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Sample records for converting redox signaling

  1. Globin-based redox signaling.

    Science.gov (United States)

    De Henau, Sasha; Braeckman, Bart P

    2016-01-01

    In recent years, moderate levels of reactive oxygen species (ROS) have become recognized as signaling cues that participate at all levels of cellular organization. Globins, with their redox-active heme iron and ubiquitous presence, seem ideally suited to participate in ROS metabolism. Here we comment on our recent findings that show the participation of a globin, GLB-12, in a redox signaling pathway in Caenorhabditis elegans. We found that GLB-12 produces superoxide, a type of ROS, after which this is converted to what appears to be a hydrogen peroxide gradient over the plasma membrane by the activity of intracellular and extracellular superoxide dismutases. In the first part, we discuss in more detail the different regulatory mechanisms that increase the effectiveness of this redox signal. In the second part, we comment on how specific structural and biochemical properties allow this globin to perform redox reactions. Interestingly, these properties are also observed in 2 other C. elegans globins that appear to be involved in redox biology. We therefore hypothesize that globins involved in redox signaling display similar structural and biochemical characteristics and propose that a subgroup of globins can be added to the group of proteins that play a vital role in redox signaling.

  2. Quantitative measures for redox signaling.

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    Pillay, Ché S; Eagling, Beatrice D; Driscoll, Scott R E; Rohwer, Johann M

    2016-07-01

    Redox signaling is now recognized as an important regulatory mechanism for a number of cellular processes including the antioxidant response, phosphokinase signal transduction and redox metabolism. While there has been considerable progress in identifying the cellular machinery involved in redox signaling, quantitative measures of redox signals have been lacking, limiting efforts aimed at understanding and comparing redox signaling under normoxic and pathogenic conditions. Here we have outlined some of the accepted principles for redox signaling, including the description of hydrogen peroxide as a signaling molecule and the role of kinetics in conferring specificity to these signaling events. Based on these principles, we then develop a working definition for redox signaling and review a number of quantitative methods that have been employed to describe signaling in other systems. Using computational modeling and published data, we show how time- and concentration- dependent analyses, in particular, could be used to quantitatively describe redox signaling and therefore provide important insights into the functional organization of redox networks. Finally, we consider some of the key challenges with implementing these methods. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Globin-based redox signaling

    OpenAIRE

    De Henau, Sasha; Braeckman, Bart

    2016-01-01

    ABSTRACT In recent years, moderate levels of reactive oxygen species (ROS) have become recognized as signaling cues that participate at all levels of cellular organization. Globins, with their redox-active heme iron and ubiquitous presence, seem ideally suited to participate in ROS metabolism. Here we comment on our recent findings that show the participation of a globin, GLB-12, in a redox signaling pathway in Caenorhabditis elegans. We found that GLB-12 produces superoxide, a type of ROS, a...

  4. Redox signaling in acute pancreatitis

    Directory of Open Access Journals (Sweden)

    Salvador Pérez

    2015-08-01

    Full Text Available Acute pancreatitis is an inflammatory process of the pancreatic gland that eventually may lead to a severe systemic inflammatory response. A key event in pancreatic damage is the intracellular activation of NF-κB and zymogens, involving also calcium, cathepsins, pH disorders, autophagy, and cell death, particularly necrosis. This review focuses on the new role of redox signaling in acute pancreatitis. Oxidative stress and redox status are involved in the onset of acute pancreatitis and also in the development of the systemic inflammatory response, being glutathione depletion, xanthine oxidase activation, and thiol oxidation in proteins critical features of the disease in the pancreas. On the other hand, the release of extracellular hemoglobin into the circulation from the ascitic fluid in severe necrotizing pancreatitis enhances lipid peroxidation in plasma and the inflammatory infiltrate into the lung and up-regulates the HIF–VEGF pathway, contributing to the systemic inflammatory response. Therefore, redox signaling and oxidative stress contribute to the local and systemic inflammatory response during acute pancreatitis.

  5. Redox signaling in acute pancreatitis.

    Science.gov (United States)

    Pérez, Salvador; Pereda, Javier; Sabater, Luis; Sastre, Juan

    2015-08-01

    Acute pancreatitis is an inflammatory process of the pancreatic gland that eventually may lead to a severe systemic inflammatory response. A key event in pancreatic damage is the intracellular activation of NF-κB and zymogens, involving also calcium, cathepsins, pH disorders, autophagy, and cell death, particularly necrosis. This review focuses on the new role of redox signaling in acute pancreatitis. Oxidative stress and redox status are involved in the onset of acute pancreatitis and also in the development of the systemic inflammatory response, being glutathione depletion, xanthine oxidase activation, and thiol oxidation in proteins critical features of the disease in the pancreas. On the other hand, the release of extracellular hemoglobin into the circulation from the ascitic fluid in severe necrotizing pancreatitis enhances lipid peroxidation in plasma and the inflammatory infiltrate into the lung and up-regulates the HIF-VEGF pathway, contributing to the systemic inflammatory response. Therefore, redox signaling and oxidative stress contribute to the local and systemic inflammatory response during acute pancreatitis.

  6. Microglia antioxidant systems and redox signaling

    DEFF Research Database (Denmark)

    Vilhardt, F; Haslund-Vinding, J; Jaquet, V

    2017-01-01

    of protein thiolation of target redox proteins the necessity for tightly localized, timed, and confined oxidant production to work in concert with antioxidant proteins to promote redox signaling. NOX2-mediated redox signaling modulate the acquisition of the classical or alternative microglia activation...... of the antioxidant response in microglia will reveal antioxidant proteins as dynamic players in redox signaling, which in concert with NOX-derived oxidants fulfill important roles in the autocrine or paracrine regulation of essential enzymes or transcriptional programs. This article is protected by copyright. All......'t stand alone however, and are not always pernicious. We discuss in general terms, and where available in microglia, GSH synthesis and relation to cystine import and glutamate export, and the thioredoxin system as the most important antioxidative defense mechanism, and further, we discuss in the context...

  7. Redox signaling in pathophysiology of hypertension.

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    Majzunova, Miroslava; Dovinova, Ima; Barancik, Miroslav; Chan, Julie Y H

    2013-09-18

    Reactive oxygen species (ROS) are products of normal cellular metabolism and derive from various sources in different cellular compartments. Oxidative stress resultant from imbalance between ROS generation and antioxidant defense mechanisms is important in pathogenesis of cardiovascular diseases, such as hypertension, heart failure, atherosclerosis, diabetes, and cardiac hypertrophy. In this review we focus on hypertension and address sources of cellular ROS generation, mechanisms involved in regulation of radical homeostasis, superoxide dismutase isoforms in pathophysiology of hypertension; as well as radical intracellular signaling and phosphorylation processes in proteins of the affected cardiovascular tissues. Finally, we discuss the transcriptional factors involved in redox-sensitive gene transcription and antioxidant response, as well as their roles in hypertension.

  8. Principles in redox signaling: from chemistry to functional significance.

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    Bindoli, Alberto; Rigobello, Maria Pia

    2013-05-01

    Reactive oxygen and nitrogen species are currently considered not only harmful byproducts of aerobic respiration but also critical mediators of redox signaling. The molecules and the chemical principles sustaining the network of cellular redox regulated processes are described. Special emphasis is placed on hydrogen peroxide (H(2)O(2)), now considered as acting as a second messenger, and on sulfhydryl groups, which are the direct targets of the oxidant signal. Cysteine residues of some proteins, therefore, act as sensors of redox conditions and are oxidized in a reversible reaction. In particular, the formation of sulfenic acid and disulfide, the initial steps of thiol oxidation, are described in detail. The many cell pathways involved in reactive oxygen species formation are reported. Central to redox signaling processes are the glutathione and thioredoxin systems controlling H(2)O(2) levels and, hence, the thiol/disulfide balance. Lastly, some of the most important redox-regulated processes involving specific enzymes and organelles are described. The redox signaling area of research is rapidly expanding, and future work will examine new pathways and clarify their importance in cellular pathophysiology.

  9. Redox regulation of cancer metastasis: molecular signaling and therapeutic opportunities.

    Science.gov (United States)

    Yang, Wenyong; Zou, Linzhi; Huang, Canhua; Lei, Yunlong

    2014-08-01

    Cancer metastasis is the major cause of cancer-related mortality. Accumulated evidence has shown that high-metastasis potential cancer cells have more reactive oxygen species (ROS) accumulation compared with low-metastasis potential cancer cells. ROS can function as second messengers to regulate multiple cancer metastasis-related signaling pathways via reversible oxidative posttranslational modifications of cysteine in key redox-sensitive proteins, which leads to the structural and functional change of these proteins. Because ROS can promote cancer metastasis, therapeutic strategies aiming at inducing/reducing cellular ROS level or targeting redox sensors involved in metastasis hold great potential in developing new efficient approaches for anticancer therapy. In this review, we summarize recent findings on regulation of tumor metastasis by key redox sensors and describe the potential of targeting redox signaling pathways for cancer therapy.

  10. Mouse models for preeclampsia: disruption of redox-regulated signaling

    Directory of Open Access Journals (Sweden)

    Chambers Anne E

    2009-01-01

    Full Text Available Abstract The concept that oxidative stress contributes to the development of human preeclampsia has never been tested in genetically-defined animal models. Homozygous deletion of catechol-O-methyl transferase (Comt-/- in pregnant mice leads to human preeclampsia-like symptoms (high blood pressure, albuminurea and preterm birth resulting from extensive vasculo-endothelial pathology, primarily at the utero-fetal interface where maternal cardiac output is dramatically increased during pregnancy. Comt converts estradiol to 2-methoxyestradiol 2 (2ME2 which counters angiogenesis by depleting hypoxia inducible factor-1 alpha (HIF-1 alpha at late pregnancy. We propose that in wild type (Comt++ pregnant mice, 2ME2 destabilizes HIF-1 alpha by inhibiting mitochondrial superoxide dismutase (MnSOD. Thus, 2ME2 acts as a pro-oxidant, disrupting redox-regulated signaling which blocks angiogenesis in wild type (WT animals in physiological pregnancy. Further, we suggest that a lack of this inhibition under normoxic conditions in mutant animals (Comt-/- stabilises HIF-1 alpha by inactivating prolyl hydroxlases (PHD. We predict that a lack of inhibition of MnSOD, leading to persistent accumulation of HIF-1 alpha, would trigger inflammatory infiltration and endothelial damage in mutant animals. Critical tests of this hypothesis would be to recreate preeclampsia symptoms by inducing oxidative stress in WT animals or to ameliorate by treating mutant mice with Mn-SOD-catalase mimetics or activators of PHD.

  11. Modulation of the matrix redox signaling by mitochondrial Ca(2.).

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    Santo-Domingo, Jaime; Wiederkehr, Andreas; De Marchi, Umberto

    2015-11-26

    Mitochondria sense, shape and integrate signals, and thus function as central players in cellular signal transduction. Ca(2+) waves and redox reactions are two such intracellular signals modulated by mitochondria. Mitochondrial Ca(2+) transport is of utmost physio-pathological relevance with a strong impact on metabolism and cell fate. Despite its importance, the molecular nature of the proteins involved in mitochondrial Ca(2+) transport has been revealed only recently. Mitochondrial Ca(2+) promotes energy metabolism through the activation of matrix dehydrogenases and down-stream stimulation of the respiratory chain. These changes also alter the mitochondrial NAD(P)H/NAD(P)(+) ratio, but at the same time will increase reactive oxygen species (ROS) production. Reducing equivalents and ROS are having opposite effects on the mitochondrial redox state, which are hard to dissect. With the recent development of genetically encoded mitochondrial-targeted redox-sensitive sensors, real-time monitoring of matrix thiol redox dynamics has become possible. The discoveries of the molecular nature of mitochondrial transporters of Ca(2+) combined with the utilization of the novel redox sensors is shedding light on the complex relation between mitochondrial Ca(2+) and redox signals and their impact on cell function. In this review, we describe mitochondrial Ca(2+) handling, focusing on a number of newly identified proteins involved in mitochondrial Ca(2+) uptake and release. We further discuss our recent findings, revealing how mitochondrial Ca(2+) influences the matrix redox state. As a result, mitochondrial Ca(2+) is able to modulate the many mitochondrial redox-regulated processes linked to normal physiology and disease.

  12. ROS-mediated redox signaling during cell differentiation in plants.

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    Schmidt, Romy; Schippers, Jos H M

    2015-08-01

    Reactive oxygen species (ROS) have emerged in recent years as important regulators of cell division and differentiation. The cellular redox state has a major impact on cell fate and multicellular organism development. However, the exact molecular mechanisms through which ROS manifest their regulation over cellular development are only starting to be understood in plants. ROS levels are constantly monitored and any change in the redox pool is rapidly sensed and responded upon. Different types of ROS cause specific oxidative modifications, providing the basic characteristics of a signaling molecule. Here we provide an overview of ROS sensors and signaling cascades that regulate transcriptional responses in plants to guide cellular differentiation and organ development. Although several redox sensors and cascades have been identified, they represent only a first glimpse on the impact that redox signaling has on plant development and growth. We provide an initial evaluation of ROS signaling cascades involved in cell differentiation in plants and identify potential avenues for future studies. This article is part of a Special Issue entitled Redox regulation of differentiation and de-differentiation. Copyright © 2015 Elsevier B.V. All rights reserved.

  13. Modulation of the matrix redox signaling by mitochondrial Ca2+

    Institute of Scientific and Technical Information of China (English)

    Jaime; Santo-Domingo; Andreas; Wiederkehr; Umberto; De; Marchi

    2015-01-01

    Mitochondria sense,shape and integrate signals,and thus function as central players in cellular signal transduction. Ca2+ waves and redox reactions are two such intracellular signals modulated by mitochondria. Mitochondrial Ca2+ transport is of utmost physio-pathological relevance with a strong impact on metabolism and cell fate. Despite its importance,the molecular nature of the proteins involvedin mitochondrial Ca2+ transport has been revealed only recently. Mitochondrial Ca2+ promotes energy metabolism through the activation of matrix dehydrogenases and downstream stimulation of the respiratory chain. These changes also alter the mitochondrial NAD(P)H/NAD(P)+ ratio,but at the same time will increase reactive oxygen species(ROS) production. Reducing equivalents and ROS are having opposite effects on the mitochondrial redox state,which are hard to dissect. With the recent development of genetically encoded mitochondrial-targeted redoxsensitive sensors,real-time monitoring of matrix thiol redox dynamics has become possible. The discoveries of the molecular nature of mitochondrial transporters of Ca2+ combined with the utilization of the novel redox sensors is shedding light on the complex relation between mitochondrial Ca2+ and redox signals and their impact on cell function. In this review,we describe mitochondrial Ca2+ handling,focusing on a number of newly identified proteins involved in mitochondrial Ca2+ uptake and release. We further discuss our recent findings,revealing how mitochondrial Ca2+ influences the matrix redox state. As a result,mitochondrial Ca2+ is able to modulate the many mitochondrial redox-regulated processes linked to normal physiology and disease.

  14. Large-signal stability analysis of PWM converters

    Energy Technology Data Exchange (ETDEWEB)

    Huynh, P.T. [Philips Labs., Briarcliff Manor, NY (United States); Cho, B.H. [Seoul National Univ. (Korea, Republic of). Dept. of Electrical Engineering

    1995-12-31

    Investigation of the effects of existing nonlinearities on the stability of PWM converters is performed. The bilinear structure, the duty cycle saturation, and the opamp saturation are the principal nonlinearities in PWM converters. These nonlinearities are incorporated in the large-signal analytical models of PWM converters, and the basic input-output stability theory is applied to analyze their stability. Design and optimization of the small-signal loop gains to counteract the undesirable nonlinear effects are also discussed.

  15. Exercise and Glycemic Control: Focus on Redox Homeostasis and Redox-Sensitive Protein Signaling

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    Parker, Lewan; Shaw, Christopher S.; Stepto, Nigel K.; Levinger, Itamar

    2017-01-01

    Physical inactivity, excess energy consumption, and obesity are associated with elevated systemic oxidative stress and the sustained activation of redox-sensitive stress-activated protein kinase (SAPK) and mitogen-activated protein kinase signaling pathways. Sustained SAPK activation leads to aberrant insulin signaling, impaired glycemic control, and the development and progression of cardiometabolic disease. Paradoxically, acute exercise transiently increases oxidative stress and SAPK signaling, yet postexercise glycemic control and skeletal muscle function are enhanced. Furthermore, regular exercise leads to the upregulation of antioxidant defense, which likely assists in the mitigation of chronic oxidative stress-associated disease. In this review, we explore the complex spatiotemporal interplay between exercise, oxidative stress, and glycemic control, and highlight exercise-induced reactive oxygen species and redox-sensitive protein signaling as important regulators of glucose homeostasis. PMID:28529499

  16. Redox-dependent regulation of epidermal growth factor receptor signaling

    Directory of Open Access Journals (Sweden)

    David E. Heppner

    2016-08-01

    Full Text Available Tyrosine phosphorylation-dependent cell signaling represents a unique feature of multicellular organisms, and is important in regulation of cell differentiation and specialized cell functions. Multicellular organisms also contain a diverse family of NADPH oxidases (NOXs that have been closely linked with tyrosine kinase-based cell signaling and regulate tyrosine phosphorylation via reversible oxidation of cysteine residues that are highly conserved within many proteins involved in this signaling pathway. An example of redox-regulated tyrosine kinase signaling involves the epidermal growth factor receptor (EGFR, a widely studied receptor system with diverse functions in normal cell biology as well as pathologies associated with oxidative stress such as cancer. The purpose of this Graphical Redox Review is to highlight recently emerged concepts with respect to NOX-dependent regulation of this important signaling pathway.

  17. Are free radicals involved in thiol-based redox signaling?

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    Winterbourn, Christine C

    2015-03-01

    Cells respond to many stimuli by transmitting signals through redox-regulated pathways. It is generally accepted that in many instances signal transduction is via reversible oxidation of thiol proteins, although there is uncertainty about the specific redox transformations involved. The prevailing view is that thiol oxidation occurs by a two electron mechanism, most commonly involving hydrogen peroxide. Free radicals, on the other hand, are considered as damaging species and not generally regarded as important in cell signaling. This paper examines whether it is justified to dismiss radicals or whether they could have a signaling role. Although there is no direct evidence that radicals are involved in transmitting thiol-based redox signals, evidence is presented that they are generated in cells when these signaling pathways are activated. Radicals produce the same thiol oxidation products as two electron oxidants, although by a different mechanism, and at this point radical-mediated pathways should not be dismissed. There are unresolved issues about how radical mechanisms could achieve sufficient selectivity, but this could be possible through colocalization of radical-generating and signal-transducing proteins. Colocalization is also likely to be important for nonradical signaling mechanisms and identification of such associations should be a priority for advancing the field.

  18. Protein cysteine oxidation in redox signaling

    DEFF Research Database (Denmark)

    Forman, Henry Jay; Davies, Michael J; Krämer, Anna C

    2017-01-01

    . Previous studies have claimed that RSOH can be detected as an adduct (e.g., with 5,5-dimethylcyclohexane-1,3-dione; dimedone). Here, kinetic data are discussed which indicate that few proteins can form RSOH under physiological signaling conditions. We also present experimental evidence that indicates......Oxidation of critical signaling protein cysteines regulated by H2O2 has been considered to involve sulfenic acid (RSOH) formation. RSOH may subsequently form either a sulfenyl amide (RSNHR') with a neighboring amide, or a mixed disulfide (RSSR') with another protein cysteine or glutathione...

  19. LARGE SIGNAL DISCRETE-TIME MODEL FOR PARALLELED BUCK CONVERTERS

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    As a number of switch-combinations are involved in operation of multi-converter-system, conventional methods for obtaining discrete-time large signal model of these converter systems result in a very complex solution. A simple sampled-data technique for modeling distributed dc-dc PWM converters system (DCS) was proposed. The resulting model is nonlinear and can be linearized for analysis and design of DCS. These models are also suitable for fast simulation of these networks. As the input and output of dc-dc converters are slow varying, suitable model for DCS was obtained in terms of the finite order input/output approximation.

  20. Cellular metabolic and autophagic pathways: traffic control by redox signaling.

    Science.gov (United States)

    Dodson, Matthew; Darley-Usmar, Victor; Zhang, Jianhua

    2013-10-01

    It has been established that the key metabolic pathways of glycolysis and oxidative phosphorylation are intimately related to redox biology through control of cell signaling. Under physiological conditions glucose metabolism is linked to control of the NADH/NAD redox couple, as well as providing the major reductant, NADPH, for thiol-dependent antioxidant defenses. Retrograde signaling from the mitochondrion to the nucleus or cytosol controls cell growth and differentiation. Under pathological conditions mitochondria are targets for reactive oxygen and nitrogen species and are critical in controlling apoptotic cell death. At the interface of these metabolic pathways, the autophagy-lysosomal pathway functions to maintain mitochondrial quality and generally serves an important cytoprotective function. In this review we will discuss the autophagic response to reactive oxygen and nitrogen species that are generated from perturbations of cellular glucose metabolism and bioenergetic function.

  1. S-Glutathionylation and Redox Protein Signaling in Drug Addiction.

    Science.gov (United States)

    Womersley, Jacqueline S; Uys, Joachim D

    2016-01-01

    Drug addiction is a chronic relapsing disorder that comes at a high cost to individuals and society. Therefore understanding the mechanisms by which drugs exert their effects is of prime importance. Drugs of abuse increase the production of reactive oxygen and nitrogen species resulting in oxidative stress. This change in redox homeostasis increases the conjugation of glutathione to protein cysteine residues; a process called S-glutathionylation. Although traditionally regarded as a protective mechanism against irreversible protein oxidation, accumulated evidence suggests a more nuanced role for S-glutathionylation, namely as a mediator in redox-sensitive protein signaling. The reversible modification of protein thiols leading to alteration in function under different physiologic/pathologic conditions provides a mechanism whereby change in redox status can be translated into a functional response. As such, S-glutathionylation represents an understudied means of post-translational protein modification that may be important in the mechanisms underlying drug addiction. This review will discuss the evidence for S-glutathionylation as a redox-sensing mechanism and how this may be involved in the response to drug-induced oxidative stress. The function of S-glutathionylated proteins involved in neurotransmission, dendritic spine structure, and drug-induced behavioral outputs will be reviewed with specific reference to alcohol, cocaine, and heroin. Copyright © 2016. Published by Elsevier Inc.

  2. Role of Redox Signaling in Neuroinflammation and Neurodegenerative Diseases

    Directory of Open Access Journals (Sweden)

    Hsi-Lung Hsieh

    2013-01-01

    Full Text Available Reactive oxygen species (ROS, a redox signal, are produced by various enzymatic reactions and chemical processes, which are essential for many physiological functions and act as second messengers. However, accumulating evidence has implicated the pathogenesis of several human diseases including neurodegenerative disorders related to increased oxidative stress. Under pathological conditions, increasing ROS production can regulate the expression of diverse inflammatory mediators during brain injury. Elevated levels of several proinflammatory factors including cytokines, peptides, pathogenic structures, and peroxidants in the central nervous system (CNS have been detected in patients with neurodegenerative diseases such as Alzheimer’s disease (AD. These proinflammatory factors act as potent stimuli in brain inflammation through upregulation of diverse inflammatory genes, including matrix metalloproteinases (MMPs, cytosolic phospholipase A2 (cPLA2, cyclooxygenase-2 (COX-2, and adhesion molecules. To date, the intracellular signaling mechanisms underlying the expression of target proteins regulated by these factors are elusive. In this review, we discuss the mechanisms underlying the intracellular signaling pathways, especially ROS, involved in the expression of several inflammatory proteins induced by proinflammatory factors in brain resident cells. Understanding redox signaling transduction mechanisms involved in the expression of target proteins and genes may provide useful therapeutic strategies for brain injury, inflammation, and neurodegenerative diseases.

  3. Cysteine-based redox regulation and signaling in plants.

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    Couturier, Jérémy; Chibani, Kamel; Jacquot, Jean-Pierre; Rouhier, Nicolas

    2013-01-01

    Living organisms are subjected to oxidative stress conditions which are characterized by the production of reactive oxygen, nitrogen, and sulfur species. In plants as in other organisms, many of these compounds have a dual function as they damage different types of macromolecules but they also likely fulfil an important role as secondary messengers. Owing to the reactivity of their thiol groups, some protein cysteine residues are particularly prone to oxidation by these molecules. In the past years, besides their recognized catalytic and regulatory functions, the modification of cysteine thiol group was increasingly viewed as either protective or redox signaling mechanisms. The most physiologically relevant reversible redox post-translational modifications (PTMs) are disulfide bonds, sulfenic acids, S-glutathione adducts, S-nitrosothiols and to a lesser extent S-sulfenyl-amides, thiosulfinates and S-persulfides. These redox PTMs are mostly controlled by two oxidoreductase families, thioredoxins and glutaredoxins. This review focuses on recent advances highlighting the variety and physiological roles of these PTMs and the proteomic strategies used for their detection.

  4. Cysteine-based redox regulation and signalling in plants

    Directory of Open Access Journals (Sweden)

    Jérémy eCouturier

    2013-04-01

    Full Text Available Living organisms are subjected to oxidative stress conditions which are characterized by the production of reactive oxygen (ROS, nitrogen (RNS and sulfur (RSS species. In plants as in other organisms, many of these compounds have a dual function as they damage different types of macromolecules but they also likely fulfil an important role as secondary messengers. Owing to the reactivity of their thiol groups, some protein cysteine residues are particularly prone to oxidation by these molecules. In the past years, besides their recognized catalytic and regulatory functions, the modification of cysteine thiol group was increasingly viewed as either protective or redox signalling mechanisms. The most physiologically relevant reversible redox post-translational modifications (PTMs are disulfide bonds, sulfenic acids, S-glutathionylated adducts, S-nitrosothiols and to a lesser extent S-sulfenylamides, thiosulfinates and S-persulfides. These redox PTMs are mostly controlled by two oxidoreductase families, thioredoxins and glutaredoxins. This review focuses on recent advances highlighting the variety and physiological roles of these PTMs and the proteomic strategies used for their detection.

  5. Small signal frequency domain model of an HVDC converter

    Energy Technology Data Exchange (ETDEWEB)

    Osauskas, C.M.; Hume, D.J.; Wood, A.R. [UnIversity of Canterbury, Christchurch (New Zealand). Dept. of Electrical and Electronic Engineering

    2001-11-01

    A small-signal analytic frequency domain model of a 6-pulse HVDC converter is presented. The model consists of a set of explicit algebraic equations which relate the transfer of distortion from AC voltage, DC current and firing angle modulation, to AC current and DC voltage. The equations represent the linearisation of the transfers around a base operating point, and are derived from a piecewise linear description of the AC current and DC voltage waveforms. The model provides an understanding of the transfer of distortion by the converter and is in excellent agreement with time domain simulations. (author)

  6. Monitoring Wind Turbine Loading Using Power Converter Signals

    Science.gov (United States)

    Rieg, C. A.; Smith, C. J.; Crabtree, C. J.

    2016-09-01

    The ability to detect faults and predict loads on a wind turbine drivetrain's mechanical components cost-effectively is critical to making the cost of wind energy competitive. In order to investigate whether this is possible using the readily available power converter current signals, an existing permanent magnet synchronous generator based wind energy conversion system computer model was modified to include a grid-side converter (GSC) for an improved converter model and a gearbox. The GSC maintains a constant DC link voltage via vector control. The gearbox was modelled as a 3-mass model to allow faults to be included. Gusts and gearbox faults were introduced to investigate the ability of the machine side converter (MSC) current (I q) to detect and quantify loads on the mechanical components. In this model, gearbox faults were not detectable in the I q signal due to shaft stiffness and damping interaction. However, a model that predicts the load change on mechanical wind turbine components using I q was developed and verified using synthetic and real wind data.

  7. Mitochondrial redox and pH signaling occurs in axonal and synaptic organelle clusters.

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    Breckwoldt, Michael O; Armoundas, Antonis A; Aon, Miguel A; Bendszus, Martin; O'Rourke, Brian; Schwarzländer, Markus; Dick, Tobias P; Kurz, Felix T

    2016-03-22

    Redox switches are important mediators in neoplastic, cardiovascular and neurological disorders. We recently identified spontaneous redox signals in neurons at the single mitochondrion level where transients of glutathione oxidation go along with shortening and re-elongation of the organelle. We now have developed advanced image and signal-processing methods to re-assess and extend previously obtained data. Here we analyze redox and pH signals of entire mitochondrial populations. In total, we quantified the effects of 628 redox and pH events in 1797 mitochondria from intercostal axons and neuromuscular synapses using optical sensors (mito-Grx1-roGFP2; mito-SypHer). We show that neuronal mitochondria can undergo multiple redox cycles exhibiting markedly different signal characteristics compared to single redox events. Redox and pH events occur more often in mitochondrial clusters (medium cluster size: 34.1 ± 4.8 μm(2)). Local clusters possess higher mitochondrial densities than the rest of the axon, suggesting morphological and functional inter-mitochondrial coupling. We find that cluster formation is redox sensitive and can be blocked by the antioxidant MitoQ. In a nerve crush paradigm, mitochondrial clusters form sequentially adjacent to the lesion site and oxidation spreads between mitochondria. Our methodology combines optical bioenergetics and advanced signal processing and allows quantitative assessment of entire mitochondrial populations.

  8. The basic chemistry of exercise-induced DNA oxidation: oxidative damage, redox signalling and their interplay

    Directory of Open Access Journals (Sweden)

    James Nathan Cobley

    2015-06-01

    Full Text Available Acute exercise increases reactive oxygen and nitrogen species generation. This phenomenon is associated with two major outcomes: (1 redox signalling and (2 macromolecule damage. Mechanistic knowledge of how exercise-induced redox signalling and macromolecule damage are interlinked is limited. This review focuses on the interplay between exercise-induced redox signalling and DNA damage, using hydroxyl radical (·OH and hydrogen peroxide (H2O2 as exemplars. It is postulated that the biological fate of H2O2 links the two processes and thus represents a bifurcation point between redox signalling and damage. Indeed, H2O2 can participate in two electron signalling reactions but its diffusion and chemical properties permit DNA oxidation following reaction with transition metals and ·OH generation. It is also considered that the sensing of DNA oxidation by repair proteins constitutes a non-canonical redox signalling mechanism. Further layers of interaction are provided by the redox regulation of DNA repair proteins and their capacity to modulate intracellular H2O2 levels. Overall, exercise-induced redox signalling and DNA damage may be interlinked to a greater extent than was previously thought but this requires further investigation.

  9. Thiol Redox Transitions in Cell Signaling: a Lesson from N-Acetylcysteine

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    Tiziana Parasassi

    2010-01-01

    Full Text Available The functional status of cells is under the control of external stimuli affecting the function of critical proteins and eventually gene expression. Signal sensing and transduction by messengers to specific effectors operate by post-translational modification of proteins, among which thiol redox switches play a fundamental role that is just beginning to be understood. The maintenance of the redox status is, indeed, crucial for cellular homeostasis and its dysregulation towards a more oxidized intracellular environment is associated with aberrant proliferation, ultimately related to diseases such as cancer, cardiovascular disease, and diabetes. Redox transitions occur in sensitive cysteine residues of regulatory proteins relevant to signaling, their evolution to metastable disulfides accounting for the functional redox switch. N-acetylcysteine (NAC is a thiol-containing compound that is able to interfere with redox transitions of thiols and, thus, in principle, able to modulate redox signaling. We here review the redox chemistry of NAC, then screen possible mechanisms to explain the effects observed in NAC-treated normal and cancer cells; such effects involve a modification of global gene expression, thus of functions and morphology, with a leitmotif of a switch from proliferation to terminal differentiation. The regulation of thiol redox transitions in cell signaling is, therefore, proposed as a new tool, holding promise not only for a deeper explanation of mechanisms, but indeed for innovative pharmacological interventions.

  10. Signaling of Escherichia coli enterotoxin on supramolecular redox bilayer vesicles

    Energy Technology Data Exchange (ETDEWEB)

    Cheng, Q.; Peng, T.; Stevens, R.C.

    1999-07-21

    Electron transport in supramolecular assemblies containing redox centers has been a subject of great interest. Depending on spatial arrangement of redox moieties in macromolecular structures, transport of electrons may occur via a diffusion mechanism or electron hopping between the neighboring redox sites. While research has largely dealt with 3-D redox polymers, some 2-D systems such as self-assembled and Langmuir-Blodgett monolayers have been exploited as well. The authors describe here a new interfacial architecture that combines the high redox concentration in 3-D polymers and controllable structure and functionality of the 2-D monolayer systems. The new interface utilizes structurally defined redox liposomes engineered with biomolecular recognition capability by incorporating cell surface receptor G{sub M1} into the bilayer membrane. The design allows for direct inspection of the dependency of electron transport on the state and extent of biomolecular recognition that has taken place on the vesicles and, thus, provides a method for direct measurement of E. coli heat-labile enterotoxin binding by electrochemistry.

  11. A redox signalling globin is essential for reproduction in Caenorhabditis elegans

    Science.gov (United States)

    de Henau, Sasha; Tilleman, Lesley; Vangheel, Matthew; Luyckx, Evi; Trashin, Stanislav; Pauwels, Martje; Germani, Francesca; Vlaeminck, Caroline; Vanfleteren, Jacques R.; Bert, Wim; Pesce, Alessandra; Nardini, Marco; Bolognesi, Martino; de Wael, Karolien; Moens, Luc; Dewilde, Sylvia; Braeckman, Bart P.

    2015-12-01

    Moderate levels of reactive oxygen species (ROS) are now recognized as redox signalling molecules. However, thus far, only mitochondria and NADPH oxidases have been identified as cellular sources of ROS in signalling. Here we identify a globin (GLB-12) that produces superoxide, a type of ROS, which serves as an essential signal for reproduction in C. elegans. We find that GLB-12 has an important role in the regulation of multiple aspects in germline development, including germ cell apoptosis. We further describe how GLB-12 displays specific molecular, biochemical and structural properties that allow this globin to act as a superoxide generator. In addition, both an intra- and extracellular superoxide dismutase act as key partners of GLB-12 to create a transmembrane redox signal. Our results show that a globin can function as a driving factor in redox signalling, and how this signal is regulated at the subcellular level by multiple control layers.

  12. A redox signalling globin is essential for reproduction in Caenorhabditis elegans.

    Science.gov (United States)

    De Henau, Sasha; Tilleman, Lesley; Vangheel, Matthew; Luyckx, Evi; Trashin, Stanislav; Pauwels, Martje; Germani, Francesca; Vlaeminck, Caroline; Vanfleteren, Jacques R; Bert, Wim; Pesce, Alessandra; Nardini, Marco; Bolognesi, Martino; De Wael, Karolien; Moens, Luc; Dewilde, Sylvia; Braeckman, Bart P

    2015-12-01

    Moderate levels of reactive oxygen species (ROS) are now recognized as redox signalling molecules. However, thus far, only mitochondria and NADPH oxidases have been identified as cellular sources of ROS in signalling. Here we identify a globin (GLB-12) that produces superoxide, a type of ROS, which serves as an essential signal for reproduction in C. elegans. We find that GLB-12 has an important role in the regulation of multiple aspects in germline development, including germ cell apoptosis. We further describe how GLB-12 displays specific molecular, biochemical and structural properties that allow this globin to act as a superoxide generator. In addition, both an intra- and extracellular superoxide dismutase act as key partners of GLB-12 to create a transmembrane redox signal. Our results show that a globin can function as a driving factor in redox signalling, and how this signal is regulated at the subcellular level by multiple control layers.

  13. H(2)S signaling in redox regulation of cellular functions.

    Science.gov (United States)

    Ju, Youngjun; Zhang, Weihua; Pei, Yanxi; Yang, Guangdong

    2013-01-01

    Hydrogen sulfide (H(2)S) is traditionally recognized as a toxic gas with a rotten-egg smell. In just the last few decades, H(2)S has been found to be one of a family of gasotransmitters, together with nitric oxide and carbon monoxide, and various physiologic effects of H(2)S have been reported. Among the most acknowledged molecular mechanisms for the cellular effects of H(2)S is the regulation of intracellular redox homeostasis and post-translational modification of proteins through S-sulfhydration. On the one side, H(2)S can promote an antioxidant effect and is cytoprotective; on the other side, H(2)S stimulates oxidative stress and is cytotoxic. This review summarizes our current knowledge of the antioxidant versus pro-oxidant effects of H(2)S in mammalian cells and describes the Janus-faced properties of this novel gasotransmitter. The redox regulation for the cellular effects of H(2)S through S-sulfhydration and the role of H(2)S in glutathione generation is also recapitulated. A better understanding of H(2)S-regualted redox homeostasis will pave the way for future design of novel pharmacological and therapeutic interventions for various diseases.

  14. Crosstalk of Signaling and Metabolism Mediated by the NAD(+)/NADH Redox State in Brain Cells.

    Science.gov (United States)

    Winkler, Ulrike; Hirrlinger, Johannes

    2015-12-01

    The energy metabolism of the brain has to be precisely adjusted to activity to cope with the organ's energy demand, implying that signaling regulates metabolism and metabolic states feedback to signaling. The NAD(+)/NADH redox state constitutes a metabolic node well suited for integration of metabolic and signaling events. It is affected by flux through metabolic pathways within a cell, but also by the metabolic state of neighboring cells, for example by lactate transferred between cells. Furthermore, signaling events both in neurons and astrocytes have been reported to change the NAD(+)/NADH redox state. Vice versa, a number of signaling events like astroglial Ca(2+) signals, neuronal NMDA-receptors as well as the activity of transcription factors are modulated by the NAD(+)/NADH redox state. In this short review, this bidirectional interdependence of signaling and metabolism involving the NAD(+)/NADH redox state as well as its potential relevance for the physiology of the brain and the whole organism in respect to blood glucose regulation and body weight control are discussed.

  15. Early redox, Src family kinase, and calcium signaling integrate wound responses and tissue regeneration in zebrafish.

    Science.gov (United States)

    Yoo, Sa Kan; Freisinger, Christina M; LeBert, Danny C; Huttenlocher, Anna

    2012-10-15

    Tissue injury can lead to scar formation or tissue regeneration. How regenerative animals sense initial tissue injury and transform wound signals into regenerative growth is an unresolved question. Previously, we found that the Src family kinase (SFK) Lyn functions as a redox sensor in leukocytes that detects H(2)O(2) at wounds in zebrafish larvae. In this paper, using zebrafish larval tail fins as a model, we find that wounding rapidly activated SFK and calcium signaling in epithelia. The immediate SFK and calcium signaling in epithelia was important for late epimorphic regeneration of amputated fins. Wound-induced activation of SFKs in epithelia was dependent on injury-generated H(2)O(2). A SFK member, Fynb, was responsible for fin regeneration. This work provides a new link between early wound responses and late regeneration and suggests that redox, SFK, and calcium signaling are immediate "wound signals" that integrate early wound responses and late epimorphic regeneration.

  16. Lipoic acid: energy metabolism and redox regulation of transcription and cell signaling.

    Science.gov (United States)

    Packer, Lester; Cadenas, Enrique

    2011-01-01

    The role of R-α-lipoic acid as a cofactor (lipoyllysine) in mitochondrial energy metabolism is well established. Lipoic acid non-covalently bound and exogenously administered to cells or supplemented in the diet is a potent modulator of the cell's redox status. The diversity of beneficial effects of lipoic acid in a variety of tissues can be mechanistically viewed in terms of thiol/disulfide exchange reactions that modulate the environment's redox and energy status. Lipoic acid-driven thiol/disulfide exchange reactions appear critical for the modulation of proteins involved in cell signaling and transcription factors. This review emphasizes the effects of lipoic acid on PI3K and AMPK signaling and related transcriptional pathways that are integrated by PGC-1α, a critical regulator of energy homoestasis. The effects of lipoic acid on the neuronal energy-redox axis are largely reviewed in terms of their outcomes for aging and age-related neurodegenerative diseases.

  17. Protein S-glutathionlyation links energy metabolism to redox signaling in mitochondria

    Directory of Open Access Journals (Sweden)

    Ryan J. Mailloux

    2016-08-01

    Full Text Available At its core mitochondrial function relies on redox reactions. Electrons stripped from nutrients are used to form NADH and NADPH, electron carriers that are similar in structure but support different functions. NADH supports ATP production but also generates reactive oxygen species (ROS, superoxide (O2·- and hydrogen peroxide (H2O2. NADH-driven ROS production is counterbalanced by NADPH which maintains antioxidants in an active state. Mitochondria rely on a redox buffering network composed of reduced glutathione (GSH and peroxiredoxins (Prx to quench ROS generated by nutrient metabolism. As H2O2 is quenched, NADPH is expended to reactivate antioxidant networks and reset the redox environment. Thus, the mitochondrial redox environment is in a constant state of flux reflecting changes in nutrient and ROS metabolism. Changes in redox environment can modulate protein function through oxidation of protein cysteine thiols. Typically cysteine oxidation is considered to be mediated by H2O2 which oxidizes protein thiols (SH forming sulfenic acid (SOH. However, problems begin to emerge when one critically evaluates the regulatory function of SOH. Indeed SOH formation is slow, non-specific, and once formed SOH reacts rapidly with a variety of molecules. By contrast, protein S-glutathionylation (PGlu reactions involve the conjugation and removal of glutathione moieties from modifiable cysteine residues. PGlu reactions are driven by fluctuations in the availability of GSH and oxidized glutathione (GSSG and thus should be exquisitely sensitive to changes ROS flux due to shifts in the glutathione pool in response to varying H2O2 availability. Here, we propose that energy metabolism-linked redox signals originating from mitochondria are mediated indirectly by H2O2 through the GSH redox buffering network in and outside mitochondria. This proposal is based on several observations that have shown that unlike other redox modifications PGlu reactions fulfill the

  18. Evolutionary Acquisition of Cysteines determines FOXO Paralog-Specific Redox Signaling

    NARCIS (Netherlands)

    Putker, Marrit; Vos, Harmjan; van Dorenmalen, Kim; de Ruiter, Hesther; Duran, Ana G; Snel, Berend; Burgering, Boudewijn Marius; Vermeulen, Michiel; Dansen, T B

    2015-01-01

    Reduction-oxidation (redox) signaling, the translation of an oxidative intracellular environment into a cellular response, is mediated by the reversible oxidation of specific cysteine thiols. The latter can result in disulfide formation between protein hetero- or homodimers that alter protein functi

  19. Evolutionary acquisition of cysteines determines FOXO paralog-specific redox signaling

    NARCIS (Netherlands)

    Putker, Marrit; Vos, HR; Van Dorenmalen, Kim; De Ruiter, Hesther; Duran, Ana G.; Snel, Berend; Burgering, Boudewijn M T; Vermeulen, M; Dansen, TB

    2015-01-01

    Reduction-oxidation (redox) signaling, the translation of an oxidative intracellular environment into a cellular response, is mediated by the reversible oxidation of specific cysteine thiols. The latter can result in disulfide formation between protein hetero- or homodimers that alter protein functi

  20. Control of a Vanadium Redox Battery and supercapacitor using a Three-Level Neutral Point Clamped converter

    Science.gov (United States)

    Etxeberria, A.; Vechiu, I.; Baudoin, S.; Camblong, H.; Kreckelbergh, S.

    2014-02-01

    The increasing use of distributed generators, which are mainly based on renewable sources, can create several issues in the operation of the electric grid. The microgrid is being analysed as a solution to the integration in the grid of the renewable sources at a high penetration level in a controlled way. The storage systems play a vital role in order to keep the energy and power balance of the microgrid. Due to the technical limitations of the currently available storage systems, it is necessary to use more than one storage technology to satisfy the requirements of the microgrid application. This work validates in simulations and experimentally the use of a Three-Level Neutral Point Clamped converter to control the power flow of a hybrid storage system formed by a SuperCapacitor and a Vanadium Redox Battery. The operation of the system is validated in two case studies in the experimental platform installed in ESTIA. The experimental results prove the validity of the proposed system as well as the designed control algorithm. The good agreement among experimental and simulation results also validates the simulation model, that can therefore be used to analyse the operation of the system in different case studies.

