encounter elevated concentrations of NO produced by the immune defense of the host. Thus, a decreased sensitivity to NO in C-type oxidases would increase the survival of these pathogens. Here we have compared the inhibitory effect of NO in C-type oxidases to that in the mitochondrial A-type. We show that O2-reduction in both the Rhodobacter sphaeroides and Vibrio cholerae C-type oxidases is strongly and reversibly inhibited by submicromolar NO, with an inhibition pattern similar to the A-type. Thus, NO tolerance in pathogens with a C-type terminal oxidase has to rely mainly on other mechanisms. Copyright © 2015 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  8. Novel Insights into the Vasoprotective Role of Heme Oxygenase-1

    Directory of Open Access Journals (Sweden)

    Emanuela Marcantoni

    2012-01-01

    Full Text Available Cardiovascular risk factors contribute to enhanced oxidative stress which leads to endothelial dysfunction. These events trigger platelet activation and their interaction with leukocytes and endothelial cells, thus contributing to the induction of chronic inflammatory processes at the vascular wall and to the development of atherosclerotic lesions and atherothrombosis. In this scenario, endogenous antioxidant pathways are induced to restrain the development of vascular disease. In the present paper, we will discuss the role of heme oxygenase (HO-1 which is an enzyme of the heme catabolism and cleaves heme to form biliverdin and carbon monoxide (CO. Biliverdin is reduced enzymatically to the potent antioxidant bilirubin. Recent evidence supports the involvement of HO-1 in the antioxidant and antiinflammatory effect of cyclooxygenase(COX-2-dependent prostacyclin in the vasculature. Moreover, the role of HO-1 in estrogen vasoprotection is emerging. Finally, possible strategies to develop novel therapeutics against cardiovascular disease by targeting the induction of HO-1 will be discussed.

  9. Human heme oxygenase oxidation of 5- and 15-phenylhemes.

    Science.gov (United States)

    Wang, Jinling; Niemevz, Fernando; Lad, Latesh; Huang, Liusheng; Alvarez, Diego E; Buldain, Graciela; Poulos, Thomas L; de Montellano, Paul R Ortiz

    2004-10-08

    Human heme oxygenase-1 (hHO-1) catalyzes the O2-dependent oxidation of heme to biliverdin, CO, and free iron. Previous work indicated that electrophilic addition of the terminal oxygen of the ferric hydroperoxo complex to the alpha-meso-carbon gives 5-hydroxyheme. Earlier efforts to block this reaction with a 5-methyl substituent failed, as the reaction still gave biliverdin IXalpha. Surprisingly, a 15-methyl substituent caused exclusive cleavage at the gamma-meso-rather than at the normal, unsubstituted alpha-meso-carbon. No CO was formed in these reactions, but the fragment cleaved from the porphyrin eluded identification. We report here that hHO-1 cleaves 5-phenylheme to biliverdin IXalpha and oxidizes 15-phenylheme at the alpha-meso position to give 10-phenylbiliverdin IXalpha. The fragment extruded in the oxidation of 5-phenylheme is benzoic acid, one oxygen of which comes from O2 and the other from water. The 2.29- and 2.11-A crystal structures of the hHO-1 complexes with 1- and 15-phenylheme, respectively, show clear electron density for both the 5- and 15-phenyl rings in both molecules of the asymmetric unit. The overall structure of 15-phenylheme-hHO-1 is similar to that of heme-hHO-1 except for small changes in distal residues 141-150 and in the proximal Lys18 and Lys22. In the 5-phenylheme-hHO-1 structure, the phenyl-substituted heme occupies the same position as heme in the heme-HO-1 complex but the 5-phenyl substituent disrupts the rigid hydrophobic wall of residues Met34, Phe214, and residues 26-42 near the alpha-meso carbon. The results provide independent support for an electrophilic oxidation mechanism and support a role for stereochemical control of the reaction regiospecificity.

  10. Giardia intestinalis incorporates heme into cytosolic cytochrome b₅.

    Science.gov (United States)

    Pyrih, Jan; Harant, Karel; Martincová, Eva; Sutak, Robert; Lesuisse, Emmanuel; Hrdý, Ivan; Tachezy, Jan

    2014-02-01

    The anaerobic intestinal pathogen Giardia intestinalis does not possess enzymes for heme synthesis, and it also lacks the typical set of hemoproteins that are involved in mitochondrial respiration and cellular oxygen stress management. Nevertheless, G. intestinalis may require heme for the function of particular hemoproteins, such as cytochrome b5 (cytb5). We have analyzed the sequences of eukaryotic cytb5 proteins and identified three distinct cytb5 groups: group I, which consists of C-tail membrane-anchored cytb5 proteins; group II, which includes soluble cytb5 proteins; and group III, which comprises the fungal cytb5 proteins. The majority of eukaryotes possess both group I and II cytb5 proteins, whereas three Giardia paralogs belong to group II. We have identified a fourth Giardia cytb5 paralog (gCYTb5-IV) that is rather divergent and possesses an unusual 134-residue N-terminal extension. Recombinant Giardia cytb5 proteins, including gCYTb5-IV, were expressed in Escherichia coli and exhibited characteristic UV-visible spectra that corresponded to heme-loaded cytb5 proteins. The expression of the recombinant gCYTb5-IV in G. intestinalis resulted in the increased import of extracellular heme and its incorporation into the protein, whereas this effect was not observed when gCYTb5-IV containing a mutated heme-binding site was expressed. The electrons for Giardia cytb5 proteins may be provided by the NADPH-dependent Tah18-like oxidoreductase GiOR-1. Therefore, GiOR-1 and cytb5 may constitute a novel redox system in G. intestinalis. To our knowledge, G. intestinalis is the first anaerobic eukaryote in which the presence of heme has been directly demonstrated.

  11. Damping of Inter-Area Low Frequency Oscillation Using an Adaptive Wide-Area Damping Controller

    DEFF Research Database (Denmark)

    Yao, Wei; Jiang, L.; Fang, Jiakun

    2013-01-01

    This paper presents an adaptive wide-area damping controller (WADC) based on generalized predictive control (GPC) and model identification for damping the inter-area low frequency oscillations in large-scale inter-connected power system. A recursive least-squares algorithm (RLSA) with a varying...... in each sampling interval. Case studies are undertaken on a two-area fourmachine power system and the New England 10-machine 39-bus power system, respectively. Simulation results show that the proposed adaptive WADC not only can damp the inter-area oscillations effectively under a wide range of operation...

  12. The heme-regulatory motif of nuclear receptor Rev-erbβ is a key mediator of heme and redox signaling in circadian rhythm maintenance and metabolism.

    Science.gov (United States)

    Carter, Eric L; Ramirez, Yanil; Ragsdale, Stephen W

    2017-07-07

    Rev-erbβ is a heme-responsive transcription factor that regulates genes involved in circadian rhythm maintenance and metabolism, effectively bridging these critical cellular processes. Heme binding to Rev-erbβ indirectly facilitates its interaction with the nuclear receptor co-repressor (NCoR1), resulting in repression of Rev-erbβ target genes. Fe 3+ -heme binds in a 6-coordinate complex with axial His and Cys ligands, the latter provided by a heme-regulatory motif (HRM). Rev-erbβ was thought to be a heme sensor based on a weak K d value for the Rev-erbβ·heme complex of 2 μm determined with isothermal titration calorimetry. However, our group demonstrated with UV-visible difference titrations that the K d value is in the low nanomolar range, and the Fe 3+ -heme off-rate is on the order of 10 -6 s -1 making Rev-erbβ ineffective as a sensor of Fe 3+ -heme. In this study, we dissected the kinetics of heme binding to Rev-erbβ and provided a K d for Fe 3+ -heme of ∼0.1 nm Loss of the HRM axial thiolate via redox processes, including oxidation to a disulfide with a neighboring cysteine or dissociation upon reduction of Fe 3+ - to Fe 2+ -heme, decreased binding affinity by >20-fold. Furthermore, as measured in a co-immunoprecipitation assay, substitution of the His or Cys heme ligands in Rev-erbβ was accompanied by a significant loss of NCoR1 binding. These results demonstrate the importance of the Rev-erbβ HRM in regulating interactions with heme and NCoR1 and advance our understanding of how signaling through HRMs affects the major cellular processes of circadian rhythm maintenance and metabolism. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  13. Reverse Osmosis

    Indian Academy of Sciences (India)

    ment of Civil Engineering and is presently the. Chairman of Center for. Sustainable Technologies,. Indian Institute of Science,. Bangalore. His research areas include, unsaturated soil behaviour, hazardous waste management, water quality and remediation of contaminated water. Keywords. Osmosis, reverse osmosis,.

  14. Reverse Osmosis

    Indian Academy of Sciences (India)

    and is an Associate Faculty at Center for Sustainable. Technologies, Indian. Institute of Science,. Bangalore. His research areas include, unsaturated soil behaviour, hazardous waste management, water quality and remediation of contaminated water. Keywords. Osmosis, reverse osmosis, desalinatiion, seawater, water.

  15. Reverse Osmosis

    Indian Academy of Sciences (India)

    /fulltext/reso/012/05/0037-0040. Keywords. Osmosis; reverse osmosis; desalinatiion; seawater; water purification. Author Affiliations. Sudhakar M Rao1. Department of Civil Engineering, Indian Institute of Science, Bangalore 560012, India.

  16. Reversible Sterilization

    Science.gov (United States)

    Largey, Gale

    1977-01-01

    Notes that difficult questions arise concerning the use of sterilization for alleged eugenic and euthenic purposes. Thus, how reversible sterilization will be used with relation to the poor, mentally ill, mentally retarded, criminals, and minors, is questioned. (Author/AM)

  17. Gyroscopic Stabilization of Indefinite Damped Systems

    DEFF Research Database (Denmark)

    Kliem, Wolfhard; Müller, Peter C.

    1996-01-01

    The paper deals with linear systems of differential equationswith symmetric system matrices M,D, and K.The mass matrix M and the stiffness matrix K are both assumed to bepositive definite. The damping matrix D is indefinite. Three questionsare of interest: 1) When is the system unstable? Apparent...

  18. Rage mediated DAMP signaling in intestinal tumorigenesis

    NARCIS (Netherlands)

    Heijmans, Jarom; Büller, Nikè V. J. A.; Muncan, Vanesa; van den Brink, Gijs R.

    2012-01-01

    In the intestine, a large variety of pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs) can instigate innate immune responses, which have been shown to promote colorectal carcinogenesis. We have recently demonstrated an important role for the receptor for

  19. Amplitude damping channel for orbital angular momentum

    CSIR Research Space (South Africa)

    Dudley, Angela L

    2010-03-01

    Full Text Available of a previously reported OAM sorting device. A Mech-Zehnder interferometer with a Dove prism in each arm is used to sort OAM states according to their parity. The authors extend this concept to implement an amplitude damping channel, and prove its...

  20. An Equivalent Circuit for Landau Damping

    DEFF Research Database (Denmark)

    Pécseli, Hans

    1976-01-01

    An equivalent circuit simulating the effect of Landau damping in a stable plasma‐loaded parallel‐plate capacitor is presented. The circuit contains a double infinity of LC components. The transition from stable to unstable plasmas is simulated by the introduction of active elements into the circuit....

  1. Hyperchaotic circuit with damped harmonic oscillators

    DEFF Research Database (Denmark)

    Lindberg, Erik; Murali, K.; Tamasevicius, A.

    2001-01-01

    A simple fourth-order hyperchaotic circuit with damped harmonic oscillators is described. ANP3 and PSpice simulations including an eigenvalue study of the linearized Jacobian are presented together with a hardware implementation. The circuit contains two inductors with series resistance, two ideal...

  2. Spatial Damping of Linear Compressional Magnetoacoustic Waves ...

    Indian Academy of Sciences (India)

    2016-01-27

    Jan 27, 2016 ... We study the spatial damping of magnetoacoustic waves in an unbounded quiescent prominence invoking the technique of MHD seismology. We consider Newtonian radiation in the energy equation and derive a fourth order general dispersion relation in terms of wavenumber . Numerical solution of ...

  3. Structural dynamic modification using additive damping

    Indian Academy of Sciences (India)

    In order to control dynamic response in structures and machines, modofications using additive viscoelastic damping materials are highlighted. The techniques described for analysis include analytical methods for structural elements, FEM and perturbation methods for reanalysis or structural dynamic modifications for ...

  4. Damping mechanisms and models in structural dynamics

    DEFF Research Database (Denmark)

    Krenk, Steen

    2002-01-01

    Several aspects of damping models for dynamic analysis of structures are investigated. First the causality condition for structural response is used to identify rules for the use of complex-valued frequency dependent material models, illustrated by the shortcomings of the elastic hysteretic model...

  5. Nonlinear Landau damping and Alfven wave dissipation

    Science.gov (United States)

    Vinas, Adolfo F.; Miller, James A.

    1995-01-01

    Nonlinear Landau damping has been often suggested to be the cause of the dissipation of Alfven waves in the solar wind as well as the mechanism for ion heating and selective preacceleration in solar flares. We discuss the viability of these processes in light of our theoretical and numerical results. We present one-dimensional hybrid plasma simulations of the nonlinear Landau damping of parallel Alfven waves. In this scenario, two Alfven waves nonresonantly combine to create second-order magnetic field pressure gradients, which then drive density fluctuations, which in turn drive a second-order longitudinal electric field. Under certain conditions, this electric field strongly interacts with the ambient ions via the Landau resonance which leads to a rapid dissipation of the Alfven wave energy. While there is a net flux of energy from the waves to the ions, one of the Alfven waves will grow if both have the same polarization. We compare damping and growth rates from plasma simulations with those predicted by Lee and Volk (1973), and also discuss the evolution of the ambient ion distribution. We then consider this nonlinear interaction in the presence of a spectrum of Alfven waves, and discuss the spectrum's influence on the growth or damping of a single wave. We also discuss the implications for wave dissipation and ion heating in the solar wind.

  6. The DAMPE silicon–tungsten tracker

    Energy Technology Data Exchange (ETDEWEB)

    Azzarello, P., E-mail: philipp.azzarello@unige.ch [Département de Physique Nucléaire et Corpusculaire, University of Geneva, Geneva (Switzerland); Ambrosi, G. [Istituto Nazionale di Fisica Nucleare Sezione di Perugia, Perugia (Italy); Asfandiyarov, R. [Département de Physique Nucléaire et Corpusculaire, University of Geneva, Geneva (Switzerland); Bernardini, P. [Dipartimento di Matematica e Fisica “E. De Giorgi”, Università del Salento, Lecce (Italy); Istituto Nazionale di Fisica Nucleare Sezione di Lecce, Lecce (Italy); Bertucci, B.; Bolognini, A. [Istituto Nazionale di Fisica Nucleare Sezione di Perugia, Perugia (Italy); Dipartimento di Fisica e Geologia, Università di Perugia, Perugia (Italy); Cadoux, F. [Département de Physique Nucléaire et Corpusculaire, University of Geneva, Geneva (Switzerland); Caprai, M. [Istituto Nazionale di Fisica Nucleare Sezione di Perugia, Perugia (Italy); De Mitri, I. [Dipartimento di Matematica e Fisica “E. De Giorgi”, Università del Salento, Lecce (Italy); Istituto Nazionale di Fisica Nucleare Sezione di Lecce, Lecce (Italy); Domenjoz, M. [Département de Physique Nucléaire et Corpusculaire, University of Geneva, Geneva (Switzerland); Dong, Y. [Institute of High Energy Physics, Chinese Academy of Sciences, Beijing (China); Duranti, M. [Istituto Nazionale di Fisica Nucleare Sezione di Perugia, Perugia (Italy); Dipartimento di Fisica e Geologia, Università di Perugia, Perugia (Italy); Fan, R. [Institute of High Energy Physics, Chinese Academy of Sciences, Beijing (China); and others

    2016-09-21

    The DArk Matter Particle Explorer (DAMPE) is a spaceborne astroparticle physics experiment, launched on 17 December 2015. DAMPE will identify possible dark matter signatures by detecting electrons and photons in the 5 GeV–10 TeV energy range. It will also measure the flux of nuclei up to 100 TeV, for the study of the high energy cosmic ray origin and propagation mechanisms. DAMPE is composed of four sub-detectors: a plastic strip scintillator, a silicon–tungsten tracker–converter (STK), a BGO imaging calorimeter and a neutron detector. The STK is composed of six tracking planes of 2 orthogonal layers of single-sided micro-strip detectors, for a total detector surface of ca. 7 m{sup 2}. The STK has been extensively tested for space qualification. Also, numerous beam tests at CERN have been done to study particle detection at silicon module level, and at full detector level. After description of the DAMPE payload and its scientific mission, we will describe the STK characteristics and assembly. We will then focus on some results of single ladder performance tests done with particle beams at CERN.

  7. Stiffness and damping in mechanical design

    National Research Council Canada - National Science Library

    Rivin, Eugene I

    1999-01-01

    ... important conceptual issues are stiffness of mechanical structures and their components and damping in mechanical systems sensitive to and/or generating vibrations. Stiffness and strength are the most important criteria for many mechanical designs. However, although there are hundreds of books on various aspects of strength, and strength issues ar...

  8. Uncertainty Models for Rudder-Roll Damping Control

    DEFF Research Database (Denmark)

    Blanke, M.

    1996-01-01

    Experience has shown that rudder-roll damping and simultaneous heading control of ships has inherent robustness problems.......Experience has shown that rudder-roll damping and simultaneous heading control of ships has inherent robustness problems....

  9. Nonlinear damping and quasi-linear modelling.

    Science.gov (United States)

    Elliott, S J; Ghandchi Tehrani, M; Langley, R S

    2015-09-28

    The mechanism of energy dissipation in mechanical systems is often nonlinear. Even though there may be other forms of nonlinearity in the dynamics, nonlinear damping is the dominant source of nonlinearity in a number of practical systems. The analysis of such systems is simplified by the fact that they show no jump or bifurcation behaviour, and indeed can often be well represented by an equivalent linear system, whose damping parameters depend on the form and amplitude of the excitation, in a 'quasi-linear' model. The diverse sources of nonlinear damping are first reviewed in this paper, before some example systems are analysed, initially for sinusoidal and then for random excitation. For simplicity, it is assumed that the system is stable and that the nonlinear damping force depends on the nth power of the velocity. For sinusoidal excitation, it is shown that the response is often also almost sinusoidal, and methods for calculating the amplitude are described based on the harmonic balance method, which is closely related to the describing function method used in control engineering. For random excitation, several methods of analysis are shown to be equivalent. In general, iterative methods need to be used to calculate the equivalent linear damper, since its value depends on the system's response, which itself depends on the value of the equivalent linear damper. The power dissipation of the equivalent linear damper, for both sinusoidal and random cases, matches that dissipated by the nonlinear damper, providing both a firm theoretical basis for this modelling approach and clear physical insight. Finally, practical examples of nonlinear damping are discussed: in microspeakers, vibration isolation, energy harvesting and the mechanical response of the cochlea. © 2015 The Author(s).

  10. Anti-damping effect of radiation reaction

    Energy Technology Data Exchange (ETDEWEB)

    Wang, G; Yuan, X Z [School of Physics and Electric Information, Wenzhou University, Wenzhou 325035 (China); Li, H [Department of Physics, Yantai University, Yantai 264005 (China); Shen, Y F [Department of Physics, China University of Mining and Technology, Xuzhou 221008 (China); Zi, J [National Laboratory of Surface Physics, Fudan University, Shanghai 200433 (China)], E-mail: gz_wang131@yahoo.cn

    2010-01-15

    The anti-damping effect of radiation reaction, which means the radiation reaction does non-negative work on a radiating charge, is investigated at length by using the Lorentz-Dirac equation (LDE) for the motion of a point charge respectively acted on by (a) a pure electric field, (b) a pure magnetic field and (c) the fields of an electromagnetic wave. We found that the curvature of the charge's trajectory plays an important role in the radiation reaction force, and the anti-damping effect cannot take place for the real macroscopic motions of a point charge. The condition for this anti-damping effect to take place is that the gradient of the external force field must exceed a certain value over the region of magnitude of the classical radius of massive charges ({approx}10{sup -15} m). Our results are potentially helpful to lessen the controversy on LDE and justify it as the correct classical equation describing the radiating charge's motion. If this anti-damping effect of LDE were a real existing physical process, it could serve as a mechanism within the context of classical electrodynamics for the stability of hydrogen atoms. Using the picture of an electron in quantum electrodynamics, namely the negative bare charge surrounded by the polarized positive charges of vacuum, we can obtain a reasonable explanation for the energy transferred to the electron during the occurrence of the anti-damping effect, on which the venerable work of Wheeler and Feynman has thrown some light.

  11. Exploring damping characteristics of composite tower of cable ...

    Indian Academy of Sciences (India)

    SHEHATA E ABDEL RAHEEM

    The process of modeling damping matrices and their experimental verification is challenging because damping cannot be determined via static tests as mass and stiffness can be. Furthermore, damping is more difficult to determine from dynamic measurements than natural frequency. There have been detailed studies on ...

  12. Active and passive damping based on piezoelectric elements -controllability issues-

    NARCIS (Netherlands)

    Holterman, J.; de Vries, Theodorus J.A.; van Amerongen, J.; Jonker, Jan B.; Jonker, J.B.

    2001-01-01

    Piezoelectric elements are widely used for damping micro-vibrations in mechanical structures. Active damping can be realised robustly by means of collocated actuator-sensor-pairs, controlled so as to extract vibration energy. Excellent damping performance is possible as long as sufficient

  13. Preliminary Study on the Damping Effect of a Lateral Damping Buffer under a Debris Flow Load

    Directory of Open Access Journals (Sweden)

    Zheng Lu

    2017-02-01

    Full Text Available Simulating the impact of debris flows on structures and exploring the feasibility of applying energy dissipation devices or shock isolators to reduce the damage caused by debris flows can make great contribution to the design of disaster prevention structures. In this paper, we propose a new type of device, a lateral damping buffer, to reduce the vulnerability of building structures to debris flows. This lateral damping buffer has two mechanisms of damage mitigation: when debris flows impact on a building, it acts as a buffer, and when the structure vibrates due to the impact, it acts as a shock absorber, which can reduce the maximum acceleration response and subsequent vibration respectively. To study the effectiveness of such a lateral damping buffer, an impact test is conducted, which mainly involves a lateral damping buffer attached to a two-degree-of-freedom structure under a simulated debris flow load. To enable the numerical study, the equation of motion of the structure along with the lateral damping buffer is derived. A subsequent parametric study is performed to optimize the lateral damping buffer. Finally, a practical design procedure is also provided.

  14. Vibration and Damping Analysis of Composite Fiber Reinforced Wind Blade with Viscoelastic Damping Control

    Directory of Open Access Journals (Sweden)

    Tai-Hong Cheng

    2015-01-01

    Full Text Available Composite materials are increasingly used in wind blade because of their superior mechanical properties such as high strength-to-weight and stiffness-to-weight ratio. This paper presents vibration and damping analysis of fiberreinforced composite wind turbine blade with viscoelastic damping treatment. The finite element method based on full layerwise displacement theory was employed to analyze the damping, natural frequency, and modal loss factor of composite shell structure. The lamination angle was considered in mathematical modeling. The curved geometry, transverse shear, and normal strains were exactly considered in present layerwise shell model, which can depict the zig-zag in-plane and out-of-plane displacements. The frequency response functions of curved composite shell structure and wind blade were calculated. The results show that the damping ratio of viscoelastic layer is found to be very sensitive to determination of magnitude of composite structures. The frequency response functions with variety of thickness of damping layer were investigated. Moreover, the natural frequency, modal loss factor, and mode shapes of composite fiber reinforced wind blade with viscoelastic damping control were calculated.

  15. Recovering the damping rates of cyclotron damped plasma waves from simulation data

    CERN Document Server

    Schreiner, Cedric; Spanier, Felix

    2016-01-01

    Plasma waves with frequencies close to the particular gyrofrequencies of the charged particles in the plasma lose energy due to cyclotron damping. We briefly discuss the gyro-resonance of low frequency plasma waves and ions particularly with regard to particle-in-cell (PiC) simulations. A setup is outlined which uses artificially excited waves in the damped regime of the wave mode's dispersion relation to track the damping of the wave's electromagnetic fields. Extracting the damping rate directly from the field data in real or Fourier space is an intricate and non-trivial task. We therefore present a simple method of obtaining the damping rate {\\Gamma} from the simulation data. This method is described in detail, focusing on a step-by-step explanation of the course of actions. In a first application to a test simulation we find that the damping rates obtained from this simulation generally are in good agreement with theoretical predictions. We then compare the results of one-, two- and three-dimensional simul...

  16. Malaria parasite-synthesized heme is essential in the mosquito and liver stages and complements host heme in the blood stages of infection.

    Directory of Open Access Journals (Sweden)

    Viswanathan Arun Nagaraj

    Full Text Available Heme metabolism is central to malaria parasite biology. The parasite acquires heme from host hemoglobin in the intraerythrocytic stages and stores it as hemozoin to prevent free heme toxicity. The parasite can also synthesize heme de novo, and all the enzymes in the pathway are characterized. To study the role of the dual heme sources in malaria parasite growth and development, we knocked out the first enzyme, δ-aminolevulinate synthase (ALAS, and the last enzyme, ferrochelatase (FC, in the heme-biosynthetic pathway of Plasmodium berghei (Pb. The wild-type and knockout (KO parasites had similar intraerythrocytic growth patterns in mice. We carried out in vitro radiolabeling of heme in Pb-infected mouse reticulocytes and Plasmodium falciparum-infected human RBCs using [4-(14C] aminolevulinic acid (ALA. We found that the parasites incorporated both host hemoglobin-heme and parasite-synthesized heme into hemozoin and mitochondrial cytochromes. The similar fates of the two heme sources suggest that they may serve as backup mechanisms to provide heme in the intraerythrocytic stages. Nevertheless, the de novo pathway is absolutely essential for parasite development in the mosquito and liver stages. PbKO parasites formed drastically reduced oocysts and did not form sporozoites in the salivary glands. Oocyst production in PbALASKO parasites recovered when mosquitoes received an ALA supplement. PbALASKO sporozoites could infect mice only when the mice received an ALA supplement. Our results indicate the potential for new therapeutic interventions targeting the heme-biosynthetic pathway in the parasite during the mosquito and liver stages.

  17. The 1.5-Å Structure of XplA-heme, an Unusual Cytochrome P450 Heme Domain That Catalyzes Reductive Biotransformation of Royal Demolition Explosive*

    Science.gov (United States)

    Sabbadin, Federico; Jackson, Rosamond; Haider, Kamran; Tampi, Girish; Turkenburg, Johan P.; Hart, Sam; Bruce, Neil C.; Grogan, Gideon

    2009-01-01

    XplA is a cytochrome P450 of unique structural organization, consisting of a heme- domain that is C-terminally fused to its native flavodoxin redox partner. XplA, along with flavodoxin reductase XplB, has been shown to catalyze the breakdown of the nitramine explosive and pollutant hexahydro-1,3,5-trinitro-1,3,5-triazine (royal demolition explosive) by reductive denitration. The structure of the heme domain of XplA (XplA-heme) has been solved in two crystal forms: as a dimer in space group P21 to a resolution of 1.9 Å and as a monomer in space group P21212 to a resolution of 1.5 Å, with the ligand imidazole bound at the heme iron. Although it shares the overall fold of cytochromes P450 of known structure, XplA-heme is unusual in that the kinked I-helix that traverses the distal face of the heme is broken by Met-394 and Ala-395 in place of the well conserved Asp/Glu plus Thr/Ser, important in oxidative P450s for the scission of the dioxygen bond prior to substrate oxygenation. The heme environment of XplA-heme is hydrophobic, featuring a cluster of three methionines above the heme, including Met-394. Imidazole was observed bound to the heme iron and is in close proximity to the side chain of Gln-438, which is situated over the distal face of the heme. Imidazole is also hydrogen-bonded to a water molecule that sits in place of the threonine side-chain hydroxyl exemplified by Thr-252 in Cyt-P450cam. Both Gln-438 → Ala and Ala-395 → Thr mutants of XplA-heme displayed markedly reduced activity compared with the wild type for royal demolition explosive degradation when combined with surrogate electron donors. PMID:19692330

  18. Alteration of the Regiospecificity of Human Heme Oxygenase-1 by Unseating of the Heme but not Disruption of the Distal Hydrogen Bonding Network†

    Science.gov (United States)

    Wang, Jinling; Evans, John P.; Ogura, Hiroshi; La Mar, Gerd N.; Ortiz de Montellano, Paul R.

    2008-01-01

    Heme oxygenase regiospecifically oxidizes heme at the α-meso position to give biliverdin IXα, CO, and iron. The heme orientation within the active site, which is thought to determine the oxidation regiospecificity, is shown here for the human enzyme (hHO1) to be largely determined by interactions between the heme carboxylic acid groups and residues Arg183 and Lys18 but not Tyr134. Mutation of either Arg183 or Lys18 individually does not significantly alter the NADPH-cytochrome P450 reductase-dependent reaction regiochemistry, but partially shifts the oxidation to the β/δ-meso positions in the reaction supported by ascorbic acid. Mutation of Glu29 to a lysine, which places a positive charge where it can interact with a heme carboxyl if the heme rotates by ~90°, causes a slight loss of regiospecificity, but combined with the R183E and K18E mutations results primarily in β/δ-meso oxidation of the heme under all conditions. NMR analysis of heme binding to the triple K18E/E29K/R183E mutant confirms rotation of the heme in the active site. Kinetic studies demonstrate that mutations of Arg183 greatly impair the rate of the P450 reductase-dependent reaction, in accord with the earlier finding that Arg183 is involved in binding of the reductase to hHO1, but have little effect on the ascorbate reaction. Mutations of Asp140 and Tyr58 that disrupt the active site hydrogen bonding network, impair catalytic rates but do not influence the oxidation regiochemistry. The results indicate both that the oxidation regiochemistry is largely controlled by ionic interactions of the heme propionic acid groups with the protein and that shifts in regiospecificity involve rotation of the heme about an axis perpendicular to the heme plane. PMID:16388581

  19. Heme utilization by pathogenic bacteria: not all pathways lead to biliverdin.

    Science.gov (United States)

    Wilks, Angela; Ikeda-Saito, Masao

    2014-08-19

    The eukaryotic heme oxygenases (HOs) (E.C. 1.14.99.3) convert heme to biliverdin, iron, and carbon monoxide (CO) in three successive oxygenation steps. Pathogenic bacteria require iron for survival and infection. Extracellular heme uptake from the host plays a critical role in iron acquisition and virulence. In the past decade, several HOs required for the release of iron from extracellular heme have been identified in pathogenic bacteria, including Corynebacterium diphtheriae, Neisseriae meningitides, and Pseudomonas aeruginosa. The bacterial enzymes were shown to be structurally and mechanistically similar to those of the canonical eukaryotic HO enzymes. However, the recent discovery of the structurally and mechanistically distinct noncanonical heme oxygenases of Staphylococcus aureus and Mycobacterium tuberculosis has expanded the reaction manifold of heme degradation. The distinct ferredoxin-like structural fold and extreme heme ruffling are proposed to give rise to the alternate heme degradation products in the S. aureus and M. tuberculosis enzymes. In addition, several "heme-degrading factors" with no structural homology to either class of HOs have recently been reported. The identification of these "heme-degrading proteins" has largely been determined on the basis of in vitro heme degradation assays. Many of these proteins were reported to produce biliverdin, although no extensive characterization of the products was performed. Prior to the characterization of the canonical HO enzymes, the nonenzymatic degradation of heme and heme proteins in the presence of a reductant such as ascorbate or hydrazine, a reaction termed "coupled oxidation", served as a model for biological heme degradation. However, it was recognized that there were important mechanistic differences between the so-called coupled oxidation of heme proteins and enzymatic heme oxygenation. In the coupled oxidation reaction, the final product, verdoheme, can readily be converted to biliverdin

  20. Heme metabolism in stress regulation and protein production: From Cinderella to a key player.

    Science.gov (United States)

    Martínez, J L; Petranovic, D; Nielsen, J

    2016-04-02

    Heme biosynthesis is a highly conserved pathway which is present in all kingdoms, from Archaea to higher organisms such as plants and mammals. The heme molecule acts as a prosthetic group for different proteins and enzymes involved in energy metabolism and reactions involved in electron transfer. Based on our recent findings and other recent reports, we here illustrate that heme is more than a co-factor. We also discuss the necessity to gain more insight into the heme biosynthesis pathway regulation, as this interacts closely with overall stress control. Understanding heme biosynthesis and its regulation could impact our ability to develop more efficient yeast cell factories for heterologous protein production.

  1. Effect of a heme oxygenase-1 inducer on NADPH oxidase ...

    African Journals Online (AJOL)

    Purpose: To investigated the effect of hemin, a heme oxygenase-1 (HO-1) inducer, on nicotinamide adenine dinucleotide phosphate oxidase (NOX) expression in rats with alcohol-induced liver injury. Methods: Male Wistar rats were randomly divided into four groups consisting of the control group, the ethanol (EtOH) group, ...

  2. Heme and HO-1 inhibition of HCV, HBV, and HIV

    Directory of Open Access Journals (Sweden)

    Warren N Schmidt

    2012-10-01

    Full Text Available Hepatitis C virus, human immunodeficiency virus, and hepatitis B virus are chronic viral infections that cause considerable morbidity and mortality throughout the world. In the decades following the identification and sequencing of these viruses, in vitro experiments demonstrated that heme oxygenase-1, its oxidative products, and related compounds of the heme oxygenase system are virucidal for all three viruses. The purpose of this review is to critically evaluate and summarize the seminal studies that described and characterized this remarkable behavior. It will also discuss more recent work that discovered the antiviral mechanisms and target sites of these unique antiviral agents. In spite of the fact that these viruses are diverse pathogens with quite profound differences in structure and life cycle, it is significant that heme and related compounds show striking similarity for viral target sites across all three species. Collectively, these findings strongly indicate that we should move forward and develop heme and related tetrapyrroles into versatile antiviral agents that could be used therapeutically in patients with single or multiple viral infections.

  3. Heme: From quantum spin crossover to oxygen manager of life

    DEFF Research Database (Denmark)

    Kepp, Kasper Planeta

    2016-01-01

    discusses the spectroscopic and computational data that have helped to elucidate the nature of this remarkable molecular system, how it works, and how it is tuned by a range of molecular strategies. This tuning enables heme to carry out the two essential functions required for oxygen management of life, i...

  4. Cysteine-independent activation/inhibition of heme oxygenase-2.

    Science.gov (United States)

    Vukomanovic, Dragic; Rahman, Mona N; Maines, Mahin D; Ozolinš, Terence Rs; Szarek, Walter A; Jia, Zongchao; Nakatsu, Kanji

    2016-03-01

    Reactive thiols of cysteine (cys) residues in proteins play a key role in transforming chemical reactivity into a biological response. The heme oxygenase-2 (HO-2) isozyme contains two cys residues that have been implicated in binding of heme and also the regulation of its activity. In this paper, we address the question of a role for cys residues for the HO-2 inhibitors or activators designed in our laboratory. We tested the activity of full length recombinant human heme oxygenase-2 (FL-hHO-2) and its analog in which cys265 and cys282 were both replaced by alanine to determine the effect on activation by menadione (MD) and inhibition by QC-2350. Similar inhibition by QC-2350 and almost identical activation by MD was observed for both recombinant FL-hHO-2s. Our findings are interpreted to mean that thiols of FL-hHO-2s are not involved in HO-2 activation or inhibition by the compounds that have been designed and identified by us. Activation or inhibition of HO-2 by our compounds should be attributed to a mechanism other than altering binding affinity of HO-2 for heme through cys265 and cys282.

  5. Identification of two genes potentially associated in iron-heme ...

    Indian Academy of Sciences (India)

    2013-03-15

    Mar 15, 2013 ... Classic characteristics are poor predictors of the risk of thromboembolism. Thus, better markers for the carotid atheroma plaque formation and symptom causing are needed. Our objective was to study by microarray analysis gene expression of genes involved in homeostasis of iron and heme in carotid ...

  6. Identification of two genes potentially associated in iron-heme ...

    Indian Academy of Sciences (India)

    Classic characteristics are poor predictors of the risk of thromboembolism. Thus, better markers for the carotid atheroma plaque formation and symptom causing are needed. Our objective was to study by microarray analysis gene expression of genes involved in homeostasis of iron and heme in carotid atheroma plaque ...

  7. Cysteine-independent activation/inhibition of heme oxygenase-2

    Directory of Open Access Journals (Sweden)

    Dragic Vukomanovic

    2016-01-01

    Full Text Available Reactive thiols of cysteine (cys residues in proteins play a key role in transforming chemical reactivity into a biological response. The heme oxygenase-2 (HO-2 isozyme contains two cys residues that have been implicated in binding of heme and also the regulation of its activity. In this paper, we address the question of a role for cys residues for the HO-2 inhibitors or activators designed in our laboratory. We tested the activity of full length recombinant human heme oxygenase-2 (FL-hHO-2 and its analog in which cys265 and cys282 were both replaced by alanine to determine the effect on activation by menadione (MD and inhibition by QC-2350. Similar inhibition by QC-2350 and almost identical activation by MD was observed for both recombinant FL-hHO-2s. Our findings are interpreted to mean that thiols of FL-hHO-2s are not involved in HO-2 activation or inhibition by the compounds that have been designed and identified by us. Activation or inhibition of HO-2 by our compounds should be attributed to a mechanism other than altering binding affinity of HO-2 for heme through cys265 and cys282.

  8. Age-related accumulation of non-heme ferric and ferrous iron in mouse ovarian stroma visualized by sensitive non-heme iron histochemistry.

    Science.gov (United States)

    Asano, Yoshiya

    2012-03-01

    Sensitive non-heme iron histochemistry--namely, the perfusion-Perls method and perfusion-Turnbull method--was applied to study the distribution and age-related accumulation of non-heme ferric iron and ferrous iron in mouse ovary. Light and electron microscopic studies revealed that non-heme ferric iron is distributed predominantly in stromal tissue, especially in macrophages. By contrast, the distribution of non-heme ferrous iron was restricted to a few ovoid macrophages. Aged ovaries exhibited remarkable non-heme iron accumulation in all stromal cells. In particular, non-heme ferrous iron level was increased in stromal tissue, suggestive of increased levels of redox-active iron, which can promote oxidative stress. Moreover, intense localization of both non-heme ferric and ferrous iron was observed in aggregated large stromal cells that were then characterized as ceroid-laden enlarged macrophages with frothy cytoplasm. Intraperitoneal iron overload in adult mice resulted in non-heme iron deposition in the entire stroma and generation of enlarged macrophages, suggesting that excessive iron accumulation induced macrophage morphological changes. The data indicated that non-heme iron accumulation in ovarian stromal tissue may be related to aging of the ovary due to increasing oxidative stress.

  9. Identification and characterization of a heme periplasmic-binding protein in Haemophilus ducreyi.

    Science.gov (United States)

    St Denis, Melissa; Sonier, Brigitte; Robinson, Renée; Scott, Fraser W; Cameron, D William; Lee, B Craig

    2011-08-01

    Haemophilus ducreyi, a gram-negative and heme-dependent bacterium, is the causative agent of chancroid, a genital ulcer sexually transmitted infection. Heme acquisition in H. ducreyi proceeds via a receptor mediated process in which the initial event involves binding of hemoglobin and heme to their cognate outer membrane proteins, HgbA and TdhA, respectively. Following this specific interaction, the fate of the periplasmic deposited heme is unclear. Using protein expression profiling of the H. ducreyi periplasmic proteome, a periplasmic-binding protein, termed hHbp, was identified whose expression was enhanced under heme-limited conditions. The gene encoding this protein was situated in a locus displaying genetic characteristics of an ABC transporter. The purified protein bound heme in a dose-dependent and saturable manner and this binding was specifically competitively inhibited by heme. The hhbp gene functionally complemented an Escherichia coli heme uptake mutant. Expression of the heme periplasmic-binding protein was detected in a limited survey of H. ducreyi and H. influenzae clinical strains. These results indicate that the passage of heme into the cytoplasm of H. ducreyi involves a heme dedicated ABC transporter.

  10. Effects of Landau-Lifshitz-Gilbert damping on domain growth

    Science.gov (United States)

    Kudo, Kazue

    2016-12-01

    Domain patterns are simulated by the Landau-Lifshitz-Gilbert (LLG) equation with an easy-axis anisotropy. If the Gilbert damping is removed from the LLG equation, it merely describes the precession of magnetization with a ferromagnetic interaction. However, even without the damping, domains that look similar to those of scalar fields are formed, and they grow with time. It is demonstrated that the damping has no significant effects on domain growth laws and large-scale domain structure. In contrast, small-scale domain structure is affected by the damping. The difference in small-scale structure arises from energy dissipation due to the damping.

  11. Dietary heme mediated PPARα activation does not affect the heme-induced epithelial hyperproliferation and hyperplasia in mouse colon

    NARCIS (Netherlands)

    IJssennagger, Noortje; Wit, de Nicole; Muller, Michael; Meer, van der Roelof

    2012-01-01

    Red meat consumption is associated with an increased colon cancer risk. Heme, present in red meat, injures the colon surface epithelium by luminal cytotoxicity and reactive oxygen species. This surface injury is overcompensated by hyperproliferation and hyperplasia of crypt cells. Transcriptome

  12. Dietary heme-mediated PPARa activation does not affect the heme-induced epithelial hyperproliferation and hyperplasia in mouse colon

    NARCIS (Netherlands)

    IJssenagger, N.; Wit, de N.J.W.; Muller, M.R.; Meer, van der R.

    2012-01-01

    Red meat consumption is associated with an increased colon cancer risk. Heme, present in red meat, injures the colon surface epithelium by luminal cytotoxicity and reactive oxygen species. This surface injury is overcompensated by hyperproliferation and hyperplasia of crypt cells. Transcriptome

  13. Bacterial Nitric Oxide Synthase Is Required for the Staphylococcus aureus Response to Heme Stress.

    Science.gov (United States)

    Surdel, Matthew C; Dutter, Brendan F; Sulikowski, Gary A; Skaar, Eric P

    2016-08-12

    Staphylococcus aureus is a pathogen that causes significant morbidity and mortality worldwide. Within the vertebrate host, S. aureus requires heme as a nutrient iron source and as a cofactor for multiple cellular processes. Although required for pathogenesis, excess heme is toxic. S. aureus employs a two-component system, the heme sensor system (HssRS), to sense and protect against heme toxicity. Upon activation, HssRS induces the expression of the heme-regulated transporter (HrtAB), an efflux pump that alleviates heme toxicity. The ability to sense and respond to heme is critical for the pathogenesis of numerous Gram-positive organisms, yet the mechanism of heme sensing remains unknown. Compound '3981 was identified in a high-throughput screen as an activator of staphylococcal HssRS that triggers HssRS independently of heme accumulation. '3981 is toxic to S. aureus; however, derivatives of '3981 were synthesized that lack toxicity while retaining HssRS activation, enabling the interrogation of the heme stress response without confounding toxic effects of the parent molecule. Using '3981 derivatives as probes of the heme stress response, numerous genes required for '3981-induced activation of HssRS were uncovered. Specifically, multiple genes involved in the production of nitric oxide were identified, including the gene encoding bacterial nitric oxide synthase (bNOS). bNOS protects S. aureus from oxidative stress imposed by heme. Taken together, this work identifies bNOS as crucial for the S. aureus heme stress response, providing evidence that nitric oxide synthesis and heme sensing are intertwined.

  14. Ibuprofen Impairs Allosterically Peroxynitrite Isomerization by Ferric Human Serum Heme-Albumin*

    Science.gov (United States)

    Ascenzi, Paolo; di Masi, Alessandra; Coletta, Massimo; Ciaccio, Chiara; Fanali, Gabriella; Nicoletti, Francesco P.; Smulevich, Giulietta; Fasano, Mauro

    2009-01-01

    Human serum albumin (HSA) participates in heme scavenging; in turn, heme endows HSA with myoglobin-like reactivity and spectroscopic properties. Here, the allosteric effect of ibuprofen on peroxynitrite isomerization to NO3− catalyzed by ferric human serum heme-albumin (HSA-heme-Fe(III)) is reported. Data were obtained at 22.0 °C. HSA-heme-Fe(III) catalyzes peroxynitrite isomerization in the absence and presence of CO2; the values of the second order catalytic rate constant (kon) are 4.1 × 105 and 4.5 × 105 m−1 s−1, respectively. Moreover, HSA-heme-Fe(III) prevents peroxynitrite-mediated nitration of free added l-tyrosine. The pH dependence of kon (pKa = 6.9) suggests that peroxynitrous acid reacts preferentially with the heme-Fe(III) atom, in the absence and presence of CO2. The HSA-heme-Fe(III)-catalyzed isomerization of peroxynitrite has been ascribed to the reactive pentacoordinated heme-Fe(III) atom. In the absence and presence of CO2, ibuprofen impairs dose-dependently peroxynitrite isomerization by HSA-heme-Fe(III) and facilitates the nitration of free added l-tyrosine; the value of the dissociation equilibrium constant for ibuprofen binding to HSA-heme-Fe(III) (L) ranges between 7.7 × 10−4 and 9.7 × 10−4 m. Under conditions where [ibuprofen] is ≫L, the kinetics of HSA-heme-Fe(III)-catalyzed isomerization of peroxynitrite is superimposable to that obtained in the absence of HSA-heme-Fe(III) or in the presence of non-catalytic HSA-heme-Fe(III)-cyanide complex and HSA. Ibuprofen binding impairs allosterically peroxynitrite isomerization by HSA-heme-Fe(III), inducing the hexacoordination of the heme-Fe(III) atom. These results represent the first evidence for peroxynitrite isomerization by HSA-heme-Fe(III), highlighting the allosteric modulation of HSA-heme-Fe(III) reactivity by heterotropic interaction(s), and outlining the role of drugs in modulating HSA functions. The present results could be relevant for the drug-dependent protective role

  15. Reverse mortgages.

    Science.gov (United States)

    Farnesi, D

    1995-09-01

    Elders and their families are often caught in a financial bind when it comes to paying for much-needed home care services. Reverse mortgages may offer a solution to elderly home care clients who own their homes but have a limited income with which to maintain their independence.