  1. Early redox, Src family kinase, and calcium signaling integrate wound responses and tissue regeneration in zebrafish

    OpenAIRE

    Yoo, Sa Kan; Freisinger, Christina M.; LeBert, Danny C.; Huttenlocher, Anna

    2012-01-01

    Tissue injury can lead to scar formation or tissue regeneration. How regenerative animals sense initial tissue injury and transform wound signals into regenerative growth is an unresolved question. Previously, we found that the Src family kinase (SFK) Lyn functions as a redox sensor in leukocytes that detects H2O2 at wounds in zebrafish larvae. In this paper, using zebrafish larval tail fins as a model, we find that wounding rapidly activated SFK and calcium signaling in epithelia. The immedi...

  2. Redox Signaling in Skeletal Muscle: Role of Aging and Exercise

    Science.gov (United States)

    Ji, Li Li

    2015-01-01

    Skeletal muscle contraction is associated with the production of ROS due to altered O[subscript 2] distribution and flux in the cell. Despite a highly efficient antioxidant defense, a small surplus of ROS, such as hydrogen peroxide and nitric oxide, may serve as signaling molecules to stimulate cellular adaptation to reach new homeostasis largely…

  3. Peroxiredoxin-2 and STAT3 form a redox relay for H2O2 signaling.

    Science.gov (United States)

    Sobotta, Mirko C; Liou, Willy; Stöcker, Sarah; Talwar, Deepti; Oehler, Michael; Ruppert, Thomas; Scharf, Annette N D; Dick, Tobias P

    2015-01-01

    Hydrogen peroxide (H(2)O(2)) acts as a signaling messenger by oxidatively modifying distinct cysteinyl thiols in distinct target proteins. However, it remains unclear how redox-regulated proteins, which often have low intrinsic reactivity towards H(2)O(2) (k(app) ∼1-10 M(-1) s(-1)), can be specifically and efficiently oxidized by H(2)O(2). Moreover, cellular thiol peroxidases, which are highly abundant and efficient H(2)O(2) scavengers, should effectively eliminate virtually all of the H(2)O(2) produced in the cell. Here, we show that the thiol peroxidase peroxiredoxin-2 (Prx2), one of the most H(2)O(2)-reactive proteins in the cell (k(app) ∼10(7)-10(8) M(-1) s(-1)), acts as a H(2)O(2) signal receptor and transmitter in transcription factor redox regulation. Prx2 forms a redox relay with the transcription factor STAT3 in which oxidative equivalents flow from Prx2 to STAT3. The redox relay generates disulfide-linked STAT3 oligomers with attenuated transcriptional activity. Cytokine-induced STAT3 signaling is accompanied by Prx2 and STAT3 oxidation and is modulated by Prx2 expression levels.

  4. Protein redox chemistry: post-translational cysteine modifications that regulate signal transduction and drug pharmacology

    Directory of Open Access Journals (Sweden)

    Revati eWani

    2014-10-01

    Full Text Available The perception of reactive oxygen species (ROS has evolved over the past decade from agents of cellular damage to secondary messengers which modify signaling proteins in physiology and the disease state (e.g. cancer. New protein targets of specific oxidation are rapidly being identified. One emerging class of redox modification occurs to the thiol side chain of cysteine residues which can produce multiple chemically-distinct alterations to the protein (e.g. sulfenic/sulfinic/sulfonic acid, disulfides. These post-translational modifications (PTM are shown to affect the protein structure and function. Because redox-sensitive proteins can traffic between subcellular compartments that have different redox environments, cysteine oxidation enables a spatio-temporal control to signaling. Understanding ramifications of these oxidative modifications to the functions of signaling proteins is crucial for understanding cellular regulation as well as for informed-drug discovery process. The effects of EGFR oxidation of Cys797 on inhibitor pharmacology are presented to illustrate the principle. Taken together, cysteine redox PTM can impact both cell biology and drug pharmacology.

  5. [Principles of design of neural-network analog-to-digital converters of bioelectric signals].

    Science.gov (United States)

    Loktiukhin, V N; Chelebaev, S V

    2007-01-01

    A design principle and a procedure for synthesis of neural-network analog-to-digital converters of bioelectric signals are suggested. An example of implementation of an FPGA-based neural-network converter for classification of bioparameters is presented.

  6. Redox Signaling as a Therapeutic Target to Inhibit Myofibroblast Activation in Degenerative Fibrotic Disease

    Directory of Open Access Journals (Sweden)

    Natalie Sampson

    2014-01-01

    Full Text Available Degenerative fibrotic diseases encompass numerous systemic and organ-specific disorders. Despite their associated significant morbidity and mortality, there is currently no effective antifibrotic treatment. Fibrosis is characterized by the development and persistence of myofibroblasts, whose unregulated deposition of extracellular matrix components disrupts signaling cascades and normal tissue architecture leading to organ failure and death. The profibrotic cytokine transforming growth factor beta (TGFβ is considered the foremost inducer of fibrosis, driving myofibroblast differentiation in diverse tissues. This review summarizes recent in vitro and in vivo data demonstrating that TGFβ-induced myofibroblast differentiation is driven by a prooxidant shift in redox homeostasis. Elevated NADPH oxidase 4 (NOX4-derived hydrogen peroxide (H2O2 supported by concomitant decreases in nitric oxide (NO signaling and reactive oxygen species scavengers are central factors in the molecular pathogenesis of fibrosis in numerous tissues and organs. Moreover, complex interplay between NOX4-derived H2O2 and NO signaling regulates myofibroblast differentiation. Restoring redox homeostasis via antioxidants or NOX4 inactivation as well as by enhancing NO signaling via activation of soluble guanylyl cyclases or inhibition of phosphodiesterases can inhibit and reverse myofibroblast differentiation. Thus, dysregulated redox signaling represents a potential therapeutic target for the treatment of wide variety of different degenerative fibrotic disorders.

  7. Redox signaling: Potential arbitrator of autophagy and apoptosis in therapeutic response.

    Science.gov (United States)

    Zhang, Lu; Wang, Kui; Lei, Yunlong; Li, Qifu; Nice, Edouard Collins; Huang, Canhua

    2015-12-01

    Redox signaling plays important roles in the regulation of cell death and survival in response to cancer therapy. Autophagy and apoptosis are discrete cellular processes mediated by distinct groups of regulatory and executioner molecules, and both are thought to be cellular responses to various stress conditions including oxidative stress, therefore controlling cell fate. Basic levels of reactive oxygen species (ROS) may function as signals to promote cell proliferation and survival, whereas increase of ROS can induce autophagy and apoptosis by damaging cellular components. Growing evidence in recent years argues for ROS that below detrimental levels acting as intracellular signal transducers that regulate autophagy and apoptosis. ROS-regulated autophagy and apoptosis can cross-talk with each other. However, how redox signaling determines different cell fates by regulating autophagy and apoptosis remains unclear. In this review, we will focus on understanding the delicate molecular mechanism by which autophagy and apoptosis are finely orchestrated by redox signaling and discuss how this understanding can be used to develop strategies for the treatment of cancer.

  8. Average and Small Signal Modeling of Negative-Output KY Boost Converter in CCM Operation

    Directory of Open Access Journals (Sweden)

    Faqiang Wang

    2014-01-01

    Full Text Available Negative-output KY Boost converter, which can obtain the negative output voltage and could be driven easily, is a good topology to overcome traditional Boost and Buck-Boost converters and it is believed that this converter will be widely used in engineering applications in the future. In this study, by using the averaging method and geometrical technique, the average and small signal model of the negative-output KY Boost converter are established. The DC equilibrium point and transfer functions of the system are derived and analyzed. Finally, the effectiveness of the established model and the correctness of the theoretical analysis are confirmed by the circuit experiment.

  9. Oversampling ad converters with improved signal transfer functions

    CERN Document Server

    Pandita, Bupesh

    2011-01-01

    This book describes techniques for designing complex, discrete-time I""IGBP ADCs with signal-transfer functions that significantly filter interfering signals. The book provides an understanding of theory, issues, and implementation of discrete complex I""IGBP ADCs. The concepts developed in each chapter are further explained by applying them to a target application of I""IGBP ADCs in DTV receivers.

  10. An appraisal of how the vitamin A-redox hypothesis can maintain honesty of carotenoid-dependent signals

    NARCIS (Netherlands)

    Simons, Mirre J. P.; Groothuis, Ton G. G.; Verhulst, Simon

    2015-01-01

    The vitamin A-redox hypothesis provides an explanation for honest signaling of phenotypic quality by carotenoid-dependent traits. A key aspect of the vitamin A-redox hypothesis, applicable to both yellow and red coloration, is the hypothesized negative feedback of tightly regulated Vitamin A plasma

  11. Electronic control of gene expression and cell behaviour in Escherichia coli through redox signalling

    Science.gov (United States)

    Tschirhart, Tanya; Kim, Eunkyoung; McKay, Ryan; Ueda, Hana; Wu, Hsuan-Chen; Pottash, Alex Eli; Zargar, Amin; Negrete, Alejandro; Shiloach, Joseph; Payne, Gregory F.; Bentley, William E.

    2017-01-01

    The ability to interconvert information between electronic and ionic modalities has transformed our ability to record and actuate biological function. Synthetic biology offers the potential to expand communication `bandwidth' by using biomolecules and providing electrochemical access to redox-based cell signals and behaviours. While engineered cells have transmitted molecular information to electronic devices, the potential for bidirectional communication stands largely untapped. Here we present a simple electrogenetic device that uses redox biomolecules to carry electronic information to engineered bacterial cells in order to control transcription from a simple synthetic gene circuit. Electronic actuation of the native transcriptional regulator SoxR and transcription from the PsoxS promoter allows cell response that is quick, reversible and dependent on the amplitude and frequency of the imposed electronic signals. Further, induction of bacterial motility and population based cell-to-cell communication demonstrates the versatility of our approach and potential to drive intricate biological behaviours.

  12. mtDNA Mutagenesis Disrupts Pluripotent Stem Cell Function by Altering Redox Signaling

    OpenAIRE

    Hämäläinen, Riikka H.; Ahlqvist, Kati J.; Ellonen, Pekka; Lepistö, Maija; Logan, Angela; Otonkoski, Timo; Murphy, Michael P.; Suomalainen, Anu

    2015-01-01

    Summary mtDNA mutagenesis in somatic stem cells leads to their dysfunction and to progeria in mouse. The mechanism was proposed to involve modification of reactive oxygen species (ROS)/redox signaling. We studied the effect of mtDNA mutagenesis on reprogramming and stemness of pluripotent stem cells (PSCs) and show that PSCs select against specific mtDNA mutations, mimicking germline and promoting mtDNA integrity despite their glycolytic metabolism. Furthermore, mtDNA mutagenesis is associate...

  13. S-Nitrosylation: NO-Related Redox Signaling to Protect Against Oxidative Stress

    OpenAIRE

    2006-01-01

    Nitric oxide (NO) plays an important role in the regulation of cardiovascular function. S-nitrosylation, the covalent attachment of an NO moiety to sulfhydryl residues of proteins, resulting in the formation of S-nitrosothiols (SNOs), is a prevalent posttranslational protein modification involved in redox-based cellular signaling. Under physiologic conditions, protein S>-nitrosylation and SNOs provide protection preventing further cellular oxidative and nitrosative stress. However, oxidative ...

  14. ENVIRONMENTAL TOXICITY, REDOX SIGNALING AND LUNG INFLAMMATION: THE ROLE OF GLUTATHIONE

    Science.gov (United States)

    Biswas, Saibal K; Rahman, Irfan

    2009-01-01

    Glutathione (γ-glutamyl-cysteinyl-glycine, GSH) is the most abundant intracellular antioxidant thiol and is central to redox defense during oxidative stress. GSH metabolism is tightly regulated and has been implicated in redox signaling and also in protection against environmental oxidant-mediated injury. Changes in the ratio of the reduced and disulfide form (GSH/GSSG) can affect signaling pathways that participate in a broad array of physiological responses from cell proliferation, autophagy and apoptosis to gene expression that involve H2O2 as a second messenger. Oxidative stress due to oxidant/antioxidant imbalance and also due to environmental oxidants is an important component during inflammation and respiratory diseases such as chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis, acute respiratory distress syndrome, and asthma. It is known to activate multiple stress kinase pathways and redox sensitive transcription factors such as Nrf2, NF-κB and AP-1, which differentially regulate the genes for pro-inflammatory cytokines as well as the protective antioxidant genes. Understanding the regulatory mechanisms for the induction of antioxidants, such as GSH, versus pro-inflammatory mediators at sites of oxidant-directed injuries may allow for the development of novel therapies which will allow pharmacological manipulation GSH synthesis during inflammation and oxidative injury. This article features the current knowledge about the role of GSH in redox signaling, GSH biosynthesis and particularly the regulation of transcription factor Nrf2 by GSH and downstream signaling during oxidative stress and inflammation in various pulmonary diseases. We also discussed the current therapeutic clinical trials using GSH and other thiol compounds, such as N-acetyl-L-cysteine, fudosteine, carbocysteine, erdosteine in environment-induced airways disease. PMID:18760298

  15. Discrete redox signaling pathways regulate photosynthetic light-harvesting and chloroplast gene transcription.

    Directory of Open Access Journals (Sweden)

    John F Allen

    Full Text Available In photosynthesis in chloroplasts, two related regulatory processes balance the actions of photosystems I and II. These processes are short-term, post-translational redistribution of light-harvesting capacity, and long-term adjustment of photosystem stoichiometry initiated by control of chloroplast DNA transcription. Both responses are initiated by changes in the redox state of the electron carrier, plastoquinone, which connects the two photosystems. Chloroplast Sensor Kinase (CSK is a regulator of transcription of chloroplast genes for reaction centres of the two photosystems, and a sensor of plastoquinone redox state. We asked whether CSK is also involved in regulation of absorbed light energy distribution by phosphorylation of light-harvesting complex II (LHC II. Chloroplast thylakoid membranes isolated from a CSK T-DNA insertion mutant and from wild-type Arabidopsis thaliana exhibit similar light- and redox-induced (32P-labelling of LHC II and changes in 77 K chlorophyll fluorescence emission spectra, while room-temperature chlorophyll fluorescence emission transients from Arabidopsis leaves are perturbed by inactivation of CSK. The results indicate indirect, pleiotropic effects of reaction centre gene transcription on regulation of photosynthetic light-harvesting in vivo. A single, direct redox signal is transmitted separately to discrete transcriptional and post-translational branches of an integrated cytoplasmic regulatory system.

  16. Plastid thioredoxins: a “one-for-all” redox-signaling system in plants

    Science.gov (United States)

    Serrato, Antonio J.; Fernández-Trijueque, Juan; Barajas-López, Juan-de-Dios; Chueca, Ana; Sahrawy, Mariam

    2013-01-01

    The sessile nature of plants forces them to face an ever-changing environment instead of escape from hostile conditions as animals do. In order to overcome this survival challenge, a fine monitoring and controlling of the status of the photosynthetic electron transport chain and the general metabolism is vital for these organisms. Frequently, evolutionary plant adaptation has consisted in the appearance of multigenic families, comprising an array of enzymes, structural components, or sensing, and signaling elements, in numerous occasions with highly conserved primary sequences that sometimes make it difficult to discern between redundancy and specificity among the members of a same family. However, all this gene diversity is aimed to sort environment-derived plant signals to efficiently channel the external incoming information inducing a right physiological answer. Oxygenic photosynthesis is a powerful source of reactive oxygen species (ROS), molecules with a dual oxidative/signaling nature. In response to ROS, one of the most frequent post-translational modifications occurring in redox signaling proteins is the formation of disulfide bridges (from Cys oxidation). This review is focused on the role of plastid thioredoxins (pTRXs), proteins containing two Cys in their active site and largely known as part of the plant redox-signaling network. Several pTRXs types have been described so far, namely, TRX f, m, x, y, and z. In recent years, improvements in proteomic techniques and the study of loss-of-function mutants have enabled us to grasp the importance of TRXs for the plastid physiology. We will analyze the specific signaling function of each TRX type and discuss about the emerging role in non-photosynthetic plastids of these redox switchers. PMID:24319449

  17. Plastid thioredoxins: a "one-for-all" redox-signaling system in plants

    Directory of Open Access Journals (Sweden)

    Antonio Jesús Serrato

    2013-11-01

    Full Text Available The sessile nature of plants forces them to face an ever-changing environment instead of escape from hostile conditions as animals do. In order to overcome this survival challenge, a fine monitoring and controlling of the status of the photosynthetic electron transport chain (PETC and the general metabolism is vital for these organisms. Frequently, evolutionary plant adaptation has consisted in the appearance of multigenic families, comprising an array of enzymes, structural components, or sensing and signaling elements, in numerous occasions with highly conserved primary sequences that sometimes make it difficult to discern between redundancy and specificity among the members of a same family. However, all this gene diversity is aimed to sort environment-derived plant signals to efficiently channel the external incoming information inducing a right physiological answer. Oxygenic photosynthesis is a powerful source of reactive oxygen species (ROS, molecules with a dual oxidative/signaling nature. In response to ROS, one of the most frequent post-translational modifications occurring in redox signaling proteins is the formation of disulfide bridges (from Cys oxidation. This review is focused on the role of plastid thioredoxins (pTRXs, proteins containing two Cys in their active site and largely known as part of the plant redox-signaling network. Several pTRXs types have been described so far, namely, TRX f, m, x, y, and z. In recent years, improvements in proteomic techniques and the study of loss-of-function mutants have enabled us to grasp the importance of TRXs for the plastid physiology. We will analyze the specific signaling function of each TRX type and discuss about the emerging role in non-photosynthetic plastids of these redox switchers.

  18. Plastid thioredoxins: a "one-for-all" redox-signaling system in plants.

    Science.gov (United States)

    Serrato, Antonio J; Fernández-Trijueque, Juan; Barajas-López, Juan-de-Dios; Chueca, Ana; Sahrawy, Mariam

    2013-11-21

    The sessile nature of plants forces them to face an ever-changing environment instead of escape from hostile conditions as animals do. In order to overcome this survival challenge, a fine monitoring and controlling of the status of the photosynthetic electron transport chain and the general metabolism is vital for these organisms. Frequently, evolutionary plant adaptation has consisted in the appearance of multigenic families, comprising an array of enzymes, structural components, or sensing, and signaling elements, in numerous occasions with highly conserved primary sequences that sometimes make it difficult to discern between redundancy and specificity among the members of a same family. However, all this gene diversity is aimed to sort environment-derived plant signals to efficiently channel the external incoming information inducing a right physiological answer. Oxygenic photosynthesis is a powerful source of reactive oxygen species (ROS), molecules with a dual oxidative/signaling nature. In response to ROS, one of the most frequent post-translational modifications occurring in redox signaling proteins is the formation of disulfide bridges (from Cys oxidation). This review is focused on the role of plastid thioredoxins (pTRXs), proteins containing two Cys in their active site and largely known as part of the plant redox-signaling network. Several pTRXs types have been described so far, namely, TRX f, m, x, y, and z. In recent years, improvements in proteomic techniques and the study of loss-of-function mutants have enabled us to grasp the importance of TRXs for the plastid physiology. We will analyze the specific signaling function of each TRX type and discuss about the emerging role in non-photosynthetic plastids of these redox switchers.

  19. Therapeutic Targeting of Redox Signaling in Myofibroblast Differentiation and Age-Related Fibrotic Disease

    Directory of Open Access Journals (Sweden)

    Natalie Sampson

    2012-01-01

    Full Text Available Myofibroblast activation plays a central role during normal wound healing. Whereas insufficient myofibroblast activation impairs wound healing, excessive myofibroblast activation promotes fibrosis in diverse tissues (including benign prostatic hyperplasia, BPH leading to organ dysfunction and also promotes a stromal response that supports tumor progression. The incidence of impaired wound healing, tissue fibrosis, BPH, and certain cancers strongly increases with age. This paper summarizes findings from in vitro fibroblast-to-myofibroblast differentiation systems that serve as cellular models to study fibrogenesis of diverse tissues. Supported by substantial in vivo data, a large body of evidence indicates that myofibroblast differentiation induced by the profibrotic cytokine transforming growth factor beta is driven by a prooxidant shift in redox homeostasis due to elevated production of NADPH oxidase 4 (NOX4-derived hydrogen peroxide and supported by concomitant decreases in nitric oxide/cGMP signaling and reactive oxygen species (ROS scavenging enzymes. Fibroblast-to-myofibroblast differentiation can be inhibited and reversed by restoring redox homeostasis using antioxidants or NOX4 inactivation as well as enhancing nitric oxide/cGMP signaling via activation of soluble guanylyl cyclases or inhibition of phosphodiesterases. Current evidence indicates the therapeutic potential of targeting the prooxidant shift in redox homeostasis for the treatment of age-related diseases associated with myofibroblast dysregulation.

  20. mtDNA Mutagenesis Disrupts Pluripotent Stem Cell Function by Altering Redox Signaling

    Directory of Open Access Journals (Sweden)

    Riikka H. Hämäläinen

    2015-06-01

    Full Text Available mtDNA mutagenesis in somatic stem cells leads to their dysfunction and to progeria in mouse. The mechanism was proposed to involve modification of reactive oxygen species (ROS/redox signaling. We studied the effect of mtDNA mutagenesis on reprogramming and stemness of pluripotent stem cells (PSCs and show that PSCs select against specific mtDNA mutations, mimicking germline and promoting mtDNA integrity despite their glycolytic metabolism. Furthermore, mtDNA mutagenesis is associated with an increase in mitochondrial H2O2, reduced PSC reprogramming efficiency, and self-renewal. Mitochondria-targeted ubiquinone, MitoQ, and N-acetyl-L-cysteine efficiently rescued these defects, indicating that both reprogramming efficiency and stemness are modified by mitochondrial ROS. The redox sensitivity, however, rendered PSCs and especially neural stem cells sensitive to MitoQ toxicity. Our results imply that stem cell compartment warrants special attention when the safety of new antioxidants is assessed and point to an essential role for mitochondrial redox signaling in maintaining normal stem cell function.

  1. An unexplored role for Peroxiredoxin in exercise-induced redox signalling?

    Directory of Open Access Journals (Sweden)

    Alex J. Wadley

    2016-08-01

    Full Text Available Peroxiredoxin (PRDX is a ubiquitous oxidoreductase protein with a conserved ionised thiol that permits catalysis of hydrogen peroxide (H2O2 up to a million times faster than any thiol-containing signalling protein. The increased production of H2O2 within active tissues during exercise is thought to oxidise conserved cysteine thiols, which may in turn facilitate a wide variety of physiological adaptations. The precise mechanisms linking H2O2 with the oxidation of signalling thiol proteins (phosphates, kinases and transcription factors are unclear due to these proteins' low reactivity with H2O2 relative to abundant thiol peroxidases such as PRDX. Recent work has shown that following exposure to H2O2 in vitro, the sulfenic acid of the PRDX cysteine can form mixed disulphides with transcription factors associated with cell survival. This implicates PRDX as an ‘active’ redox relay in transmitting the oxidising equivalent of H2O2 to downstream proteins. Furthermore, under oxidative stress, PRDX can form stable oxidised dimers that can be secreted into the extracellular space, potentially acting as an extracellular ‘stress’ signal. There is extensive literature assessing non-specific markers of oxidative stress in response to exercise, however the PRDX catalytic cycle may offer a more robust approach for measuring changes in redox balance following exercise. This review discusses studies assessing PRDX-mediated cellular signalling and integrates the recent advances in redox biology with investigations that have examined the role of PRDX during exercise in humans and animals. Future studies should explore the role of PRDX as a key regulator of peroxide mediated-signal transduction during exercise in humans.

  2. Complex oscillatory redox dynamics with signaling potential at the edge between normal and pathological mitochondrial function.

    Science.gov (United States)

    Kembro, Jackelyn M; Cortassa, Sonia; Aon, Miguel A

    2014-01-01

    The time-keeping properties bestowed by oscillatory behavior on functional rhythms represent an evolutionarily conserved trait in living systems. Mitochondrial networks function as timekeepers maximizing energetic output while tuning reactive oxygen species (ROS) within physiological levels compatible with signaling. In this work, we explore the potential for timekeeping functions dependent on mitochondrial dynamics with the validated two-compartment mitochondrial energetic-redox (ME-R) computational model, that takes into account (a) four main redox couples [NADH, NADPH, GSH, Trx(SH)2], (b) scavenging systems (glutathione, thioredoxin, SOD, catalase) distributed in matrix and extra-matrix compartments, and (c) transport of ROS species between them. Herein, we describe that the ME-R model can exhibit highly complex oscillatory dynamics in energetic/redox variables and ROS species, consisting of at least five frequencies with modulated amplitudes and period according to power spectral analysis. By stability analysis we describe that the extent of steady state-as against complex oscillatory behavior-was dependent upon the abundance of Mn and Cu, Zn SODs, and their interplay with ROS production in the respiratory chain. Large parametric regions corresponding to oscillatory dynamics of increasingly complex waveforms were obtained at low Cu, Zn SOD concentration as a function of Mn SOD. This oscillatory domain was greatly reduced at higher levels of Cu, Zn SOD. Interestingly, the realm of complex oscillations was located at the edge between normal and pathological mitochondrial energetic behavior, and was characterized by oxidative stress. We conclude that complex oscillatory dynamics could represent a frequency- and amplitude-modulated H2O2 signaling mechanism that arises under intense oxidative stress. By modulating SOD, cells could have evolved an adaptive compromise between relative constancy and the flexibility required under stressful redox/energetic conditions.

  3. A novel Modulation Topology for Power Converters utilizing Multiple Carrier Signals

    DEFF Research Database (Denmark)

    Knott, Arnold; Pfaffinger, Gerhard; Andersen, Michael Andreas E.

    2008-01-01

    Power converters are known to generate spectral components in the range of interest of electromagnetic compatibility measurements. Common approaches to manipulate some selected components in these frequency ranges are shown here. These approaches add components to the input signal of the modulator...... to derive a slightly varied spectrum. To achieve a rectangular output signal, those modulators use a triangular or saw tooth carrier signal. A novel family of modulators is shown here, using more than one carrier signal to obtain a completely changed spectrum while maintaining the rectangular shaped...... waveform at the output. The multiple carriers are fed into multiple comparators and their outputs are intelligently combined by logic gates to get a single signal to drive one power stage of any type of converter. This commutation distinguishes between the four members of the novel family: the first one...

  4. Influence of PAS domain flanking regions on oligomerisation and redox signalling by NifL.

    Directory of Open Access Journals (Sweden)

    Richard Little

    Full Text Available Per-ARNT-Sim (PAS domains constitute a typically dimeric, conserved α/β tertiary fold of approximately 110 amino acids that perform signalling roles in diverse proteins from all kingdoms of life. The amino terminal PAS1 domain of NifL from Azotobacter vinelandii accommodates a redox-active FAD group; elevation of cytosolic oxygen concentrations result in FAD oxidation and a concomitant conformational re-arrangement that is relayed via a short downstream linker to a second PAS domain, PAS2. At PAS2, the signal is amplified and passed on to effector domains generating the 'on' (inhibitory state of the protein. Although the crystal structure of oxidised PAS1 reveals regions that contribute to the dimerisation interface, 21 amino acids at the extreme N-terminus of NifL, are unresolved. Furthermore, the structure and function of the linker between the two PAS domains has not been determined. In this study we have investigated the importance to signalling of residues extending beyond the core PAS fold. Our results implicate the N-terminus of PAS1 and the helical linker connecting the two PAS domains in redox signal transduction and demonstrate a role for these flanking regions in controlling the oligomerisation state of PAS1 in solution.

  5. Ageing-induced changes in the redox status of peripheral motor nerves imply an effect on redox signalling rather than oxidative damage.

    Science.gov (United States)

    McDonagh, Brian; Scullion, Siobhan M; Vasilaki, Aphrodite; Pollock, Natalie; McArdle, Anne; Jackson, Malcolm J

    2016-05-01

    Ageing is associated with loss of skeletal muscle fibres, atrophy of the remaining fibres and weakness. These changes in muscle are accompanied by disruption of motor neurons and neuromuscular junctions although the direct relationship between the nerve and muscle degeneration is not understood. Oxidative changes have been implicated in the mechanisms leading to age-related loss of muscle mass and in degeneration of the central nervous system, but little is known about age-related changes in oxidation in specific peripheral nerves that supply muscles that are affected by ageing. We have therefore examined the sciatic nerve of old mice at an age when loss of tibialis anterior muscle mass and function is apparent. Sciatic nerve from old mice did not show a gross increase in oxidative damage, but electron paramagnetic resonance (EPR) studies indicated an increase in the activity of superoxide and/or peroxynitrite in the nerves of old mice at rest that was further exacerbated by electrical stimulation of the nerve to activate muscle contractions. Proteomic analyses indicated that specific redox-sensitive proteins are increased in content in the nerves of old mice that may reflect an adaptation to regulate the increased superoxide/peroxynitrite and maintain redox homoeostasis. Analysis of redox active cysteines showed some increase in reversible oxidation in specific proteins in nerves of old mice, but this was not universally seen across all redox-active cysteines. Detailed analysis of the redox-active cysteine in one protein in the nerve of old mice that is key to redox signalling (Peroxiredoxin 6, Cys 47) showed a minor increase in reversible oxidation that would be compatible with a change in its redox signalling function. In conclusion, the data presented indicate that sciatic nerve from old mice does not show a gross increase in oxidative damage similar to that seen in the TA and other muscles that it innervates. Our results indicate an adaptation to increased

  6. Epigenetic oxidative redox shift (EORS) theory of aging unifies the free radical and insulin signaling theories.

    Science.gov (United States)

    Brewer, Gregory J

    2010-03-01

    Harman's free radical theory of aging posits that oxidized macromolecules accumulate with age to decrease function and shorten life-span. However, nutritional and genetic interventions to boost anti-oxidants have generally failed to increase life-span. Furthermore, the free radical theory fails to explain why exercise causes higher levels of oxyradical damage, but generally promotes healthy aging. The separate anti-aging paradigms of genetic or caloric reductions in the insulin signaling pathway is thought to slow the rate of living to reduce metabolism, but recent evidence from Westbrook and Bartke suggests metabolism actually increases in long-lived mice. To unify these disparate theories and data, here, we propose the epigenetic oxidative redox shift (EORS) theory of aging. According to EORS, sedentary behavior associated with age triggers an oxidized redox shift and impaired mitochondrial function. In order to maintain resting energy levels, aerobic glycolysis is upregulated by redox-sensitive transcription factors. As emphasized by DeGrey, the need to supply NAD(+) for glucose oxidation and maintain redox balance with impaired mitochondrial NADH oxidoreductase requires the upregulation of other oxidoreductases. In contrast to the 2% inefficiency of mitochondrial reduction of oxygen to the oxyradical, these other oxidoreductases enable glycolytic energy production with a deleterious 100% efficiency in generating oxyradicals. To avoid this catastrophic cycle, lactate dehydrogenase is upregulated at the expense of lactic acid acidosis. This metabolic shift is epigenetically enforced, as is insulin resistance to reduce mitochondrial turnover. The low mitochondrial capacity for efficient production of energy reinforces a downward spiral of more sedentary behavior leading to accelerated aging, increased organ failure with stress, impaired immune and vascular functions and brain aging. Several steps in the pathway are amenable to reversal for exit from the vicious

  7. A Design of High—precision High—Voltage Fiber—Optic Analog Signal Isolation Converter

    Institute of Scientific and Technical Information of China (English)

    李建伟; 许留伟; 等

    2002-01-01

    This paper introduces a design of high-precision high-voltage fiber-optic analog signal isolation converter based on the technology of Voltage-to-Frequency(V/F) and Frequency-to-Voltage(F/V) conversion.It describes the principle,system configuration and hardware desin.

  8. A design of High-precision High-Voltage Fiber-Optic Analog Signal Isolation Converter

    Institute of Scientific and Technical Information of China (English)

    李建伟; 许留伟; 刘小宁; 杨雷

    2002-01-01

    This paper introduces a design of high-prectison high-voltage fiber-optic analog sig-nal isoaltion converter based on the technology of Voltage-to-Fequency (V/F)and Frequency -to Voltage(F/V) conversion It describes the principle ,system configuration and hardware design

  9. Observation of small sub-pulses out of the delayed-interference signal-wavelength converter

    DEFF Research Database (Denmark)

    Sakaguchi, J.; Nielsen, Mads Lønstrup; Ohira, T.;

    2005-01-01

    The generation of small sub-pulses in the delayed-interference signal-wavelength converter (DISC), which has been studied for use in future 160-Gb/s optical time division multiplexing-wavelength division multiplexing (OTDM-WDM) communication systems, was recently predicted as a potential problem....

  10. Atorvastatin ameliorates arsenic-induced hypertension and enhancement of vascular redox signaling in rats

    Energy Technology Data Exchange (ETDEWEB)

    Sarath, Thengumpallil Sasindran; Waghe, Prashantkumar; Gupta, Priyanka; Choudhury, Soumen; Kannan, Kandasamy [Division of Pharmacology and Toxicology, Indian Veterinary Research Institute, Izatnagar, 243122 Bareilly, Uttar Pradesh (India); Pillai, Ayyappan Harikrishna [Division of Animal Biochemistry, Indian Veterinary Research Institute, Izatnagar, 243122 Bareilly, Uttar Pradesh (India); Harikumar, Sankaran Kutty; Mishra, Santosh Kumar [Division of Pharmacology and Toxicology, Indian Veterinary Research Institute, Izatnagar, 243122 Bareilly, Uttar Pradesh (India); Sarkar, Souvendra Nath, E-mail: snsarkar1911@rediffmail.com [Division of Pharmacology and Toxicology, Indian Veterinary Research Institute, Izatnagar, 243122 Bareilly, Uttar Pradesh (India)

    2014-11-01

    Chronic arsenic exposure has been linked to elevated blood pressure and cardiovascular diseases, while statins reduce the incidence of cardiovascular disease predominantly by their low density lipoprotein-lowering effect. Besides, statins have other beneficial effects, including antioxidant and anti-inflammatory activities. We evaluated whether atorvastatin, a widely used statin, can ameliorate arsenic-induced increase in blood pressure and alteration in lipid profile and also whether the amelioration could relate to altered NO and ROS signaling. Rats were exposed to sodium arsenite (100 ppm) through drinking water for 90 consecutive days. Atorvastatin (10 mg/kg bw, orally) was administered once daily during the last 30 days of arsenic exposure. On the 91st day, blood was collected for lipid profile. Western blot of iNOS and eNOS protein, NO and 3-nitrotyrosine production, Nox-4 and p22Phox mRNA expression, Nox activity, ROS generation, lipid peroxidation and antioxidants were evaluated in thoracic aorta. Arsenic increased systolic, diastolic and mean arterial blood pressure, while it decreased HDL-C and increased LDL-C, total cholesterol and triglycerides in serum. Arsenic down-regulated eNOS and up-regulated iNOS protein expression and increased basal NO and 3-nitrotyrosine level. Arsenic increased aortic Nox-4 and p22Phox mRNA expression, Nox activity, ROS generation and lipid peroxidation. Further, arsenic decreased the activities of superoxide dismutase, catalase, and glutathione peroxidase and depleted aortic GSH content. Atorvastatin regularized blood pressure, improved lipid profile and attenuated arsenic-mediated redox alterations. The results demonstrate that atorvastatin has the potential to ameliorate arsenic-induced hypertension by improving lipid profile, aortic NO signaling and restoring vascular redox homeostasis. - Highlights: • Arsenic increased systolic, diastolic and mean arterial blood pressure and caused dyslipidemia. • Arsenic increased

  11. A continuous nonlinear model approach to study the behavior of large signal DC to DC converters

    Science.gov (United States)

    Guinjoan, Francisco

    The study of signal switching DC-DC converters behavior is addressed. Given the fact that the linear methods cannot be used in this case, a nonlinear model was developed. The power stage nonlinear continuous model, which can be applied in both conduction modes (continuous and discontinuous), is obtained from the partition of the characteristic state vector variables in two subsets. This method is applied to the elementary switching cells (buck, boost, and buck-boost) and Cuk converter. It is oriented to the fast numerical simulation by means of general purpose simulation programs. Different results from numerical simulations, confirming the accuracy of the method used, either in an open loop or in a closed loop, are obtained, provided the validity of its domain is respected. The nonlinear model linearization made it possible to obtain equivalent transmittances for the DC-DC converters. Its application to a boost converter operating in the discontinuous condition mode at variable frequency rate enables the comparison of the obtained results with other existing methods and equivalence between the two of them to be easily established. The revision of the initial hypothesis leads to the establishment of a small signal model valid in the high frequency domain and to the results obtained being derived in a more systematic way. A model for switching DC-DC converters is given. Its validity is established, whatever its order and conduction modes, either in an open loop or a closed loop.

  12. Comparison of two different high performance mixed signal controllers for DC/DC converters

    DEFF Research Database (Denmark)

    Jakobsen, Lars Tønnes; Andersen, Michael Andreas E.

    2006-01-01

    This paper describes how mixed signal controllers combining a cheap microcontroller with a simple analogue circuit can offer high performance digital control for DC/DC converters. Mixed signal controllers have the same versatility and performance as DSP based controllers. It is important to have...... an engineer experienced in microcontroller programming write the software algorithms to achieve optimal performance. Two mixed signal controller designs based on the same 8-bit microcontroller are compared both theoretically and experimentally. A 16-bit PID compensator with a sampling frequency of 200 k......Hz implemented in the 16 MIPS, 8-bit ATTiny26 microcontroller is demonstrated....

  13. Manganese superoxide dismutase (SOD2): is there a center in the universe of mitochondrial redox signaling?

    Science.gov (United States)

    Zou, Xianghui; Ratti, Bianca A; O'Brien, Joseph Gerald; Lautenschlager, Sueli O; Gius, David R; Bonini, Marcelo G; Zhu, Yueming

    2017-06-14

    It is becoming increasingly clear that mitochondria drive cellular functions and in vivo phenotypes by directing the production rate and abundance of metabolites that are proposed to function as signaling molecules (Chandel 2015; Selak et al. 2005; Etchegaray and Mostoslavsky 2016). Many of these metabolites are intermediates that make up cellular metabolism, part of which occur in mitochondria (i.e. the TCA and urea cycles), while others are produced "on demand" mainly in response to alterations in the microenvironment in order to participate in the activation of acute adaptive responses (Mills et al. 2016; Go et al. 2010). Reactive oxygen species (ROS) are well suited for the purpose of executing rapid and transient signaling due to their short lived nature (Bae et al. 2011). Hydrogen peroxide (H2O2), in particular, possesses important characteristics including diffusibility and faster reactivity with specific residues such as methionine, cysteine and selenocysteine (Bonini et al. 2014). Therefore, it is reasonable to propose that H2O2 functions as a relatively specific redox signaling molecule. Even though it is now established that mtH2O2 is indispensable, at least for hypoxic adaptation and energetic and/or metabolic homeostasis (Hamanaka et al. 2016; Guzy et al. 2005), the question of how H2O2 is produced and regulated in the mitochondria is only partially answered. In this review, some roles of this indispensable signaling molecule in driving cellular metabolism will be discussed. In addition, we will discuss how H2O2 formation in mitochondria depends on and is controlled by MnSOD. Finally, we will conclude this manuscript by highlighting why a better understanding of redox hubs in the mitochondria will likely lead to new and improved therapeutics of a number of diseases, including cancer.

  14. Reactive oxygen species (ROS) homeostasis and redox regulation in cellular signaling.

    Science.gov (United States)

    Ray, Paul D; Huang, Bo-Wen; Tsuji, Yoshiaki

    2012-05-01

    Reactive oxygen species (ROS) are generated during mitochondrial oxidative metabolism as well as in cellular response to xenobiotics, cytokines, and bacterial invasion. Oxidative stress refers to the imbalance due to excess ROS or oxidants over the capability of the cell to mount an effective antioxidant response. Oxidative stress results in macromolecular damage and is implicated in various disease states such as atherosclerosis, diabetes, cancer, neurodegeneration, and aging. Paradoxically, accumulating evidence indicates that ROS also serve as critical signaling molecules in cell proliferation and survival. While there is a large body of research demonstrating the general effect of oxidative stress on signaling pathways, less is known about the initial and direct regulation of signaling molecules by ROS, or what we term the "oxidative interface." Cellular ROS sensing and metabolism are tightly regulated by a variety of proteins involved in the redox (reduction/oxidation) mechanism. This review focuses on the molecular mechanisms through which ROS directly interact with critical signaling molecules to initiate signaling in a broad variety of cellular processes, such as proliferation and survival (MAP kinases, PI3 kinase, PTEN, and protein tyrosine phosphatases), ROS homeostasis and antioxidant gene regulation (thioredoxin, peroxiredoxin, Ref-1, and Nrf-2), mitochondrial oxidative stress, apoptosis, and aging (p66Shc), iron homeostasis through iron-sulfur cluster proteins (IRE-IRP), and ATM-regulated DNA damage response.

  15. A generalizable platform for interrogating target- and signal-specific consequences of electrophilic modifications in redox-dependent cell signaling.

    Science.gov (United States)

    Lin, Hong-Yu; Haegele, Joseph A; Disare, Michael T; Lin, Qishan; Aye, Yimon

    2015-05-20

    Despite the known propensity of small-molecule electrophiles to react with numerous cysteine-active proteins, biological actions of individual signal inducers have emerged to be chemotype-specific. To pinpoint and quantify the impacts of modifying one target out of the whole proteome, we develop a target-protein-personalized "electrophile toolbox" with which specific intracellular targets can be selectively modified at a precise time by specific reactive signals. This general methodology, T-REX (targetable reactive electrophiles and oxidants), is established by (1) constructing a platform that can deliver a range of electronic and sterically different bioactive lipid-derived signaling electrophiles to specific proteins in cells; (2) probing the kinetics of targeted delivery concept, which revealed that targeting efficiency in cells is largely driven by initial on-rate of alkylation; and (3) evaluating the consequences of protein-target- and small-molecule-signal-specific modifications on the strength of downstream signaling. These data show that T-REX allows quantitative interrogations into the extent to which the Nrf2 transcription factor-dependent antioxidant response element (ARE) signaling is activated by selective electrophilic modifications on Keap1 protein, one of several redox-sensitive regulators of the Nrf2-ARE axis. The results document Keap1 as a promiscuous electrophile-responsive sensor able to respond with similar efficiencies to discrete electrophilic signals, promoting comparable strength of Nrf2-ARE induction. T-REX is also able to elicit cell activation in cases in which whole-cell electrophile flooding fails to stimulate ARE induction prior to causing cytotoxicity. The platform presents a previously unavailable opportunity to elucidate the functional consequences of small-molecule-signal- and protein-target-specific electrophilic modifications in an otherwise unaffected cellular background.

  16. Redox-regulated cargo binding and release by the peroxisomal targeting signal receptor, Pex5.

    Science.gov (United States)

    Ma, Changle; Hagstrom, Danielle; Polley, Soumi Guha; Subramani, Suresh

    2013-09-20

    In its role as a mobile receptor for peroxisomal matrix cargo containing a peroxisomal targeting signal called PTS1, the protein Pex5 shuttles between the cytosol and the peroxisome lumen. Pex5 binds PTS1 proteins in the cytosol via its C-terminal tetratricopeptide domains and delivers them to the peroxisome lumen, where the receptor·cargo complex dissociates. The cargo-free receptor is exported to the cytosol for another round of import. How cargo release and receptor recycling are regulated is poorly understood. We found that Pex5 functions as a dimer/oligomer and that its protein interactions with itself (homo-oligomeric) and with Pex8 (hetero-oligomeric) control the binding and release of cargo proteins. These interactions are controlled by a redox-sensitive amino acid, cysteine 10 of Pex5, which is essential for the formation of disulfide bond-linked Pex5 forms, for high affinity cargo binding, and for receptor recycling. Disulfide bond-linked Pex5 showed the highest affinity for PTS1 cargo. Upon reduction of the disulfide bond by dithiothreitol, Pex5 transitioned to a noncovalent dimer, concomitant with the partial release of PTS1 cargo. Additionally, dissipation of the redox balance between the cytosol and the peroxisome lumen caused an import defect. A hetero-oligomeric interaction between the N-terminal domain (amino acids 1-110) of Pex5 and a conserved motif at the C terminus of Pex8 further facilitates cargo release, but only under reducing conditions. This interaction is also important for the release of PTS1 proteins. We suggest a redox-regulated model for Pex5 function during the peroxisomal matrix protein import cycle.

  17. Zinc and redox signaling: perturbations associated with cardiovascular disease and diabetes mellitus.

    Science.gov (United States)

    Foster, Meika; Samman, Samir

    2010-11-15

    Cellular signal transduction pathways are influenced by the zinc and redox status of the cell. Numerous chronic diseases, including cardiovascular disease (CVD) and diabetes mellitus (DM), have been associated with impaired zinc utilization and increased oxidative stress. In humans, mutations in the MT-1A and ZnT8 genes, both of which are involved in the maintenance of zinc homeostasis, have been linked with DM development. Changes in levels of intracellular free zinc may exacerbate oxidative stress in CVD and DM by impacting glutathione homeostasis, nitric oxide signaling, and nuclear factor-kappa B-dependent cellular processes. Zinc ions have been shown to influence insulin and leptin signaling via the phosphoinositide 3′-kinase/Akt pathway, potentially linking an imbalance of zinc at the cellular level to insulin resistance and dyslipidemia. The oxidative modification of cysteine residues in zinc coordination sites in proteins has been implicated in cellular signaling and regulatory pathways. Despite the many interactions between zinc and cellular stress responses, studies investigating the potential therapeutic benefit of zinc supplementation in the prevention and treatment of oxidative stress-related chronic disease in humans are few and inconsistent. Further well-designed randomized controlled trials are needed to determine the effects of zinc supplementation in populations at various stages of CVD and DM progression.

  18. Low-Voltage Analog-to-Digital Converters and Mixed-Signal Interfaces

    OpenAIRE

    Harikumar, Prakash

    2016-01-01

    Analog-to-digital converters (ADCs) are crucial blocks which form the interface between the physical world and the digital domain. ADCs are indispensable in numerous applications such as wireless sensor networks (WSNs), wireless/wireline communication receivers and data acquisition systems. To achieve long-term, autonomous operation for WSNs, the nodes are powered by harvesting energy from ambient sources such as solar energy, vibrational energy etc. Since the signal frequencies in these dist...

  19. Thioredoxin-dependent Redox Regulation of Cellular Signaling and Stress Response through Reversible Oxidation of Methionines

    Energy Technology Data Exchange (ETDEWEB)

    Bigelow, Diana J.; Squier, Thomas C.

    2011-06-01

    Generation of reactive oxygen species (ROS) is a common feature of many forms of stress to which plants are exposed. Successful adaptation to changing environmental conditions requires sensitive sensors of ROS such as protein-bound methionines that are converted to their corresponding methionine sulfoxides, which in turn can influence cellular signaling pathways. Such a signaling protein is calmodulin, which represents an early and central point in calcium signaling pathways important to stress response in plants. We describe recent work elucidating fundamental mechanisms of reversible methionine oxidation within calmodulin, including the sensitivity of individual methionines within plant and animal calmodulin to ROS, the structural and functional consequences of their oxidation, and the interactions of oxidized calmodulin with methionine sulfoxide reductase enzymes.

  20. Small-Signal Stability Analysis of Full-Load Converter Interfaced Wind Turbines

    DEFF Research Database (Denmark)

    Knüppel, Thyge; Akhmatov, Vladislav; Nielsen, Jørgen Nygård

    2009-01-01

    Power system stability investigations of wind farms often cover the tasks of low-voltage-fault-ride-through, voltage and reactive power control, and power balancing, but not much attention has yet been paid to the task of small-signal stability. Small-signal stability analysis needs increasing...... focus since the share of wind power increases substituting power generation from conventional power plants. Here, a study based on modal analysis is presented which investigate the effect of large scale integration of full-load converter interfaced wind turbines on inter-area oscillations in a three...

  1. Thylakoid redox signals are integrated into organellar-gene-expression-dependent retrograde signalling in the prors1-1 mutant

    Directory of Open Access Journals (Sweden)

    Luca eTadini

    2012-12-01

    Full Text Available Perturbations in organellar gene expression (OGE and the thylakoid redox state (TRS activate retrograde signalling pathways that adaptively modify nuclear gene expression (NGE, according to developmental and metabolic needs. The prors1-1 mutation in Arabidopsis down-regulates the expression of the nuclear gene Prolyl-tRNA Synthetase1 (PRORS1 which acts in both plastids and mitochondria, thereby impairing protein synthesis in both organelles and triggering OGE-dependent retrograde signalling. Because the mutation also affects thylakoid electron transport, TRS-dependent signals may likewise have an impact on the changes in NGE observed in this genotype. In this study, we have investigated whether signals related to TRS are actually integrated into the OGE-dependent retrograde signalling pathway. To this end, the chaos mutation (for chlorophyll a/b binding protein harvesting-organelle specific, which shows a partial loss of PSII antennae proteins and thus a reduction in PSII light absorption capability, was introduced into the prors1-1 mutant background. The resulting double mutant displayed a prors1-1-like reduction in plastid translation rate and a chaos-like decrease in PSII antenna size, whereas the hyper-reduction of the thylakoid electron transport chain, caused by the prors1-1 mutation, was alleviated, as determined by monitoring chlorophyll (Chl fluorescence and thylakoid phosphorylation. Interestingly, a substantial fraction of the nucleus-encoded photosynthesis genes down-regulated in the prors1-1 mutant are expressed at nearly wild-type rates in prors1-1 chaos leaves, and this recovery is reflected in the steady-state levels of their protein products in the chloroplast. We therefore conclude that signals related to photosynthetic electron transport and TRS, and indirectly to carbohydrate metabolism and energy balance, are indeed fed into the OGE-dependent retrograde pathway to modulate NGE and adjust the abundance of chloroplast proteins.

  2. Oxygen in human health from life to death – An approach to teaching redox biology and signaling to graduate and medical students

    Directory of Open Access Journals (Sweden)

    Margaret M. Briehl

    2015-08-01

    Full Text Available In the absence of oxygen human life is measured in minutes. In the presence of oxygen, normal metabolism generates reactive species (ROS that have the potential to cause cell injury contributing to human aging and disease. Between these extremes, organisms have developed means for sensing oxygen and ROS and regulating their cellular processes in response. Redox signaling contributes to the control of cell proliferation and death. Aberrant redox signaling underlies many human diseases. The attributes acquired by altered redox homeostasis in cancer cells illustrate this particularly well. This teaching review and the accompanying illustrations provide an introduction to redox biology and signaling aimed at instructors of graduate and medical students.

  3. Thiol-based redox signaling in the nitrogen-fixing symbiosis

    Directory of Open Access Journals (Sweden)

    Pierre eFrendo

    2013-09-01

    Full Text Available In nitrogen poor soils legumes establish a symbiotic interaction with rhizobia that results in the formation of root nodules. These are unique plant organs where bacteria differentiate into bacteroids, which express the nitrogenase enzyme complex that reduces atmospheric N2 to ammonia. Nodule metabolism requires a tight control of the concentrations of reactive oxygen and nitrogen species (RONS so that they can perform useful signaling roles while avoiding nitro-oxidative damage. In nodules a thiol-dependent regulatory network that senses, transmits and responds to redox changes is starting to be elucidated. A combination of enzymatic, immunological, pharmacological and molecular analyses has allowed to conclude that glutathione and its legume-specific homolog, homoglutathione, are abundant in meristematic and infected cells, their spatio-temporally distribution is correlated with the corresponding (homoglutathione synthetase activities, and are crucial for nodule development and function. Glutathione is at high concentrations in the bacteroids and at moderate amounts in the mitochondria, cytosol and nuclei. Less information is available on other components of the network. The expression of multiple isoforms of glutathione peroxidases, peroxiredoxins, thioredoxins, glutaredoxins and NADPH-thioredoxin reductases has been detected in nodule cells using antibodies and proteomics. Peroxiredoxins and thioredoxins are essential to regulate and in some cases to detoxify RONS in nodules. Further research is necessary to clarify the regulation of the expression and activity of thiol redox-active proteins in response to abiotic, biotic and developmental cues, their interactions with downstream targets by disulfide-exchange reactions, and their participation in signaling cascades. The availability of mutants and transgenic lines will be crucial to facilitate systematic investigations into the function of the various proteins in the legume

  4. Cyclophilin 20-3 relays a 12-oxo-phytodienoic acid signal during stress responsive regulation of cellular redox homeostasis.

    Science.gov (United States)

    Park, Sang-Wook; Li, Wei; Viehhauser, Andrea; He, Bin; Kim, Soonok; Nilsson, Anders K; Andersson, Mats X; Kittle, Joshua D; Ambavaram, Madana M R; Luan, Sheng; Esker, Alan R; Tholl, Dorothea; Cimini, Daniela; Ellerström, Mats; Coaker, Gitta; Mitchell, Thomas K; Pereira, Andy; Dietz, Karl-Josef; Lawrence, Christopher B

    2013-06-04

    The jasmonate family of phytohormones plays central roles in plant development and stress acclimation. However, the architecture of their signaling circuits remains largely unknown. Here we describe a jasmonate family binding protein, cyclophilin 20-3 (CYP20-3), which regulates stress-responsive cellular redox homeostasis. (+)-12-Oxo-phytodienoic acid (OPDA) binding promotes CYP20-3 to form a complex with serine acetyltransferase 1, which triggers the formation of a hetero-oligomeric cysteine synthase complex with O-acetylserine(thiol)lyase B in chloroplasts. The cysteine synthase complex formation then activates sulfur assimilation that leads to increased levels of thiol metabolites and the buildup of cellular reduction potential. The enhanced redox capacity in turn coordinates the expression of a subset of OPDA-responsive genes. Thus, we conclude that CYP20-3 is a key effector protein that links OPDA signaling to amino acid biosynthesis and cellular redox homeostasis in stress responses.

  5. The plastid redox insensitive 2 mutant of Arabidopsis is impaired in PEP activity and high light-dependent plastid redox signalling to the nucleus

    DEFF Research Database (Denmark)

    Kindgren, Peter; Kremnev, Dmitry; Blanco, Nicolás E

    2012-01-01

    involved in redox-mediated retrograde signalling. The allelic mutants prin2-1 and prin2-2 demonstrated a misregulation of photosynthesis-associated nuclear gene expression in response to excess light, and an inhibition of photosynthetic electron transport. As a consequence of the misregulation of LHCB1...... is required for full expression of genes transcribed by the plastid-encoded RNA polymerase (PEP). Similarly to the prin2 mutants, the ys1 mutant with impaired PEP activity also demonstrated a misregulation of LHCB1.1 and LHCB2.4 expression in response to excess light, suggesting a direct role for PEP activity...

  6. The Genome of the Generalist Plant Pathogen Fusarium avenaceum Is Enriched with Genes Involved in Redox, Signaling and Secondary Metabolism

    DEFF Research Database (Denmark)

    Lysøe, Erik; Harris, Linda J.; Walkowiak, Sean

    2014-01-01

    . avenaceum, such as transcription factors, and proteins involved in redox reactions and signal transduction, suggesting evolutionary adaptation to a diverse and cosmopolitan ecology. We found that 20% of all predicted proteins were considered to be secreted, supporting a life in the extracellular space...

  7. A study of the Apollo aqueous redox process for converting hydrogen sulfide in biogas to elemental sulfur

    Energy Technology Data Exchange (ETDEWEB)

    Ellenor, D.T.

    2004-07-01

    An experimental study was conducted to develop a commercial biogas scrubber for municipal and agricultural use. The specific objectives were to provide design and scaling parameters that would improve the performance while minimizing the capital and operating costs of the biogas scrubber; provide a useful reaction model of the aqueous phase iron chelate catalyzed oxide of hydrogen sulfide to elemental sulfur; develop hypotheses and determine what data are of relevance in comprehending the interfacial phenomena of colloidal sulfur in aqueous solutions that could result in unwanted sulfur deposition and poor sulfur quality; obtain interfacial chemistry data that could improve the understanding of how sulfur particles behave during flocculation and deposition on surfaces, and the factors that lead to poor surface quality; and, determine whether crystal size and characteristics of deposited and flocculated sulfur could be changed by surfactants to enhance sulfur purity and reduce process operability. Interfacial chemistry experiments were performed to determine the factors that influence the operating problems and poor quality associated with the sulfur product. Results suggest that a low foaming nonionic surfactant can improve the quality and processability of the elemental sulfur product. It was concluded that the addition of surfactant to the redox solution reduces the mean hydrogen removal efficiency of the process. The addition of surfactants also decreases the mean particle size of the precipitated sulfur product, but increases the purity of the precipitated product. This study contributed to the successful installation by Apollo Environmental Systems of a commercial biogas scrubber that is very resistant to sulfur plugging.

  8. Legume nodule senescence: roles for redox and hormone signalling in the orchestration of the natural aging process.

    Science.gov (United States)

    Puppo, Alain; Groten, Karin; Bastian, Fabiola; Carzaniga, Raffaella; Soussi, Mariam; Lucas, M Mercedes; de Felipe, Maria Rosario; Harrison, Judith; Vanacker, Hélène; Foyer, Christine H

    2005-03-01

    Research on legume nodule development has contributed greatly to our current understanding of plant-microbe interactions. However, the factors that orchestrate root nodule senescence have received relatively little attention. Accumulating evidence suggests that redox signals contribute to the establishment of symbiosis and senescence. Although degenerative in nature, nodule senescence is an active process programmed in development in which reactive oxygen species (ROS), antioxidants, hormones and proteinases have key roles. Nodules have high levels of the redox buffers, ascorbate and glutathione, which are important in the nodulation process and in senescence. These metabolites decline with N-fixation as the nodule ages but the resultant decrease in redox buffering capacity does not necessarily lead to enhanced ROS or oxidative stress. We propose models by which ROS and antioxidants interact with hormones such as abscisic acid in the orchestration of nodule senescence.

  9. Integration between anticipatory blocking and redox signaling by the peroxiredoxin/thioredoxin/thioredoxin-reductase system.

    Science.gov (United States)

    Selvaggio, Gianluca; Coelho, Pedro M B M; Salvador, Armindo

    2014-10-01

    Cells are occasionally exposed to high H2O2 concentrations, often preceding exposure to other electrophylic compounds. Both H2O2 and these compounds can irreversibly modify protein thiols, with deleterious consequences. Induction of enzymatic defenses against those agents is too slow to avoid significant damage. Cells may solve this conundrum by reversibly "blocking" the thiols once H2O2 concentrations begin to increase. We term this mechanism "anticipatory blocking" because it acts in anticipation of irreversible damage upon detection of early signs of stress. Here we examine the design requirements for the Peroxiredoxin/Thioredoxin/Thioredoxin-Reductase/Protein-Dithiol System (PTTRDS) to effectively integrate H2O2 signaling and anticipatory blocking of protein dithiols as disulfides, and we compared them to the designs found in cells. To that effect, we developed a minimal model of the PTTRDS, and we defined a set of quantitative performance criteria that embody the requirements for (a) efficient scavenging capacity, (b) low NADPH consumption, (c) effective signal propagation, and (d) effective anticipatory blocking. We then sought the design principles (relationships among rate constants and species concentrations) that warrant fulfillment of all these criteria. Experimental data indicates that the design of the PTTRDS in human erythrocytes fulfills these principles and thus accomplishes effective integration between anticipatory blocking, antioxidant protection and redox signaling. A more general analysis suggests that the same principles hold in a wide variety of cell types and organisms. We acknowledge grants PEst-C/SAU/LA0001/2013-2014, PEst-OE/QUI/UI0612/2013, FCOMP-01-0124-FEDER-020978 (PTDC/QUI-BIQ/119657/2010) financed by FEDER through the "Programa Operacional Factores de Competitividade, COMPETE" and by national funds through "FCT, Fundação para a Ciência e a Tecnologia".

  10. Nitric oxide promotes nicotine-triggered ERK signaling via redox reactions in PC12 cells.

    Science.gov (United States)

    Miyamoto, Yoshiaki; Sakai, Ryosuke; Maeda, Chiharu; Takata, Tsuyoshi; Ihara, Hideshi; Tsuchiya, Yukihiro; Watanabe, Yasuo

    2011-10-30

    Nitric oxide (NO), produced by neuronal NO synthase (nNOS), serves as a signaling molecule with diverse biological responses in the central nervous system (CNS). In the present study, we demonstrated that nNOS expression enhances the nicotine-triggered activation of extracellular signal-regulated kinase 1/2 (ERK1/2) in nNOS-transfected PC12 (NPC12) cells. Treatment with nicotine increased the phosphorylation level of ERK1/2 in the NPC12 cells as compared with that in control PC12 cells. However, nicotine treatment failed to enhance ERK1/2 phosphorylation when NPC12 cells were pretreated with several selective inhibitors of NOS, the nicotinic acetylcholine receptors, L-type voltage-dependent Ca(2+) channels, protein kinase C, Src, epidermal growth factor receptor, and MEK. The nicotine-induced ERK1/2 phosphorylation in PC12 cells was observed by their pretreatment with a NO donor. Moreover, the enhancement of nicotine-induced ERK1/2 phosphorylation in the NPC12 cells was regulated by intracellular glutathione levels, but not by the soluble guanylate cyclase-cGMP-protein kinase G signaling. Meanwhile, depolarization stimulated ERK1/2 phosphorylation in both PC12 and NPC12 cells. Taken together, these findings suggest that nicotine modulates NO-dependent redox condition; the resulting calcium influx, would increase ERK1/2 phosphorylation in nNOS expressing cells. Blockade of NO pathway may be selective target to reduce ERK1/2 phosphorylation via attenuation of the nicotine responses in the CNS.

  11. Small-Signal Stability of Wind Power System With Full-Load Converter Interfaced Wind Turbines

    DEFF Research Database (Denmark)

    Knüppel, Thyge; Nielsen, Jørgen Nygaard; Jensen, Kim Høj;

    2012-01-01

    Small-signal stability analysis of power system oscillations is a well established field within power system analysis, but not much attention has yet been paid to systems with a high penetration of wind turbines and with large wind power plants (WPP). In this paper a comprehensive analysis...... is presented which assesses the impact of full-load converter interfaced wind turbines on power system small-signal stability. The study is based on a 7 generator network with lightly damped inter-area modes. A detailed wind turbine (WT) model with all grid relevant control functions is used in the study....... The WT is, furthermore, equipped with a park level WPP voltage controller and comparisons are presented. The WT model for this work is a validated dynamic model of the 3.6 MW Siemens Wind Power WT. The study is based on modal analysis which is complemented with time domain simulations on the nonlinear...

  12. Redox Signaling in Diabetic Nephropathy: Hypertrophy versus Death Choices in Mesangial Cells and Podocytes

    Directory of Open Access Journals (Sweden)

    Gina Manda

    2015-01-01

    Full Text Available This review emphasizes the role of oxidative stress in diabetic nephropathy, acting as trigger, modulator, and linker within the complex network of pathologic events. It highlights key molecular pathways and new hypothesis in diabetic nephropathy, related to the interferences of metabolic, oxidative, and inflammatory stresses. Main topics this review is addressing are biomarkers of oxidative stress in diabetic nephropathy, the sources of reactive oxygen species (mitochondria, NADPH-oxidases, hyperglycemia, and inflammation, and the redox-sensitive signaling networks (protein kinases, transcription factors, and epigenetic regulators. Molecular switches deciding on the renal cells fate in diabetic nephropathy are presented, such as hypertrophy versus death choices in mesangial cells and podocytes. Finally, the antioxidant response of renal cells in diabetic nephropathy is tackled, with emphasis on targeted therapy. An integrative approach is needed for identifying key molecular networks which control cellular responses triggered by the array of stressors in diabetic nephropathy. This will foster the discovery of reliable biomarkers for early diagnosis and prognosis, and will guide the discovery of new therapeutic approaches for personalized medicine in diabetic nephropathy.

  13. Redox Signaling in Diabetic Nephropathy: Hypertrophy versus Death Choices in Mesangial Cells and Podocytes.

    Science.gov (United States)

    Manda, Gina; Checherita, Alexandru-Ionel; Comanescu, Maria Victoria; Hinescu, Mihail Eugen

    2015-01-01

    This review emphasizes the role of oxidative stress in diabetic nephropathy, acting as trigger, modulator, and linker within the complex network of pathologic events. It highlights key molecular pathways and new hypothesis in diabetic nephropathy, related to the interferences of metabolic, oxidative, and inflammatory stresses. Main topics this review is addressing are biomarkers of oxidative stress in diabetic nephropathy, the sources of reactive oxygen species (mitochondria, NADPH-oxidases, hyperglycemia, and inflammation), and the redox-sensitive signaling networks (protein kinases, transcription factors, and epigenetic regulators). Molecular switches deciding on the renal cells fate in diabetic nephropathy are presented, such as hypertrophy versus death choices in mesangial cells and podocytes. Finally, the antioxidant response of renal cells in diabetic nephropathy is tackled, with emphasis on targeted therapy. An integrative approach is needed for identifying key molecular networks which control cellular responses triggered by the array of stressors in diabetic nephropathy. This will foster the discovery of reliable biomarkers for early diagnosis and prognosis, and will guide the discovery of new therapeutic approaches for personalized medicine in diabetic nephropathy.

  14. Gsk3 Signalling and Redox Status in Bipolar Disorder: Evidence from Lithium Efficacy

    Science.gov (United States)

    2016-01-01

    Objective. To discuss the link between glycogen synthase kinase-3 (GSK3) and the main biological alterations demonstrated in bipolar disorder (BD), with special attention to the redox status and the evidence supporting the efficacy of lithium (a GSK3 inhibitor) in the treatment of BD. Methods. A literature research on the discussed topics, using Pubmed and Google Scholar, has been conducted. Moreover, a manual selection of interesting references from the identified articles has been performed. Results. The main biological alterations of BD, pertaining to inflammation, oxidative stress, membrane ion channels, and circadian system, seem to be intertwined. The dysfunction of the GSK3 signalling pathway is involved in all the aforementioned “biological causes” of BD. In a complex scenario, it can be seen as the common denominator linking them all. Lithium inhibition of GSK3 could, at least in part, explain its positive effect on these biological dysfunctions and its superiority in terms of clinical efficacy. Conclusions. Deepening the knowledge on the molecular bases of BD is fundamental to identifying the biochemical pathways that must be targeted in order to provide patients with increasingly effective therapeutic tools against an invalidating disorder such as BD. PMID:27630757

  15. Gsk3 Signalling and Redox Status in Bipolar Disorder: Evidence from Lithium Efficacy

    Directory of Open Access Journals (Sweden)

    Antonina Luca

    2016-01-01

    Full Text Available Objective. To discuss the link between glycogen synthase kinase-3 (GSK3 and the main biological alterations demonstrated in bipolar disorder (BD, with special attention to the redox status and the evidence supporting the efficacy of lithium (a GSK3 inhibitor in the treatment of BD. Methods. A literature research on the discussed topics, using Pubmed and Google Scholar, has been conducted. Moreover, a manual selection of interesting references from the identified articles has been performed. Results. The main biological alterations of BD, pertaining to inflammation, oxidative stress, membrane ion channels, and circadian system, seem to be intertwined. The dysfunction of the GSK3 signalling pathway is involved in all the aforementioned “biological causes” of BD. In a complex scenario, it can be seen as the common denominator linking them all. Lithium inhibition of GSK3 could, at least in part, explain its positive effect on these biological dysfunctions and its superiority in terms of clinical efficacy. Conclusions. Deepening the knowledge on the molecular bases of BD is fundamental to identifying the biochemical pathways that must be targeted in order to provide patients with increasingly effective therapeutic tools against an invalidating disorder such as BD.

  16. Gsk3 Signalling and Redox Status in Bipolar Disorder: Evidence from Lithium Efficacy.

    Science.gov (United States)

    Luca, Antonina; Calandra, Carmela; Luca, Maria

    2016-01-01

    Objective. To discuss the link between glycogen synthase kinase-3 (GSK3) and the main biological alterations demonstrated in bipolar disorder (BD), with special attention to the redox status and the evidence supporting the efficacy of lithium (a GSK3 inhibitor) in the treatment of BD. Methods. A literature research on the discussed topics, using Pubmed and Google Scholar, has been conducted. Moreover, a manual selection of interesting references from the identified articles has been performed. Results. The main biological alterations of BD, pertaining to inflammation, oxidative stress, membrane ion channels, and circadian system, seem to be intertwined. The dysfunction of the GSK3 signalling pathway is involved in all the aforementioned "biological causes" of BD. In a complex scenario, it can be seen as the common denominator linking them all. Lithium inhibition of GSK3 could, at least in part, explain its positive effect on these biological dysfunctions and its superiority in terms of clinical efficacy. Conclusions. Deepening the knowledge on the molecular bases of BD is fundamental to identifying the biochemical pathways that must be targeted in order to provide patients with increasingly effective therapeutic tools against an invalidating disorder such as BD.

  17. Missing links in understanding redox signaling via thiol/disulfide modulation: How is glutathione oxidized in plants?

    Directory of Open Access Journals (Sweden)

    Marie-Sylviane eRahantaniaina

    2013-11-01

    Full Text Available Glutathione is a small redox-active molecule existing in two main stable forms: the thiol (GSH and the disulphide (GSSG. In plants growing in optimal conditions, the GSH:GSSG ratio is high in most cell compartments. Challenging environmental conditions are known to alter this ratio, notably by inducing the accumulation of GSSG, an effect that may be influential in the perception or transduction of stress signals. Despite the potential importance of glutathione status in redox signalling, the reactions responsible for the oxidation of GSH to GSSG have not been clearly identified. Most attention has focused on the ascorbate-glutathione pathway, but several other candidate pathways may couple the availability of oxidants such as H2O2 to changes in glutathione and thus impact on signalling pathways through regulation of protein thiol-disulfide status. We provide an overview of the main candidate pathways and discuss the available biochemical, transcriptomic, and genetic evidence relating to each. Our analysis emphasizes how much is still to be elucidated on this question, which is likely important for a full understanding of how stress-related redox regulation might impinge on phytohormone-related and other signalling pathways in plants.

  18. Oxidative stress, redox signalling and endothelial dysfunction in ageing-related neurodegenerative diseases: a role of NADPH oxidase 2.

    Science.gov (United States)

    Cahill-Smith, Sarah; Li, Jian-Mei

    2014-09-01

    Chronic oxidative stress and oxidative damage of the cerebral microvasculature and brain cells has become one of the most convincing theories in neurodegenerative pathology. Controlled oxidative metabolism and redox signalling in the central nervous system are crucial for maintaining brain function; however, excessive production of reactive oxygen species and enhanced redox signalling damage neurons. While several enzymes and metabolic processes can generate intracellular reactive oxygen species in the brain, recently an O2−-generating enzyme, NADPH oxidase 2 (Nox2), has emerged as a major source of oxidative stress in ageing-related vascular endothelial dysfunction and neurodegenerative diseases. The currently available inhibitors of Nox2 are not specific, and general antioxidant therapy is not effective in the clinic; therefore, insights into the mechanism of Nox2 activation and its signalling pathways are needed for the discovery of novel drug targets to prevent or treat these neurodegenerative diseases. This review summarizes the recent developments in understanding the mechanisms of Nox2 activation and redox-sensitive signalling pathways and biomarkers involved in the pathophysiology of the most common neurodegenerative diseases, such as ageing-related mild cognitive impairment, Alzheimer's disease and Parkinson's disease.

  19. Chemical Biology of Hydropersulfides and Related Species: Possible Roles in Cellular Protection and Redox Signaling.

    Science.gov (United States)

    Álvarez, Lucía; Bianco, Christopher L; Toscano, John P; Lin, Joseph; Akaike, Takaaki; Fukuto, Jon M

    2017-10-01

    For >20 years, physiological signaling associated with the endogenous generation of hydrogen sulfide (H2S) has been of significant interest. Despite its presumed importance, the biochemical mechanisms associated with its actions have not been elucidated. Recent Advances: Recently it has been found that H2S-related or derived species are highly prevalent in mammalian systems and that these species may be responsible for some, if not the majority, of the biological actions attributed to H2S. One of the most prevalent and intriguing species are hydropersulfides (RSSH), which can be present at significant levels. Indeed, it appears that H2S and RSSH are intimately linked in biological systems and likely to be mutually inclusive. The fact that H2S and polysulfides such as RSSH are present simultaneously means that the biological actions previously assigned to H2S can be instead because of the presence of RSSH (or other polysulfides). Thus, it remains possible that hydropersulfides are the biological effectors, and H2S serves, to a certain extent, as a marker for persulfides and polysulfides. Addressing this possibility will to a large extent be based on the chemistry of these species. Currently, it is known that persulfides possess unique and novel chemical properties that may explain their biological prevalence. However, significantly more work will be required to establish the possible physiological roles of these species. Moreover, an understanding of the regulation of their biosynthesis and degradation will become important topics in piecing together their biology. Antioxid. Redox Signal. 00, 000-000.

  20. Special Issue: Redox Active Natural Products and Their Interaction with Cellular Signalling Pathways

    Directory of Open Access Journals (Sweden)

    Claus Jacob

    2014-11-01

    Full Text Available During the last decade, research into natural products has experienced a certain renaissance. The urgent need for more and more effective antibiotics in medicine, the demand for ecologically friendly plant protectants in agriculture, “natural” cosmetics and the issue of a sustainable and healthy nutrition in an ageing society have fuelled research into Nature’s treasure chest of “green gold”. Here, redox active secondary metabolites from plants, fungi, bacteria and other (micro-organisms often have been at the forefront of the most interesting developments. These agents provide powerful means to interfere with many, probably most cellular signaling pathways in humans, animals and lower organisms, and therefore can be used to protect, i.e., in form of antioxidants, and to frighten off or even kill, i.e., in form of repellants, antibiotics, fungicides and selective, often catalytic “sensor/effector” anticancer agents. Interestingly, whilst natural product research dates back many decades, in some cases even centuries, and compounds such as allicin and various flavonoids have been investigated thoroughly in the past, it has only recently become possible to investigate their precise interactions and mode(s of action inside living cells. Here, fluorescent staining and labelling on the one side, and appropriate detection, either qualitatively under the microscope or quantitatively in flow cytometers and plate readers, on the other, enable researchers to obtain the various pieces of information necessary to construct a fairly complete puzzle of how such compounds act and interact in living cells. Complemented by the more traditional activity assays and Western Blots, and increasingly joined by techniques such as proteomics, chemogenetic screening and mRNA profiling, these cell based bioanalytical techniques form a powerful platform for “intracellular diagnostics”. In the case of redox active compounds, especially of Reactive Sulfur

  1. Glutamate dehydrogenase 1 signals through antioxidant glutathione peroxidase 1 to regulate redox homeostasis and tumor growth.

    Science.gov (United States)

    Jin, Lingtao; Li, Dan; Alesi, Gina N; Fan, Jun; Kang, Hee-Bum; Lu, Zhou; Boggon, Titus J; Jin, Peng; Yi, Hong; Wright, Elizabeth R; Duong, Duc; Seyfried, Nicholas T; Egnatchik, Robert; DeBerardinis, Ralph J; Magliocca, Kelly R; He, Chuan; Arellano, Martha L; Khoury, Hanna J; Shin, Dong M; Khuri, Fadlo R; Kang, Sumin

    2015-02-09

    How mitochondrial glutaminolysis contributes to redox homeostasis in cancer cells remains unclear. Here we report that the mitochondrial enzyme glutamate dehydrogenase 1 (GDH1) is commonly upregulated in human cancers. GDH1 is important for redox homeostasis in cancer cells by controlling the intracellular levels of its product alpha-ketoglutarate and subsequent metabolite fumarate. Mechanistically, fumarate binds to and activates a reactive oxygen species scavenging enzyme glutathione peroxidase 1. Targeting GDH1 by shRNA or a small molecule inhibitor R162 resulted in imbalanced redox homeostasis, leading to attenuated cancer cell proliferation and tumor growth.

  2. Systemic induction of NO-, redox- and cGMP signalling in the pumpkin extrafascicular phloem upon local leaf wounding

    Directory of Open Access Journals (Sweden)

    Frank eGaupels

    2016-02-01

    Full Text Available Cucurbits developed the unique extrafascicular phloem (EFP as a defensive structure against herbivorous animals. Mechanical leaf injury was previously shown to induce a systemic wound response in the EFP of pumpkin (Cucurbita maxima. Here, we demonstrate that the phloem antioxidant system and protein modifications by NO are strongly regulated during this process. Activities of the central antioxidant enzymes dehydroascorbate reductase, glutathione reductase and ascorbate reductase were rapidly down-regulated at 30 min with a second minimum at 24 h after wounding. As a consequence levels of total ascorbate and glutathione also decreased with similar bi-phasic kinetics. These results hint towards a wound-induced shift in the redox status of the EFP. Nitric oxide (NO is another important player in stress-induced redox signalling in plants. Therefore, we analysed NO-dependent protein modifications in the EFP. Six to 48 h after leaf damage total S-nitrosothiol content and protein S-nitrosylation were clearly reduced, which was contrasted by a pronounced increase in protein tyrosine nitration. Collectively, these findings suggest that NO-dependent S-nitrosylation turned into peroxynitrite-mediated protein nitration upon a stress-induced redox shift probably involving the accumulation of reactive oxygen species within the EFP. Using the biotin switch assay and anti-nitrotyrosine antibodies we identified 9 candidate S-nitrosylated and 6 candidate tyrosine-nitrated phloem proteins. The wound-responsive Phloem Protein 16-1 (PP16-1 and Cyclophilin 18 (CYP18 as well as the 26.5 kD isoform of Phloem Protein 2 (PP2 were amenable to both NO modifications and could represent important redox-sensors within the cucurbit EFP. We also found that leaf injury triggered the systemic accumulation of cyclic guanosine monophosphate (cGMP in the EFP and discuss the possible function of this second messenger in systemic NO and redox signalling within the EFP.

  3. Technical training seminar: Data Converters and Linear Products for Signal Processing and Control

    CERN Multimedia

    Davide Vitè

    2006-01-01

    Monday 23 January 2006 TECHNICAL TRAINING SEMINAR from 14:00 to 17:30, Training Centre Auditorium (bldg. 503) Data Converters and Linear Products for Signal Processing and Control Marco Corsi, William Bright, Olrik Maier, Andrea Huder / TEXAS INSTRUMENTS (US, D, CH) Texas Instruments will present recent technology advances in design and manufacturing of A/D and D/A converters, and of operational amplifiers. 14:00 - 15:30 HIGH SPEED - Technology and the new process BiCom3: High speed ADCs, DACs, operational amplifiers 15:30 - 15:45 coffee 15:45 - 17:15 HIGH PRECISION - Technology and the new process HPA07: High precision ADCs, DACs, operational amplifiers questions, discussion Industrial partners: Robert Medioni, François Caloz Spoerle Electronic, CH-1440 Montagny (VD), Switzerland Phone: + 41 24 447 01 37, email: RMedioni@spoerle.com, http://www.spoerle.com Language: English. Free seminar (no registration). Organiser: Davide Vitè / HR-PMD-ATT / 75141 For more information, visit the Te...

  4. Ultra-low-power silicon photonics wavelength converter for phase-encoded telecommunication signals

    Science.gov (United States)

    Lacava, C.; Ettabib, M. A.; Cristiani, I.; Fedeli, J.-M.; Richardson, D. J.; Petropoulos, P.

    2016-03-01

    The development of compact, low power, silicon photonics CMOS compatible components for all-optical signal processing represents a key step towards the development of fully functional platforms for next generation all-optical communication networks. The wavelength conversion functionality at key nodes is highly desirable to achieve transparent interoperability and wavelength routing allowing efficient management of network resources operated with high speed, phase encoded signals. All optical wavelength conversion has already been demonstrated in Si-based devices, mainly utilizing the strong Kerr effect that silicon exhibits at telecommunication wavelengths. Unfortunately, Two Photon Absorption (TPA) and Free Carrier (FC) effects strongly limit their performance, even at moderate power levels, making them unsuitable for practical nonlinear applications. Amorphous silicon has recently emerged as a viable alternative to crystalline silicon (c-Si), showing both an enhanced Kerr as well as a reduced TPA coefficient at telecom wavelengths, with respect to its c-Si counterpart. Here we present an ultra-low power wavelength converter based on a passive, CMOS compatible, 1-mm long amorphous silicon waveguide operated at a maximum pump power level of only 70 mW. We demonstrate TPA-free Four Wave Mixing (FWM)-based wavelength conversion of Binary Phase Shift Keyed (BPSK) and Quadrature Phase Shift Keyed (QPSK) signals at 20 Gbit/s with <1 dB power penalty at BER = 10-5.

  5. Mycobacterium tuberculosis eis regulates autophagy, inflammation, and cell death through redox-dependent signaling.

    Directory of Open Access Journals (Sweden)

    Dong-Min Shin

    Full Text Available The "enhanced intracellular survival" (eis gene of Mycobacterium tuberculosis (Mtb is involved in the intracellular survival of M. smegmatis. However, its exact effects on host cell function remain elusive. We herein report that Mtb Eis plays essential roles in modulating macrophage autophagy, inflammatory responses, and cell death via a reactive oxygen species (ROS-dependent pathway. Macrophages infected with an Mtb eis-deletion mutant H37Rv (Mtb-Δeis displayed markedly increased accumulation of massive autophagic vacuoles and formation of autophagosomes in vitro and in vivo. Infection of macrophages with Mtb-Δeis increased the production of tumor necrosis factor-α and interleukin-6 over the levels produced by infection with wild-type or complemented strains. Elevated ROS generation in macrophages infected with Mtb-Δeis (for which NADPH oxidase and mitochondria were largely responsible rendered the cells highly sensitive to autophagy activation and cytokine production. Despite considerable activation of autophagy and proinflammatory responses, macrophages infected with Mtb-Δeis underwent caspase-independent cell death. This cell death was significantly inhibited by blockade of autophagy and c-Jun N-terminal kinase-ROS signaling, suggesting that excessive autophagy and oxidative stress are detrimental to cell survival. Finally, artificial over-expression of Eis or pretreatment with recombinant Eis abrogated production of both ROS and proinflammatory cytokines, which depends on the N-acetyltransferase domain of the Eis protein. Collectively, these data indicate that Mtb Eis suppresses host innate immune defenses by modulating autophagy, inflammation, and cell death in a redox-dependent manner.

  6. Soft Switched Synchronous Rectifier with Phase-Shifted Full Bridge Converter and Its Small-Signal Analysis

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    By using the output inductors and body capacitances without adding any component compared with hard switching synchronous rectifier,the topology of a soft switched synchronous rectifier with phase-shifted full bridge zero voltage switching DC/DC converter is proposed. The converter efficiency is maximized due to soft switching of the full bridge MOSFETs and the synchronous MOSFETs, and also the low conduction loss of synchronous MOSFET. The operation principles of the circuit are analyzed in detail and the small-signal model is derived, also the converter dynamic characteristics are analyzed. Frequency responses of transfer functions under different values of transformer primary leakage inductance are discussed. The experimental results were obtained from a 400 V input and 100 A/12 V output DC/DC converter operating at 100 kHz. The results show that the converter efficiency is 2% higher in rated power than traditional diode rectifier.

  7. AC Small Signal Modeling of PWM Y-Source Converter by Circuit Averaging and Averaged Switch Modeling Technique

    DEFF Research Database (Denmark)

    Forouzesh, Mojtaba; Siwakoti, Yam Prasad; Blaabjerg, Frede

    2016-01-01

    Magnetically coupled Y-source impedance network is a newly proposed structure with versatile features intended for various power converter applications e.g. in the renewable energy technologies. The voltage gain of the Y-source impedance network rises exponentially as a function of turns ratio......, which is inherited from a special coupled inductor with three windings. Due to the importance of modeling in the converter design procedure, this paper is dedicated to dc and ac small signal modeling of the PWM Y-source converter. The derived transfer functions are presented in detail and have been...

  8. Converting mid-infrared signals to near-infrared through optomechanical transduction

    Science.gov (United States)

    Kapsalis, A.; Mesaritakis, C.; Bogris, A.; Syvridis, D.

    2015-01-01

    Mid-infrared silicon photonics emerge as the dominant technology to bridge photonics and electronics in multifunctional high-speed integrated chips. The transmission and processing of optical signals lying at the mid-infrared wavelength region is ideal for sensing, absorption-spectroscopy and free-space communications and the use of group IV materials becomes principally promising as the vehicle towards their realization. In parallel, optical forces originating from modes and cavities can reach to outstandingly large values when sizes drop into the nanoscale. In this work, we propose the exploitation of large gradient optical forces generated between suspended silicon beams and optomechanical transduction as a means of converting signals from the mid-infrared to the near-infrared region. A midinfrared signal is injected into the waveguide system so as to excite the fundamental symmetric mode. In the 2-5μm wavelength range, separation gaps in the 100nm order and waveguide widths ranging from 300-600nm, the mode is mostly guided in the air slot between the waveguides which maximizes the optomechanical coupling coefficient and optical force. The resulting attractive force deflects the waveguides and the deflection is linearly dependent on the midinfrared optical power. A simple read-out technique using 1.55μm signals with conventional waveguiding in the directional coupler formed by the two beams is analyzed. A positive conversion efficiency (index unconventional guiding in mid-infrared could be a key component towards multifunctional lab-on-a-chip devices.

  9. Preprotein import into chloroplasts via the Toc and Tic complexes is regulated by redox signals in Pisum sativum.

    Science.gov (United States)

    Stengel, Anna; Benz, J Philipp; Buchanan, Bob B; Soll, Jürgen; Bölter, Bettina

    2009-11-01

    The import of nuclear-encoded preproteins is necessary to maintain chloroplast function. The recognition and transfer of most precursor proteins across the chloroplast envelopes are facilitated by two membrane-inserted protein complexes, the translocons of the chloroplast outer and inner envelope (Toc and Tic complexes, respectively). Several signals have been invoked to regulate the import of preproteins. In our study, we were interested in redox-based import regulation mediated by two signals: regulation based on thiols and on the metabolic NADP+/NADPH ratio. We sought to identify the proteins participating in the regulation of these transport pathways and to characterize the preprotein subgroups whose import is redox-dependent. Our results provide evidence that the formation and reduction of disulfide bridges in the Toc receptors and Toc translocation channel have a strong influence on import yield of all tested preproteins that depend on the Toc complex for translocation. Furthermore, the metabolic NADP+/NADPH ratio influences not only the composition of the Tic complex, but also the import efficiency of most, but not all, preproteins tested. Thus, several Tic subcomplexes appear to participate in the translocation of different preprotein subgroups, and the redox-active components of these complexes likely play a role in regulating transport.

  10. Transfer of a redox-signal through the cytosol by redox-dependent microcompartmentation of glycolytic enzymes at mitochondria and actin cytoskeleton

    Directory of Open Access Journals (Sweden)

    Joanna eWojtera-Kwiczor

    2013-01-01

    Full Text Available The cytosolic glyceraldehyde-3-phosphate dehydrogenase (GAPDH, EC 1.2.1.12, GapC plays an important role in glycolysis by providing the cell with ATP and NADH. Interestingly, despite its glycolytic function in the cytosol, GAPDH was reported to possess additional non-glycolytic activities, correlating with its nuclear or cytoskeletal localization in animal cells. In transiently transformed mesophyll protoplasts from Arabidopsis. thaliana colocalization and interaction of the glycolytic enzymes with the mitochondria and with the actin cytoskeleton was visualized by confocal laser scanning microscopy (cLSM using fluorescent protein fusions and by bimolecular fluorescence complementation (BiFC, respectively. Yeast two-hybrid screens, dot-blot overlay assays, and co-sedimentation assays were used to identify potential protein-protein interactions between two cytosolic GAPDH isoforms (GapC1, At3g04120; GapC2, At1g13440 from A. thaliana with the neighbouring glycolytic enzyme, fructose 1,6-bisphosphate aldolase (FBA6, At2g36460, the mitochondrial porin (VDAC3; At5g15090, and actin in vitro. From these experiments, a mitochondrial association is suggested for both glycolytic enzymes, GAPDH and aldolase, which appear to bind to the outer mitochondrial membrane, in a redox-dependent manner. In addition, both glycolytic enzymes were found to bind to F-actin in cosedimentation assays, and lead to bundling of purified rabbit actin, as visualized by cLSM. Actin binding and bundling occurred reversibly under oxidizing conditions. We speculate that such dynamic formation of microcompartments is part of a redox-dependent retrograde signal transduction network for adaptation upon oxidative stress.