  16. Reversible Computing

    Science.gov (United States)

    1980-02-01

    will have been introduced. 9. Reversible celular autemata We shall assume the reader to have some familiarity with the concept of cel- lular...10003 Mr. Kin B. Thcmpson 1 copy Technical Director Information Systems Divisia.i Naval Research Laboratory (OP-91T) Technical Information Division

  17. Damping performance of cocured composite laminates with embedded viscoelastic layers

    Science.gov (United States)

    Biggerstaff, Janet M.; Kosmatka, John B.

    1998-06-01

    Cocuring viscoelastic damping materials in composites has been shown to be successful in greatly increasing the damping of composite structures. The damping performance, however, is often not as high in cocured composites as in secondarily bonded composites, where the damping material does not undergo the cure process. The reason for the discrepancy in damping between the cocured and secondarily bonded samples was found to be resin penetration into the damping material. Samples with a barrier layer between the damping material and the epoxy resin had a 15.7% to 92.3% higher loss factor (depending on the frequency) than cocured FasTapeTM 1125 samples without the barrier and at least 168% higher loss factor than cocured ISD 112 samples without the barrier. These higher damping values are very close to the values achieved by secondarily bonding. Viscoelastic damping materials typically have maximum recommended temperatures below that of the composite cure cycles. The effect of cure temperature on viscoelastic damping materials was also studied and it was determined that most damping materials are marginally affected by cure cycle temperature.

  18. A tapered damped accelerating structure for CLIC

    CERN Document Server

    Dehler, M; Wuensch, Walter

    1998-01-01

    A new 30 GHz multibunch accelerating structure incorporating both damping and detuning has been designed for the Compact LInear Collider (CLIC). Each cell of the 150-cell structure is damped by its ow n set of four radial waveguides resulting in a Q of 16 for the lowest dipole mode. A simple linear taper of the beam-pipe dimension provides a detuning frequency spread of 2 GHz (5.4%). Predictions of the transverse wakefield levels in this structure have been made using both uncoupled, and two-band coupled equivalent circuit models with non-perfect loads. The short-range wakefield has been calcula ted to be about 1000 V/(pC.mm.m) decreasing to less than 1% at the second bunch (0.67 ns) and with a long time level below 0.1%.

  19. Classical acoustic waves in damped media.

    Science.gov (United States)

    Albuquerque, E L; Mauriz, P W

    2003-05-01

    A Green function technique is employed to investigate the propagation of classical damped acoustic waves in complex media. The calculations are based on the linear response function approach, which is very convenient to deal with this kind of problem. Both the displacement and the gradient displacement Green functions are determined. All deformations in the media are supposed to be negligible, so the motions considered here are purely acoustic waves. The damping term gamma is included in a phenomenological way into the wave vector expression. By using the fluctuation-dissipation theorem, the power spectrum of the acoustic waves is also derived and has interesting properties, the most important of them being a possible relation with the analysis of seismic reflection data.

  20. Barotropic FRW cosmologies with Chiellini damping

    Energy Technology Data Exchange (ETDEWEB)

    Rosu, Haret C., E-mail: hcr@ipicyt.edu.mx [IPICyT, Instituto Potosino de Investigacion Cientifica y Tecnologica, Camino a la presa San José 2055, Col. Lomas 4a Sección, 78216 San Luis Potosí, SLP (Mexico); Mancas, Stefan C., E-mail: stefan.mancas@erau.edu [Department of Mathematics, Embry–Riddle Aeronautical University, Daytona Beach, FL 32114-3900 (United States); Chen, Pisin, E-mail: pisinchen@phys.ntu.edu.tw [Leung Center for Cosmology and Particle Astrophysics (LeCosPA) and Department of Physics, National Taiwan University, Taipei 10617, Taiwan (China)

    2015-05-08

    It is known that barotropic FRW equations written in the conformal time variable can be reduced to simple linear equations for an exponential function involving the conformal Hubble rate. Here, we show that an interesting class of barotropic universes can be obtained in the linear limit of a special type of nonlinear dissipative Ermakov–Pinney equations with the nonlinear dissipation built from Chiellini's integrability condition. These cosmologies, which evolutionary are similar to the standard ones, correspond to barotropic fluids with adiabatic indices rescaled by a particular factor and have amplitudes of the scale factors inverse proportional to the adiabatic index. - Highlights: • Chiellini-damped Ermakov–Pinney equations are used in barotropic FRW cosmological context. • Chiellini-damped scale factors of the barotropic FRW universes are introduced. • These scale factors are similar to the undamped ones.

  1. System Reduction and Damping of Flexible Structures

    DEFF Research Database (Denmark)

    Høgsberg, Jan Riess; Krenk, Steen

    2007-01-01

    An increasing number of flexible structures such as cable-stayed bridges, pedestrian bridges and high-rise buildings are fitted with local dampers to mitigate vibration problems. In principle the effect of local dampers can be analyzed by use of complex modes, e.g. in conjunction with an averaging...... technique for local linearization of the damper characteristics. However, the complex mode shapes and frequencies depend on the magnitude of the damper and therefore are less suitable for design of the damper system. An efficient alternative consists in the use of a two-component representation...... of the damped modes of the structure. The idea is to represent the damped mode as a linear combination of the modes that occur in two distinctly different situations representing extreme conditions: the mode shape of the structure without the damper(s), and the mode shape of the structure, when the damper...

  2. DAMPING OF SUBSYNCHRONOUS MODES OF OSCILLATIONS

    Directory of Open Access Journals (Sweden)

    JAGADEESH PASUPULETI

    2006-06-01

    Full Text Available The IEEE bench mark model 2 series compensated system is considered for analysis. It consists of single machine supplying power to infinite bus through two parallel lines one of which is series compensated. The mechanical system considered consists of six mass, viz, high pressure turbine, intermediate pressure turbine, two low pressure turbines, generator and an exciter. The excitation system considered is IEEE type 1 with saturation. The auxiliary controls considered to damp the unstable subsynchronous modes of oscillations are Power System Stabilizer (PSS and Static var Compensator (SVC. The different cases of power system stabilizer and reactive power controls are adapted to study the effectiveness of damping these unstable subsynchronous modes of oscillations.

  3. Fabrication Process of Rounded Damped Detuned Structure

    CERN Document Server

    Hitomi, N; Higashi, Y; Higo, T; Koike, S; Suzuki, T; Takata, K; Takatomi, T; Toge, T; Watanabe, Y

    2000-01-01

    Following the successful design and fabrication of Damped Detuned Structures (DDS), the JLC/NLC linear collider project advanced to Rounded Damped Detuned Structures (RDDS) with curved cross section of the cavity shape for increased shunt impedance. Various advanced techniques for fabricating RDDS1 disks comparing to those for DDS were established to satisfy the dimension accuracy of +-1 micron over the entire surface made by ultra-precision turning. These disks were assembled with almost the same stacking and bonding jigs and processes as those of DDS3 assembly. In consequence, the assembly showed little disk-to-disk misalignment within 1 micron before and after the process. Though, it had 200 micron smooth bowing, which was subsequently corrected as DDS3, and flares at both ends.

  4. A Novel Strain Gauge with Damping Capability

    Directory of Open Access Journals (Sweden)

    Xiaohua LI

    2009-10-01

    Full Text Available The goal of this work is to investigate the properties of a new type of multifunctional composite which is based on multi-walled carbon nanotubes (MWCNT. The composite was prepared from a paper like MWCNT film which was sandwiched between two adhesive layers. Two point probe and four point probe methods were used to test its mechanical strain sensing properties. Nanoindentation and direct shear tests were used to acquire the Young’s modulus and shear modulus of MWCNT film composite. Its structural damping properties were investigated via a free vibration test. This new type of carbon nanotube based composite may potentially serve simultaneously as both a strain gauge and a damping treatment for use in structural vibration control.

  5. Rapidly moving contact lines and damping contributions

    Science.gov (United States)

    Xia, Yi; Daniel, Susan; Steen, Paul

    2017-11-01

    Contact angle varies dynamically with contact line (CL) speed when a liquid moves across a solid support, as when a liquid spreads rapidly. For sufficiently rapid spreading, inertia competes with capillarity to influence the interface shape near the support. We use resonant-mode plane-normal support oscillations of droplets to drive lateral contact-line motion. Reynolds numbers based on CL speeds are high and capillary numbers are low. These are inertial-capillary motions. By scanning the driving frequency, we locate the frequency at peak amplification (resonance), obtain the scaled peak height (amplification factor) and a measure of band-width (damping ratio). We report how a parameter for CL mobility depends on these scanning metrics, with the goal of distinguishing contributions from the bulk- and CL-dissipation to overall damping.

  6. Proceedings of Damping Volume 1 of 3

    Science.gov (United States)

    1993-06-01

    passive damping studies familiar to him in the last decade. As mentioned above, many current space missions require stringent performance...friction within the alpha joint is thought to be sufficient to keep the joint locked, producing essentially linear behavior and the familiar modal peak...effects. ACKNOWLEDGMENTS This work is sponsored in part by Consiglio Nazionale delle Ricerche under grant CTB 91.2073.CTll :"Analisi dinamica combinata

  7. Gyroscopic stabilization and indefimite damped systems

    DEFF Research Database (Denmark)

    Pommer, Christian

    matrix. d and g are scaling factors used to control the stability of the system. It is quite astonnishing that when the damping matrix D is indefinite the system can under certain conditions be stable even if there are no gyroscopic forces G present The Lyapunov matrix equation is used to predict...... the stabilty limit for pure dissipative systems as well as for dissipative systems with gyroscopic stabilization....

  8. Transfection of the Human Heme Oxygenase Gene Into Rabbit Coronary Microvessel Endothelial Cells: Protective Effect Against Heme and Hemoglobin Toxicity

    Science.gov (United States)

    Abraham, N. G.; Lavrovsky, Y.; Schwartzman, M. L.; Stoltz, R. A.; Levere, R. D.; Gerritsen, M. E.

    1995-07-01

    Heme oxygenase (HO) is a stress protein and has been suggested to participate in defense mechanisms against agents that may induce oxidative injury such as metals, endotoxin, heme/hemoglobin, and various cytokines. Overexpression of HO in cells might therefore protect against oxidative stress produced by certain of these agents, specifically heme and hemoglobin, by catalyzing their degradation to bilirubin, which itself has antioxidant properties. We report here the successful in vitro transfection of rabbit coronary microvessel endothelial cells with a functioning gene encoding the human HO enzyme. A plasmid containing the cytomegalovirus promoter and the human HO cDNA complexed to cationic liposomes (Lipofectin) was used to transfect rabbit endothelial cells. Cells transfected with human HO exhibited an ≈3.0-fold increase in enzyme activity and expressed a severalfold induction of human HO mRNA as compared with endogenous rabbit HO mRNA. Transfected and nontransfected cells expressed factor VIII antigen and exhibited similar acetylated low-density lipoprotein uptake (two important features that characterize endothelial cells) with >85% of cells staining positive for each marker. Moreover, cells transfected with the human HO gene acquired substantial resistance to toxicity produced by exposure to recombinant hemoglobin and heme as compared with nontransfected cells. The protective effect of HO overexpression against heme/hemoglobin toxicity in endothelial cells shown in these studies provides direct evidence that the inductive response of human HO to such injurious stimuli represents an important tissue adaptive mechanism for moderating the severity of cell damage produced by these blood components.

  9. Metabolite-driven Regulation of Heme Uptake by the Biliverdin IXβ/δ-Selective Heme Oxygenase (HemO) of Pseudomonas aeruginosa.

    Science.gov (United States)

    Mouriño, Susana; Giardina, Bennett J; Reyes-Caballero, Hermes; Wilks, Angela

    2016-09-23

    Pseudomonas aeruginosa acquires extracellular heme via the Phu (Pseudomonas heme uptake) and Has (heme assimilation system) systems. We have previously shown the catalytic actions of heme oxygenase (HemO) along with the cytoplasmic heme transport protein PhuS control heme flux into the cell. To further investigate the role of the PhuS-HemO couple in modulating heme uptake, we have characterized two HemO variants, one that is catalytically inactive (HemO H26A/K34A/K132A or HemOin) and one that has altered regioselectivity (HemO N19K/K34A/F117Y/K132A or HemOα), producing biliverdin IXα (BVIXα). HemOα similar to wild type was able to interact and acquire heme from holo-PhuS. In contrast, the HemOin variant did not interact with holo-PhuS and showed no enzymatic activity. Complementation of a hemO deletion strain with the hemOin or hemOα variants in combination with [(13)C]heme isotopic labeling experiments revealed that the absence of BVIXβ and BVIXδ leads to a decrease in extracellular levels of hemophore HasA. We propose BVIXβ and/or BVIXδ transcriptionally or post-transcriptionally regulates HasA. Thus, coupling the PhuS-dependent flux of heme through HemO to feedback regulation of the cell surface signaling system through HasA allows P. aeruginosa to rapidly respond to fluctuating extracellular heme levels independent of the iron status of the cell. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  10. Structure of the heme/hemoglobin outer membrane receptor ShuA from Shigella dysenteriae: heme binding by an induced fit mechanism.

    Science.gov (United States)

    Cobessi, David; Meksem, Ahmed; Brillet, Karl

    2010-02-01

    Shigella dysentriae and other Gram-negative human pathogens are able to use iron from heme bound to hemoglobin for growing. We solved at 2.6 A resolution the 3D structure of the TonB-dependent heme/hemoglobin outer membrane receptor ShuA from S. dysenteriae. ShuA binds to hemoglobin and transports heme across the outer membrane. The structure consists of a C-terminal domain that folds into a 22-stranded transmembrane beta-barrel, which is filled by the N-terminal plug domain. One distal histidine ligand of heme is located at the apex of the plug, exposed to the solvent. His86 is situated 9.86 A apart from His420, the second histidine involved in the heme binding. His420 is in the extracellular loop L7. The heme coordination by His86 and His420 involves conformational changes. The comparisons with the hemophore receptor HasR of Serratia marcescens bound to HasA-Heme suggest an extracellular induced fit mechanism for the heme binding. The loop L7 contains hydrophobic residues which could interact with the hydrophobic porphyring ring of heme. The energy required for the transport by ShuA is derived from the proton motive force after interactions between the periplasmic N-terminal TonB-box of ShuA and the inner membrane protein, TonB. In ShuA, the TonB-box is buried and cannot interact with TonB. The structural comparisons with HasR suggest its conformational change upon the heme binding for interacting with TonB. The signaling of the heme binding could involve a hydrogen bond network going from His86 to the TonB-box. (c) 2009 Wiley-Liss, Inc.

  11. First Results from the DAMPE Mission

    CERN Document Server

    CERN. Geneva

    2018-01-01

    DAMPE (DArk Matter Particle Explorer) is a satellite mission of the Chinese Academy of Sciences (CAS) dedicated to high energy cosmic ray detections. Since its successful launch on December 17th, 2015 a large amount of cosmic ray data has been collected. With relatively large acceptance, DAMPE is designed to detect electrons (and positrons) up to 10 TeV with unprecedented energy resolution to search for new features in the cosmic ray electron plus positron (CRE) spectrum. It will also study cosmic ray nuclei up to 100 TeV with good precision, which will bring new input to the study of their still unknown origin and their propagation through the Galaxy. In this talk, the DAMPE mission will be introduced, together with some details of the construction and on-ground calibration of the detector subsystems. The in-orbit detector commissioning, calibration and operation will be described. First data analysis results, including the recently published CRE spectrum from 25 GeV to 4.6 TeV based on the data collected i...

  12. Minimizing Emittance for the CLIC Damping Ring

    CERN Document Server

    Braun, H; Levitchev, E; Piminov, P; Schulte, Daniel; Siniatkin, S; Vobly, P P; Zimmermann, Frank; Zolotarev, Konstantin V; CERN. Geneva

    2006-01-01

    The CLIC damping rings aim at unprecedented small normalized equilibrium emittances of 3.3 nm vertical and 550 nm horizontal, for a bunch charge of 2.6·109 particles and an energy of 2.4 GeV. In this parameter regime the dominant emittance growth mechanism is intra-beam scattering. Intense synchrotron radiation damping from wigglers is required to counteract its effect. Here the overall optimization of the wiggler parameters is described, taking into account state-of-the-art wiggler technologies, wiggler effects on dynamic aperture, and problems of wiggler radiation absorption. Two technical solutions, one based on superconducting magnet technology the other on permanent magnets are presented. Although dynamic aperture and tolerances of this ring design remain challenging, benefits are obtained from the strong damping. For optimized wigglers, only bunches for a single machine pulse may need to be stored, making injection/extraction particularly simple and limiting the synchrotron-radiation power. With a 36...

  13. Isoporphyrin intermediate in heme oxygenase catalysis. Oxidation of alpha-meso-phenylheme.

    Science.gov (United States)

    Evans, John P; Niemevz, Fernando; Buldain, Graciela; de Montellano, Paul Ortiz

    2008-07-11

    Human heme oxygenase-1 (hHO-1) catalyzes the O2- and NADPH-dependent oxidation of heme to biliverdin, CO, and free iron. The first step involves regiospecific insertion of an oxygen atom at the alpha-meso carbon by a ferric hydroperoxide and is predicted to proceed via an isoporphyrin pi-cation intermediate. Here we report spectroscopic detection of a transient intermediate during oxidation by hHO-1 of alpha-meso-phenylheme-IX, alpha-meso-(p-methylphenyl)-mesoheme-III, and alpha-meso-(p-trifluoromethylphenyl)-mesoheme-III. In agreement with previous experiments (Wang, J., Niemevz, F., Lad, L., Huang, L., Alvarez, D. E., Buldain, G., Poulos, T. L., and Ortiz de Montellano, P. R. (2004) J. Biol. Chem. 279, 42593-42604), only the alpha-biliverdin isomer is produced with concomitant formation of the corresponding benzoic acid. The transient intermediate observed in the NADPH-P450 reductase-catalyzed reaction accumulated when the reaction was supported by H2O2 and exhibited the absorption maxima at 435 and 930 nm characteristic of an isoporphyrin. Product analysis by reversed phase high performance liquid chromatography and liquid chromatography electrospray ionization mass spectrometry of the product generated with H2O2 identified it as an isoporphyrin that, on quenching, decayed to benzoylbiliverdin. In the presence of H218O2, one labeled oxygen atom was incorporated into these products. The hHO-1-isoporphyrin complexes were found to have half-lives of 1.7 and 2.4 h for the p-trifluoromethyl- and p-methyl-substituted phenylhemes, respectively. The addition of NADPH-P450 reductase to the H2O2-generated hHO-1-isoporphyrin complex produced alpha-biliverdin, confirming its role as a reaction intermediate. Identification of an isoporphyrin intermediate in the catalytic sequence of hHO-1, the first such intermediate observed in hemoprotein catalysis, completes our understanding of the critical first step of heme oxidation.

  14. The dppBCDF gene cluster of Haemophilus influenzae: Role in heme utilization

    Directory of Open Access Journals (Sweden)

    Morton Daniel J

    2009-08-01

    Full Text Available Abstract Background Haemophilus influenzae requires a porphyrin source for aerobic growth and possesses multiple mechanisms to obtain this essential nutrient. This porphyrin requirement may be satisfied by either heme alone, or protoporphyrin IX in the presence of an iron source. One protein involved in heme acquisition by H. influenzae is the periplasmic heme binding protein HbpA. HbpA exhibits significant homology to the dipeptide and heme binding protein DppA of Escherichia coli. DppA is a component of the DppABCDF peptide-heme permease of E. coli. H. influenzae homologs of dppBCDF are located in the genome at a point distant from hbpA. The object of this study was to investigate the potential role of the H. influenzae dppBCDF locus in heme utilization. Findings An insertional mutation in dppC was constructed and the impact of the mutation on the utilization of both free heme and various proteinaceous heme sources as well as utilization of protoporphyrin IX was determined in growth curve studies. The dppC insertion mutant strain was significantly impacted in utilization of all tested heme sources and protoporphyin IX. Complementation of the dppC mutation with an intact dppCBDF gene cluster in trans corrected the growth defects seen in the dppC mutant strain. Conclusion The dppCBDF gene cluster constitutes part of the periplasmic heme-acquisition systems of H. influenzae.

  15. Heme A synthase in bacteria depends on one pair of cysteinyls for activity.

    Science.gov (United States)

    Lewin, Anna; Hederstedt, Lars

    2016-02-01

    Heme A is a prosthetic group unique for cytochrome a-type respiratory oxidases in mammals, plants and many microorganisms. The poorly understood integral membrane protein heme A synthase catalyzes the synthesis of heme A from heme O. In bacteria, but not in mitochondria, this enzyme contains one or two pairs of cysteine residues that are present in predicted hydrophilic polypeptide loops on the extracytoplasmic side of the membrane. We used heme A synthase from the eubacterium Bacillus subtilis and the hyperthermophilic archeon Aeropyrum pernix to investigate the functional role of these cysteine residues. Results with B. subtilis amino acid substituted proteins indicated the pair of cysteine residues in the loop connecting transmembrane segments I and II as being essential for catalysis but not required for binding of the enzyme substrate, heme O. Experiments with isolated A. pernix and B. subtilis heme A synthase demonstrated that a disulfide bond can form between the cysteine residues in the same loop and also between loops showing close proximity of the two loops in the folded enzyme protein. Based on the findings, we propose a classification scheme for the four discrete types of heme A synthase found so far in different organisms and propose that essential cysteinyls mediate transfer of reducing equivalents required for the oxygen-dependent catalysis of heme A synthesis from heme O. Copyright © 2015 Elsevier B.V. All rights reserved.

  16. Alteration by irradiation and storage at amount of heme iron in poultry meat; Alteracoes provocadas pela irradiacao e armazenamento nos teores de ferro heme em carne de frango

    Energy Technology Data Exchange (ETDEWEB)

    Souza, Adriana Regia Marques de; Arthur, Valter Arthur [Centro de Energia Nuclear na Agricultura (CENA), Piracicaba, SP (Brazil). Lab. de Irradiacao de Alimentos e Radioentomologia; Canniatti-Brazaca, Solange Guidolin [Escola Superior de Agricultura Luiz de Queiroz (ESALQ/USP), Piracicaba, SP (Brazil). Dept. de Agroindustria, Alimentos e Nutricao]. E-mail: sgcbraza@esalq.usp.br

    2007-04-15

    Studies of irradiation and storage effects in chicken were carried out to discover the influence in iron heme, non-heme amount, color and total pigments. Chicken thighs and chicken breast were studied. These were irradiated to 0, 1 and 2 kGy stored by 14 days to 4 deg C in refrigerator. Determining the heme content and non-heme of meat was done using the colorimeter method and the Ferrozine reagent. The values of iron heme were influenced both by the irradiation and the storage, reducing the amount throughout the course of time. The iron non-heme was also influenced by the doses and the storage time, however the values increased throughout the course of time, because of the conversion of iron heme in non-heme. The color did not show that it was influenced by the studied doses, except for the storage, and the total number of pigments was affected by the irradiation and the time, reducing the values with the increase of storage. Irradiation was shown to be a good method to conserve iron. (author)

  17. Redox and light control the heme-sensing activity of AppA.

    Science.gov (United States)

    Yin, Liang; Dragnea, Vladimira; Feldman, George; Hammad, Loubna A; Karty, Jonathan A; Dann, Charles E; Bauer, Carl E

    2013-08-27

    The DNA binding activity of the photosystem-specific repressor PpsR is known to be repressed by the antirepressor AppA. AppA contains a blue-light-absorbing BLUF domain and a heme-binding SCHIC domain that controls the interaction of AppA with PpsR in response to light and heme availability. In this study, we have solved the structure of the SCHIC domain and identified the histidine residue that is critical for heme binding. We also demonstrate that dark-adapted AppA binds heme better than light-excited AppA does and that heme bound to the SCHIC domain significantly reduces the length of the BLUF photocycle. We further show that heme binding to the SCHIC domain is affected by the redox state of a disulfide bridge located in the Cys-rich carboxyl-terminal region. These results demonstrate that light, redox, and heme are integrated inputs that control AppA's ability to disrupt the DNA binding activity of PpsR. Photosynthetic bacteria must coordinate synthesis of the tetrapyrroles cobalamin, heme, and bacteriochlorophyll, as overproduction of the latter two is toxic to cells. A key regulator controlling tetrapyrrole biosynthesis is PpsR, and the activity of PpsR is controlled by the heme-binding and light-regulated antirepressor AppA. We show that AppA binds heme only under dark conditions and that heme binding significantly affects the length of the AppA photocycle. Since AppA interacts with PpsR only in the dark, bound heme thus stimulates the antirepressor activity of PpsR. This causes the redirection of tetrapyrrole biosynthesis away from heme into the bacteriochlorophyll branch.

  18. Suboptimal Rayleigh damping coefficients in seismic analysis of viscously-damped structures

    Science.gov (United States)

    Pan, Danguang; Chen, Genda; Wang, Zuocai

    2014-12-01

    An optimization method for the consistent evaluation of two Rayleigh damping coefficients is proposed. By minimizing an objective function such as an error term of the peak displacement of a structure, the two coefficients can be determined with response spectral analysis. The optimization method degenerates into the conventional method used in current practices when only two modes of vibration are included in the objective function. Therefore, the proposed method with all significant modes included for simplicity in practical applications results in suboptimal damping coefficients. The effects of both spatial distribution and frequency content of excitations as well as structural dynamic characteristics on the evaluation of Rayleigh damping coefficients were investigated with a five-story building structure. Two application examples with a 62-story high-rise building and a 840 m long cable-stayed bridge under ten earthquake excitations demonstrated the accuracy and effectiveness of the proposed method to account for all of the above effects.

  19. Non-Linear Slosh Damping Model Development and Validation

    Science.gov (United States)

    Yang, H. Q.; West, Jeff

    2015-01-01

    Propellant tank slosh dynamics are typically represented by a mechanical model of spring mass damper. This mechanical model is then included in the equation of motion of the entire vehicle for Guidance, Navigation and Control (GN&C) analysis. For a partially-filled smooth wall propellant tank, the critical damping based on classical empirical correlation is as low as 0.05%. Due to this low value of damping, propellant slosh is potential sources of disturbance critical to the stability of launch and space vehicles. It is postulated that the commonly quoted slosh damping is valid only under the linear regime where the slosh amplitude is small. With the increase of slosh amplitude, the critical damping value should also increase. If this nonlinearity can be verified and validated, the slosh stability margin can be significantly improved, and the level of conservatism maintained in the GN&C analysis can be lessened. The purpose of this study is to explore and to quantify the dependence of slosh damping with slosh amplitude. Accurately predicting the extremely low damping value of a smooth wall tank is very challenging for any Computational Fluid Dynamics (CFD) tool. One must resolve thin boundary layers near the wall and limit numerical damping to minimum. This computational study demonstrates that with proper grid resolution, CFD can indeed accurately predict the low damping physics from smooth walls under the linear regime. Comparisons of extracted damping values with experimental data for different tank sizes show very good agreements. Numerical simulations confirm that slosh damping is indeed a function of slosh amplitude. When slosh amplitude is low, the damping ratio is essentially constant, which is consistent with the empirical correlation. Once the amplitude reaches a critical value, the damping ratio becomes a linearly increasing function of the slosh amplitude. A follow-on experiment validated the developed nonlinear damping relationship. This discovery can

  20. Principles of TRIP Steel Optimization for Passive Damping Applications

    Science.gov (United States)

    Fraley, George Jay

    Globally many historic structures of cultural significance which do not have systems to mitigate seismic damage are located in areas with heavy seismic activity. Efforts have been undertaken to develop strategies to retrofit such structures, however any intervention must be limited in size for aesthetic reasons. To contribute to this effort, ArcelorMittal aims to create steel-based solutions for passive energy dissipation through plastic deformation during cyclic loading. High-strength TRansformation-Induced Plasticity (TRIP) steels are proposed as an excellent candidate material for this application, due to the extreme combination of high strength and large ductility they are well-known to exhibit. To evaluate high-strength TRIP steels for passive damping applications, isothermal, fully-reversed, displacement-controlled Ultra-Low Cycle Fatigue (ULCF) experiments (Nf sigma = -8 °C) was found to have approximately twice the fatigue life and a lower rate of cyclic hardening at fixed displacement amplitudes for low to intermediate levels of plastic strain range (2-10%) compared to the lower stability austenite condition (Mssigma = 27 °C). However, at higher levels of plastic straining (10-16% strain range) the fatigue lives and strain hardening behavior converged for the two stabilities, indicating a likely exhaustion of transformation during the first few cycles. ULCF life behavior for the high-stability austenite condition compared favorably with literature values for structural stainless steel 316, despite having a yield strength approximately four times larger. For a similar number of cycles to failure the high stability condition dissipated 2.4 times more energy than stainless steel 316 upon initial cycling. The stress-strain hysteresis curves and fatigue life data generated can be input into computational models of passive damping devices for initial concurrent material/device design iterations. Evidence of shear lips, large primary inclusions serving as

  1. Challenging Density Functional Theory Calculations with Hemes and Porphyrins

    Directory of Open Access Journals (Sweden)

    Sam P. de Visser

    2016-04-01

    Full Text Available In this paper we review recent advances in computational chemistry and specifically focus on the chemical description of heme proteins and synthetic porphyrins that act as both mimics of natural processes and technological uses. These are challenging biochemical systems involved in electron transfer as well as biocatalysis processes. In recent years computational tools have improved considerably and now can reproduce experimental spectroscopic and reactivity studies within a reasonable error margin (several kcal·mol−1. This paper gives recent examples from our groups, where we investigated heme and synthetic metal-porphyrin systems. The four case studies highlight how computational modelling can correctly reproduce experimental product distributions, predicted reactivity trends and guide interpretation of electronic structures of complex systems. The case studies focus on the calculations of a variety of spectroscopic features of porphyrins and show how computational modelling gives important insight that explains the experimental spectra and can lead to the design of porphyrins with tuned properties.

  2. Using heme as an energy boost for lactic acid bacteria.

    Science.gov (United States)

    Lechardeur, Delphine; Cesselin, Bénédicte; Fernandez, Annabelle; Lamberet, Gilles; Garrigues, Christel; Pedersen, Martin; Gaudu, Philippe; Gruss, Alexandra

    2011-04-01

    Lactic acid bacteria (LAB) are a phylogenetically diverse group named for their main attribute in food fermentations, that is, production of lactic acid. However, several LAB are genetically equipped for aerobic respiration metabolism when provided with exogenous sources of heme (and menaquinones for some species). Respiration metabolism is energetically favorable and leads to less oxidative and acid stress during growth. As a consequence, the growth and survival of several LAB can be dramatically improved under respiration-permissive conditions. Respiration metabolism already has industrial applications for the production of dairy starter cultures. In view of the growth and survival advantages conferred by respiration, and the availability of heme and menaquinones in natural environments, we recommend that respiration be accepted as a part of the natural lifestyle of numerous LAB. Copyright © 2010 Elsevier Ltd. All rights reserved.

  3. Challenging Density Functional Theory Calculations with Hemes and Porphyrins

    Science.gov (United States)

    de Visser, Sam P.; Stillman, Martin J.

    2016-01-01

    In this paper we review recent advances in computational chemistry and specifically focus on the chemical description of heme proteins and synthetic porphyrins that act as both mimics of natural processes and technological uses. These are challenging biochemical systems involved in electron transfer as well as biocatalysis processes. In recent years computational tools have improved considerably and now can reproduce experimental spectroscopic and reactivity studies within a reasonable error margin (several kcal·mol−1). This paper gives recent examples from our groups, where we investigated heme and synthetic metal-porphyrin systems. The four case studies highlight how computational modelling can correctly reproduce experimental product distributions, predicted reactivity trends and guide interpretation of electronic structures of complex systems. The case studies focus on the calculations of a variety of spectroscopic features of porphyrins and show how computational modelling gives important insight that explains the experimental spectra and can lead to the design of porphyrins with tuned properties. PMID:27070578

  4. Functional imaging: monitoring heme oxygenase-1 gene expression in vivo

    Science.gov (United States)

    Zhang, Weisheng; Reilly-Contag, Pamela; Stevenson, David K.; Contag, Christopher H.

    1999-07-01

    The regulation of genetic elements can be monitored in living animals using photoproteins as reporters. Heme oxygenase (HO) is the key catabolic enzyme in the heme degradation pathway. Here, HO expression serves as a model for in vivo functional imaging of transcriptional regulation of a clinically relevant gene. HO enzymatic activity is inhibited by heme analogs, metalloporphyrins, but many members of this family of compounds also activate transcription of the HO-1 promoter. The degree of transcriptional activation by twelve metalloporphyrins, differing at the central metal and porphyrin ring substituents, was evaluated in both NIH 3T3 stable lines and transgenic animals containing HO-1 promoter-luciferase gene fusions. In the correlative cell culture assays, the metalloporphyrins increased transcription form the full length HO promoter fusion to varying degrees, but none increased transcription from a truncated HO-1 promoter. These results suggested that one or both of the two distal enhancer elements located at -4 and -10 Kb upstream from transcriptional start are required for HO-1 induction by heme and its analogs. The full-length HO-1-luc fusion was then evaluated as a transgene in mice. It was possible to monitor the effects of the metalloporphyrins, SnMP and ZnPP, in living animals over time. This spatiotemporal analyses of gene expression in vivo implied that alterations in porphyrin ring substituents and the central metal may affect the extent of gene activation. These data further indicate that using photoprotein reporters, subtle differences in gene expression can be monitored in living animals.

  5. Cyanide binding to human plasma heme-hemopexin: A comparative study

    Energy Technology Data Exchange (ETDEWEB)

    Ascenzi, Paolo, E-mail: ascenzi@uniroma3.it [Laboratorio Interdipartimentale di Microscopia Elettronica, Universita Roma Tre, Roma (Italy); Istituto Nazionale di Biostrutture e Biosistemi, Roma (Italy); Leboffe, Loris [Istituto Nazionale di Biostrutture e Biosistemi, Roma (Italy); Polticelli, Fabio [Dipartimento di Biologia, Universita Roma Tre, Roma (Italy)

    2012-11-16

    Highlights: Black-Right-Pointing-Pointer Cyanide binding to ferric HHPX-heme-Fe. Black-Right-Pointing-Pointer Cyanide binding to ferrous HHPX-heme-Fe. Black-Right-Pointing-Pointer Dithionite-mediated reduction of ferric HHPX-heme-Fe-cyanide. Black-Right-Pointing-Pointer Cyanide binding to HHPX-heme-Fe is limited by ligand deprotonation. Black-Right-Pointing-Pointer Cyanide dissociation from HHPX-heme-Fe-cyanide is limited by ligand protonation. -- Abstract: Hemopexin (HPX) displays a pivotal role in heme scavenging and delivery to the liver. In turn, heme-Fe-hemopexin (HPX-heme-Fe) displays heme-based spectroscopic and reactivity properties. Here, kinetics and thermodynamics of cyanide binding to ferric and ferrous hexa-coordinate human plasma HPX-heme-Fe (HHPX-heme-Fe(III) and HHPX-heme-Fe(II), respectively), and for the dithionite-mediated reduction of the HHPX-heme-Fe(III)-cyanide complex, at pH 7.4 and 20.0 Degree-Sign C, are reported. Values of thermodynamic and kinetic parameters for cyanide binding to HHPX-heme-Fe(III) and HHPX-heme-Fe(II) are K = (4.1 {+-} 0.4) Multiplication-Sign 10{sup -6} M, k{sub on} = (6.9 {+-} 0.5) Multiplication-Sign 10{sup 1} M{sup -1} s{sup -1}, and k{sub off} = 2.8 Multiplication-Sign 10{sup -4} s{sup -1}; and H = (6 {+-} 1) Multiplication-Sign 10{sup -1} M, h{sub on} = 1.2 Multiplication-Sign 10{sup -1} M{sup -1} s{sup -1}, and h{sub off} = (7.1 {+-} 0.8) Multiplication-Sign 10{sup -2} s{sup -1}, respectively. The value of the rate constant for the dithionite-mediated reduction of the HHPX-heme-Fe(III)-cyanide complex is l = 8.9 {+-} 0.8 M{sup -1/2} s{sup -1}. HHPX-heme-Fe reactivity is modulated by proton acceptor/donor amino acid residue(s) (e.g., His236) assisting the deprotonation and protonation of the incoming and outgoing ligand, respectively.

  6. Dietary Heme Induces Gut Dysbiosis, Aggravates Colitis, and Potentiates the Development of Adenomas in Mice

    Directory of Open Access Journals (Sweden)

    Marco Constante

    2017-09-01

    Full Text Available Dietary heme can be used by colonic bacteria equipped with heme-uptake systems as a growth factor and thereby impact on the microbial community structure. The impact of heme on the gut microbiota composition may be particularly pertinent in chronic inflammation such as in inflammatory bowel disease (IBD, where a strong association with gut dysbiosis has been consistently reported. In this study we investigated the influence of dietary heme on the gut microbiota and inferred metagenomic composition, and on chemically induced colitis and colitis-associated adenoma development in mice. Using 16S rRNA gene sequencing, we found that mice fed a diet supplemented with heme significantly altered their microbiota composition, characterized by a decrease in α-diversity, a reduction of Firmicutes and an increase of Proteobacteria, particularly Enterobacteriaceae. These changes were similar to shifts seen in dextran sodium sulfate (DSS-treated mice to induce colitis. In addition, dietary heme, but not systemically delivered heme, contributed to the exacerbation of DSS-induced colitis and facilitated adenoma formation in the azoxymethane/DSS colorectal cancer (CRC mouse model. Using inferred metagenomics, we found that the microbiota alterations elicited by dietary heme resulted in non-beneficial functional shifts, which were also characteristic of DSS-induced colitis. Furthermore, a reduction in fecal butyrate levels was found in mice fed the heme supplemented diet compared to mice fed the control diet. Iron metabolism genes known to contribute to heme release from red blood cells, heme uptake, and heme exporter proteins, were significantly enriched, indicating a shift toward favoring the growth of bacteria able to uptake heme and protect against its toxicity. In conclusion, our data suggest that luminal heme, originating from dietary components or gastrointestinal bleeding in IBD and, to lesser extent in CRC, directly contributes to microbiota dysbiosis

  7. Microsomal prostaglandin E synthase type 2 (mPGES2) is a glutathione-dependent heme protein, and dithiothreitol dissociates the bound heme to produce active prostaglandin E2 synthase in vitro.

    Science.gov (United States)

    Takusagawa, Fusao

    2013-04-05

    An x-ray study indicated that microsomal prostaglandin E synthase type 2 (mPGES2) is a heme-bound protein and catalyzes prostaglandin (PG) H2 degradation, but not PGE2 formation (Yamada, T., and Takusagawa, F. (2007) Biochemistry 46, 8414-8424). In response to the x-ray study, Watanabe et al. claimed that mPGES2 is a heme-free protein and that both the heme-free and heme-bound proteins have PGE2 synthesis activity in the presence of dithiothreitol (Watanabe, K., Ito, S., and Yamamoto, S. (2008) Biochem. Biophys. Res. Commun. 367, 782-786). To resolve the contradictory results, the heme-binding scheme of mPGES2 was further characterized in vivo and in vitro by absorption and fluorescence spectroscopies. A substantial amount of heme-bound mPGES2 was detected in cell extracts. The heme content in mPGES2 was increased along with an increase in Fe(3+) in the culture medium. Heme-free mPGES2 was converted to the heme-bound form by mixing it with pig liver extract, indicating that mPGES2 is capable of forming a complex with heme in mammalian cells. Heme binds to mPGES2 only in the presence of glutathione. The newly determined heme dissociation constant (2.9 nM) supports strongly that mPGES2 is a heme-bound protein in vivo. The bound heme was not dissociated by oxidation by H2O2 or reduction by glutathione or 2-mercaptoethanol. However, reduction by dithiothreitol (an artificial reducing compound) induced the bound heme to dissociate from mPGES2 and released heme-free mPGES2, which exhibited PGE2 synthesis activity in vitro. Imidazole bound to mPGES2 by stacking on the bound heme and inhibited heme oxidation by H2O2 and reduction by dithiothreitol.

  8. Heme oxygenase-1 enhances autophagy in podocytes as a protective mechanism against high glucose-induced apoptosis

    Energy Technology Data Exchange (ETDEWEB)

    Dong, Chenglong [Department of Endocrinology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing (China); Zheng, Haining [Department of Hyperbaric Oxygen, Nanjing General Hospital of Nanjing Military Command, Nanjing (China); Huang, Shanshan; You, Na; Xu, Jiarong; Ye, Xiaolong; Zhu, Qun; Feng, Yamin; You, Qiang; Miao, Heng [Department of Endocrinology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing (China); Ding, Dafa, E-mail: dingdafa2004@aliyun.com [Department of Endocrinology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing (China); Lu, Yibing, E-mail: luyibing2004@126.com [Department of Endocrinology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing (China)

    2015-10-01

    Injury and loss of podocytes play vital roles in diabetic nephropathy progression. Emerging evidence suggests autophagy, which is induced by multiple stressors including hyperglycemia, plays a protective role. Meanwhile, heme oxygenase-1 (HO-1) possesses powerful anti-apoptotic properties. Therefore, we investigated the impact of autophagy on podocyte apoptosis under diabetic conditions and its association with HO-1. Mouse podocytes were cultured in vitro; apoptosis was detected by flow cytometry. Transmission electron microscopy and biochemical autophagic flux assays were used to measure the autophagy markers microtubule-associated protein 1 light chain 3-II (LC3-II) and beclin-1. LC3-II and beclin-1 expression peaked 12–24 h after exposing podocytes to high glucose. Inhibition of autophagy with 3-methyladenine or Beclin-1 siRNAs or Atg 5 siRNAs sensitized cells to apoptosis, suggesting autophagy is a survival mechanism. HO-1 inactivation inhibited autophagy, which aggravated podocyte injury in vitro. Hemin-induced autophagy also protected podocytes from hyperglycemia in vitro and was abrogated by HO-1 siRNA. Adenosine monophosphate-activated protein kinase phosphorylation was higher in hemin-treated and lower in HO-1 siRNA-treated podocytes. Suppression of AMPK activity reversed HO-1-mediated Beclin-1 upregulation and autophagy, indicating HO-1-mediated autophagy is AMPK dependent. These findings suggest HO-1 induction and regulation of autophagy are potential therapeutic targets for diabetic nephropathy. - Highlights: • High glucose leads to increased autophagy in podocytes at an early stage. • The early autophagic response protects against high glucose-induced apoptosis. • Heme oxygenase-1 enhances autophagy and decreases high glucose -mediated apoptosis. • Heme oxygenase-1 induces autophagy through the activation of AMPK.

  9. Lysophospholipids and Their Receptors Serve as Conditional DAMPs and DAMP Receptors in Tissue Oxidative and Inflammatory Injury.

    Science.gov (United States)

    Shao, Ying; Nanayakkara, Gayani; Cheng, Jiali; Cueto, Ramon; Yang, William Y; Park, Joon-Young; Wang, Hong; Yang, Xiaofeng

    2017-04-26

    We proposed lysophospholipids (LPLs) and LPL-G-protein-coupled receptors (GPCRs) as conditional danger-associated molecular patterns (DAMPs) and conditional DAMP receptors as a paradigm shift to the widely accepted classical DAMP and DAMP receptor model. Recent Advances: The aberrant levels of LPLs and GPCRs activate pro-inflammatory signal transduction pathways, trigger innate immune response, and lead to tissue oxidative and inflammatory injury. Classical DAMP model specifies only the endogenous metabolites that are released from damaged/dying cells as DAMPs, but fails to identify elevated endogenous metabolites secreted from viable/live cells during pathologies as DAMPs. The current classification of DAMPs also fails to clarify the following concerns: (i) Are molecules, which bind to pattern recognition receptors (PRRs), the only DAMPs contributing to inflammation and tissue injury? (ii) Are all DAMPs acting only via classical PRRs during cellular stress? To answer these questions, we reviewed the molecular characteristics and signaling mechanisms of LPLs, a group of endogenous metabolites and their specific receptors and analyzed the significant progress achieved in characterizing oxidative stress mechanisms of LPL mediated tissue injury. Further LPLs and LPL-GPCRs may serve as potential therapeutic targets for the treatment of pathologies induced by sterile inflammation. Antioxid. Redox Signal. 00, 000-000.

  10. Dual role of the active-center cysteine in human peroxiredoxin 1: Peroxidase activity and heme binding.

    Science.gov (United States)

    Watanabe, Yuta; Ishimori, Koichiro; Uchida, Takeshi

    2017-02-12

    HBP23, a 23-kDa heme-binding protein identified in rats, is a member of the peroxiredoxin (Prx) family, the primary peroxidases involved in hydrogen peroxide catabolism. Although HBP23 has a characteristic Cys-Pro heme-binding motif, the significance of heme binding to Prx family proteins remains to be elucidated. Here, we examined the effect of heme binding to human peroxiredoxin-1 (PRX1), which has 97% amino acid identity to HBP23. PRX1 was expressed in Escherichia coli and purified to homogeneity. Spectroscopic titration demonstrated that PRX1 binds heme with a 1:1 stoichiometry and a dissociation constant of 0.17 μM. UV-vis spectra of heme-PRX1 suggested that Cys52 is the axial ligand of ferric heme. PRX1 peroxidase activity was lost upon heme binding, reflecting the fact that Cys52 is not only the heme-binding site but also the active center of peroxidase activity. Interestingly, heme binding to PRX1 caused a decrease in the toxicity and degradation of heme, significantly suppressing H2O2-dependent heme peroxidase activity and degradation of PRX1-bound heme compared with that of free hemin. By virtue of its cytosolic abundance (∼20 μM), PRX1 thus functions as a scavenger of cytosolic hemin (dual role; Cys-dependent peroxidase activity and cytosolic heme scavenger. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Heme-mediated cell activation: the inflammatory puzzle of sickle cell anemia.