  11. Cell signaling (mechanism and reproductive toxicity): redox chains, radicals, electrons, relays, conduit, electrochemistry, and other medical implications.

    Science.gov (United States)

    Kovacic, Peter; Pozos, Robert S

    2006-12-01

    This article deals with a novel, simple, integrated approach to cell signaling involving basic biochemical principles, and their relationship to reproductive toxicity. Initially, an overview of the biological aspects is presented. According to the hypothetical approach, cell signaling entails interaction of redox chains, involving initiation, propagation, and termination. The messengers are mainly radicals and electrons that are generated during electron transfer (ET) and hydrogen atom abstraction reactions. Termination and initiation processes in the chain occur at relay sites occupied by redox functionalities, including quinones, metal complexes, and imines, as well as redox amino acids. Conduits for the messengers, comprising species with nonbonding electrons, are omnipresent. Details are provided for the various electron transfer processes. In relation to the varying rates of cell communication, rationale is based on electrons and size of radicals. Another fit is similarly seen in inspection of endogenous precursors of reactive oxygen species (ROS); namely, proteins bearing redox moieties, lipid oxidation products, and carbohydrate radicals. A hypothesis is advanced in which electromagnetic fields associated with mobile radicals and electrons play a role. Although radicals have previously been investigated as messengers, the area occupies a minor part of the research, and it has not attracted broad consensus as an important component. For the first time, an integrated framework is presented composed of radicals, electrons, relays, conduits, and electrical fields. The approach is in keeping with the vast majority of experimental observations. Cell signaling also plays an important role in reproductive toxicity. The main classes that cause birth defects, including ROS, radiation, metal compounds, medicinals, abused drugs, and miscellaneous substances, are known to participate in the signaling process. A unifying basis exists, in that both signaling and

  12. Redox modulation of adjacent thiols in VLA-4 by AS101 converts myeloid leukemia cells from a drug-resistant to drug-sensitive state.

    Science.gov (United States)

    Layani-Bazar, Adi; Skornick, Itai; Berrebi, Alain; Pauker, Maor H; Noy, Elad; Silberman, Alon; Albeck, Michael; Longo, Dan L; Kalechman, Yona; Sredni, Benjamin

    2014-06-01

    Interaction between the integrin VLA-4 on acute myelogenous leukemia (AML) cells with stromal fibronectin is a decisive factor in chemotherapeutic resistance. In this study, we provide a rationale for a drug repositioning strategy to blunt integrin activation in AML cells and restore their sensitivity to chemotherapy. Specifically, we demonstrate that the nontoxic tellurium compound AS101, currently being evaluated in clinical trials, can abrogate the acquired resistance of AML. Mechanistic investigations revealed that AS101 caused redox inactivation of adjacent thiols in the exofacial domain of VLA-4 after its ligation to stromal fibronectin. This effect triggered cytoskeletal conformational changes that decreased PI3K/Akt/Bcl2 signaling, an obligatory step in chemosensitization by AS101. In a mouse xenograft of AML derived from patient leukemic cells with high VLA-4 expression and activity, we demonstrated that AS101 abrogated drug resistance and prolonged survival in mice receiving chemotherapy. Decreased integrin activity was confirmed on AML cells in vivo. The chemosensitizing activity of AS101 persisted in hosts with defective adaptive and innate immunity, consistent with evidence that integrin deactivation was not mediated by heightening immune attack. Our findings provide a mechanistic rationale to reposition the experimental clinical agent, AS101, to degrade VLA-4-mediated chemoresistance and improve clinical responses in patients with AML.

  13. Oxidative stress, redox signaling pathways, and autophagy in cachectic muscles of male patients with advanced COPD and lung cancer.

    Science.gov (United States)

    Puig-Vilanova, Ester; Rodriguez, Diego A; Lloreta, Josep; Ausin, Pilar; Pascual-Guardia, Sergio; Broquetas, Joan; Roca, Josep; Gea, Joaquim; Barreiro, Esther

    2015-02-01

    Muscle dysfunction and wasting are predictors of mortality in advanced COPD and malignancies. Redox imbalance and enhanced protein catabolism are underlying mechanisms in COPD. We hypothesized that the expression profile of several biological markers share similarities in patients with cachexia associated with either COPD or lung cancer (LC). In vastus lateralis of cachectic patients with either LC (n=10) or advanced COPD (n=16) and healthy controls (n=10), markers of redox balance, inflammation, proteolysis, autophagy, signaling pathways, mitochondrial function, muscle structure, and sarcomere damage were measured using laboratory and light and electron microscopy techniques. Systemic redox balance and inflammation were also determined. All subjects were clinically evaluated. Compared to controls, in both cachectic groups of patients, a similar expression profile of different biological markers was observed in their muscles: increased levels of muscle protein oxidation and ubiquitination (pmuscle structural abnormalities and sarcomere disruptions were significantly greater (pmuscles of both cachectic patient groups than in controls (pmuscles of cachectic COPD patients (pmuscle wasting and sarcomere disruption in patients with respiratory cachexia: LC and COPD.

  14. Synthesis of redox-active molecules and their signaling functions during the expression of plant disease resistance.

    Science.gov (United States)

    Skelly, Michael J; Loake, Gary J

    2013-09-20

    Activation of immune responses in plants is associated with a parallel burst of both reactive oxygen intermediates (ROIs) and nitric oxide (NO). The mechanisms by which these small redox-active molecules are synthesized and their signaling functions are critical for plants to defend themselves against pathogen infection. The synthesis of apoplastic ROIs by plants after pathogen recognition has long been attributed to membrane-bound NAPDH oxidases. However, the emerging data suggest a role for other enzymes in various subcellular locations in ROI production after defense activation. It is becoming widely appreciated that NO exerts its biochemical function through the S-nitrosylation of reactive cysteine thiols on target proteins, constituting a key post-translational modification. Recent evidence suggests that S-nitrosylation of specific defense-related proteins regulates their activity. The source(s) of NO production after pathogen recognition remain(s) poorly understood. Some NO synthesis can be attributed to the activity of nitrate reductase but to date, no nitric oxide synthase (NOS) has been identified in higher plants. However, the signaling functions of S-nitrosylation are becoming more apparent and thus dissecting the molecular machinery underpinning this redox-based modification is vital to further our understanding of plant disease resistance. In addition to identifying new contributors to the oxidative burst, the discovery of an NOS in higher plants would significantly move the field forward. Since S-nitrosylation has now been confirmed to play various roles in immune signaling, this redox-based modification is a potential target to exploit for improving disease resistance in crop species.

  15. Caenorhabditis elegans as Model System in Pharmacology and Toxicology: Effects of Flavonoids on Redox-Sensitive Signalling Pathways and Ageing

    Directory of Open Access Journals (Sweden)

    Karoline Koch

    2014-01-01

    Full Text Available Flavonoids are secondary plant compounds that mediate diverse biological activities, for example, by scavenging free radicals and modulating intracellular signalling pathways. It has been shown in various studies that distinct flavonoid compounds enhance stress resistance and even prolong the life span of organisms. In the last years the model organism C. elegans has gained increasing importance in pharmacological and toxicological sciences due to the availability of various genetically modified nematode strains, the simplicity of modulating genes by RNAi, and the relatively short life span. Several studies have been performed demonstrating that secondary plant compounds influence ageing, stress resistance, and distinct signalling pathways in the nematode. Here we present an overview of the modulating effects of different flavonoids on oxidative stress, redox-sensitive signalling pathways, and life span in C. elegans introducing the usability of this model system for pharmacological and toxicological research.

  16. Opposing regulation of histamine-induced calcium signaling by sodium selenite and ebselen via alterations of thiol redox status.

    Science.gov (United States)

    Zhang, Huihui; Zhong, Liangwei

    2010-01-25

    Elevated blood histamine plays a role in the pathogenesis of atherosclerosis. Calcium signaling mediates histamine action in endothelial cells. Selenium (Se) is a dietary essential trace element for humans. Se compounds in different oxidation states were found to exhibit an opposing effect on the histamine-induced calcium signaling in the ECV304 cell line. When Se in the form of sodium selenite was added in the cell culture, the reactivity of the histamine H(1)-receptor was increased as reported in our previous paper. We here show that as a culture supplement, sodium selenite enhanced the activity of selenoprotein thioredoxin reductase (TrxR) and the calcium response to histamine stimulation, which were reversed by treating the cells with gold thioglucose, a nucleophilic drug that selectively modifies thiolate/selenolate groups. Sodium selenite most likely caused a reductive shift in the thiol/disulfide redox balance through increasing TrxR activity. In contrast, when the cells were treated with Se in the form of ebselen, a thiol oxidant with peroxidase-like activity, histamine-induced calcium release and calcium entry were significantly suppressed. This effect appeared related to the thiol-directed modification rather than the peroxidase-like activity of ebselen, because this inhibitory effect was not replicated by increasing cellular peroxidase activity. Thus, the opposing effects of sodium selenite and ebselen on histamine-induced calcium signaling are achieved, at least in part, through their opposite actions in modulating the thiol/disulfide redox state.

  17. Analysis of subpulse generation from delayed-interference signal-wavelength converter for wide carrier recovery rate range

    DEFF Research Database (Denmark)

    Sakaguchi, J.; Nielsen, Mads Lønstrup; Ohira, T.;

    2008-01-01

    The generation of subpulses in delayed-interference signal-wavelength converters (DISCS) had been suspected as a Curse of waveform degradation in their application in ultrafast (similar to 160GHz) optical time division multiplexing (OTDM) communication systems. We reported its first observation i...

  18. High-resolution imaging of redox signaling in live cells through an oxidation-sensitive yellow fluorescent protein

    DEFF Research Database (Denmark)

    Maulucci, Giuseppe; Labate, Valentina; Mele, Marina;

    2008-01-01

    quantitation of the distribution of fluorescence by confocal microscopy, allows us to draw real-time "redox maps" of adherent cells and to score subtle changes in the intracellular redox state, such as those induced by overexpression of redox-active proteins. This strategy for in vivo imaging of redox...

  19. A Methodology to Teach Advanced A/D Converters, Combining Digital Signal Processing and Microelectronics Perspectives

    Science.gov (United States)

    Quintans, C.; Colmenar, A.; Castro, M.; Moure, M. J.; Mandado, E.

    2010-01-01

    ADCs (analog-to-digital converters), especially Pipeline and Sigma-Delta converters, are designed using complex architectures in order to increase their sampling rate and/or resolution. Consequently, the learning of ADC devices also encompasses complex concepts such as multistage synchronization, latency, oversampling, modulation, noise shaping,…

  20. Maternal inflammation contributes to brain overgrowth and autism-associated behaviors through altered redox signaling in stem and progenitor cells.

    Science.gov (United States)

    Le Belle, Janel E; Sperry, Jantzen; Ngo, Amy; Ghochani, Yasmin; Laks, Dan R; López-Aranda, Manuel; Silva, Alcino J; Kornblum, Harley I

    2014-11-11

    A period of mild brain overgrowth with an unknown etiology has been identified as one of the most common phenotypes in autism. Here, we test the hypothesis that maternal inflammation during critical periods of embryonic development can cause brain overgrowth and autism-associated behaviors as a result of altered neural stem cell function. Pregnant mice treated with low-dose lipopolysaccharide at embryonic day 9 had offspring with brain overgrowth, with a more pronounced effect in PTEN heterozygotes. Exposure to maternal inflammation also enhanced NADPH oxidase (NOX)-PI3K pathway signaling, stimulated the hyperproliferation of neural stem and progenitor cells, increased forebrain microglia, and produced abnormal autism-associated behaviors in affected pups. Our evidence supports the idea that a prenatal neuroinflammatory dysregulation in neural stem cell redox signaling can act in concert with underlying genetic susceptibilities to affect cellular responses to environmentally altered cellular levels of reactive oxygen species.

  1. Maternal Inflammation Contributes to Brain Overgrowth and Autism-Associated Behaviors through Altered Redox Signaling in Stem and Progenitor Cells

    Directory of Open Access Journals (Sweden)

    Janel E. Le Belle

    2014-11-01

    Full Text Available A period of mild brain overgrowth with an unknown etiology has been identified as one of the most common phenotypes in autism. Here, we test the hypothesis that maternal inflammation during critical periods of embryonic development can cause brain overgrowth and autism-associated behaviors as a result of altered neural stem cell function. Pregnant mice treated with low-dose lipopolysaccharide at embryonic day 9 had offspring with brain overgrowth, with a more pronounced effect in PTEN heterozygotes. Exposure to maternal inflammation also enhanced NADPH oxidase (NOX-PI3K pathway signaling, stimulated the hyperproliferation of neural stem and progenitor cells, increased forebrain microglia, and produced abnormal autism-associated behaviors in affected pups. Our evidence supports the idea that a prenatal neuroinflammatory dysregulation in neural stem cell redox signaling can act in concert with underlying genetic susceptibilities to affect cellular responses to environmentally altered cellular levels of reactive oxygen species.

  2. All optical up-converted signal generation with high dispersion tolerance using frequency quadrupling technique for radio over fiber system

    Science.gov (United States)

    Gu, Yiying; Zhao, Jiayi; Hu, Jingjing; Kang, Zijian; Zhu, Wenwu; Fan, Feng; Han, Xiuyou; Zhao, Mingshan

    2016-05-01

    A novel all optical up-converted signal generation scheme with optical single-sideband (OSSB) technique for radio over fiber (RoF) application is presented and experimentally demonstrated using low-bandwidth devices. The OSSB signal is generated by one low-bandwidth intensity LiNbO3 Mach-Zehnder modulator (LN-MZM) under frequency quadrupling modulation scheme and one low-bandwidth LN-MZM under double sideband carrier suppressed modulation (DSB-CS) scheme. The proposed all OSSB generation scheme is capable of high tolerance of fiber chromatic dispersion induced power fading (DIPF) effect. Benefiting from this novel OSSB generation scheme, a 26 GHz radio frequency (RF) signal up-conversion is realized successfully when one sideband of the optical LO signal is reused as the optical carrier for intermediate frequency (IF) signal modulation. The received vector signal transmission over long distance single-mode fiber (SMF) shows negligible DIPF effect with the error vector magnitude (EVM) of 15.7% rms. In addition, a spurious free dynamic range (SFDR) of the OSSB up-converting system is measured up to 81 dB Hz2/3. The experiment results indicate that the proposed system may find potential applications in future wireless communication networks, especially in microcellular personal communication system (MPCS).

  3. Design, development, and fabrication of a electronic analog microminiaturized electronic analog signal to discrete time interval converter

    Science.gov (United States)

    Schoenfeld, A. D.; Schuegraf, K. K.

    1973-01-01

    The microminiaturization of an electronic analog signal to discrete time interval converter is presented. Discrete components and integrated circuits comprising the converter were assembled on a thin-film ceramic substrate containing nichrome resistors with gold interconnections. The finished assembly is enclosed in a flat package measuring 3.30 by 4.57 centimeters. The module can be used whenever conversion of analog to digital signals is required, in particular for the purpose of regulation by means of pulse modulation. In conjunction with a precision voltage reference, the module was applied to control the duty cycle of a switching regulator within a temperature range of -55 C to +125 C, and an input voltage range of 10V to 35V. The output-voltage variation was less than + or - 300 parts per million, i.e., less than + or - 3mV for a 10V output.

  4. PARTICIPATION OF REDOX SIGNALIZATION IN NITRIC OXIDE-, CARBON MONOXIDE- AND HUDROGEN SULFIDE-MEDIATED REGULATION OF APOPTOSIS AND CELL CYCLE

    Directory of Open Access Journals (Sweden)

    Ye. G. Starikova

    2013-01-01

    Full Text Available The study has demonstrated that proapoptic concentrations of donors of NO (100 mmol SNP and 100 µmol NOC-5, H2S  (10 mmol NaHS, and CO (50 µmol CORM-2 gases caused an increase in the intracellular level of active forms of oxygen in Jurkat cells. As this took place, the activation of redox-dependent transcription factor р53 was observed as Jurkat cells were exposed to 100 mmol SNP and 10 mmol NaHS. In the case of 100 µmol NOC-5 and 50 µmol CORM-2, an increase of р53 was not observed, but the expression of target gens of this transcription factor р21 (under the effect of NO and СО and bax (under the effect of NO increased. The antiproliferative concentration of hydrogen sulfide donor (50 µmol did not cause an increase in the intracellular production of active forms of oxygen and the activation of redox-dependent signal mechanisms.

  5. Cold Atmospheric Plasma Treatment Induces Anti-Proliferative Effects in Prostate Cancer Cells by Redox and Apoptotic Signaling Pathways.

    Directory of Open Access Journals (Sweden)

    Martin Weiss

    Full Text Available One of the promising possibilities of the clinical application of cold plasma, so-called cold atmospheric plasma (CAP, is its application on malignant cells and cancer tissue using its anti-neoplastic effects, primarily through the delivery of reactive oxygen and nitrogen species (ROS, RNS. In this study, we investigated the impact of CAP on cellular proliferation and consecutive molecular response mechanisms in established prostate cancer (PC cell lines. PC cells showed a significantly reduced cell growth following CAP treatment as a result of both an immediate increase of intracellular peroxide levels and through the induction of apoptosis indicated by annexin V assay, TUNEL assay, and the evaluation of changes in nuclear morphology. Notably, co-administration of N-acetylcysteine (NAC completely neutralized CAP effects by NAC uptake and rapid conversion to glutathione (GSH. Vitamin C could not counteract the CAP induced effects on cell growth. In summary, relatively short treatments with CAP of 10 seconds were sufficient to induce a significant inhibition of cancer proliferation, as observed for the first time in urogenital cancer. Therefore, it is important to understand the mode of CAP related cell death and clarify and optimize CAP as cancer therapy. Increased levels of peroxides can alter redox-regulated signaling pathways and can lead to growth arrest and apoptosis. We assume that the general intracellular redox homeostasis, especially the levels of cellular GSH and peroxidases such as peroxiredoxins affect the outcome of the CAP treatment.

  6. Cold Atmospheric Plasma Treatment Induces Anti-Proliferative Effects in Prostate Cancer Cells by Redox and Apoptotic Signaling Pathways.

    Science.gov (United States)

    Weiss, Martin; Gümbel, Denis; Hanschmann, Eva-Maria; Mandelkow, Robert; Gelbrich, Nadine; Zimmermann, Uwe; Walther, Reinhard; Ekkernkamp, Axel; Sckell, Axel; Kramer, Axel; Burchardt, Martin; Lillig, Christopher H; Stope, Matthias B

    2015-01-01

    One of the promising possibilities of the clinical application of cold plasma, so-called cold atmospheric plasma (CAP), is its application on malignant cells and cancer tissue using its anti-neoplastic effects, primarily through the delivery of reactive oxygen and nitrogen species (ROS, RNS). In this study, we investigated the impact of CAP on cellular proliferation and consecutive molecular response mechanisms in established prostate cancer (PC) cell lines. PC cells showed a significantly reduced cell growth following CAP treatment as a result of both an immediate increase of intracellular peroxide levels and through the induction of apoptosis indicated by annexin V assay, TUNEL assay, and the evaluation of changes in nuclear morphology. Notably, co-administration of N-acetylcysteine (NAC) completely neutralized CAP effects by NAC uptake and rapid conversion to glutathione (GSH). Vitamin C could not counteract the CAP induced effects on cell growth. In summary, relatively short treatments with CAP of 10 seconds were sufficient to induce a significant inhibition of cancer proliferation, as observed for the first time in urogenital cancer. Therefore, it is important to understand the mode of CAP related cell death and clarify and optimize CAP as cancer therapy. Increased levels of peroxides can alter redox-regulated signaling pathways and can lead to growth arrest and apoptosis. We assume that the general intracellular redox homeostasis, especially the levels of cellular GSH and peroxidases such as peroxiredoxins affect the outcome of the CAP treatment.

  7. Fyn is a redox sensor involved in solar ultraviolet light-induced signal transduction in skin carcinogenesis

    Science.gov (United States)

    Kim, Jong-Eun; Roh, Eunmiri; Lee, Mee Hyun; Yu, Dong Hoon; Kim, Dong Joon; Lim, Tae-Gyu; Jung, Sung Keun; Peng, Cong; Cho, Yong-Yeon; Dickinson, Sally; Alberts, Dave; Bowden, G. Tim; Einspahr, Janine; Stratton, Steven P; Curiel, Clara; Bode, Ann M.; Lee, Ki Won; Dong, Zigang

    2015-01-01

    Solar ultraviolet (UV) light is a major etiological factor in skin carcinogenesis, with solar UV-stimulated signal transduction inducing pathological changes and skin damage. The primary sensor of solar UV-induced cellular signaling has not been identified. We use an experimental system of solar simulated light (SSL) to mimic solar UV and we demonstrate that Fyn is a primary redox sensor involved in SSL-induced signal transduction. Reactive oxygen species (ROS) generated by SSL exposure directly oxidize Cys488 of Fyn, resulting in increased Fyn kinase activity. Fyn oxidation was increased in mouse skin after SSL exposure, and Fyn knockout (Fyn−/−) mice formed larger and more tumors compared to Fyn wildtype mice when exposed to SSL for an extended period of time. Murine embryonic fibroblasts (MEFs) lacking Fyn as well as cells in which Fyn expression was knocked down were resistant to SSL-induced apoptosis. Furthermore, cells expressing mutant Fyn (C448A) were resistant to SSL-induced apoptosis. These findings suggest that Fyn acts as a regulatory nexus between solar UV, ROS and signal transduction during skin carcinogenesis. PMID:26686094

  8. Nitric oxide-induced murine hematopoietic stem cell fate involves multiple signaling proteins, gene expression, and redox modulation.

    Science.gov (United States)

    Nogueira-Pedro, Amanda; Dias, Carolina C; Regina, Helena; Segreto, C; Addios, Priscilla C; Lungato, Lisandro; D'Almeida, Vania; Barros, Carlos C; Higa, Elisa M S; Buri, Marcus V; Ferreira, Alice T; Paredes-Gamero, Edgar Julian

    2014-11-01

    There are a growing number of reports showing the influence of redox modulation in cellular signaling. Although the regulation of hematopoiesis by reactive oxygen species (ROS) and reactive nitrogen species (RNS) has been described, their direct participation in the differentiation of hematopoietic stem cells (HSCs) remains unclear. In this work, the direct role of nitric oxide (NO(•)), a RNS, in the modulation of hematopoiesis was investigated using two sources of NO(•) , one produced by endothelial cells stimulated with carbachol in vitro and another using the NO(•)-donor S-nitroso-N-acetyl-D,L-penicillamine (SNAP) in vivo. Two main NO(•) effects were observed: proliferation of HSCs-especially of the short-term HSCs-and its commitment and terminal differentiation to the myeloid lineage. NO(•)-induced proliferation was characterized by the increase in the number of cycling HSCs and hematopoietic progenitor cells positive to BrdU and Ki-67, upregulation of Notch-1, Cx43, PECAM-1, CaR, ERK1/2, Akt, p38, PKC, and c-Myc. NO(•)-induced HSCs differentiation was characterized by the increase in granulocytic-macrophage progenitors, granulocyte-macrophage colony forming units, mature myeloid cells, upregulation of PU.1, and C/EBPα genes concomitantly to the downregulation of GATA-3 and Ikz-3 genes, activation of Stat5 and downregulation of the other analyzed proteins mentioned above. Also, redox status modulation differed between proliferation and differentiation responses, which is likely associated with the transition of the proliferative to differentiation status. Our findings provide evidence of the role of NO(•) in inducing HSCs proliferation and myeloid differentiation involving multiple signaling. © 2014 AlphaMed Press.

  9. Plant redox proteomics

    DEFF Research Database (Denmark)

    Navrot, Nicolas; Finnie, Christine; Svensson, Birte

    2011-01-01

    In common with other aerobic organisms, plants are exposed to reactive oxygen species resulting in formation of post-translational modifications related to protein oxidoreduction (redox PTMs) that may inflict oxidative protein damage. Accumulating evidence also underscores the importance of redox...... PTMs in regulating enzymatic activities and controlling biological processes in plants. Notably, proteins controlling the cellular redox state, e.g. thioredoxin and glutaredoxin, appear to play dual roles to maintain oxidative stress resistance and regulate signal transduction pathways via redox PTMs....... To get a comprehensive overview of these types of redox-regulated pathways there is therefore an emerging interest to monitor changes in redox PTMs on a proteome scale. Compared to some other PTMs, e.g. protein phosphorylation, redox PTMs have received less attention in plant proteome analysis, possibly...

  10. Redox signaling via oxidative inactivation of PTEN modulates pressure-dependent myogenic tone in rat middle cerebral arteries.

    Directory of Open Access Journals (Sweden)

    Debebe Gebremedhin

    Full Text Available The present study examined the level of generation of reactive oxygen species (ROS and roles of inactivation of the phosphatase PTEN and the PI3K/Akt signaling pathway in response to an increase in intramural pressure-induced myogenic cerebral arterial constriction. Step increases in intraluminal pressure of cannulated cerebral arteries induced myogenic constriction and concomitant formation of superoxide (O2 (.- and its dismutation product hydrogen peroxide (H2O2 as determined by fluorescent HPLC analysis, microscopic analysis of intensity of dihydroethidium fluorescence and attenuation of pressure-induced myogenic constriction by pretreatment with the ROS scavenger 4,hydroxyl-2,2,6,6-tetramethylpiperidine1-oxyl (tempol or Mito-tempol or MitoQ in the presence or absence of PEG-catalase. An increase in intraluminal pressure induced oxidation of PTEN and activation of Akt. Pharmacological inhibition of endogenous PTEN activity potentiated pressure-dependent myogenic constriction and caused a reduction in NPo of a 238 pS arterial KCa channel current and an increase in [Ca(2+]i level in freshly isolated cerebral arterial muscle cells (CAMCs, responses that were attenuated by Inhibition of the PI3K/Akt pathway. These findings demonstrate an increase in intraluminal pressure induced increase in ROS production triggered redox-sensitive signaling mechanism emanating from the cross-talk between oxidative inactivation of PTEN and activation of the PI3K/Akt signaling pathway that involves in the regulation of pressure-dependent myogenic cerebral arterial constriction.

  11. An Analysis of the Solution Structure and Signaling Mechanism of LovK, a Sensor Histidine Kinase Integrating Light and Redox Signals

    Energy Technology Data Exchange (ETDEWEB)

    Purcell, Erin B.; McDonald, Claudia A.; Palfey, Bruce A.; Crosson, Sean (Michigan-Med); (UC)

    2010-12-07

    Flavin-binding LOV domains are broadly conserved in plants, fungi, archaea, and bacteria. These {approx}100-residue photosensory modules are generally encoded within larger, multidomain proteins that control a range of blue light-dependent physiologies. The bacterium Caulobacter crescentus encodes a soluble LOV-histidine kinase, LovK, that regulates the adhesive properties of the cell. Full-length LovK is dimeric as are a series of systematically truncated LovK constructs containing only the N-terminal LOV sensory domain. Nonconserved sequence flanking the LOV domain functions to tune the signaling lifetime of the protein. Size exclusion chromatography and small-angle X-ray scattering (SAXS) demonstrate that the LOV sensor domain does not undergo a large conformational change in response to photon absorption. However, limited proteolysis identifies a sequence flanking the C-terminus of the LOV domain as a site of light-induced change in protein conformation and dynamics. On the basis of SAXS envelope reconstruction and bioinformatic prediction, we propose this dynamic region of structure is an extended C-terminal coiled coil that links the LOV domain to the histidine kinase domain. To test the hypothesis that LOV domain signaling is affected by cellular redox state in addition to light, we measured the reduction potential of the LovK FMN cofactor. The measured potential of -258 mV is congruent with the redox potential of Gram-negative cytoplasm during logarithmic growth (-260 to -280 mV). Thus, a fraction of LovK in the cytosol may be in the reduced state under typical growth conditions. Chemical reduction of the FMN cofactor of LovK attenuates the light-dependent ATPase activity of the protein in vitro, demonstrating that LovK can function as a conditional photosensor that is regulated by the oxidative state of the cellular environment.

  12. Light intensity regulation of cab gene transcription is signaled by the redox state of the plastoquinone pool

    Energy Technology Data Exchange (ETDEWEB)

    Escoubas, J.M.; Lomas, M.; LaRoche, J. [Brookhaven National Lab., Upton, NY (United States)] [and others

    1995-10-24

    The eukaryotic green alga Dunaliella tertiolecta acclimates to decreased growth irradiance by increasing cellular levels of light-harvesting chlorophyll protein complex apoproteins associated with photosystem II (LHCIIs), whereas increased growth irradiance elicits the opposite response. Nuclear run-on transcription assays and measurements of cab mRNA stability established that light intensity-dependent changes in LHCII are controlled at the level of transcription. cab gene transcription in high-intensity light was partially enhanced by reducing plastoquinone with 3-(3,4-dichlorophenyl)-1,1-dimethyl urea (DCMU), whereas it was repressed in low-intensity light by partially inhibiting the oxidation of plastoquinol with 2,5-dibromo-3-methyl-6-isopropyl-p-benzoquinone (DBMIB). Uncouplers of photosynthetic electron transport and inhibition of water splitting had no effect on LHCII levels. These results strongly implicate the redox state of the plastoquinone pool in the chloroplast as a photon-sensing system that is coupled to the light-intensity regulation of nuclear-encoded cab gene transcription. The accumulation of cellular chlorophyll at low-intensity light can be blocked by cytoplasmically directed phosphatase inhibitors, such as okadaic acid, microcystin L-R, and tautomycin. Gel mobility-shift assays revealed that cells grown in high-intensity light contained proteins that bind to the promoter region of a cab gene carrying sequences homologous to higher plant light-responsive elements. On the basis of these experimental results, we propose a model for a light intensity signaling system where cab gene expression is reversibly repressed by a phosphorylated factor coupled to the redox status of plastoquinone through a chloroplast protein kinase. 54 refs., 5 figs.

  13. Redox Modulation of Cellular Signaling and Metabolism Through Reversible Oxidation of Methionine Sensors in Calcium Regulatory Proteins

    Energy Technology Data Exchange (ETDEWEB)

    Bigelow, Diana J.; Squier, Thomas C.

    2005-01-17

    Adaptive responses associated with environmental stressors are critical to cell survival. These involve the modulation of central signaling protein functions through site-specific and enzymatically reversible oxidative modifications of methionines to coordinate cellular metabolism, energy utilization, and calcium signaling. Under conditions when cellular redox and antioxidant defenses are overwhelmed, the selective oxidation of critical methionines within selected protein sensors functions to down-regulate energy metabolism and the further generation of reactive oxygen species (ROS). Mechanistically, these functional changes within protein sensors take advantage of the helix-breaking character of methionine sulfoxide. Thus, depending on either the ecological niche of the organism or the cellular milieu of different organ systems, cellular metabolism can be fine-tuned to maintain optimal function in the face of variable amounts of collateral oxidative damage. The sensitivity of several calcium regulatory proteins to oxidative modification provides cellular sensors that link oxidative stress to cellular response and recovery. Calmodulin (CaM) is one such critical calcium regulatory protein, which is functionally sensitive to methionine oxidation. Helix destabilization resulting from the oxidation of either Met{sup 144} or Met{sup 145} results in the nonproductive association between CaM and target proteins. The ability of oxidized CaM to stabilize its target proteins in an inhibited state with an affinity similar to that of native (unoxidized) CaM permits this central regulatory protein to function as a cellular rheostat that down-regulates energy metabolism in response to oxidative stress. Likewise, oxidation of a methionine within a critical switch region of the regulatory protein phospholamban is expected to destabilize the phosphorylationdependent helix formation necessary for the release of enzyme inhibition, resulting in a down-regulation of the Ca-ATPase in

  14. Redox regulation of epidermal growth factor receptor signaling during the development of pulmonary hypertension.

    Science.gov (United States)

    Rafikova, Olga; Rafikov, Ruslan; Kangath, Archana; Qu, Ning; Aggarwal, Saurabh; Sharma, Shruti; Desai, Julin; Fields, Taylor; Ludewig, Britta; Yuan, Jason X-Y; Jonigk, Danny; Black, Stephen M

    2016-06-01

    The development of pulmonary hypertension (PH) involves the uncontrolled proliferation of pulmonary smooth muscle cells via increased growth factor receptor signaling. However, the role of epidermal growth factor receptor (EGFR) signaling is controversial, as humans with advanced PH exhibit no changes in EGFR protein levels and purpose of the present study was to determine whether there are post-translational mechanisms that enhance EGFR signaling in PH. The EGFR inhibitor, gefinitib, significantly attenuated EGFR signaling and prevented the development of PH in monocrotaline (MCT)-exposed rats, confirming the contribution of EGFR activation in MCT induced PH. There was an early MCT-mediated increase in hydrogen peroxide, which correlated with the binding of the active metabolite of MCT, monocrotaline pyrrole, to catalase Cys377, disrupting its multimeric structure. This early oxidative stress was responsible for the oxidation of EGFR and the formation of sodium dodecyl sulfate (SDS) stable EGFR dimers through dityrosine cross-linking. These cross-linked dimers exhibited increased EGFR autophosphorylation and signaling. The activation of EGFR signaling did not correlate with pp60(src) dependent Y845 phosphorylation or EGFR ligand expression. Importantly, the analysis of patients with advanced PH revealed the same enhancement of EGFR autophosphorylation and covalent dimer formation in pulmonary arteries, while total EGFR protein levels were unchanged. As in the MCT exposed rat model, the activation of EGFR in human samples was independent of pp60(src) phosphorylation site and ligand expression. This study provides a novel molecular mechanism of oxidative stress stimulated covalent EGFR dimerization via tyrosine dimerization that contributes into development of PH.

  15. Natural dietary anti-cancer chemopreventive compounds: redox-mediated differential signaling mechanisms in cytoprotection of normal cellsversus cytotoxicity in tumor cells

    Institute of Scientific and Technical Information of China (English)

    Sujit NAIR; Wenge LI; Ah-Ng Tony KONG

    2007-01-01

    Many dietary phytochemicals exhibit health-beneficial effects including preven-tion of diseases such as cancer, as well as neurological, cardiovascular, inflam-matory, and metabolic diseases. Evolutionarily, herbivorous and omnivorous animals have been ingesting plants. This interaction between "animal-plant"ecosystems has resulted in an elaborate system of detoxification and defense mechanisms evolved by animals including humans. Mammalian cells, including human cells, respond to these dietary phytochemicals by "non-classical receptor sensing" mechanisms of electrophilic chemical-stress typified by "thiol-modu-lated" cellular signaling events primarily leading to the gene expression of phar-macologically beneficial effects, but sometimes unwanted cytotoxicity also. Our laboratory has been studying two groups of dietary phytochemical cancer-chemopreventive compounds (isothiocyanates and polyphenols), which are effective in chemical-induced, as well as genetically-induced, animal carcinogen-esis models. These compounds typically generate "cellular stress" and modulate gene expression of phase Ⅱ detoxifying/antioxidant enzymes. Electrophiles, reac-tive oxygen species, and reactive nitrogen species are known to act as second messengers in the modulation of many cellular signaling pathways leading to gene expression changes and pharmacological responses. Redox-sensitive tran-scription factors such as nuclear factor-E2-related factor 2 (Nrf2), AP-1, NF-κB, to cite a few examples, sense and transduce changes in the cellular redox status and modulate gene expression responses to oxidative and electrophilic stresses, pre-sumably via sulfhydryl modification of critical cysteine residues found on these proteins and/or other upstream redox-sensitive molecular targets. In the current review, we will explore dietary cancer chemopreventive phytochemicals, discuss the link between oxidative/electrophilic stresses and the redox circuitry, and con-sider different redox

  16. Fusarium oxysporum f.sp. ciceri race 1 induced redox state alterations are coupled to downstream defense signaling in root tissues of chickpea (Cicer arietinum L.).

    Science.gov (United States)

    Gupta, Sumanti; Bhar, Anirban; Chatterjee, Moniya; Das, Sampa

    2013-01-01

    Reactive oxygen species are known to play pivotal roles in pathogen perception, recognition and downstream defense signaling. But, how these redox alarms coordinate in planta into a defensive network is still intangible. Present study illustrates the role of Fusarium oxysporum f.sp ciceri Race1 (Foc1) induced redox responsive transcripts in regulating downstream defense signaling in chickpea. Confocal microscopic studies highlighted pathogen invasion and colonization accompanied by tissue damage and deposition of callose degraded products at the xylem vessels of infected roots of chickpea plants. Such depositions led to the clogging of xylem vessels in compatible hosts while the resistant plants were devoid of such obstructions. Lipid peroxidation assays also indicated fungal induced membrane injury. Cell shrinkage and gradual nuclear adpression appeared as interesting features marking fungal ingress. Quantitative real time polymerase chain reaction exhibited differential expression patterns of redox regulators, cellular transporters and transcription factors during Foc1 progression. Network analysis showed redox regulators, cellular transporters and transcription factors to coordinate into a well orchestrated defensive network with sugars acting as internal signal modulators. Respiratory burst oxidase homologue, cationic peroxidase, vacuolar sorting receptor, polyol transporter, sucrose synthase, and zinc finger domain containing transcription factor appeared as key molecular candidates controlling important hubs of the defense network. Functional characterization of these hub controllers may prove to be promising in understanding chickpea-Foc1 interaction and developing the case study as a model for looking into the complexities of wilt diseases of other important crop legumes.

  17. Fusarium oxysporum f.sp. ciceri race 1 induced redox state alterations are coupled to downstream defense signaling in root tissues of chickpea (Cicer arietinum L..

    Directory of Open Access Journals (Sweden)

    Sumanti Gupta

    Full Text Available Reactive oxygen species are known to play pivotal roles in pathogen perception, recognition and downstream defense signaling. But, how these redox alarms coordinate in planta into a defensive network is still intangible. Present study illustrates the role of Fusarium oxysporum f.sp ciceri Race1 (Foc1 induced redox responsive transcripts in regulating downstream defense signaling in chickpea. Confocal microscopic studies highlighted pathogen invasion and colonization accompanied by tissue damage and deposition of callose degraded products at the xylem vessels of infected roots of chickpea plants. Such depositions led to the clogging of xylem vessels in compatible hosts while the resistant plants were devoid of such obstructions. Lipid peroxidation assays also indicated fungal induced membrane injury. Cell shrinkage and gradual nuclear adpression appeared as interesting features marking fungal ingress. Quantitative real time polymerase chain reaction exhibited differential expression patterns of redox regulators, cellular transporters and transcription factors during Foc1 progression. Network analysis showed redox regulators, cellular transporters and transcription factors to coordinate into a well orchestrated defensive network with sugars acting as internal signal modulators. Respiratory burst oxidase homologue, cationic peroxidase, vacuolar sorting receptor, polyol transporter, sucrose synthase, and zinc finger domain containing transcription factor appeared as key molecular candidates controlling important hubs of the defense network. Functional characterization of these hub controllers may prove to be promising in understanding chickpea-Foc1 interaction and developing the case study as a model for looking into the complexities of wilt diseases of other important crop legumes.

  18. The roles of conditional disorder in redox proteins.

    Science.gov (United States)

    Reichmann, Dana; Jakob, Ursula

    2013-06-01

    Cells are constantly exposed to various oxidants, either generated endogenously due to metabolic activity or exogenously. One way that cells respond to oxidants is through the action of redox-regulated proteins. These proteins also play important roles in oxidant signaling and protein biogenesis events. The key sensors built into redox-regulated proteins are cysteines, which undergo reversible thiol oxidation in response to changes in the oxidation status of the cellular environment. In this review, we discuss three examples of redox-regulated proteins found in bacteria, mitochondria, and chloroplasts. These proteins use oxidation of their redox-sensitive cysteines to reversibly convert large structural domains into more disordered regions or vice versa. These massive structural rearrangements are directly implicated in the functions of these proteins. Copyright © 2013 Elsevier Ltd. All rights reserved.

  19. A review of redox signaling and the control of MAP kinase pathway in plants

    Directory of Open Access Journals (Sweden)

    Yukun Liu

    2017-04-01

    Full Text Available Mitogen-activated protein kinase (MAPK cascades are evolutionarily conserved modules among eukaryotic species that range from yeast, plants, flies to mammals. In eukaryotic cells, reactive oxygen species (ROS has both physiological and toxic effects. Both MAPK cascades and ROS signaling are involved in plant response to various biotic and abiotic stresses. It has been observed that not only can ROS induce MAPK activation, but also that disturbing MAPK cascades can modulate ROS production and responses. This review will discuss the potential mechanisms by which ROS may activate and/or regulate MAPK cascades in plants. The role of MAPK cascades and ROS signaling in regulating gene expression, stomatal function, and programmed cell death (PCD is also discussed. In addition, the relationship between Rboh-dependent ROS production and MAPK activation in PAMP-triggered immunity will be reviewed.

  20. Redox modulation of cellular metabolism through targeted degradation of signaling proteins by the proteasome

    Energy Technology Data Exchange (ETDEWEB)

    Squier, Thomas C.

    2006-02-01

    Under conditions of oxidative stress, the 20S proteasome plays a critical role in maintaining cellular homeostasis through the selective degradation of oxidized and damaged proteins. This adaptive stress response is distinct from ubiquitin-dependent pathways in that oxidized proteins are recognized and degraded in an ATP-independent mechanism, which can involve the molecular chaperone Hsp90. Like the regulatory complexes 19S and 11S REG, Hsp90 tightly associates with the 20S proteasome to mediate the recognition of aberrant proteins for degradation. In the case of the calcium signaling protein calmodulin, proteasomal degradation results from the oxidation of a single surface exposed methionine (i.e., Met145); oxidation of the other eight methionines has a minimal effect on the recognition and degradation of calmodulin by the proteasome. Since cellular concentrations of calmodulin are limiting, the targeted degradation of this critical signaling protein under conditions of oxidative stress will result in the downregulation of cellular metabolism, serving as a feedback regulation to diminish the generation of reactive oxygen species. The targeted degradation of critical signaling proteins, such as calmodulin, can function as sensors of oxidative stress to downregulate global rates of metabolism and enhance cellular survival.

  1. OSTEOPOROSIS AND ALZHEIMER PATHOLOGY: ROLE OF CELLULAR STRESS RESPONSE AND HORMETIC REDOX SIGNALING IN AGING AND BONE REMODELING

    Directory of Open Access Journals (Sweden)

    Vittorio eCalabrese

    2014-06-01

    Full Text Available Alzheimer’s disease (AD as well as osteoporosis are multifactorial progressive degenerative disorders characterized by low parenchymal density and microarchitectural deterioration of tissue. Though not referred to as one of the major complications of AD, osteoporosis and hip fracture are commonly observed in patients with AD, however, the mechanisms underlying this association remain poorly understood. Reactive oxygen species (ROS are generally recognized as intracellular redox signaling molecules involved in the regulation of bone metabolism, including receptor activator of nuclear factor-kB ligand (RANKL-dependent osteoclast differentiation, but they also have cytotoxic effects that include peroxidation of lipids and oxidative damage to proteins and DNA. ROS formation, which is positively implicated in cellular stress response mechanisms, is a highly regulated process controlled by a complex network of intracellular signaling pathways which regulate life span across species including vitagenes which are genes involved in preserving cellular homeostasis during stressful conditions. Vitagenes encode for heat shock proteins (Hsp Hsp32, Hsp70, the thioredoxin and the sirtuin protein systems. Dietary antioxidants, have recently been demonstrated to be neuroprotective through the activation of hormetic pathways, including vitagenes. The hormetic dose–response, has the potential to affect significantly the design of pre-clinical studies and clinical trials as well as strategies for optimal patient dosing in the treatment of numerous diseases. Given the broad cytoprotective properties of the heat shock response there is now strong interest in discovering and developing pharmacological agents capable of inducing stress responses. Here we focus on possible signaling mechanisms involved in bone remodeling and activation of vitagenes resulting in enhanced defense against energy and stress resistance homeostasis dysruption with consequent impact on

  2. Sensitive Electrochemical Detection of Human Methyltransferase Based on a Dual Signal Amplification Strategy Coupling Gold Nanoparticle-DNA Complexes with Ru(III) Redox Recycling.

    Science.gov (United States)

    Zhang, Hui; Dong, Huilei; Yang, Guoqing; Chen, Hongfei; Cai, Chenxin

    2016-11-15

    Effective detection of DNA methyltransferase (DNMT) activity is significant for cancer research. Herein, we developed a sensitive electroanalytical method to detect human DNA (cytosine-5)-methyltransferase 1 (DNMT1) from crude lysates of cancer cells. In this assay, capture DNA having a preferred DNMT1 methylation site was immobilized on a gold electrode and then hybridized with gold nanoparticle (Au NP)-DNA complexes. The modified electrodes were equilibrated with the lysate and then incubated with methylation-sensitive restriction enzyme. If the lysate was negative for DNMT1 activity, the Au NP-DNA complexes would be cut by the restriction enzyme and released from the electrode. Conversely, restriction enzyme cleavage would be blocked by the fully methylated duplexes, and the Au NP-DNA complexes would remain on the electrode. Electroactive Ru(NH3)6(3+) was used as the signal reporter, because of its electrostatic attraction to DNA, resulting in an electrochemical signal. Since the electrochemical signal reflects the amount of Ru(III) redox and the amount of Ru(III) redox is correlated with the activity of DNMT1, the activity of DNMT1 is proportional to the electrochemical signal. The signal could be amplified by the numerous DNAs on the Au NPs and further amplified by Ru(III) redox recycling. With this method, a detection limit down to 0.3 U/mL for pure DNMT1 and 8 MCF-7 cells was achieved. DNMT1 activities of different cell lines were also successfully evaluated.

  3. On Small-Signal Stability of Wind Power System with Full-Load Converter Interfaced Wind Turbines

    DEFF Research Database (Denmark)

    Knüppel, Thyge; Akhmatov, Vladislav; Nielsen, Jørgen Nygård;

    2010-01-01

    (WPP) equipped with a WPP voltage controller and comparisons are presented. The models of wind turbine and WPP voltage controller are kindly provided by Siemens Wind Power A/S for this work. The study is based on modal analysis which are complemented with simulations on the nonlinear system.......Small-signal stability analysis of power system oscillations is a well established field within power system analysis, but not much attention has yet been paid to systems with a high penetration of wind turbines and with large wind power plants. In this paper an analysis is presented which assess...... the impact of full-load converter interfaced wind turbines on power system small-signal stability. The study is based on a 7 generator network with lightly damped inter-area modes. A detailed wind turbine model with all grid relevant control functions is used in the study. Furthermore is the wind power plant...

  4. CMOS time-to-digital converters for mixed-mode signal processing

    Directory of Open Access Journals (Sweden)

    Fei Yuan

    2014-04-01

    Full Text Available This study provides an in-depth review of the principles, architectures and design techniques of CMOS time-to-digital converters (TDCs. The classification of TDCs is introduced. It is followed by the examination of the parameters quantifying the performance of TDCs. Sampling TDCs including direct-counter TDCs, tapped delay-line TDCs, pulse-shrinking delay-line TDCs, cyclic pulse-shrinking TDCs, direct-counter TDCs with interpolation, vernier TDCs, flash TDCs, successive approximation TDCs and pipelined TDCs are studied and their pros and cons are compared. Noise-shaping TDCs that reduce in-band noise below technology limit are investigated. These TDCs include gated ring oscillator TDCs, switched ring oscillator TDCs, relaxation oscillator TDCs, ΔΣ TDCs and MASH TDCs. The performance of sampling and noise-shaping TDCs is compared. The direction of future research on TDCs is explored.

  5. Role of CBFs as Integrators of Chloroplast Redox, Phytochrome and Plant Hormone Signaling during Cold Acclimation

    Directory of Open Access Journals (Sweden)

    Norman P. A. Hüner

    2013-06-01

    Full Text Available Cold acclimation of winter cereals and other winter hardy species is a prerequisite to increase subsequent freezing tolerance. Low temperatures upregulate the expression of C-repeat/dehydration-responsive element binding transcription factors (CBF/DREB1 which in turn induce the expression of COLD-REGULATED (COR genes. We summarize evidence which indicates that the integration of these interactions is responsible for the dwarf phenotype and enhanced photosynthetic performance associated with cold-acclimated and CBF-overexpressing plants. Plants overexpressing CBFs but grown at warm temperatures mimic the cold-tolerant, dwarf, compact phenotype; increased photosynthetic performance; and biomass accumulation typically associated with cold-acclimated plants. In this review, we propose a model whereby the cold acclimation signal is perceived by plants through an integration of low temperature and changes in light intensity, as well as changes in light quality. Such integration leads to the activation of the CBF-regulon and subsequent upregulation of COR gene and GA 2-oxidase (GA2ox expression which results in a dwarf phenotype coupled with increased freezing tolerance and enhanced photosynthetic performance. We conclude that, due to their photoautotrophic nature, plants do not rely on a single low temperature sensor, but integrate changes in light intensity, light quality, and membrane viscosity in order to establish the cold-acclimated state. CBFs appear to act as master regulators of these interconnecting sensing/signaling pathways.

  6. Chloroplast Redox Poise

    DEFF Research Database (Denmark)

    Steccanella, Verdiana

    the redox status of the plastoquinone pool and chlorophyll biosynthesis. Furthermore, in the plant cell, the equilibrium between redox reactions and ROS signals is also maintained by various balancing mechanisms among which the thioredoxin reductase-thioredoxin system (TR-Trx) stands out as a mediator......The redox state of the chloroplast is maintained by a delicate balance between energy production and consumption and is affected by the need to avoid increased production of reactive oxygen species (ROS). Redox power and ROS generated in the chloroplast are essential for maintaining physiological...... metabolic pathways and for optimizing chloroplast functions. The redox poise of photosynthetic electron transport components like plastoquinone is crucial to initiate signaling cascades and might also be involved in key biosynthetic pathways such as chlorophyll biosynthesis. We, therefore, explored...

  7. The genome of the generalist plant pathogen Fusarium avenaceum is enriched with genes involved in redox, signaling and secondary metabolism.

    Directory of Open Access Journals (Sweden)

    Erik Lysøe

    Full Text Available Fusarium avenaceum is a fungus commonly isolated from soil and associated with a wide range of host plants. We present here three genome sequences of F. avenaceum, one isolated from barley in Finland and two from spring and winter wheat in Canada. The sizes of the three genomes range from 41.6-43.1 MB, with 13217-13445 predicted protein-coding genes. Whole-genome analysis showed that the three genomes are highly syntenic, and share>95% gene orthologs. Comparative analysis to other sequenced Fusaria shows that F. avenaceum has a very large potential for producing secondary metabolites, with between 75 and 80 key enzymes belonging to the polyketide, non-ribosomal peptide, terpene, alkaloid and indole-diterpene synthase classes. In addition to known metabolites from F. avenaceum, fuscofusarin and JM-47 were detected for the first time in this species. Many protein families are expanded in F. avenaceum, such as transcription factors, and proteins involved in redox reactions and signal transduction, suggesting evolutionary adaptation to a diverse and cosmopolitan ecology. We found that 20% of all predicted proteins were considered to be secreted, supporting a life in the extracellular space during interaction with plant hosts.

  8. The Genome of the Generalist Plant Pathogen Fusarium avenaceum Is Enriched with Genes Involved in Redox, Signaling and Secondary Metabolism

    Science.gov (United States)

    Lysøe, Erik; Harris, Linda J.; Walkowiak, Sean; Subramaniam, Rajagopal; Divon, Hege H.; Riiser, Even S.; Llorens, Carlos; Gabaldón, Toni; Kistler, H. Corby; Jonkers, Wilfried; Kolseth, Anna-Karin; Nielsen, Kristian F.; Thrane, Ulf; Frandsen, Rasmus J. N.

    2014-01-01

    Fusarium avenaceum is a fungus commonly isolated from soil and associated with a wide range of host plants. We present here three genome sequences of F. avenaceum, one isolated from barley in Finland and two from spring and winter wheat in Canada. The sizes of the three genomes range from 41.6–43.1 MB, with 13217–13445 predicted protein-coding genes. Whole-genome analysis showed that the three genomes are highly syntenic, and share>95% gene orthologs. Comparative analysis to other sequenced Fusaria shows that F. avenaceum has a very large potential for producing secondary metabolites, with between 75 and 80 key enzymes belonging to the polyketide, non-ribosomal peptide, terpene, alkaloid and indole-diterpene synthase classes. In addition to known metabolites from F. avenaceum, fuscofusarin and JM-47 were detected for the first time in this species. Many protein families are expanded in F. avenaceum, such as transcription factors, and proteins involved in redox reactions and signal transduction, suggesting evolutionary adaptation to a diverse and cosmopolitan ecology. We found that 20% of all predicted proteins were considered to be secreted, supporting a life in the extracellular space during interaction with plant hosts. PMID:25409087

  9. Method of signal detection from silicon photomultipliers using fully differential Charge to Time Converter and fast shaper

    Energy Technology Data Exchange (ETDEWEB)

    Baszczyk, M., E-mail: baszczyk@agh.edu.pl [AGH University of Science and Technology, Department of Electronics, Krakow (Poland); Dorosz, P.; Glab, S.; Kucewicz, W. [AGH University of Science and Technology, Department of Electronics, Krakow (Poland); Mik, L. [AGH University of Science and Technology, Department of Electronics, Krakow (Poland); State Higher Vocational School, Tarnow (Poland); Sapor, M. [AGH University of Science and Technology, Department of Electronics, Krakow (Poland)

    2016-07-11

    The paper presents an implementation of fully differential readout method for Silicon Photomultipliers (SiPM). Front-end electronics consists of a fast and slow path. The former creates the trigger signal while the latter produces a pulse of width proportional to the input charge. The fast shaper generates unipolar pulse and utilizes the pole-zero cancelation circuit. The peaking time for single photoelectron is equal to 3.6 ns and the FWHM is 3.8 ns. The pulse width of the Charge to Time Converter (QTC) depends on the number of photons entering the SiPM at the moment of measurement. The QTC response is nonlinear but it allows us to work with signals in a wide dynamic range. The proposed readout method is effective in measurements of random signals where frequent events tend to pile-up. Thermal generation and afterpulses have a strong influence on the width of pulses from QTC. The proposed method enables us to distinguish those overlapping signals and get the reliable information on the number of detected photons.

  10. Stress-responsive sestrins link p53 with redox regulation and mammalian target of rapamycin signaling.

    Science.gov (United States)

    Budanov, Andrei V

    2011-09-15

    The tumor suppressor p53 protects organisms from most types of cancer through multiple mechanisms. The p53 gene encodes a stress-activated transcriptional factor that transcriptionally regulates a large set of genes with versatile functions. These p53-activated genes mitigate consequences of stress regulating cell viability, growth, proliferation, repair, and metabolism. Recently, we described a novel antioxidant function of p53, which is important for its tumor suppressor activity. Among the many antioxidant genes activated by p53, Sestrins (Sesns) are critical for suppression of reactive oxygen species (ROS) and protection from oxidative stress, transformation, and genomic instability. Sestrins can regulate ROS through their direct effect on antioxidant peroxiredoxin proteins and through the AMP-activated protein kinase-target of rapamycin signaling pathway. The AMP-activated protein kinase-target of rapamycin axis is critical for regulation of metabolism and autophagy, two processes associated with ROS production, and deregulation of this pathway increases vulnerability of the organism to stress, aging, and age-related diseases, including cancer. Recently, we have shown that inactivation of Sestrin in fly causes accumulation of age-associated damage. Hence, Sestrins can link p53 with aging and age-related diseases.

  11. Reactive cysteine persulfides and S-polythiolation regulate oxidative stress and redox signaling.

    Science.gov (United States)

    Ida, Tomoaki; Sawa, Tomohiro; Ihara, Hideshi; Tsuchiya, Yukihiro; Watanabe, Yasuo; Kumagai, Yoshito; Suematsu, Makoto; Motohashi, Hozumi; Fujii, Shigemoto; Matsunaga, Tetsuro; Yamamoto, Masayuki; Ono, Katsuhiko; Devarie-Baez, Nelmi O; Xian, Ming; Fukuto, Jon M; Akaike, Takaaki

    2014-05-27

    Using methodology developed herein, it is found that reactive persulfides and polysulfides are formed endogenously from both small molecule species and proteins in high amounts in mammalian cells and tissues. These reactive sulfur species were biosynthesized by two major sulfurtransferases: cystathionine β-synthase and cystathionine γ-lyase. Quantitation of these species indicates that high concentrations of glutathione persulfide (perhydropersulfide >100 μM) and other cysteine persulfide and polysulfide derivatives in peptides/proteins were endogenously produced and maintained in the plasma, cells, and tissues of mammals (rodent and human). It is expected that persulfides are especially nucleophilic and reducing. This view was found to be the case, because they quickly react with H2O2 and a recently described biologically generated electrophile 8-nitroguanosine 3',5'-cyclic monophosphate. These results indicate that persulfides are potentially important signaling/effector species, and because H2S can be generated from persulfide degradation, much of the reported biological activity associated with H2S may actually be that of persulfides. That is, H2S may act primarily as a marker for the biologically active of persulfide species.

  12. Redox Signaling Is an Early Event in the Pathogenesis of Renovascular Hypertension

    Directory of Open Access Journals (Sweden)

    Joseph P. Grande

    2013-09-01

    Full Text Available Activation of the renin-angiotensin-aldosterone system plays a critical role in the development of chronic renal damage in patients with renovascular hypertension. Although angiotensin II (Ang II promotes oxidative stress, inflammation, and fibrosis, it is not known how these pathways intersect to produce chronic renal damage. We tested the hypothesis that renal parenchymal cells are subjected to oxidant stress early in the development of RVH and produce signals that promote influx of inflammatory cells, which may then propagate chronic renal injury. We established a reproducible murine model of RVH by placing a tetrafluoroethhylene cuff on the right renal artery. Three days after cuff placement, renal tissue demonstrates no histologic abnormalities despite up regulation of both pro- and anti-oxidant genes. Mild renal atrophy was observed after seven days and was associated with induction of Tnfα and influx of CD3+ T cells and F4/80+ macrophages. By 28 days, kidneys developed severe renal atrophy with interstitial inflammation and fibrosis, despite normalization of plasma renin activity. Based on these considerations, we propose that renal parenchymal cells initiate a progressive cascade of events leading to oxidative stress, interstitial inflammation, renal fibrosis, and atrophy.

  13. Therapeutic Approach to Neurodegenerative Diseases by Medical Gases: Focusing on Redox Signaling and Related Antioxidant Enzymes

    Directory of Open Access Journals (Sweden)

    Kyota Fujita

    2012-01-01

    Full Text Available Oxidative stress in the central nervous system is strongly associated with neuronal cell death in the pathogenesis of several neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis. In order to overcome the oxidative damage, there are some protective signaling pathways related to transcriptional upregulation of antioxidant enzymes, such as heme oxygenase-1 (HO-1 and superoxide dismutase (SOD-1/-2. Their expression is regulated by several transcription factors and/or cofactors like nuclear factor-erythroid 2 (NF-E2 related factor 2 (Nrf2 and peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α. These antioxidant enzymes are associated with, and in some cases, prevent neuronal death in animal models of neurodegenerative diseases. They are activated by endogenous mediators and phytochemicals, and also by several gases such as carbon monoxide (CO, hydrogen sulphide (H2S, and hydrogen (H2. These might thereby protect the brain from severe oxidative damage and resultant neurodegenerative diseases. In this paper, we discuss how the expression levels of these antioxidant enzymes are regulated. We also introduce recent advances in the therapeutic uses of medical gases against neurodegenerative diseases.

  14. The Prediction of Metal Slopping in LD Converter on Base an Acoustic Signal

    Directory of Open Access Journals (Sweden)

    Kostúr, K.

    2006-01-01

    Full Text Available The negative influences of slopping in a BOF are pollution to the environment. They give lower yield and cause equipment damage. The prediction of these phenomena is based on information processing from the measuring microphone. The change of frequency in certain range is done by a signal for the prediction of slopping. In this paper two methods for prediction of slopping are described. The first method is based on measuring and processing of sound emitted from the vessel during the blow. The second method utilizes Fourier’s transformation for processing of acoustic signal from sonic meter. The success rate of prediction has been evaluated by help of five criterions. It is possible to forecast the slopping on selected frequency (band. It is the essence of the second method, because this method has high success (criterion K1. Note, that criterion K5 defines acknowledgment of duration slopping. This criterion has the highest value.

  15. Redox Regulation Of Metabolic And Signaling Pathways By Thioredoxin And Glutaredoxin In Nitric Oxide Treated Hepatoblastoma Cells

    Directory of Open Access Journals (Sweden)

    C. Alicia Padilla Peña

    2015-08-01

    Conclusions: Trx1 and Grx1 exert contradictory influences on HepG2 cells. They are required for proliferation but they also contribute to antiproliferative effect of NO, associated to Akt1 redox changes.

  16. Impact of Wind Power Plants with Full Converter Wind Turbines on Power System Small-Signal Stability

    DEFF Research Database (Denmark)

    Knüppel, Thyge; Nygaard Nielsen, Jørgen; Dixon, Andrew

    of operation. The participation of the WT mechanical system in the inter-area modes were found to be orders of magnitudes smaller than the participation of the synchronous generators. The reactive power controller of the WPP and the WT were found have the highest participation among the WPP and WT states. WPPs......Wind power is being developed in power systems all around the world, and already today wind power covers more than 20 % of the electricity consumption in some countries. As the size of each wind power plant (WPP) increases and as the levels of penetration reaches certain magnitudes, the inclusion...... of the dynamic properties of the WPPs in the power system stability studies become important. The work presented in this report deal with the impact of WPPs based on full converter wind turbines (WTs) on the power system small-signal rotor angle stability. During small disturbances in the power system, the rotor...

  17. Using reservoir-engineering to convert a coherent signal in optomechanics with small optomechanical cooperativity

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Tao, E-mail: suiyueqiaoqiao@163.com [Key Lab of Coherent Light, Atomic and Molecular Spectroscopy, Ministry of Education, and College of Physics, Jilin University, Changchun 130012 (China); College of Physics, Tonghua Normal University, Tonghua 134000 (China); Wang, Tie [Department of Physics, College of Science, Yanbian University, Yanji, Jilin 133002 (China); Fu, Changbao [College of Physics, Tonghua Normal University, Tonghua 134000 (China); Su, Xuemei, E-mail: suxm@jlu.edu.cn [Key Lab of Coherent Light, Atomic and Molecular Spectroscopy, Ministry of Education, and College of Physics, Jilin University, Changchun 130012 (China)

    2017-05-10

    Optomechanical dark mode plays a central role in effective mechanically-mediated conversion of two different cavity fields. In this paper, we present a more efficient method to utilize the dark mode to transfer a coherent signal. When an auxiliary cavity mode is exploited, two approaches are proposed to effectively eliminate the optomechanical bright mode, and only the optomechanical dark mode is left to facilitate state transfer. Even with small cooperativity and different losses for the two target modes, the internal cavity mode-conversion efficiency can also reach unity. - Highlights: • Reservoir-engineering is used for state conversion. • The optomechanical bright mode can be absolutely eliminated. • Small cooperativity and different losses are feasible for ideal conversion efficiency.

  18. Signal transducer and activator of transcription 3 and 5 regulate system Xc- and redox balance in human breast cancer cells.

    Science.gov (United States)

    Linher-Melville, Katja; Haftchenary, Sina; Gunning, Patrick; Singh, Gurmit

    2015-07-01

    System Xc- is a cystine/glutamate antiporter that contributes to the maintenance of cellular redox balance. The human xCT (SLC7A11) gene encodes the functional subunit of system Xc-. Transcription factors regulating antioxidant defense mechanisms including system Xc- are of therapeutic interest, especially given that aggressive breast cancer cells exhibit increased system Xc- function. This investigation provides evidence that xCT expression is regulated by STAT3 and/or STAT5A, functionally affecting the antiporter in human breast cancer cells. Computationally analyzing two kilobase pairs of the xCT promoter/5' flanking region identified a distal gamma-activated site (GAS) motif, with truncations significantly increasing luciferase reporter activity. Similar transcriptional increases were obtained after treating cells transiently transfected with the full-length xCT promoter construct with STAT3/5 pharmacological inhibitors. Knock-down of STAT3 or STAT5A with siRNAs produced similar results. However, GAS site mutation significantly reduced xCT transcriptional activity, suggesting that STATs may interact with other transcription factors at more proximal promoter sites. STAT3 and STAT5A were bound to the xCT promoter in MDA-MB-231 cells, and binding was disrupted by pre-treatment with STAT inhibitors. Pharmacologically suppressing STAT3/5 activation significantly increased xCT mRNA and protein levels, as well as cystine uptake, glutamate release, and total levels of intracellular glutathione. Our data suggest that STAT proteins negatively regulate basal xCT expression. Blocking STAT3/5-mediated signaling induces an adaptive, compensatory mechanism to protect breast cancer cells from stress, including reactive oxygen species, by up-regulating xCT expression and the function of system Xc-. We propose that targeting system Xc- together with STAT3/5 inhibitors may heighten therapeutic anti-cancer effects.

  19. Angiotensin receptor-mediated oxidative stress is associated with impaired cardiac redox signaling and mitochondrial function in insulin-resistant rats.

    Science.gov (United States)

    Vázquez-Medina, José Pablo; Popovich, Irina; Thorwald, Max A; Viscarra, Jose A; Rodriguez, Ruben; Sonanez-Organis, Jose G; Lam, Lisa; Peti-Peterdi, Janos; Nakano, Daisuke; Nishiyama, Akira; Ortiz, Rudy M

    2013-08-15

    Activation of angiotensin receptor type 1 (AT1) contributes to NADPH oxidase (Nox)-derived oxidative stress during metabolic syndrome. However, the specific role of AT1 in modulating redox signaling, mitochondrial function, and oxidative stress in the heart remains more elusive. To test the hypothesis that AT1 activation increases oxidative stress while impairing redox signaling and mitochondrial function in the heart during diet-induced insulin resistance in obese animals, Otsuka Long Evans Tokushima Fatty (OLETF) rats (n = 8/group) were treated with the AT1 blocker (ARB) olmesartan for 6 wk. Cardiac Nox2 protein expression increased 40% in OLETF compared with age-matched, lean, strain-control Long Evans Tokushima Otsuka (LETO) rats, while mRNA and protein expression of the H₂O₂-producing Nox4 increased 40-100%. ARB treatment prevented the increase in Nox2 without altering Nox4. ARB treatment also normalized the increased levels of protein and lipid oxidation (nitrotyrosine, 4-hydroxynonenal) and increased the redox-sensitive transcription factor Nrf2 by 30% and the activity of antioxidant enzymes (SOD, catalase, GPx) by 50-70%. Citrate synthase (CS) and succinate dehydrogenase (SDH) activities decreased 60-70%, whereas cardiac succinate levels decreased 35% in OLETF compared with LETO, suggesting that mitochondrial function in the heart is impaired during obesity-induced insulin resistance. ARB treatment normalized CS and SDH activities, as well as succinate levels, while increasing AMPK and normalizing Akt, suggesting that AT1 activation also impairs cellular metabolism in the diabetic heart. These data suggest that the cardiovascular complications associated with metabolic syndrome may result from AT1 receptor-mediated Nox2 activation leading to impaired redox signaling, mitochondrial activity, and dysregulation of cellular metabolism in the heart.

  20. Acute High-intensity Interval Exercise-induced Redox Signaling is Associated with Enhanced Insulin Sensitivity in Obese Middle-aged Men.

    Directory of Open Access Journals (Sweden)

    Lewan Parker

    2016-09-01

    Full Text Available Background. Obesity and ageing are associated with increased oxidative stress, activation of stress and mitogen activated protein kinases (SAPK, and the development of insulin resistance and metabolic disease. In contrast, acute exercise also increases oxidative stress and SAPK signaling, yet is reported to enhance insulin sensitivity and reduce the risk of metabolic disease. This study explored this paradox by investigating the effect of a single session of high-intensity interval-exercise (HIIE on redox status, muscle SAPK and insulin protein signaling in eleven middle-aged obese men. Methods. Participants completed a 2 hour hyperinsulinaemic-euglycaemic clamp at rest, and 60 minutes after HIIE (4x4 mins at 95% HRpeak; 2 min recovery periods, separated by 1-3 weeks. Results. Irrespective of exercise-induced changes to redox status, insulin stimulation both at rest and after HIIE similarly increased plasma superoxide dismutase activity, plasma catalase activity, and skeletal muscle 4-HNE; and significantly decreased plasma TBARS and hydrogen peroxide. The SAPK signaling pathways of p38 MAPK, NF-κB p65, and JNK, and the distal insulin signaling protein AS160Ser588, were activated with insulin stimulation at rest and to a greater extent with insulin stimulation after a prior bout of HIIE. Higher insulin sensitivity after HIIE was associated with higher insulin-stimulated SAPK phosphorylation (JNK, p38 MAPK and NF-κB and SOD activity (p<0.05. Conclusion. These findings support a role for redox homeostasis and SAPK signaling in insulin-stimulated glucose uptake which may contribute to the enhancement of insulin sensitivity in obese men 3 hours after HIIE.

  1. Angiotensin-converting enzyme inhibitor captopril prevents activation-induced apoptosis by interfering with T cell activation signals

    Science.gov (United States)

    Odaka, C; Mizuochi, T

    2000-01-01

    Captopril is an orally active inhibitor of angiotensin-converting enzyme (ACE) which is widely used as an anti-hypertensive agent. In addition to its ability to reduce blood pressure, captopril has a number of other biological activities. Recently the drug was shown to inhibit Fas-induced apoptosis in human activated peripheral T cells and human lung epithelial cells. In this study, we investigated whether captopril blocks activation-induced apoptosis in murine T cell hybridomas, and found that captopril inhibited IL-2 synthesis and apoptotic cell death upon activation with anti-CD3 antibody. In addition, captopril inhibited an inducible caspase-3-like activity during activation-induced apoptosis. On the other hand, captopril did not interfere with Fas signalling, since anti-Fas antibody-induced apoptosis in Fas+ Jurkat cells was unaffected by the drug. Furthermore, we examined whether captopril blocks activation-induced apoptosis by interfering with expression of Fas, Fas ligand (FasL), or both on T cell hybridomas. FasL expression on activated T cells was significantly inhibited by captopril, whereas up-expression of Fas was partially inhibited, as assessed by cell surface staining. Taking all data together, we conclude that captopril prevents activation-induced apoptosis in T cell hybridomas by interfering with T cell activation signals. Captopril has been reported to induce systemic lupus erythematosus syndrome, and our findings may be useful for elucidating the mechanism of captopril-induced autoimmunity. PMID:10971519

  2. Redox-capacitor to connect electrochemistry to redox-biology.

    Science.gov (United States)

    Kim, Eunkyoung; Leverage, W Taylor; Liu, Yi; White, Ian M; Bentley, William E; Payne, Gregory F

    2014-01-07

    It is well-established that redox-reactions are integral to biology for energy harvesting (oxidative phosphorylation), immune defense (oxidative burst) and drug metabolism (phase I reactions), yet there is emerging evidence that redox may play broader roles in biology (e.g., redox signaling). A critical challenge is the need for tools that can probe biologically-relevant redox interactions simply, rapidly and without the need for a comprehensive suite of analytical methods. We propose that electrochemistry may provide such a tool. In this tutorial review, we describe recent studies with a redox-capacitor film that can serve as a bio-electrode interface that can accept, store and donate electrons from mediators commonly used in electrochemistry and also in biology. Specifically, we (i) describe the fabrication of this redox-capacitor from catechols and the polysaccharide chitosan, (ii) discuss the mechanistic basis for electron exchange, (iii) illustrate the properties of this redox-capacitor and its capabilities for promoting redox-communication between biology and electrodes, and (iv) suggest the potential for enlisting signal processing strategies to "extract" redox information. We believe these initial studies indicate broad possibilities for enlisting electrochemistry and signal processing to acquire "systems level" redox information from biology.

  3. The Triangle of Death in Alzheimer's Disease Brain: The Aberrant Cross-Talk Among Energy Metabolism, Mammalian Target of Rapamycin Signaling, and Protein Homeostasis Revealed by Redox Proteomics.

    Science.gov (United States)

    Di Domenico, Fabio; Barone, Eugenio; Perluigi, Marzia; Butterfield, D Allan

    2017-03-10

    Alzheimer's disease (AD) is a multifactorial neurodegenerative disorder and represents one of the most disabling conditions. AD shares many features in common with systemic insulin resistance diseases, suggesting that it can be considered as a metabolic disease, characterized by reduced insulin-stimulated growth and survival signaling, increased oxidative stress (OS), proinflammatory cytokine activation, mitochondrial dysfunction, impaired energy metabolism, and altered protein homeostasis. Recent Advances: Reduced glucose utilization and energy metabolism in AD have been associated with the buildup of amyloid-β peptide and hyperphosphorylated tau, increased OS, and the accumulation of unfolded/misfolded proteins. Mammalian target of rapamycin (mTOR), which is aberrantly activated in AD since early stages, plays a key role during AD neurodegeneration by, on one side, inhibiting insulin signaling as a negative feedback mechanism and, on the other side, regulating protein homeostasis (synthesis/clearance). It is likely that the concomitant and mutual alterations of energy metabolism-mTOR signaling-protein homeostasis might represent a self-sustaining triangle of harmful events that trigger the degeneration and death of neurons and the development and progression of AD. Intriguingly, the altered cross-talk between the components of such a triangle of death, beyond altering the redox homeostasis of the neuron, is further exacerbated by increased levels of OS that target and impair key components of the pathways involved. Redox proteomic studies in human samples and animal models of AD-like dementia led to identification of oxidatively modified components of the pathways composing the triangle of death, therefore revealing the crucial role of OS in fueling this aberrant vicious cycle. The identification of compounds able to restore the function of the pathways targeted by oxidative damage might represent a valuable therapeutic approach to slow or delay AD. Antioxid

  4. Thioredoxin-like 2 regulates human cancer cell growth and metastasis via redox homeostasis and NF-kB signaling

    Science.gov (United States)

    Cancer cells have an efficient antioxidant system to counteract their increased generation of ROS. However, whether this ability to survive high levels of ROS has an important role in the growth and metastasis of tumors is not well understood. Here, we demonstrate that the redox protein thioredoxin-...

  5. Wavelength Converters

    DEFF Research Database (Denmark)

    Kloch, Allan; Hansen, Peter Bukhave; Wolfson, David;

    1999-01-01

    at 2.5 Gbit/s, the regeneration causes a reduction of the required input power to an in-line EDFA of ~6 dB for a power penalty of 1 dB at a bit error rate of 10-9. If two converters are concatenated the power requirement is reduced ~8 dB. Obviously, the power reduction allows for longer spans between....... It is predicted that jitter accumulation can be minimised by using a 9-10 dB ratio between the signal and CW power also assuring a high extinction ratio. Using this guideline simulations show that 20 cross-gain modulation converters can be cascaded at 10 Gbit/s with only ~20 ps of accumulated jitter...... and an extinction ratio of ~10 dB.The regenerative capabilities of the cross-phase converters are described and verified experimentally at 20 Gbit/s, where the noise redistribution and improvement of the signal-to-noise ratio clearly is demonstrated by controlling the input power to an EDFA. In a similar experiment...

  6. PHOSPHORYLATION/DEPHOSPHORYLATION OF MITOCHONDRIAL PROTEINS IN REDOX-SIGNALLING OF HIGHER PLANTS UNDER ABIOTIC STRESS CONDITIONS

    Directory of Open Access Journals (Sweden)

    Subota I.Yu.

    2012-08-01

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

  7. A3 adenosine receptor agonist prevents the development of paclitaxel-induced neuropathic pain by modulating spinal glial-restricted redox-dependent signaling pathways.

    Science.gov (United States)

    Janes, Kali; Esposito, Emanuela; Doyle, Timothy; Cuzzocrea, Salvatore; Tosh, Dillip K; Jacobson, Kenneth A; Salvemini, Daniela

    2014-12-01

    Chemotherapy-induced peripheral neuropathy accompanied by chronic neuropathic pain is the major dose-limiting toxicity of several anticancer agents including the taxane paclitaxel (Taxol). A critical mechanism underlying paclitaxel-induced neuropathic pain is the increased production of peroxynitrite in spinal cord generated in response to activation of the superoxide-generating enzyme, NADPH oxidase. Peroxynitrite in turn contributes to the development of neuropathic pain by modulating several redox-dependent events in spinal cord. We recently reported that activation of the Gi/Gq-coupled A3 adenosine receptor (A3AR) with selective A3AR agonists (ie, IB-MECA) blocked the development of chemotherapy induced-neuropathic pain evoked by distinct agents, including paclitaxel, without interfering with anticancer effects. The mechanism or mechanisms of action underlying these beneficial effects has yet to be explored. We now demonstrate that IB-MECA attenuates the development of paclitaxel-induced neuropathic pain by inhibiting the activation of spinal NADPH oxidase and two downstream redox-dependent systems. The first relies on inhibition of the redox-sensitive transcription factor (NFκB) and mitogen activated protein kinases (ERK and p38) resulting in decreased production of neuroexcitatory/proinflammatory cytokines (TNF-α, IL-1β) and increased formation of the neuroprotective/anti-inflammatory IL-10. The second involves inhibition of redox-mediated posttranslational tyrosine nitration and modification (inactivation) of glia-restricted proteins known to play key roles in regulating synaptic glutamate homeostasis: the glutamate transporter GLT-1 and glutamine synthetase. Our results unravel a mechanistic link into biomolecular signaling pathways employed by A3AR activation in neuropathic pain while providing the foundation to consider use of A3AR agonists as therapeutic agents in patients with chemotherapy-induced peripheral neuropathy. Copyright © 2014

  8. Reduced expression of DNA repair and redox signaling protein APE1/Ref-1 impairs human pancreatic cancer cell survival, proliferation, and cell cycle progression.

    Science.gov (United States)

    Jiang, Yanlin; Zhou, Shaoyu; Sandusky, George E; Kelley, Mark R; Fishel, Melissa L

    2010-11-01

    Pancreatic cancer is a deadly disease that is virtually never cured. Understanding the chemoresistance intrinsic to this cancer will aid in developing new regimens. High expression of APE1/Ref-1, a DNA repair and redox signaling protein, is associated with resistance, poor outcome, and angiogenesis; little is known in pancreatic cancer. Immunostaining of adenocarcinoma shows greater APE1/Ref-1 expression than in normal pancreas tissue. A decrease in APE1/Ref-1 protein levels results in pancreatic cancer cell growth inhibition, increased apoptosis, and altered cell cycle progression. Endogenous cell cycle inhibitors increase when APE1/ Ref-1 is reduced, demonstrating its importance to proliferation and growth of pancreatic cancer.

  9. Fully Integrated on-Chip Switched DC–DC Converter for Battery-Powered Mixed-Signal SoCs

    Directory of Open Access Journals (Sweden)

    Heungjun Jeon

    2017-01-01

    Full Text Available This paper presents a fully integrated on-chip switched-capacitor (SC DC–DC converter that supports a programmable regulated power supply ranging from 2.6 to 3.2 V out of a 5 V input supply. The proposed 4-to-3 step-down topology utilizes two conventional 2-to-1 step-down topologies; each of them (2-to-1_up and 2-to-1_dw has a different flying capacitance to maximize the load current driving capability while minimizing the bottom-plate capacitance loss. The control circuits use a low power supply provided by a small internal low-drop output (LDO connected to the internal load voltage (VL_dw from the 2-to-1_dw, and low swing level-shifted gate-driving signals are generated using the internal load voltage (VL_dw. Therefore, the proposed implementation reduces control circuit and switching power consumptions. The programmable power supply voltage is regulated by means of a pulse frequency modulation (PFM technique with the compensated two-stage operational transconductance amplifier (OTA and the current-starved voltage controlled oscillator (VCO to maintain high efficiency over a wide range of load currents. The proposed on-chip SC DC–DC converter is designed and simulated using high-voltage 0.35 μm bipolar, complementary metal-oxide-semiconductor (CMOS and DMOS (BCDMOS technology. It achieves a peak efficiency of 74% when delivering an 8 mA load current at a 3.2 V supply voltage level, and it provides a maximum output power of 48 mW (IL = 15 mA at VL_up = 3.2 V at 70.5% efficiency. The proposed on-chip SC voltage regulator shows better efficiency than the ideal linear regulator over a wide range of output power, from 2.6 mW to 48 mW. The 18-phase interleaving technique enables the worst-case output voltage ripple to be less than 5.77% of the load voltage.

  10. Chloroplast Redox Poise

    DEFF Research Database (Denmark)

    Steccanella, Verdiana

    The redox state of the chloroplast is maintained by a delicate balance between energy production and consumption and is affected by the need to avoid increased production of reactive oxygen species (ROS). Redox power and ROS generated in the chloroplast are essential for maintaining physiological...... the redox status of the plastoquinone pool and chlorophyll biosynthesis. Furthermore, in the plant cell, the equilibrium between redox reactions and ROS signals is also maintained by various balancing mechanisms among which the thioredoxin reductase-thioredoxin system (TR-Trx) stands out as a mediator...... it lacks some of the key enzymes for ROS scavenging and it is the only, so far, known species to have two NTRC genes. Our aim was to elucidate the role of the two NTRC isoforms found in moss as an alternative system for protection against oxidative damage, providing the first partial attempt of a molecular...

  11. Expression of Extracellular Signal-regulated Kinase and Angiotensin-converting Enzyme in Human Atria during Atrial Fibrillation

    Institute of Scientific and Technical Information of China (English)

    戴友平; 王祥; 曹林生; 杨杪; 邬堂春

    2004-01-01

    Summary: In order to investigate the changes in the expression of extracellular signal-regulated kinase (ERK1/ERK2) and angiotensin-converting enzyme (ACE) in the patients with atrial fibrillation (AF), 52 patients with rheumatic heart diseases were examined. Nineteen patients had chronic persistent AF (AF≥6 months, CAF), 12 patients had paroxymal AF (PAF) and 21 patients had no history of AF. The ERK expression was detected at the mRNA level by reverse transcription polymerase chain reaction, at the protein level by Western blotting and at atrial tissue level by immunohistochemistry. ERK-activating kinases (MEK1/2) and ACE were determined by Western blotting techniques. The expression of ERK2-mRNA was increased in the patients with CAF (74±19 U vs sinus rhythm: 32±24 U, P<0.05). Activated ERK1/ERK2 and MEK1/2 were increased to more than 150 % in the patients with AF compared to those with sinus rhythm. No significant difference between CAF and PAF was found. The expression of ACE was three-fold increased in the patients with CAF compared to those with sinus rhythm. Patients with AF showed an increased expression of ERK1/ERK2 in atrial interstitial cells and marked atrial fibrosis. An ACE-dependent increase in the amounts of activated ERK1/ERK2 in atrial interstitial cells may be one of molecular mechanisms for the development of atrial fibrosis in the patients with AF. These findings may have important impact on the treatment of AF.

  12. COX19 mediates the transduction of a mitochondrial redox signal from SCO1 that regulates ATP7A-mediated cellular copper efflux

    Science.gov (United States)

    Leary, Scot C.; Cobine, Paul A.; Nishimura, Tamiko; Verdijk, Robert M.; de Krijger, Ronald; de Coo, René; Tarnopolsky, Mark A.; Winge, Dennis R.; Shoubridge, Eric A.

    2013-01-01

    SCO1 and SCO2 are metallochaperones whose principal function is to add two copper ions to the catalytic core of cytochrome c oxidase (COX). However, affected tissues of SCO1 and SCO2 patients exhibit a combined deficiency in COX activity and total copper content, suggesting additional roles for these proteins in the regulation of cellular copper homeostasis. Here we show that both the redox state of the copper-binding cysteines of SCO1 and the abundance of SCO2 correlate with cellular copper content and that these relationships are perturbed by mutations in SCO1 or SCO2, producing a state of apparent copper overload. The copper deficiency in SCO patient fibroblasts is rescued by knockdown of ATP7A, a trans-Golgi, copper-transporting ATPase that traffics to the plasma membrane during copper overload to promote efflux. To investigate how a signal from SCO1 could be relayed to ATP7A, we examined the abundance and subcellular distribution of several soluble COX assembly factors. We found that COX19 partitions between mitochondria and the cytosol in a copper-dependent manner and that its knockdown partially rescues the copper deficiency in patient cells. These results demonstrate that COX19 is necessary for the transduction of a SCO1-dependent mitochondrial redox signal that regulates ATP7A-mediated cellular copper efflux. PMID:23345593

  13. Direct electrochemical DNA detection originated from the self-redox signal of sulfonated polyaniline enhanced by graphene oxide in neutral solution.

    Science.gov (United States)

    Yang, Tao; Meng, Le; Wang, Xinxing; Wang, Longlong; Jiao, Kui

    2013-11-13

    In this paper, a type of direct DNA impedance detection using the self-redox signal change of sulfonated polyaniline (SPAN) enhanced by graphene oxide (GNO) was reported, here SPAN is a copolymer obtained from aniline and m-aminobenzenesulfonic acid. The resulting nanocomposite was characterized by scanning electron microscopy, transmission electron microscopy, Fourier transform infrared spectroscopy, cyclic voltammetry, and electrochemical impedance spectroscopy. The π-π planar structure of GNO and the carboxyl groups on the surface of GNO ensured it could act as an excellent substrate for adsorption and polymerization of aniline monomer. Because of the existence of GNO, the electrochemical activities of SPAN were enhanced obviously. Because of abundant sulfonic acid groups, the resulting nanocomposite showed obvious self-redox signal even at physiological pH, which is beneficial for biosensing field. DNA probes with amine groups could be covalently attached to the modified electrode surface through the acyl chloride cross-linking reaction of sulfonic groups and amines. When the flexible probe DNA was successfully grafted, the electrode was coated and electron transfer between electrode and buffer was restrained. Thus, the inner impedance value of SPAN (rather than using outer classic EIS probe, [Fe(CN)6](3-/4-)) increased significantly. After hybridization, the rigid helix opened the electron channel, which induced impedance value decreased dramatically. As an initial application of this system, the PML/RARA fusion gene sequence formed from promyelocytic leukemia (PML) and retinoic acid receptor alpha (RARA) was successfully detected.

  14. Cyclophilin 20-3 is positioned as a regulatory hub between light-dependent redox and 12-oxo-phytodienoic acid signaling.

    Science.gov (United States)

    Cheong, Hoon; Barbosa Dos Santos, Izailda; Liu, Wenshan; Gosse, Heather N; Park, Sang-Wook

    2017-08-14

    The jasmonate family of phytohormones plays central roles in plant development and stress acclimation. However, the regulatory modes of their signaling circuitry remain largely unknown. Here we describe that cyclophilin 20-3 (CYP20-3), a binding protein of (+)-12-oxo-phytodienoic acid (OPDA), crisscrosses stress responses with light-dependent redox reactions, which fine-tunes the activity of key enzymes in the plastid photosynthetic carbon assimilation and sulfur assimilation pathways. Under stressed states, OPDA - accumulated in the chloroplasts - binds and promotes CYP20-3 to transfer electron (e(-)) from thioredoxins (i.e., type-f2 and -x) to 2-Cys peroxiredoxin B (2-CysPrxB) or serine acetyltransferase 1 (SAT1). Reduction (activation) of 2-CysPrxB then optimizes peroxide detoxification and carbon metabolisms in the photosynthesis, whereas the activation of SAT1 stimulates sulfur assimilation which in turn coordinates redox-resolved nucleus gene expressions in defense responses against biotic and abiotic stresses. Thus, we conclude that CYP20-3 is positioned as a unique metabolic hub in the interface between photosynthesis (light) and OPDA signaling, where controls resource (e(-)) allocations between plant growth and defense responses.