    Science.gov (United States)

    Guarda, Caroline Conceição da; Santiago, Rayra Pereira; Fiuza, Luciana Magalhães; Aleluia, Milena Magalhães; Ferreira, Júnia Raquel Dutra; Figueiredo, Camylla Vilas Boas; Yahouedehou, Setondji Cocou Modeste Alexandre; Oliveira, Rodrigo Mota de; Lyra, Isa Menezes; Gonçalves, Marilda de Souza

    2017-06-01

    Hemolysis triggers the onset of several clinical manifestations of sickle cell anemia (SCA). During hemolysis, heme, which is derived from hemoglobin (Hb), accumulates due to the inability of detoxification systems to scavenge sufficiently. Heme exerts multiple harmful effects, including leukocyte activation and migration, enhanced adhesion molecule expression by endothelial cells and the production of pro-oxidant molecules. Area covered: In this review, we describe the effects of heme on leukocytes and endothelial cells, as well as the features of vascular endothelial cells related to vaso-occlusion in SCA. Expert commentary: Free Hb, heme and iron, potent cytotoxic intravascular molecules released during hemolysis, can exacerbate, modulate and maintain the inflammatory response, a main feature of SCA. Endothelial cells in the vascular environment, as well as leukocytes, can become activated via the molecular signaling effects of heme. Due to the hemolytic nature of SCA, hemolysis represents an interesting therapeutic target for heme-scavenging purposes.

  12. Shear measurements of viscoelastic damping materials embedded in composite plates

    Science.gov (United States)

    Biggerstaff, Janet M.; Kosmatka, John B.

    1999-06-01

    Embedding viscoelastic damping materials into graphite/epoxy composites can greatly increase the damping of composite structures. Cocuring the damping material with the composite, however, has been shown to increase the modulus and lower the damping in many viscoelastic materials because epoxy penetrates many damping materials (especially acrylics). In this paper, the changes in shear modulus were measured using double lap shear tests. Also presented are shear moduli comparisons of samples cured with three different barrier film layers, KaptonR, TedlarR,and polyester, which are used to prevent the epoxy penetration. Lastly, samples with an embedded loosely woven scrim cloth placed between two damping material layers are tested to measure how the scrim affects the shear modulus.

  13. Damping in high-temperature superconducting levitation systems

    Energy Technology Data Exchange (ETDEWEB)

    Hull, John R.

    2009-12-15

    Methods and apparatuses for improved damping in high-temperature superconducting levitation systems are disclosed. A superconducting element (e.g., a stator) generating a magnetic field and a magnet (e.g. a rotor) supported by the magnetic field are provided such that the superconducting element is supported relative to a ground state with damped motion substantially perpendicular to the support of the magnetic field on the magnet. Applying this, a cryostat housing the superconducting bearing may be coupled to the ground state with high damping but low radial stiffness, such that its resonant frequency is less than that of the superconducting bearing. The damping of the cryostat may be substantially transferred to the levitated magnetic rotor, thus, providing damping without affecting the rotational loss, as can be derived applying coupled harmonic oscillator theory in rotor dynamics. Thus, damping can be provided to a levitated object, without substantially affecting the rotational loss.

  14. Air damping effect on the air-based CMUT operation

    Science.gov (United States)

    Cha, Bu-Sang; Kanashima, Takeshi; Lee, Seung-Mok; Okuyama, Masanori

    2015-08-01

    The vibration amplitude, damping ratio and viscous damping force in capacitive micromachinedultrasonic transducers (CMUTs) with a perforated membrane have been calculated theoretically and compared with the experimental data on its vibration behavior. The electrical bias of the DC and the AC voltages and the operation frequency conditions influence the damping effect because leads to variations in the gap height and the vibration velocity of the membrane. We propose a new estimation method to determine the damping ratio by the decay rate of the vibration amplitudes of the perforated membrane plate are measured using a laser vibrometer at each frequency, and the damping ratios were calculated from those results. The influences of the vibration frequency and the electrostatic force on the damping effect under the various operation conditions have been studied.

  15. Damping characteristics of a footbridge: Mysteries and truths

    DEFF Research Database (Denmark)

    Cantieni, Reto; Bajric, Anela; Brincker, Rune

    2016-01-01

    As a consequence of a paper presented by Michael Mistler at the VDI-Baudynamik-Tagung in Kassel, Germany, in April 2015, the authors checked the damping coefficients having been estimated for a footbridge in autumn 2014. Mistler stated that the critical damping ratio estimated from a halfpower...... world but not in the world of engineers applying OMA in practice. In this paper it is presented how the leakage on the spectral density estimate is affecting the damping estimation through OMA based frequency domain identification. Finally the paper compares the damping estimated in the time...... and frequency domain from ambient tests, with the damping estimated from the free decays. Unfortunately, bias error on damping values determined from analyses in the frequency domain is worst on low frequency modes usually being the most important ones when dealing with a resonance problem in practice....

  16. Dynamic analysis of systems having large damping variations

    Energy Technology Data Exchange (ETDEWEB)

    Philippacopoulos, A.J.

    1985-01-01

    In the earthquake response analysis of structures in which the damping characteristics between the elements varies significantly the standard mode superposition method cannot be used. Several approximations have been proposed that allow the application of the modal superposition method for cases in which the damping matrix is not orthogonal with respect to the modal shapes. The most commonly used approximation is based on a composite damping value which is employed in the modal equations. This value is a weighted average of the damping values of the individual components of the structural model. In this paper an investigation of the errors introduced by the composite damping in the response of simple structures is presented. The results given in the paper can be used for benchmarking the approximations in more complex systems for which composite damping solutions are employed.

  17. Study of Track Reconstruction for DAMPE

    Science.gov (United States)

    Lu, Tong-suo; Lei, Shi-jun; Zang, Jing-jing; Chang, Jin; Wu, Jian

    2017-07-01

    The Dark Matter Particle Explorer (DAMPE) is aimed to study the existence and distribution of dark matter via the observation of high-energy particles in space with a large energy bandwidth, high energy resolution, and high spatial resolution. The track reconstruction is to restore the positions and angles of the incident particles using the multiple observations of different channels at different positions, and its accuracy determines the angular resolution of the explorer. The track reconstruction is mainly based on the observations of two sub-detectors, namely, the Silicon Tracker (STK) and the BGO (Bi4Ge3O12) calorimeter. In accordance with the design and structure of the two sub-detectors, and using the data collected during the beam tests and ground tests of cosmic rays, we discuss in detail the method of track reconstruction for the DAMPE, which includes mainly three basic procedures: the selection of track hits, the fitting of track hits, and the judgement of the optimal track. Since an energetic particle most probably leaves multiple hits in different layers of the STK and BGO crystals, we first provide a method to obtain a rough track in the BGO calorimeter by the centroid method, and hereby to constrain the track hits in the STK. Then for the selected one group of possible track hits in the STK, we apply two different algorithms, the Kalman filter and the least square linear fitting, to fit these track hits. The consistency of the results obtained independently via the two algorithms confirms the validity of our track reconstruction results. Finally, several criteria for picking out the most possible track among all the tracks found in the reconstruction by combining the results of the BGO calorimeter and STK are discussed. Using the track reconstruction method proposed in this article and the beam test data, we confirm that the angular resolution of the DAMPE satisfies its design requirement.

  18. Loss of Landau Damping in the LHC

    CERN Document Server

    Shaposhnikova, E N; Bohl, T; Bhat, C M; Baudrenghien, P; Butterworth, A C; Mastoridis, T; Esteban Muller, J; Papotti, G; Tuckmantel, J; Venturini Delsolaro, W; Wehrle, U

    2011-01-01

    Loss of Landau damping leading to a single bunch longitudinal instability has been observed in the LHC during the ramp and on the 3.5 TeV flat top for small injected longitudinal emittances. The first measurements are in reasonable agreement with the threshold calculated for the expected longitudinal reactive impedance budget of the LHC as well as with the threshold dependence on beam energy. The cure is a controlled longitudinal emittance blow-up during the ramp which for a constant threshold through the cycle should provide an emittance proportional to the square root of energy.

  19. Quantum information reclaiming after amplitude damping

    Energy Technology Data Exchange (ETDEWEB)

    Memarzadeh, Laleh; Cafaro, Carlo; Mancini, Stefano, E-mail: laleh.memarzadeh@unicam.it, E-mail: carlo.cafaro@unicam.it, E-mail: stefano.mancini@unicam.it [School of Science and Technology, University of Camerino, I-62032 Camerino (Italy)

    2011-01-28

    We design an effective method to investigate the quantum information reclaim from the environment after amplitude damping has occurred. In particular, we address the question of optimal measurement on the environment to perform the best possible correction on two- and three-dimensional quantum systems. While for qubits we show that the entanglement fidelity is the same for all possible measurements, for qutirits we find that different measurements give rise to different values of the entanglement fidelity. By searching over all possible measurements on the environment we uncover the optimal one leading to the maximum entanglement fidelity.

  20. Human and rodent amyloid-beta peptides differentially bind heme: relevance to the human susceptibility to Alzheimer's disease.

    Science.gov (United States)

    Atamna, Hani; Frey, William H; Ko, Novie

    2009-07-01

    Amyloid-beta (Abeta) peptides are implicated in the neurodegeneration of Alzheimer's disease (AD). We previously investigated the mechanism of neurotoxicity of Abeta and found that human Abeta (huAbeta) binds and depletes heme, forming an Abeta-heme complex with peroxidase activity. Rodent Abeta (roAbeta) is identical to huAbeta, except for three amino acids within the proposed heme-binding motif (Site-H). We studied and compared heme-binding between roAbeta and huAbeta. Unlike roAbeta, huAbeta binds heme tightly (K(d)=140+/-60 nM) and forms a peroxidase. The plot of bound (huAbeta-heme) vs. unbound heme fits best to a two site binding hyperbola, suggesting huAbeta possesses two heme-binding sites. Consistently, a second high affinity heme-binding site was identified in the lipophilic region (site-L) of huAbeta (K(d)=210+/-80 nM). The plot of (roAbeta-heme) vs. unbound heme, on the other hand, was different as it fits best to a sigmoidal binding curve, indicating different binding and lower affinity of roAbeta for heme (K(d)=1 microM). The effect of heme-binding to site-H on heme-binding to site-L in roAbeta and huAbeta is discussed. While both roAbeta and huAbeta form aggregates equally, rodents lack AD-like neuropathology. High huAbeta/heme ratio increases the peroxidase activity. These findings suggest that depletion of regulatory heme and formation of Abeta-heme peroxidase contribute to huAbeta's neurotoxicity in the early stages of AD. Phylogenic variations in the amino acid sequence of Abeta explain tight heme-binding to huAbeta and likely contribute to the increased human susceptibility to AD.

  1. Molecular Dynamics Simulations of Cytochrome c un-folding in AOT Reverse Micelles: the first steps

    CERN Document Server

    Abel, Stéphane; Marchi, Massimo

    2009-01-01

    This paper explores the reduced form of horse cytochrome c confined in reverse micelles (RM) of so-dium bis-(2-ethylhexyl) sulfosuccinate (AOT) in isooctane by molecular dynamics simulation. RMs of two sizes were constructed at a water content of Wo = [H2O]/[AOT] = 5.5 and 9.1. Our results show that the protein secondary structure and the heme conformation both depend on micellar hydration. At low hydration, the protein structure and the heme moiety remain stable, whereas at high water content the protein becomes unstable and starts to unfold. At Wo = 9.1, according to the X-ray structure, conforma-tional changes are mainly localized on protein loops and around the heme moiety, where we observe a partial opening of the heme crevice. These findings suggest that within our time window (10 ns), the structural changes observed at the heme level are the first steps of the protein denaturation process, pre-viously described experimentally in micellar solutions. In addition, a specific binding of AOT molecules to a ...

  2. Viscous damping of gravity waves over a permeable bed

    Directory of Open Access Journals (Sweden)

    K. K. Puri

    1978-01-01

    Full Text Available The damping of gravity waves over the surface of a layer of viscous fluid which overlies a porous bed saturated with the same fluid is studied. It is shown that viscosity may not be the dominant influence in the damping mechanism; the damping effects due to percolation in the fixed bed may be of the same or even higher order than those due to viscosity.

  3. Irradiation of bovine meat: effect of heme-iron concentration.; Irradiacao de carne bovina: efeito na concentracao de ferro heme

    Energy Technology Data Exchange (ETDEWEB)

    Mistura, Liliana Perazzini Furtado

    2002-07-01

    The irradiation is often used, nowadays, for meat conservation and it is important to know how much this process interferes with the nutritional quality of the meat. In this study round cut meat, ground and steaks (from a local supermarket) was irradiated with doses of O; 1; 2; 3; 4; 5; 7,5 and 10 kGy (JS-7500 Nordium Inc -Canada) and the interference of irradiation and the process of food preparation on heme-iron (H Fe) content was determined. Half of the sample was kept raw and the other half was grilled in a pre-warmed oven at 250 deg C for 9 min and a controlled humidity of 70%. The chemical composition, the total iron (T Fe) (EM) and the heme iron concentration were determined (Hornsey,1956) and the sensorial quality evaluated. The average T Fe concentration of raw and ground , ground and grilled, raw steaks and grilled steak meat, on dry and degreased basis was 113 mug/g, 121 mug/g , 91 mug/g and 77 mug/g; and the H Fe concentration 105 mug/g (93% of T Fe) , 88 mug/g (73% of T Fe), 90 mug/g (99% of T Fe) and 52 mug/g (68% of T Fe) respectively. Data were evaluated by ANOVA with fixed effects and multiple comparisons. The irradiation neither altered the chemical composition nor the proportion of heme iron of meat. The preparation conditions (temperature, cooking time, environment humidity, meat presentation) of the sample interfered more with the heme iron content than the irradiation. With the sensorial analysis we verified that meats irradiated with doses of 3 kGy were better evaluated in softness and succulency attributes than the others. Meat submitted to irradiation doses up to 3 kGy were accepted by the specialists' panel. (author)

  4. Altered heme catabolism by heme oxygenase-1 caused by mutations in human NADPH cytochrome P450 reductase

    Energy Technology Data Exchange (ETDEWEB)

    Pandey, Amit V., E-mail: amit@pandeylab.org [Pediatric Endocrinology, Diabetology and Metabolism, Department of Clinical Research, University of Bern, Tiefenaustrasse 120c, CH-3004 Bern (Switzerland); Flueck, Christa E.; Mullis, Primus E. [Pediatric Endocrinology, Diabetology and Metabolism, Department of Clinical Research, University of Bern, Tiefenaustrasse 120c, CH-3004 Bern (Switzerland)

    2010-09-24

    Research highlights: {yields} Mutations in POR identified from patients lead to reduced HO-1 activities. {yields} POR mutation Y181D affecting FMN binding results in total loss of HO-1 activity. {yields} POR mutations A287P, C569Y and V608F, lost 50-70% activity. {yields} Mutations in FAD binding domain, R457H, Y459H and V492E lost all HO-1 activity. {yields} POR polymorphisms P228L, R316W, G413S, A503V and G504R have normal activity. -- Abstract: Human heme oxygenase-1 (HO-1) carries out heme catabolism supported by electrons supplied from the NADPH through NADPH P450 reductase (POR, CPR). Previously we have shown that mutations in human POR cause a rare form of congenital adrenal hyperplasia. In this study, we have evaluated the effects of mutations in POR on HO-1 activity. We used purified preparations of wild type and mutant human POR and in vitro reconstitution with purified HO-1 to measure heme degradation in a coupled assay using biliverdin reductase. Here we show that mutations in POR found in patients may reduce HO-1 activity, potentially influencing heme catabolism in individuals carrying mutant POR alleles. POR mutants Y181D, A457H, Y459H, V492E and R616X had total loss of HO-1 activity, while POR mutations A287P, C569Y and V608F lost 50-70% activity. The POR variants P228L, R316W and G413S, A503V and G504R identified as polymorphs had close to WT activity. Loss of HO-1 activity may result in increased oxidative neurotoxicity, anemia, growth retardation and iron deposition. Further examination of patients affected with POR deficiency will be required to assess the metabolic effects of reduced HO-1 activity in affected individuals.

  5. Resonance Raman Spectra of Five-Coordinate Heme-Nitrosyl Cytochromes c': Effect of the Proximal Heme-NO Environment.

    Science.gov (United States)

    Servid, Amy E; McKay, Alison L; Davis, Cherry A; Garton, Elizabeth M; Manole, Andreea; Dobbin, Paul S; Hough, Michael A; Andrew, Colin R

    2015-06-02

    Five-coordinate heme nitrosyl complexes (5cNO) underpin biological heme-NO signal transduction. Bacterial cytochromes c' are some of the few structurally characterized 5cNO proteins, exhibiting a distal to proximal 5cNO transition of relevance to NO sensing. Establishing how 5cNO coordination (distal vs proximal) depends on the heme environment is important for understanding this process. Recent 5cNO crystal structures of Alcaligenes xylosoxidans cytochrome c' (AXCP) and Shewanella frigidimarina cytochrome c' (SFCP) show a basic residue (Arg124 and Lys126, respectively) near the proximal NO binding sites. Using resonance Raman (RR) spectroscopy, we show that structurally characterized 5cNO complexes of AXCP variants and SFCP exhibit a range of ν(NO) (1651-1671 cm(-1)) and ν(FeNO) (519-536 cm(-1)) vibrational frequencies, depending on the nature of the proximal heme pocket and the sample temperature. While the AXCP Arg124 residue appears to have little impact on 5cNO vibrations, the ν(NO) and ν(FeNO) frequencies of the R124K variant are consistent with (electrostatically) enhanced Fe(II) → (NO)π* backbonding. Notably, RR frequencies for SFCP and R124A AXCP are significantly displaced from the backbonding trendline, which in light of recent crystallographic data and density functional theory modeling may reflect changes in the Fe-N-O angle and/or extent of σ-donation from the NO(π*) to the Fe(II) (dz(2)) orbital. For R124A AXCP, correlation of vibrational and crystallographic data is complicated by distal and proximal 5cNO populations. Overall, this study highlights the complex structure-vibrational relationships of 5cNO proteins that allow RR spectra to distinguish 5cNO coordination in certain electrostatic and steric environments.

  6. Damp Flat Artist's Books:Retrospective of Damp Flat Artist's Books

    OpenAIRE

    Batey, Jacqueline

    2013-01-01

    As part of the Phoenix Gallery's Press & Release artists' books exhibition, I will be showing everything in the Damp Flat Books catalogue. All 22 artists' book titles, along with 14 issues of my art-zine Future Fantasteek! and a selection of sketchbooks. http://www.phoenixbrighton.org/archive/2013-2/press-release/

  7. Investigations of ultrafast ligand rebinding to heme and heme proteins using temperature and strong magnetic field perturbations

    Science.gov (United States)

    Zhang, Zhenyu

    This thesis is written to summarize investigations of the mechanisms that underlie the kinetics of diatomic ligand rebinding to the iron atom of the heme group, which is chelated inside heme proteins. The family of heme proteins is a major object of studies for several branches of scientific research activity. Understanding the ligand binding mechanisms and pathways is one of the major goals for biophysics. My interests mainly focus on the physics of this ligand binding process. Therefore, to investigate the problem, isolated from the influence of the protein matrix, Fe-protophorphyrin IX is chosen as the prototype system in my studies. Myoglobin, the most extensively and intensively studied protein, is another ideal system that allows coupling the protein polypeptide matrix into the investigation. A technique to synchro-lock two laser pulse trains electronically is applied to our pump-probe spectroscopic studies. Based on this technique, a two color, fs/ps pump-probe system is developed which extends the temporal window for our investigation to 13ns and fills a gap existing in previous pump-probe investigations. In order to apply this newly-developed pump-probe laser system to implement systematic studies on the kinetics of diatomic ligand (NO, CO, O2) rebinding to heme and heme proteins, several experimental setups are utilized. In Chapter 1, the essential background knowledge, which helps to understand the iron-ligand interaction, is briefly described. In Chapter 2, in addition to a description of the preparation protocols of protein samples and details of the method for data analysis, three home-made setups are described, which include: a picosecond laser regenerative amplifier, a pump-probe application along the bore (2-inch in diameter) of a superconducting magnet and a temperature-controllable cryostat for spinning sample cell. Chapter 3 presents high magnetic field studies of several heme-ligand or protein-ligand systems. Pump-probe spectroscopy is used to

  8. Adenoviral transfer of the heme oxygenase-1 gene protects striatal astrocytes from heme-mediated oxidative injury.

    Science.gov (United States)

    Teng, Zhi-Ping; Chen, Jing; Chau, Lee-Young; Galunic, Nicholas; Regan, Raymond F

    2004-11-01

    Heme oxygenase-1 (HO-1) is induced in the CNS after hemorrhage, and may have an effect on injury to surrounding tissue. Hemin, the preferred substrate of HO, is a neurotoxin that is present in intracranial hematomas. In a prior study, we observed that HO inhibitors increased the vulnerability of cultured cortical astrocytes to heme-mediated oxidative injury. To investigate the effect of HO more specifically, we used an adenoviral vector encoding the human HO-1 gene to specifically increase HO-1 expression. Incubation with 100 MOI of the HO-1 adenovirus (Adv-HHO-1) for 24 h increased both HO-1 protein and HO activity; a control adenovirus lacking the HO-1 gene had no effect. Using a DNA probe that was specific for human HO-1, 80.5 +/- 7.2% of astrocytes were observed to be infected by in situ hybridization. The cell death produced by 30-60 microM hemin was significantly reduced by pretreatment with 100 MOI Adv-HHO-1, as assessed by LDH release, propidium iodide exclusion, and MTT reduction assay. The threefold increase in cell protein oxidation produced by hemin was also attenuated in cultures pretreated with Adv-HHO-1. These results support the hypothesis that HO-1 protects astrocytes from heme-mediated oxidative injury. Specifically increasing astrocytic HO-1 by gene transfer may have a beneficial effect on hemorrhagic CNS injury.

  9. Damping element for reducing the vibration of an airfoil

    Science.gov (United States)

    Campbell, Christian X; Marra, John J

    2013-11-12

    An airfoil (10) is provided with a tip (12) having an opening (14) to a center channel (24). A damping element (16) is inserted within the opening of the center channel, to reduce an induced vibration of the airfoil. The mass of the damping element, a spring constant of the damping element within the center channel, and/or a mounting location (58) of the damping element within the center channel may be adjustably varied, to shift a resonance frequency of the airfoil outside a natural operating frequency of the airfoil.

  10. Serum proteomes of hypertension patients with abundant phlegm-dampness.

    Science.gov (United States)

    Chu, Yu-guang; Shi, Jie; Hu, Yuan-hui; Wu, Hua-qin; Liu, Gui-jian; Hu, Chao-jun; Li, Yong-zhe; Li, Yi; Chen, Zi-jing; He, Qing

    2009-07-01

    To study the serum proteomes of essential hypertension (EH) patients with abundant phlegm-dampness, and try to find special proteins associated with abundant phlegm-dampness syndrome. Fifty-nine hypertension patients were included, and the patients were divided into abundant phlegm-dampness syndrome group (39 cases) and non-phlegm-dampness syndrome group (20 cases). To find the special proteins associated with abundant phlegm-dampness, the EH patients with non-phlegm-dampness and another 30 healthy persons were regarded as control. Weak cation nano-magnetic beads were used to capture proteins in serum, and proteomic fingerprint was made by matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS). All the proteomic fingerprints were analyzed by Biomarker Wizard 3.1 Software. Then Biomarker Patterns Software (BPS) 5.0 was used to identify the differentiated proteins, which could induce phlegm-dampness. There were 102 differentiated protein peaks between abundant phlegm-dampness and the control group. The best markers of abundant phlegm-dampness were protein peaks with the mass to charge ratio (m/z) of 9,334.958 m/z (the expression increased), 9,280.191 m/z (the expression decreased), 8,030.794 m/z (the expression increased), and 2,941.551 m/z (the expression increased). These four protein peaks found by BPS could induce abundant phlegm-dampness. They could be used to separate the abundant phlegm-dampness syndrome from the healthy persons and the hypertension patients with non-phlegm-dampness. The sensitivity of the model was 93.103% (27/29), specificity was 92% (23/25), false positive rate was 8% (2/25), false negative rate was 6.897% (2/29) and Youden's index was 85.103%. Blind test data indicated a sensitivity of 90% (9/10) and a specificity of 88% (22/25), and the false positive rate was 12% (3/25), false negative rate was 10% (1/10), and Youden's index was 78%. The differentiated proteins between the abundant phlegm-dampness

  11. Simulating Nonlinear Oscillations of Viscoelastically Damped Mechanical Systems

    Directory of Open Access Journals (Sweden)

    M. D. Monsia

    2014-12-01

    Full Text Available The aim of this work is to propose a mathematical model in terms of an exact analytical solution that may be used in numerical simulation and prediction of oscillatory dynamics of a one-dimensional viscoelastic system experiencing large deformations response. The model is represented with the use of a mechanical oscillator consisting of an inertial body attached to a nonlinear viscoelastic spring. As a result, a second-order first-degree Painlevé equation has been obtained as a law, governing the nonlinear oscillatory dynamics of the viscoelastic system. Analytical resolution of the evolution equation predicts the existence of three solutions and hence three damping modes of free vibration well known in dynamics of viscoelastically damped oscillating systems. Following the specific values of damping strength, over-damped, critically-damped and under-damped solutions have been obtained. It is observed that the rate of decay is not only governed by the damping degree but, also by the magnitude of the stiffness nonlinearity controlling parameter. Computational simulations demonstrated that numerical solutions match analytical results very well. It is found that the developed mathematical model includes a nonlinear extension of the classical damped linear harmonic oscillator and incorporates the Lambert nonlinear oscillatory equation with well-known solutions as special case. Finally, the three damped responses of the current mathematical model devoted for representing mechanical systems undergoing large deformations and viscoelastic behavior are found to be asymptotically stable.

  12. NLSE for quantum plasmas with the radiation damping

    CERN Document Server

    Andreev, Pavel A

    2014-01-01

    We consider contribution of the radiation damping in the quantum hydrodynamic equations for spinless particles. We discuss possibility of obtaining of corresponding non-linear Schrodinger equation (NLSE) for the macroscopic wave function. We compare contribution of the radiation damping with weakly (or semi-) relativistic effects appearing in the second order by v/c. The radiation damping appears in the third order by v/c. So it might be smaller than weakly relativistic effects, but it gives damping of the Langmuir waves which can be considerable.

  13. In vivo and in vitro olefin cyclopropanation catalyzed by heme enzymes

    Energy Technology Data Exchange (ETDEWEB)

    Coelho, Pedro S.; Brustad, Eric M.; Arnold, Frances H.; Wang, Zhan; Lewis, Jared C.

    2016-11-15

    The present invention provides methods for catalyzing the conversion of an olefin to any compound containing one or more cyclopropane functional groups using heme enzymes. In certain aspects, the present invention provides a method for producing a cyclopropanation product comprising providing an olefinic substrate, a diazo reagent, and a heme enzyme; and admixing the components in a reaction for a time sufficient to produce a cyclopropanation product. In other aspects, the present invention provides heme enzymes including variants and fragments thereof that are capable of carrying out in vivo and in vitro olefin cyclopropanation reactions. Expression vectors and host cells expressing the heme enzymes are also provided by the present invention.

  14. In vivo and in vitro olefin cyclopropanation catalyzed by heme enzymes

    Science.gov (United States)

    Coelho, Pedro S; Brustad, Eric M; Arnold, Frances H; Wang, Zhan; Lewis, Jared C

    2015-03-31

    The present invention provides methods for catalyzing the conversion of an olefin to any compound containing one or more cyclopropane functional groups using heme enzymes. In certain aspects, the present invention provides a method for producing a cyclopropanation product comprising providing an olefinic substrate, a diazo reagent, and a heme enzyme; and admixing the components in a reaction for a time sufficient to produce a cyclopropanation product. In other aspects, the present invention provides heme enzymes including variants and fragments thereof that are capable of carrying out in vivo and in vitro olefin cyclopropanation reactions. Expression vectors and host cells expressing the heme enzymes are also provided by the present invention.

  15. Heme, an Essential Nutrient from Dietary Proteins, Critically Impacts Diverse Physiological and Pathological Processes

    Directory of Open Access Journals (Sweden)

    Jagmohan Hooda

    2014-03-01

    Full Text Available Heme constitutes 95% of functional iron in the human body, as well as two-thirds of the average person’s iron intake in developed countries. Hence, a wide range of epidemiological studies have focused on examining the association of dietary heme intake, mainly from red meat, with the risks of common diseases. High heme intake is associated with increased risk of several cancers, including colorectal cancer, pancreatic cancer and lung cancer. Likewise, the evidence for increased risks of type-2 diabetes and coronary heart disease associated with high heme intake is compelling. Furthermore, recent comparative metabolic and molecular studies of lung cancer cells showed that cancer cells require increased intracellular heme biosynthesis and uptake to meet the increased demand for oxygen-utilizing hemoproteins. Increased levels of hemoproteins in turn lead to intensified oxygen consumption and cellular energy generation, thereby fueling cancer cell progression. Together, both epidemiological and molecular studies support the idea that heme positively impacts cancer progression. However, it is also worth noting that heme deficiency can cause serious diseases in humans, such as anemia, porphyrias, and Alzheimer’s disease. This review attempts to summarize the latest literature in understanding the role of dietary heme intake and heme function in diverse diseases.

  16. Unconjugated bilirubin mediates heme oxygenase-1-induced vascular benefits in diabetic mice.

    Science.gov (United States)

    Liu, Jian; Wang, Li; Tian, Xiao Yu; Liu, Limei; Wong, Wing Tak; Zhang, Yang; Han, Quan-Bin; Ho, Hing-Man; Wang, Nanping; Wong, Siu Ling; Chen, Zhen-Yu; Yu, Jun; Ng, Chi-Fai; Yao, Xiaoqiang; Huang, Yu

    2015-05-01

    Heme oxygenase-1 (HO-1) exerts vasoprotective effects. Such benefit in diabetic vasculopathy, however, remains unclear. We hypothesize that bilirubin mediates HO-1-induced vascular benefits in diabetes. Diabetic db/db mice were treated with hemin (HO-1 inducer) for 2 weeks, and aortas were isolated for functional and molecular assays. Nitric oxide (NO) production was measured in cultured endothelial cells. Hemin treatment augmented endothelium-dependent relaxations (EDRs) and elevated Akt and endothelial NO synthase (eNOS) phosphorylation in db/db mouse aortas, which were reversed by the HO-1 inhibitor SnMP or HO-1 silencing virus. Hemin treatment increased serum bilirubin, and ex vivo bilirubin treatment improved relaxations in diabetic mouse aortas, which was reversed by the Akt inhibitor. Biliverdin reductase silencing virus attenuated the effect of hemin. Chronic bilirubin treatment improved EDRs in db/db mouse aortas. Hemin and bilirubin reversed high glucose-induced reductions in Akt and eNOS phosphorylation and NO production. The effect of hemin but not bilirubin was inhibited by biliverdin reductase silencing virus. Furthermore, bilirubin augmented EDRs in renal arteries from diabetic patients. In summary, HO-1-induced restoration of endothelial function in diabetic mice is most likely mediated by bilirubin, which preserves NO bioavailability through the Akt/eNOS/NO cascade, suggesting bilirubin as a potential therapeutic target for clinical intervention of diabetic vasculopathy. © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

  17. Superelastic behavior and damping capacity of CuAlBe alloys

    Energy Technology Data Exchange (ETDEWEB)

    Montecinos, Susana [Universidad de Chile and CIMAT, Blanco Encalada 2008, Santiago (Chile); Moroni, Maria Ofelia [Universidad de Chile, Depto. de Ingenieria Civil, Casilla 228/3, Santiago (Chile)]. E-mail: mmoroni@cec.uchile.cl; Sepulveda, Aquiles [Universidad de Chile, Depto. de Ingenieria Mecanica, Casilla 2777, Santiago (Chile)

    2006-03-15

    Shape memory alloys (SMAs) showing the superelastic effect, dissipate energy through hysteretic cycles up to large strain amplitudes, without remnant strains after unloading. This effect is associated with a reversible stress-induced martensitic transformation. In this paper, the behavior of copper-based SMAs is examined, with the perspective of potential applications in seismic-energy dissipative devices. In particular, two different compositions of CuAlBe are characterized using chemical analysis, differential scanning calorimetry (DSC), light and scanning electron microscopy and X-rays diffraction. Mechanical and hysteretic damping properties are determined from cyclic tensile and tension-compression tests, for different strain amplitudes and frequencies. Both alloys show superelastic behavior, although hysteresis loops differ, due to differences in the composition and transformation phase temperatures. Equivalent damping up to 5% was obtained for the largest strain imposed. Frequency, in the range of interest for seismic applications, had a small influence on the damping values. It is concluded that alloy Cu-11.8 wt.% Al-0.5 wt.% Be best exhibited properties for the application intended.

  18. Interaction between Non-Heme Iron of Lipoxygenases and Cumene Hydroperoxide: Basis for Enzyme Activation, Inactivation, and Inhibition

    Energy Technology Data Exchange (ETDEWEB)

    Vahedi-Faridi, Ardeshir; Brault, Pierre-Alexandre; Shah, Priya; Kim, Yong-Wah; Dunham, William R.; Funk, Jr., Max O. (Toledo)

    2010-11-16

    Lipoxygenase catalysis depends in a critical fashion on the redox properties of a unique mononuclear non-heme iron cofactor. The isolated enzyme contains predominantly, if not exclusively, iron(II), but the catalytically active form of the enzyme has iron(III). The activating oxidation of the iron takes place in a reaction with the hydroperoxide product of the catalyzed reaction. In a second peroxide-dependent process, lipoxygenases are also inactivated. To examine the redox activation/inactivation dichotomy in lipoxygenase chemistry, the interaction between lipoxygenase-1 (and -3) and cumene hydroperoxide was investigated. Cumene hydroperoxide was a reversible inhibitor of the reaction catalyzed by lipoxygenase-1 under standard assay conditions at high substrate concentrations. Reconciliation of the data with the currently held kinetic mechanism requires simultaneous binding of substrate and peroxide. The enzyme also was both oxidized and largely inactivated in a reaction with the peroxide in the absence of substrate. The consequences of this reaction for the enzyme included the hydroxylation at C{beta} of two amino acid side chains in the vicinity of the cofactor, Trp and Leu. The modifications were identified by mass spectrometry and X-ray crystallography. The peroxide-induced oxidation of iron was also accompanied by a subtle rearrangement in the coordination sphere of the non-heme iron atom. Since the enzyme retains catalytic activity, albeit diminished, after treatment with cumene hydroperoxide, the structure of the iron site may reflect the catalytically relevant form of the cofactor.

  19. Gastroprotective effect of ghrelin against indomethacin-induced gastric injury in rats: possible role of heme oxygenase-1 pathway.

    Science.gov (United States)

    Allam, Mona M; El-Gohary, Ola A

    2017-07-01

    Ghrelin has been shown to ameliorate gastric injury by several mechanisms in experimental animal models. The present study aimed to investigate the effect of pretreatment with ghrelin on indomethacin-induced gastric injury in rats and the role of heme oxygenase-1(HO-1) pathway as a novel mechanism underlying the gastroprotective effect of ghrelin. In all groups studied, ulcer score (U.S), ulcer index (U.I) and preventive index (P.I) were evaluated and the gastric inflammatory biomarkers including levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and myeloperoxidase (MPO) activity as well as prostaglandin E2 (PGE2), malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), HO-1 and bilirubin as an indicator of heme oxygenase activity were measured. Indomethacin induced significant elevation in U.S and U.I as well as the inflammatory and the oxidative markers and reduced the PGE2 in addition to HO-1 level and activity. Pretreatment with ghrelin reversed these results. In order to elucidate the possible role of HO-1 in mediating the protective effects of ghrelin, tin protoporphyrin (SnPP) HO-1 blocker was administrated; it significantly attenuated the gastroprotective effect of ghrelin. In conclusion HO-1 activity significantly contributes toward ghrelin-mediated gastroprotection.

  20. Calcium-Dependent Conformation of a Heme and Fingerprint Peptide of the Di-Heme Cytochrome c Peroxidase from Paracoccus Pantotrophus

    Energy Technology Data Exchange (ETDEWEB)

    PAULETA,SOFIA R.; LU,YI; GOODHEW,CELIA F.; MOURA,ISABEL; PETTIGREW,GRAHAM W.; SHELNUTT,JOHN A.

    2000-12-18

    The structural changes in the heme macrocycle and substituents caused by binding of Ca{sup 2+} to the diheme cytochrome c peroxidase from Paracoccuspantotrophus were clarified by resonance Raman spectroscopy of the inactive filly oxidized form of the enzyme. The changes in the macrocycle vibrational modes are consistent with a Ca{sup 2+}-dependent increase in the out-of-plane distortion of the low-potential heme, the proposed peroxidatic heme. Most of the increase in out-of-plane distortion occurs when the high affinity site I is occupied, but a small further increase in distortion occurs when site II is also occupied by Ca{sup 2+}or Mg{sup 2+}. This increase in the heme distortion also explains the red shift in the Soret absorption band that occurs upon Ca{sup 2+} binding. Changes also occur in the low frequency substituent modes of the heme, indicating that a structural change in the covalently attached fingerprint pentapeptide of the LP heme occurs upon CM{sup 2+} binding to site I. These structural changes, possibly enhanced in the semi-reduced form of the enzyme, may lead to loss of the sixth ligand at the peroxidatic heme and activation of the enzyme.

  1. NOISE AND VIBRATION DAMPING FOR YACHT INTERIOR

    Directory of Open Access Journals (Sweden)

    Murat Aydın

    2016-12-01

    Full Text Available Vibration damping and sound insulation are essential for all vehicles. Because moving parts and external factors such as wind, tracks, etc. can cause vibration and noise. Wave which is a dynamic force, drive system and HVAC systems are the main vibration and noise generators in a vessel. These all can affect comfort level on board yachts. Different types of isolators and absorbers such as sylomer®, cork panels, etc. are used to reduce these effects. Comfort level on board yachts can be increased using these types of materials. Otherwise, discomfort of passenger and crew may increase. These materials not only reduce structure-borne and air-borne noise and vibrations from waves, air, engines, pumps, generators and HVAC systems but also protect vibration sensitive interior or fittings. Noise and vibration evaluation is an important issue for this reason. And, measurement tools must be used not only to minimize this problem but also fulfill the regulations such as “comfort class”. Besides, providing quiet and low vibration increases the costs too. From this point of view, this study aims to explain clearly how noise and vibration damping can be done in a yacht.

  2. Reversible Statistics

    DEFF Research Database (Denmark)

    Tryggestad, Kjell

    2004-01-01

    The study aims is to describe how the inclusion and exclusion of materials and calculative devices construct the boundaries and distinctions between statistical facts and artifacts in economics. My methodological approach is inspired by John Graunt's (1667) Political arithmetic and more recent work...... within constructivism and the field of Science and Technology Studies (STS). The result of this approach is here termed reversible statistics, reconstructing the findings of a statistical study within economics in three different ways. It is argued that all three accounts are quite normal, albeit...... in different ways. The presence and absence of diverse materials, both natural and political, is what distinguishes them from each other. Arguments are presented for a more symmetric relation between the scientific statistical text and the reader. I will argue that a more symmetric relation can be achieved...

  3. Characterization of the outer membrane receptor ShuA from the heme uptake system of Shigella dysenteriae. Substrate specificity and identification of the heme protein ligands.

    Science.gov (United States)

    Burkhard, Kimberly A; Wilks, Angela

    2007-05-18

    Shigella dysenteriae, like many bacterial pathogens, has evolved outer membrane receptor-mediated pathways for the uptake and utilization of heme as an iron source. As a first step toward understanding the mechanism of heme uptake we have undertaken a site-directed mutagenesis, spectroscopic, and kinetic analysis of the outer membrane receptor ShuA of S. dysenteriae. Purification of the outer membrane receptor gave a single band of molecular mass 73 kDa on SDS-PAGE. Initial spectroscopic analysis of the protein in either detergent micelles or lipid bicelles revealed residual heme bound to the receptor, with a Soret maximum at 413 nm. Titration of the protein with exogenous heme gave a Soret peak at 437 nm in detergent micelles, and 402 nm in lipid bicelles. However, transfer of heme from hemoglobin yields a Soret maximum at 413 nm identical to that of the isolated protein. Further spectroscopic and kinetic analysis revealed that hemoglobin in the oxidized state is the most likely physiological substrate for ShuA. In addition, mutation of the conserved histidines, H86A or H420A, resulted in a loss of the ability of the receptor to efficiently extract heme from hemoglobin. In contrast the double mutant H86A/H420A was unable to extract heme from hemoglobin. These findings taken together confirm that both His-86 and His-420 are essential for substrate recognition, heme coordination, and transfer. Furthermore, the full-length TonB was shown to form a 1:1 complex with either apo-ShuA H86A/H420A or the wild-type ShuA. These observations provide a basis for future studies on the coordination and transport of heme by the TonB-dependent outer membrane receptors.

  4. The five near-iron transporter (NEAT) domain anthrax hemophore, IsdX2, scavenges heme from hemoglobin and transfers heme to the surface protein IsdC.

    Science.gov (United States)

    Honsa, Erin Sarah; Fabian, Marian; Cardenas, Ana Maria; Olson, John S; Maresso, Anthony William

    2011-09-23

    Pathogenic bacteria require iron to replicate inside mammalian hosts. Recent studies indicate that heme acquisition in Gram-positive bacteria is mediated by proteins containing one or more near-iron transporter (NEAT) domains. Bacillus anthracis is a spore-forming, Gram-positive pathogen and the causative agent of anthrax disease. The rapid, extensive, and efficient replication of B. anthracis in host tissues makes this pathogen an excellent model organism for the study of bacterial heme acquisition. B. anthracis secretes two NEAT hemophores, IsdX1 and IsdX2. IsdX1 contains a single NEAT domain, whereas IsdX2 has five, a novel property among hemophores. To understand the functional significance of harboring multiple, non-identical NEAT domains, we purified each individual NEAT domain of IsdX2 as a GST fusion and analyzed the specific function of each domain as it relates to heme acquisition and transport. NEAT domains 1, 3, 4, and 5 all bind heme, with domain 5 having the highest affinity. All NEATs associate with hemoglobin, but only NEAT1 and -5 can extract heme from hemoglobin, seemingly by a specific and active process. NEAT1, -3, and -4 transfer heme to IsdC, a cell wall-anchored anthrax NEAT protein. These results indicate that IsdX2 has all the features required to acquire heme from the host and transport heme to the bacterial cell wall. Additionally, these results suggest that IsdX2 may accelerate iron import rates by acting as a "heme sponge" that enhances B. anthracis replication in iron-starved environments.

  5. The Five Near-iron Transporter (NEAT) Domain Anthrax Hemophore, IsdX2, Scavenges Heme from Hemoglobin and Transfers Heme to the Surface Protein IsdC*

    Science.gov (United States)

    Honsa, Erin Sarah; Fabian, Marian; Cardenas, Ana Maria; Olson, John S.; Maresso, Anthony William

    2011-01-01

    Pathogenic bacteria require iron to replicate inside mammalian hosts. Recent studies indicate that heme acquisition in Gram-positive bacteria is mediated by proteins containing one or more near-iron transporter (NEAT) domains. Bacillus anthracis is a spore-forming, Gram-positive pathogen and the causative agent of anthrax disease. The rapid, extensive, and efficient replication of B. anthracis in host tissues makes this pathogen an excellent model organism for the study of bacterial heme acquisition. B. anthracis secretes two NEAT hemophores, IsdX1 and IsdX2. IsdX1 contains a single NEAT domain, whereas IsdX2 has five, a novel property among hemophores. To understand the functional significance of harboring multiple, non-identical NEAT domains, we purified each individual NEAT domain of IsdX2 as a GST fusion and analyzed the specific function of each domain as it relates to heme acquisition and transport. NEAT domains 1, 3, 4, and 5 all bind heme, with domain 5 having the highest affinity. All NEATs associate with hemoglobin, but only NEAT1 and -5 can extract heme from hemoglobin, seemingly by a specific and active process. NEAT1, -3, and -4 transfer heme to IsdC, a cell wall-anchored anthrax NEAT protein. These results indicate that IsdX2 has all the features required to acquire heme from the host and transport heme to the bacterial cell wall. Additionally, these results suggest that IsdX2 may accelerate iron import rates by acting as a “heme sponge” that enhances B. anthracis replication in iron-starved environments. PMID:21808055

  6. Tridentate copper ligand influences on heme-peroxo-copper formation and properties: reduced, superoxo, and mu-peroxo iron/copper complexes.

    Science.gov (United States)

    Kim, Eunsuk; Helton, Matthew E; Lu, Shen; Moënne-Loccoz, Pierre; Incarvito, Christopher D; Rheingold, Arnold L; Kaderli, Susan; Zuberbühler, Andreas D; Karlin, Kenneth D

    2005-10-03

    In cytochrome c oxidase synthetic modeling studies, we recently reported a new mu-eta2:eta2-peroxo binding mode in the heteronuclear heme/copper complex [(2L)Fe(III)-(O2(2-))-CuII]+ (6) which is effected by tridentate copper chelation (J. Am. Chem. Soc. 2004, 126, 12716). To establish fundamental coordination and O2-reactivity chemistry, we have studied and describe here (i) the structure and dioxygen reactivity of the copper-free compound (2L)FeII (1), (ii) detailed spectroscopic properties of 6 in comparisons with those of known mu-eta2:eta1 heme-peroxo-copper complexes, (iii) formation of 6 from the reactions of [(2L)FeIICuI]+ (3) and dioxygen by stopped-flow kinetics, and (iv) reactivities of 6 with CO and PPh3. In the absence of copper, 1 serves as a myoglobin model compound possessing a pyridine-bound five-coordinate iron(II)-porphyrinate which undergoes reversible dioxygen binding. Oxygenation of 3 below -60 degrees C generates the heme-peroxo-copper complex 6 with strong antiferromagnetic coupling between high-spin iron(III) and copper(II) to yield an S = 2 spin system. Stopped-flow kinetics in CH2Cl2/6% EtCN show that dioxygen reacts with iron(II) first to form a heme-superoxide moiety, [(EtCN)(2L)FeIII-(O2-)...CuI(EtCN)]+ (5), which further reacts with Cu(I) to generate 6. Compared to those properties of a known mu-eta2:eta1-heme-peroxo-copper complex, 6 has a significantly diminished resonance Raman nu(O-O) stretching frequency at 747 cm(-1) and distinctive visible absorptions at 485, 541, and 572 nm, all of which seem to be characteristics of a mu-eta2:eta2-heme-peroxo-copper system. Addition of CO or PPh3 to 6 yields a bis-CO adduct of 3 or a PPh(3) adduct of 5, the latter with a remaining FeIII-(O2-) moiety.

  7. O{sub 2}-mediated oxidation of ferrous nitrosylated human serum heme-albumin is limited by nitrogen monoxide dissociation

    Energy Technology Data Exchange (ETDEWEB)

    Ascenzi, Paolo, E-mail: ascenzi@uniroma3.it [Interdepartmental Laboratory of Electron Microscopy, University Roma Tre, Via della Vasca Navale 79, I-00146 Roma (Italy); National Institute for Infectious Diseases I.R.C.C.S. ' Lazzaro Spallanzani' , Via Portuense 292, I-00149 Roma (Italy); Gullotta, Francesca; Gioia, Magda; Coletta, Massimo [Department of Experimental Medicine and Biochemical Sciences, University of Roma ' Tor Vergata' , Via Montpellier 1, I-00133 Roma (Italy); Interuniversity Consortium for the Research on the Chemistry of Metals in Biological Systems, Piazza Umberto I 1, I-87100 Bari (Italy); Fasano, Mauro [Department of Structural and Functional Biology, and Center of Neuroscience, University of Insubria, Via Alberto da Giussano 12a, I-21052 Busto Arsizio, VA (Italy)

    2011-03-04

    Research highlights: {yields} Human serum heme-albumin displays globin-like properties. {yields} O{sub 2}-mediated oxidation of ferrous nitrosylated human serum heme-albumin. {yields} Allosteric modulation of human serum heme-albumin reactivity. {yields} Rifampicin is an allosteric effector of human serum heme-albumin. {yields} Human serum heme-albumin is a ROS and NOS scavenger. -- Abstract: Human serum heme-albumin (HSA-heme-Fe) displays globin-like properties. Here, kinetics of O{sub 2}-mediated oxidation of ferrous nitrosylated HSA-heme-Fe (HSA-heme-Fe(II)-NO) is reported. Values of the first-order rate constants for O{sub 2}-mediated oxidation of HSA-heme-Fe(II)-NO (i.e., for ferric HSA-heme-Fe formation) and for NO dissociation from HSA-heme-Fe(II)-NO (i.e., for NO replacement by CO) are k = 9.8 x 10{sup -5} and 8.3 x 10{sup -4} s{sup -1}, and h = 1.3 x 10{sup -4} and 8.5 x 10{sup -4} s{sup -1}, in the absence and presence of rifampicin, respectively, at pH = 7.0 and T = 20.0 {sup o}C. The coincidence of values of k and h indicates that NO dissociation represents the rate limiting step of O{sub 2}-mediated oxidation of HSA-heme-Fe(II)-NO. Mixing HSA-heme-Fe(II)-NO with O{sub 2} does not lead to the formation of the transient adduct(s), but leads to the final ferric HSA-heme-Fe derivative. These results reflect the fast O{sub 2}-mediated oxidation of ferrous HSA-heme-Fe and highlight the role of drugs in modulating allosterically the heme-Fe-atom reactivity.

  8. Dietary hemoglobin rescues young piglets from severe iron deficiency anemia: Duodenal expression profile of genes involved in heme iron absorption.

    Directory of Open Access Journals (Sweden)

    Robert Staroń

    Full Text Available Heme is an efficient source of iron in the diet, and heme preparations are used to prevent and cure iron deficiency anemia in humans and animals. However, the molecular mechanisms responsible for heme absorption remain only partially characterized. Here, we employed young iron-deficient piglets as a convenient animal model to determine the efficacy of oral heme iron supplementation and investigate the pathways of heme iron absorption. The use of bovine hemoglobin as a dietary source of heme iron was found to efficiently counteract the development of iron deficiency anemia in piglets, although it did not fully rebalance their iron status. Our results revealed a concerted increase in the expression of genes responsible for apical and basolateral heme transport in the duodenum of piglets fed a heme-enriched diet. In these animals the catalytic activity of heme oxygenase 1 contributed to the release of elemental iron from the protoporphyrin ring of heme within enterocytes, which may then be transported by the strongly expressed ferroportin across the basolateral membrane to the circulation. We hypothesize that the well-recognized high bioavailability of heme iron may depend on a split pathway mediating the transport of heme-derived elemental iron and intact heme from the interior of duodenal enterocytes to the bloodstream.

  9. Bounce-harmonic Landau Damping of Plasma Waves

    Science.gov (United States)

    Anderegg, Francois

    2015-11-01

    We present measurement of plasma wave damping, spanning the temperature regimes of direct Landau damping, bounce-harmonic Landau damping, inter-species drag damping, and viscous damping. Direct Landau damping is dominant at high temperatures, but becomes negligible as v harmonics damping, controlled by an applied ``squeeze'' potential, which generates harmonics in the wave potential and in the particle dynamics. A particle moving in z experiences a non-sinusoidal mode potential caused by the squeeze, producing high spatial harmonics with lower phase velocity. These harmonics are Landau damped even when the mode phase velocity vph is large compared to the thermal velocity v , since the nth harmonic is resonant with a particle bouncing at velocity vb =vph / n . Here we increase the bounce harmonics through applied squeeze potential; but some harmonics are always present in finite length systems. For our centered squeeze geometry, theory shows that only odd harmonics are generated, and predicts the Landau damping rate from vph / n . Experimentally, the squeeze potential increases the wave damping and reduces its frequency. The frequency shift occurs because the squeeze potential reduces the number of particle where the mode velocity is the largest, therefore reducing the mode frequency. We observe an increase in the damping proportional to Vs2,and a frequency reduction proportional to Vs , in quantitative agreement with theory. Wave-coherent laser induced fluorescence allows direct observation of bounce resonances on the particle distribution, here predominantly at vph / 3 . A clear increase of the bounce harmonics is visible on the particle distribution when the squeeze potential is applied. Supported by NSF Grant PHY-1414570, and DOE Grants DE-SC0002451 and DE-SC0008693.

  10. Public health and economic impact of dampness and mold.

    Science.gov (United States)

    Mudarri, D; Fisk, W J

    2007-06-01

    The public health risk and economic impact of dampness and mold exposures was assessed using current asthma as a health endpoint. Individual risk of current asthma from exposure to dampness and mold in homes from W.J. Fisk, Q. Lei-Gomez & M.J. Mendell [(2007) Indoor Air, [corrected] 17, 284-296], and [corrected] asthma risks calculated from additional studies that reported the prevalence of dampness and mold in homes were used to estimate the proportion of US current asthma cases that are attributable to dampness and mold exposure at 21% (95% confidence internal 12-29%). An examination of the literature covering dampness and mold in schools, offices, and institutional buildings, which is summarized in the Appendix, suggests that risks from exposure in these buildings are similar to risks from exposures in homes. Of the 21.8 million people reported to have asthma in the USA, approximately 4.6 (2.7-6.3) million cases are estimated to be attributable to dampness and mold exposure in the home. Estimates of the national cost of asthma from two prior studies were updated to 2004 and used to estimate the economic impact of dampness and mold exposures. By applying the attributable fraction to the updated national annual cost of asthma, the national annual cost of asthma that is attributable to dampness and mold exposure in the home is estimated to be $3.5 billion ($2.1-4.8 billion). Analysis indicates that exposure to dampness and mold in buildings poses significant public health and economic risks in the USA. These findings are compatible with public policies and programs that help control moisture and mold in buildings. There is a need to control moisture in both new and existing construction because of the significant health consequences that can result from dampness and mold. This paper demonstrates that dampness and mold in buildings is a significant public health problem with substantial economic impact.

  11. Osmopriming-induced salt tolerance during seed germination of alfalfa most likely mediates through H2O2 signaling and upregulation of heme oxygenase.

    Science.gov (United States)

    Amooaghaie, Rayhaneh; Tabatabaie, Fatemeh

    2017-07-01

    The present study showed that osmopriming or pretreatment with low H2O2 doses (2 mM) for 6 h alleviated salt-reduced seed germination. The NADPH oxidase activity was the main source, and superoxide dismutase (SOD) activity might be a secondary source of H2O2 generation during osmopriming or H2O2 pretreatment. Hematin pretreatment similar to osmopriming improved salt-reduced seed germination that was coincident with the enhancement of heme oxygenase (HO) activity. The semi-quantitative RT-PCR confirmed that osmopriming or H2O2 pretreatment was able to upregulate heme oxygenase HO-1 transcription, while the application of N,N-dimethyl thiourea (DMTU as trap of endogenous H2O2) and diphenyleneiodonium (DPI as inhibitor of NADPHox) not only blocked the upregulation of HO but also reversed the osmopriming-induced salt attenuation. The addition of CO-saturated aqueous rescued the inhibitory effect of DMTU and DPI on seed germination and α-amylase activity during osmopriming or H2O2 pretreatment, but H2O2 could not reverse the inhibitory effect of ZnPPIX (as HO inhibitor) or Hb (as CO scavenger) that indicates that the CO acts downstream of H2O2 in priming-driven salt acclimation. The antioxidant enzymes and proline synthesis were upregulated in roots of seedlings grown from primed seeds, and these responses were reversed by adding DMTU, ZnPPIX, and Hb during osmopriming. These findings for the first time suggest that H2O2 signaling and upregulation of heme oxygenase play a crucial role in priming-driven salt tolerance.

  12. Chlamydomonas reinhardtii LFO1 Is an IsdG Family Heme Oxygenase.

    Science.gov (United States)

    Lojek, Lisa J; Farrand, Allison J; Wisecaver, Jennifer H; Blaby-Haas, Crysten E; Michel, Brian W; Merchant, Sabeeha S; Rokas, Antonis; Skaar, Eric P

    2017-01-01

    Heme is essential for respiration across all domains of life. However, heme accumulation can lead to toxicity if cells are unable to either degrade or export heme or its toxic by-products. Under aerobic conditions, heme degradation is performed by heme oxygenases, enzymes which utilize oxygen to cleave the tetrapyrrole ring of heme. The HO-1 family of heme oxygenases has been identified in both bacterial and eukaryotic cells, whereas the IsdG family has thus far been described only in bacteria. We identified a hypothetical protein in the eukaryotic green alga Chlamydomonas reinhardtii, which encodes a protein containing an antibiotic biosynthesis monooxygenase (ABM) domain consistent with those associated with IsdG family members. This protein, which we have named LFO1, degrades heme, contains similarities in predicted secondary structures to IsdG family members, and retains the functionally conserved catalytic residues found in all IsdG family heme oxygenases. These data establish LFO1 as an IsdG family member and extend our knowledge of the distribution of IsdG family members beyond bacteria. To gain further insight into the distribution of the IsdG family, we used the LFO1 sequence to identify 866 IsdG family members, including representatives from all domains of life. These results indicate that the distribution of IsdG family heme oxygenases is more expansive than previously appreciated, underscoring the broad relevance of this enzyme family. IMPORTANCE This work establishes a protein in the freshwater alga Chlamydomonas reinhardtii as an IsdG family heme oxygenase. This protein, LFO1, exhibits predicted secondary structure and catalytic residues conserved in IsdG family members, in addition to a chloroplast localization sequence. Additionally, the catabolite that results from the degradation of heme by LFO1 is distinct from that of other heme degradation products. Using LFO1 as a seed, we performed phylogenetic analysis, revealing that the IsdG family is

  13. Iron-coordinating tyrosine is a key determinant of NEAT domain heme transfer.

    Science.gov (United States)

    Grigg, Jason C; Mao, Cherry X; Murphy, Michael E P

    2011-10-28

    In humans, heme iron is the most abundant iron source, and bacterial pathogens such as Staphylococcus aureus acquire it for growth. IsdB of S. aureus acquires Fe(III)-protoporphyrin IX (heme) from hemoglobin for transfer to IsdC via IsdA. These three cell-wall-anchored Isd (iron-regulated surface determinant) proteins contain conserved NEAT (near iron transport) domains. The purpose of this work was to delineate the mechanism of heme binding and transfer between the NEAT domains of IsdA, IsdB, and IsdC using a combination of structural and spectroscopic studies. X-ray crystal structures of IsdA NEAT domain (IsdA-N1) variants reveal that removing the native heme-iron ligand Tyr166 is compensated for by iron coordination by His83 on the distal side and that no single mutation of distal loop residues is sufficient to perturb the IsdA-heme complex. Also, alternate heme-iron coordination was observed in structures of IsdA-N1 bound to reduced Fe(II)-protoporphyrin IX and Co(III)-protoporphyrin IX. The IsdA-N1 structural data were correlated with heme transfer kinetics from the NEAT domains of IsdB and IsdC. We demonstrated that the NEAT domains transfer heme at rates comparable to full-length proteins. The second-order rate constant for heme transfer from IsdA-N1 was modestly affected (15-fold (to 100-fold excess IsdC). We propose a heme transfer model wherein NEAT domain complexes pass heme iron directly from an iron-coordinating Tyr of the donor protein to the homologous Tyr residues of the acceptor protein. Copyright © 2011 Elsevier Ltd. All rights reserved.

  14. Reciprocal Effects of Oxidative Stress on Heme Oxygenase Expression and Activity Contributes to Reno-Vascular Abnormalities in EC-SOD Knockout Mice

    Directory of Open Access Journals (Sweden)

    Tomoko Kawakami

    2012-01-01

    although, HO activity was significantly (P<0.05 attenuated along with attenuation of serum adiponectin and vascular epoxide levels (P<0.05. CoPP, in EC-SOD(−/− mice, enhanced HO activity (P<0.05 and reversed aforementioned pathophysiological abnormalities along with restoration of vascular EET, p-eNOS, p-AKT and serum adiponectin levels in these animals. Taken together our results implicate a causative role of insufficient activation of heme-HO-adiponectin system in pathophysiological abnormalities observed in animal models of chronic oxidative stress such as EC-SOD(−/− mice.

  15. PID motion control tuning rules in a damping injection framework

    NARCIS (Netherlands)

    Tadele, T.S.; de Vries, Theodorus J.A.; Stramigioli, Stefano

    2013-01-01

    This paper presents a general design approach for a performance based tuning of a damping injection framework impedance controller by using insights from PID motion control tuning rules. The damping injection framework impedance controller is suitable for human friendly robots as it enhances safety

  16. Analysis of damping characteristics of arterial catheter blood ...

    African Journals Online (AJOL)

    Background. For many reasons, the invasive measurement of systolic and diastolic blood pressure should be accurate. Accuracy is determined, in part, by the damping characteristics of the arterial catheter blood pressure monitoring system. Objectives. To ascertain the damping characteristics of arterial catheter blood ...

  17. Simple model with damping of the mode-coupling instability

    Energy Technology Data Exchange (ETDEWEB)

    Pestrikov, D.V. [AN SSSR, Novosibirsk (Russian Federation). Inst. Yadernoj Fiziki

    1996-08-01

    In this paper we use a simple model to study the suppression of the transverse mode-coupling instability. Two possibilities are considered. One is due to the damping of particular synchrobetatron modes, and another - due to Landau damping, caused by the nonlinearity of betatron oscillations. (author)

  18. The effect of damping on the perception of hardness

    NARCIS (Netherlands)

    van Beek, F.E.; Heck, D.J.F.; Nijmeijer, H.; Bergmann Tiest, W.M.; Kappers, A.M.L.

    2015-01-01

    In controlling teleoperation systems subject to communication delays, unstable behavior is often prevented by injecting damping. A proper perception of hardness is required to efficiently interact with an object, but it is unknown if and how this injected damping influences the perceived hardness of

  19. The Study of Damped Harmonic Oscillations Using an Electronic Counter

    Science.gov (United States)

    Wadhwa, Ajay

    2009-01-01

    We study damped harmonic oscillations in mechanical systems like the loaded spring and simple pendulum with the help of an oscillation measuring electronic counter. The experimental data are used in a software program that solves the differential equation for damped vibrations of any system and determines its position, velocity and acceleration as…

  20. Exponential decay for solutions to semilinear damped wave equation

    KAUST Repository

    Gerbi, Stéphane

    2011-10-01

    This paper is concerned with decay estimate of solutions to the semilinear wave equation with strong damping in a bounded domain. Intro- ducing an appropriate Lyapunov function, we prove that when the damping is linear, we can find initial data, for which the solution decays exponentially. This result improves an early one in [4].

  1. Study of Ion Acoustic Wave Damping through Green's Functions

    DEFF Research Database (Denmark)

    Hsuan, H.C.S.; Jensen, Vagn Orla

    1973-01-01

    Green's function analyses of ion acoustic waves in streaming plasmas show that, in general, the waves damp algebraically rather than exponentially with distance from exciter.......Green's function analyses of ion acoustic waves in streaming plasmas show that, in general, the waves damp algebraically rather than exponentially with distance from exciter....

  2. Complex modes and frequencies in damped structural vibrations

    DEFF Research Database (Denmark)

    Krenk, Steen

    2004-01-01

    It is demonstrated that the state space formulation of the equation of motion of damped structural elements like cables and beams leads to a symmetric eigenvalue problem if the stiffness and damping operators are self-adjoint, and that this is typically the case in the absence of gyroscopic force...

  3. Dynamic stability of a lightly damped column trapped by a ...

    African Journals Online (AJOL)

    In this paper we initiate an analytical approach for determining the dynamic buckling load of a finite viscously damped column acted upon by a harmonically slowly varying explicitly time dependent load. The viscous damping is considered light and the column rests on an elastic foundation that produces a nonlinear ...

  4. Estimation of hysteretic damping of structures by stochastic subspace identification

    DEFF Research Database (Denmark)

    Bajric, Anela; Høgsberg, Jan Becker

    2018-01-01

    identification method suitable for random response of dynamic systems with hysteretic damping. The method applies the concept of Stochastic Subspace Identification (SSI) to estimate the model parameters of a dynamic system with hysteretic damping. The restoring force is represented by the Bouc-Wen model...

  5. Quantum theory of damped harmonic oscillator | Antia | Global ...

    African Journals Online (AJOL)

    The exact solutions of the Schrödinger equation for damped harmonic oscillator with pulsating mass and modified Caldirola-Kanai Hamiltonian are evaluated. We also investigated the case of under-damped for the two models constructed and the results obtained in both cases do not violate Heisenberg uncertainty principle ...

  6. Dynamic response analysis of a 24-story damped steel structure

    Science.gov (United States)

    Feng, Demin; Miyama, Takafumi

    2017-10-01

    In Japanese and Chinese building codes, a two-stage design philosophy, damage limitation (small earthquake, Level 1) and life safety (extreme large earthquake, Level 2), is adopted. It is very interesting to compare the design method of a damped structure based on the two building codes. In the Chinese code, in order to be consistent with the conventional seismic design method, the damped structure is also designed at the small earthquake level. The effect of damper systems is considered by the additional damping ratio concept. The design force will be obtained from the damped design spectrum considering the reduction due to the additional damping ratio. The additional damping ratio by the damper system is usually calculated by a time history analysis method at the small earthquake level. The velocity dependent type dampers such as viscous dampers can function well even in the small earthquake level. But, if steel damper is used, which usually remains elastic in the small earthquake, there will be no additional damping ratio achieved. On the other hand, a time history analysis is used in Japan both for small earthquake and extreme large earthquake level. The characteristics of damper system and ductility of the structure can be modelled well. An existing 24-story steel frame is modified to demonstrate the design process of the damped structure based on the two building codes. Viscous wall type damper and low yield steel panel dampers are studied as the damper system.

  7. Multicopper manganese oxidase accessory proteins bind Cu and heme.

    Science.gov (United States)

    Butterfield, Cristina N; Tao, Lizhi; Chacón, Kelly N; Spiro, Thomas G; Blackburn, Ninian J; Casey, William H; Britt, R David; Tebo, Bradley M

    2015-12-01

    Multicopper oxidases (MCOs) catalyze the oxidation of a diverse group of metal ions and organic substrates by successive single-electron transfers to O2 via four bound Cu ions. MnxG, which catalyzes MnO2 mineralization by oxidizing both Mn(II) and Mn(III), is unique among multicopper oxidases in that it carries out two energetically distinct electron transfers and is tightly bound to accessory proteins. There are two of these, MnxE and MnxF, both approximately 12kDa. Although their sequences are similar to those found in the genomes of several Mn-oxidizing Bacillus species, they are dissimilar to those of proteins with known function. Here, MnxE and MnxF are co-expressed independent of MnxG and are found to oligomerize into a higher order stoichiometry, likely a hexamer. They bind copper and heme, which have been characterized by electron paramagnetic resonance (EPR), X-ray absorption spectroscopy (XAS), and UV-visible (UV-vis) spectrophotometry. Cu is found in two distinct type 2 (T2) copper centers, one of which appears to be novel; heme is bound as a low-spin species, implying coordination by two axial ligands. MnxE and MnxF do not oxidize Mn in the absence of MnxG and are the first accessory proteins to be required by an MCO. This may indicate that Cu and heme play roles in electron transfer and/or Cu trafficking. Copyright © 2015 Elsevier B.V. All rights reserved.

  8. Pilot-scale tests of HEME and HEPA dissolution process

    Energy Technology Data Exchange (ETDEWEB)

    Qureshi, Z.H.; Strege, D.K.

    1994-06-01

    A series of pilot-scale demonstration tests for the dissolution of High Efficiency Mist Eliminators (HEME`s) and High Efficiency Particulate Airfilters (HEPA) were performed on a 1/5th linear scale. These fiberglass filters are to be used in the Defense Waste Processing Facility (DWPF) to decontaminate the effluents from the off-gases generated during the feed preparation process and vitrification. When removed, these filters will be dissolved in the Decontamination Waste Treatment Tank (DWTT) using 5 wt% NaOH solution. The contaminated fiberglass is converted to an aqueous stream which will be transferred to the waste tanks. The filter metal structure will be rinsed with process water before its disposal as low-level solid waste. The pilot-scale study reported here successfully demonstrated a simple one step process using 5 wt% NaOH solution. The proposed process requires the installation of a new water spray ring with 30 nozzles. In addition to the reduced waste generated, the total process time is reduced to 48 hours only (66% saving in time). The pilot-scale tests clearly demonstrated that the dissolution process of HEMEs has two stages - chemical digestion of the filter and mechanical erosion of the digested filter. The digestion is achieved by a boiling 5 wt% caustic solutions, whereas the mechanical break down of the digested filter is successfully achieved by spraying process water on the digested filter. An alternate method of breaking down the digested filter by increased air sparging of the solution was found to be marginally successful are best. The pilot-scale tests also demonstrated that the products of dissolution are easily pumpable by a centrifugal pump.

  9. Heme oxygenase-1 accelerates tumor angiogenesis of human pancreatic cancer.

    Science.gov (United States)

    Sunamura, Makoto; Duda, Dan G; Ghattas, Maivel H; Lozonschi, Lucian; Motoi, Fuyuhiko; Yamauchi, Jun-Ichiro; Matsuno, Seiki; Shibahara, Shigeki; Abraham, Nader G

    2003-01-01

    Angiogenesis is necessary for the continued growth of solid tumors, invasion and metastasis. Several studies clearly showed that heme oxygenase-1 (HO-1) plays an important role in angiogenesis. In this study, we used the vital microscope system, transparent skinfold model, lung colonization model and transduced pancreatic cancer cell line (Panc-1)/human heme oxygenase-1 (hHO-1) cells, to precisely analyze, for the first time, the effect of hHO-1 gene on tumor growth, angiogenesis and metastasis. Our results revealed that HO-1 stimulates angiogenesis of pancreatic carcinoma in severe combined immune deficient mice. Overexpression of human hHO-1 after its retroviral transfer into Panc-1 cells did not interfere with tumor growth in vitro. While in vivo the development of tumors was accelerated upon transfection with hHO-1. On the other hand, inhibition of heme oxygenase (HO) activity by stannous mesoporphyrin was able transiently to delay tumor growth in a dose dependent manner. Tumor angiogenesis was markedly increased in Panc-1/hHO-1 compared to mock transfected and wild type. Lectin staining and Ki-67 proliferation index confirmed these results. In addition hHO-1 stimulated in vitro tumor angiogenesis and increased endothelial cell survival. In a lung colonization model, overexpression of hHO-1 increased the occurrence of metastasis, while inhibition of HO activity by stannous mesoporphyrin completely inhibited the occurrence of metastasis. In conclusion, overexpression of HO-1 genes potentiates pancreatic cancer aggressiveness, by increasing tumor growth, angiogenesis and metastasis and that the inhibition of the HO system may be of useful benefit for the future treatment of the disease.

  10. Self-damping cementitious composites with multi-layer graphene

    Science.gov (United States)

    Ruan, Yanfeng; Zhou, Daocheng; Sun, Shengwei; Wu, Xinyi; Yu, Xun; Hou, Jilin; Dong, Xufeng; Han, Baoguo

    2017-07-01

    Cementitious composites are quasi-brittle and susceptible to damage under dynamic loads. The addition of nanoscale fillers into cementitious composites is an effective approach to address this issue. In this paper, multi-layer graphenes (MLGs) are incorporated into cementitious composites to enhance its damping property. The underlying modification mechanism of MLGs to cementitous composites is also investigated. Experimental results showed that the addition of MLGs can effectively modify the damping property of cementitious composites. Compared with cementitious composites without MLGs, the damping ratio of cementitious composites filled with 1% and 5% of MLGs increases by 16.22% and 45.73%, respectively. The improvement of MLGs to damping property of cementitious composites can be attributed to the interlayer slip of MLGs, viscous friction between MLGs and matrix, and excellent thermal conductivity of MLGs. Moreover, the damping ratio measured by time-domain exponential decay method and frequency-domain half-power bandwidth method is consistent.

  11. Collisional damping rates for electron plasma waves reassessed

    Science.gov (United States)

    Banks, J. W.; Brunner, S.; Berger, R. L.; Arrighi, W. J.; Tran, T. M.

    2017-10-01

    Collisional damping of electron plasma waves, the primary damping for high phase velocity waves, is proportional to the electron-ion collision rate, νei ,th. Here, it is shown that the damping rate normalized to νei ,th depends on the charge state, Z , on the magnitude of νei ,th and the wave number k in contrast with the commonly used damping rate in plasma wave research. Only for weak collision rates in low-Z plasmas for which the electron self-collision rate is comparable to the electron-ion collision rate is the damping rate given by the commonly accepted value. The result presented here corrects the result presented in textbooks at least as early as 1973. The complete linear theory requires the inclusion of both electron-ion pitch-angle and electron-electron scattering, which itself contains contributions to both pitch-angle scattering and thermalization.

  12. Prevalence of dampness and mold in European housing stock.

    Science.gov (United States)

    Haverinen-Shaughnessy, Ulla

    2012-09-01

    An assessment of the prevalence of dampness and mold in European housing stock was carried out. It is based on general indicators of dampness and mold in dwellings reported in the literature. The assessment relies on recent studies, taking into account regional and climatic differences, as well as differences in study design, methodology, and definitions. Data were available from 31 European countries. Weighted prevalence estimates are 12.1% for damp, 10.3% for mold, 10.0% for water damage, and 16.5% for a combination of any one or more indicators. Significant (up to 18%) differences were observed for dampness and mold prevalence estimates depending on survey factors, region, and climate. In conclusion, dampness and/or mold problems could be expected to occur in one of every six of the dwellings in Europe. Prevalence and occurrence of different types of problems may vary across geographical areas, which can be partly explained by differences in climate.

  13. Passively Damped Laminated Piezoelectric Shell Structures with Integrated Electric Networks

    Science.gov (United States)

    Saravanos, Dimitris A.

    1999-01-01

    Multi-field mechanics are presented for curvilinear piezoelectric laminates interfaced with distributed passive electric components. The equations of motion for laminated piezoelectric shell structures with embedded passive electric networks are directly formulated and solved using a finite element methodology. The modal damping and frequencies of the piezoelectric shell are calculated from the poles of the system. Experimental and numerical results are presented for the modal damping and frequency of composite beams with a resistively shunted piezoceramic patch. The modal damping and frequency of plates, cylindrical shells and cylindrical composite blades with piezoelectric-resistor layers are predicted. Both analytical and experimental studies illustrate a unique dependence of modal damping and frequencies on the shunting resistance and show the effect of structural shape and curvature on piezoelectric damping.

  14. Digital notch filter based active damping for LCL filters

    DEFF Research Database (Denmark)

    Yao, Wenli; Yang, Yongheng; Zhang, Xiaobin

    2015-01-01

    LCL filters are widely used in Pulse Width Modulation (PWM) inverters. However, it also introduces a pair of unstable resonant poles that may challenge the controller stability. The passive damping is a convenient possibility to tackle the resonance problem at the cost of system overall efficiency....... In contrast, the active damping does not require any dissipation elements, and thus has become of increasing interest. As a result, a vast of active damping solutions have been reported, among which multi-loop control systems and additional sensors are necessary, leading to increased cost and complexity....... In this paper, a notch filter based active damping without the requirement of additional sensors is proposed, where the inverter current is employed as the feedback variable. Firstly, a design method of the notch filter for active damping is presented. The entire system stability has then been investigated...

  15. Fast damping in mismatched high intensity beam transportation

    Directory of Open Access Journals (Sweden)

    V. Variale

    2001-08-01

    Full Text Available A very fast damping of beam envelope oscillation amplitudes was recently observed in simulations of high intensity beam transport, through periodic FODO cells, in mismatched conditions [V. Variale, Nuovo Cimento Soc. Ital. Fis. 112A, 1571–1582 (1999 and T. Clauser et al., in Proceedings of the Particle Accelerator Conference, New York, 1999 (IEEE, Piscataway, NJ, 1999, p. 1779]. A Landau damping mechanism was proposed at the origin of observed effect. In this paper, to further investigate the source of this fast damping, extensive simulations have been carried out. The results presented here support the interpretation of the mechanism at the origin of the fast damping as a Landau damping effect.

  16. Passively Shunted Piezoelectric Damping of Centrifugally-Loaded Plates

    Science.gov (United States)

    Duffy, Kirsten P.; Provenza, Andrew J.; Trudell, Jeffrey J.; Min, James B.

    2009-01-01

    Researchers at NASA Glenn Research Center have been investigating shunted piezoelectric circuits as potential damping treatments for turbomachinery rotor blades. This effort seeks to determine the effects of centrifugal loading on passively-shunted piezoelectric - damped plates. Passive shunt circuit parameters are optimized for the plate's third bending mode. Tests are performed both non-spinning and in the Dynamic Spin Facility to verify the analysis, and to determine the effectiveness of the damping under centrifugal loading. Results show that a resistive shunt circuit will reduce resonant vibration for this configuration. However, a tuned shunt circuit will be required to achieve the desired damping level. The analysis and testing address several issues with passive shunt circuit implementation in a rotating system, including piezoelectric material integrity under centrifugal loading, shunt circuit implementation, and tip mode damping.

  17. Calibrating damping rates with LEGACY linewidths

    Science.gov (United States)

    Houdek, Günter

    2017-10-01

    Linear damping rates of radial oscillation modes in selected Kepler stars are estimated with the help of a nonadiabatic stability analysis. The convective fluxes are obtained from a nonlocal, time-dependent convection model. The mixing-length parameter is calibrated to the surface-convection-zone depth of a stellar model obtained from fitting adiabatic frequencies to the LEGACY* observations, and two of the three nonlocal convection parameters are calibrated to the corresponding LEGACY* linewidth measurements. The atmospheric structure in the 1D stability analysis adopts a temperature-optical-depth relation derived from 3D hydrodynamical simulations. Results from 3D simulations are also used to calibrate the turbulent pressure and to guide the functional form of the depth-dependence of the anisotropy of the turbulent velocity field in the 1D stability computations.

  18. Active vibration damping using smart material

    Science.gov (United States)

    Baras, John S.; Yan, Zhuang

    1994-01-01

    We consider the modeling and active damping of an elastic beam using distributed actuators and sensors. The piezoelectric ceramic material (PZT) is used to build the actuator. The sensor is made of the piezoelectric polymer polyvinylidene fluoride (PVDF). These materials are glued on both sides of the beam. For the simple clamped beam, the closed loop controller has been shown to be able to extract energy from the beam. The shape of the actuator and its influence on the closed loop system performance are discussed. It is shown that it is possible to suppress the selected mode by choosing the appropriate actuator layout. It is also shown that by properly installing the sensor and determining the sensor shape we can further extract and manipulate the sensor signal for our control need.

  19. problem for the damped Boussinesq equation

    Directory of Open Access Journals (Sweden)

    Vladimir V. Varlamov

    1997-01-01

    Full Text Available For the damped Boussinesq equation utt−2butxx=−αuxxxx+uxx+β(u2xx,x∈(0,π,t>0;α,b=const>0,β=const∈R1, the second initial-boundary value problem is considered with small initial data. Its classical solution is constructed in the form of a series in small parameter present in the initial conditions and the uniqueness of solutions is proved. The long-time asymptotics is obtained in the explicit form and the question of the blow up of the solution in a certain case is examined. The possibility of passing to the limit b→+0 in the constructed solution is investigated.

  20. State protection under collective damping and diffusion

    Energy Technology Data Exchange (ETDEWEB)

    Ponte, M. A. de [Instituto de Fisica de Sao Carlos, Universidade de Sao Paulo, Caixa Postal 369, 13560-590 Sao Carlos, SP (Brazil); Departamento de Fisica, Universidade Regional do Cariri, 63010-970 Juazeiro do Norte, CE (Brazil); Mizrahi, S. S. [Departamento de Fisica, Universidade Federal de Sao Carlos, 13565-905 Sao Carlos, SP (Brazil); Moussa, M. H. Y. [Instituto de Fisica de Sao Carlos, Universidade de Sao Paulo, Caixa Postal 369, 13560-590 Sao Carlos, SP (Brazil)

    2011-07-15

    In this paper we provide a recipe for state protection in a network of oscillators under collective damping and diffusion. Our strategy is to manipulate the network topology, i.e., the way the oscillators are coupled together, the strength of their couplings, and their natural frequencies, in order to create a relaxation-diffusion-free channel. This protected channel defines a decoherence-free subspace (DFS) for nonzero-temperature reservoirs. Our development also furnishes an alternative approach to build up DFSs that offers two advantages over the conventional method: it enables the derivation of all the network-protected states at once, and also reveals, through the network normal modes, the mechanism behind the emergence of these protected domains.

  1. Eddy-current-damped microelectromechanical switch

    Energy Technology Data Exchange (ETDEWEB)

    Christenson, Todd R. (Albuquerque, NM); Polosky, Marc A. (Tijeras, NM)

    2007-10-30

    A microelectromechanical (MEM) device is disclosed that includes a shuttle suspended for movement above a substrate. A plurality of permanent magnets in the shuttle of the MEM device interact with a metal plate which forms the substrate or a metal portion thereof to provide an eddy-current damping of the shuttle, thereby making the shuttle responsive to changes in acceleration or velocity of the MEM device. Alternately, the permanent magnets can be located in the substrate, and the metal portion can form the shuttle. An electrical switch closure in the MEM device can occur in response to a predetermined acceleration-time event. The MEM device, which can be fabricated either by micromachining or LIGA, can be used for sensing an acceleration or deceleration event (e.g. in automotive applications such as airbag deployment or seat belt retraction).

  2. Eddy-current-damped microelectromechanical switch

    Energy Technology Data Exchange (ETDEWEB)

    Christenson, Todd R [Albuquerque, NM; Polosky, Marc A [Tijeras, NM

    2009-12-15

    A microelectromechanical (MEM) device is disclosed that includes a shuttle suspended for movement above a substrate. A plurality of permanent magnets in the shuttle of the MEM device interact with a metal plate which forms the substrate or a metal portion thereof to provide an eddy-current damping of the shuttle, thereby making the shuttle responsive to changes in acceleration or velocity of the MEM device. Alternately, the permanent magnets can be located in the substrate, and the metal portion can form the shuttle. An electrical switch closure in the MEM device can occur in response to a predetermined acceleration-time event. The MEM device, which can be fabricated either by micromachining or LIGA, can be used for sensing an acceleration or deceleration event (e.g. in automotive applications such as airbag deployment or seat belt retraction).

  3. Cloning and Expression of cDNA for Rat Heme Oxygenase

    Science.gov (United States)

    Shibahara, Shigeki; Muller, Rita; Taguchi, Hayao; Yoshida, Tadashi

    1985-12-01

    Two cDNA clones for rat heme oxygenase have been isolated from a rat spleen cDNA library in λ gt11 by immunological screening using a specific polyclonal antibody. One of these clones has an insert of 1530 nucleotides that contains the entire protein-coding region. To confirm that the isolated cDNA encodes heme oxygenase, we transfected monkey kidney cells (COS-7) with the cDNA carried in a simian virus 40 vector. The heme oxygenase was highly expressed in endoplasmic reticulum of transfected cells. The nucleotide sequence of the cloned cDNA was determined and the primary structure of heme oxygenase was deduced. Heme oxygenase is composed of 289 amino acids and has one hydrophobic segment at its carboxyl terminus, which is probably important for the insertion of heme oxygenase into endoplasmic reticulum. The cloned cDNA was used to analyze the induction of heme oxygenase in rat liver by treatment with CoCl2 or with hemin. RNA blot analysis showed that both CoCl2 and hemin increased the amount of hybridizable mRNA, suggesting that these substances may act at the transcriptional level to increase the amount of heme oxygenase.

  4. Stanniocalcin 1 binds hemin through a partially conserved heme regulatory motif

    Energy Technology Data Exchange (ETDEWEB)

    Westberg, Johan A., E-mail: johan.westberg@helsinki.fi [Department of Pathology, Haartman Institute, University of Helsinki and HUSLAB, P.O. Box 21, Haartmaninkatu 3, FI-00014 Helsinki (Finland); Jiang, Ji, E-mail: ji.jiang@helsinki.fi [Department of Pathology, Haartman Institute, University of Helsinki and HUSLAB, P.O. Box 21, Haartmaninkatu 3, FI-00014 Helsinki (Finland); Andersson, Leif C., E-mail: leif.andersson@helsinki.fi [Department of Pathology, Haartman Institute, University of Helsinki and HUSLAB, P.O. Box 21, Haartmaninkatu 3, FI-00014 Helsinki (Finland)

    2011-06-03

    Highlights: {yields} Stanniocalcin 1 (STC1) binds heme through novel heme binding motif. {yields} Central iron atom of heme and cysteine-114 of STC1 are essential for binding. {yields} STC1 binds Fe{sup 2+} and Fe{sup 3+} heme. {yields} STC1 peptide prevents oxidative decay of heme. -- Abstract: Hemin (iron protoporphyrin IX) is a necessary component of many proteins, functioning either as a cofactor or an intracellular messenger. Hemoproteins have diverse functions, such as transportation of gases, gas detection, chemical catalysis and electron transfer. Stanniocalcin 1 (STC1) is a protein involved in respiratory responses of the cell but whose mechanism of action is still undetermined. We examined the ability of STC1 to bind hemin in both its reduced and oxidized states and located Cys{sup 114} as the axial ligand of the central iron atom of hemin. The amino acid sequence differs from the established (Cys-Pro) heme regulatory motif (HRM) and therefore presents a novel heme binding motif (Cys-Ser). A STC1 peptide containing the heme binding sequence was able to inhibit both spontaneous and H{sub 2}O{sub 2} induced decay of hemin. Binding of hemin does not affect the mitochondrial localization of STC1.

  5. The effect of irradiation and thermal process on beef heme iron concentration and color properties

    Energy Technology Data Exchange (ETDEWEB)

    Mistura, Liliana Perazzini Furtado; Colli, Celia [Universidade de Sao Paulo (USP), SP (Brazil). Faculdade de Ciencias Farmaceuticas. Dept. de Alimentos e Nutricao Experimental], e-mail: cecolli@usp.br

    2009-01-15

    The aim of this study was to evaluate the influence of irradiation and thermal process on the heme iron (heme-Fe) concentration and color properties of Brazilian cattle beef. Beef samples (patties and steaks) were irradiated at 0-10 kGy and cooked in a combination oven at 250 deg C for 9 minutes with 70% humidity. Total iron and heme iron (heme-Fe) concentrations were determined. The data were compared by multiple comparisons and fixed- effects ANOVA. Irradiation at doses higher than 5 kGy significantly altered the heme-Fe concentration. However, the sample preparation conditions interfered more in the heme-Fe content than did the irradiation. Depending on the animal species, meat heme iron levels between 35 and 52% of the total iron are used for dietetic calculations. In this study the percentage of heme-iron was, on average, 70% of the total iron showing that humidity is an important factor for its preservation. The samples were analyzed instrumentally for CIE L{sup *}, a{sup *}, and b{sup *} values. (author)

  6. Dietary heme adversely affects experimental colitis in rats, despite heat-shock protein induction

    NARCIS (Netherlands)

    Schepens, Marloes A. A.; Vink, Carolien; Schonewille, Arjan J.; Dijkstra, Gerard; van der Meer, Roelof; Bovee-Oudenhoven, Ingeborg M. J.

    Objective: Research on dietary modulation of inflammatory bowel disease is in its infancy. Dietary heme, mimicking red meat, is cytotoxic to colonic epithelium and thus may aggravate colitis. Alternatively, heme-induced colonic stress might also result in potential protective heat-shock proteins

  7. Long-term dietary heme iron and red meat intake in relation to endometrial cancer risk

    NARCIS (Netherlands)

    Genkinger, J.M.; Friberg, E.; Goldbohm, R.A.; Wolk, A.

    2012-01-01

    Background: Heme and total iron, present in meat, have been hypothesized to promote carcinogenesis. Few prospective studies have examined the associations between intakes of heme and total iron, types of meat, and endometrial cancer risk. Objective: We evaluated the associations between intakes of

  8. Unsaturated Glycerophospholipids Mediate Heme Crystallization: Biological Implications for Hemozoin Formation in the Kissing Bug Rhodnius prolixus

    DEFF Research Database (Denmark)

    Stiebler, R.; Majerowicz, David; Knudsen, Jens

    2014-01-01

    Hemozoin (Hz) is a heme crystal produced by some blood-feeding organisms, as an efficient way to detoxify heme derived from hemoglobin digestion. In the triatomine insect Rhodnius prolixus, Hz is essentially produced by midgut extracellular phospholipid membranes known as perimicrovillar membranes...

  9. Dietary heme modulates microbiota and mucosa of mouse colon without significant host-microbe cross talk

    NARCIS (Netherlands)

    IJssennagger, Noortje; Rijnierse, A.; Muller, Michael; Meer, van der Roelof

    2013-01-01

    Previously, we showed that dietary heme injured the colonic surface epithelium and induced hyperproliferation by changing the surface to crypt signaling. In this study we investigated whether bacteria play a role in this changed signaling. Dietary heme increased the Bacteroidetes and decreased the

  10. Natural chlorophyll but not chlorophyllin prevents heme-induced cytotoxic and hyperproliferative effects in rat colon

    NARCIS (Netherlands)

    Vogel, de J.; Jonker-Termont, D.S.M.L.; Katan, M.B.; Meer, van der R.

    2005-01-01

    Diets high in red meat and low in green vegetables are associated with an increased risk of colon cancer. In rats, dietary heme, mimicking red meat, increases colonic cytotoxicity and proliferation of the colonocytes, whereas addition of chlorophyll from green vegetables inhibits these heme-induced

  11. Heme and chlorophyll intake and risk of colorectal cancer in the Netherlands cohort study

    NARCIS (Netherlands)

    Balder, H.F.; Vogel, J. de; Jansen, M.C.J.F.; Weijenberg, M.P.; Brandt, P.A. van den; Westenbrink, S.; Meer, R.D. van der; Goldbohm, R.A.

    2006-01-01

    Background: The evidence for red meat as a determinant of colorectal cancer remains equivocal, which might be explained by differences in heme content. Heme is the prooxidant, iron-containing porphyrin pigment of meat and its content depends on the type of meat. Chlorophyll from green vegetables

  12. Heme metabolism in stress regulation and protein production: from Cinderella to a key player

    DEFF Research Database (Denmark)

    Martinez Ruiz, José Luis; Petranovic, D.; Nielsen, Jens

    2016-01-01

    Heme biosynthesis is a highly conserved pathway which is present in all kingdoms, from Archaea to higher organisms such as plants and mammals. The heme molecule acts as a prosthetic group for different proteins and enzymes involved in energy metabolism and reactions involved in electron transfer....