  15. Redox control of teratogenesis.

    Science.gov (United States)

    Hansen, Jason M; Harris, Craig

    2013-01-01

    A number of human teratogens elicit their deleterious effects through mechanisms involving the generation of reactive oxygen species (ROS) and oxidative stress. However, classic definitions of oxidative stress do not fully coincide with basic fundamental principles of teratology. Newer definitions of oxidative stress focus on the targeted redox modification of cysteine/thiol functional groups found in the regulatory domains of critical signaling pathway proteins, suggesting that the targeted disruption of signaling through specific redox couples may account for the specificity of teratogen-induced malformations which previously could not be rationalized. Here, we review examples of teratogens that induce ROS and oxidative injury, describe oxidative stress-related teratogenic mechanisms, and provide rationale for developmental periods of sensitivity and species susceptibility. Understanding how chemicals disrupt redox status, induce oxidative stress leading to dysmorphogenesis becomes important to identify potential teratogens and develop therapeutic interventions for attenuation of harmful chemical effects in utero following exposure.

  16. Labeling of Oxidizable Proteins with a Photoactivatable Analog of the Antitumor Agent DMXAA: Evidence for Redox Signaling in Its Mode of Action

    Directory of Open Access Journals (Sweden)

    Romy Brauer

    2010-09-01

    Full Text Available The signaling pathway(s and molecular target(s for 5,6-dimethylxanthenone-4-acetic acid (DMXAA, a tumor vascular disrupting agent in late stages of clinical development, are still undefined. As an approach toward identifying potential targets for DMXAA, a tritiated azido-analog of DMXAA was used to probe for cellular binding proteins. More than 20 cytosolic proteins from murine splenocytes, RAW 264.7 cells, and the HECPP immortalized endothelial cells were photoaffinity-labeled. Although no protein domain, fold, or binding site for a specific ligand was found to be shared by all the candidate proteins, essentially all were noted to be oxidizable proteins, implicating a role for redox signaling in the action of DMXAA. Consistent with this hypothesis, DMXAA caused an increase in concentrations of reactive oxygen species (ROS in RAW264.7 cells during the first 2 hours. This increase in ROS was suppressed in the presence of the antioxidant, N-acetyl-L-cysteine, which also suppressed DMXAA-induced cytokine production in the RAW 264.7 cells with no effects on cell viability. Short interfering RNA (siRNA-mediated knockdown of one of the photoaffinity-labeled proteins, superoxide dismutase 1, an ROS scavenger, resulted in an increase in tumor necrosis factor-α production by RAW 264.7 cells in response to DMXAA compared with negative or positive controls transfected with nontargeting or lamin A/C-targeting siRNA molecules, respectively. The results from these lines of study all suggest that redox signaling plays a central role in cytokine induction by DMXAA.

  17. 平均电流控制下的DC/DC变换器大小信号统一动态模型%A Unified Large Signal and Small Signal Model for DC/DC Converters With Average Current Control

    Institute of Scientific and Technical Information of China (English)

    刘雁飞

    2007-01-01

    A unified large signal and small signal model for DC/DC converters under average current control is presented in the paper. The model can be applied to Buck, Boost and Buck-Boost converters. The proposed model consists of two parts. The first part is an averaged circuit model, and the second part is a model for average current mode control with pulse width modulation (PWM). The model is verified by a Boost converter prototype under average current mode control. The experimental results demonstrate that the model can accurately predict the steady-state, small signal and large signal dynamic behavior of DC/DC converter under average current control.%提出了适合平均电流控制下DC/DC开关变换器的大小信号统一模型.此模型可用于Buck、Boost和Buck-Boost变换器.它由两部份组成:一部份是开关变换器的平均电路模型;另一部分是平均电流控制器的电路模型.以平均电流控制下的Boost变换器为例,通过实验证明所提出的模型能够准确地预测平均电流控制下DC/DC变换器的稳态、小信号和大信号动态特性.

  18. Protein electron transfer (mechanism and reproductive toxicity): iminium, hydrogen bonding, homoconjugation, amino acid side chains (redox and charged), and cell signaling.

    Science.gov (United States)

    Kovacic, Peter

    2007-03-01

    This contribution presents novel biochemical perspectives of protein electron transfer (ET) with focus on the iminium nature of the peptide link, along with relationships to reproductive toxicity. The favorable influence of hydrogen bonding on protein ET has been widely documented. Hydrogen bonding of the zwitterionic peptide enhances iminium character. A wide array of such bonding agents is available in vivo, with many reports on the peptide link itself. ET proceeds along the backbone, due in part, to homoconjugation. Redox amino acids (AAs), mainly tyrosine (Tyr), tryptophan (Typ), histidine (His), cysteine (Cys), disulfide, and methionine (Met), are involved in the competing processes for radical formation: direct hydrogen atom abstraction versus electron and proton loss. It appears that the radical or radical cation generated during the redox process is capable of interacting with n-electrons of the backbone. Beneficial effects of cationic AAs impact the conduction process. A relationship apparently exists involving cell signaling, protein conduction, and radicals or electrons. In addition, the link between protein ET and reproductive toxicity is examined. A key element is the role of reactive oxygen species (ROS) generated by protein ET. There is extensive evidence for involvement of ROS in generation of birth defects. The radical species arise in protein mainly by ET transformations by enzymes, as illustrated in the case of alcoholism. (c) 2007 Wiley-Liss, Inc.

  19. Nitric oxide is a ubiquitous signal for maintaining redox balance in plant cells: regulation of ascorbate peroxidase as a case study.

    Science.gov (United States)

    Correa-Aragunde, Natalia; Foresi, Noelia; Lamattina, Lorenzo

    2015-05-01

    Oxidative and nitrosative stresses and their respective antioxidant responses are common metabolic adjustments operating in all biological systems. These stresses result from an increase in reactive oxygen species (ROS) and reactive nitrogen species (RNS) and an imbalance in the antioxidant response. Plants respond to ROS and RNS accumulation by increasing the level of the antioxidant molecules glutathione and ascorbate and by activating specific antioxidant enzymes. Nitric oxide (NO) is a free radical considered to be toxic or protective depending on its concentration, combination with ROS compounds, and subcellular localization. In this review we focus on the mechanisms of NO action in combination with ROS on the regulation of the antioxidant system in plants. In particular, we describe the redox post-translational modifications of cytosolic ascorbate peroxidase and its influence on enzyme activity. The regulation of ascorbate peroxidase activity by NO as a redox sensor of acute oxidative stress or as part of a hormone-induced signalling pathway leading to lateral root development is presented and discussed.

  20. Catechol, a major component of smoke, influences primary root growth and root hair elongation through reactive oxygen species-mediated redox signaling.

    Science.gov (United States)

    Wang, Ming; Schoettner, Matthias; Xu, Shuqing; Paetz, Christian; Wilde, Julia; Baldwin, Ian T; Groten, Karin

    2017-03-01

    Nicotiana attenuata germinates from long-lived seedbanks in native soils after fires. Although smoke signals have been known to break seed dormancy, whether they also affect seedling establishment and root development remains unclear. In order to test this, seedlings were treated with smoke solutions. Seedlings responded in a dose-dependent manner with significantly increased primary root lengths, due mainly to longitudinal cell elongation, increased numbers of lateral roots and impaired root hair development. Bioassay-driven fractionations and NMR were used to identify catechol as the main active compound for the smoke-induced root phenotype. The transcriptome analysis revealed that mainly genes related to auxin biosynthesis and redox homeostasis were altered after catechol treatment. However, histochemical analyses of reactive oxygen species (ROS) and the inability of auxin applications to rescue the phenotype clearly indicated that highly localized changes in the root's redox-status, rather than in levels of auxin, are the primary effector. Moreover, H2 O2 application rescued the phenotype in a dose-dependent manner. Chemical cues in smoke not only initiate seed germination, but also influence seedling root growth; understanding how these cues work provides new insights into the molecular mechanisms by which plants adapt to post-fire environments.

  1. Design of Mine-used Multi-function WiFi Signal Converter%矿用多功能WiFi信号转换器的设计

    Institute of Scientific and Technical Information of China (English)

    孙钢; 刘炜; 景振兴

    2011-01-01

    The paper introduced composition and signal transform mode of mine-used multi-function WiFi signal converter. The converter uses wireless antenna to receive and transmit wireless signals,and realizes mutual change of wireless signal and wire signals of RS485,Ethernet port,sensor and voice port,so as to expediently realize interconnection among various interfaces of mine monitoring device,and effectively slove compatibility problem among various kinds of monitoring systems and communication systems.%介绍了矿用多功能WiFi信号转换器的组成及信号的转换方式.该转换器可通过天线收发无线信号,可实现无线信号与RS485口、以太网口、传感器接口和语音接口等有线信号的相互转换,方便地完成了煤矿井下各种监控设备接口之间的互联,有效解决了各种监控系统和通信系统之间的兼容性问题.

  2. 运动与氧化还原信号调控%Exercise and Redox Signaling Regulation

    Institute of Scientific and Technical Information of China (English)

    刘静; 龙建纲; 刘健康

    2014-01-01

    ROS,identifiedassignalingmolecules,areresponsibleformaintainingredoxhomeostasisin vivo.Appropriate exercise promotes the generation of physiological ROS,enhances the antioxidative po-tential,promotes exercise performance,and improves metabolism,as well as retards aging and related diseases;whereas overload exercise causes excess ROS,resulting in exercise-induced fatigue or even ex-ercise-induced injury.Mitochondria are the main pool of ROS production and act as the key organelles in modulating intracellular redox homeostasis.Mitochondrial nutrients not only maintain physiological redox homeostasis,but also ameliorate oxidative stress and fatigue induced by overload exercise,eventually im-proving exercise performance and preventing/ameliorating exercise-induced injury.%活性氧既是细胞内的信号分子,也是引起细胞氧化应激的主要分子。适当强度的运动促进生理水平活性氧的生成,增强机体抗氧化能力,有助于改善代谢、延缓衰老及相关疾病;而过度运动则会导致机体内大量活性氧的产生,造成运动疲劳甚至运动损伤。线粒体是产生活性氧及维护细胞氧化还原稳态的主要细胞器。合理补充线粒体营养素可以维护细胞氧化还原稳态,部分模拟运动的生理效应;同时,能够缓解过度运动引起的运动疲劳,有助于提升运动能力并改善运动损伤。

  3. Novel, unifying mechanism for mescaline in the central nervous system: electrochemistry, catechol redox metabolite, receptor, cell signaling and structure activity relationships.

    Science.gov (United States)

    Kovacic, Peter; Somanathan, Ratnasamy

    2009-01-01

    A unifying mechanism for abused drugs has been proposed previously from the standpoint of electron transfer. Mescaline can be accommodated within the theoretical framework based on redox cycling by the catechol metabolite with its quinone counterpart. Electron transfer may play a role in electrical effects involving the nervous system in the brain. This approach is in accord with structure activity relationships involving mescaline, abused drugs, catecholamines, and etoposide. Inefficient demethylation is in keeping with the various drug properties, such as requirement for high dosage and slow acting. There is a discussion of receptor binding, electrical effects, cell signaling and other modes of action. Mescaline is a nonselective, seretonin receptor agonist. 5-HTP receptors are involved in the stimulus properties. Research addresses the aspect of stereochemical requirements. Receptor binding may involve the proposed quinone metabolite and/or the amino sidechain via protonation. Electroencephalographic studies were performed on the effects of mescaline on men. Spikes are elicited by stimulation of a cortical area. The potentials likely originate in nonsynaptic dendritic membranes. Receptor-mediated signaling pathways were examined which affect mescaline behavior. The hallucinogen belongs to the class of 2AR agonists which regulate pathways in cortical neurons. The research identifies neural and signaling mechanisms responsible for the biological effects. Recently, another hallucinogen, psilocybin, has been included within the unifying mechanistic framework. This mushroom constituent is hydrolyzed to the phenol psilocin, also active, which is subsequently oxidized to an ET o-quinone or iminoquinone.

  4. Apurinic/apyrimidinic endonuclease1/redox factor-1 (Ape1/Ref-1) is essential for IL-21-induced signal transduction through ERK1/2 pathway

    Energy Technology Data Exchange (ETDEWEB)

    Juliana, Farha M.; Nara, Hidetoshi [Department of Immunology, Yamagata University Faculty of Medicine, Yamagata (Japan); Onoda, Tadashi [Department of Immunology, Yamagata University Faculty of Medicine, Yamagata (Japan); Department of Pediatrics, Yamagata University Faculty of Medicine, Yamagata (Japan); Rahman, Mizanur; Araki, Akemi; Jin, Lianjin [Department of Immunology, Yamagata University Faculty of Medicine, Yamagata (Japan); Fujii, Hodaka [Combined Program on Microbiology and Immunology, Research Institute for Microbial Diseases, Osaka University, Suita (Japan); Tanaka, Nobuyuki [Division of Immunology, Miyagi Cancer Center Research Institute, Natori (Japan); Department of Cancer Medical Science, Tohoku University Graduate School of Medicine, Sendai (Japan); Hoshino, Tomoaki [Department of Internal Medicine 1, Kurume University School of Medicine, Kurume (Japan); Asao, Hironobu, E-mail: asao-h@med.id.yamagata-u.ac.jp [Department of Immunology, Yamagata University Faculty of Medicine, Yamagata (Japan)

    2012-04-13

    Highlights: Black-Right-Pointing-Pointer IL-21 induces nuclear accumulation of Ape1/Ref-1 protein. Black-Right-Pointing-Pointer Ape1/Ref-1 is indispensable in IL-21-induced cell proliferation and survival signal. Black-Right-Pointing-Pointer Ape1/Ref-1 is required for IL-21-induced ERK1/2 activation. -- Abstract: IL-21 is a pleiotropic cytokine that regulates T-cell and B-cell differentiation, NK-cell activation, and dendritic cell functions. IL-21 activates the JAK-STAT, ERK, and PI3K pathways. We report here that Ape1/Ref-1 has an essential role in IL-21-induced cell growth signal transduction. Overexpression of Ape1/Ref-1 enhances IL-21-induced cell proliferation, but it is suppressed by overexpressing an N-terminal deletion mutant of Ape1/Ref-1 that lacks the redox domain. Furthermore, knockdown of the Ape1/Ref-1 mRNA dramatically compromises IL-21-induced ERK1/2 activation and cell proliferation with increasing cell death. These impaired activities are recovered by the re-expression of Ape1/Ref-1 in the knockdown cells. Our findings are the first demonstration that Ape1/Ref-1 is an indispensable molecule for the IL-21-mediated signal transduction through ERK1/2 activation.

  5. "Only a life lived for others is worth living:" Redox Signaling by Oxygenated Phospholipids in Cell Fate Decisions.

    Science.gov (United States)

    Tyurina, Yulia Y; Shrivastava, Indira; Tyurin, Vladimir A; Mao, Gaowei; Dar, Haider H; Watkins, Simon; Epperly, Michael; Bahar, Ivet; Shvedova, Anna A; Pitt, Bruce; Wenzel, Sally E; Mallampalli, Rama K; Sadovsky, Yoel; Gabrilovich, Dmitry; Greenberger, Joel S; Bayır, Hülya; Kagan, Valerian E

    2017-08-23

    Oxygenated polyunsaturated lipids are known to play multi-functional roles as essential signals coordinating metabolism and physiology. Among them are well studied eicosanoids and docosanoids generated via phospholipase A2 hydrolysis of membrane phospholipids and subsequent oxygenation of free polyunsaturated fatty acids (PUFA) by cyclooxygenases and lipoxygenases. Recent Advances: There is an emerging understanding that oxygenated PUFA-phospholipids also represent a rich signaling language with yet to be deciphered details of the execution machinery - oxygenating enzymes, regulators, receptors. Both free and esterified oxygenated PUFA signals are generated in cells and their cross-talk and inter-conversion through the de-acylation/re-acylation reactions is not sufficiently explored. Here we review recent data related to oxygenated phospholipids as important damage signals that trigger programmed cell death pathways to eliminate irreparably injured cells and preserve the health of multicellular environments. We discuss the mechanisms underlying the trans-membrane redistribution and generation of oxygenated cardiolipins in mitochondria by cytochrome c as pro-apoptotic signals. We also consider the role of oxygenated phosphatidylethanolamines as proximate pro-ferroptotic signals. We highlight the importance of sequential processes of phospholipid oxygenation and signaling in disease contexts as opportunities to use their regulatory mechanisms for the identification of new therapeutic targets.

  6. Reactive oxygen species via redox signaling to PI3K/AKT pathway contribute to the malignant growth of 4-hydroxy estradiol-transformed mammary epithelial cells.

    Directory of Open Access Journals (Sweden)

    Victor O Okoh

    Full Text Available The purpose of this study was to investigate the effects of 17-β-estradiol (E2-induced reactive oxygen species (ROS on the induction of mammary tumorigenesis. We found that ROS-induced by repeated exposures to 4-hydroxy-estradiol (4-OH-E2, a predominant catechol metabolite of E2, caused transformation of normal human mammary epithelial MCF-10A cells with malignant growth in nude mice. This was evident from inhibition of estrogen-induced breast tumor formation in the xenograft model by both overexpression of catalase as well as by co-treatment with Ebselen. To understand how 4-OH-E2 induces this malignant phenotype through ROS, we investigated the effects of 4-OH-E2 on redox-sensitive signal transduction pathways. During the malignant transformation process we observed that 4-OH-E2 treatment increased AKT phosphorylation through PI3K activation. The PI3K-mediated phosphorylation of AKT in 4-OH-E2-treated cells was inhibited by ROS modifiers as well as by silencing of AKT expression. RNA interference of AKT markedly inhibited 4-OH-E2-induced in vitro tumor formation. The expression of cell cycle genes, cdc2, PRC1 and PCNA and one of transcription factors that control the expression of these genes - nuclear respiratory factor-1 (NRF-1 was significantly up-regulated during the 4-OH-E2-mediated malignant transformation process. The increased expression of these genes was inhibited by ROS modifiers as well as by silencing of AKT expression. These results indicate that 4-OH-E2-induced cell transformation may be mediated, in part, through redox-sensitive AKT signal transduction pathways by up-regulating the expression of cell cycle genes cdc2, PRC1 and PCNA, and the transcription factor - NRF-1. In summary, our study has demonstrated that: (i 4-OH-E2 is one of the main estrogen metabolites that induce mammary tumorigenesis and (ii ROS-mediated signaling leading to the activation of PI3K/AKT pathway plays an important role in the generation of 4-OH-E2

  7. Redox signaling via the molecular chaperone BiP protects cells against endoplasmic reticulum-derived oxidative stress

    Science.gov (United States)

    Wang, Jie; Pareja, Kristeen A; Kaiser, Chris A; Sevier, Carolyn S

    2014-01-01

    Oxidative protein folding in the endoplasmic reticulum (ER) has emerged as a potentially significant source of cellular reactive oxygen species (ROS). Recent studies suggest that levels of ROS generated as a byproduct of oxidative folding rival those produced by mitochondrial respiration. Mechanisms that protect cells against oxidant accumulation within the ER have begun to be elucidated yet many questions still remain regarding how cells prevent oxidant-induced damage from ER folding events. Here we report a new role for a central well-characterized player in ER homeostasis as a direct sensor of ER redox imbalance. Specifically we show that a conserved cysteine in the lumenal chaperone BiP is susceptible to oxidation by peroxide, and we demonstrate that oxidation of this conserved cysteine disrupts BiP's ATPase cycle. We propose that alteration of BiP activity upon oxidation helps cells cope with disruption to oxidative folding within the ER during oxidative stress. DOI: http://dx.doi.org/10.7554/eLife.03496.001 PMID:25053742

  8. ROS production and scavenging under anoxia and re-oxygenation in Arabidopsis cells: a balance between redox signaling and impairment.

    Directory of Open Access Journals (Sweden)

    Annalisa Paradiso

    2016-12-01

    Full Text Available Plants can frequently experience low oxygen concentrations due to environmental factors such as flooding or waterlogging. It has been reported that both anoxia and the transition from anoxia to re-oxygenation determine a strong imbalance in the cellular redox state involving the production of reactive oxygen species (ROS and nitric oxide (NO. Plant cell cultures can be a suitable system to study the response to oxygen deprivation stress since a close control of physicochemical parameters is available when using bioreactors. For this purpose, Arabidopsis cell suspension cultures grown in a stirred bioreactor were subjected to a severe anoxic stress and analyzed during anoxia and re-oxygenation for alteration in ROS and NO as well as in antioxidant enzymes and metabolites. The results obtained by confocal microscopy showed the dramatic increase of ROS, H2O2 and NO during the anoxic shock. All the ascorbate-glutathione related parameters were altered during anoxia but restored during re-oxygenation. Anoxia also induced a slight but significant increase of α-tocopherol levels measured at the end of the treatment. Overall, the evaluation of cell defenses during anoxia and re-oxygenation in Arabidopsis cell cultures revealed that the immediate response involving the overproduction of reactive species activated the antioxidant machinery including ascorbate-glutathione system, α-tocopherol and the ROS-scavenging enzymes ascorbate peroxidase, catalase and peroxidase making cells able to counteract the stress towards cell survival.

  9. Redox Homeostasis in Pancreatic Cells

    Directory of Open Access Journals (Sweden)

    Petr Ježek

    2012-01-01

    Full Text Available We reviewed mechanisms that determine reactive oxygen species (redox homeostasis, redox information signaling and metabolic/regulatory function of autocrine insulin signaling in pancreatic β cells, and consequences of oxidative stress and dysregulation of redox/information signaling for their dysfunction. We emphasize the role of mitochondrion in β cell molecular physiology and pathology, including the antioxidant role of mitochondrial uncoupling protein UCP2. Since in pancreatic β cells pyruvate cannot be easily diverted towards lactate dehydrogenase for lactate formation, the respiration and oxidative phosphorylation intensity are governed by the availability of glucose, leading to a certain ATP/ADP ratio, whereas in other cell types, cell demand dictates respiration/metabolism rates. Moreover, we examine the possibility that type 2 diabetes mellitus might be considered as an inevitable result of progressive self-accelerating oxidative stress and concomitantly dysregulated information signaling in peripheral tissues as well as in pancreatic β cells. It is because the redox signaling is inherent to the insulin receptor signaling mechanism and its impairment leads to the oxidative and nitrosative stress. Also emerging concepts, admiting participation of redox signaling even in glucose sensing and insulin release in pancreatic β cells, fit in this view. For example, NADPH has been firmly established to be a modulator of glucose-stimulated insulin release.

  10. The Impact of Previous Physical Training on Redox Signaling after Traumatic Brain Injury in Rats: A Behavioral and Neurochemical Approach.

    Science.gov (United States)

    da Silva Fiorin, Fernando; de Oliveira Ferreira, Ana P; Ribeiro, Leandro R; Silva, Luiz F A; de Castro, Mauro R T; da Silva, Luís R H; da Silveira, Mauro E P; Zemolin, Ana P P; Dobrachinski, Fernando; Marchesan de Oliveira, Sara; Franco, Jeferson L; Soares, Félix A; Furian, Ana F; Oliveira, Mauro S; Fighera, Michele R; Freire Royes, Luiz F

    2016-07-15

    Throughout the world, traumatic brain injury (TBI) is one of the major causes of disability, which can include deficits in motor function and memory, as well as acquired epilepsy. Although some studies have shown the beneficial effects of physical exercise after TBI, the prophylactic effects are poorly understood. In the current study, we demonstrated that TBI induced by fluid percussion injury (FPI) in adult male Wistar rats caused early motor impairment (24 h), learning deficit (15 days), spontaneous epileptiform events (SEE), and hilar cell loss in the hippocampus (35 days) after TBI. The hippocampal alterations in the redox status, which were characterized by dichlorofluorescein diacetate oxidation and superoxide dismutase (SOD) activity inhibition, led to the impairment of protein function (Na(+), K(+)-adenosine triphosphatase [ATPase] activity inhibition) and glutamate uptake inhibition 24 h after neuronal injury. The molecular adaptations elicited by previous swim training protected against the glutamate uptake inhibition, oxidative stress, and inhibition of selected targets for free radicals (e.g., Na(+), K(+)-ATPase) 24 h after neuronal injury. Our data indicate that this protocol of exercise protected against FPI-induced motor impairment, learning deficits, and SEE. In addition, the enhancement of the hippocampal phosphorylated nuclear factor erythroid 2-related factor (P-Nrf2)/Nrf2, heat shock protein 70, and brain-derived neurotrophic factor immune content in the trained injured rats suggests that protein expression modulation associated with an antioxidant defense elicited by previous physical exercise can prevent toxicity induced by TBI, which is characterized by cell loss in the dentate gyrus hilus at 35 days after TBI. Therefore, this report suggests that previous physical exercise can decrease lesion progression in this model of brain damage.

  11. Dose-Response Analysis of Chemotactic Signaling Response in Salmonella typhimurium LT2 upon Exposure to Cysteine/Cystine Redox Pair.

    Science.gov (United States)

    Rosier, Bob T; Lazova, Milena D

    2016-01-01

    The chemotaxis system enables motile bacteria to search for an optimum level of environmental factors. Salmonella typhimurium senses the amino acid cysteine as an attractant and its oxidized dimeric form, cystine, as a repellent. We investigated the dose-response dependence of changes in chemotactic signaling activity upon exposure to cysteine and cystine of S. typhimurium LT2 using in vivo fluorescence resonance energy transfer (FRET) measurements. The dose-response curve of the attractant response to cysteine had a sigmoidal shape, typical for receptor-ligand interactions. However, in a knockout strain of the chemoreceptor genes tsr and tar, we detected a repellent response to cysteine solutions, scaling linearly with the logarithm of the cysteine concentration. Interestingly, the magnitude of the repellent response to cystine also showed linear dependence to the logarithm of the cystine concentration. This linear dependence was observed over more than four orders of magnitude, where detection started at nanomolar concentrations. Notably, low concentrations of another oxidized compound, benzoquinone, triggered similar responses. In contrast to S. typhimurium 14028, where no response to cystine was observed in a knockout strain of chemoreceptor genes mcpB and mcpC, here we showed that McpB/McpC-independent responses to cystine existed in the strain S. typhimurium LT2 even at nanomolar concentrations. Additionally, knocking out mcpB and mcpC did not affect the linear dose-response dependence, whereas enhanced responses were only observed to solutions that where not pH neutral (>100 μM cystine) in the case of McpC overexpression. We discuss that the linear dependence of the response on the logarithm of cystine concentrations could be a result of a McpB/C-independent redox-sensing pathway that exists in S. typhimurium LT2. We supported this hypothesis with experiments with defined cysteine/cystine mixed solutions, where a transition from repellent to attractant

  12. Information processing through a bio-based redox capacitor: signatures for redox-cycling.

    Science.gov (United States)

    Liu, Yi; Kim, Eunkyoung; White, Ian M; Bentley, William E; Payne, Gregory F

    2014-08-01

    Redox-cycling compounds can significantly impact biological systems and can be responsible for activities that range from pathogen virulence and contaminant toxicities, to therapeutic drug mechanisms. Current methods to identify redox-cycling activities rely on the generation of reactive oxygen species (ROS), and employ enzymatic or chemical methods to detect ROS. Here, we couple the speed and sensitivity of electrochemistry with the molecular-electronic properties of a bio-based redox-capacitor to generate signatures of redox-cycling. The redox capacitor film is electrochemically-fabricated at the electrode surface and is composed of a polysaccharide hydrogel with grafted catechol moieties. This capacitor film is redox-active but non-conducting and can engage diffusible compounds in either oxidative or reductive redox-cycling. Using standard electrochemical mediators ferrocene dimethanol (Fc) and Ru(NH3)6Cl3 (Ru(3+)) as model redox-cyclers, we observed signal amplifications and rectifications that serve as signatures of redox-cycling. Three bio-relevant compounds were then probed for these signatures: (i) ascorbate, a redox-active compound that does not redox-cycle; (ii) pyocyanin, a virulence factor well-known for its reductive redox-cycling; and (iii) acetaminophen, an analgesic that oxidatively redox-cycles but also undergoes conjugation reactions. These studies demonstrate that the redox-capacitor can enlist the capabilities of electrochemistry to generate rapid and sensitive signatures of biologically-relevant chemical activities (i.e., redox-cycling).

  13. Redox Signaling and CBF-Responsive Pathway are Involved in Salicylic Acid-Improved Photosynthesis and Growth under Chilling Stress in Watermelon

    Directory of Open Access Journals (Sweden)

    Fei Cheng

    2016-10-01

    Full Text Available Salicylic acid (SA plays an important role in plant response to abiotic stresses. This study investigated the potential role of SA in alleviating the adverse effects of chilling stress on photosynthesis and growth in watermelon (Citrullus lanatus. Chilling stress induced the simultaneous accumulation of free and conjugated SA in watermelon plants, and the chilling-induced SA production was attributed to the phenylalanine ammonia-lyase pathway. Applying SA at moderate concentrations induced chilling tolerance, whereas inhibition of SA biosynthesis by L-ɑ-aminooxy-β-phenylpropionic acid (AOPP increased the photooxidation of PS II under chilling stress in watermelon, resulting in reduced photosynthesis and growth. Chilling induced a transient increase in the ratios of reduced to oxidized glutathione and reduced ascorbate to dehydroascorbate. Then, the expression of antioxidant genes was upregulated, and the activities of antioxidant enzymes were enhanced. Furthermore, SA-induced chilling tolerance was associated with cellular glutathione and ascorbate homeostasis, which served as redox signals to regulate antioxidant metabolism under chilling stress. AOPP treatment stimulated the chilling-induced expression of cold-responsive genes, particularly via C-repeat binding factors CBF3 and CBF4. These results confirm the synergistic role of SA signaling and the CBF-dependent responsive pathway during chilling stress in watermelon.

  14. Apurinic/apyrimidinic endonuclease1/redox factor-1 (Ape1/Ref-1) is essential for IL-21-induced signal transduction through ERK1/2 pathway.

    Science.gov (United States)

    Juliana, Farha M; Nara, Hidetoshi; Onoda, Tadashi; Rahman, Mizanur; Araki, Akemi; Jin, Lianjin; Fujii, Hodaka; Tanaka, Nobuyuki; Hoshino, Tomoaki; Asao, Hironobu

    2012-04-13

    IL-21 is a pleiotropic cytokine that regulates T-cell and B-cell differentiation, NK-cell activation, and dendritic cell functions. IL-21 activates the JAK-STAT, ERK, and PI3K pathways. We report here that Ape1/Ref-1 has an essential role in IL-21-induced cell growth signal transduction. Overexpression of Ape1/Ref-1 enhances IL-21-induced cell proliferation, but it is suppressed by overexpressing an N-terminal deletion mutant of Ape1/Ref-1 that lacks the redox domain. Furthermore, knockdown of the Ape1/Ref-1 mRNA dramatically compromises IL-21-induced ERK1/2 activation and cell proliferation with increasing cell death. These impaired activities are recovered by the re-expression of Ape1/Ref-1 in the knockdown cells. Our findings are the first demonstration that Ape1/Ref-1 is an indispensable molecule for the IL-21-mediated signal transduction through ERK1/2 activation.

  15. Redox Signaling and CBF-Responsive Pathway Are Involved in Salicylic Acid-Improved Photosynthesis and Growth under Chilling Stress in Watermelon

    Science.gov (United States)

    Cheng, Fei; Lu, Junyang; Gao, Min; Shi, Kai; Kong, Qiusheng; Huang, Yuan; Bie, Zhilong

    2016-01-01

    Salicylic acid (SA) plays an important role in plant response to abiotic stresses. This study investigated the potential role of SA in alleviating the adverse effects of chilling stress on photosynthesis and growth in watermelon (Citrullus lanatus). Chilling stress induced the simultaneous accumulation of free and conjugated SA in watermelon plants, and the chilling-induced SA production was attributed to the phenylalanine ammonia-lyase pathway. Applying SA at moderate concentrations induced chilling tolerance, whereas inhibition of SA biosynthesis by L-α-aminooxy-β-phenylpropionic acid (AOPP) increased the photooxidation of PS II under chilling stress in watermelon, resulting in reduced photosynthesis and growth. Chilling induced a transient increase in the ratios of reduced to oxidized glutathione and reduced ascorbate to dehydroascorbate. Then, the expression of antioxidant genes was upregulated, and the activities of antioxidant enzymes were enhanced. Furthermore, SA-induced chilling tolerance was associated with cellular glutathione and ascorbate homeostasis, which served as redox signals to regulate antioxidant metabolism under chilling stress. AOPP treatment stimulated the chilling-induced expression of cold-responsive genes, particularly via C-repeat binding factors CBF3 and CBF4. These results confirm the synergistic role of SA signaling and the CBF-dependent responsive pathway during chilling stress in watermelon. PMID:27777580

  16. Selective silencing of 2Cys and type-IIB Peroxiredoxins discloses their roles in cell redox state and stress signaling

    Institute of Scientific and Technical Information of China (English)

    Patrcia Vidigal; Clia Guiu-Aragons; Sara Amncio; Lusa Carvalho

    2015-01-01

    Peroxiredoxins (Prx) catalyse the reduction of hydrogen peroxide (H2O2) and, in association with catalases and other peroxidases, may participate in signal transduction by regulating intercel ular H2O2 concentration that in turn can control gene transcription and cel signaling. Using virus-induced-gene-silencing (VIGS), 2-Cys Peroxiredoxin (2CysPrx) family and type-II Peroxiredoxin B (PrxI B) gene were silenced in Nicotiana benthamiana, to study the impact that the loss of function of each Prx would have in the antioxidant system under control (22 °C) and severe heat stress conditions (48 °C). The results showed that both Prxs, although in different organel es, influence the regeneration of ascorbate to a significant extent, but with different purposes. 2CysPrx affects abscisic acid (ABA) biosynthesis through ascorbate, while PrxIIB does it probably through the xanthophyl cycle. Moreover, 2CysPrx is key in H2O2 scavenging and in consequence in the regulation of ABA signal-ing downstream of reactive oxygen species and PrxIIB provides an important assistance for H2O2 peroxisome scavenges.

  17. Experimental characterization of an all-optical wavelength converter of OFDM signals using two-mode injection-locking in a Fabry-Pérot laser.

    Science.gov (United States)

    Dang, Juntao; Yi, Xingwen; Zhang, Jing; Ye, Taiping; Xu, Bo; Qiu, Kun

    2016-07-25

    While optical OFDM has been demonstrated for superior transmission performance, its analogue waveform in the time domain challenges many conventional all-optical wavelength converters (AOWC) that are needed for future flexible optical networks. There only exist a few reports on AOWC of OFDM signals, which are mainly based on the low-efficient four-wave mixing. In this paper, we propose an AOWC for OFDM signals by using two-mode injection-locking in a low-cost Fabry-Pérot laser. The control signal and the probe signal at a milliwatt power level are combined and injected into the FP laser. By a proper control, they can be injection-locked to two longitudinal modes in the FP laser and subsequently, the transmission of the probe signal is conditioned by the control signal. We conduct an experimental study on various aspects of this AOWC. Despite a vendor-specified electrical-to-optical (E/O) modulation bandwidth of 2.5 GHz, we find that the optical-to-optical (O/O) modulation bandwidth of AOWC is free from this limit and can be much wider. We examine the linear transfer curve of the AOWC by simply using the OFDM waveforms as the stimulus. The performance tolerance to the wavelength detuning and injected power ratio is also measured. The proposed AOWC can provide a linear transfer function from the control signal to the probe signal to support the random-fluctuated OFDM waveform. We also investigate the maximum capacity of the AOWC by using the adaptive bit-loading OFDM. Finally, we measure the power penalty after the AOWC at two different bit rates to show the tradeoff between the penalty and capacity.

  18. Wnt/β-catenin signaling cell-autonomously converts non-hepatic endodermal cells to a liver fate

    Directory of Open Access Journals (Sweden)

    Juhoon So

    2012-07-01

    Wnt/β-catenin signaling plays multiple roles in liver development including hepatoblast proliferation and differentiation, hepatocyte differentiation, and liver zonation. A positive role for Wnt/β-catenin signaling in liver specification was recently identified in zebrafish; however, its underlying cellular mechanisms are unknown. Here, we present two cellular mechanisms by which Wnt/β-catenin signaling regulates liver specification. First, using lineage tracing we show that ectopic hepatoblasts, which form in the endoderm posterior to the liver upon activation of Wnt/β-catenin signaling, are derived from the direct conversion of non-hepatic endodermal cells, but not from the posterior migration of hepatoblasts. We found that endodermal cells at the 4–6th somite levels, which normally give rise to the intestinal bulb or intestine, gave rise to hepatoblasts in Wnt8a-overexpressing embryos, and that the distribution of traced endodermal cells in Wnt8a-overexpressing embryos was similar to that in controls. Second, by using an endoderm-restricted cell-transplantation technique and mosaic analysis with transgenic lines that cell-autonomously suppress or activate Wnt/β-catenin signaling upon heat-shock, we show that Wnt/β-catenin signaling acts cell-autonomously in endodermal cells to induce hepatic conversion. Altogether, these data demonstrate that Wnt/β-catenin signaling can induce the fate-change of non-hepatic endodermal cells into a liver fate in a cell-autonomous manner. These findings have potential application to hepatocyte differentiation protocols for the generation of mature hepatocytes from induced pluripotent stem cells, supplying a sufficient amount of hepatocytes for cell-based therapies to treat patients with severe liver diseases.

  19. On-chip frequency compensation with a dual signal path operational transconductance amplifier for a voltage mode control DC/DC converter

    Science.gov (United States)

    Qiang, Ye; Jie, Liu; Bing, Yuan; Xinquan, Lai; Ning, Liu

    2012-04-01

    A novel on-chip frequency compensation circuit for a voltage-mode control DC/DC converter is presented. By employing an RC network in the two signal paths of an operational transconductance amplifier (OTA), the proposed circuit generates two zeros to realize high closed-loop stability. Meanwhile, full on-chip integration is also achieved due to its simple structure. Hence, the number of off-chip components and the board space is greatly reduced. The structure of the dual signal path OTA is also optimized to help get a better transition response. Implemented in a 0.5 μm CMOS process, the voltage mode control DC/DC converter with the proposed frequency compensation circuit exhibits good stability. The test results show that both load and line regulations are less than 0.3%, and the output voltage can be recovered within 15 μs for a 400 mA load step. Moreover, the compensation components area is less than 2% of the die's area and the board space is also reduced by 11%. The efficiency of the whole chip can be up to 95%.

  20. Salvianolic acid B protects against paraquat-induced pulmonary injury by mediating Nrf2/Nox4 redox balance and TGF-β1/Smad3 signaling.

    Science.gov (United States)

    Liu, Bin; Cao, Bo; Zhang, Di; Xiao, Na; Chen, Hong; Li, Guo-Qiang; Peng, Shou-Chun; Wei, Lu-Qing

    2016-10-15

    The present study was aimed at exploring the protective effects of Salvianolic acid B (SalB) against paraquat (PQ)-induced lung injury in mice. Lung fibrotic injuries were induced in mice by a single intragastrical administration of 300mg/kg PQ, then the mice were administrated with 200mg/kg, 400mg/kg SalB, 100mg/kg vitamin C (Vit C) and dexamethasone (DXM) for 14days. PQ-triggered structure distortion, collagen overproduction, excessive inflammatory infiltration, pro-inflammatory cytokine release, and oxidative stress damages in lung tissues and mortality of mice were attenuated by SalB in a dose-dependent manner. Furthermore, SalB was noted to enhance the expression and nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) and reduce expression of the reactive oxygen species-generating enzyme Nox4 [NADPH (reduced form of nicotinamide adenine dinucleotide phosphate) oxidase-4]. SalB also inhibited the increasing expression of transforming growth factor (TGF)-β1 and the phosphorylation of its downstream target Smad3 which were enhanced by PQ. These results suggest that SalB may exert protective effects against PQ-induced lung injury and pulmonary fibrosis. Its mechanisms involve the mediation of Nrf2/Nox4 redox balance and TGF-β1/Smad3 signaling.

  1. A redox-silent analogue of tocotrienol inhibits cobalt(II) chloride-induced VEGF expression via Yes signaling in mesothelioma cells.

    Science.gov (United States)

    Sato, Ayami; Virgona, Nantiga; Ando, Akira; Ota, Masako; Yano, Tomohiro

    2014-01-01

    Vascular endothelial growth factor (VEGF) plays a crucial role in tumor angiogenesis and represents an attractive anticancer target. We have previously demonstrated that a redox-silent analogue of α-tocotrienol, 6-O-carboxypropyl-α-tocotrienol (T3E) exhibits potent anti-carcinogenic property in human malignant mesothelioma (MM) cells. However, inhibition of tumor growth by targeting VEGF pathway remains undetermined. In this study, we explored the inhibitory effect of T3E on the paracrine secretion of VEGF in MM cells under mimicked hypoxia by cobalt chloride (CoCl2). In this study we examine whether T3E can suppress the secretion of VEGF in MM cells exposed to mimic hypoxia by cobalt chloride (CoCl2). We found that CoCl2-induced hypoxia treatment leads to increased up-regulated hypoxia-inducible factor-2α (HIF-2α) and subsequently induced the secretion of VEGF in MM cells. This up-regulation activation mainly depended on the activation of Yes, a member of the Src family of kinases. Treatment of hypoxic MM cells with T3E effectively inhibited the secretion of VEGF, On the other hand, T3E inhibited CoCl2-induced gene expression of VEGF due to the inactivation of Yes/HIF-2α signaling. These data suggest that Yes/HIF2-α/VEGF could be a promising therapeutic target of T3E in MM cells.

  2. Low-dose spiruchostatin-B, a potent histone deacetylase inhibitor enhances radiation-induced apoptosis in human lymphoma U937 cells via modulation of redox signaling.

    Science.gov (United States)

    Rehman, Mati Ur; Jawaid, Paras; Zhao, Qing Li; Li, Peng; Narita, Koichi; Katoh, Tadashi; Shimizu, Tadamichi; Kondo, Takashi

    2016-06-01

    Spiruchostatin B (SP-B), is a potent histone deacetylase (HDAC) inhibitor, in addition to HDAC inhibition, the pharmacological effects of SP-B are also attributed to its ability to produce intracellular reactive oxygen species (ROS), particularly H2O2. In this study, we investigated the effects of low dose (non-toxic) SP-B on radiation-induced apoptosis in human lymphoma U937 cells in vitro. The treatment of cells with low-dose SP-B induced the acetylation of histones, however, does not induce apoptosis. Whereas, the combined treatment with SP-B and radiation significantly enhanced the radiation-induced apoptosis, suggesting the potential role of this combined treatment for future radiation therapy. Interestingly, the enhancement of apoptosis was accompanied by significant increased in the ROS generation. Pre-treatment with an antioxidant, N-acetyl-l-cysteine (NAC) significantly inhibited the enhancement of apoptosis induced by combined treatment, indicating that ROS play an essential role. It was also found that SP-B combined with radiation caused the activation of death receptor and intrinsic apoptotic pathways, via modulation of ROS-mediated signaling. Moreover, SP-B also significantly enhanced the radiation-induced apoptosis in other lymphoma cell lines such as Molt-4 and HL-60. Taken together, our findings suggest that the low-dose SP-B enhances radiation-induced apoptosis via modulation of redox signaling because of its ability to serve as an intracellular ROS generating agent, mainly (H2O2 or [Formula: see text]). This study provides further insights into the mechanism of action of SP-B with radiation and demonstrates that SP-B can be used as a future novel sensitizer for radiation therapy.

  3. Signal and binding. II. Converting physico-chemical responses to macromolecule-ligand interactions into thermodynamic binding isotherms.

    Science.gov (United States)

    Bujalowski, Wlodzimierz; Jezewska, Maria J; Bujalowski, Paul J

    2017-03-01

    Physico-chemical titration techniques are the most commonly used methods in characterizing molecular interactions. These methods are mainly based on spectroscopic, calorimetric, hydrodynamic, etc., measurements. However, truly quantitative physico-chemical methods are absolutely based on the determination of the relationship between the measured signal and the total average degree of binding in order to obtain meaningful interaction parameters. The relationship between the observed physico-chemical signal of whatever nature and the degree of binding must be determined and not assumed, based on some ad hoc intuitive relationship/model, leading to determination of the true binding isotherm. The quantitative methods reviewed and discussed here allow an experimenter to rigorously determine the degree of binding and the free ligand concentration, i.e., they lead to the construction of the thermodynamic binding isotherm in a model-independent fashion from physico-chemical titration curves. Copyright © 2016. Published by Elsevier B.V.