  13. Experimental Observations on Material Damping at Cryogenic Temperatures

    Science.gov (United States)

    Peng, Chia-Yen; Levine, Marie; Shido, Lillian; Leland, Robert

    2004-01-01

    This paper describes a unique experimental facility designed to measure damping of materials at cryogenic temperatures for the Terrestrial Planet Finder (TPF) mission at the Jet Propulsion Laboratory. The test facility removes other sources of damping in the measurement by avoiding frictional interfaces, decoupling the test specimen from the support system, and by using a non-contacting measurement device. Damping data reported herein are obtained for materials (Aluminum, Aluminum/Terbium/Dysprosium, Titanium, Composites) vibrating in free-free bending modes with low strain levels (< 10(exp -6) ppm). The fundamental frequencies of material samples are ranged from 14 to 202 Hz. To provide the most beneficial data relevant to TPF-like precision optical space missions, the damping data are collected from room temperatures (around 293 K) to cryogenic temperatures (below 40 K) at unevenly-spaced intervals. More data points are collected over any region of interest. The test data shows a significant decrease in viscous damping at cryogenic temperatures. The cryogenic damping can be as low as 10(exp -4) %, but the amount of the damping decrease is a function of frequency and material. However, Titanium 15-3-3-3 shows a remarkable increase in damping at cryogenic temperatures. It demonstrates over one order of magnitude increase in damping in comparison to Aluminum 6061-T6. Given its other properties (e.g., good stiffness and low conductivity) this may prove itself to be a good candidate for the application on TPF. At room temperatures, the test data are correlated well with the damping predicted by the Zener theory. However, large discrepancies at cryogenic temperatures between the Zener theory and the test data are observed.

  14. Molecularly Imprinted Electropolymer for a Hexameric Heme Protein with Direct Electron Transfer and Peroxide Electrocatalysis

    Science.gov (United States)

    Peng, Lei; Yarman, Aysu; Jetzschmann, Katharina J.; Jeoung, Jae-Hun; Schad, Daniel; Dobbek, Holger; Wollenberger, Ulla; Scheller, Frieder W.

    2016-01-01

    For the first time a molecularly imprinted polymer (MIP) with direct electron transfer (DET) and bioelectrocatalytic activity of the target protein is presented. Thin films of MIPs for the recognition of a hexameric tyrosine-coordinated heme protein (HTHP) have been prepared by electropolymerization of scopoletin after oriented assembly of HTHP on a self-assembled monolayer (SAM) of mercaptoundecanoic acid (MUA) on gold electrodes. Cavities which should resemble the shape and size of HTHP were formed by template removal. Rebinding of the target protein sums up the recognition by non-covalent interactions between the protein and the MIP with the electrostatic attraction of the protein by the SAM. HTHP bound to the MIP exhibits quasi-reversible DET which is reflected by a pair of well pronounced redox peaks in the cyclic voltammograms (CVs) with a formal potential of −184.4 ± 13.7 mV vs. Ag/AgCl (1 M KCl) at pH 8.0 and it was able to catalyze the cathodic reduction of peroxide. At saturation the MIP films show a 12-fold higher electroactive surface concentration of HTHP than the non-imprinted polymer (NIP). PMID:26907299

  15. Design, Fabrication, and Properties of High Damping Metal Matrix Composites?A Review

    OpenAIRE

    Qianfeng Fang; Zhijun Cheng; Tao Zhang; Xianping Wang; Hui Lu

    2009-01-01

    Nowadays it is commonly considered that high damping materials which have both the good mechanical properties as structural materials and the high damping capacity for vibration damping are the most direct vibration damping solution. In metals and alloys however, exhibiting simultaneously high damping capacity and good mechanical properties has been noted to be normally incompatible because the microscopic mechanisms responsible for internal friction (namely damping capacity) are dependent up...

  16. Prognostic and predictive value of DAMPs and DAMP-associated processes in cancer

    Directory of Open Access Journals (Sweden)

    Jitka eFucikova

    2015-08-01

    Full Text Available It is now clear that human neoplasms form, progress and respond to therapy in the context of an intimate crosstalk with the host immune system. In particular, accumulating evidence demonstrates that the efficacy of most, if not all, chemo- and radiotherapeutic agents commonly employed in the clinic critically depends on the (reactivation of tumor-targeting immune response. One of the mechanisms whereby conventional chemotherapeutics, targeted anticancer agents and radiotherapy can provoke a therapeutically relevant, adaptive immune response against malignant cells is commonly known as „immunogenic cell death (ICD. Importantly, dying cancer cells are perceived as immunogenic only when they emit a set of immunostimulatory signals upon the activation of intracellular stress response pathways. The emission of these signals, which are generally referred to as „damage-associated molecular patterns (DAMPs, may therefore predict whether patients will respond to chemotherapy or not, at least in some settings. Here, we review clinical data indicating that DAMPs and DAMP-associated stress responses might have prognostic or predictive value for cancer patients.

  17. Artificial Self-Sufficient P450 in Reversed Micelles

    Directory of Open Access Journals (Sweden)

    Teruyuki Nagamune

    2010-04-01

    Full Text Available Cytochrome P450s are heme-containing monooxygenases that require electron transfer proteins for their catalytic activities. They prefer hydrophobic compounds as substrates and it is, therefore, desirable to perform their reactions in non-aqueous media. Reversed micelles can stably encapsulate proteins in nano-scaled water pools in organic solvents. However, in the reversed micellar system, when multiple proteins are involved in a reaction they can be separated into different micelles and it is then difficult to transfer electrons between proteins. We show here that an artificial self-sufficient cytochrome P450, which is an enzymatically crosslinked fusion protein composed of P450 and electron transfer proteins, showed micelle-size dependent catalytic activity in a reversed micellar system. Furthermore, the presence of thermostable alcohol dehydrogenase promoted the P450-catalyzed reaction due to cofactor regeneration.

  18. Cyanide does more to inhibit heme enzymes, than merely serving as an active-site ligand

    Energy Technology Data Exchange (ETDEWEB)

    Parashar, Abhinav [Center for Biomedical Research, VIT University, Vellore, Tamil Nadu, 632014 India (India); Venkatachalam, Avanthika [REDOx Lab, PSG Institute of Advanced Studies, Avinashi Road, Peelamedu, Coimbatore, Tamil Nadu, 641004 (India); Gideon, Daniel Andrew [Center for Biomedical Research, VIT University, Vellore, Tamil Nadu, 632014 India (India); Manoj, Kelath Murali, E-mail: satyamjayatu@yahoo.com [REDOx Lab, PSG Institute of Advanced Studies, Avinashi Road, Peelamedu, Coimbatore, Tamil Nadu, 641004 (India)

    2014-12-12

    Highlights: • Cyanide (CN) is a well-studied toxic principle, known to inhibit heme-enzymes. • Inhibition is supposed to result from CN binding at the active site as a ligand. • Diverse heme enzymes’ CN inhibition profiles challenge prevailing mechanism. • Poor binding efficiency of CN at low enzyme concentrations and ligand pressures. • CN-based diffusible radicals cause ‘non-productive electron transfers’ (inhibition). - Abstract: The toxicity of cyanide is hitherto attributed to its ability to bind to heme proteins’ active site and thereby inhibit their activity. It is shown herein that the long-held interpretation is inadequate to explain several observations in heme-enzyme reaction systems. Generation of cyanide-based diffusible radicals in heme-enzyme reaction milieu could shunt electron transfers (by non-active site processes), and thus be detrimental to the efficiency of oxidative outcomes.

  19. Atomistic Mechanisms for Viscoelastic Damping in Inorganic Solids

    Science.gov (United States)

    Ranganathan, Raghavan

    Viscoelasticity, a ubiquitous material property, can be tuned to engineer a wide range of fascinating applications such as mechanical dampers, artificial tissues, functional foams and optoelectronics, among others. Traditionally, soft matter such as polymers and polymer composites have been used extensively for viscoelastic damping applications, owing to the inherent viscous nature of interactions between polymer chains. Although this leads to good damping characteristics, the stiffness in these materials is low, which in turn leads to limitations. In this context, hard inorganic materials and composites are promising candidates for enhanced damping, owing to their large stiffness and, in some cases large loss modulus. Viscoelasticity in these materials has been relatively unexplored and atomistic mechanisms responsible for damping are not apparent. Therefore, the overarching goal of this work is to understand mechanisms for viscoelastic damping in various classes of inorganic composites and alloys at an atomistic level from molecular dynamics simulations. We show that oscillatory shear deformation serves as a powerful probe to explain mechanisms for exceptional damping in hitherto unexplored systems. The first class of inorganic materials consists of crystalline phases of a stiff inclusion in a soft matrix. The two crystals within the composite, namely the soft and a stiff phase, individually show a highly elastic behavior and a very small loss modulus. On the other hand, a composite with the two phases is seen to exhibit damping that is about 20 times larger than predicted theoretical bounds. The primary reason for the damping is due to large anharmonicity in phonon-phonon coupling, resulting from the composite microstructure. A concomitant effect is the distribution of shear strain, which is observed to be highly inhomogeneous and mostly concentrated in the soft phase. Interestingly, the shear frequency at which the damping is greatest is observed to scale with

  20. Posttranslational Modification of Heme b in a Bacterial Peroxidase: The Role of Heme to Protein Ester Bonds in Ligand Binding and Catalysis.

    Science.gov (United States)

    Nicolussi, Andrea; Auer, Markus; Weissensteiner, Julia; Schütz, Georg; Katz, Sonja; Maresch, Daniel; Hofbauer, Stefan; Bellei, Marzia; Battistuzzi, Gianantonio; Furtmüller, Paul G; Obinger, Christian

    2017-08-29

    The existence of covalent heme to protein bonds is the most striking structural feature of mammalian peroxidases, including myeloperoxidase and lactoperoxidase (LPO). These autocatalytic posttranslational modifications (PTMs) were shown to strongly influence the biophysical and biochemical properties of these oxidoreductases. Recently, we reported the occurrence of stable LPO-like counterparts with two heme to protein ester linkages in bacteria. This study focuses on the model wild-type peroxidase from the cyanobacterium Lyngbya sp. PCC 8106 (LspPOX) and the mutants D109A, E238A, and D109A/E238A that could be recombinantly produced as apoproteins in Escherichia coli, fully reconstituted to the respective heme b proteins, and posttranslationally modified by hydrogen peroxide. This for the first time allows not only a direct comparison of the catalytic properties of the heme b and PTM forms but also a study of the impact of D109 and E238 on PTM and catalysis, including Compound I formation and the two-electron reduction of Compound I by bromide, iodide, and thiocyanate. It is demonstrated that both heme to protein ester bonds can form independently and that elimination of E238, in contrast to exchange of D109, does not cause significant structural rearrangements or changes in the catalytic properties neither in heme b nor in the PTM form. The obtained findings are discussed with respect to published structural and functional data of human peroxidases.

  1. Direct Tests of Enzymatic Heme Degradation by the Malaria Parasite Plasmodium falciparum*

    Science.gov (United States)

    Sigala, Paul A.; Crowley, Jan R.; Hsieh, Samantha; Henderson, Jeffrey P.; Goldberg, Daniel E.

    2012-01-01

    Malaria parasites generate vast quantities of heme during blood stage infection via hemoglobin digestion and limited de novo biosynthesis, but it remains unclear if parasites metabolize heme for utilization or disposal. Recent in vitro experiments with a heme oxygenase (HO)-like protein from Plasmodium falciparum suggested that parasites may enzymatically degrade some heme to the canonical HO product, biliverdin (BV), or its downstream metabolite, bilirubin (BR). To directly test for BV and BR production by P. falciparum parasites, we DMSO-extracted equal numbers of infected and uninfected erythrocytes and developed a sensitive LC-MS/MS assay to quantify these tetrapyrroles. We found comparable low levels of BV and BR in both samples, suggesting the absence of HO activity in parasites. We further tested live parasites by targeted expression of a fluorescent BV-binding protein within the parasite cytosol, mitochondrion, and plant-like plastid. This probe could detect exogenously added BV but gave no signal indicative of endogenous BV production within parasites. Finally, we recombinantly expressed and tested the proposed heme degrading activity of the HO-like protein, PfHO. Although PfHO bound heme and protoporphyrin IX with modest affinity, it did not catalyze heme degradation in vivo within bacteria or in vitro in UV absorbance and HPLC assays. These observations are consistent with PfHO's lack of a heme-coordinating His residue and suggest an alternative function within parasites. We conclude that P. falciparum parasites lack a canonical HO pathway for heme degradation and thus rely fully on alternative mechanisms for heme detoxification and iron acquisition during blood stage infection. PMID:22992734

  2. Heme Attenuation Ameliorates Irritant Gas Inhalation-Induced Acute Lung Injury.

    Science.gov (United States)

    Aggarwal, Saurabh; Lam, Adam; Bolisetty, Subhashini; Carlisle, Matthew A; Traylor, Amie; Agarwal, Anupam; Matalon, Sadis

    2016-01-10

    Exposure to irritant gases, such as bromine (Br2), poses an environmental and occupational hazard that results in severe lung and systemic injury. However, the mechanism(s) of Br2 toxicity and the therapeutic responses required to mitigate lung damage are not known. Previously, it was demonstrated that Br2 upregulates the heme degrading enzyme, heme oxygenase-1 (HO-1). Since heme is a major inducer of HO-1, we determined whether an increase in heme and heme-dependent oxidative injury underlies the pathogenesis of Br2 toxicity. C57BL/6 mice were exposed to Br2 gas (600 ppm, 30 min) and returned to room air. Thirty minutes postexposure, mice were injected intraperitoneally with a single dose of the heme scavenging protein, hemopexin (Hx) (3 μg/gm body weight), or saline. Twenty-four hours postexposure, saline-treated mice had elevated total heme in bronchoalveolar lavage fluid (BALF) and plasma and acute lung injury (ALI) culminating in 80% mortality after 10 days. Hx treatment significantly lowered heme, decreased evidence of ALI (lower protein and inflammatory cells in BALF, lower lung wet-to-dry weight ratios, and decreased airway hyperreactivity to methacholine), and reduced mortality. In addition, Br2 caused more severe ALI and mortality in mice with HO-1 gene deletion (HO-1-/-) compared to wild-type controls, while transgenic mice overexpressing the human HO-1 gene (hHO-1) showed significant protection. This is the first study delineating the role of heme in ALI caused by Br2. The data suggest that attenuating heme may prove to be a useful adjuvant therapy to treat patients with ALI.

  3. Enhanced heme function and mitochondrial respiration promote the progression of lung cancer cells.

    Science.gov (United States)

    Hooda, Jagmohan; Cadinu, Daniela; Alam, Md Maksudul; Shah, Ajit; Cao, Thai M; Sullivan, Laura A; Brekken, Rolf; Zhang, Li

    2013-01-01

    Lung cancer is the leading cause of cancer-related mortality, and about 85% of the cases are non-small-cell lung cancer (NSCLC). Importantly, recent advance in cancer research suggests that altering cancer cell bioenergetics can provide an effective way to target such advanced cancer cells that have acquired mutations in multiple cellular regulators. This study aims to identify bioenergetic alterations in lung cancer cells by directly measuring and comparing key metabolic activities in a pair of cell lines representing normal and NSCLC cells developed from the same patient. We found that the rates of oxygen consumption and heme biosynthesis were intensified in NSCLC cells. Additionally, the NSCLC cells exhibited substantially increased levels in an array of proteins promoting heme synthesis, uptake and function. These proteins include the rate-limiting heme biosynthetic enzyme ALAS, transporter proteins HRG1 and HCP1 that are involved in heme uptake, and various types of oxygen-utilizing hemoproteins such as cytoglobin and cytochromes. Several types of human tumor xenografts also displayed increased levels of such proteins. Furthermore, we found that lowering heme biosynthesis and uptake, like lowering mitochondrial respiration, effectively reduced oxygen consumption, cancer cell proliferation, migration and colony formation. In contrast, lowering heme degradation does not have an effect on lung cancer cells. These results show that increased heme flux and function are a key feature of NSCLC cells. Further, increased generation and supply of heme and oxygen-utilizing hemoproteins in cancer cells will lead to intensified oxygen consumption and cellular energy production by mitochondrial respiration, which would fuel cancer cell proliferation and progression. The results show that inhibiting heme and respiratory function can effectively arrest the progression of lung cancer cells. Hence, understanding heme function can positively impact on research in lung cancer

  4. Endogenous Estrogen-Mediated Heme Oxygenase Regulation in Experimental Menopause

    Directory of Open Access Journals (Sweden)

    Anikó Pósa

    2015-01-01

    Full Text Available Estrogen deficiency is one of the main causes of age-associated diseases in the cardiovascular system. Female Wistar rats were divided into four experimental groups: pharmacologically ovariectomized, surgically ovariectomized, and 24-month-old intact aging animals were compared with a control group. The activity and expression of heme oxygenases (HO in the cardiac left ventricle, the concentrations of cardiac interleukin-6 (IL-6 and tumor necrosis factor-α (TNF-α, the myeloperoxidase (MPO activity in the cardiac left ventricle, and the effects of heme oxygenase blockade (by 24-hour and 1-hour pretreatment with tin-protoporphyrin IX, SnPP on the epinephrine and phentolamine-induced electrocardiogram ST segment changes in vivo were investigated. The cardiac HO activity and the expression of HO-1 and HO-2 were significantly decreased in the aged rats and after ovariectomy. Estrogen depletion was accompanied by significant increases in the expression of IL-6 and TNF-α. The aged and ovariectomized animals exhibited a significantly elevated MPO activity and a significant ST segment depression. After pretreatment with SnPP augmented ST segment changes were determined. These findings demonstrate that the sensitivity to cardiac ischemia in estrogen depletion models is associated with suppression of the activity and expression of the HO system and increases in the secretion of proinflammatory cytokines and biomarkers.

  5. Studies of multi-heme cytochromes from Geobacter sulfurreducens

    Energy Technology Data Exchange (ETDEWEB)

    Londer, Yuri; Pokkuluri, P. Raj; Orshonsky, Valerie; Duke, Norma; Schiffer, Marianne

    2004-03-17

    The Geobacteraceae family predominates in the reduction of uranium in subsurface environments. We are focusing on the model organism, Geobacter sulfurreducens; its genome contains a large number (>100) of cytochromes c that function in metal reduction pathways. Intensive functional genomics and physiological studies are in progress in Prof. Derek Lovley's laboratory, and the complete genome sequence of this organism has been determined by Methe et al. 2003. We are studying cytochromes from the c{sub 7} family that are required for the reduction of Fe(III). Previously, we expressed in E. coli (Londer et al., 2002) and determined the three-dimensional structure at 1.45 {angstrom} resolution (Pokkuluri et al., 2004a) of the three-heme cytochrome c{sub 7} (PpcA, coded by ORF01023) characterized by Lloyd et al., 2003. Further we identified in the G. sulfurreducens genome ORFs for several of its homologs (Pokkuluri et al., 2004a). Four of the ORFs are the same size as PpcA; three other ORFs are polymers of c{sub 7}-type domains, two of which consist of four domains and one of nine domains, that contain 12 and 27 hemes respectively.

  6. Endogenous Estrogen-Mediated Heme Oxygenase Regulation in Experimental Menopause

    Science.gov (United States)

    Pósa, Anikó; Veszelka, Médea; Berkó, Anikó Magyariné; Baráth, Zoltán; Ménesi, Rudolf; Pávó, Imre; László, Ferenc; Varga, Csaba

    2015-01-01

    Estrogen deficiency is one of the main causes of age-associated diseases in the cardiovascular system. Female Wistar rats were divided into four experimental groups: pharmacologically ovariectomized, surgically ovariectomized, and 24-month-old intact aging animals were compared with a control group. The activity and expression of heme oxygenases (HO) in the cardiac left ventricle, the concentrations of cardiac interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), the myeloperoxidase (MPO) activity in the cardiac left ventricle, and the effects of heme oxygenase blockade (by 24-hour and 1-hour pretreatment with tin-protoporphyrin IX, SnPP) on the epinephrine and phentolamine-induced electrocardiogram ST segment changes in vivo were investigated. The cardiac HO activity and the expression of HO-1 and HO-2 were significantly decreased in the aged rats and after ovariectomy. Estrogen depletion was accompanied by significant increases in the expression of IL-6 and TNF-α. The aged and ovariectomized animals exhibited a significantly elevated MPO activity and a significant ST segment depression. After pretreatment with SnPP augmented ST segment changes were determined. These findings demonstrate that the sensitivity to cardiac ischemia in estrogen depletion models is associated with suppression of the activity and expression of the HO system and increases in the secretion of proinflammatory cytokines and biomarkers. PMID:26064421

  7. Disrupted postnatal lung development in heme oxygenase-1 deficient mice

    Directory of Open Access Journals (Sweden)

    Zhang Huayan

    2010-10-01

    Full Text Available Abstract Background Heme oxygenase (HO degrades cellular heme to carbon monoxide, iron and biliverdin. The HO-1 isoform is both inducible and cyto-protective during oxidative stress, inflammation and lung injury. However, little is known about its precise role and function in lung development. We hypothesized that HO-1 is required for mouse postnatal lung alveolar development and that vascular expression of HO-1 is essential and protective during postnatal alveolar development. Methods Neonatal lung development in wildtype and HO-1 mutant mice was evaluated by histological and molecular methods. Furthermore, these newborn mice were treated with postnatal dexamethasone (Dex till postnatal 14 days, and evaluated for lung development. Results Compared to wildtype littermates, HO-1 mutant mice exhibited disrupted lung alveolar structure including simplification, disorganization and reduced secondary crest formation. These defects in alveolar development were more pronounced when these mice were challenged with Dex treatment. Expression levels of both vascular endothelial and alveolar epithelial markers were also further decreased in HO-1 mutants after Dex treatment. Conclusions These experiments demonstrate that HO-1 is required in normal lung development and that HO-1 disruption and dexamethasone exposure are additive in the disruption of postnatal lung growth. We speculate that HO-1 is involved in postnatal lung development through modulation of pulmonary vascular development.

  8. A novel and sensitive assay for heme oxygenase activity.

    Science.gov (United States)

    Iwamori, Saki; Sato, Emiko; Saigusa, Daisuke; Yoshinari, Kouichi; Ito, Sadayoshi; Sato, Hiroshi; Takahashi, Nobuyuki

    2015-10-01

    Heme oxygenase (HO) is a renoprotective protein in the microsome that degrades heme and produces biliverdin. Biliverdin is then reduced to a potent antioxidant bilirubin by biliverdin reductase in the cytosol. Because HO activity does not necessarily correlate with HO mRNA or protein levels, a reliable assay is needed to determine HO activity. Spectrophotometric measurement is tedious and requires a relatively large amount of kidney samples. Moreover, bilirubin is unstable and spontaneously oxidized to biliverdin in vitro. We developed a novel and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method to quantify biliverdin to measure HO activity in mice. Biliverdin and its internal standard, a deuterated biliverdin-d4, have MS/MS fragments with m/z transitions of 583 to 297 and 587 to 299, respectively. We prepared lysates of mouse kidneys, and added excess hemin, NADPH, and bilirubin oxidase to convert all bilirubin produced to biliverdin. After 30-min incubation at 37 or 4°C, the samples were analyzed by LC-MS/MS. The difference in the amount of biliverdin between the two temperatures is HO activity. Treating mice with cobalt protoporphyrin, which induces the expression of HO, increased HO activity as determined by biliverdin production. Measuring the production of biliverdin using LC-MS/MS is a more sensitive and specific way to determine HO activity than the spectrophotometric method and allows the detection of subtle changes in renal or other HO activity. Copyright © 2015 the American Physiological Society.

  9. Heme oxygenase-1-generated biliverdin ameliorates experimental murine colitis.

    Science.gov (United States)

    Berberat, Pascal O; A-Rahim, Yousif I; Yamashita, Kenichiro; Warny, Michel M; Csizmadia, Eva; Robson, Simon C; Bach, Fritz H

    2005-04-01

    Heme oxygenase-1 (HO-1) seems to have an important protective role in acute and chronic inflammation. The products of heme catalysis, biliverdin/bilirubin, carbon monoxide (CO), and iron (that induces apoferritin) mediate the beneficial effects of HO-1. Blockade of HO-1 activity results in exacerbation of experimental colitis. We tested whether HO-1 has protective effects in the development of colitis and determined that specific enzymatic products of HO-1 are responsible for these effects. Colitis was induced by oral administration of dextran sodium sulfate (5%) to C57BL/6 mice for 7 days. HO-1 was up-regulated by cobalt-protoporphyrin (5 mg/kg, intraperitoneally). Biliverdin, exogenous CO, or the iron chelator desferrioxamine was administered to other groups. Cobalt-protoporphyrin treatment resulted in significant up-regulation of HO-1 protein in mucosal and submucosal cells. Induction of HO-1 was associated with significantly less loss of body weight in mice with induced colitis (-12% versus -22% in the control animals, P biliverdin administration (50 micromol/kg, 3 times per day, intraperitoneally). We conclude that heightened HO-1 expression or administration of biliverdin ameliorates dextran sodium sulfate-induced experimental colitis. Novel therapeutic strategies based on HO-1 and/or biliverdin administration may have use in inflammatory bowel disease.

  10. Heme oxygenase-1 comes back to endoplasmic reticulum

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Hong Pyo [School of Biological Sciences, Ulsan University (Korea, Republic of); Pae, Hyun-Ock [Department of Immunology, Wonkwang University School of Medicine (Korea, Republic of); Back, Sung Hun; Chung, Su Wol [School of Biological Sciences, Ulsan University (Korea, Republic of); Woo, Je Moon [Department of Opthalmology, Ulasn University Hospital (Korea, Republic of); Son, Yong [Department of Anesthesiology and Pain Medicine, Wonkwang University School of Medicine (Korea, Republic of); Chung, Hun-Taeg, E-mail: chung@ulsan.ac.kr [School of Biological Sciences, Ulsan University (Korea, Republic of)

    2011-01-07

    Research highlights: {yields} Although multiple compartmentalization of HO-1 has been documented, the functional implication of this enzyme at these subcellular organelles is only partially elucidated. {yields} HO-1 expression at ER is induced by a diverse set of conditions that cause ER stressors. {yields} CO may induce HO-1 expression in human ECs by activating Nrf2 through PERK phosphorylation in a positive-feedback manner. {yields} ER-residing HO-1 and its cytoprotective activity against ER stress is discussed. -- Abstract: Originally identified as a rate-limiting enzyme for heme catabolism, heme oxygenase-1 (HO-1) has expanded its roles in anti-inflammation, anti-apoptosis and anti-proliferation for the last decade. Regulation of protein activity by location is well appreciated. Even though multiple compartmentalization of HO-1 has been documented, the functional implication of this enzyme at these subcellular organelles is only partially elucidated. In this review we discuss the endoplasmic reticulum (ER)-residing HO-1 and its cytoprotective activity against ER stress.

  11. Homeostatic response under carcinogen withdrawal, heme oxygenase 1 expression and cell cycle association

    Directory of Open Access Journals (Sweden)

    Batlle Alcira

    2006-12-01

    Full Text Available Abstract Background Chronic injury deregulates cellular homeostasis and induces a number of alterations leading to disruption of cellular processes such as cell cycle checkpoints and apoptosis, driving to carcinogenesis. The stress protein heme oxygenase-1 (HO-1 catalyzes heme degradation producing biliverdin, iron and CO. Induction of HO-1 has been suggested to be essential for a controlled cell growth. The aim of this work was to analyze the in vivo homeostatic response (HR triggered by the withdrawal of a potent carcinogen, p-dimethylaminoazobenzene (DAB, after preneoplastic lesions were observed. We analyzed HO-1 cellular localization and the expression of HO-1, Bcl-2 and cell cycle related proteins under these conditions comparing them to hepatocellular carcinoma (HC. Methods The intoxication protocol was designed based on previous studies demonstrating that preneoplastic lesions were evident after 89 days of chemical carcinogen administration. Male CF1 mice (n = 18 were used. HR group received DAB (0.5 % w/w in the diet for 78 days followed by 11 days of carcinogen deprivation. The HC group received the carcinogen and control animals the standard diet during 89 days. The expression of cell cycle related proteins, of Bcl-2 and of HO-1 were analyzed by western blot. The cellular localization and expression of HO-1 were detected by immnunohistochemistry. Results Increased expression of cyclin E/CDK2 was observed in HR, thus implicating cyclin E/CDK2 in the liver regenerative process. p21cip1/waf1 and Bcl-2 induction in HC was restituted to basal levels in HR. A similar response profile was found for HO-1 expression levels, showing a lower oxidative status in the carcinogen-deprived liver. The immunohistochemical studies revealed the presence of macrophages surrounding foci of necrosis and nodular lesions in HR indicative of an inflammatory response. Furthermore, regenerative cells displayed changes in type, size and intensity of HO-1

  12. Damping and energy dissipation in soft tissue vibrations during running.

    Science.gov (United States)

    Khassetarash, Arash; Hassannejad, Reza; Enders, Hendrik; Ettefagh, Mir Mohammad

    2015-01-21

    It has been well accepted that the vibrations of soft tissue cannot be simulated by a single sinusoidal function. In fact, these vibrations are a combination of several vibration modes. In this study, these modes are extracted applying a recently developed method namely, partly ensemble empirical mode decomposition (PEEMD). Then, a methodology for estimating the damping properties and energy dissipation caused by damping for each mode is used. Applying this methodology on simulated signals demonstrates high accuracy. This methodology is applied to the acceleration signals of the gastrocnemius muscle during sprinting and the differences between the damping properties of different vibration modes were identified. The results were 1) the damping property of high-frequency mode was higher than that for low-frequency modes. 2) All identified modes were in under damped condition, therefore, the vibrations had an oscillatory nature. 3) The damping ratios of lower modes are about 100% increased compared to higher modes. 4) The energy dissipation occurred in lower modes were much more than that for higher mode; According to the power spectrum of the ground reaction force (GRF), which is the input force into the body, the recent finding supports the muscle tuning paradigm. It is suggested that the damping properties and energy dissipation can be used to distinguish between different running conditions (surface, fatigue, etc.). Copyright © 2014 Elsevier Ltd. All rights reserved.

  13. Low-temperature UV-visible and NMR spectroscopic investigations of O(2) binding to ((6)L)Fe(II), a ferrous heme bearing covalently tethered axial pyridine ligands.

    Science.gov (United States)

    Ghiladi, Reza A; Karlin, Kenneth D

    2002-05-06

    In this report, we describe the reversible dioxygen reactivity of ((6)L)Fe(II) (1) [(6)L = partially fluorinated tetraphenylporphyrin with covalently appended TMPA moiety; TMPA = tris(2-pyridylmethyl)amine] using a combination of low-temperature UV-vis and multinuclear ((1)H and (2)H) NMR spectroscopies. Complex 1, or its pyrrole-deuterated analogue ((6)L-d(8))Fe(II) (1-d(8)), exhibits downfield shifted pyrrole resonances (delta 28-60 ppm) in all solvents utilized [CH(2)Cl(2), (CH(3))(2)C(O), CH(3)CN, THF], indicative of a five-coordinate high-spin ferrous heme, even when there is no exogenous axial solvent ligand present (i.e., in methylene chloride). Furthermore, ((6)L)Fe(II) (1) exhibits non-pyrrolic upfield and downfield shifted peaks in CH(2)Cl(2), (CH(3))(2)C(O), and CH(3)CN solvents, which we ascribed to resonances arising from the intra- or intermolecular binding of a TMPA-pyridyl arm to the ferrous heme. Upon exposure to dioxygen at 193 K in methylene chloride, ((6)L)Fe(II) (1) [UV-vis: lambda(max) = 433 (Soret), 529 (sh), 559 nm] reversibly forms a dioxygen adduct [UV-vis: lambda(max) = 422 (Soret), 542 nm], formulated as the six-coordinate low-spin [delta(pyrrole) 9.3 ppm, 193 K] heme-superoxo complex ((6)L)Fe(III)-(O(2)(-)) (2). The coordination of the tethered pyridyl arm to the heme-superoxo complex as axial base ligand is suggested. In coordinating solvents such as THF, reversible oxygenation (193 K) of ((6)L)Fe(II) (1) [UV-vis: lambda(max) = 424 (Soret), 542 nm] also occurs to give a similar adduct ((6)L)Fe(III)-(O(2)(-)) (2) [UV-vis: lambda(max) = 418 (Soret), 537 nm. (2)H NMR: delta(pyrrole) 8.9 ppm, 193 K]. Here, we are unable to distinguish between a bound solvent ligand or tethered pyridyl arm as axial base ligand. In all solvents, the dioxygen adducts decompose (thermally) to the ferric-hydroxy complex ((6)L)Fe(III)-OH (3) [UV-vis: lambda(max) = 412-414 (Soret), 566-575 nm; approximately delta(pyrrole) 120 ppm at 193 K]. This study on the O(2

  14. Experimental validation of solid rocket motor damping models

    Science.gov (United States)

    Riso, Cristina; Fransen, Sebastiaan; Mastroddi, Franco; Coppotelli, Giuliano; Trequattrini, Francesco; De Vivo, Alessio

    2017-12-01

    In design and certification of spacecraft, payload/launcher coupled load analyses are performed to simulate the satellite dynamic environment. To obtain accurate predictions, the system damping properties must be properly taken into account in the finite element model used for coupled load analysis. This is typically done using a structural damping characterization in the frequency domain, which is not applicable in the time domain. Therefore, the structural damping matrix of the system must be converted into an equivalent viscous damping matrix when a transient coupled load analysis is performed. This paper focuses on the validation of equivalent viscous damping methods for dynamically condensed finite element models via correlation with experimental data for a realistic structure representative of a slender launch vehicle with solid rocket motors. A second scope of the paper is to investigate how to conveniently choose a single combination of Young's modulus and structural damping coefficient—complex Young's modulus—to approximate the viscoelastic behavior of a solid propellant material in the frequency band of interest for coupled load analysis. A scaled-down test article inspired to the Z9-ignition Vega launcher configuration is designed, manufactured, and experimentally tested to obtain data for validation of the equivalent viscous damping methods. The Z9-like component of the test article is filled with a viscoelastic material representative of the Z9 solid propellant that is also preliminarily tested to investigate the dependency of the complex Young's modulus on the excitation frequency and provide data for the test article finite element model. Experimental results from seismic and shock tests performed on the test configuration are correlated with numerical results from frequency and time domain analyses carried out on its dynamically condensed finite element model to assess the applicability of different equivalent viscous damping methods to describe

  15. Key Role of DAMP in Inflammation, Cancer, and Tissue Repair.

    Science.gov (United States)

    Pandolfi, Franco; Altamura, Simona; Frosali, Simona; Conti, Pio

    2016-05-01

    This review aimed to take stock of the current status of research on damage-associated molecular pattern (DAMP) protein. We discuss the Janus-faced role of DAMP molecules in inflammation, cancer, and tissue repair. The high-mobility group box (HMGB)-1 and adenosine triphosphate proteins are well-known DAMP molecules and have been primarily associated with inflammation. However, as we shall see, recent data have linked these molecules to tissue repair. HMGB1 is associated with cancer-related inflammation. It activates nuclear factor kB, which is involved in cancer regulation via its receptor for advanced glycation end-products (RAGE), Toll-like receptors 2 and 4. Proinflammatory activity and tissue repair may lead to pharmacologic intervention, by blocking DAMP RAGE and Toll like receptor 2 and 4 role in inflammation and by increasing their concentration in tissue repair, respectively. We conducted a MEDLINE search for articles pertaining to the various issues related to DAMP, and we discuss the most relevant articles especially (ie, not only those published in journals with a higher impact factor). A cluster of remarkable articles on DAMP have appeared in the literature in recent years. Regarding inflammation, several strategies have been proposed to target HMGB1, from antibodies to recombinant box A, which interacts with RAGE, competing with the full molecule. In tissue repair, it was reported that the overexpression of HMGB1 or the administration of exogenous HMGB1 significantly increased the number of vessels and promoted recovery in skin-wound, ischemic injury. Due to the bivalent nature of DAMP, it is often difficult to explain the relative role of DAMP in inflammation versus its role in tissue repair. However, this point is crucial as DAMP-related treatments move into clinical practice. Copyright © 2016 Elsevier HS Journals, Inc. All rights reserved.

  16. Public health and economic impact of dampness and mold

    Energy Technology Data Exchange (ETDEWEB)

    Mudarri, David; Fisk, William J.

    2007-06-01

    The public health risk and economic impact of dampness and mold exposures was assessed using current asthma as a health endpoint. Individual risk of current asthma from exposure to dampness and mold in homes from Fisk et al. (2007), and asthma risks calculated from additional studies that reported the prevalence of dampness and mold in homes were used to estimate the proportion of U.S. current asthma cases that are attributable to dampness and mold exposure at 21% (95% confidence internal 12-29%). An examination of the literature covering dampness and mold in schools, offices, and institutional buildings, which is summarized in the appendix, suggests that risks from exposure in these buildings are similar to risks from exposures in homes. Of the 21.8 million people reported to have asthma in the U.S., approximately 4.6 (2.7-6.3) million cases are estimated to be attributable to dampness and mold exposure in the home. Estimates of the national cost of asthma from two prior studies were updated to 2004 and used to estimate the economic impact of dampness and mold exposures. By applying the attributable fraction to the updated national annual cost of asthma, the national annual cost of asthma that is attributable to dampness and mold exposure in the home is estimated to be $3.5 billion ($2.1-4.8 billion). Analysis indicates that exposure to dampness and mold in buildings poses significant public health and economic risks in the U.S. These findings are compatible with public policies and programs that help control moisture and mold in buildings.

  17. Effect of particulate tougheners on the damping of composite laminates

    Science.gov (United States)

    Biggerstaff, Janet M.; Kosmatka, John B.

    2000-04-01

    Rubber is commonly added to composites to increase the toughness. This research investigates adding toughening particles to graphite/epoxy composites for the purpose of increasing the vibrational damping. Adding toughening particles to the interlaminar regions of graphite/epoxy is shown to significantly increase the loss factor, although the increase is much less than can be achieved by embedding a viscoelastic damping layer. The bending stiffness and shear modulus, however, are much higher for the samples with embedded particles than samples with a viscoelastic layer. The addition of damping particles could therefore be used for stiffness-critical parts.

  18. Damping and support in high-temperature superconducting levitation systems

    Energy Technology Data Exchange (ETDEWEB)

    Hull, John R [Sammamish, WA; McIver, Carl R [Everett, WA; Mittleider, John A [Kent, WA

    2009-12-15

    Methods and apparatuses to provide improved auxiliary damping for superconducting bearings in superconducting levitation systems are disclosed. In a superconducting bearing, a cryostat housing the superconductors is connected to a ground state with a combination of a damping strip of material, a set of linkage arms to provide vertical support, and spring washers to provide stiffness. Alternately, the superconducting bearing may be supported by a cryostat connected to a ground state by posts constructed from a mesh of fibers, with the damping and stiffness controlled by the fiber composition, size, and mesh geometry.

  19. An Improved Model for Air Damping of Perforated Structures

    Science.gov (United States)

    Lu, Cunhao; Li, Pu

    2017-07-01

    the prediction of air damping of micromachined mechanical resonant structures is significant in the design of high quality factor devices. In rarefied air, based on Bao’s molecule model, Li gives an analytical model for air damping of perforated structures. By studying the action of molecules going through holes and reflected by the fixed plate, this paper gives a probability of molecules through holes going into the gap between the moving plate and the fixed one. Comparison with Li’s model, the new model can play a better performance of air damping for perforated structures, at a wide range of size of holes.

  20. A frequency domain analysis for damped space structures

    Science.gov (United States)

    Hagood, Nesbitt W.; Crawley, Edward F.

    1989-01-01

    A method is presented for the analysis of damped structural systems in which the structural components are represented by impedance models and analyzed in the frequency domain. Methods are presented to assemble and condense system impedance matrices, and then to identify approximate mass, stiffness, and damping matrices for systems whose impedances are complicated functions of frequency. Formulas are derived for determination of approximate values for system natural frequencies and damping using frequency domain quantities. The sensitivities of these approximate values to system parameter changes are analyzed. The implementation of these analysis tools is discussed and applied to a simple mechanical system.

  1. Active Damping of Oscillations in Off-Road Vehicles

    DEFF Research Database (Denmark)

    Andersen, T. O.; Hansen, M. R.; Conrad, Finn

    2003-01-01

    This paper relates to analyse and control of the oscillations occuring in many off-road vehicles, which are designed without any suspension. Without suspension, the tire is the only elastic element acting between the vichle and the ground, but the suspension and damping properties of the tires...... simulation model that describes dynamics of the tractor with mechanica栬inkkages, and the hitch actuator and an typical implemenet. The developed model was used and is in use for both stability and damping analysis, and for evaluation of control strategies, incliding active damping of oscillations....

  2. Indirect linear locally distributed damping of coupled systems

    Directory of Open Access Journals (Sweden)

    Annick BEYRATH

    2004-11-01

    Full Text Available The aim of this paper is to prove indirect internal stabilization results for different coupled systems with linear locally distributed damping (coupled wave equations, wave equations with different speeds of propagation. In our case, a linear local damping term appears only in the first equation whereas no damping term is applied to the second one (this is indirect stabilization, see [11]. Using thepiecewise multiplier method we prove that the full system is stabilized and that the total energy of the solution of this system decays polynomially.

  3. Comparing Sources of Damping of Cross-Wind Motion

    DEFF Research Database (Denmark)

    Tarp-Johansen, Niels Jacob; Mørch, Christian; Andersen, Lars

    2009-01-01

    Cross-wind vibrations due to wave loading misaligned with the wind causes fatigue known to be design driving for support structures of large turbines offshore increasing fatigue loads notably compared to the along-wind fatigue. The small amount of damping assumed for cross-wind motion in current...... practise plays a key role in this. The questions are: does more damping exist and is one of the sources of damping the main contributor allowing for site-independent guidelines. The aim of this paper is to address these issues. It is demonstrated that tower dampers are important in order to tackle...

  4. Damping and Frequency Shift of Large Amplitude Electron Plasma Waves

    DEFF Research Database (Denmark)

    Thomsen, Kenneth; Juul Rasmussen, Jens

    1983-01-01

    The initial evolution of large-amplitude one-dimensional electron waves is investigated by applying a numerical simulation. The initial wave damping is found to be strongly enhanced relative to the linear damping and it increases with increasing amplitude. The temporal evolution of the nonlinear...... damping rate γ(t) shows that it increases with time within the initial phase of propagation, t≲π/ωB (ωB is the bounce frequency), whereafter it decreases and changes sign implying a regrowth of the wave. The shift in the wave frequency δω is observed to be positive for t≲π/ωB; then δω changes sign...

  5. Dampness and Moisture Problems in Norwegian Homes

    Directory of Open Access Journals (Sweden)

    Rune Becher

    2017-10-01

    Full Text Available The occurrence of dampness and mold in the indoor environment is associated with respiratory-related disease outcomes. Thus, it is pertinent to know the magnitude of such indoor environment problems to be able to estimate the potential health impact in the population. In the present study, the moisture damage in 10,112 Norwegian dwellings was recorded based on building inspection reports. The levels of moisture damage were graded based on a condition class (CC, where CC0 is immaculate and CC1 acceptable (actions not required, while CC2 and CC3 indicate increased levels of damage that requires action. Of the 10,112 dwellings investigated, 3125 had verified moisture or mold damage. This amounts to 31% of the surveyed dwellings. Of these, 27% had CC2 as the worst grade, whereas 4% had CC3 as the worst grade level. The room types and building structures most prone to moisture damage were (in rank order crawl spaces, basements, un-insulated attics, cooling rooms, and bathrooms. The high proportion of homes with moisture damage indicate a possible risk for respiratory diseases in a relatively large number of individuals, even if only the more extensive moisture damages and those located in rooms where occupants spend the majority of their time would have a significant influence on adverse health effects.

  6. Seismic Analysis of a Viscoelastic Damping Isolator

    Directory of Open Access Journals (Sweden)

    Bo-Wun Huang

    2015-01-01

    Full Text Available Seismic prevention issues are discussed much more seriously around the world after Fukushima earthquake, Japan, April 2011, especially for those countries which are near the earthquake zone. Approximately 1.8×1012 kilograms of explosive energy will be released from a magnitude 9 earthquake. It destroys most of the unprotected infrastructure within several tens of miles in diameter from the epicenter. People can feel the earthquake even if living hundreds of miles away. This study is a seismic simulation analysis for an innovated and improved design of viscoelastic damping isolator, which can be more effectively applied to earthquake prevention and damage reduction of high-rise buildings, roads, bridges, power generation facilities, and so forth, from earthquake disaster. Solidworks graphic software is used to draw the 3D geometric model of the viscoelastic isolator. The dynamic behavior of the viscoelastic isolator through shock impact of specific earthquake loading, recorded by a seismometer, is obtained via ANSYS finite element package. The amplitude of the isolator is quickly reduced by the viscoelastic material in the device and is shown in a time response diagram. The result of this analysis can be a crucial reference when improving the design of a seismic isolator.

  7. Root parsley protection against damping off

    Directory of Open Access Journals (Sweden)

    Bogdan Nowicki

    2013-12-01

    Full Text Available Seed treatment ofroot parsley was done to protect Petroselinum santivum seedlings against damping off. Fungicides used as seed dressers were applied in 3 doses: 3, 5 and 10 g/kg. Seeds were treated with 7 dressers (Table l used separately and in mixture with 3 g/kg of Rovral 50 WP (50% iprodione and 1 g/kg of Apron 35 SD (35% metalaxyl. Two seed samples of Berlińska cultivar were used: first sample was strongly infected by Alternaria petroselini and A.radicina both 27,6% and also by Fusarium spp. 5,4% (Test I, and second sample revealed lower percentage of infection 4,6% and 1,2%, respectively (Test II. The experiments were conducted under laboratory, glasshouse and field conditions. Complete seedlings protection in all experiments was achieved for treatments when fungicide mixture was used in the highest dose (10 g/kg. Decrease of fungicides concentrations were connected with lower effectiveness of disease control. No phytotoxic effects of the tested fungicide mixtures were observed under the glasshouse or field conditions.

  8. Investigation of damping liquids for aircraft instruments

    Science.gov (United States)

    Keulegan, G H

    1929-01-01

    This report covers the results of an investigation carried on at the Bureau of Standards under a research authorization from, and with the financial assistance of, the National Advisory Committee for Aeronautics. The choice of a damping liquid for aircraft instruments is difficult owing to the range of temperature at which aircraft operate. Temperature changes affect the viscosity tremendously. The investigation was undertaken with the object of finding liquids of various viscosities otherwise suitable which had a minimum change in viscosity with temperature. The new data relate largely to solutions. The effect of temperature on the kinematic viscosity of the following liquids and solutions was determined in the temperature interval -18 degrees to +30 degrees C. (1) solutions of animal and vegetable oils in xylene. These were poppy-seed oil, two samples of neat's-foot oils, castor oil, and linseed oil. (2) solutions of mineral oil in xylene. These were Squibb's petrolatum of naphthene base and transformer oil. (3) glycerine solutions in ethyl alcohol and in mixture of 50-50 ethyl alcohol and water. (4) mixtures of normal butyl alcohol with methyl alcohol. (5) individual liquids, kerosene, mineral spirits, xylene, recoil oil. The apparatus consisted of four capillary-tube viscometers, which were immersed in a liquid bath in order to secure temperature control. The method of calibration and the related experimental data are presented.

  9. Spring pendulum with dry and viscous damping

    Science.gov (United States)

    Butikov, Eugene I.

    2015-01-01

    Free and forced oscillations of a torsion spring pendulum damped by viscous and dry friction are investigated analytically and with the help of numerical simulations. A simplified mathematical model is assumed (Coulomb law) which nevertheless can explain many peculiarities in behavior of various oscillatory systems with dry friction. The amplitude of free oscillations diminishes under dry friction linearly, and the motion stops after a final number of cycles. The amplitude of sinusoidally driven pendulum with dry friction grows at resonance without limit if the threshold is exceeded. At strong enough non-resonant sinusoidal forcing dry friction causes transients that typically lead to definite limit cycles - periodic steady-state regimes of symmetric non-sticking forced oscillations which are independent of initial conditions. However, at the subharmonic sinusoidal forcing interesting peculiarities of the steady-state response are revealed such as multiple coexisting regimes of asymmetric oscillations that depend on initial conditions. Under certain conditions simple dry friction pendulum shows complicated stick-slip motions and chaos.

  10. Dampness and Moisture Problems in Norwegian Homes

    Science.gov (United States)

    Becher, Rune; Høie, Anja Hortemo; Bakke, Jan Vilhelm; Holøs, Sverre Bjørn; Øvrevik, Johan

    2017-01-01

    The occurrence of dampness and mold in the indoor environment is associated with respiratory-related disease outcomes. Thus, it is pertinent to know the magnitude of such indoor environment problems to be able to estimate the potential health impact in the population. In the present study, the moisture damage in 10,112 Norwegian dwellings was recorded based on building inspection reports. The levels of moisture damage were graded based on a condition class (CC), where CC0 is immaculate and CC1 acceptable (actions not required), while CC2 and CC3 indicate increased levels of damage that requires action. Of the 10,112 dwellings investigated, 3125 had verified moisture or mold damage. This amounts to 31% of the surveyed dwellings. Of these, 27% had CC2 as the worst grade, whereas 4% had CC3 as the worst grade level. The room types and building structures most prone to moisture damage were (in rank order) crawl spaces, basements, un-insulated attics, cooling rooms, and bathrooms. The high proportion of homes with moisture damage indicate a possible risk for respiratory diseases in a relatively large number of individuals, even if only the more extensive moisture damages and those located in rooms where occupants spend the majority of their time would have a significant influence on adverse health effects. PMID:29039816

  11. Loss of Landau Damping for Bunch Oscillations

    Energy Technology Data Exchange (ETDEWEB)

    Burov, A.; /Fermilab

    2011-04-11

    Conditions for the existence, uniqueness and stability of self-consistent bunch steady states are considered. For the existence and uniqueness problems, simple algebraic criteria are derived for both the action and Hamiltonian domain distributions. For the stability problem, van Kampen theory is used. The onset of a discrete van Kampen mode means the emergence of a coherent mode without any Landau damping; thus, even a tiny couple-bunch or multi-turn wake is sufficient to drive the instability. The method presented here assumes an arbitrary impedance, RF shape, and beam distribution function. Available areas on the intensity-emittance plane are shown for resistive wall wake and single harmonic, bunch shortening and bunch lengthening RF configurations. Thresholds calculated for the Tevatron parameters and impedance model are in agreement with the observations. These thresholds are found to be extremely sensitive to the small-argument behaviour of the bunch distribution function. Accordingly, a method to increase the LLD threshold is suggested. This article summarizes and extends recent author's publications.

  12. Ion Landau Damping on Drift Tearing Modes

    CERN Document Server

    Connor, J W; Zocco, A

    2012-01-01

    The equations governing the ion Landau damping (ILD) layers for a drift tearing mode are derived and solved to provide a matching to ideal MHD solutions at large $x$ and to the drift tearing solution emerging from the ion kinetic region, $k\\rho_{i}\\sim1$, at small $x,$ the distance from the rational surface. The ILD layers lie on either side of the mode rational surface at locations defined by $k_{y}xV_{Ti}/L_{s}=\\omega_{*e}(1+0.73\\eta_{e})$ and have been ignored in many previous analyses of linear drift tearing stability. The effect of the ILD layer on the drift tearing mode is to introduce an additional stabilizing contribution, requiring even larger values of the stability index, $\\Delta^{\\prime}$ for instability, than predicted by Connor Hastie and Zocco [PPCF,54, 035003, (2012)] and Cowley, Kulsrud and Hahm [Phys. Fluids,29, 3230, (1986)]. The magnitude and scaling of the new stabilizing effect in slab geometry is discussed.

  13. Reduced heme levels underlie the exponential growth defect of the Shewanella oneidensis hfq mutant.

    Directory of Open Access Journals (Sweden)

    Christopher M Brennan

    Full Text Available The RNA chaperone Hfq fulfills important roles in small regulatory RNA (sRNA function in many bacteria. Loss of Hfq in the dissimilatory metal reducing bacterium Shewanella oneidensis strain MR-1 results in slow exponential phase growth and a reduced terminal cell density at stationary phase. We have found that the exponential phase growth defect of the hfq mutant in LB is the result of reduced heme levels. Both heme levels and exponential phase growth of the hfq mutant can be completely restored by supplementing LB medium with 5-aminolevulinic acid (5-ALA, the first committed intermediate synthesized during heme synthesis. Increasing expression of gtrA, which encodes the enzyme that catalyzes the first step in heme biosynthesis, also restores heme levels and exponential phase growth of the hfq mutant. Taken together, our data indicate that reduced heme levels are responsible for the exponential growth defect of the S. oneidensis hfq mutant in LB medium and suggest that the S. oneidensis hfq mutant is deficient in heme production at the 5-ALA synthesis step.

  14. Heme Oxygenase, Inflammation, and Fibrosis: The Good, the Bad, and the Ugly?

    Science.gov (United States)

    Lundvig, Ditte M. S.; Immenschuh, Stephan; Wagener, Frank A. D. T. G.

    2012-01-01

    Upon injury, prolonged inflammation and oxidative stress may cause pathological wound healing and fibrosis, leading to formation of excessive scar tissue. Fibrogenesis can occur in most organs and tissues and may ultimately lead to organ dysfunction and failure. The underlying mechanisms of pathological wound healing still remain unclear, and are considered to be multifactorial, but so far, no efficient anti-fibrotic therapies exist. Extra- and intracellular levels of free heme may be increased in a variety of pathological conditions due to release from hemoproteins. Free heme possesses pro-inflammatory and oxidative properties, and may act as a danger signal. Effects of free heme may be counteracted by heme-binding proteins or by heme degradation. Heme is degraded by heme oxygenase (HO) that exists as two isoforms: inducible HO-1 and constitutively expressed HO-2. HO generates the effector molecules biliverdin/bilirubin, carbon monoxide, and free iron/ferritin. HO deficiency in mouse and man leads to exaggerated inflammation following mild insults, and accumulating epidemiological and preclinical studies support the widely recognized notion of the cytoprotective, anti-oxidative, and anti-inflammatory effects of the activity of the HO system and its effector molecules. In this review, we address the potential effects of targeted HO-1 induction or administration of HO-effector molecules as therapeutic targets in fibrotic conditions to counteract inflammatory and oxidative insults. This is exemplified by various clinically relevant conditions, such as hypertrophic scarring, chronic inflammatory liver disease, chronic pancreatitis, and chronic graft rejection in transplantation. PMID:22586396

  15. Regulation of human heme oxygenase-1 gene expression under thermal stress.

    Science.gov (United States)

    Okinaga, S; Takahashi, K; Takeda, K; Yoshizawa, M; Fujita, H; Sasaki, H; Shibahara, S

    1996-06-15

    Heme oxygenase-1 is an essential enzyme in heme catabolism, and its human gene promoter contains a putative heat shock element (HHO-HSE). This study was designed to analyze the regulation of human heme oxygenase-1 gene expression under thermal stress. The amounts of heme oxygenase-1 protein were not increased by heat shock (incubation at 42 degrees C) in human alveolar macrophages and in a human erythroblastic cell line, YN-1-0-A, whereas heat shock protein 70 (HSP70) was noticeably induced. However, heat shock factor does bind in vitro to HHO-HSE and the synthetic HHO-HSE by itself is sufficient to confer the increase in the transient expression of a reporter gene upon heat shock. The deletion of the sequence, located downstream from HHO-HSE, resulted in the activation of a reporter gene by heat shock. These results suggest that HHO-HSE is potentially functional but is repressed in vivo. Interestingly, heat shock abolished the remarkable increase in the levels of heme oxygenase-1 mRNA in YN-1-0-A cells treated with hemin or cadmium, in which HSP70 mRNA was noticeably induced. Furthermore, transient expression assays showed that heat shock inhibits the cadmium-mediated activation of the heme oxygenase-1 promoter, whereas the HSP70 gene promoter was activated upon heat shock. Such regulation of heme oxygenase-1 under thermal stress may be of physiologic significance in erythroid cells.

  16. Regulation of heme metabolism in normal and sideroblastic bone marrow cells in culture

    Energy Technology Data Exchange (ETDEWEB)

    Ibraham, N.G.; Lutton, J.D.; Hoffman, R.; Levere, R.D.

    1985-05-01

    Heme metabolism was examined in developing in vitro erythroid colonies (CFUE) and in bone marrow samples taken directly from four normal donors and four patients with sideroblastic anemia. Maximum activities of delta-aminolevulinic acid synthase (ALAS), ALA dehydratase (ALAD), and /sup 14/C-ALA incorporation into heme were achieved in normal marrow CFUE after 8 days of culture, whereas heme oxygenase progressively decreased to low levels of activity during the same period. Assays on nucleated bone marrow cells taken directly from patients revealed that ALAS activity was considerably reduced in idiopathic sideroblastic anemia (IASA) and X-linked sideroblastic anemia (X-SA) bone marrow specimens, whereas the activity increased more than twofold (normal levels) when cells were assayed from 8-day CFUE. In all cases, ALAD activity appeared to be within normal levels. Measurement of heme synthesis revealed that normal levels of /sup 14/C-ALA incorporation into heme were achieved in IASA cells but were reduced in X-SA cells. In marked contrast to levels in normal cells, heme oxygenase was found to be significantly elevated (two- to fourfold) in bone marrow cells taken directly from patients with IASA and X-SA. Results from this study demonstrate that IASA and X-SA bone marrow cells have disturbances in ALAS and heme metabolism, and that erythropoiesis (CFUE) can be restored to normal levels when cells are cultured in methylcellulose.

  17. Heme-induced Trypanosoma cruzi proliferation is mediated by CaM kinase II

    Energy Technology Data Exchange (ETDEWEB)

    Souza, C.F. [Laboratorio de Imunomodulacao e Protozoologia, Instituto Oswaldo Cruz, Fiocruz (Brazil); Carneiro, A.B.; Silveira, A.B. [Laboratorio de Sinalizacao Celular, Instituto de Bioquimica Medica, UFRJ (Brazil); Laranja, G.A.T. [Laboratorio de Interacao Tripanosomatideos e Vetores, Departamento de Bioquimica, IBRAG, UERJ, 20551-030 Rio de Janeiro (Brazil); Silva-Neto, M.A.C. [Laboratorio de Sinalizacao Celular, Instituto de Bioquimica Medica, UFRJ (Brazil); INCT, Entomologia Molecular (Brazil); Costa, S.C. Goncalves da [Laboratorio de Imunomodulacao e Protozoologia, Instituto Oswaldo Cruz, Fiocruz (Brazil); Paes, M.C., E-mail: mcpaes@uerj.br [Laboratorio de Interacao Tripanosomatideos e Vetores, Departamento de Bioquimica, IBRAG, UERJ, 20551-030 Rio de Janeiro (Brazil); INCT, Entomologia Molecular (Brazil)

    2009-12-18

    Trypanosoma cruzi, the etiologic agent of Chagas disease, is transmitted through triatomine vectors during their blood-meal on vertebrate hosts. These hematophagous insects usually ingest approximately 10 mM of heme bound to hemoglobin in a single meal. Blood forms of the parasite are transformed into epimastigotes in the crop which initiates a few hours after parasite ingestion. In a previous work, we investigated the role of heme in parasite cell proliferation and showed that the addition of heme significantly increased parasite proliferation in a dose-dependent manner . To investigate whether the heme effect is mediated by protein kinase signalling pathways, parasite proliferation was evaluated in the presence of several protein kinase (PK) inhibitors. We found that only KN-93, a classical inhibitor of calcium-calmodulin-dependent kinases (CaMKs), blocked heme-induced cell proliferation. KN-92, an inactive analogue of KN-93, was not able to block this effect. A T. cruzi CaMKII homologue is most likely the main enzyme involved in this process since parasite proliferation was also blocked when Myr-AIP, an inhibitory peptide for mammalian CaMKII, was included in the cell proliferation assay. Moreover, CaMK activity increased in parasite cells with the addition of heme as shown by immunological and biochemical assays. In conclusion, the present results are the first strong indications that CaMKII is involved in the heme-induced cell signalling pathway that mediates parasite proliferation.

  18. Proinflammatory Responses of Heme in Alveolar Macrophages: Repercussion in Lung Hemorrhagic Episodes

    Directory of Open Access Journals (Sweden)

    Rafael L. Simões

    2013-01-01

    Full Text Available Clinical and experimental observations have supported the notion that free heme released during hemorrhagic and hemolytic episodes may have a major role in lung inflammation. With alveolar macrophages (AM being the main line of defense in lung environments, the influence of free heme on AM activity and function was investigated. We observed that heme in a concentration range found during hemolytic episodes (3–30 μM elicits AM to present a proinflammatory profile, stimulating reactive oxygen species (ROS and nitric oxide (NO generation and inducing IL-1β, IL-6, and IL-10 secretion. ROS production is NADPH oxidase-dependent, being inhibited by DPI and apocynin, and involves p47 subunit phosphorylation. Furthermore, heme induces NF-κB nuclear translocation, iNOS, and also HO-1 expression. Moreover, AM stimulated with free heme show enhanced phagocytic and bactericidal activities. Taken together, the data support a dual role for heme in the inflammatory response associated with lung hemorrhage, acting as a proinflammatory molecule that can either act as both an adjuvant of the innate immunity and as an amplifier of the inflammatory response, leading tissue injury. The understanding of heme effects on pulmonary inflammatory processes can lead to the development of new strategies to ameliorate tissue damage associated with hemorrhagic episodes.

  19. XAS study of the active site of a bacterial heme-sensor

    Energy Technology Data Exchange (ETDEWEB)

    Della Longa, S [Dipartimento di Medicina Sperimentale, Universita dell' Aquila via Vetoio, loc. Coppito II 67100 L' Aquila (Italy); Arcovito, A [Istituto di Biochimica e Biochimica Clinica, Universita Cattolica del Sacro Cuore, Largo F. Vito 1, 00168, Roma (Italy); Brunori, M; Castiglione, N; Cutruzzola, F; Giardina, G; Rinaldo, S [Dipartimento di Scienze Biochimiche ' A. Rossi Fanelli' , Sapienza Universit/a di Roma, P. le A. Moro 5, 00185 Roma (Italy); D' Angelo, P, E-mail: dlonga@caspur.i [Dipartimento di Chimica, Sapienza Universita di Roma, P. le A.Moro 5, 00185 Roma (Italy)

    2009-11-15

    Denitrifying bacteria control NO and NO{sub 2} cytosolic levels by regulating the expression of denitrification gene clusters via REDOX signalling of specific transcriptional factors that may act as NO sensors in vivo. A protein belonging to the subclass DNR (dissimilative nitrate respiration regulator) from Pseudomonas aeruginosa has been recently suggested to be a heme containing protein. Very recently the three dimensional structure of the apo-form of DNR (in the absence of heme) has been determined by X-Ray crystallography, whereas the holo-form (in the presence of heme) has not yet been crystallized. We have investigated the heme local structure in solution of ferric and ferrous holo-DNR by XAS. The Fe K-edge XANES spectrum of the ferric adduct displays typical features of a low-spin hexacoordinate Fe-heme complex, having two histidines ligated. After chemical reduction, relevant changes of the XANES fingerprints suggest a repositioning of the heme inside the hydrophobic core of the protein in agreement with previously reported structural and spectroscopic evidence. Partial release of the axial ligands leaves the Fe(II)heme available, and very reactive, to bind exogenous ligands like NO, thus supporting its role as the cofactor involved in NO sensing activity.

  20. Crystal structure of rat heme oxygenase-1 in complex with biliverdin-iron chelate. Conformational change of the distal helix during the heme cleavage reaction.

    Science.gov (United States)

    Sugishima, Masakazu; Sakamoto, Hiroshi; Higashimoto, Yuichiro; Noguchi, Masato; Fukuyama, Keiichi

    2003-08-22

    The crystal structure of rat heme oxygenase-1 in complex with biliverdin-iron chelate (biliverdin(Fe)-HO-1), the immediate precursor of the final product, biliverdin, has been determined at a 2.4-A resolution. The electron density in the heme pocket clearly showed that the tetrapyrrole ring of heme is cleaved at the alpha-meso edge. Like the heme bound to HO-1, biliverdin-iron chelate is located between the distal and proximal helices, but its accommodation state seems to be less stable in light of the disordering of the solvent-exposed propionate and vinyl groups. The middle of the distal helix is shifted away from the center of the active site in biliverdin(Fe)-HO-1, increasing the size of the heme pocket. The hydrogen-bonding interaction between Glu-29 and Gln-38, considered to restrain the orientation of the proximal helix in the heme-HO-1 complex, was lost in biliverdin(Fe)-HO-1, leading to relaxation of the helix. Biliverdin has a distorted helical conformation; the lactam oxygen atom of its pyrrole ring-A interacted with Asp-140 through a hydrogen-bonding solvent network. Because of the absence of a distal water ligand, the iron atom is five-coordinated with His-25 and four pyrrole nitrogen atoms. The coordination geometry deviates considerably from a square pyramid, suggesting that the iron may be readily dissociated. We speculate that the opened conformation of the heme pocket facilitates sequential product release, first iron then biliverdin, and that because of biliverdin's increased flexibility, iron release triggers its slow dissociation.

  1. Protein expressed by the ho2 gene of the cyanobacterium Synechocystis sp. PCC 6803 is a true heme oxygenase. Properties of the heme and enzyme complex.

    Science.gov (United States)

    Zhang, Xuhong; Migita, Catharina T; Sato, Michihiko; Sasahara, Masanao; Yoshida, Tadashi

    2005-02-01

    Two isoforms of a heme oxygenase gene, ho1 and ho2, with 51% identity in amino acid sequence have been identified in the cyanobacterium Synechocystis sp. PCC 6803. Isoform-1, Syn HO-1, has been characterized, while isoform-2, Syn HO-2, has not. In this study, a full-length ho2 gene was cloned using synthetic DNA and Syn HO-2 was demonstrated to be highly expressed in Escherichia coli as a soluble, catalytically active protein. Like Syn HO-1, the purified Syn HO-2 bound hemin stoichiometrically to form a heme-enzyme complex and degraded heme to biliverdin IXalpha, CO and iron in the presence of reducing systems such as NADPH/ferredoxin reductase/ferredoxin and sodium ascorbate. The activity of Syn HO-2 was found to be comparable to that of Syn HO-1 by measuring the amount of bilirubin formed. In the reaction with hydrogen peroxide, Syn HO-2 converted heme to verdoheme. This shows that during the conversion of hemin to alpha-meso-hydroxyhemin, hydroperoxo species is the activated oxygen species as in other heme oxygenase reactions. The absorption spectrum of the hemin-Syn HO-2 complex at neutral pH showed a Soret band at 412 nm and two peaks at 540 nm and 575 nm, features observed in the hemin-Syn HO-1 complex at alkaline pH, suggesting that the major species of iron(III) heme iron at neutral pH is a hexa-coordinate low spin species. Electron paramagnetic resonance (EPR) revealed that the iron(III) complex was in dynamic equilibrium between low spin and high spin states, which might be caused by the hydrogen bonding interaction between the distal water ligand and distal helix components. These observations suggest that the structure of the heme pocket of the Syn HO-2 is different from that of Syn HO-1.

  2. Allocation of Heme is Differentially Regulated by Ferrochelatase Isoforms in Arabidopsis Cells

    Directory of Open Access Journals (Sweden)

    Nino Asuela Espinas

    2016-08-01

    Full Text Available Heme is involved in various biological processes as a cofactor of hemoproteins located in various organelles. In plant cells, heme is synthesized by two isoforms of plastid-localized ferrochelatase, FC1 and FC2. In this study, by characterizing Arabidopsis T-DNA insertional mutants, we showed that the allocation of heme is differentially regulated by ferrochelatase isoforms in plant cells. Analyses of weak (fc1-1 and null (fc1-2 mutants suggest that FC1-producing heme is required for initial growth of seedling development. In contrast, weak (fc2-1 and null (fc2-2 mutants of FC2 showed pale green leaves and retarded growth, indicating that FC2-producing heme is necessary for chloroplast development. During the initial growth stage, FC2 deficiency caused reduction of plastid cytochromes. In addition, although FC2 deficiency marginally affected the assembly of photosynthetic reaction center complexes, it caused relatively larger but insufficient light-harvesting antenna to reaction centers, resulting in lower efficiency of photosynthesis. In the later vegetative growth, however, fc2-2 recovered photosynthetic growth, showing that FC1-producing heme may complement the FC2 deficiency. On the other hand, reduced level of cytochromes in microsomal fraction was discovered in fc1-1, suggesting that FC1-producing heme is mainly allocated to extraplastidic organelles. Furthermore, the expression of FC1 is induced by the treatment of an elicitor flg22 while that of FC2 was reduced, and fc1-1 abolished the flg22-dependent induction of FC1 expression and peroxidase activity. Consequently, our results clarified that FC2 produces heme for the photosynthetic machinery in the chloroplast, while FC1 is the housekeeping enzyme providing heme cofactor to the entire cell. In addition, FC1 can partly complement FC2 deficiency and is also involved in defense against stressful conditions.

  3. Determining the effective system damping of highway bridges.

    Science.gov (United States)

    2009-06-01

    This project investigates four methods for modeling modal damping ratios of short-span and isolated : concrete bridges subjected to strong ground motion, which can be used for bridge seismic analysis : and design based on the response spectrum method...

  4. Elasticity modulus and damping ratio of macaw palm rachillas

    National Research Council Canada - National Science Library

    Villar, Flora Maria de Melo; Pinto, Francisco de Assis de Carvalho; Santos, Fábio Lúcio; Grossi, José Antônio Saraiva; Velloso, Nara Silveira

    2017-01-01

    .... Thus, this study seeks to determine the modulus of elasticity and the damping ratio of four different plant accessions obtained from the Active Germplasm Bank of the Universidade Federal de Viçosa (UFV...

  5. Highly Damping Hard Coatings for Protection of Titanium Blades

    National Research Council Canada - National Science Library

    Movchan, Boris A; Ustinov, Anatolii I

    2005-01-01

    Sn-Cr-MgO system is used as an example to show the basic capability to produce by EBPVD protective metal-ceramic coatings with a high adhesion strength, high values of hardness and damping capacity...

  6. Influence of damping on quantum interference - An exactly soluble model

    Science.gov (United States)

    Caldeira, A. O.; Leggett, A. J.

    1985-01-01

    This paper reports the result of a calculation which shows the effect of damping on the quantum interference of two Gaussian wave packets in a harmonic potential. The influence-functional method, which seems to be the most appropriate one for this kind of calculation, is used. It is shown that quantum-interference effects are severely diminished by the presence of damping even when its influence on the system is only light. The corrections to the undamped formulas are always expressible in terms of the phenomenological damping constant, the temperature (in the high-temperature limit), the cutoff frequency of the reservoir oscillators, and the mean number of quanta of energy intially present in the system. Both weakly and strongly damped systems are analyzed in the regime of low and high temperatures.

  7. Breathing pulses in the damped-soliton model for nerves

    Science.gov (United States)

    Fongang Achu, G.; Moukam Kakmeni, F. M.; Dikande, A. M.

    2018-01-01

    Unlike the Hodgkin-Huxley picture in which the nerve impulse results from ion exchanges across the cell membrane through ion-gate channels, in the so-called soliton model the impulse is seen as an electromechanical process related to thermodynamical phenomena accompanying the generation of the action potential. In this work, account is taken of the effects of damping on the nerve impulse propagation, within the framework of the soliton model. Applying the reductive perturbation expansion on the resulting KdV-Burgers equation, a damped nonlinear Schrödinger equation is derived and shown to admit breathing-type solitary wave solutions. Under specific constraints, these breathing pulse solitons become self-trapped structures in which the damping is balanced by nonlinearity such that the pulse amplitude remains unchanged even in the presence of damping.

  8. Mimicking an amplitude damping channel for Laguerre Gaussian Modes

    CSIR Research Space (South Africa)

    Dudley, Angela L

    2010-10-01

    Full Text Available An amplitude damping channel for Laguerre-Gaussian (LG) modes is presented. Experimentally the action of the channel on LG modes is in good agreement with that predicted theoretically....

  9. Nonlinear damped Schrodinger equation in two space dimensions

    Directory of Open Access Journals (Sweden)

    Tarek Saanouni

    2015-04-01

    Full Text Available In this article, we study the initial value problem for a semi-linear damped Schrodinger equation with exponential growth nonlinearity in two space dimensions. We show global well-posedness and exponential decay.

  10. Projectile Motion with Quadratic Damping in a Constant ...

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 19; Issue 5. Projectile Motion with Quadratic Damping in a Constant Gravitational Field. Chandra Das Dhiranjan Roy. General Article Volume 19 Issue 5 May 2014 pp 446-465 ...

  11. Extracting Damping Ratio from Dynamic Data and Numerical Solutions

    Science.gov (United States)

    Casiano, M. J.

    2016-01-01

    There are many ways to extract damping parameters from data or models. This Technical Memorandum provides a quick reference for some of the more common approaches used in dynamics analysis. Described are six methods of extracting damping from data: the half-power method, logarithmic decrement (decay rate) method, an autocorrelation/power spectral density fitting method, a frequency response fitting method, a random decrement fitting method, and a newly developed half-quadratic gain method. Additionally, state-space models and finite element method modeling tools, such as COMSOL Multiphysics (COMSOL), provide a theoretical damping via complex frequency. Each method has its advantages which are briefly noted. There are also likely many other advanced techniques in extracting damping within the operational modal analysis discipline, where an input excitation is unknown; however, these approaches discussed here are objective, direct, and can be implemented in a consistent manner.

  12. Development of Composite Materials with High Passive Damping Properties

    National Research Council Canada - National Science Library

    Crocker, Malcolm J

    2006-01-01

    ... structure with high damping. Composite sandwich structures have several advantages, such as their high strength-to-weight ratio, excellent thermal insulation, and good performance as water and vapor barriers...

  13. Damping of Torsional Beam Vibrations by Control of Warping Displacement

    DEFF Research Database (Denmark)

    Høgsberg, Jan Becker; Hoffmeyer, David; Ejlersen, Christian

    2016-01-01

    Supplemental damping of torsional beam vibrations is considered by viscous bimoments acting on the axial warping displacement at the beam supports. The concept is illustrated by solving the governing eigenvalue problem for various support configurations with the applied bimoments represented...

  14. An Active Damping at Blade Resonances Using Piezoelectric Transducers

    Science.gov (United States)

    Choi, Benjamin; Morrison, Carlos; Duffy, Kirsten

    2008-01-01

    The NASA Glenn Research Center (GRC) is developing an active damping at blade resonances using piezoelectric structure to reduce excessive vibratory stresses that lead to high cycle fatigue (HCF) failures in aircraft engine turbomachinery. Conventional passive damping work was shown first on a nonrotating beam made by Ti-6A1-4V with a pair of identical piezoelectric patches, and then active feedback control law was derived in terms of inductor, resister, and capacitor to control resonant frequency only. Passive electronic circuit components and adaptive feature could be easily programmable into control algorithm. Experimental active damping was demonstrated on two test specimens achieving significant damping on tip displacement and patch location. Also a multimode control technique was shown to control several modes.

  15. Mooring line damping estimation for a floating wind turbine.

    Science.gov (United States)

    Qiao, Dongsheng; Ou, Jinping

    2014-01-01

    The dynamic responses of mooring line serve important functions in the station keeping of a floating wind turbine (FWT). Mooring line damping significantly influences the global motions of a FWT. This study investigates the estimation of mooring line damping on the basis of the National Renewable Energy Laboratory 5 MW offshore wind turbine model that is mounted on the ITI Energy barge. A numerical estimation method is derived from the energy absorption of a mooring line resulting from FWT motion. The method is validated by performing a 1/80 scale model test. Different parameter changes are analyzed for mooring line damping induced by horizontal and vertical motions. These parameters include excitation amplitude, excitation period, and drag coefficient. Results suggest that mooring line damping must be carefully considered in the FWT design.

  16. Mooring Line Damping Estimation for a Floating Wind Turbine

    Directory of Open Access Journals (Sweden)

    Dongsheng Qiao

    2014-01-01

    Full Text Available The dynamic responses of mooring line serve important functions in the station keeping of a floating wind turbine (FWT. Mooring line damping significantly influences the global motions of a FWT. This study investigates the estimation of mooring line damping on the basis of the National Renewable Energy Laboratory 5 MW offshore wind turbine model that is mounted on the ITI Energy barge. A numerical estimation method is derived from the energy absorption of a mooring line resulting from FWT motion. The method is validated by performing a 1/80 scale model test. Different parameter changes are analyzed for mooring line damping induced by horizontal and vertical motions. These parameters include excitation amplitude, excitation period, and drag coefficient. Results suggest that mooring line damping must be carefully considered in the FWT design.

  17. Soil Damping at Walney 2 Offshore Wind Farm

    DEFF Research Database (Denmark)

    Andersen, Lars

    The present report presents the results of a finite-element analysis carried out in order to quantify the soil damping for a specific offshore wind turbine to be placed at the Walney 2 site.......The present report presents the results of a finite-element analysis carried out in order to quantify the soil damping for a specific offshore wind turbine to be placed at the Walney 2 site....

  18. Eddy damping effect of additional conductors in superconducting levitation systems

    Energy Technology Data Exchange (ETDEWEB)

    Jiang, Zhao-Fei; Gou, Xiao-Fan, E-mail: xfgou@hhu.edu.cn

    2015-12-15

    Highlights: • In this article, for the eddy current damper attached to the HTSC, we • quantitatively investigated the damping coefficient c, damping ratio, Joule heating of the copper damper, and the vibration frequency of the PM as well. • presented four different arrangements of the copper damper, and comparatively studied their damping effects and Joule heating, and finally proposed the most advisable arrangement. - Abstract: Passive superconducting levitation systems consisting of a high temperature superconductor (HTSC) and a permanent magnet (PM) have demonstrated several fascinating applications such as the maglev system, flywheel energy storage. Generally, for the HTSC–PM levitation system, the HTSC with higher critical current density J{sub c} can obtain larger magnetic force to make the PM levitate over the HTSC (or suspended below the HTSC), however, the process of the vibration of the levitated PM, provides very limited inherent damping (essentially hysteresis). To improve the dynamic stability of the levitated PM, eddy damping of additional conductors can be considered as the most simple and effective approach. In this article, for the HTSC–PM levitation system with an additional copper damper attached to the HTSC, we numerically and comprehensively investigated the damping coefficient c, damping ratio, Joule heating of the copper damper, and the vibration frequency of the PM as well. Furthermore, we comparatively studied four different arrangements of the copper damper, on the comprehensive analyzed the damping effect, efficiency (defined by c/V{sub Cu}, in which V{sub Cu} is the volume of the damper) and Joule heating, and finally presented the most advisable arrangement.

  19. Viscous damping of toroidal angular momentum in tokamaks

    Energy Technology Data Exchange (ETDEWEB)

    Stacey, W. M. [Georgia Tech Fusion Research Center, Atlanta, Georgia 30332 (United States)

    2014-09-15

    The Braginskii viscous stress tensor formalism was generalized to accommodate non-axisymmetric 3D magnetic fields in general toroidal flux surface geometry in order to provide a representation for the viscous damping of toroidal rotation in tokamaks arising from various “neoclassical toroidal viscosity” mechanisms. In the process, it was verified that the parallel viscosity contribution to damping toroidal angular momentum still vanishes even in the presence of toroidal asymmetries, unless there are 3D radial magnetic fields.

  20. Coordination Chemistry of Linear Oligopyrrolic Fragments Inspired by Heme Metabolites

    Science.gov (United States)

    Gautam, Ritika

    Linear oligopyrroles are degradation products of heme, which is converted in the presence of heme oxygenase to bile pigments, such as biliverdin and bilirubin. These tetrapyrrolic oligopyrroles are ubiquitously present in biological systems and find applications in the fields of catalysis and sensing. These linear tetrapyrrolic scaffolds are further degraded into linear tripyrrolic and dipyrrolic fragments. Although these lower oligopyrroles are abundantly present, their coordination chemistry requires further characterization. This dissertation focuses mainly on two classes of bioinspired linear oligopyrroles, propentdyopent and tripyrrindione, and their transition metal complexes, which present a rich ligand-based redox chemistry. Chapter 1 offers an overview of heme degradation to different classes of linear oligopyrroles and properties of their transition metal complexes. Chapter 2 is focused on the tripyrrin-1,14-dione scaffold of the urinary pigment uroerythrin, which coordinates divalent transition metals palladium and copper with square planar geometry. Specifically, the tripyrrin-1, 14-dione ligand binds Cu(II) and Pd(II) as a dianionic organic radical under ambient conditions. The electrochemical study confirms the presence of ligand based redox chemistry, and one electron oxidation or reduction reactions do not alter the planar geometry around the metal center. The X-Ray analysis and the electron paramagnetic resonance (EPR) studies of the complexes in the solid and solution phase reveals intermolecular interactions between the ligand based unpaired electrons and therefore formation of neutral pi-pi dimers. In Chapter 3, the antioxidant activity and the fluorescence sensor properties of the tripyrrin-1,14-dione ligand in the presence of superoxide are described. We found that the tripyrrindione ligand undergoes one-electron reduction in the presence of the superoxide radical anion (O2•- ) to form highly fluorescent H3TD1•- radical anion, which emits

  1. Heme Oxygenase-1 Promotes Delayed Wound Healing in Diabetic Rats

    Directory of Open Access Journals (Sweden)

    Qing-Ying Chen

    2016-01-01

    Full Text Available Diabetic ulcers are one of the most serious and costly chronic complications for diabetic patients. Hyperglycemia-induced oxidative stress may play an important role in diabetes and its complications. The aim of the study was to explore the effect of heme oxygenase-1 on wound closure in diabetic rats. Diabetic wound model was prepared by making an incision with full thickness in STZ-induced diabetic rats. Wounds from diabetic rats were treated with 10% hemin ointment for 21 days. Increase of HO-1 protein expression enhanced anti-inflammation and antioxidant in diabetic rats. Furthermore, HO-1 increased the levels of VEGF and ICAM-1 and expressions of CBS and CSE protein. In summary, HO-1 promoted the wound closure by augmenting anti-inflammation, antioxidant, and angiogenesis in diabetic rats.

  2. Effects of extreme wind shear on aeroelastic modal damping of wind turbines

    DEFF Research Database (Denmark)

    Skjoldan, P.F.; Hansen, Morten Hartvig

    2013-01-01

    to stall. The first longitudinal tower mode decreases slightly in damping, whereas the first flapwise backward whirling and symmetric modes increase in damping. This change in damping is attributed to an interaction between the periodic blade mode shapes and the azimuth-dependent local aerodynamic damping...

  3. Heme oxygenase system and hypertension: a comprehensive insight.

    Science.gov (United States)

    Tiwari, Shuchita; Ndisang, Joseph Fomusi

    2014-01-01

    Hypertension is a complex interplay of interrelated etiologies, and the leading risk factor for many cardiovascular morbidity and mortality worldwide. Cardinal pathophysiological features of hypertension include enhanced vascular inflammation, vascular remodeling, vascular contractility and increased oxidative stress. In response to oxidative, inflammatory or other noxious stimuli, many physiological pathways like the heme oxygenase (HO) system are activated in an attempt to counteract tissue insults. However, the pathophysiological activation of the HO system only results to a transient increase of HO activity that fall below the necessary threshold capable of activating the downstream signaling components of the HO system like the soluble guanylyl cyclase (sGC)/cyclic guanosine monophosphate (cGMP) secondary messenger system. Therefore, a more robust potentiation of the HO system by pharmacological agents such as hemin, heme-arginate, cobalt protoporphyrin or through retroviral HO-1 gene delivery would be needed to surmount the threshold for cytoprotection. The HO system modulates cellular homeostasis. Importantly, the HO system plays a vital role in a wide spectrum of physiologic including the regulation of blood vessel tone. Alterations in the activity and expression of HO has been correlated to pathophysiology of hypertension and related complications such as hypertrophy, myocardial infarction and heart failure. Moreover, the cytoprotection exerted by HO is attributable to its catabolic products namely, carbon monoxide, bilirubin/biliverdin, and ferritin that are known to modulate immune, inflammatory and oxidative insults. The growing incidence of hypertension and associated cardiometabolic complications has prompted the need for the exploration of alternative therapeutic strategies like substances capable of potentiating the HO system. This review briefly, highlights the functional significance of the HO system and its downstream signaling molecules

  4. Heme oxygenase-1 promoter polymorphisms and risk of spina bifida.

    Science.gov (United States)

    Fujioka, Kazumichi; Yang, Wei; Wallenstein, Matthew B; Zhao, Hui; Wong, Ronald J; Stevenson, David K; Shaw, Gary M

    2015-09-01

    Spina bifida is the most common form of neural tube defects (NTDs). Etiologies of NTDs are multifactorial, and oxidative stress is believed to play a key role in NTD development. Heme oxygenase (HO), the rate-limiting enzyme in heme degradation, has multiple protective properties including mediating antioxidant processes, making it an ideal candidate for study. The inducible HO isoform (HO-1) has two functional genetic polymorphisms: (GT)n dinucleotide repeats and A(-413)T SNP (rs2071746), both of which can affect its promoter activity. However, no study has investigated a possible association between HO-1 genetic polymorphisms and risk of NTDs. This case-control study included 152 spina bifida cases (all myelomeningoceles) and 148 non-malformed controls obtained from the California Birth Defects Monitoring Program reflecting births during 1990 to 1999. Genetic polymorphisms were determined by polymerase chain reaction and amplified fragment length polymorphisms/restriction fragment length polymorphisms using genomic DNA extracted from archived newborn blood spots. Genotype and haplotype frequencies of two HO-1 promoter polymorphisms between cases and controls were compared. For (GT)n dinucleotide repeat lengths and the A(-413)T SNP, no significant differences in allele frequencies or genotypes were found. Linkage disequilibrium was observed between the HO-1 polymorphisms (D': 0.833); however, haplotype analyses did not show increased risk of spina bifida overall or by race/ethnicity. Although, an association was not found between HO-1 polymorphisms and risk of spina bifida, we speculate that the combined effect of low HO-1 expression and exposures to known environmental oxidative stressors (low folate status or diabetes), may overwhelm antioxidant defenses and increase risk of NTDs and warrants further study. © 2015 Wiley Periodicals, Inc.

  5. Improving capacitance/damping ratio in a capacitive MEMS transducer

    Science.gov (United States)

    Dias, Rosana A.; Rocha, Luis A.

    2014-01-01

    Damping forces play an important role in capacitive MEMS (microelectromechanical systems) behavior, and typical damper design (parallel-plates) cannot address the design conflict between increase in electrical capacitance and damping reduction. Squeeze-film damping in in-plane parallel-plate MEMS is discussed here and a novel damper geometry for gap-varying parallel-plates is introduced and used to increase the capacitance/damping ratio. The new geometry is compared with a typical parallel-plate design for an silicon-on-insulator process (25 µm thick) and experimental data shows an approximate 25% to 50% reduction for the damping coefficient in structures with 500 µm long dampers (for a gap variation between 0.75 and 3.75 µm), in agreement with computational fluid dynamics simulations, without significantly affecting the capacitance value (∼4% reduction). Preliminary simulations to study the role of the different geometric parameters involved in the improved geometry are also performed and reveal that the channel width is the most critical value for effective damping reduction.

  6. Landau damping in Kaniadakis and Tsallis distributed electron plasmas

    Science.gov (United States)

    López, Rodrigo A.; Navarro, Roberto E.; Pons, Sebastian I.; Araneda, Jaime A.

    2017-10-01

    The damping arrest and saturation stages in the evolution of the electric field amplitude are characteristic imprint of the nonlinear Landau damping. Scaling laws for the wave amplitudes and times and critical parameters which separate the monotonic damping from nondamping regimes are well known for Maxwellian and Tsallis-like plasmas. Here, the properties of electrostatic waves in unmagnetized, collisionless, and non-Maxwellian electron plasmas are studied by taking into account the α-deformed Kaniadakis distribution and compared with results using the q-Tsallis formalism. It is checked that the damping arrest and saturation characteristics scale as power-laws for the α-Kaniadakis, similarly as for the q-Tsallis parameter, indicating that a universal behaviour exists for the transition between linear and non-linear regimes. It is shown that the damping of electrostatic waves is much weaker when using Kaniadakis distributions, even in situations where this distribution exhibits more enhanced high-velocity tails. Furthermore, it is observed that in cases where the Tsallis distribution damps out completely the initial perturbation, the equivalent Kaniadakis distributed plasmas still support particle trapping, or even if wider Kaniadakis distributions are used. This important signature may provide a new tool to diagnose the nature of the distribution function and its relation to wave measurements in laboratory and space plasmas.

  7. Peroxide-Dependent Analyte Conversion by the Heme Prosthetic Group, the Heme Peptide “Microperoxidase-11” and Cytochrome c on Chitosan Capped Gold Nanoparticles Modified Electrodes

    Directory of Open Access Journals (Sweden)

    Frieder W. Scheller

    2012-05-01

    Full Text Available In view of the role ascribed to the peroxidatic activity of degradation products of cytochrome c (cyt c in the processes of apoptosis, we investigate the catalytic potential of heme and of the cyt c derived heme peptide MP-11 to catalyse the cathodic reduction of hydrogen peroxide and to oxidize aromatic compounds. In order to check whether cyt c has an enzymatic activity in the native state where the protein matrix should suppress the inherent peroxidatic activity of its heme prosthetic group, we applied a biocompatible immobilization matrix and very low concentrations of the co-substrate H2O2. The biocatalysts were entrapped on the surface of a glassy carbon electrode in a biocompatible chitosan layer which contained gold nanoparticles. The electrochemical signal for the peroxide reduction is generated by the redox conversion of the heme group, whilst a reaction product of the substrate oxidation is cathodically reduced in the substrate indication. The catalytic efficiency of microperoxidase-11 is sufficient for sensors indicating HRP substrates, e.g., p-aminophenol, paracetamol and catechol, but also the hydroxylation of aniline and dehalogenation of 4-fluoroaniline. The lower limit of detection for p-aminophenol is comparable to previously published papers with different enzyme systems. The peroxidatic activity of cyt c immobilized in the chitosan layer for catechol was found to be below 1 per mill and for p-aminophenol about 3% as compared with that of heme or MP-11.