  4. Oxidative stress and redox regulation of phospholipase D in myocardial disease.

    Science.gov (United States)

    Tappia, Paramjit S; Dent, Melissa R; Dhalla, Naranjan S

    2006-08-01

    Oxidative stress may be viewed as an imbalance between reactive oxygen species (ROS) and oxidant production and the state of glutathione redox buffer and antioxidant defense system. Recently, a new paradigm of redox signaling has emerged whereby ROS and oxidants can function as intracellular signaling molecules, where ROS- and oxidant-induced death signal is converted into a survival signal. It is now known that oxidative stress is involved in cardiac hypertrophy and in the pathogenesis of cardiomyopathies, ischemic heart disease and congestive heart failure. Phospholipase D (PLD) is an important signaling enzyme in mammalian cells, including cardiomyocytes. PLD catalyzes the hydrolysis of phosphatidylcholine to produce phosphatidic acid (PA). Two mammalian PLD isozymes, PLD1 and PLD2 have been identified, characterized and cloned. The importance of PA in heart function is evident from its ability to stimulate cardiac sarcolemmal membrane and sarcoplasmic reticular Ca2+-related transport systems and to increase the intracellular concentration of free Ca2+ in adult cardiomyocytes and augment cardiac contractile activity of the normal heart. In addition, PA is also considered an important signal transducer in cardiac hypertrophy. Accordingly, this review discusses a role for redox signaling mediated via PLD in ischemic preconditioning and examines how oxidative stress affects PLD in normal hearts and during different myocardial diseases. In addition, the review provides a comparative account on the regulation of PLD activities in vascular smooth muscle cells under conditions of oxidative stress.

  5. Redox homeostasis: The Golden Mean of healthy living

    OpenAIRE

    Fulvio Ursini; Matilde Maiorino; Henry Jay Forman

    2016-01-01

    The notion that electrophiles serve as messengers in cell signaling is now widely accepted. Nonetheless, major issues restrain acceptance of redox homeostasis and redox signaling as components of maintenance of a normal physiological steady state. The first is that redox signaling requires sudden switching on of oxidant production and bypassing of antioxidant mechanisms rather than a continuous process that, like other signaling mechanisms, can be smoothly turned up or down. The second is the...

  6. Redox control of cellular signalling

    NARCIS (Netherlands)

    Putker, M.

    2014-01-01

    Reactive oxygen species (ROS) are natural by-products of cellular energy production. Consequently, mammalian cells encounter them on a daily basis. Increased ROS levels are associated with the onset of cancer and accelerated ageing, and historically, ROS are therefore considered harmful molecules.

  7. Redox regulation of mitochondrial biogenesis.

    Science.gov (United States)

    Piantadosi, Claude A; Suliman, Hagir B

    2012-12-01

    The cell renews, adapts, or expands its mitochondrial population during episodes of cell damage or periods of intensified energy demand by the induction of mitochondrial biogenesis. This bigenomic program is modulated by redox-sensitive signals that respond to physiological nitric oxide (NO), carbon monoxide (CO), and mitochondrial reactive oxygen species production. This review summarizes our current ideas about the pathways involved in the activation of mitochondrial biogenesis by the physiological gases leading to changes in the redox milieu of the cell, with an emphasis on the responses to oxidative stress and inflammation. The cell's energy supply is protected from conditions that damage mitochondria by an inducible transcriptional program of mitochondrial biogenesis that operates in large part through redox signals involving the nitric oxide synthase and the heme oxygenase-1/CO systems. These redox events stimulate the coordinated activities of several multifunctional transcription factors and coactivators also involved in the elimination of defective mitochondria and the expression of counterinflammatory and antioxidant genes, such as IL10 and SOD2, as part of a unified damage-control network. The redox-regulated mechanisms of mitochondrial biogenesis schematically outlined in the graphical abstract link mitochondrial quality control to an enhanced capacity to support the cell's metabolic needs while improving its resistance to metabolic failure and avoidance of cell death during periods of oxidative stress.

  8. The three-component signalling system HbpS-SenS-SenR as an example of a redox sensing pathway in bacteria

    NARCIS (Netherlands)

    Ortiz de Orué Lucana, Darío; Groves, Matthew R

    The two-component system SenS-SenR and the extracellular HbpS protein of the cellulose degrader Streptomyces reticuli have been shown to act in concert as a novel system which detects redox stress. In vivo and in vitro experiments have led to the hypothesis that HbpS binds and degrades heme,

  9. multilevel buck converter for automotive electrical load

    African Journals Online (AJOL)

    user

    development of DCM based buck converter and its applications in the HEVs/EVs using ... The paper also highlights the implications of implementing a single stage buck converter, and ..... instance when the saw tooth signal within the internal.

  10. Small-Signal Analysis of Single-Phase and Three-phase DC/AC and AC/DC PWM Converters with the Frequency-Shift Technique

    DEFF Research Database (Denmark)

    Blaabjerg, Frede; Aquila, A. Dell’; Liserre, Marco;

    2004-01-01

    A systematic approach to study dc/ac and ac/dc converters without the use of synchronous transformation is proposed. The use of a frequency-shift technique allows a straightforward analysis of single-phase and three-phase systems. The study of dc/ac and of ac/dc converters is reported to the study...... of dc/dc converters via a 50 Hz frequency-shift. The input admittance is calculated and measured for two study examples (a three-phase active rectifier and a single-phase photovoltaic inverter). These examples show that the purpose of a well designed controller for grid-connected converters...

  11. Redox subpopulations and the risk of cancer progression: a new method for characterizing redox heterogeneity

    Science.gov (United States)

    Xu, He N.; Li, Lin Z.

    2016-02-01

    It has been shown that a malignant tumor is akin to a complex organ comprising of various cell populations including tumor cells that are genetically, metabolically and functionally different. Our redox imaging data have demonstrated intra-tumor redox heterogeneity in all mouse xenografts derived from human melanomas, breast, prostate, and colon cancers. Based on the signals of NADH and oxidized flavoproteins (Fp, including flavin adenine dinucleotide (FAD)) and their ratio, i.e., the redox ratio, which is an indicator of mitochondrial metabolic status, we have discovered several distinct redox subpopulations in xenografts of breast tumors potentially recapitulating functional/metabolic heterogeneity within the tumor. Furthermore, xenografts of breast tumors with higher metastatic potential tend to have a redox subpopulation whose redox ratio is significantly different from that of tumors with lower metastatic potential and usually have a bi-modal distribution of the redox ratio. The redox subpopulations from human breast cancer samples can also be very complex with multiple subpopulations as determined by fitting the redox ratio histograms with multi- Gaussian functions. In this report, we present a new method for identifying the redox subpopulations within individual breast tumor xenografts and human breast tissues, which may be used to differentiate between breast cancer and normal tissue and among breast cancer with different risks of progression.

  12. Redox regulation and overreduction control in the photosynthesizing cell: complexity in redox regulatory networks.

    Science.gov (United States)

    Oelze, Marie-Luise; Kandlbinder, Andrea; Dietz, Karl-Josef

    2008-11-01

    Regulation of the photosynthetic apparatus between efficient energy conversion at low light and avoidance of overreduction and damage development at excess light resembles dangerous navigating between Scylla and Charybdis. Photosynthesis is a high rate redox metabolic pathway that generates redox intermediates with extreme redox potentials and eventually reactive oxygen species and oxidative stress. Therefore it is not surprising that the states of defined redox reactions in the chloroplast provide the predominant information and thus directly or indirectly the decisive signals for the multilevel control of cell activities in the chloroplast, cytoplasm, mitochondrion and nucleus. This review elaborates on the diversity of photosynthesis-derived redox signals such as the plastoquinone and thiol redox state that regulate and coordinate light use efficiency, electron transport activity, metabolic reactions, gene transcription and translation not only in the chloroplast but through retrograde signaling also essentially in all other cell compartments. The synergistic and antagonistic interrelations between the redox-dependent signaling pathways and their interactions with other signals such as abscisic acid and tetrapyrol intermediates constitute a redundant and probably buffered regulatory network to optimize performance of photosynthesis on the cellular and whole leaf level.

  13. Microprocessor controlled static converter

    Directory of Open Access Journals (Sweden)

    Stefan Szabo

    2005-10-01

    Full Text Available This paper wants to demonstrate a way of implementing a microcontroller into an DC motor speed control loop. The static power converter is a fully controlled rectifier bridge, using standard SCR's. The bridge's control signals are supplied by the microcontroller and are phase-angle or burst types. The automation loop contains a software PI-style regulator. All the experimental results shows that this aproach is flexibile enough to be used on a large scale.

  14. DSP controlled power converter

    OpenAIRE

    Chan, CH; Pong, MH

    1995-01-01

    A digital controller is designed and implemented by a Digital Signal Processor (DSP) to replace the Pulse Width Modulator (PWM) and error amplifier compensation network in a two wheeler forward converter. The DSP controller is designed in three approaches: a) Discretization of analog controller - the design is based on the transfer function of the error amplifier compensation network. b) Digital PID controller design - the design is based on the general form of the pulse transfer function of ...

  15. Altered Glutathione Redox State in Schizophrenia

    Directory of Open Access Journals (Sweden)

    Jeffrey K. Yao

    2006-01-01

    Full Text Available Altered antioxidant status has been reported in schizophrenia. The glutathione (GSH redox system is important for reducing oxidative stress. GSH, a radical scavenger, is converted to oxidized glutathione (GSSG through glutathione peroxidase (GPx, and converted back to GSH by glutathione reductase (GR. Measurements of GSH, GSSG and its related enzymatic reactions are thus important for evaluating the redox and antioxidant status. In the present study, levels of GSH, GSSG, GPx and GR were assessed in the caudate region of postmortem brains from schizophrenic patients and control subjects (with and without other psychiatric disorders. Significantly lower levels of GSH, GPx, and GR were found in schizophrenic group than in control groups without any psychiatric disorders. Concomitantly, a decreased GSH:GSSG ratio was also found in schizophrenic group. Moreover, both GSSG and GR levels were significantly and inversely correlated to age of schizophrenic patients, but not control subjects. No significant differences were found in any GSH redox measures between control subjects and individuals with other types of psychiatric disorders. There were, however, positive correlations between GSH and GPx, GSH and GR, as well as GPx and GR levels in control subjects without psychiatric disorders. These positive correlations suggest a dynamic state is kept in check during the redox coupling under normal conditions. By contrast, lack of such correlations in schizophrenia point to a disturbance of redox coupling mechanisms in the antioxidant defense system, possibly resulting from a decreased level of GSH as well as age-related decreases of GSSG and GR activities.

  16. Engineered Proteins: Redox Properties and Their Applications

    Science.gov (United States)

    Prabhulkar, Shradha; Tian, Hui; Wang, Xiaotang; Zhu, Jun-Jie

    2012-01-01

    Abstract Oxidoreductases and metalloproteins, representing more than one third of all known proteins, serve as significant catalysts for numerous biological processes that involve electron transfers such as photosynthesis, respiration, metabolism, and molecular signaling. The functional properties of the oxidoreductases/metalloproteins are determined by the nature of their redox centers. Protein engineering is a powerful approach that is used to incorporate biological and abiological redox cofactors as well as novel enzymes and redox proteins with predictable structures and desirable functions for important biological and chemical applications. The methods of protein engineering, mainly rational design, directed evolution, protein surface modifications, and domain shuffling, have allowed the creation and study of a number of redox proteins. This review presents a selection of engineered redox proteins achieved through these methods, resulting in a manipulation in redox potentials, an increase in electron-transfer efficiency, and an expansion of native proteins by de novo design. Such engineered/modified redox proteins with desired properties have led to a broad spectrum of practical applications, ranging from biosensors, biofuel cells, to pharmaceuticals and hybrid catalysis. Glucose biosensors are one of the most successful products in enzyme electrochemistry, with reconstituted glucose oxidase achieving effective electrical communication with the sensor electrode; direct electron-transfer-type biofuel cells are developed to avoid thermodynamic loss and mediator leakage; and fusion proteins of P450s and redox partners make the biocatalytic generation of drug metabolites possible. In summary, this review includes the properties and applications of the engineered redox proteins as well as their significance and great potential in the exploration of bioelectrochemical sensing devices. Antioxid. Redox Signal. 17, 1796–1822. PMID:22435347

  17. Redox regulation of Janus kinase: The elephant in the room.

    Science.gov (United States)

    Duhé, Roy J

    2013-10-01

    The redox regulation of Janus kinases (JAKs) is a complex subject. Due to other redox-sensitive kinases in the kinome, redox-sensitive phosphatases, and cellular antioxidant systems and reactive oxygen species (ROS) production systems, the net biological outcomes of oxidative stress on JAK-dependent signal transduction vary according to the specific biological system examined. This review begins with a discussion of the biochemical evidence for a cysteine-based redox switch in the catalytic domain of JAKs, proceeds to consider direct and indirect regulatory mechanisms involved in biological experiments, and ends with a discussion of the role(s) of redox regulation of JAKs in various diseases.

  18. Redox homeostasis: The Golden Mean of healthy living.

    Science.gov (United States)

    Ursini, Fulvio; Maiorino, Matilde; Forman, Henry Jay

    2016-08-01

    The notion that electrophiles serve as messengers in cell signaling is now widely accepted. Nonetheless, major issues restrain acceptance of redox homeostasis and redox signaling as components of maintenance of a normal physiological steady state. The first is that redox signaling requires sudden switching on of oxidant production and bypassing of antioxidant mechanisms rather than a continuous process that, like other signaling mechanisms, can be smoothly turned up or down. The second is the misperception that reactions in redox signaling involve "reactive oxygen species" rather than reaction of specific electrophiles with specific protein thiolates. The third is that hormesis provides protection against oxidants by increasing cellular defense or repair mechanisms rather than by specifically addressing the offset of redox homeostasis. Instead, we propose that both oxidant and antioxidant signaling are main features of redox homeostasis. As the redox shift is rapidly reversed by feedback reactions, homeostasis is maintained by continuous signaling for production and elimination of electrophiles and nucleophiles. Redox homeostasis, which is the maintenance of nucleophilic tone, accounts for a healthy physiological steady state. Electrophiles and nucleophiles are not intrinsically harmful or protective, and redox homeostasis is an essential feature of both the response to challenges and subsequent feedback. While the balance between oxidants and nucleophiles is preserved in redox homeostasis, oxidative stress provokes the establishment of a new radically altered redox steady state. The popular belief that scavenging free radicals by antioxidants has a beneficial effect is wishful thinking. We propose, instead, that continuous feedback preserves nucleophilic tone and that this is supported by redox active nutritional phytochemicals. These nonessential compounds, by activating Nrf2, mimic the effect of endogenously produced electrophiles (parahormesis). In summary

  19. Redox homeostasis: The Golden Mean of healthy living

    Directory of Open Access Journals (Sweden)

    Fulvio Ursini

    2016-08-01

    Full Text Available The notion that electrophiles serve as messengers in cell signaling is now widely accepted. Nonetheless, major issues restrain acceptance of redox homeostasis and redox signaling as components of maintenance of a normal physiological steady state. The first is that redox signaling requires sudden switching on of oxidant production and bypassing of antioxidant mechanisms rather than a continuous process that, like other signaling mechanisms, can be smoothly turned up or down. The second is the misperception that reactions in redox signaling involve “reactive oxygen species” rather than reaction of specific electrophiles with specific protein thiolates. The third is that hormesis provides protection against oxidants by increasing cellular defense or repair mechanisms rather than by specifically addressing the offset of redox homeostasis. Instead, we propose that both oxidant and antioxidant signaling are main features of redox homeostasis. As the redox shift is rapidly reversed by feedback reactions, homeostasis is maintained by continuous signaling for production and elimination of electrophiles and nucleophiles. Redox homeostasis, which is the maintenance of nucleophilic tone, accounts for a healthy physiological steady state. Electrophiles and nucleophiles are not intrinsically harmful or protective, and redox homeostasis is an essential feature of both the response to challenges and subsequent feedback. While the balance between oxidants and nucleophiles is preserved in redox homeostasis, oxidative stress provokes the establishment of a new radically altered redox steady state. The popular belief that scavenging free radicals by antioxidants has a beneficial effect is wishful thinking. We propose, instead, that continuous feedback preserves nucleophilic tone and that this is supported by redox active nutritional phytochemicals. These nonessential compounds, by activating Nrf2, mimic the effect of endogenously produced electrophiles

  20. Aconitase post-translational modification as a key in linkage between Krebs cycle, iron homeostasis, redox signaling, and metabolism of reactive oxygen species.

    Science.gov (United States)

    Lushchak, Oleh V; Piroddi, Marta; Galli, Francesco; Lushchak, Volodymyr I

    2014-01-01

    Aconitase, an enzyme possessing an iron-sulfur cluster that is sensitive to oxidation, is involved in the regulation of cellular metabolism. There are two isoenzymes of aconitase (Aco)--mitochondrial (mAco) and cytosolic (cAco) ones. The primary role of mAdco is believed to be to control cellular ATP production via regulation of intermediate flux in the Krebs cycle. The cytosolic Aco in its reduced form operates as an enzyme, whereas in the oxidized form it is involved in the control of iron homeostasis as iron regulatory protein 1 (IRP1). Reactive oxygen species (ROS) play a central role in regulation of Aco functions. Catalytic Aco activity is regulated by reversible oxidation of [4Fe-4S]²⁺ cluster and cysteine residues, so redox-dependent posttranslational modifications (PTMs) have gained increasing consideration as regards possible regulatory effects. These include modifications of cysteine residues by oxidation, nitrosylation and thiolation, as well as Tyr nitration and oxidation of Lys residues to carbonyls. Redox-independent PTMs such as phosphorylation and transamination also have been described. In the presence of a sustained ROS flux, redox-dependent PTMs may lead to enzyme damage and cell stress by impaired energy and iron metabolism. Aconitase has been identified as a protein that undergoes oxidative modification and inactivation in aging and certain oxidative stress-related disorders. Here we describe possible mechanisms of involvement of the two aconitase isoforms, cAco and mAco, in the control of cell metabolism and iron homeostasis, balancing the regulatory, and damaging effects of ROS.

  1. COX19 mediates the transduction of a mitochondrial redox signal from SCO1 that regulates ATP7A-mediated cellular copper efflux

    OpenAIRE

    Leary, Scot C; Cobine, Paul A.; Nishimura, Tamiko; Verdijk, Robert M; de Krijger, Ronald; Coo, René; Tarnopolsky, Mark A.; Winge, Dennis R; Eric A Shoubridge

    2013-01-01

    SCO1 and SCO2 are metallochaperones whose principal function is to add two copper ions to the catalytic core of cytochrome c oxidase (COX). However, affected tissues of SCO1 and SCO2 patients exhibit a combined deficiency in COX activity and total copper content, suggesting additional roles for these proteins in the regulation of cellular copper homeostasis. Here we show that both the redox state of the copper-binding cysteines of SCO1 and the abundance of SCO2 correlate with cellular copper ...

  2. Novel, Unifying Mechanism for Mescaline in The Central Nervous System: Electrochemistry, Catechol Redox Metabolite, Receptor, Cell Signaling and Structure Activity Relationships

    Directory of Open Access Journals (Sweden)

    Peter Kovacic

    2009-01-01

    Full Text Available A unifying mechanism for abused drugs has been proposed previously from the standpoint of electron transfer. Mescaline can be accommodated within the theoretical framework based on redox cycling by the catechol metabolite with its quinone counterpart. Electron transfer may play a role in electrical effects involving the nervous system in the brain. This approach is in accord with structure activity relationships involving mescaline, abused drugs, catecholamines and etoposide. Inefficient demethylation is in keeping with the various drug properties, such as requirement for high dosage and slow acting.

  3. Mitochondrially targeted fluorescent redox sensors.

    Science.gov (United States)

    Yang, Kylie; Kolanowski, Jacek L; New, Elizabeth J

    2017-04-06

    The balance of oxidants and antioxidants within the cell is crucial for maintaining health, and regulating physiological processes such as signalling. Consequently, imbalances between oxidants and antioxidants are now understood to lead to oxidative stress, a physiological feature that underlies many diseases. These processes have spurred the field of chemical biology to develop a plethora of sensors, both small-molecule and fluorescent protein-based, for the detection of specific oxidizing species and general redox balances within cells. The mitochondrion, in particular, is the site of many vital redox reactions. There is therefore a need to target redox sensors to this particular organelle. It has been well established that targeting mitochondria can be achieved by the use of a lipophilic cation-targeting group, or by utilizing natural peptidic mitochondrial localization sequences. Here, we review how these two approaches have been used by a number of researchers to develop mitochondrially localized fluorescent redox sensors that are already proving useful in providing insights into the roles of reactive oxygen species in the mitochondria.

  4. Redox regulation of transient receptor potential channels.

    OpenAIRE

    2014-01-01

    Abstract Significance: Environmental and endogenous reactive species such as reactive oxygen species (ROS), reactive nitrogen species (RNS), and other electrophiles are not only known to exert toxic effects on organisms, but are also emerging as molecules that mediate cell signaling responses. However, the mechanisms underlying this cellular redox signaling by reactive species remains largely uncharacterized.

  5. Simulation Results of Double Forward Converter

    Directory of Open Access Journals (Sweden)

    P. Vijaya KUMAR

    2009-12-01

    Full Text Available This work aims to find a better forward converter for DC to DC conversion.Simulation of double forward converter in SMPS system is discussed in this paper. Aforward converter with RCD snubber to synchronous rectifier and/or to current doubleris also discussed. The evolution of the forward converter is first reviewed in a tutorialfashion. Performance parameters are discussed including operating principle, voltageconversion ratio, efficiency, device stress, small-signal dynamics, noise and EMI. Itscircuit operation and its performance characteristics of the forward converter with RCDsnubber and double forward converter are described and the simulation results arepresented.

  6. Measurement of Reactive Oxygen Species, Reactive Nitrogen Species, and Redox-Dependent Signaling in the Cardiovascular System: A Scientific Statement From the American Heart Association.

    Science.gov (United States)

    Griendling, Kathy K; Touyz, Rhian M; Zweier, Jay L; Dikalov, Sergey; Chilian, William; Chen, Yeong-Renn; Harrison, David G; Bhatnagar, Aruni

    2016-08-19

    Reactive oxygen species and reactive nitrogen species are biological molecules that play important roles in cardiovascular physiology and contribute to disease initiation, progression, and severity. Because of their ephemeral nature and rapid reactivity, these species are difficult to measure directly with high accuracy and precision. In this statement, we review current methods for measuring these species and the secondary products they generate and suggest approaches for measuring redox status, oxidative stress, and the production of individual reactive oxygen and nitrogen species. We discuss the strengths and limitations of different methods and the relative specificity and suitability of these methods for measuring the concentrations of reactive oxygen and reactive nitrogen species in cells, tissues, and biological fluids. We provide specific guidelines, through expert opinion, for choosing reliable and reproducible assays for different experimental and clinical situations. These guidelines are intended to help investigators and clinical researchers avoid experimental error and ensure high-quality measurements of these important biological species.

  7. Oxidized ATM promotes abnormal proliferation of breast CAFs through maintaining intracellular redox homeostasis and activating the PI3K-AKT, MEK-ERK, and Wnt-β-catenin signaling pathways.

    Science.gov (United States)

    Tang, Shifu; Hou, Yixuan; Zhang, Hailong; Tu, Gang; Yang, Li; Sun, Yifan; Lang, Lei; Tang, Xi; Du, Yan-E; Zhou, Mingli; Yu, Tenghua; Xu, Liyun; Wen, Siyang; Liu, Chunming; Liu, Manran

    2015-01-01

    Abnormal proliferation is one characteristic of cancer-associated fibroblasts (CAFs), which play a key role in tumorigenesis and tumor progression. Oxidative stress (OS) is the root cause of CAFs abnormal proliferation. ATM (ataxia-telangiectasia mutated protein kinase), an important redox sensor, is involved in DNA damage response and cellular homeostasis. Whether and how oxidized ATM regulating CAFs proliferation remains unclear. In this study, we show that there is a high level of oxidized ATM in breast CAFs in the absence of double-strand breaks (DSBs) and that oxidized ATM plays a critical role in CAFs proliferation. The effect of oxidized ATM on CAFs proliferation is mediated by its regulation of cellular redox balance and the activity of the ERK, PI3K-AKT, and Wnt signaling pathways. Treating cells with antioxidant N-acetyl-cysteine (NAC) partially rescues the proliferation defect of the breast CAFs caused by ATM deficiency. Administrating cells with individual or a combination of specific inhibitors of the ERK, PI3K-AKT, and Wnt signaling pathways mimics the effect of ATM deficiency on breast CAF proliferation. This is mainly ascribed to the β-catenin suppression and down-regulation of c-Myc, thus further leading to the decreased cyclinD1, cyclinE, and E2F1 expression and the enhanced p21(Cip1) level. Our results reveal an important role of oxidized ATM in the regulation of the abnormal proliferation of breast CAFs. Oxidized ATM could serve as a potential target for treating breast cancer.

  8. Acupuncture mechanism and redox equilibrium.

    Science.gov (United States)

    Zeng, Xiang-Hong; Li, Qian-Qian; Xu, Qian; Li, Fang; Liu, Cun-Zhi

    2014-01-01

    Oxidative stress participates in the pathological process of various diseases. Acupuncture is a component of the health care system in China that can be traced back for at least 3000 years. Recently, increased evidences indicate that acupuncture stimulation could reduce oxidative damage in organisms under pathological state, but the exact mechanism remains unclear. This review focuses on the emerging links between acupuncture and redox modulation in various disorders, such as vascular dementia, Parkinson's disease, and hypertension, ranging from redox system, antioxidant system, anti-inflammatory system, and nervous system to signaling pathway. Although the molecular and cellular pathways studies of acupuncture effect on oxidative stress are preliminary, they represent an important step forward in the research of acupuncture antioxidative effect.

  9. Acupuncture Mechanism and Redox Equilibrium

    Directory of Open Access Journals (Sweden)

    Xiang-Hong Zeng

    2014-01-01

    Full Text Available Oxidative stress participates in the pathological process of various diseases. Acupuncture is a component of the health care system in China that can be traced back for at least 3000 years. Recently, increased evidences indicate that acupuncture stimulation could reduce oxidative damage in organisms under pathological state, but the exact mechanism remains unclear. This review focuses on the emerging links between acupuncture and redox modulation in various disorders, such as vascular dementia, Parkinson’s disease, and hypertension, ranging from redox system, antioxidant system, anti-inflammatory system, and nervous system to signaling pathway. Although the molecular and cellular pathways studies of acupuncture effect on oxidative stress are preliminary, they represent an important step forward in the research of acupuncture antioxidative effect.

  10. Redox properties of extracellular polymeric substances (EPS) from electroactive bacteria

    Science.gov (United States)

    Li, Shan-Wei; Sheng, Guo-Ping; Cheng, Yuan-Yuan; Yu, Han-Qing

    2016-12-01

    Although the capacity for electroactive bacteria to convert environmental metallic minerals and organic pollutants is well known, the role of the redox properties of microbial extracellular polymeric substances (EPS) in this process is poorly understood. In this work, the redox properties of EPS from two widely present electroactive bacterial strains (Shewanella oneidensis and Pseudomonas putida) were explored. Electrochemical analysis demonstrates that the EPS extracted from the two strains exhibited redox properties. Spectroelectrochemical and protein electrophoresis analyses indicate that the extracted EPS from S. oneidensis and P. putida contained heme-binding proteins, which were identified as the possible redox components in the EPS. The results of heme-mediated behavior of EPS may provide an insight into the important roles of EPS in electroactive bacteria to maximize their redox capability for biogeochemical cycling, environmental bioremediation and wastewater treatment.

  11. Unity power factor converter

    Science.gov (United States)

    Wester, Gene W. (Inventor)

    1980-01-01

    A unity power factor converter capable of effecting either inversion (dc-to-dc) or rectification (ac-to-dc), and capable of providing bilateral power control from a DC source (or load) through an AC transmission line to a DC load (or source) for power flow in either direction, is comprised of comparators for comparing the AC current i with an AC signal i.sub.ref (or its phase inversion) derived from the AC ports to generate control signals to operate a switch control circuit for high speed switching to shape the AC current waveform to a sine waveform, and synchronize it in phase and frequency with the AC voltage at the AC ports, by selectively switching the connections to a series inductor as required to increase or decrease the current i.

  12. Redox interplay between mitochondria and peroxisomes

    Directory of Open Access Journals (Sweden)

    Celien eLismont

    2015-05-01

    Full Text Available Reduction-oxidation or ‘redox’ reactions are an integral part of a broad range of cellular processes such as gene expression, energy metabolism, protein import and folding, and autophagy. As many of these processes are intimately linked with cell fate decisions, transient or chronic changes in cellular redox equilibrium are likely to contribute to the initiation and progression of a plethora of human diseases. Since a long time, it is known that mitochondria are major players in redox regulation and signaling. More recently, it has become clear that also peroxisomes have the capacity to impact redox-linked physiological processes. To serve this function, peroxisomes cooperate with other organelles, including mitochondria. This review provides a comprehensive picture of what is currently known about the redox interplay between mitochondria and peroxisomes in mammals. We first outline the pro- and antioxidant systems of both organelles and how they may function as redox signaling nodes. Next, we critically review and discuss emerging evidence that peroxisomes and mitochondria share an intricate redox-sensitive relationship and cooperate in cell fate decisions. Key issues include possible physiological roles, messengers, and mechanisms. We also provide examples of how data mining of publicly-available datasets from ‘omics’ technologies can be a powerful means to gain additional insights into potential redox signaling pathways between peroxisomes and mitochondria. Finally, we highlight the need for more studies that seek to clarify the mechanisms of how mitochondria may act as dynamic receivers, integrators, and transmitters of peroxisome-derived mediators of oxidative stress. The outcome of such studies may open up exciting new avenues for the community of researchers working on cellular responses to organelle-derived oxidative stress, a research field in which the role of peroxisomes is currently highly underestimated and an issue of

  13. Proteomics links the redox state to calcium signaling during bleaching of the scleractinian coral Acropora microphthalma on exposure to high solar irradiance and thermal stress.

    Science.gov (United States)

    Weston, Andrew J; Dunlap, Walter C; Beltran, Victor H; Starcevic, Antonio; Hranueli, Daslav; Ward, Malcolm; Long, Paul F

    2015-03-01

    Shipboard experiments were each performed over a 2 day period to examine the proteomic response of the symbiotic coral Acropora microphthalma exposed to acute conditions of high temperature/low light or high light/low temperature stress. During these treatments, corals had noticeably bleached. The photosynthetic performance of residual algal endosymbionts was severely impaired but showed signs of recovery in both treatments by the end of the second day. Changes in the coral proteome were determined daily and, using recently available annotated genome sequences, the individual contributions of the coral host and algal endosymbionts could be extracted from these data. Quantitative changes in proteins relevant to redox state and calcium metabolism are presented. Notably, expression of common antioxidant proteins was not detected from the coral host but present in the algal endosymbiont proteome. Possible roles for elevated carbonic anhydrase in the coral host are considered: to restore intracellular pH diminished by loss of photosynthetic activity, to indirectly limit intracellular calcium influx linked with enhanced calmodulin expression to impede late-stage symbiont exocytosis, or to enhance inorganic carbon transport to improve the photosynthetic performance of algal symbionts that remain in hospite. Protein effectors of calcium-dependent exocytosis were present in both symbiotic partners. No caspase-family proteins associated with host cell apoptosis, with exception of the autophagy chaperone HSP70, were detected, suggesting that algal loss and photosynthetic dysfunction under these experimental conditions were not due to host-mediated phytosymbiont destruction. Instead, bleaching occurred by symbiont exocytosis and loss of light-harvesting pigments of algae that remain in hospite. These proteomic data are, therefore, consistent with our premise that coral endosymbionts can mediate their own retention or departure from the coral host, which may manifest as

  14. A standardized way to select, evaluate, and test an analog-to-digital converter for ultrawide bandwidth radiofrequency signals based on user's needs, ideal, published,and actual specifications

    Science.gov (United States)

    Chang, Daniel Y.; Rowe, Neil C.

    2012-06-01

    The most important adverse impact on the Electronic Warfare (EW) simulation is that the number of signal sources that can be tested simultaneously is relatively small. When the number of signal sources increases, the analog hardware, complexity and costs grow by the order of N2, since the number of connections among N components is O(N*N) and the signal communication is bi-directional. To solve this problem, digitization of the signal is suggested. In digitizing a radiofrequency signal, an Analog-to-Digital Converter (ADC) is widely used. Most research studies on ADCs are conducted from designer/test engineers' perspective. Some research studies are conducted from market's perspective. This paper presents a generic way to select, evaluate and test ultra high bandwidth COTS ADCs and generate requirements for digitizing continuous time signals from the perspective of user's needs. Based on user's needs, as well as vendor's published, ideal and actual specifications, a decision can be made in selecting a proper ADC for an application. To support our arguments and illustrate the methodology, we evaluate a Tektronix TADC-1000, an 8-bit and 12 gigasamples per second ADC. This project is funded by JEWEL lab, NAWCWD at Point Mugu, CA.

  15. High-Performance Data Converters

    DEFF Research Database (Denmark)

    Steensgaard-Madsen, Jesper

    Novel techniques for multi-bit oversampled data conversion are described. State-of-the-art oversampled data converters are analyzed, leading to the conclusion that their performance is limited mainly by low-resolution signal representation. To increase the resolution, high-performance, high...

  16. Reciprocal Control of the Circadian Clock and Cellular Redox State - a Critical Appraisal.

    Science.gov (United States)

    Putker, Marrit; O'Neill, John Stuart

    2016-01-01

    Redox signalling comprises the biology of molecular signal transduction mediated by reactive oxygen (or nitrogen) species. By specific and reversible oxidation of redox-sensitive cysteines, many biological processes sense and respond to signals from the intracellular redox environment. Redox signals are therefore important regulators of cellular homeostasis. Recently, it has become apparent that the cellular redox state oscillates in vivo and in vitro, with a period of about one day (circadian). Circadian time-keeping allows cells and organisms to adapt their biology to resonate with the 24-hour cycle of day/night. The importance of this innate biological time-keeping is illustrated by the association of clock disruption with the early onset of several diseases (e.g. type II diabetes, stroke and several forms of cancer). Circadian regulation of cellular redox balance suggests potentially two distinct roles for redox signalling in relation to the cellular clock: one where it is regulated by the clock, and one where it regulates the clock. Here, we introduce the concepts of redox signalling and cellular timekeeping, and then critically appraise the evidence for the reciprocal regulation between cellular redox state and the circadian clock. We conclude there is a substantial body of evidence supporting circadian regulation of cellular redox state, but that it would be premature to conclude that the converse is also true. We therefore propose some approaches that might yield more insight into redox control of cellular timekeeping.

  17. Redox regulation in cancer stem cells

    Science.gov (United States)

    Reactive oxygen species (ROS) and ROS-dependent (redox regulation) signaling pathways and transcriptional activities are thought to be critical in stem cell self-renewal and differentiation during growth and organogenesis. Aberrant ROS burst and dysregulation of those ROS-dependent cellular processe...

  18. REDOX IMAGING OF THE p53-DEPENDENT MITOCHONDRIAL REDOX STATE IN COLON CANCER EX VIVO

    Directory of Open Access Journals (Sweden)

    HE N. XU

    2013-07-01

    Full Text Available The mitochondrial redox state and its heterogeneity of colon cancer at tissue level have not been previously reported. Nor has how p53 regulates mitochondrial respiration been measured at (deep tissue level, presumably due to the unavailability of the technology that has sufficient spatial resolution and tissue penetration depth. Our prior work demonstrated that the mitochondrial redox state and its intratumor heterogeneity is associated with cancer aggressiveness in human melanoma and breast cancer in mouse models, with the more metastatic tumors exhibiting localized regions of more oxidized redox state. Using the Chance redox scanner with an in-plane spatial resolution of 200 μm, we imaged the mitochondrial redox state of the wild-type p53 colon tumors (HCT116 p53 wt and the p53-deleted colon tumors (HCT116 p53-/- by collecting the fluorescence signals of nicotinamide adenine dinucleotide (NADH and oxidized flavoproteins [Fp, including flavin adenine dinucleotide (FAD] from the mouse xenografts snap-frozen at low temperature. Our results show that: (1 both tumor lines have significant degree of intratumor heterogeneity of the redox state, typically exhibiting a distinct bi-modal distribution that either correlates with the spatial core–rim pattern or the "hot/cold" oxidation-reduction patches; (2 the p53-/- group is significantly more heterogeneous in the mitochondrial redox state and has a more oxidized tumor core compared to the p53 wt group when the tumor sizes of the two groups are matched; (3 the tumor size dependence of the redox indices (such as Fp and Fp redox ratio is significant in the p53-/- group with the larger ones being more oxidized and more heterogeneous in their redox state, particularly more oxidized in the tumor central regions; (4 the H&E staining images of tumor sections grossly correlate with the redox images. The present work is the first to reveal at the submillimeter scale the intratumor heterogeneity pattern of

  19. The Redox System in C. elegans, a Phylogenetic Approach

    Directory of Open Access Journals (Sweden)

    Andrew D. Johnston

    2012-01-01

    Full Text Available Oxidative stress is a toxic state caused by an imbalance between the production and elimination of reactive oxygen species (ROS. ROS cause oxidative damage to cellular components such as proteins, lipids, and nucleic acids. While the role of ROS in cellular damage is frequently all that is noted, ROS are also important in redox signalling. The “Redox Hypothesis" has been proposed to emphasize a dual role of ROS. This hypothesis suggests that the primary effect of changes to the redox state is modified cellular signalling rather than simply oxidative damage. In extreme cases, alteration of redox signalling can contribute to the toxicity of ROS, as well as to ageing and age-related diseases. The nematode species Caenorhabditis elegans provides an excellent model for the study of oxidative stress and redox signalling in animals. We use protein sequences from central redox systems in Homo sapiens, Drosophila melanogaster, and Saccharomyces cerevisiae to query Genbank for homologous proteins in C. elegans. We then use maximum likelihood phylogenetic analysis to compare protein families between C. elegans and the other organisms to facilitate future research into the genetics of redox biology.

  20. Redox control of GTPases: from molecular mechanisms to functional significance in health and disease.

    Science.gov (United States)

    Heo, Jongyun

    2011-02-15

    Small GTPases, including the proto-oncoprotein Ras and Rho GTPases, are involved in various cellular signaling events. Some of these small GTPases are redox sensitive, including Ras, Rho, Ran, Dexras1, and Rhes GTPases. Thus, the redox-mediated regulation of these GTPases often determines the course of their cellular signaling cascades. This article takes into consideration the application of Marcus theory to potential redox-based molecular mechanisms in the regulation of these redox-sensitive GTPases and the relevance of such mechanisms to a specific redox-sensitive motif. The discussion also takes into account various diseases, including cancers, heart, and neuronal disorders, that are often linked with the dysregulation of the redox signaling cascades associated with these redox-sensitive GTPases.

  1. Redox Stable Anodes for Solid Oxide Fuel Cells

    Directory of Open Access Journals (Sweden)

    Guoliang eXiao

    2014-06-01

    Full Text Available Solid oxide fuel cells (SOFCs can convert chemical energy from the fuel directly to electrical energy with high efficiency and fuel flexibility. Ni-based cermets have been the most widely adopted anode for SOFCs. However, the conventional Ni-based anode has low tolerance to sulfur-contamination, is vulnerable to deactivation by carbon build-up (coking from direct oxidation of hydrocarbon fuels, and suffers volume instability upon redox cycling. Among these limitations, the redox instability of the anode is particularly important and has been intensively studied since the SOFC anode may experience redox cycling during fuel cell operations even with the ideal pure hydrogen as the fuel. This review aims to highlight recent progresses on improving redox stability of the conventional Ni-based anode through microstructure optimization and exploration of alternative ceramic-based anode materials.

  2. Wide range operation of regenerative optical parametric wavelength converter using ASE-degraded 43-Gb/s RZ-DPSK signals.

    Science.gov (United States)

    Gao, Mingyi; Kurumida, Junya; Namiki, Shu

    2011-11-07

    For sustainable growth of the Internet, wavelength-tunable optical regeneration is the key to scaling up high energy-efficiency dynamic optical path networks while keeping the flexibility of the network. Wavelength-tunable optical parametric regenerator (T-OPR) based on the gain saturation effect of parametric amplification in a highly nonlinear fiber is promising for noise reduction in phase-shift keying signals. In this paper, we experimentally evaluated the T-OPR performance for ASE-degraded 43-Gb/s RZ-DPSK signals over a 20-nm input wavelength range between 1527 nm and 1547 nm. As a result, we achieved improved power penalty performance for the regenerated idler with a proper pump power range.

  3. 具有数据转换和处理功能的信号调理器%Signal Conditioner With Data Converter and Processor Function

    Institute of Scientific and Technical Information of China (English)

    纪宗南

    2002-01-01

    详细介绍了信号调理器MAX1462的特点,主要电气参数,内部功能模块电路.最后给出该器件的典型应用电路.%This paper introduces the features, main electrical parameters, internal function of signal conditioner MA 1462 in detail, its typical application circuit is also provided.

  4. Adaptive controller design based on input-output signal selection for voltage source converter high voltage direct current systems to improve power system stability

    Institute of Scientific and Technical Information of China (English)

    Abdolkhalegh Hamidi; Jamal Beiza; Ebrahim Babaei; Sohrab Khanmohammadi

    2016-01-01

    An input-output signal selection based on Phillips-Heffron model of a parallel high voltage alternative current/high voltage direct current (HVAC/HVDC) power system is presented to study power system stability. It is well known that appropriate coupling of inputs-outputs signals in the multivariable HVDC-HVAC system can improve the performance of designed supplemetary controller. In this work, different analysis techniques are used to measure controllability and observability of electromechanical oscillation mode. Also inputs–outputs interactions are considered and suggestions are drawn to select the best signal pair through the system inputs-outputs. In addition, a supplementary online adaptive controller for nonlinear HVDC to damp low frequency oscillations in a weakly connected system is proposed. The results obtained using MATLAB software show that the best output-input for damping controller design is rotor speed deviation as out put and phase angle of rectifier as in put. Also response of system equipped with adaptive damping controller based on HVDC system has appropriate performance when it is faced with faults and disturbance.

  5. Redox biology in normal cells and cancer: restoring function of the redox/Fyn/c-Cbl pathway in cancer cells offers new approaches to cancer treatment.

    Science.gov (United States)

    Noble, Mark; Mayer-Pröschel, Margot; Li, Zaibo; Dong, Tiefei; Cui, Wanchang; Pröschel, Christoph; Ambeskovic, Ibro; Dietrich, Joerg; Han, Ruolan; Yang, Yin Miranda; Folts, Christopher; Stripay, Jennifer; Chen, Hsing-Yu; Stevens, Brett M

    2015-02-01

    This review discusses a unique discovery path starting with novel findings on redox regulation of precursor cell and signaling pathway function and identification of a new mechanism by which relatively small changes in redox status can control entire signaling networks that regulate self-renewal, differentiation, and survival. The pathway central to this work, the redox/Fyn/c-Cbl (RFC) pathway, converts small increases in oxidative status to pan-activation of the c-Cbl ubiquitin ligase, which controls multiple receptors and other proteins of central importance in precursor cell and cancer cell function. Integration of work on the RFC pathway with attempts to understand how treatment with systemic chemotherapy causes neurological problems led to the discovery that glioblastomas (GBMs) and basal-like breast cancers (BLBCs) inhibit c-Cbl function through altered utilization of the cytoskeletal regulators Cool-1/βpix and Cdc42, respectively. Inhibition of these proteins to restore normal c-Cbl function suppresses cancer cell division, increases sensitivity to chemotherapy, disrupts tumor-initiating cell (TIC) activity in GBMs and BLBCs, controls multiple critical TIC regulators, and also allows targeting of non-TICs. Moreover, these manipulations do not increase chemosensitivity or suppress division of nontransformed cells. Restoration of normal c-Cbl function also allows more effective harnessing of estrogen receptor-α (ERα)-independent activities of tamoxifen to activate the RFC pathway and target ERα-negative cancer cells. Our work thus provides a discovery strategy that reveals mechanisms and therapeutic targets that cannot be deduced by standard genetics analyses, which fail to reveal the metabolic information, isoform shifts, protein activation, protein complexes, and protein degradation critical to our discoveries.