  8. Damping Ring R&D at CESR-TA

    Energy Technology Data Exchange (ETDEWEB)

    Rubin, David L. [Cornell Univ., Ithaca, NY (United States). Dept. of Physics

    2015-01-23

    Accelerators that collide high energy beams of matter and anti-matter are essential tools for the investigation of the fundamental constituents of matter, and the search for new forms of matter and energy. A “Linear Collider” is a machine that would bring high energy and very compact bunches of electrons and positrons (anti-electrons) into head-on collision. Such a machine would produce (among many other things) the newly discovered Higgs particle, enabling a detailed study of its properties. Among the most critical and challenging components of a linear collider are the damping rings that produce the very compact and intense beams of electrons and positrons that are to be accelerated into collision. Hot dilute particle beams are injected into the damping rings, where they are compressed and cooled. The size of the positron beam must be reduced more than a thousand fold in the damping ring, and this compression must be accomplished in a fraction of a second. The cold compact beams are then extracted from the damping ring and accelerated into collision at high energy. The proposed International Linear Collider (ILC), would require damping rings that routinely produce such cold, compact and intense beams. The goal of the Cornell study was a credible design for the damping rings for the ILC. Among the technical challenges of the damping rings; the development of instrumentation that can measure the properties of the very small beams in a very narrow window of time, and mitigation of the forces that can destabilize the beams and prevent adequate cooling, or worse lead to beam loss. One of the most pernicious destabilizing forces is due to the formation of clouds of electrons in the beam pipe. The electron cloud effect is a phenomenon in particle accelerators in which a high density of low energy electrons, build up inside the vacuum chamber. At the outset of the study, it was anticipated that electron cloud effects would limit the intensity of the positron ring

  9. Damping of toroidal ion temperature gradient modes

    Energy Technology Data Exchange (ETDEWEB)

    Sugama, H. [National Inst. for Fusion Science, Toki, Gifu (Japan)

    1999-04-01

    The temporal evolution of linear toroidal ion temperature gradient (ITG) modes is studied based on a kinetic integral equation including an initial condition. It is shown how to evaluate the analytic continuation of the integral kernel as a function of a complex-valued frequency, which is useful for analytical and numerical calculations of the asymptotic damping behavior of the ITG mode. In the presence of the toroidal {nabla}B-curvature drift, the temporal dependence of the density and potential perturbations consists of normal modes and a continuum mode, which correspond to contributions from poles and from an integral along a branch cut, respectively, of the Laplace-transformed potential function of the complex-valued frequency. The normal modes have exponential time dependence with frequencies and growth rates determined by the dispersion relation while the continuum mode, which has a ballooning structure, shows a power law decay {proportional_to} t{sup -2} in the asymptotic limit, where t is the time variable. Therefore, the continuum mode dominantly describes the long-time asymptotic behavior of the density and potential perturbations for the stable system where all normal modes have negative growth rates. By performing proper analytic continuation for the homogeneous version of the kinetic integral equation, dependences of the normal modes` growth rate, real frequency, and eigenfunction on {eta}{sub i} (the ratio of the ion temperature gradient to the density gradient), k{sub {theta}} (the poloidal wavenumber), s (the magnetic shear parameter), and {theta}{sub k} (the ballooning angle corresponding to the minimum radial wavenumber) are numerically obtained for both stable and unstable cases. (author)

  10. Blockade of RAGE ameliorates elastase-induced emphysema development and progressionviaRAGE-DAMP signaling.

    Science.gov (United States)

    Lee, Hanbyeol; Park, Jeong-Ran; Kim, Woo Jin; Sundar, Isaac K; Rahman, Irfan; Park, Sung-Min; Yang, Se-Ran

    2017-05-01

    The receptor for advanced glycan end products (RAGE) has been identified as a susceptibility gene for chronic obstructive pulmonary disease (COPD) in genome-wide association studies (GWASs). However, less is known about how RAGE is involved in the pathogenesis of COPD. To determine the molecular mechanism by which RAGE influences COPD in experimental COPD models, we investigated the efficacy of the RAGE-specific antagonist FPS-ZM1 administration in in vivo and in vitro COPD models. We injected elastase intratracheally and the RAGE antagonist FPS-ZM1 in mice, and the infiltrated inflammatory cells and cytokines were assessed by ELISA. Cellular expression of RAGE was determined in protein, serum, and bronchoalveolar lavage fluid of mice and lungs and serum of human donors and patients with COPD. Downstream damage-associated molecular pattern (DAMP) pathway activation in vivo and in vitro and in patients with COPD was assessed by immunofluorescence staining, Western blot analysis, and ELISA. The expression of membrane RAGE in initiating the inflammatory response and of soluble RAGE acting as a decoy were associated with up-regulation of the DAMP-related signaling pathway via Nrf2. FPS-ZM1 administration significantly reversed emphysema in the lung of mice. Moreover, FPS-ZM1 treatment significantly reduced lung inflammation in Nrf2 +/+ , but not in Nrf2 -/- mice. Thus, our data indicate for the first time that RAGE inhibition has an essential protective role in COPD. Our observation of RAGE inhibition provided novel insight into its potential as a therapeutic target in emphysema/COPD.-Lee, H., Park, J.-R., Kim, W. J., Sundar, I. K., Rahman, I., Park, S.-M., Yang. S.-R. Blockade of RAGE ameliorates elastase-induced emphysema development and progression via RAGE-DAMP signaling. © FASEB.

  11. Mechanism-based inactivation of cytochromes P450 2E1 and 2E1 T303A by tert-butyl acetylenes: characterization of reactive intermediate adducts to the heme and apoprotein.

    Science.gov (United States)

    Blobaum, Anna L; Kent, Ute M; Alworth, William L; Hollenberg, Paul F

    2002-12-01

    The kinetics for the inactivation of cytochrome P450 2E1 and the mutant P450 2E1 T303A by tert-butyl acetylene (tBA) and tert-butyl 1-methyl-2-propynyl ether (tBMP) were investigated. The two acetylenes inactivated the 7-ethoxy-4-(trifluoromethyl)coumarin (7-EFC) O-deethylation activity of purified rabbit P450s 2E1 and 2E1 T303A in a reconstituted system in a time-, concentration-, and NADPH-dependent manner. The K(I) values for the inactivation of P450s 2E1 and 2E1 T303A by tBA were 1.0 and 2.0 mM, the k(inact) values were 0.20 and 0.38 min(-)(1), and the t(1/2) values were 3.5 and 1.8 min, respectively. The K(I) values for the tBMP-inactivated P450s were 0.1 and 1.0 mM, the k(inact) values were 0.12 and 0.07 min(-)(1), and the t(1/)(2) values were 5.9 and 10.2 min, respectively. Losses in enzyme activity occurred with concurrent losses in the P450 CO spectrum and P450 heme, which were accompanied by the appearance of two different tBA- or tBMP-modified heme products in each inactivated sample. LC-MS analysis of the adducts showed masses of 661 or 705 Da, consistent with the mass of an iron-depleted heme plus the masses of a tBA or tBMP reactive intermediate and one oxygen atom, respectively. Only the tBA-inactivated P450 2E1 revealed a tBA-adducted apoprotein with an increase in mass of 99 Da, corresponding to the mass of tBA plus one oxygen atom. Surprisingly, the inactivation, CO spectral and heme loss, and heme adduct formation of the tBA-inactivated T303A mutant were completely reversible after dialysis. In addition, metabolism of para-nitrophenol was not compromised by the tBA-inactivated T303A mutant. Therefore, our studies on the inactivation of P450s 2E1 and 2E1 T303A by tBA and tBMP suggest the existence of three distinct mechanisms for inactivation, among which includes a novel, reversible heme alkylation that has not been previously described with P450 enzymes.

  12. The Role of Heme and Reactive Oxygen Species in Proliferation and Survival of Trypanosoma cruzi

    Directory of Open Access Journals (Sweden)

    Marcia Cristina Paes

    2011-01-01

    Full Text Available Trypanosoma cruzi, the protozoan responsible for Chagas disease, has a complex life cycle comprehending two distinct hosts and a series of morphological and functional transformations. Hemoglobin degradation inside the insect vector releases high amounts of heme, and this molecule is known to exert a number of physiological functions. Moreover, the absence of its complete biosynthetic pathway in T. cruzi indicates heme as an essential molecule for this trypanosomatid survival. Within the hosts, T. cruzi has to cope with sudden environmental changes especially in the redox status and heme is able to increase the basal production of reactive oxygen species (ROS which can be also produced as byproducts of the parasite aerobic metabolism. In this regard, ROS sensing is likely to be an important mechanism for the adaptation and interaction of these organisms with their hosts. In this paper we discuss the main features of heme and ROS susceptibility in T. cruzi biology.

  13. Identification and phylogenetic analysis of heme synthesis genes in trypanosomatids and their bacterial endosymbionts.

    Directory of Open Access Journals (Sweden)

    João M P Alves

    Full Text Available It has been known for decades that some insect-infecting trypanosomatids can survive in culture without heme supplementation while others cannot, and that this capability is associated with the presence of a betaproteobacterial endosymbiont in the flagellate's cytoplasm. However, the specific mechanisms involved in this process remained obscure. In this work, we sequence and phylogenetically analyze the heme pathway genes from the symbionts and from their hosts, as well as from a number of heme synthesis-deficient Kinetoplastida. Our results show that the enzymes responsible for synthesis of heme are encoded on the symbiont genomes and produced in close cooperation with the flagellate host. Our evidence suggests that this synergistic relationship is the end result of a history of extensive gene loss and multiple lateral gene transfer events in different branches of the phylogeny of the Trypanosomatidae.

  14. Heme Binding Proteins of Bartonella henselae Are Required when Undergoing Oxidative Stress During Cell and Flea Invasion

    Science.gov (United States)

    Liu, MaFeng; Ferrandez, Yann; Bouhsira, Emilie; Monteil, Martine; Franc, Michel; Boulouis, Henri-Jean; Biville, Francis

    2012-01-01

    Bartonella are hemotropic bacteria responsible for emerging zoonoses. These heme auxotroph alphaproteobacteria must import heme for their growth, since they cannot synthesize it. To import exogenous heme, Bartonella genomes encode for a complete heme uptake system enabling transportation of this compound into the cytoplasm and degrading it to release iron. In addition, these bacteria encode for four or five outer membrane heme binding proteins (Hbps). The structural genes of these highly homologous proteins are expressed differently depending on oxygen, temperature and heme concentrations. These proteins were hypothesized as being involved in various cellular processes according to their ability to bind heme and their regulation profile. In this report, we investigated the roles of the four Hbps of Bartonella henselae, responsible for cat scratch disease. We show that Hbps can bind heme in vitro. They are able to enhance the efficiency of heme uptake when co-expressed with a heme transporter in Escherichia coli. Using B. henselae Hbp knockdown mutants, we show that these proteins are involved in defense against the oxidative stress, colonization of human endothelial cell and survival in the flea. PMID:23144761

  15. Impact of heme on specific antibody production in mice: promotive, inhibitive or null outcome is determined by its concentration

    Directory of Open Access Journals (Sweden)

    Guofu Li

    2017-05-01

    Full Text Available Free heme is an endogenous danger signal that provokes innate immunity. Active innate immunity provides a precondition of an effective adaptive immune response. However, heme catabolites, CO, biliverdin and bilirubin trigger immunosuppression. Furthermore, free heme induces expression of heme oxygenase-1 to increase production of CO, biliverdin and bilirubin. As such, free heme can play a paradoxical role in adaptive immunity. What is the outcome of the animal immune response to an antigen in the presence of free heme? This question remains to be explored. Here, we report the immunization results of rats and mice after intraperitoneal injection of formulations containing BSA and heme. When the heme concentrations were below 1 μM, between 1 μM and 5 μM and above 5 μM, production of anti-BSA IgG and IgM was unaffected, enhanced and suppressed, respectively. The results suggest that heme can influence adaptive immunity by double concentration-thresholds. If the heme concentrations are less than the first threshold, there is no effect on adaptive immunity; if the concentrations are more than the first but less than the second threshold, there is promotion effect; and if the concentrations are more than the second threshold, there is an inhibitory effect. A hypothesis is also presented here to explain the mechanism.

  16. Managing Reverse Logistics or Reversing Logistics Management?

    OpenAIRE

    Brito, Marisa

    2004-01-01

    textabstractIn the past, supply chains were busy fine-tuning the logistics from raw material to the end customer. Today an increasing flow of products is going back in the chain. Thus, companies have to manage reverse logistics as well.This thesis contributes to a better understanding of reverse logistics. The thesis brings insights on reverse logistics decision-making and it lays down theoretical principles for reverse logistics as a research field.In particular it puts together a framework ...

  17. Faster heme loss from hemoglobin E than HbS, in acidic pH: Effect ...

    Indian Academy of Sciences (India)

    We report studies on loss of heme at or below pH 3.0 from two clinically important hemoglobin variants, HbE and HbS, in the presence and absence of phopholipid membranes. The kinetics of heme loss has been studied at pH 3.0 to simulate the same at a faster rate than at physiological pH, for spectroscopic investigation.

  18. Heme-Containing Metal-Organic Frameworks for the Oxidative Degradation of Chemical Warfare Agents

    Science.gov (United States)

    2016-04-14

    coordinate cobaltous porphyrin site in a metal – organic framework: structural , EPR, and O, Inorg. Chem. Front., (04 2016): 536. doi: 10.1039...SECURITY CLASSIFICATION OF: This project sought to employ heme-containing metal - organic framework (MOF) materials to carry out the oxidative...15-Apr-2015 14-Jan-2016 Final Report: Heme-Containing Metal - Organic Frameworks for the Oxidative Degradation of Chemical Warfare Agents The views

  19. In vitro Activation of heme oxygenase-2 by menadione and its analogs.

    Science.gov (United States)

    Vukomanovic, Dragic; Rahman, Mona N; Bilokin, Yaroslav; Golub, Andriy G; Brien, James F; Szarek, Walter A; Jia, Zongchao; Nakatsu, Kanji

    2014-02-18

    Previously, we reported that menadione activated rat, native heme oxygenase-2 (HO-2) and human recombinant heme oxygenase-2 selectively; it did not activate spleen, microsomal heme oxygenase-1. The purpose of this study was to explore some structure-activity relationships of this activation and the idea that redox properties may be an important aspect of menadione efficacy. Heme oxygenase activity was determined in vitro using rat spleen and brain microsomes as the sources of heme oxygenase-1 and -2, respectively, as well as recombinant, human heme oxygenase-2. Menadione analogs with bulky aliphatic groups at position-3, namely vitamins K1 and K2, were not able to activate HO-2. In contrast, several compounds with similar bulky but less lipophilic moieties at position-2 (and -3) were able to activate HO-2 many fold; these compounds included polar, rigid, furan-containing naphthoquinones, furan-benzoxazine naphthoquinones, 2-(aminophenylphenyl)-3-piperidin-1-yl naphthoquinones. To explore the idea that redox properties might be involved in menadione efficacy, we tested analogs such as 1,4-dimethoxy-2-methylnaphthalene, pentafluoromenadione, monohalogenated naphthoquinones, α-tetralone and 1,4-naphthoquinone. All of these compounds were inactive except for 1,4-naphthoquinone. Menadione activated full-length recombinant human heme oxygenase-2 (FL-hHO-2) as effectively as rat brain enzyme, but it did not activate rat spleen heme oxygenase. These observations are consistent with the idea that naphthoquinones such as menadione bind to a receptor in HO-2 and activate the enzyme through a mechanism that may involve redox properties.

  20. Heme A synthesis and CcO activity are essential forTrypanosoma cruziinfectivity and replication.

    Science.gov (United States)

    Merli, Marcelo L; Cirulli, Brenda A; Menéndez-Bravo, Simón M; Cricco, Julia A

    2017-06-27

    Trypanosoma cruzi , the causative agent of Chagas disease, presents a complex life cycle and adapts its metabolism to nutrients' availability. Although T. cruzi is an aerobic organism, it does not produce heme. This cofactor is acquired from the host and is distributed and inserted into different heme-proteins such as respiratory complexes in the parasite's mitochondrion. It has been proposed that T. cruzi's energy metabolism relies on a branched respiratory chain with a cytochrome c oxidase-type aa 3 (C c O) as the main terminal oxidase. Heme A, the cofactor for all eukaryotic C c O, is synthesized via two sequential enzymatic reactions catalyzed by heme O synthase (HOS) and heme A synthase (HAS). Previously, TcCox10 and TcCox15 ( Trypanosoma cruzi Cox10 and Cox15 proteins) were identified in T. cruzi They presented HOS and HAS activity, respectively, when they were expressed in yeast. Here, we present the first characterization of TcCox15 in T. cruzi , confirming its role as HAS. It was differentially detected in the different T. cruzi stages, being more abundant in the replicative forms. This regulation could reflect the necessity of more heme A synthesis, and therefore more C c O activity at the replicative stages. Overexpression of a non-functional mutant caused a reduction in heme A content. Moreover, our results clearly showed that this hindrance in the heme A synthesis provoked a reduction on C c O activity and, in consequence, an impairment on T. cruzi survival, proliferation and infectivity. This evidence supports that T. cruzi depends on the respiratory chain activity along its life cycle, being C c O an essential terminal oxidase. © 2017 The Author(s); published by Portland Press Limited on behalf of the Biochemical Society.

  1. Protective effect of heme oxygenase-1 gene transfer against oxyhemoglobin-induced endothelial dysfunction.

    Science.gov (United States)

    Eguchi, D; Weiler, D; Alam, J; Nath, K; Katusic, Z S

    2001-10-01

    The current study was designed to determine the effect of recombinant heme oxygenase-1 (HO-1) gene expression on endothelial function in cerebral arteries. Isolated canine basilar arteries were exposed ex vivo (30 minutes at 37 degrees C) to an adenoviral vector (10(10) PFU/mL, total volume 300 microL) encoding either the HO-1 gene (AdCMVHO-1) or the beta-galactosidase (beta-Gal) reporter gene (AdCMVbeta-Gal). Twenty-four hours after transduction, arterial rings were suspended in organ chamber for isometric force recording. Endothelium-dependent relaxations were obtained in response to bradykinin (10(-10) to 10(-6) mol/L) during contraction to uridine-5'-triphosphate (UTP; 3 x 10(-6) to 3 x 10(-5) mol/L). Certain rings were incubated with oxyhemoglobin (OxyHb; 10(-5) mol/L) overnight (16 to 18 hours of 24 hours). Expression and localization of recombinant protein were shown by Western blot analysis and immunohistochemistry. Endothelium-dependent relaxation to bradykinin and endothelium-independent relaxation to forskolin (10(-9) to 10(-5) mol/L) and DEA-NONOate (10(-10) to 10(-5) mol/L) were identical in beta-Gal- and HO-1-transduced arteries. Exposure to OxyHb caused impairment of endothelium-dependent relaxation to bradykinin (P arteries expressing recombinant HO-1 ( P > 0.05). This protective effect of HO-1 was reversed by coincubation with tin protoporphyrin (SnPP9; 10(-5) mol/L), a selective inhibitor of HO-1 (P arteries, and that expression of recombinant HO-1 in cerebral arteries protects vasomotor function against OxyHb-induced injury.

  2. Nicotinic receptor activation by epibatidine induces heme oxygenase-1 and protects chromaffin cells against oxidative stress.

    Science.gov (United States)

    Egea, Javier; Rosa, Angelo O; Cuadrado, Antonio; García, Antonio G; López, Manuela G

    2007-09-01

    Activation of neuronal nicotinic acetylcholine receptors (nAChR) provides neuroprotection against different toxic stimuli that often lead to overproduction of reactive oxygen species (ROS) and cell death. ROS production has been related with disease progression in several neurodegenerative pathologies such as Alzheimer's or Parkinson's diseases. In this context, we investigated here if the exposure of bovine chromaffin cells to the potent nAChR agonist epibatidine protected against rotenone (30 micromol/L) plus oligomycin (10 micromol/L) (rot/oligo) toxicity, an in vitro model of mitochondrial ROS production. Epibatidine induced a concentration- and time-dependent protection, which was maximal at 3 mumol/L after 24 h. Pre-incubation with dantrolene (100 micromol/L) (a blocker of the ryanodine receptor channel), chelerythrine (1 micromol/L) (a protein kinase C inhibitor), or PD98059 (50 micromol/L) (a MEK inhibitor), aborted epibatidine-elicited cytoprotection. Mitochondrial depolarization, ROS, and caspase 3 active produced by rot/oligo were also prevented by epibatidine. Epibatidine doubled the amount of heme oxygenase-1 (HO-1), a critical cell defence enzyme against oxidative stress. Furthermore, the HO-1 inhibitor Sn(IV) protoporphyrin IX dichloride reversed the epibatidine protecting effects and HO-1 inducer Co (III) protoporphyrin IX dichloride exhibited neuroprotective effects by itself. The results of this study point to HO-1 as the cytoprotective target of nAChR activation through the following pathway: endoplasmic reticulum Ca(2+)-induced Ca(2+)-release activates the protein kinase C/extracellular regulated kinase/HO-1 axis to mitigate mitochondrial depolarization and ROS production. This study provides a mechanistic insight on how nAChR activation translates into an antioxidant and antiapoptotic signal through up-regulation of HO-1.

  3. Knockdown of Heme Oxygenase-2 Impairs Corneal Epithelial Cell Wound Healing

    Science.gov (United States)

    Halilovic, Adna; Patil, Kiran A.; Bellner, Lars; Marrazzo, Giuseppina; Castellano, Kirkland; Cullaro, Giuseppe; Dunn, Michael W.; Schwartzman, Michal Laniado

    2010-01-01

    Heme oxygenase (HO) represents an intrinsic cytoprotective system based on its anti-oxidative and anti-inflammatory properties mediated via its products biliverdin/bilirubin and carbon monoxide (CO). We showed that deletion of HO-2 results in impaired corneal wound healing with associated chronic inflammatory complications. This study was undertaken to examine the role of HO activity and the contribution of HO-1 and HO-2 to corneal wound healing in an in vitro epithelial scratch injury model. A scratch wound model was established using human corneal epithelial (HCE) cells. These cells expressed both HO-1 and HO-2 proteins. Injury elicited a rapid and transient increase in HO-1 and HO activity; HO-2 expression was unchanged. Treatment with biliverdin or CORM-A1, a CO donor, accelerated wound closure by 10% at 24 h. Inhibition of HO activity impaired wound closure by more than 50%. However, addition of biliverdin or CORM-A1 reversed the effect of HO inhibition on wound healing. Moreover, knockdown of HO-2 expression, but not HO-1, significantly impaired wound healing. These results indicate that HO activity is required for corneal epithelial cell migration. Inhibition of HO activity impairs wound healing while amplification of its activity restores and accelerates healing. Importantly, HO-2, which is highly expressed in the corneal epithelium, appears to be critical for the wound healing process in the cornea. The mechanisms by which it contributes to cell migration in response to injury may reside in the cytoprotective properties of CO and biliverdin. PMID:21506105

  4. Crystal structure of human heme oxygenase-1 in a complex with biliverdin.

    Science.gov (United States)

    Lad, Latesh; Friedman, Jonathan; Li, Huying; Bhaskar, B; Ortiz de Montellano, Paul R; Poulos, Thomas L

    2004-04-06

    Heme oxygenase oxidatively cleaves heme to biliverdin, leading to the release of iron and CO through a process in which the heme participates both as a cofactor and as a substrate. Here we report the crystal structure of the product, iron-free biliverdin, in a complex with human HO-1 at 2.19 A. Structural comparisons of the human biliverdin-HO-1 structure with its heme complex and the recently published rat HO-1 structure in a complex with the biliverdin-iron chelate [Sugishima, M., Sakamoto, H., Higashimoto, Y., Noguchi, M., and Fukuyama, K. (2003) J. Biol. Chem. 278, 32352-32358] show two major differences. First, in the absence of an Fe-His bond and solvent structure in the active site, the distal and proximal helices relax and adopt an "open" conformation which most likely encourages biliverdin release. Second, iron-free biliverdin occupies a different position and orientation relative to heme and the biliverdin-iron complex. Biliverdin adopts a more linear conformation and moves from the heme site to an internal cavity. These structural results provide insight into the rate-limiting step in HO-1 catalysis, which is product, biliverdin, release.

  5. Two Coregulated Efflux Transporters Modulate Intracellular Heme and Protoporphyrin IX Availability in Streptococcus agalactiae

    Science.gov (United States)

    Fernandez, Annabelle; Lechardeur, Delphine; Derré-Bobillot, Aurélie; Couvé, Elisabeth; Gaudu, Philippe; Gruss, Alexandra

    2010-01-01

    Streptococcus agalactiae is a major neonatal pathogen whose infectious route involves septicemia. This pathogen does not synthesize heme, but scavenges it from blood to activate a respiration metabolism, which increases bacterial cell density and is required for full virulence. Factors that regulate heme pools in S. agalactiae are unknown. Here we report that one main strategy of heme and protoporphyrin IX (PPIX) homeostasis in S. agalactiae is based on a regulated system of efflux using two newly characterized operons, gbs1753 gbs1752 (called pefA pefB), and gbs1402 gbs1401 gbs1400 (called pefR pefC pefD), where pef stands for ‘porphyrin-regulated efflux’. In vitro and in vivo data show that PefR, a MarR-superfamily protein, is a repressor of both operons. Heme or PPIX both alleviate PefR-mediated repression. We show that bacteria inactivated for both Pef efflux systems display accrued sensitivity to these porphyrins, and give evidence that they accumulate intracellularly. The ΔpefR mutant, in which both pef operons are up-regulated, is defective for heme-dependent respiration, and attenuated for virulence. We conclude that this new efflux regulon controls intracellular heme and PPIX availability in S. agalactiae, and is needed for its capacity to undergo respiration metabolism, and to infect the host. PMID:20421944

  6. Characterization of Human and Yeast Mitochondrial Glycine Carriers with Implications for Heme Biosynthesis and Anemia.

    Science.gov (United States)

    Lunetti, Paola; Damiano, Fabrizio; De Benedetto, Giuseppe; Siculella, Luisa; Pennetta, Antonio; Muto, Luigina; Paradies, Eleonora; Marobbio, Carlo Marya Thomas; Dolce, Vincenza; Capobianco, Loredana

    2016-09-16

    Heme is an essential molecule in many biological processes, such as transport and storage of oxygen and electron transfer as well as a structural component of hemoproteins. Defects of heme biosynthesis in developing erythroblasts have profound medical implications, as represented by sideroblastic anemia. The synthesis of heme requires the uptake of glycine into the mitochondrial matrix where glycine is condensed with succinyl coenzyme A to yield δ-aminolevulinic acid. Herein we describe the biochemical and molecular characterization of yeast Hem25p and human SLC25A38, providing evidence that they are mitochondrial carriers for glycine. In particular, the hem25Δ mutant manifests a defect in the biosynthesis of δ-aminolevulinic acid and displays reduced levels of downstream heme and mitochondrial cytochromes. The observed defects are rescued by complementation with yeast HEM25 or human SLC25A38 genes. Our results identify new proteins in the heme biosynthetic pathway and demonstrate that Hem25p and its human orthologue SLC25A38 are the main mitochondrial glycine transporters required for heme synthesis, providing definitive evidence of their previously proposed glycine transport function. Furthermore, our work may suggest new therapeutic approaches for the treatment of congenital sideroblastic anemia. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  7. Protein Machineries Involved in the Attachment of Heme to Cytochrome c: Protein Structures and Molecular Mechanisms

    Directory of Open Access Journals (Sweden)

    Carlo Travaglini-Allocatelli

    2013-01-01

    Full Text Available Cytochromes c (Cyt c are ubiquitous heme-containing proteins, mainly involved in electron transfer processes, whose structure and functions have been and still are intensely studied. Surprisingly, our understanding of the molecular mechanism whereby the heme group is covalently attached to the apoprotein (apoCyt in the cell is still largely unknown. This posttranslational process, known as Cyt c biogenesis or Cyt c maturation, ensures the stereospecific formation of the thioether bonds between the heme vinyl groups and the cysteine thiols of the apoCyt heme binding motif. To accomplish this task, prokaryotic and eukaryotic cells have evolved distinctive protein machineries composed of different proteins. In this review, the structural and functional properties of the main maturation apparatuses found in gram-negative and gram-positive bacteria and in the mitochondria of eukaryotic cells will be presented, dissecting the Cyt c maturation process into three functional steps: (i heme translocation and delivery, (ii apoCyt thioreductive pathway, and (iii apoCyt chaperoning and heme ligation. Moreover, current hypotheses and open questions about the molecular mechanisms of each of the three steps will be discussed, with special attention to System I, the maturation apparatus found in gram-negative bacteria.

  8. Two coregulated efflux transporters modulate intracellular heme and protoporphyrin IX availability in Streptococcus agalactiae.

    Directory of Open Access Journals (Sweden)

    Annabelle Fernandez

    2010-04-01

    Full Text Available Streptococcus agalactiae is a major neonatal pathogen whose infectious route involves septicemia. This pathogen does not synthesize heme, but scavenges it from blood to activate a respiration metabolism, which increases bacterial cell density and is required for full virulence. Factors that regulate heme pools in S. agalactiae are unknown. Here we report that one main strategy of heme and protoporphyrin IX (PPIX homeostasis in S. agalactiae is based on a regulated system of efflux using two newly characterized operons, gbs1753 gbs1752 (called pefA pefB, and gbs1402 gbs1401 gbs1400 (called pefR pefC pefD, where pef stands for 'porphyrin-regulated efflux'. In vitro and in vivo data show that PefR, a MarR-superfamily protein, is a repressor of both operons. Heme or PPIX both alleviate PefR-mediated repression. We show that bacteria inactivated for both Pef efflux systems display accrued sensitivity to these porphyrins, and give evidence that they accumulate intracellularly. The DeltapefR mutant, in which both pef operons are up-regulated, is defective for heme-dependent respiration, and attenuated for virulence. We conclude that this new efflux regulon controls intracellular heme and PPIX availability in S. agalactiae, and is needed for its capacity to undergo respiration metabolism, and to infect the host.

  9. Managing Reverse Logistics or Reversing Logistics Management?

    NARCIS (Netherlands)

    M.P. de Brito (Marisa)

    2004-01-01

    textabstractIn the past, supply chains were busy fine-tuning the logistics from raw material to the end customer. Today an increasing flow of products is going back in the chain. Thus, companies have to manage reverse logistics as well.This thesis contributes to a better understanding of reverse

  10. Damping Effects Induced by a Mass Moving along a Pendulum

    Directory of Open Access Journals (Sweden)

    E. Gandino

    2014-01-01

    Full Text Available The experimental study of damping in a time-varying inertia pendulum is presented. The system consists of a disk travelling along an oscillating pendulum: large swinging angles are reached, so that its equation of motion is not only time-varying but also nonlinear. Signals are acquired from a rotary sensor, but some remarks are also proposed as regards signals measured by piezoelectric or capacitive accelerometers. Time-varying inertia due to the relative motion of the mass is associated with the Coriolis-type effects appearing in the system, which can reduce and also amplify the oscillations. The analytical model of the pendulum is introduced and an equivalent damping ratio is estimated by applying energy considerations. An accurate model is obtained by updating the viscous damping coefficient in accordance with the experimental data. The system is analysed through the application of a subspace-based technique devoted to the identification of linear time-varying systems: the so-called short-time stochastic subspace identification (ST-SSI. This is a very simple method recently adopted for estimating the instantaneous frequencies of a system. In this paper, the ST-SSI method is demonstrated to be capable of accurately estimating damping ratios, even in the challenging cases when damping may turn to negative due to the Coriolis-type effects, thus causing amplifications of the system response.

  11. Eddy damping effect of additional conductors in superconducting levitation systems

    Science.gov (United States)

    Jiang, Zhao-Fei; Gou, Xiao-Fan

    2015-12-01

    Passive superconducting levitation systems consisting of a high temperature superconductor (HTSC) and a permanent magnet (PM) have demonstrated several fascinating applications such as the maglev system, flywheel energy storage. Generally, for the HTSC-PM levitation system, the HTSC with higher critical current density Jc can obtain larger magnetic force to make the PM levitate over the HTSC (or suspended below the HTSC), however, the process of the vibration of the levitated PM, provides very limited inherent damping (essentially hysteresis). To improve the dynamic stability of the levitated PM, eddy damping of additional conductors can be considered as the most simple and effective approach. In this article, for the HTSC-PM levitation system with an additional copper damper attached to the HTSC, we numerically and comprehensively investigated the damping coefficient c, damping ratio, Joule heating of the copper damper, and the vibration frequency of the PM as well. Furthermore, we comparatively studied four different arrangements of the copper damper, on the comprehensive analyzed the damping effect, efficiency (defined by c/VCu, in which VCu is the volume of the damper) and Joule heating, and finally presented the most advisable arrangement.

  12. DAMP-TLR-cytokine axis dictates the fate of tumor.

    Science.gov (United States)

    Patidar, Ashok; Selvaraj, Sathishkumar; Sarode, Aditya; Chauhan, Prashant; Chattopadhyay, Debprasad; Saha, Bhaskar

    2017-10-09

    Random mutations leading to loss of cell cycle control is not a rare occurrence in an organism but the mutated cells are recognized and eliminated preventing the development of a tumor. These potentially tumorigenic cells release damage-associated molecular patterns (DAMPs), which are recognized by toll-like receptors (TLRs) on macrophages and dendritic cells. The initial TLR-DAMP interactions lead to different responses such as altered antigen presentation and cytokine release that directly affect T cell activation and removal of the tumorigenic cells. The indirect effects of TLR-DAMP interaction include chemokine-directed altered T cell trafficking, angiogenesis for both T cell infiltration and tumor cell metastasis, and alteration of intra-tumoral milieu contributing to the development of tumor cells heterogeneity. Thus, the initial TLR-DAMP interaction has a set of local effects that modulate tumor cell growth and heterogeneity and a disseminating set of central effects that dynamically affect T cell trafficking and functions. Herein, we argue that the DAMP-TLR-cytokine axis in the tumor microenvironment serves as the mainstay that orchestrates and regulates the pro- and anti-tumor elements which dynamically interact between themselves eventuating in tumor regression or growth. The knowledge of this TLR-based immuno-surveillance framework is a key to developing a novel immunotherapy against cancer. Copyright © 2017. Published by Elsevier Ltd.

  13. Nonlinear wave damping due to multi-plasmon resonances

    Science.gov (United States)

    Brodin, G.; Ekman, R.; Zamanian, J.

    2018-02-01

    For short wavelengths, it is well known that the linearized Wigner–Moyal equation predicts wave damping due to wave-particle interaction, where the resonant velocity shifted from the phase velocity by a velocity {v}q={{\\hslash }}k/2m. Here {{\\hslash }} is the reduced Planck constant, k is the wavenumber and m is the electron mass. Going beyond linear theory, we find additional resonances with velocity shifts {{nv}}q,n=2,3, \\ldots , giving rise to a new wave-damping mechanism that we term multi-plasmon damping, as it can be seen as the simultaneous absorption (or emission) of multiple plasmon quanta. Naturally this wave damping is not present in classical plasmas. For a temperature well below the Fermi temperature, if the linear (n = 1) resonant velocity is outside the Fermi sphere, the number of linearly resonant particles is exponentially small, while the multi-plasmon resonances can be located in the bulk of the distribution. We derive sets of evolution equations for the case of two-plasmon and three-plasmon resonances for Langmuir waves in the simplest case of a fully degenerate plasma. By solving these equations numerically for a range of wave-numbers we find the corresponding damping rates, and we compare them to results from linear theory to estimate the applicability. Finally, we discuss the effects due to a finite temperature.

  14. Study of modal coupling procedures for the shuttle: A matrix method for damping synthesis

    Science.gov (United States)

    Hasselman, T. K.

    1972-01-01

    The damping method was applied successfully to real structures as well as analytical models. It depends on the ability to determine an appropriate modal damping matrix for each substructure. In the past, modal damping matrices were assumed diagonal for lack of being able to determine the coupling terms which are significant in the general case of nonproportional damping. This problem was overcome by formulating the damped equations of motion as a linear perturbation of the undamped equations for light structural damping. Damped modes are defined as complex vectors derived from the complex frequency response vectors of each substructure and are obtained directly from sinusoidal vibration tests. The damped modes are used to compute first order approximations to the modal damping matrices. The perturbation approach avoids ever having to solve a complex eigenvalue problem.

  15. Reversible Thermoset Adhesives

    Science.gov (United States)

    Mac Murray, Benjamin C. (Inventor); Tong, Tat H. (Inventor); Hreha, Richard D. (Inventor)

    2016-01-01

    Embodiments of a reversible thermoset adhesive formed by incorporating thermally-reversible cross-linking units and a method for making the reversible thermoset adhesive are provided. One approach to formulating reversible thermoset adhesives includes incorporating dienes, such as furans, and dienophiles, such as maleimides, into a polymer network as reversible covalent cross-links using Diels Alder cross-link formation between the diene and dienophile. The chemical components may be selected based on their compatibility with adhesive chemistry as well as their ability to undergo controlled, reversible cross-linking chemistry.

  16. Rapid, convenient method for screening imidazole-containing compounds for heme oxygenase inhibition.

    Science.gov (United States)

    Vlahakis, Jason Z; Rahman, Mona N; Roman, Gheorghe; Jia, Zongchao; Nakatsu, Kanji; Szarek, Walter A

    2011-01-01

    Sensitive assays for measuring heme oxygenase activity have been based on the gas-chromatographic detection of carbon monoxide using elaborate, expensive equipment. The present study describes a rapid and convenient method for screening imidazole-containing candidates for inhibitory activity against heme oxygenase using a plate reader, based on the spectroscopic evaluation of heme degradation. A PowerWave XS plate reader was used to monitor the absorbance (as a function of time) of heme bound to purified truncated human heme oxygenase-1 (hHO-1) in the individual wells of a standard 96-well plate (with or without the addition of a test compound). The degradation of heme by heme oxygenase-1 was initiated using l-ascorbic acid, and the collected relevant absorbance data were analyzed by three different methods to calculate the percent control activity occurring in wells containing test compounds relative to that occurring in control wells with no test compound present. In the cases of wells containing inhibitory compounds, significant shifts in λ(max) from 404 to near 412 nm were observed as well as a decrease in the rate of heme degradation relative to that of the control. Each of the three methods of data processing (overall percent drop in absorbance over 1.5h, initial rate of reaction determined over the first 5 min, and estimated pseudo first-order reaction rate constant determined over 1.5h) gave similar and reproducible results for percent control activity. The fastest and easiest method of data analysis was determined to be that using initial rates, involving data acquisition for only 5 min once reactions have been initiated using l-ascorbic acid. The results of the study demonstrate that this simple assay based on the spectroscopic detection of heme represents a rapid, convenient method to determine the relative inhibitory activity of candidate compounds, and is useful in quickly screening a series or library of compounds for heme oxygenase inhibition

  17. Electron Flow in Multiheme Bacterial Cytochromes is a Balancing Act Between Heme Electronic Interaction and Redox Potentials

    Energy Technology Data Exchange (ETDEWEB)

    Breuer, Marian; Rosso, Kevin M.; Blumberger, Jochen

    2014-01-14

    The naturally widespread process of electron transfer from metal reducing bacteria to extracellular solid metal oxides entails unique biomolecular machinery optimized for long-range electron transport. To perform this function efficiently microorganisms have adapted multi-heme c-type cytochromes to arrange heme cofactors into wires that cooperatively span the cellular envelope, transmitting electrons along distances greater than 100 Angstroms. Implications and opportunities for bionanotechnological device design are self-evident. However, at the molecular level how these proteins shuttle electrons along their heme wires, navigating intraprotein intersections and interprotein interfaces effciently, remains a mystery so far inaccessible to experiment. To shed light on this critical topic, we carried out extensive computer simulations to calculate Marcus theory quantities for electron transfer along the ten heme cofactors in the recently crystallized outer membrane cytochrome MtrF. The combination of electronic coupling matrix elements with free energy calculations of heme redox potentials and reorganization energies for heme-to-heme electron transfer allows the step-wise and overall electron transfer rate to be estimated and understood in terms of structural and dynamical characteristics of the protein. By solving a master equation for electron hopping, we estimate an intrinsic, maximum possible electron flux through solvated MtrF of 104-105 s-1, consistent with recently measured rates for the related MtrCAB protein complex. Intriguingly, this flux must navigate thermodynamically uphill steps past low potential hemes. Our calculations show that the rapid electron transport through MtrF is the result of a clear correlation between heme redox potential and the strength of electronic coupling along the wire: Thermodynamically uphill steps occur only between electronically well connected stacked heme pairs. This suggests that the protein evolved to harbor low potential

  18. Structural and biochemical characterization of two heme binding sites on α1-microglobulin using site directed mutagenesis and molecular simulation.

    Science.gov (United States)

    Rutardottir, Sigurbjörg; Karnaukhova, Elena; Nantasenamat, Chanin; Songtawee, Napat; Prachayasittikul, Virapong; Rajabi, Mohsen; Rosenlöf, Lena Wester; Alayash, Abdu I; Åkerström, Bo

    2016-01-01

    α1-Microglobulin (A1M) is a reductase and radical scavenger involved in physiological protection against oxidative damage. These functions were previously shown to be dependent upon cysteinyl-, C34, and lysyl side-chains, K(92, 118,130). A1M binds heme and the crystal structure suggests that C34 and H123 participate in a heme binding site. We have investigated the involvement of these five residues in the interactions with heme. Four A1M-variants were expressed: with cysteine to serine substitution in position 34, lysine to threonine substitutions in positions (92, 118, 130), histidine to serine substitution in position 123 and a wt without mutations. Heme binding was investigated by tryptophan fluorescence quenching, UV-Vis spectrophotometry, circular dichroism, SPR, electrophoretic migration shift, gel filtration, catalase-like activity and molecular simulation. All A1M-variants bound to heme. Mutations in C34, H123 or K(92, 118, 130) resulted in significant absorbance changes, CD spectral changes, and catalase-like activity, suggesting involvement of these side-groups in coordination of the heme-iron. Molecular simulation support a model with two heme-binding sites in A1M involving the mutated residues. Binding of the first heme induces allosteric stabilization of the structure predisposing for a better fit of the second heme. The results suggest that one heme-binding site is located in the lipocalin pocket and a second binding site between loops 1 and 4. Reactions with the hemes involve the side-groups of C34, K(92, 118, 130) and H123. The model provides a structural basis for the functional activities of A1M: heme binding activity of A1M. Copyright © 2015 Elsevier B.V. All rights reserved.

  19. Breatherlike excitations in discrete lattices with noise and nonlinear damping

    DEFF Research Database (Denmark)

    Christiansen, Peter Leth; Gaididei, Yuri B.; Johansson, Magnus

    1997-01-01

    are included as multiplicative white noise and nonlinear damping. Numerical analysis shows that the lifetime of the breather is always finite and, in a large parameter regime, inversely proportional to the noise variance for fixed damping and nonlinearity. We also find that the decay rate of the breather...... decreases with increasing nonlinearity and with increasing damping. Using a collective-coordinate approximation, we show how the qualitative features of the numerical results can be analytically understood. Finally, in the dimer case we show that the multiplicative noise can be transformed into additive...... noise, and an exact stationary solution to the Fokker-Planck equation is obtained. From this solution, the dimer system is found to exhibit a noise (temperature) induced phase transition....

  20. Damping of prominence longitudinal oscillations due to mass accretion

    Science.gov (United States)

    Ruderman, Michael S.; Luna, Manuel

    2016-06-01

    We study the damping of longitudinal oscillations of a prominence thread caused by the mass accretion. We suggested a simple model describing this phenomenon. In this model we considered a thin curved magnetic tube filled with the plasma. The prominence thread is in the central part of the tube and it consists of dense cold plasma. The parts of the tube at the two sides of the thread are filled with hot rarefied plasma. We assume that there are flows of rarefied plasma toward the thread caused by the plasma evaporation at the magnetic tube footpoints. Our main assumption is that the hot plasma is instantaneously accommodated by the thread when it arrives at the thread, and its temperature and density become equal to those of the thread. Then we derive the system of ordinary differential equations describing the thread dynamics. We solve this system of ordinary differential equations in two particular cases. In the first case we assume that the magnetic tube is composed of an arc of a circle with two straight lines attached to its ends such that the whole curve is smooth. A very important property of this model is that the equations describing the thread oscillations are linear for any oscillation amplitude. We obtain the analytical solution of the governing equations. Then we obtain the analytical expressions for the oscillation damping time and periods. We find that the damping time is inversely proportional to the accretion rate. The oscillation periods increase with time. We conclude that the oscillations can damp in a few periods if the inclination angle is sufficiently small, not larger that 10°, and the flow speed is sufficiently large, not less that 30 km s-1. In the second model we consider the tube with the shape of an arc of a circle. The thread oscillates with the pendulum frequency dependent exclusively on the radius of curvature of the arc. The damping depends on the mass accretion rate and the initial mass of the threads, that is the mass of the

  1. Damping augmentation of helicopter rotors using magnetorheological dampers

    Science.gov (United States)

    Zhao, Yongsheng

    This dissertation describes an investigation exploring the use of magnetorheological (MR) dampers to augment the stability of helicopter rotors. Helicopters with advanced soft in-plane rotors are susceptible to ground resonance instabilities due to the coupling of the lightly damped rotor lag modes and fuselage modes. Traditional passive lag dampers, such as hydraulic or elastomeric dampers, can be used to alleviate these instabilities. However, these passive dampers suffer from the disadvantages that they produce large damper loads in forward flight conditions. These damper forces increase fatigue loads and reduce component life. Thus, it is desirable to have lag dampers controllable or adaptable, so that the damper can apply loads only when needed. MR fluid based dampers have recently been considered for helicopter lag damping augmentation because the forces generated by these dampers can be controlled by an applied magnetic field. In this dissertation, control schemes to integrate MR dampers with helicopters are developed and the influences of the MR dampers on rotorcraft ground resonance are studied. Specifically, the MR dampers are incorporated into the ground resonance model in two ways: using a linear equivalent viscous damping and using a nonlinear damper model. The feasibility of using MR dampers to stabilize ground resonance is studied. The open loop on-off control is utilized where MR dampers are turned on over RPM where ground resonance occurs, and turned off otherwise. To further explore the damping control ability of MR dampers, the nonlinear semi-active closed loop feedback control strategies are developed: feedback linearization control and sliding mode control. The performance of the two control strategies is evaluated using two examples: to stabilize an unstable rotor and to augment the stability of a marginally stable rotor. In addition, the robustness of the closed loop control strategies is studied using two cases: damper degradation and

  2. An Estimate of P-Mode Damping by Wave Leakage

    Science.gov (United States)

    De Moortel, I.; Rosner, R.

    2007-11-01

    High-cadence TRACE observations show that outward-propagating intensity disturbances are a common feature in large, quiescent coronal loops. Analysis of the frequency distribution of these modes shows peaks at both three- and five-minute periods, indicating that they may be driven by the solar surface oscillations ( p modes). The energy flux contained within the coronal intensity disturbances is of the order of (1.1±0.4)×103 ergs cm-2 s-1. A simple order-of-magnitude estimate of the damping rate of the relevant p modes allows us to put an observational constraint on the damping of p modes and shows that leakage into the overlying coronal atmosphere might be able to account for a significant fraction of p-mode damping.

  3. Landau damping dynamic aperture and octupole in LHC

    CERN Document Server

    Gareyte, Jacques; Ruggiero, F

    1997-01-01

    Maximization of the dynamic aperture and Landau damping of the collective instabilities are partly conflicting requirements. On the one hand, the non-linearities of the lattice must be minimized at large oscillation amplitude to guarantee the stability of the single particle motion. On the other hand, a spread of the betatron frequencies is necessary to guarantee the stability of the collective motion of bunches of particles; this requires the introduction of non-linearities effective at small amplitudes. We show in this note that the `natural' spread of betatron tunes due to the field imperfections is inadequate or Landau damping. An octupole scheme is required to provide collective stability at high energy. At low energy it may be used to find the optimum between the correction of the octupolar field imperfections and Landau damping. The solution of the stability problem taking into account the two degrees of freedom of the transverse motion allows a significant saving in octupole strength: 144 octupoles wi...

  4. Heterogeneous phase fibrinolysis rates by damped oscillation rheometry.

    Science.gov (United States)

    Lee, Jae-Suk; Kaibara, Makoto; O'Rear, Edgar A

    2016-07-29

    Devices gauging viscoelastic properties of blood during coagulation like the thromboelastograph support fundamental research as well as point of care needs. Associated fibrinolysis data are based on endogenous species or plasminogen activator added to a homogeneous sample prior to clot formation. Digestion in a monolithic structure differs from the physical situation of thrombolytic therapy where surface reactions dominate. This study aims to develop rheological testing for heterogeneous phase fibrinolysis. Fibrinolysis rates were determined by phase change of a solid clot induced by autologous plasma/streptokinase (SK) in a rheometer sensitive to viscous damping. Initial slope or overall change in the logarithmic damping factor indicated fibrinolytic rates. Rates depended on clot geometry, phase volumes, clot composition and SK concentration. The damped oscillation rheometer can be adapted to determine relative rates of heterogeneous fibrinolysis in vitro.

  5. Enhancing the Damping Properties of Viscoelastic Composites by Topology Optimization

    DEFF Research Database (Denmark)

    Andreasen, Casper Schousboe; Andreassen, Erik; Sigmund, Ole

    in engineering structures. Thus, materials or composites with high stiffness and high damping are of great interest to the industry. The inherent compromise between high stiffness and high damping in viscoelastic materials has been treated theoretically [2, 3] and experimentally [1]. It has been shown that high...... stiffness and high damping can be realized by Hashin-type composites or Rank-N laminates. However, in order to manufacture such composites it is favorable to obtain single length scale microstructures, i.e. without multiscale structures such that the materials can be manufactured by modern manufacturing...... techniques. As an example, by the use of e.g. SLM/SLS - Selective Laser Melting/Sintering, an open metallic microstructure can be printed and in a subsequent process the porespace can be filled with a high loss compliant material. Yi and co-workers [6] applied topology optimization to design the 2D...

  6. Experimental identification of viscous damping in linear vibration

    Science.gov (United States)

    Srikantha Phani, A.; Woodhouse, J.

    2009-01-01

    This paper is concerned with the experimental evaluation of the performance of viscous damping identification methods in linear vibration theory. Both existing and some new methods proposed by the present authors [A.S. Phani, J. Woodhouse, Viscous damping identification in linear vibration, Journal of Sound and Vibration 303 (3-5) (2007) 475-500] are applied to experimental data measured on two test structures: a coupled three cantilever beam with moderate modal overlap and a free-free beam with low modal overlap. The performance of each method is quantified and compared based on three norms and the best methods are identified. The role of complex modes in damping identification from vibration measurements is critically assessed.

  7. Simulations of moving effect of coastal vegetation on tsunami damping

    Science.gov (United States)

    Tsai, Ching-Piao; Chen, Ying-Chi; Octaviani Sihombing, Tri; Lin, Chang

    2017-05-01

    A coupled wave-vegetation simulation is presented for the moving effect of the coastal vegetation on tsunami wave height damping. The problem is idealized by solitary wave propagation on a group of emergent cylinders. The numerical model is based on general Reynolds-averaged Navier-Stokes equations with renormalization group turbulent closure model by using volume of fluid technique. The general moving object (GMO) model developed in computational fluid dynamics (CFD) code Flow-3D is applied to simulate the coupled motion of vegetation with wave dynamically. The damping of wave height and the turbulent kinetic energy along moving and stationary cylinders are discussed. The simulated results show that the damping of wave height and the turbulent kinetic energy by the moving cylinders are clearly less than by the stationary cylinders. The result implies that the wave decay by the coastal vegetation may be overestimated if the vegetation was represented as stationary state.

  8. Research overview on vibration damping of mistuned bladed disk assemblies

    Directory of Open Access Journals (Sweden)

    Liang ZHANG

    2016-04-01

    Full Text Available Bladed disk assemblies are very important parts in auto engine and gas turbine, and is widely used in practical engineering. The mistuning existing commonly in the bladed disk assemblies can destroy the vibration characteristics of the bladed disk assemblies, which is one of the reasons for the high cycle fatigue failure of bladed disk assemblies, so it is necessary to research how to reduce the vibration of the bladed disk assemblies. On the basis of the review of relevant research at home and abroad, the mistuning vibration mechanism of the bladed disk assemblies is introduced, and the main technical methods of the vibration damping of bladed disk assemblies are reviewed, such as artificially active mistuning, collision damping, friction damping and optimization of the blade position. Some future research directions are presented.

  9. ENGINEERING NON-HEME MONO- AND DIOXYGENASES FOR BIOCATALYSIS

    Directory of Open Access Journals (Sweden)

    Adi Dror

    2012-09-01

    Full Text Available Oxygenases are ubiquitous enzymes that catalyze the introduction of one or two oxygen atoms to unreactive chemical compounds. They require reduction equivalents from NADH or NADPH and comprise metal ions, metal ion complexes, or coenzymes in their active site. Thus, for industrial purposes, oxygenases are most commonly employed using whole cell catalysis, to alleviate the need for co-factor regeneration. Biotechnological applications include bioremediation, chiral synthesis, biosensors, fine chemicals, biofuels, pharmaceuticals, food ingredients and polymers. Controlling activity and selectivity of oxygenases is therefore of great importance and of growing interest to the scientific community. This review focuses on protein engineering of non-heme monooxygenases and dioxygenases for generating improved or novel functionalities. Rational mutagenesis based on x-ray structures and sequence alignment, as well as random methods such as directed evolution, have been utilized. It is concluded that knowledge-based protein engineering accompanied with targeted libraries, is most efficient for the design and tuning of biocatalysts towards novel substrates and enhanced catalytic activity while minimizing the screening efforts.

  10. Engineering Non-Heme Mono- and Dioxygenases for Biocatalysis

    Directory of Open Access Journals (Sweden)

    Adi Dror

    2012-09-01

    Full Text Available Oxygenases are ubiquitous enzymes that catalyze the introduction of one or two oxygen atoms to unreactive chemical compounds. They require reduction equivalents from NADH or NADPH and comprise metal ions, metal ion complexes, or coenzymes in their active site. Thus, for industrial purposes, oxygenases are most commonly employed using whole cell catalysis, to alleviate the need for co-factor regeneration. Biotechnological applications include bioremediation, chiral synthesis, biosensors, fine chemicals, biofuels, pharmaceuticals, food ingredients and polymers. Controlling activity and selectivity of oxygenases is therefore of great importance and of growing interest to the scientific community. This review focuses on protein engineering of non-heme monooxygenases and dioxygenases for generating improved or novel functionalities. Rational mutagenesis based on x-ray structures and sequence alignment, as well as random methods such as directed evolution, have been utilized. It is concluded that knowledge-based protein engineering accompanied with targeted libraries, is most efficient for the design and tuning of biocatalysts towards novel substrates and enhanced catalytic activity while minimizing the screening efforts.

  11. A product of heme catabolism modulates bacterial function and survival.

    Directory of Open Access Journals (Sweden)

    Christopher L Nobles

    Full Text Available Bilirubin is the terminal metabolite in heme catabolism in mammals. After deposition into bile, bilirubin is released in large quantities into the mammalian gastrointestinal (GI tract. We hypothesized that intestinal bilirubin may modulate the function of enteric bacteria. To test this hypothesis, we investigated the effect of bilirubin on two enteric pathogens; enterohemorrhagic E. coli (EHEC, a Gram-negative that causes life-threatening intestinal infections, and E. faecalis, a Gram-positive human commensal bacterium known to be an opportunistic pathogen with broad-spectrum antibiotic resistance. We demonstrate that bilirubin can protect EHEC from exogenous and host-generated reactive oxygen species (ROS through the absorption of free radicals. In contrast, E. faecalis was highly susceptible to bilirubin, which causes significant membrane disruption and uncoupling of respiratory metabolism in this bacterium. Interestingly, similar results were observed for other Gram-positive bacteria, including B. cereus and S. aureus. A model is proposed whereby bilirubin places distinct selective pressure on enteric bacteria, with Gram-negative bacteria being protected from ROS (positive outcome and Gram-positive bacteria being susceptible to membrane disruption (negative outcome. This work suggests bilirubin has differential but biologically relevant effects on bacteria and justifies additional efforts to determine the role of this neglected waste catabolite in disease processes, including animal models.

  12. Increased Plasma Levels of Heme Oxygenase-1 in Human Brucellosis.

    Science.gov (United States)

    Chen, Zhe; Zhang, Yu-Xue; Fu, Dong-Wei; Gao, Qing-Feng; Ge, Feng-Xia; Liu, Wei-Hua

    2016-08-01

    Brucellosis is associated with inflammation and the oxidative stress response. Heme oxygenase-1 (HO-1) is a cytoprotective stress-responsive enzyme that has anti-inflammatory and anti-oxidant effects. Nevertheless, the role of HO-1 in human brucellosis has not yet been studied. The aim of this study was to examine the plasma levels of HO-1 in patients with brucellosis and to evaluate the ability of plasma HO-1 levels as an auxiliary diagnosis, a severity predictor, and a monitor for brucellosis treatments. A total of 75 patients with brucellosis were divided into the acute, subacute, chronic active, and chronic stable groups. An additional 20 volunteers were included as the healthy control group. The plasma HO-1 levels and other laboratory parameters were measured in all groups. Furthermore, the plasma levels of HO-1 in the acute group were compared before and after treatment. The plasma HO-1 levels were considerably increased in the acute (4.97 ± 3.55), subacute (4.98 ± 3.23), and chronic active groups (4.43 ± 3.00) with brucellosis compared to the healthy control group (1.03 ± 0.63) (p brucellosis (r = 0.707, p brucellosis status and may be used as a supplementary plasma marker for diagnosing brucellosis and monitoring its treatment.

  13. Improving the Magnetic Damping of an AS-1 Seismometer

    Science.gov (United States)

    Marton, F.; Echreshzadeh, M.; Tokman, T. L.; Palaric, K. D.; Filippone, N. V.; Balzarette, M.; Sivo, J.

    2016-12-01

    Last year, students working on the SeismoSTEM project at Bergen Community College in New Jersey successfully manufactured and assembled an AS-1 seismometer1. For 2016, our objective has been to improve the magnetic damping mechanism invented by Chris Chapman2. As the mass on the boom is displaced by seismic waves, the spring will cause the mass to oscillate, therefore, damping is required. To achieve this, a paddle-shaped piece of copper, along with steel plates holding strong neodymium magnets are used. A localized eddy current is then induced, which then creates an opposing magnetic field. The challenges we faced for the summer internship was the fact that there was either too much or too little damping to distinguish the waves of an earthquake. However, we resolved the issue by designing our own prototype for moving the steel plates away and toward the copper paddle, to achieve critical damping. This was successfully completed by attaching two L-shaped pieces of aluminum, along with a cylindrical piece, to form a yoke. We then drilled a hole through the cylindrical piece and a plastic block for a bolt to slide through. Finally, the head of the bolt would then be used as a knob to shift the two plates away from and toward the paddle simultaneously. Although this was our solution for moving the plates horizontally, we also needed to find a way to lock the plates in place once we found the correct amount of damping. We accomplished this task by drilling two slotted holes on two symmetrical sheets of aluminum, which will allow us to slide the plates, and finally, lock them into place to avoid wobbling. References: 1Tokman, T.L. et al., What's shaking? Manufacturing & assembling an AS-1 educational seismometer for undergraduate stem research, Geological Society of America Abstracts with Programs. Vol. 47, No. 7, p.524, 2015. 2http://www.jclahr.com/science/psn/chapman/as1%20damping/

  14. Enhancing the damping of wind turbine rotor blades, the DAMPBLADE project

    DEFF Research Database (Denmark)

    Chaviaropoulos, P.K.; Politis, E.S.; Lekou, D.J.

    2006-01-01

    : tailoring of laminate damping anisotropy, damping layers and damped polymer matrices. Additional objectives of the project were the development of the missing critical analytical technologies enabling the explicit modelling of composite structural damping and a novel ‘composite blade design capacity...... glass/polyester damped blade was designed, manufactured and tested using the know-how acquired. Modal analysis of this blade at the testing facility of CRES showed a nearly 80% increase in the damping ratio of both the first flap and lag modes compared with the earlier, standard, design practice...

  15. Oxidative stability of a heme iron-fortified bakery product: Effectiveness of ascorbyl palmitate and co-spray-drying of heme iron with calcium caseinate.

    Science.gov (United States)

    Alemán, Mercedes; Bou, Ricard; Tres, Alba; Polo, Javier; Codony, Rafael; Guardiola, Francesc

    2016-04-01

    Fortification of food products with iron is a common strategy to prevent or overcome iron deficiency. However, any form of iron is a pro-oxidant and its addition will cause off-flavours and reduce a product's shelf life. A highly bioavailable heme iron ingredient was selected to fortify a chocolate cream used to fill sandwich-type cookies. Two different strategies were assessed for avoiding the heme iron catalytic effect on lipid oxidation: ascorbyl palmitate addition and co-spray-drying of heme iron with calcium caseinate. Oxidation development and sensory acceptability were monitored in the cookies over one-year of storage at room temperature in the dark. The addition of ascorbyl palmitate provided protection against oxidation and loss of tocopherols and tocotrienols during the preparation of cookies. In general, ascorbyl palmitate, either alone or in combination with the co-spray-dried heme iron, prevented primary oxidation and hexanal formation during storage. The combination of both strategies resulted in cookies that were acceptable from a sensory point of view after 1year of storage. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. Identification of residues in the heme domain of soluble guanylyl cyclase that are important for basal and stimulated catalytic activity.

    Directory of Open Access Journals (Sweden)

    Padmamalini Baskaran

    Full Text Available Nitric oxide signals through activation of soluble guanylyl cyclase (sGC, a heme-containing heterodimer. NO binds to the heme domain located in the N-terminal part of the β subunit of sGC resulting in increased production of cGMP in the catalytic domain located at the C-terminal part of sGC. Little is known about the mechanism by which the NO signaling is propagated from the receptor domain (heme domain to the effector domain (catalytic domain, in particular events subsequent to the breakage of the bond between the heme iron and Histidine 105 (H105 of the β subunit. Our modeling of the heme-binding domain as well as previous homologous heme domain structures in different states point to two regions that could be critical for propagation of the NO activation signal. Structure-based mutational analysis of these regions revealed that residues T110 and R116 in the αF helix-β1 strand, and residues I41 and R40 in the αB-αC loop mediate propagation of activation between the heme domain and the catalytic domain. Biochemical analysis of these heme mutants allows refinement of the map of the residues that are critical for heme stability and propagation of the NO/YC-1 activation signal in sGC.

  17. The 2-Cys Peroxiredoxin Alkyl Hydroperoxide Reductase C Binds Heme and Participates in Its Intracellular Availability in Streptococcus agalactiae*

    Science.gov (United States)

    Lechardeur, Delphine; Fernandez, Annabelle; Robert, Bruno; Gaudu, Philippe; Trieu-Cuot, Patrick; Lamberet, Gilles; Gruss, Alexandra

    2010-01-01

    Heme is a redox-reactive molecule with vital and complex roles in bacterial metabolism, survival, and virulence. However, few intracellular heme partners were identified to date and are not well conserved in bacteria. The opportunistic pathogen Streptococcus agalactiae (group B Streptococcus) is a heme auxotroph, which acquires exogenous heme to activate an aerobic respiratory chain. We identified the alkyl hydroperoxide reductase AhpC, a member of the highly conserved thiol-dependent 2-Cys peroxiredoxins, as a heme-binding protein. AhpC binds hemin with a Kd of 0.5 μm and a 1:1 stoichiometry. Mutagenesis of cysteines revealed that hemin binding is dissociable from catalytic activity and multimerization. AhpC reductase activity was unchanged upon interaction with heme in vitro and in vivo. A group B Streptococcus ahpC mutant displayed attenuation of two heme-dependent functions, respiration and activity of a heterologous catalase, suggesting a role for AhpC in heme intracellular fate. In support of this hypothesis, AhpC-bound hemin was protected from chemical degradation in vitro. Our results reveal for the first time a role for AhpC as a heme-binding protein. PMID:20332091

  18. Heme binding in the NEAT domains of IsdA and IsdC of Staphylococcus aureus.

    Science.gov (United States)

    Pluym, Mark; Muryoi, Naomi; Heinrichs, David E; Stillman, Martin J

    2008-03-01

    Absorption, magnetic circular dichroism (MCD), and electrospray mass spectral (ESI-MS) data are reported for the heme binding NEAr iron Transporter (NEAT) domains of IsdA and IsdC, two proteins involved in heme scavenging by Staphylococcus aureus. The mass spectrometry data show that the NEAT domains are globular in structure and efficiently bind a single heme molecule. In this work, the IsdA NEAT domain is referred to as NEAT-A, the IsdC NEAT domain is referred to as NEAT-C, heme-free NEAT-C is NEAT-A and NEAT-C are inaccessible to small anionic ligands. Reduction of the high-spin Fe(III) heme iron to 5-coordinate high-spin Fe(II) in NEAT-A results in coordination by histidine and opens access, allowing for CO axial ligation, yielding 6-coordinate low-spin Fe(II) heme. In contrast, reduction of the high-spin Fe(III) heme iron to 5-coordinate high-spin Fe(II) in NEAT-C results in loss of the heme from the binding site of the protein due to the absence of a proximal histidine. The absorption and MCD data for NEAT-A closely match those previously reported for the whole IsdA protein, providing evidence that heme binding is primarily a property of the NEAT domain.

  19. Plasmodium-infected erythrocytes (pRBC induce endothelial cell apoptosis via a heme-mediated signaling pathway

    Directory of Open Access Journals (Sweden)

    Liu M

    2016-03-01

    Full Text Available Mingli Liu, Carmen Dickinson-Copeland, Salifu Hassana, Jonathan K Stiles Department of Microbiology, Biochemistry and Immunology, Morehouse School of Medicine, Atlanta, GA, USA Abstract: Heme is cytotoxic to the plasmodium parasite, which converts it to an insoluble crystalline form called hemozoin (malaria pigment in erythrocytes during replication. The increased serum levels of free heme cause tissue damage, activation of microvascular endothelial and glial cells, focal inflammation, activation of apoptotic pathways, and neuronal tissue damage. Several hypotheses have been proposed to explain how these causative factors exacerbate fatal malaria. However, none of them fully explain the detailed mechanisms leading to the high morbidity and mortality associated with malaria. We have previously reported that heme-induced brain microvascular endothelial cell (HBVEC apoptosis is a major contributor to severe malaria pathogenesis. Here, we hypothesized that heme (at clinically relevant levels induces inflammation and apoptosis in HBVEC, a process that is mediated by independent proinflammatory and proapoptotic signaling pathways. In this study, we determined the key signaling molecules associated with heme-mediated apoptosis in HBVEC in vitro using RT2 profiler polymerase chain reaction array technology and confirmed results using immunostaining techniques. While several expressed genes in HBVEC were altered upon heme stimulation, we determined that the apoptotic effects of heme were mediated through p73 (tumor protein p73. The results provide an opportunity to target heme-mediated apoptosis therapeutically in malaria-infected individuals. Keywords: heme, endothelial cells, signaling pathways, cerebral malaria

  20. The Nonlinear Landau Damping Rate of a Driven Plasma Wave

    Energy Technology Data Exchange (ETDEWEB)

    Benisti, D; Strozzi, D J; Gremillet, L; Morice, O

    2009-08-04

    In this Letter, we discuss the concept of the nonlinear Landau damping rate, {nu}, of a driven electron plasma wave, and provide a very simple, practical, analytic formula for {nu} which agrees very well with results inferred from Vlasov simulations of stimulated Raman scattering. {nu} actually is more complicated an operator than a plain damping rate, and it may only be seen as such because it assumes almost constant values before abruptly dropping to 0. The decrease of {nu} to 0 is moreover shown to occur later when the wave amplitude varies in the direction transverse to its propagation.

  1. A practical multiscale approach for optimization of structural damping

    DEFF Research Database (Denmark)

    Andreassen, Erik; Jensen, Jakob Søndergaard

    2016-01-01

    A simple and practical multiscale approach suitable for topology optimization of structural damping in a component ready for additive manufacturing is presented.The approach consists of two steps: First, the homogenized loss factor of a two-phase material is maximized. This is done in order...... to obtain a range of isotropic microstructures that have a connected stiff material phase. Second,the structural damping of the component is maximized using material interpolations based on the homogenized properties of the microstructures. In order to achieve convergence towards a discrete set of material...

  2. On strain-rate independent damping in continuum mechanics

    Science.gov (United States)

    Mulder, Gerben

    2017-10-01

    Strain-rate independent damping is a theory of energy dissipation in solids. It is based on the assumption that an increase or decrease in the strain-energy density correlates with a multiplication of 1+η or 1-η respectively, of the material stiffness matrix, with 0≤ η derived for strain-rate independent damping can be solved for 1, 2 or 3 dimensions via direct integration, provided that the software supports PDE coefficients that are functions of the solution and its space and time derivatives. A 3D problem with 22,000 DOF's and 10,000 time steps was solved successfully and convincingly.

  3. Parametric resonance induced chaos in magnetic damped driven pendulum

    Energy Technology Data Exchange (ETDEWEB)

    Khomeriki, Giorgi, E-mail: giokhomeriki123@gmail.com

    2016-07-15

    A damped driven pendulum with a magnetic driving force, appearing from a solenoid, where ac current flows is considered. The solenoid acts on the magnet, which is located at a free end of the pendulum. In this system the existence and interrelation of chaos and parametric resonance is theoretically examined. Derived analytical results are supported by numerical simulations and conducted experiments. - Highlights: • A damped magnetic pendulum is considered driven by off resonant magnetic field. • Our system is chaotic only when the conditions for parametric resonance are fulfilled. • Conducted experiments give a good agreement with theory and numerical simulations. • Calculated Lyapunov exponents are compared with parametric instability growth rates.

  4. Constraint damping in the Z4 formulation and harmonic gauge

    Energy Technology Data Exchange (ETDEWEB)

    Gundlach, Carsten [School of Mathematics, University of Southampton, Southampton SO17 1BJ (United Kingdom); Calabrese, Gioel [School of Mathematics, University of Southampton, Southampton SO17 1BJ (United Kingdom); Hinder, Ian [School of Mathematics, University of Southampton, Southampton SO17 1BJ (United Kingdom); Martin-GarcIa, Jose M [Instituto de Estructura de la Materia, Centro de Fisica Miguel A Catalan, CSIC, Serrano 123, 28006 Madrid (Spain)

    2005-09-07

    We show that by adding suitable lower-order terms to the Z4 formulation of the Einstein equations, all constraint violations except constant modes are damped. This makes the Z4 formulation a particularly simple example of a {lambda}-system as suggested by Brodbeck et al (1999 J. Math. Phys. 40 909). We also show that the Einstein equations in harmonic coordinates can be obtained from the Z4 formulation by a change of variables that leaves the implied constraint evolution system unchanged. Therefore, the same method can be used to damp all constraints in the Einstein equations in harmonic gauge.

  5. Dynamic stiffness and damping of foundations for jacket structures

    DEFF Research Database (Denmark)

    Latini, Chiara; Zania, Varvara; Johannesson, Björn

    2015-01-01

    resistance as defined by Nogami & Novak (1977) is determined, considering 3D wave propagation within linear soil layer with hysteretic damping. Thereafter, the dynamic response of the pile is estimated assuming soil pressure equal to the soil resistance and imposing displacement compatibility. A parametric...... study clarifies the role of the parameters involved i.e. the depth of the soil layer, the pile diameter and the soil layer shear wave velocity. Results are presented in terms of dimensionless graphs which highlight the frequency dependency of the dynamic stiffness and damping....

  6. Turbulence damping as a measure of the flow dimensionality

    CERN Document Server

    Shats, M; Xia, H

    2010-01-01

    The dimensionality of turbulence in fluid layers determines their properties. We study electromagnetically driven flows in finite depth fluid layers and show that eddy viscosity, which appears as a result of three-dimensional motions, leads to increased bottom damping. The anomaly coefficient, which characterizes the deviation of damping from the one derived using a quasi-two-dimensional model, can be used as a measure of the flow dimensionality. Experiments in turbulent layers show that when the anomaly coefficient becomes high, the turbulent inverse energy cascade is suppressed. In the opposite limit turbulence can self-organize into a coherent flow.

  7. Investigation of Landau-damping effects on shock formation

    DEFF Research Database (Denmark)

    Andersen, H.K.; D'Angelo, N.; Michelsen, Poul

    1967-01-01

    Landau damping in plasmas of equal ion and electron temperatures (alkali plasmas) may prevent the formation of a shock. Shocks are produced when the ratio Te/Ti is increased to about 8 or so by cooling the ions through i-n collisions.......Landau damping in plasmas of equal ion and electron temperatures (alkali plasmas) may prevent the formation of a shock. Shocks are produced when the ratio Te/Ti is increased to about 8 or so by cooling the ions through i-n collisions....

  8. Impairment of nitric oxide synthase but not heme oxygenase accounts for baroreflex dysfunction caused by chronic nicotine in female rats.

    Directory of Open Access Journals (Sweden)

    Mohamed A Fouda

    Full Text Available We recently reported that chronic nicotine impairs reflex chronotropic activity in female rats. Here, we sought evidence to implicate nitric oxide synthase (NOS and/or heme oxygenase (HO in the nicotine-baroreflex interaction. Baroreflex curves relating changes in heart rate to increases (phenylephrine or decreases (sodium nitroprusside in blood pressure were generated in conscious female rats treated with nicotine or saline in absence and presence of pharmacological modulators of NOS or HO activity. Compared with saline-treated rats, nicotine (2 mg/kg/day i.p., for 14 days significantly reduced the slopes of baroreflex curves, a measure of baroreflex sensitivity (BRS. Findings that favor the involvement of NOS inhibition in the nicotine effect were (i NOS inhibition (Nω-Nitro-L-arginine methyl ester, L-NAME reduced BRS in control rats but failed to do so in nicotine-treated rats, (ii L-arginine, NO donor, reversed the BRS inhibitory effect of nicotine. Alternatively, HO inhibition (zinc protoporphyrin IX, ZnPP had no effect on BRS in nicotine- or control rats and failed to reverse the beneficial effect of L-arginine on nicotine-BRS interaction. Similar to female rats, BRS was reduced by L-NAME, but not ZnPP, in male rats and the L-NAME effect was not accentuated after concomitant administration of nicotine. Baroreflex dysfunction caused by nicotine in female rats was blunted after supplementation with hemin (HO inducer but not tricarbonyldichlororuthenium(II dimer (CORM-2, a carbon monoxide (CO releasing molecule, or bilirubin, the breakdown product of heme catabolism. The facilitatory effect of hemin was abolished upon simultaneous treatment with L-NAME or 1H-[1], [2], [4] oxadiazolo[4,3-a] quinoxalin-1-one (inhibitor of soluble guanylate cyclase, sGC. The activities of HO and NOS in brainstem tissues were also significantly increased by hemin. Thus, the inhibition of NOS, but not HO, accounts for the baroreflex depressant of chronic nicotine

  9. ATP Binding Cassette Transporter Mediates Both Heme and Pesticide Detoxification in Tick Midgut Cells.

    Directory of Open Access Journals (Sweden)

    Flavio Alves Lara

    Full Text Available In ticks, the digestion of blood occurs intracellularly and proteolytic digestion of hemoglobin takes place in a dedicated type of lysosome, the digest vesicle, followed by transfer of the heme moiety of hemoglobin to a specialized organelle that accumulates large heme aggregates, called hemosomes. In the present work, we studied the uptake of fluorescent metalloporphyrins, used as heme analogs, and amitraz, one of the most regularly used acaricides to control cattle tick infestations, by Rhipicephalus (Boophilus microplus midgut cells. Both compounds were taken up by midgut cells in vitro and accumulated inside the hemosomes. Transport of both molecules was sensitive to cyclosporine A (CsA, a well-known inhibitor of ATP binding cassette (ABC transporters. Rhodamine 123, a fluorescent probe that is also a recognized ABC substrate, was similarly directed to the hemosome in a CsA-sensitive manner. Using an antibody against conserved domain of PgP-1-type ABC transporter, we were able to immunolocalize PgP-1 in the digest vesicle membranes. Comparison between two R. microplus strains that were resistant and susceptible to amitraz revealed that the resistant strain detoxified both amitraz and Sn-Pp IX more efficiently than the susceptible strain, a process that was also sensitive to CsA. A transcript containing an ABC transporter signature exhibited 2.5-fold increased expression in the amitraz-resistant strain when compared with the susceptible strain. RNAi-induced down-regulation of this ABC transporter led to the accumulation of metalloporphyrin in the digestive vacuole, interrupting heme traffic to the hemosome. This evidence further confirms that this transcript codes for a heme transporter. This is the first report of heme transport in a blood-feeding organism. While the primary physiological function of the hemosome is to detoxify heme and attenuate its toxicity, we suggest that the use of this acaricide detoxification pathway by ticks may

  10. Heme oxygenase, inflammation, and fibrosis: the good, the bad, and the ugly?

    Directory of Open Access Journals (Sweden)

    Ditte M. S. Lundvig

    2012-05-01

    Full Text Available Upon injury, prolonged inflammation and oxidative stress may cause pathological wound healing and fibrosis, leading to formation of excessive scar tissue. Fibrogenesis can occur in most organs and tissues and may ultimately lead to organ dysfunction and failure. The underlying mechanisms of pathological wound healing still remains unclear, but are considered to have a multifactoral pathogenesis, and so far, no efficient anti-fibrotic therapies exists.Extra- and intracellular levels of free heme may be increased in a variety of pathological conditions due to heme-release from hemoproteins. Free heme possesses pro-inflammatory and oxidative effects, and may act as a danger signal, which counteracted by protein scavenging via various heme-binding proteins and by heme degradation. Heme is degraded by heme oxygenase (HO that exists as two isoforms: inducible HO-1 and constitutively expressed HO-2. This generates the effector molecules biliverdin, carbon monoxide, and free iron. HO deficiency in mouse and man leads to exaggerated inflammation upon insults, and still accumulating epidemiological and preclinical studies support the widely recognized notion of the cytoprotective, anti-oxidative, and anti-inflammatory effects of the activity of the HO system and the generated effector molecules. In this review, we address the potential applications of targeted HO-1 induction or administration of its effector molecules as therapeutic targets in fibrotic and inflammatory conditions to counteract inflammatory and oxidative insults. This is shown in various clinically relevant conditions, such as hypertrophic scarring, chronic inflammatory liver disease, chronic pancreatitis, and chronic graft rejection in transplantation.

  11. Heme iron polypeptide for the management of anaemia of chronic kidney disease.

    Science.gov (United States)

    Dull, R B; Davis, E

    2015-08-01

    Anaemia is a common clinical finding among patients with chronic kidney disease (CKD) and is associated with significant morbidity and healthcare costs. Iron deficiency is an important contributing factor, and adequate iron supplementation is essential to optimize the management of anaemia of CKD. Oral iron is convenient and inexpensive but is poorly absorbed and associated with gastrointestinal distress. Intravenous iron overcomes these limitations but is more expensive, requires additional clinical visits for administration and is associated with serious adverse events. Oral heme iron polypeptide (HIP) is a newer dosage form that has been reported to have higher bioavailability and fewer side effects when compared with non-heme iron in healthy subjects, but data in patients with CKD are limited. The purpose of this review is to evaluate the safety and effectiveness of HIP for the management of CKD. Searches for PubMed (1947-2015) and International Pharmaceutical Abstracts (1970-2015) were conducted using the following terms: heme iron, heme iron polypeptide, oral iron, anaemia and chronic kidney disease. The bibliography of each relevant article was evaluated for additional studies. Articles were selected for review if they were published in the English language and were randomized controlled trials evaluating the bioavailability, tolerability or efficacy of oral HIP in human subjects with CKD. This search yielded three clinical studies. The safety and efficacy of HIP was evaluated in a total of 161 subjects with anaemia and various stages of CKD. HIP was consistently associated with lower ferritin values when compared with traditional iron supplementation. With few exceptions, the effect of HIP on haemoglobin, haematocrit, transferrin saturation and recombinant human erythropoietin dose, and adverse effects appeared similar to intravenous and oral non-heme iron supplementation. The cost of HIP is substantially more than non-heme iron and comparable to

  12. Chemistry and Molecular Dynamics Simulations of Heme b-HemQ and Coproheme-HemQ.

    Science.gov (United States)

    Hofbauer, Stefan; Dalla Sega, Marco; Scheiblbrandner, Stefan; Jandova, Zuzana; Schaffner, Irene; Mlynek, Georg; Djinović-Carugo, Kristina; Battistuzzi, Gianantonio; Furtmüller, Paul G; Oostenbrink, Chris; Obinger, Christian

    2016-09-27

    Recently, a novel pathway for heme b biosynthesis in Gram-positive bacteria has been proposed. The final poorly understood step is catalyzed by an enzyme called HemQ and includes two decarboxylation reactions leading from coproheme to heme b. Coproheme has been suggested to act as both substrate and redox active cofactor in this reaction. In the study presented here, we focus on HemQs from Listeria monocytogenes (LmHemQ) and Staphylococcus aureus (SaHemQ) recombinantly produced as apoproteins in Escherichia coli. We demonstrate the rapid and two-phase uptake of coproheme by both apo forms and the significant differences in thermal stability of the apo forms, coproheme-HemQ and heme b-HemQ. Reduction of ferric high-spin coproheme-HemQ to the ferrous form is shown to be enthalpically favored but entropically disfavored with standard reduction potentials of -205 ± 3 mV for LmHemQ and -207 ± 3 mV for SaHemQ versus the standard hydrogen electrode at pH 7.0. Redox thermodynamics suggests the presence of a pronounced H-bonding network and restricted solvent mobility in the heme cavity. Binding of cyanide to the sixth coproheme position is monophasic but relatively slow (∼1 × 10(4) M(-1) s(-1)). On the basis of the available structures of apo-HemQ and modeling of both loaded forms, molecular dynamics simulation allowed analysis of the interaction of coproheme and heme b with the protein as well as the role of the flexibility at the proximal heme cavity and the substrate access channel for coproheme binding and heme b release. Obtained data are discussed with respect to the proposed function of HemQ in monoderm bacteria.

  13. ATP Binding Cassette Transporter Mediates Both Heme and Pesticide Detoxification in Tick Midgut Cells

    Science.gov (United States)

    Lara, Flavio Alves; Pohl, Paula C.; Gandara, Ana Caroline; Ferreira, Jessica da Silva; Nascimento-Silva, Maria Clara; Bechara, Gervásio Henrique; Sorgine, Marcos H. F.; Almeida, Igor C.; Vaz, Itabajara da Silva; Oliveira, Pedro L.

    2015-01-01

    In ticks, the digestion of blood occurs intracellularly and proteolytic digestion of hemoglobin takes place in a dedicated type of lysosome, the digest vesicle, followed by transfer of the heme moiety of hemoglobin to a specialized organelle that accumulates large heme aggregates, called hemosomes. In the present work, we studied the uptake of fluorescent metalloporphyrins, used as heme analogs, and amitraz, one of the most regularly used acaricides to control cattle tick infestations, by Rhipicephalus (Boophilus) microplus midgut cells. Both compounds were taken up by midgut cells in vitro and accumulated inside the hemosomes. Transport of both molecules was sensitive to cyclosporine A (CsA), a well-known inhibitor of ATP binding cassette (ABC) transporters. Rhodamine 123, a fluorescent probe that is also a recognized ABC substrate, was similarly directed to the hemosome in a CsA-sensitive manner. Using an antibody against conserved domain of PgP-1-type ABC transporter, we were able to immunolocalize PgP-1 in the digest vesicle membranes. Comparison between two R. microplus strains that were resistant and susceptible to amitraz revealed that the resistant strain detoxified both amitraz and Sn-Pp IX more efficiently than the susceptible strain, a process that was also sensitive to CsA. A transcript containing an ABC transporter signature exhibited 2.5-fold increased expression in the amitraz-resistant strain when compared with the susceptible strain. RNAi-induced down-regulation of this ABC transporter led to the accumulation of metalloporphyrin in the digestive vacuole, interrupting heme traffic to the hemosome. This evidence further confirms that this transcript codes for a heme transporter. This is the first report of heme transport in a blood-feeding organism. While the primary physiological function of the hemosome is to detoxify heme and attenuate its toxicity, we suggest that the use of this acaricide detoxification pathway by ticks may represent a new

  14. SCMHBP: prediction and analysis of heme binding proteins using propensity scores of dipeptides.

    Science.gov (United States)

    Liou, Yi-Fan; Charoenkwan, Phasit; Srinivasulu, Yerukala; Vasylenko, Tamara; Lai, Shih-Chung; Lee, Hua-Chin; Chen, Yi-Hsiung; Huang, Hui-Ling; Ho, Shinn-Ying

    2014-01-01

    Heme binding proteins (HBPs) are metalloproteins that contain a heme ligand (an iron-porphyrin complex) as the prosthetic group. Several computational methods have been proposed to predict heme binding residues and thereby to understand the interactions between heme and its host proteins. However, few in silico methods for identifying HBPs have been proposed. This work proposes a scoring card method (SCM) based method (named SCMHBP) for predicting and analyzing HBPs from sequences. A balanced dataset of 747 HBPs (selected using a Gene Ontology term GO:0020037) and 747 non-HBPs (selected from 91,414 putative non-HBPs) with an identity of 25% was firstly established. Consequently, a set of scores that quantified the propensity of amino acids and dipeptides to be HBPs is estimated using SCM to maximize the predictive accuracy of SCMHBP. Finally, the informative physicochemical properties of 20 amino acids are identified by utilizing the estimated propensity scores to be used to categorize HBPs. The training and mean test accuracies of SCMHBP applied to three independent test datasets are 85.90% and 71.57%, respectively. SCMHBP performs well relative to comparison with such methods as support vector machine (SVM), decision tree J48, and Bayes classifiers. The putative non-HBPs with high sequence propensity scores are potential HBPs, which can be further validated by experimental confirmation. The propensity scores of individual amino acids and dipeptides are examined to elucidate the interactions between heme and its host proteins. The following characteristics of HBPs are derived from the propensity scores: 1) aromatic side chains are important to the effectiveness of specific HBP functions; 2) a hydrophobic environment is important in the interaction between heme and binding sites; and 3) the whole HBP has low flexibility whereas the heme binding residues are relatively flexible. SCMHBP yields knowledge that improves our understanding of HBPs rather than merely

  15. Chemistry and Molecular Dynamics Simulations of Heme b-HemQ and Coproheme-HemQ

    Science.gov (United States)

    2016-01-01

    Recently, a novel pathway for heme b biosynthesis in Gram-positive bacteria has been proposed. The final poorly understood step is catalyzed by an enzyme called HemQ and includes two decarboxylation reactions leading from coproheme to heme b. Coproheme has been suggested to act as both substrate and redox active cofactor in this reaction. In the study presented here, we focus on HemQs from Listeria monocytogenes (LmHemQ) and Staphylococcus aureus (SaHemQ) recombinantly produced as apoproteins in Escherichia coli. We demonstrate the rapid and two-phase uptake of coproheme by both apo forms and the significant differences in thermal stability of the apo forms, coproheme-HemQ and heme b-HemQ. Reduction of ferric high-spin coproheme-HemQ to the ferrous form is shown to be enthalpically favored but entropically disfavored with standard reduction potentials of −205 ± 3 mV for LmHemQ and −207 ± 3 mV for SaHemQ versus the standard hydrogen electrode at pH 7.0. Redox thermodynamics suggests the presence of a pronounced H-bonding network and restricted solvent mobility in the heme cavity. Binding of cyanide to the sixth coproheme position is monophasic but relatively slow (∼1 × 104 M–1 s–1). On the basis of the available structures of apo-HemQ and modeling of both loaded forms, molecular dynamics simulation allowed analysis of the interaction of coproheme and heme b with the protein as well as the role of the flexibility at the proximal heme cavity and the substrate access channel for coproheme binding and heme b release. Obtained data are discussed with respect to the proposed function of HemQ in monoderm bacteria. PMID:27599156

  16. Reverse logistics - a framework

    OpenAIRE

    Brito, Marisa; Dekker, Rommert

    2002-01-01

    textabstractIn this paper we define and compare Reverse Logistics definitions. We start by giving an understanding framework of Reverse Logistics: the why-what-how. By this means, we put in context the driving forces for Reverse Logistics, a typology of return reasons, a classification of products, processes and actors. In addition we provide a decision framework for Reverse Logistics and we present it according to long, medium and short term decisions, i.e. strategic-tactic-operational decis...

  17. Reverse logistics - a framework

    NARCIS (Netherlands)

    M.P. de Brito (Marisa); R. Dekker (Rommert)

    2002-01-01

    textabstractIn this paper we define and compare Reverse Logistics definitions. We start by giving an understanding framework of Reverse Logistics: the why-what-how. By this means, we put in context the driving forces for Reverse Logistics, a typology of return reasons, a classification of

  18. Therapeutic Roles of Heme Oxygenase-1 in Metabolic Diseases: Curcumin and Resveratrol Analogues as Possible Inducers of Heme Oxygenase-1

    Directory of Open Access Journals (Sweden)

    Yong Son

    2013-01-01

    Full Text Available Metabolic diseases, such as insulin resistance, type II diabetes, and obesity, are associated with a low-grade chronic inflammation (inflammatory stress, oxidative stress, and endoplasmic reticulum (ER stress. Because the integration of these stresses is critical to the pathogenesis of metabolic diseases, agents and cellular molecules that can modulate these stress responses are emerging as potential targets for intervention and treatment of metabolic diseases. It has been recognized that heme oxygenase-1 (HO-1 plays an important role in cellular protection. Because HO-1 can reduce inflammatory stress, oxidative stress, and ER stress, in part by exerting antioxidant, anti-inflammatory, and antiapoptotic effects, HO-1 has been suggested to play important roles in pathogenesis of metabolic diseases. In the present review, we will explore our current understanding of the protective mechanisms of HO-1 in metabolic diseases and present some emerging therapeutic options for HO-1 expression in treating metabolic diseases, together with the therapeutic potential of curcumin and resveratrol analogues that have their ability to induce HO-1 expression.

  19. Respiratory and allergic health effects of dampness, mold, and dampness-related agents: a review of the epidemiologic evidence.

    Science.gov (United States)

    Mendell, Mark J; Mirer, Anna G; Cheung, Kerry; Tong, My; Douwes, Jeroen

    2011-06-01

    Many studies have shown consistent associations between evident indoor dampness or mold and respiratory or allergic health effects, but causal links remain unclear. Findings on measured microbiologic factors have received little review. We conducted an updated, comprehensive review on these topics. We reviewed eligible peer-reviewed epidemiologic studies or quantitative meta-analyses, up to late 2009, on dampness, mold, or other microbiologic agents and respiratory or allergic effects. We evaluated evidence for causation or association between qualitative/subjective assessments of dampness or mold (considered together) and specific health outcomes. We separately considered evidence for associations between specific quantitative measurements of microbiologic factors and each health outcome. Evidence from epidemiologic studies and meta-analyses showed indoor dampness or mold to be associated consistently with increased asthma development and exacerbation, current and ever diagnosis of asthma, dyspnea, wheeze, cough, respiratory infections, bronchitis, allergic rhinitis, eczema, and upper respiratory tract symptoms. Associations were found in allergic and nonallergic individuals. Evidence strongly suggested causation of asthma exacerbation in children. Suggestive evidence was available for only a few specific measured microbiologic factors and was in part equivocal, suggesting both adverse and protective associations with health. Evident dampness or mold had consistent positive associations with multiple allergic and respiratory effects. Measured microbiologic agents in dust had limited suggestive associations, including both positive and negative associations for some agents. Thus, prevention and remediation of indoor dampness and mold are likely to reduce health risks, but current evidence does not support measuring specific indoor microbiologic factors to guide health-protective actions.

  20. Enhancing teleportation fidelity by means of weak measurements or reversal

    Energy Technology Data Exchange (ETDEWEB)

    Qiu, Liang, E-mail: lqiu@cumt.edu.cn [College of Sciences, China University of Mining and Technology, Xuzhou 221116 (China); Tang, Gang; Yang, Xianqing [College of Sciences, China University of Mining and Technology, Xuzhou 221116 (China); Wang, Anmin [Department of Modern Physics, University of Science and Technology of China, Hefei 230026 (China)

    2014-11-15

    The enhancement of teleportation fidelity by weak measurement or quantum measurement reversal is investigated. One qubit of a maximally entangled state undergoes the amplitude damping, and the subsequent application of weak measurement or quantum measurement reversal could improve the teleportation fidelity beyond the classical region. The improvement could not be attributed to the increasing of entanglement, quantum discord, classical correlation or total correlation. We declare that it should be owed to the probabilistic nature of the method. - Highlights: • The method’s probabilistic nature should be responsible for the improvement. • Quantum or classical correlation cannot explain the improvement. • The receiver cannot apply weak measurements. • The sender’s quantum measurement reversal is only useful for |Ψ{sup ±}〉.