  6. 3',5-dihydroxy-3,4',7-trimethoxyflavone-induces ER-stress-associated HCT-116 programmed cell death via redox signaling.

    Science.gov (United States)

    Singh, Mahendra Pal; Han, Jaehong; Kang, Sun Chul

    2017-04-01

    Quercetin, a well cognized bioactive flavone possessing great medicinal value, has limited usage. The rapid gastrointestinal digestion of quercetin is also a major obstacle for its clinical implementation due to low bioavailability and poor aqueous solubility. 3',5-dihydroxy-3,4',7-trimethoxyflavone (DTMF), a novel semi-synthetic derivative of quercetin, is known to modulate several biological activities. Therefore, in the present study we examined the cytotoxic mechanism of DTMF in concentration-dependent manner (25, 50, and 100μM; 24h) against HCT-116 human colon carcinoma cells. The cytotoxic potential of DTMF was characterized based on deformed cell morphology, increased ROS accumulation, loss of mitochondrial membrane potential (ΔѰm), increased mitochondrial mass, chromatin condensation, and typical DNA-fragmentation in HCT-116 cells. The results showed that DTMF-induced enhanced ROS production at higher concentration (100μM) as evidenced by upregulated expression of ER stress and apoptotic proteins with concomitant increase in PERK, CHOP, and JNK levels, when compared to N-acetyl cysteine (NAC, ROS inhibitor) treated HCT-116 cells, which depicts that DTMF might act as a crucial mediator of apoptosis signaling. Collectively, our results suggest that DTMF stimulates ROS-mediated oxidative stress, which in turn induces PERK-CHOP and JNK pathway of apoptosis to promote HCT-116 cell death. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  7. Aflatoxin Biosynthesis Is a Novel Source of Reactive Oxygen Species—A Potential Redox Signal to Initiate Resistance to Oxidative Stress?

    Science.gov (United States)

    Roze, Ludmila V.; Laivenieks, Maris; Hong, Sung-Yong; Wee, Josephine; Wong, Shu-Shyan; Vanos, Benjamin; Awad, Deena; Ehrlich, Kenneth C.; Linz, John E.

    2015-01-01

    Aflatoxin biosynthesis in the filamentous fungus Aspergillus parasiticus involves a minimum of 21 enzymes, encoded by genes located in a 70 kb gene cluster. For aflatoxin biosynthesis to be completed, the required enzymes must be transported to specialized early and late endosomes called aflatoxisomes. Of particular significance, seven aflatoxin biosynthetic enzymes are P450/monooxygenases which catalyze reactions that can produce reactive oxygen species (ROS) as byproducts. Thus, oxidative reactions in the aflatoxin biosynthetic pathway could potentially be an additional source of intracellular ROS. The present work explores the hypothesis that the aflatoxin biosynthetic pathway generates ROS (designated as “secondary” ROS) in endosomes and that secondary ROS possess a signaling function. We used specific dyes that stain ROS in live cells and demonstrated that intracellular ROS levels correlate with the levels of aflatoxin synthesized. Moreover, feeding protoplasts with precursors of aflatoxin resulted in the increase in ROS generation. These data support the hypothesis. Our findings also suggest that secondary ROS may fulfill, at least in part, an important mechanistic role in increased tolerance to oxidative stress in germinating spores (seven-hour germlings) and in regulation of fungal development. PMID:25928133

  8. NADPH OXIDASE AND LIPID RAFT-ASSOCIATED REDOX SIGNALING ARE REQUIRED FOR PCB153-INDUCED UPREGULATION OF CELL ADHESION MOLECULES IN HUMAN BRAIN ENDOTHELIAL CELLS

    Science.gov (United States)

    Eum, Sung Yong; Andras, Ibolya; Hennig, Bernhard; Toborek, Michal

    2009-01-01

    Exposure to persistent organic pollutants, such as polychlorinated biphenyls (PCBs), can lead to chronic inflammation and the development of vascular diseases. Because cell adhesion molecules (CAMs) of the cerebrovascular endothelium regulate infiltration of inflammatory cells into the brain, we have explored the molecular mechanisms by which ortho-substituted polychlorinated biphenyls (PCBs), such as PCB153, can upregulate CAMs in brain endothelial cells. Exposure to PCB153 increased expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1), as well as elevated adhesion of leukocytes to brain endothelial cells. These effects were impeded by inhibitors of EGFR, JAKs, or Src activity. In addition, pharmacological inhibition of NADPH oxidase or disruption of lipid rafts by cholesterol depleting agents blocked PCB153-induced phosphorylation of JAK and Src kinases and upregulation of CAMs. In contrast, silencing of caveolin-1 by siRNA interference did not affect upregulation of ICAM-1 and VCAM-1 in brain endothelial cells stimulated by PCB153. Results of the present study indicate that lipid raft-dependent NADPH oxidase/JAK/EGFR signaling mechanisms regulate the expression of CAMs in brain endothelial cells and adhesion of leukocytes to endothelial monolayers. Due to its role in leukocyte infiltration, induction of CAMs may contribute to PCB-induced cerebrovascular disorders and neurotoxic effects in the CNS. PMID:19632255

  9. Fundamentals and hard-switching converters

    CERN Document Server

    Ioinovici, Adrian

    2013-01-01

    Volume 1 Fundamentals and Hard-switching Converters introduces the key challenges in power electronics from basic components to operation principles and presents classical hard- and soft-switching DC to DC converters, rectifiers and inverters. At a more advanced level, it provides comprehensive analysis of DC and AC models comparing the available approaches for their derivation and results. A full treatment of DC to DC hard-switching converters is given, from fundamentals to modern industrial solutions and practical engineering insight. The author elucidates various contradictions and misunderstandings in the literature, for example, in the treatment of the discontinuous conduction operation or in deriving AC small-signal models of converters.

  10. The decay of Redox-stress Response Capacity is a substantive characteristic of aging: Revising the redox theory of aging.

    Science.gov (United States)

    Meng, Jiao; Lv, Zhenyu; Qiao, Xinhua; Li, Xiaopeng; Li, Yazi; Zhang, Yuying; Chen, Chang

    2017-04-01

    Aging is tightly associated with redox events. The free radical theory of aging indicates that redox imbalance may be an important factor in the aging process. Most studies about redox and aging focused on the static status of oxidative stress levels, there has been little research investigating differential responses to redox challenge during aging. In this study, we used Caenorhabditis elegans and human fibroblasts as models to compare differential responses to oxidative stress challenge in young and old individuals. In response to paraquat stress, young individuals generated more ROS and activated signaling pathways including p-ERK, p-AKT and p-AMPKα/β. After the initial response, young individuals then promoted NRF2 translocation and induced additional antioxidant enzymes and higher expression of phase II enzymes, including SOD, CAT, GPX, HO-1, GSTP-1and others, to maintain redox homeostasis. Moreover, young individuals also demonstrated a better ability to degrade damaged proteins by up-regulating the expression of chaperones and improving proteasome activity. Based on these data, we propose a new concept "Redox-stress Response Capacity (RRC)", which suggests cells or organisms are capable of generating dynamic redox responses to activate cellular signaling and maintain cellular homeostasis. The decay of RRC is the substantive characteristic of aging, which gives a new understand of the redox theory of aging. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  11. A New Hard Switching Bidirectional Converter With High Power Density

    Directory of Open Access Journals (Sweden)

    Bahador Fani

    2010-01-01

    Full Text Available In this paper, a new isolated dc-dc bidirectional converter is proposed. This converter consists of two transformers (flyback and forward and only one switch in primary side and one switch in secondary side of transformers. In this converter energy transfers to the output in both on and off switch states so power density of this converter is high This converter controlled by PWM signal. Also this converter operates over a wide input voltage range. Theoretical analysis is presented and computer simulation and experimental results verify the converter analysis.

  12. Wavelength converter technology

    DEFF Research Database (Denmark)

    Kloch, Allan; Hansen, Peter Bukhave; Poulsen, Henrik Nørskov;

    1999-01-01

    Wavelength conversion is important since it ensures full flexibility of the WDM network layer. Progress in optical wavelength converter technology is reviewed with emphasis on all-optical wavelength converter types based on semiconductor optical amplifiers....

  13. Wavelength converter technology

    DEFF Research Database (Denmark)

    Kloch, Allan; Hansen, Peter Bukhave; Poulsen, Henrik Nørskov;

    1999-01-01

    Wavelength conversion is important since it ensures full flexibility of the WDM network layer. Progress in optical wavelength converter technology is reviewed with emphasis on air-optical wavelength converter types based on semiconductor optical amplifiers....

  14. Periodic Control of Power Electronic Converters

    DEFF Research Database (Denmark)

    Zhou, Keliang; Danwei, Wang; Yang, Yongheng

    Advanced power electronic converters convert, control and condition electricity. Power converters require control strategies for periodic signal compensation to assure good power quality and stable power system operation. This comprehensive text presents the most recent internal model principle...... based periodic control technology, which offers the perfect periodic control solution for power electronic conversion. It also provides complete analysis and synthesis methods for periodic control systems, and plenty of practical examples to demonstrate the validity of proposed periodic control...... technology for power converters. It proposes a unified framework for housing periodic control schemes for power converters, and provides a general proportional-integral-derivative control solution to periodic signal compensation in extensive engineering applications. Periodic Control of Power Electronic...

  15. Time interleaved counter analog to digital converters

    OpenAIRE

    Danesh, Seyed Amir Ali

    2011-01-01

    The work explores extending time interleaving in A/D converters, by applying a high-level of parallelism to one of the slowest and simplest types of data-converters, the counter ADC. The motivation for the work is to realise high-performance re-configurable A/D converters for use in multi-standard and multi-PHY communication receivers with signal bandwidths in the 10s to 100s of MHz. The counter ADC requires only a comparator, a ramp signal, and a digital counter, where the ...

  16. Technologies for converter topologies

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, Yan; Zhang, Haiyu

    2017-02-28

    In some embodiments of the disclosed inverter topologies, an inverter may include a full bridge LLC resonant converter, a first boost converter, and a second boost converter. In such embodiments, the first and second boost converters operate in an interleaved manner. In other disclosed embodiments, the inverter may include a half-bridge inverter circuit, a resonant circuit, a capacitor divider circuit, and a transformer.

  17. Power Converters for Accelerators

    CERN Document Server

    Visintini, R

    2015-01-01

    Particle accelerators use a great variety of power converters for energizing their sub-systems; while the total number of power converters usually depends on the size of the accelerator or combination of accelerators (including the experimental setup), the characteristics of power converters depend on their loads and on the particle physics requirements: this paper aims to provide an overview of the magnet power converters in use in several facilities worldwide.

  18. Redox mechanisms in hepatic chronic wound healing and fibrogenesis

    Directory of Open Access Journals (Sweden)

    Novo Erica

    2008-10-01

    Full Text Available Abstract Reactive oxygen species (ROS generated within cells or, more generally, in a tissue environment, may easily turn into a source of cell and tissue injury. Aerobic organisms have developed evolutionarily conserved mechanisms and strategies to carefully control the generation of ROS and other oxidative stress-related radical or non-radical reactive intermediates (that is, to maintain redox homeostasis, as well as to 'make use' of these molecules under physiological conditions as tools to modulate signal transduction, gene expression and cellular functional responses (that is, redox signalling. However, a derangement in redox homeostasis, resulting in sustained levels of oxidative stress and related mediators, can play a significant role in the pathogenesis of major human diseases characterized by chronic inflammation, chronic activation of wound healing and tissue fibrogenesis. This review has been designed to first offer a critical introduction to current knowledge in the field of redox research in order to introduce readers to the complexity of redox signalling and redox homeostasis. This will include ready-to-use key information and concepts on ROS, free radicals and oxidative stress-related reactive intermediates and reactions, sources of ROS in mammalian cells and tissues, antioxidant defences, redox sensors and, more generally, the major principles of redox signalling and redox-dependent transcriptional regulation of mammalian cells. This information will serve as a basis of knowledge to introduce the role of ROS and other oxidative stress-related intermediates in contributing to essential events, such as the induction of cell death, the perpetuation of chronic inflammatory responses, fibrogenesis and much more, with a major focus on hepatic chronic wound healing and liver fibrogenesis.

  19. A Level Converter provided with Slew-Rate Controlling Means

    NARCIS (Netherlands)

    Annema, Anne J.

    2000-01-01

    A level converter for the converting of a first digital signal (U1) having a first voltage range into a second digital signal (U2) having a second voltage range comprising an amplifier (T0) having an input for receiving the first digital signal (U1) and an output for supplying the second digital

  20. Potential role of redox cycling as a mechanism for chemical teratogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Juchau, M.R.; Fantel, A.G.; Harris, C.; Beyer, B.K.

    1986-12-01

    A survey of the literature indicates that several chemicals whose reduced metabolites are capable of undergoing redox cycling in biological systems also possess significant teratogenic properties when tested in vivo. The authors have initiated investigations to determine whether the embryotoxic effects of such chemicals could result from their redox cycling properties and whether redox cycling could be an important mechanism in chemical teratogenesis. In order to obviate the potentially confounding influences of maternal factors, the initial studies have been performed with a whole embryo culture system with redox cycling agents added directly to the culture medium. Several representative redox cycling agents including doxorubicin, paraquat, a series of nitroheterocycles, nitrosofluorene, and diethylstilbestrol (converted metabolically to redox cycling quinone/semiquinone radicals) have been investigated thus far. The nitroheterocycles which bear nitro groups with comparatively high redox potentials produced a striking, asymmetric defect involving primarily the right half of the prosencephalic and mesencephalic regions. The effect was exacerbated under conditions of low O/sub 2/ tension. Accumulated data to date strongly suggest that reduction of the nitro group is an essential feature in the embryotoxic mechanism. Quinones (doxorubicin, paraquat) and compounds metabolically converted to quinones (diethylstilbestrol) appeared to produce embryotoxic effects via mechanisms not associated with redox cycling. Nitrosofluorene embryotoxicity was markedly exacerbated by changes in both intra- and extracellular glutathione levels, but definitive dependence on a radical-mediated effect or redox cycling was not demonstrated.

  1. MATtrack: A MATLAB-Based Quantitative Image Analysis Platform for Investigating Real-Time Photo-Converted Fluorescent Signals in Live Cells.

    Directory of Open Access Journals (Sweden)

    Jane Courtney

    Full Text Available We introduce here MATtrack, an open source MATLAB-based computational platform developed to process multi-Tiff files produced by a photo-conversion time lapse protocol for live cell fluorescent microscopy. MATtrack automatically performs a series of steps required for image processing, including extraction and import of numerical values from Multi-Tiff files, red/green image classification using gating parameters, noise filtering, background extraction, contrast stretching and temporal smoothing. MATtrack also integrates a series of algorithms for quantitative image analysis enabling the construction of mean and standard deviation images, clustering and classification of subcellular regions and injection point approximation. In addition, MATtrack features a simple user interface, which enables monitoring of Fluorescent Signal Intensity in multiple Regions of Interest, over time. The latter encapsulates a region growing method to automatically delineate the contours of Regions of Interest selected by the user, and performs background and regional Average Fluorescence Tracking, and automatic plotting. Finally, MATtrack computes convenient visualization and exploration tools including a migration map, which provides an overview of the protein intracellular trajectories and accumulation areas. In conclusion, MATtrack is an open source MATLAB-based software package tailored to facilitate the analysis and visualization of large data files derived from real-time live cell fluorescent microscopy using photoconvertible proteins. It is flexible, user friendly, compatible with Windows, Mac, and Linux, and a wide range of data acquisition software. MATtrack is freely available for download at eleceng.dit.ie/courtney/MATtrack.zip.

  2. MATtrack: A MATLAB-Based Quantitative Image Analysis Platform for Investigating Real-Time Photo-Converted Fluorescent Signals in Live Cells.

    Science.gov (United States)

    Courtney, Jane; Woods, Elena; Scholz, Dimitri; Hall, William W; Gautier, Virginie W

    2015-01-01

    We introduce here MATtrack, an open source MATLAB-based computational platform developed to process multi-Tiff files produced by a photo-conversion time lapse protocol for live cell fluorescent microscopy. MATtrack automatically performs a series of steps required for image processing, including extraction and import of numerical values from Multi-Tiff files, red/green image classification using gating parameters, noise filtering, background extraction, contrast stretching and temporal smoothing. MATtrack also integrates a series of algorithms for quantitative image analysis enabling the construction of mean and standard deviation images, clustering and classification of subcellular regions and injection point approximation. In addition, MATtrack features a simple user interface, which enables monitoring of Fluorescent Signal Intensity in multiple Regions of Interest, over time. The latter encapsulates a region growing method to automatically delineate the contours of Regions of Interest selected by the user, and performs background and regional Average Fluorescence Tracking, and automatic plotting. Finally, MATtrack computes convenient visualization and exploration tools including a migration map, which provides an overview of the protein intracellular trajectories and accumulation areas. In conclusion, MATtrack is an open source MATLAB-based software package tailored to facilitate the analysis and visualization of large data files derived from real-time live cell fluorescent microscopy using photoconvertible proteins. It is flexible, user friendly, compatible with Windows, Mac, and Linux, and a wide range of data acquisition software. MATtrack is freely available for download at eleceng.dit.ie/courtney/MATtrack.zip.

  3. Redox Flow Batteries, a Review

    Energy Technology Data Exchange (ETDEWEB)

    Knoxville, U. Tennessee; U. Texas Austin; U, McGill; Weber, Adam Z.; Mench, Matthew M.; Meyers, Jeremy P.; Ross, Philip N.; Gostick, Jeffrey T.; Liu, Qinghua

    2011-07-15

    Redox flow batteries are enjoying a renaissance due to their ability to store large amounts of electrical energy relatively cheaply and efficiently. In this review, we examine the components of redox flow batteries with a focus on understanding the underlying physical processes. The various transport and kinetic phenomena are discussed along with the most common redox couples.

  4. HMGB1 redox during sepsis.

    Science.gov (United States)

    Abdulmahdi, Wasan; Patel, Devika; Rabadi, May M; Azar, Tala; Jules, Edson; Lipphardt, Mark; Hashemiyoon, Rameen; Ratliff, Brian B

    2017-10-01

    During sepsis, the alarmin HMGB1 is released from tissues and promotes systemic inflammation that results in multi-organ damage, with the kidney particularly susceptible to injury. The severity of inflammation and pro-damage signaling mediated by HMGB1 appears to be dependent on the alarmin's redox state. Therefore, we examined HMGB1 redox in kidney cells during sepsis. Using intravital microscopy, CellROX labeling of kidneys in live mice indicated increased ROS generation in the kidney perivascular endothelium and tubules during lipopolysaccharide (LPS)-induced sepsis. Subsequent CellROX and MitoSOX labeling of LPS-stressed endothelial and kidney proximal tubule cells demonstrated increased ROS generation in these cells as sepsis worsens. Consequently, HMGB1 oxidation increased in the cytoplasm of kidney cells during its translocation from the nucleus to the circulation, with the degree of oxidation dependent on the severity of sepsis, as measured in in vivo mouse samples using a thiol assay and mass spectrometry (LC-MS/MS). The greater the oxidation of HMGB1, the greater the ability of the alarmin to stimulate pro-inflammatory cyto-/chemokine release (measured by Luminex Multiplex) and alter mitochondrial ATP generation (Luminescent ATP Detection Assay). Administration of glutathione and thioredoxin inhibitors to cell cultures enhanced HMGB1 oxidation during sepsis in endothelial and proximal tubule cells, respectively. In conclusion, as sepsis worsens, ROS generation and HMGB1 oxidation increases in kidney cells, which enhances HMGB1's pro-inflammatory signaling. Conversely, the glutathione and thioredoxin systems work to maintain the protein in its reduced state. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  5. Structural redox control in a 7Fe ferredoxin isolated from Desulfovibrio alaskensis.

    Science.gov (United States)

    Grazina, Raquel; de Sousa, Patrícia M Paes; Brondino, Carlos D; Carepo, Marta S P; Moura, Isabel; Moura, José J G

    2011-08-01

    The redox behaviour of a ferredoxin (Fd) from Desulfovibrio alaskensis was characterized by electrochemistry. The protein was isolated and purified, and showed to be a tetramer containing one [3Fe-4S] and one [4Fe-4S] centre. This ferredoxin has high homology with FdI from Desulfovibrio vulgaris Miyazaki and Hildenborough and FdIII from Desulfovibrio africanus. From differential pulse voltammetry the following signals were identified: [3Fe-4S](+1/0) (E(0')=-158±5mV); [4Fe-4S](+2/+1) (E(0')=-474±5mV) and [3Fe-4S](0/-2) (E(0')=-660±5mV). The effect of pH on these signals showed that the reduced [3Fe-4S](0) cluster has a pK'(red)(')=5.1±0.1, the [4Fe-4S](+2/+1) centre is pH independent, and the [3Fe-4S](0/-2) reduction is accompanied by the binding of two protons. The ability of the [3Fe-4S](0) cluster to be converted into a new [4Fe-4S] cluster was proven. The redox potential of the original [4Fe-4S] centre showed to be dependent on the formation of the new [4Fe-4S] centre, which results in a positive shift (ca. 70mV) of the redox potential of the original centre. Being most [Fe-S] proteins involved in electron transport processes, the electrochemical characterization of their clusters is essential to understand their biological function. Complementary EPR studies were performed.

  6. Redox-regulated transcription in plants: Emerging concepts

    Directory of Open Access Journals (Sweden)

    Jehad Shaikhali

    2017-09-01

    Full Text Available In plants, different stimuli, both internal and external, activate production of reactive oxygen species (ROS. Photosynthesis is considered as high rate redox-metabolic process with rapid transients including light/photon capture, electron fluxes, and redox potentials that can generate ROS; thus, regulatory systems are required to minimize ROS production. Despite their potential for causing harmful oxidations, it is now accepted that redox homeostasis mechanisms that maintain the intracellular reducing environment make it possible to use ROS as powerful signaling molecules within and between cells. Redox and ROS information from the chloroplasts is a fine-tuning mechanism both inside the chloroplast and as retrograde signal to the cytosol and nucleus to control processes such as gene expression/transcription and translation. Wide repertoires of downstream target genes expression (activation/repression is regulated by transcription factors. In many cases, transcription factors function through various mechanisms that affect their subcellular localization and or activity. Some post-translational modifications (PTMs known to regulate the functional state of transcription factors are phosphorylation, acetylation, and SUMOylation, ubiquitylation and disulfide formation. Recently, oxPTMs, targeted in redox proteomics, can provide the bases to study redox regulation of low abundant nuclear proteins. This review summarizes the recent advances on how cellular redox status can regulate transcription factor activity, the implications of this regulation for plant growth and development, and by which plants respond to environmental/abiotic stresses.

  7. REACTIVE OXYGEN SPECIES, CELLULAR REDOX SYSTEMS AND APOPTOSIS

    OpenAIRE

    2010-01-01

    Reactive oxygen species (ROS) are products of normal metabolism and xenobiotic exposure, and depending on concentrations, ROS can be beneficial or harmful to cells and tissues. At physiological low levels, ROS function as “redox messengers” in intracellular signaling and regulation while excess ROS induce oxidative modification of cellular macromolecules, inhibit protein function and promote cell death. Additionally, various redox systems, such as the glutathione, thioredoxin, and pyridine nu...

  8. The photoelectric displacement converter

    Science.gov (United States)

    Dragoner, Valeriu V.

    2005-02-01

    In the article are examined questions of constructing photoelectric displacement converter satisfying demands that are stated above. Converter has channels of approximate and precise readings. The approximate reading may be accomplished either by the method of reading from a code mask or by the method of the consecutive calculation of optical scale gaps number. Phase interpolator of mouar strips" gaps is determined as a precise measuring. It is shown mathematical model of converter that allow evaluating errors and operating speed of conversion.

  9. Computation of the Redox and Protonation Properties of Quinones: Towards the Prediction of Redox Cycling Natural Products.

    Energy Technology Data Exchange (ETDEWEB)

    Cape, Jonathan L.; Bowman, Michael K.; Kramer, David M.

    2006-08-01

    Quinone metabolites perform a variety of key functions in plants, including pathogen protection, oxidative phosphorylation, and redox signaling. Many of these structurally diverse compounds have been shown to exhibit potent antimicrobial, anticancer, and anti-inflammatory properties, although the exact mechanisms of action are far from understood. Redox cycling has been proposed as a possible mechanism of action for many quinine species. Experimental determination of the essential thermodynamic data (i.e. electrochemical and pKa values) required to predict the propensity towards redox cycling is often difficult or impossible to obtain due to the experimental limitations. We demonstrate a practical computational approach to obtain reasonable estimates of these parameters.

  10. Modelling, analyses and design of switching converters

    Science.gov (United States)

    Cuk, S. M.; Middlebrook, R. D.

    1978-01-01

    A state-space averaging method for modelling switching dc-to-dc converters for both continuous and discontinuous conduction mode is developed. In each case the starting point is the unified state-space representation, and the end result is a complete linear circuit model, for each conduction mode, which correctly represents all essential features, namely, the input, output, and transfer properties (static dc as well as dynamic ac small-signal). While the method is generally applicable to any switching converter, it is extensively illustrated for the three common power stages (buck, boost, and buck-boost). The results for these converters are then easily tabulated owing to the fixed equivalent circuit topology of their canonical circuit model. The insights that emerge from the general state-space modelling approach lead to the design of new converter topologies through the study of generic properties of the cascade connection of basic buck and boost converters.

  11. Redox theory of aging

    Directory of Open Access Journals (Sweden)

    Dean P. Jones

    2015-08-01

    Full Text Available Metazoan genomes encode exposure memory systems to enhance survival and reproductive potential by providing mechanisms for an individual to adjust during lifespan to environmental resources and challenges. These systems are inherently redox networks, arising during evolution of complex systems with O2 as a major determinant of bioenergetics, metabolic and structural organization, defense, and reproduction. The network structure decreases flexibility from conception onward due to differentiation and cumulative responses to environment (exposome. The redox theory of aging is that aging is a decline in plasticity of genome–exposome interaction that occurs as a consequence of execution of differentiation and exposure memory systems. This includes compromised mitochondrial and bioenergetic flexibility, impaired food utilization and metabolic homeostasis, decreased barrier and defense capabilities and loss of reproductive fidelity and fecundity. This theory accounts for hallmarks of aging, including failure to maintain oxidative or xenobiotic defenses, mitochondrial integrity, proteostasis, barrier structures, DNA repair, telomeres, immune function, metabolic regulation and regenerative capacity.

  12. Microfluidic redox battery.

    Science.gov (United States)

    Lee, Jin Wook; Goulet, Marc-Antoni; Kjeang, Erik

    2013-07-01

    A miniaturized microfluidic battery is proposed, which is the first membraneless redox battery demonstrated to date. This unique concept capitalizes on dual-pass flow-through porous electrodes combined with stratified, co-laminar flow to generate electrical power on-chip. The fluidic design is symmetric to allow for both charging and discharging operations in forward, reverse, and recirculation modes. The proof-of-concept device fabricated using low-cost materials integrated in a microfluidic chip is shown to produce competitive power levels when operated on a vanadium redox electrolyte. A complete charge/discharge cycle is performed to demonstrate its operation as a rechargeable battery, which is an important step towards providing sustainable power to lab-on-a-chip and microelectronic applications.

  13. Ediacaran Redox Fluctuations

    Science.gov (United States)

    Sahoo, S. K.; Jiang, G.; Planavsky, N. J.; Kendall, B.; Owens, J. D.; Anbar, A. D.; Lyons, T. W.

    2013-12-01

    Evidence for pervasive oxic conditions, and likely even deep ocean oxygenation has been documented at three intervals in the lower (ca. 632 Ma), middle (ca. 580 Ma) and upper (ca. 551 Ma) Ediacaran. The Doushantuo Formation in South China hosts large enrichments of redox-sensitive trace element (e.g., molybdenum, vanadium and uranium) in anoxic shales, which are indicative of a globally oxic ocean-atmosphere system. However, ocean redox conditions between these periods continue to be a topic of debate and remain elusive. We have found evidence for widespread anoxic conditions through much of the Ediacaran in the deep-water Wuhe section in South China. During most of the Ediacaran-early Cambrian in basinal sections is characterized by Fe speciation data and pyrite morphologies that indicate deposition under euxinic conditions with near-crustal enrichments of redox-sensitive element and positive pyrite-sulfur isotope values, which suggest low levels of marine sulfate and widespread euxinia. Our work reinforces an emerging view that the early Earth, including the Ediacaran, underwent numerous rises and falls in surface oxidation state, rather than a unidirectional rise as originally imagined. The Ediacaran ocean thus experienced repetitive expansion and contraction of marine chalcophilic trace-metal levels that may have had fundamental impact on the slow evolution of early animals and ecosystems. Further, this framework forces us to re-examine the relationship between Neoproterozoic oxygenation and metazoan diversification. Varying redox conditions through the Cryogenian and Ediacaran may help explain molecular clock and biomarker evidence for an early appearance and initial diversification of metazoans but with a delay in the appearance of most major metazoan crown groups until close to Ediacaran-Cambrian boundary.

  14. Switching power converters medium and high power

    CERN Document Server

    Neacsu, Dorin O

    2013-01-01

    An examination of all of the multidisciplinary aspects of medium- and high-power converter systems, including basic power electronics, digital control and hardware, sensors, analog preprocessing of signals, protection devices and fault management, and pulse-width-modulation (PWM) algorithms, Switching Power Converters: Medium and High Power, Second Edition discusses the actual use of industrial technology and its related subassemblies and components, covering facets of implementation otherwise overlooked by theoretical textbooks. The updated Second Edition contains many new figures, as well as

  15. High speed data converters

    CERN Document Server

    Ali, Ahmed MA

    2016-01-01

    This book covers high speed data converters from the perspective of a leading high speed ADC designer and architect, with a strong emphasis on high speed Nyquist A/D converters. For our purposes, the term 'high speed' is defined as sampling rates that are greater than 10 MS/s.

  16. Electrical Power Converter

    NARCIS (Netherlands)

    Ferreira, J.A.

    2014-01-01

    Electrical power converter for converting electrical power of a power source connected or connectable at an input to electrical DC-power at an output, wherein between the input and the output a first circuit of submodules is provided, wherein said first circuit of submodules and the power source for

  17. Development of Redox Metabolic Imaging Using Endogenous Molecules.

    Science.gov (United States)

    Hyodo, Fuminori; Ito, Shinji; Eto, Hinako; Nakaji, Tomoko; Yasukawa, Keiji; Kobayashi, Ryoma; Utsumi, Hideo

    2016-01-01

    Redox metabolism plays a central role in maintaining homeostasis in living organisms. The electron transfer system in mitochondria produces ATP via endogenous redox molecules such as flavin mononucleotide (FMN), flavin adenine dinucleotide (FAD), and coenzyme Q10 (CoQ10), which have flavin or quinone moieties. One-electron transfer reactions convert FMN, FAD, and CoQ10 to the free radical intermediates FMNH and FADH, and CoQ10H, respectively. Dynamic nuclear polarization-magnetic resonance imaging (DNP-MRI) allows us to visualize free radicals in vitro and in vivo. We present a spectroscopic imaging technology with DNP-MRI, which enables the imaging of multiple free radical intermediates such as FADH and CoQH. DNP-MRI can also identify various endogenous free radical intermediates derived from redox transformations.

  18. Cascaded resonant bridge converters

    Science.gov (United States)

    Stuart, Thomas A. (Inventor)

    1989-01-01

    A converter for converting a low voltage direct current power source to a higher voltage, high frequency alternating current output for use in an electrical system where it is desired to use low weight cables and other circuit elements. The converter has a first stage series resonant (Schwarz) converter which converts the direct current power source to an alternating current by means of switching elements that are operated by a variable frequency voltage regulator, a transformer to step up the voltage of the alternating current, and a rectifier bridge to convert the alternating current to a direct current first stage output. The converter further has a second stage series resonant (Schwarz) converter which is connected in series to the first stage converter to receive its direct current output and convert it to a second stage high frequency alternating current output by means of switching elements that are operated by a fixed frequency oscillator. The voltage of the second stage output is controlled at a relatively constant value by controlling the first stage output voltage, which is accomplished by controlling the frequency of the first stage variable frequency voltage controller in response to second stage voltage. Fault tolerance in the event of a load short circuit is provided by making the operation of the first stage variable frequency voltage controller responsive to first and second stage current limiting devices. The second stage output is connected to a rectifier bridge whose output is connected to the input of the second stage to provide good regulation of output voltage wave form at low system loads.

  19. Voltage Regulator for a dc-to-dc Converter

    Science.gov (United States)

    Mclyman, C. W.

    1983-01-01

    New voltage regulator isolates signals from power-switching converter without use of complex circuitry or optical couplers. Only addition is extra secondary winding on existing interstage transformer. Error signals shortcircuit new winding and inhibit converter action. Resistor in series with primary winding limits short-circuit current to prevent damage to circuit components. Extra transformer winding eliminates need for isolation components.

  20. A nano switch mechanism for the redox-responsive sulfotransferase.

    Science.gov (United States)

    Lin, Chih-Heng; Lin, En-Shyh; Su, Tian-Mu; Hung, Kuo-Sheng; Yang, Yuh-Shyong

    2012-07-15

    Cellular redox signaling is important in diverse physiological and pathological processes. The activity of rat phenol sulfotransferase (rSULT1A1), which is important for the metabolism of hormone and drug, is subjected to redox regulation. Two cysteines, Cys232 and Cys66, nanometer away from each other and from the enzyme active site were proposed to form disulfide bond to regulate the activity of rSULT1A1. A nano switch, composed of a flexible loop from amino acid residues 59-70, explained how this long distance interaction between two cysteines can be achieved. The enzyme properties were investigated through site-directed muatagnesis, circular dichroism, enzyme kinetics and homologous modeling of the rSULT1A1 structures. We proposed that the formation of disulfide bond between Cys232 and Cys66 induced conformational changes of sulfotransferase, then in turn affected its nucleotide binding and enzyme activity. This discovery was extended to understand the possible redox regulation of other sulfotransferases from different organisms. The redox switch can be created in other redox-insensitive sulfotransferases, such as human phenol sulfotransferase (hSULT1A1) and human alcohol sulfotransferase (hSULT2A1), to produce mutant enzymes with redox regulation capacity. This study strongly suggested that redox regulation of drug and hormone metabolism can be significantly varied even though the sequence and structure of SULT1A1 of human and rat have a high degree of homology.

  1. Signal enhancement for gene detection based on a redox reaction of [Fe(CN)(6)](4-) mediated by ferrocene at the terminal of a peptide nucleic acid as a probe with hybridization-amenable conformational flexibility.

    Science.gov (United States)

    Aoki, Hiroshi; Tao, Hiroaki

    2008-07-01

    Electrochemically enhanced DNA detection was demonstrated by utilizing the couple of a synthesized ferrocene-terminated peptide nucleic acid (PNA) with a cysteine anchor and a sacrificial electron donor [Fe(CN)(6)](4-). DNA detection sensors were prepared by modifying a gold electrode surface with a mixed monolayer of the probe PNA and 11-hydroxy-1-undecanethiol (11-HUT), protecting [Fe(CN)(6)](4-) from any unexpected redox reaction. Before hybridization, the terminal ferrocene moiety of the probe was subject to a redox reaction due to the flexible probe structure and, in the presence of [Fe(CN)(6)](4-), the observed current was amplified based on regeneration of the ferrocene moiety. Hybridization decreased the redox current of the ferrocene. This occurred because hybridization rigidified the probe structure: the ferrocene moiety was then removed from the electrode surface, and the redox reaction of [Fe(CN)(6)](4-) was again prevented. The change in the anodic current before and after hybridization was enhanced 1.75-fold by using the electron donor [Fe(CN)(6)](4-). Sequence-specific detection of the complementary target DNA was also demonstrated.

  2. Vegetarian diets and public health: biomarker and redox connections.

    Science.gov (United States)

    Benzie, Iris F F; Wachtel-Galor, Sissi

    2010-11-15

    Vegetarian diets are rich in antioxidant phytochemicals. However, they may not act as antioxidants in vivo, and yet still have important signaling and regulatory functions. Some may act as pro-oxidants, modulating cellular redox tone and oxidizing redox sensitive sites. In this review, evidence for health benefits of vegetarian diets is presented from different perspectives: epidemiological, biomarker, evolutionary, and public health, as well as antioxidant. From the perspective of molecular connections between diet and health, evidence of a role for plasma ascorbic acid as a biomarker for future disease risk is presented. Basic concepts of redox-based cell signaling are presented, and effects of antioxidant phytochemicals on signaling, especially via redox tone, sulfur switches and the Antioxidant Response Element (ARE), are explored. Sufficient scientific evidence exists for public health policy to promote a plant-rich diet for health promotion. This does not need to wait for science to provide all the answers as to why and how. However, action and interplay of dietary antioxidants in the nonequilibrium systems that control redox balance, cell signaling, and cell function provide rich ground for research to advance understanding of orthomolecular nutrition and provide science-based evidence to advance public health in our aging population.

  3. Design of Monolithic Integrator for Strain-to-Frequency Converter

    Directory of Open Access Journals (Sweden)

    Tuan Mohd. Khairi Tuan Mat

    2012-01-01

    Full Text Available Strain-to-Frequency converter (SFC is a one of the analog conditioner tools that converts any strain signal to the frequency signal. The basic concept of SFC is by detecting any changing of strains, then converting the strain to the voltage signal and converting the voltage signal to the frequency signal. This tool consists of 3 main  components which are strain gauge, differential integrator and comparator. This paper presents the designing and analysis of monolithic integrator that to be used in the Strain-toFrequency converter. The primary goal is to design and simulate the performance of monolithic integrator for SFC using GATEWAY Silvaco Electronic Design Automation (S EDA tools and EXPERT software. The performances of SFC using the designed monolithic integrator are also investigated.

  4. The Impact of Age-Related Dysregulation of the Angiotensin System on Mitochondrial Redox Balance

    Directory of Open Access Journals (Sweden)

    Ramya eVajapey

    2014-11-01

    Full Text Available Aging is associated with the accumulation of various deleterious changes in cells. According to the free radical and mitochondrial theory of aging, mitochondria initiate most of the deleterious changes in aging and govern life span. The failure of mitochondrial reduction-oxidation (redox homeostasis and the formation of excessive free radicals are tightly linked to dysregulation in the Renin Angiotensin System (RAS. A main rate-controlling step in RAS is renin, an enzyme that hydrolyzes angiotensinogen to generate angiotensin I. Angiotensin I is further converted to Angiotensin II (Ang II by angiotensin-converting enzyme (ACE. Ang II binds with equal affinity to two main angiotensin receptors—type 1 (AT1R and type 2 (AT2R. The binding of Ang II to AT1R activates NADPH oxidase, which leads to increased generation of cytoplasmic reactive oxygen species (ROS. This Ang II-AT1R–NADPH-ROS signal triggers the opening of mitochondrial KATP channels and mitochondrial ROS production in a positive feedback loop. Furthermore, RAS has been implicated in the decrease of many of ROS scavenging enzymes, thereby leading to detrimental levels of free radicals in the cell.AT2R is less understood, but evidence supports an anti-oxidative and mitochondria-protective function for AT2R. The overlap between age related changes in RAS and mitochondria, and the consequences of this overlap on age-related diseases are quite complex. RAS dysregulation has been implicated in many pathological conditions due to its contribution to mitochondrial dysfunction. Decreased age-related, renal and cardiac mitochondrial dysfunction was seen in patients treated with angiotensin receptor blockers. The aim of this review is to: (a report the most recent information elucidating the role of RAS in mitochondrial redox hemostasis and (b discuss the effect of age-related activation of RAS on generation of free radicals.

  5. Converting Nonclassicality into Entanglement

    Science.gov (United States)

    Killoran, N.; Steinhoff, F. E. S.; Plenio, M. B.

    2016-02-01

    Quantum mechanics exhibits a wide range of nonclassical features, of which entanglement in multipartite systems takes a central place. In several specific settings, it is well known that nonclassicality (e.g., squeezing, spin squeezing, coherence) can be converted into entanglement. In this work, we present a general framework, based on superposition, for structurally connecting and converting nonclassicality to entanglement. In addition to capturing the previously known results, this framework also allows us to uncover new entanglement convertibility theorems in two broad scenarios, one which is discrete and one which is continuous. In the discrete setting, the classical states can be any finite linearly independent set. For the continuous setting, the pertinent classical states are "symmetric coherent states," connected with symmetric representations of the group S U (K ). These results generalize and link convertibility properties from the resource theory of coherence, spin coherent states, and optical coherent states, while also revealing important connections between local and nonlocal pictures of nonclassicality.

  6. Improving Power Converter Reliability

    DEFF Research Database (Denmark)

    Ghimire, Pramod; de Vega, Angel Ruiz; Beczkowski, Szymon

    2014-01-01

    The real-time junction temperature monitoring of a high-power insulated-gate bipolar transistor (IGBT) module is important to increase the overall reliability of power converters for industrial applications. This article proposes a new method to measure the on-state collector?emitter voltage...... of a high-power IGBT module during converter operation, which may play a vital role in improving the reliability of the power converters. The measured voltage is used to estimate the module average junction temperature of the high and low-voltage side of a half-bridge IGBT separately in every fundamental...... is measured in a wind power converter at a low fundamental frequency. To illustrate more, the test method as well as the performance of the measurement circuit are also presented. This measurement is also useful to indicate failure mechanisms such as bond wire lift-off and solder layer degradation...

  7. Converting Nonclassicality into Entanglement.

    Science.gov (United States)

    Killoran, N; Steinhoff, F E S; Plenio, M B

    2016-02-26

    Quantum mechanics exhibits a wide range of nonclassical features, of which entanglement in multipartite systems takes a central place. In several specific settings, it is well known that nonclassicality (e.g., squeezing, spin squeezing, coherence) can be converted into entanglement. In this work, we present a general framework, based on superposition, for structurally connecting and converting nonclassicality to entanglement. In addition to capturing the previously known results, this framework also allows us to uncover new entanglement convertibility theorems in two broad scenarios, one which is discrete and one which is continuous. In the discrete setting, the classical states can be any finite linearly independent set. For the continuous setting, the pertinent classical states are "symmetric coherent states," connected with symmetric representations of the group SU(K). These results generalize and link convertibility properties from the resource theory of coherence, spin coherent states, and optical coherent states, while also revealing important connections between local and nonlocal pictures of nonclassicality.

  8. Redox Changes during the Legume-Rhizobium Symbiosis

    Institute of Scientific and Technical Information of China (English)

    Christine Chang; Isabelle Damiani; Alain Puppo; Pierre Frendol

    2009-01-01

    Reactive Oxygen Species (ROS) are continuously produced as a result of aerobic metabolism or in response to biotic and abiotic stresses.ROS are not only toxic by-products of aerobic metabolism,but are also signaling molecules involved in plant growth and environmental adaptation.Antioxidants can protect the cell from oxidative damage by scav-enging the ROS.Thus,they play an important role in optimizing cell function by regulating cellular redox state and mod-ifying gene expression.This article aims to review recent studies highlighting the role of redox signals in establishing and maintaining symbiosis between rhizobia and legumes.

  9. The energy-redox axis in aging and age-related neurodegeneration.

    Science.gov (United States)

    Yap, Li-Peng; Garcia, Jerome V; Han, Derick; Cadenas, Enrique

    2009-11-30

    Decrease in mitochondrial energy-transducing capacity is a feature of the aging process that accompanies redox alterations, such as increased generation of mitochondrial oxidants, altered GSH status, and increased protein oxidation. The decrease in mitochondrial energy-transducing capacity and altered redox status should be viewed as a concerted process that embodies the mitochondrial energy-redox axis and is linked through various mechanisms including: (a) an inter-convertible reducing equivalents pool (i.e., NAD(P)(+)/NAD(P)H) and (b) redox-mediated protein post-translational modifications involved in energy metabolism. The energy-redox axis provides the rationale for therapeutic approaches targeted to each or both component(s) of the axis that effectively preserves or improve mitochondrial function and that have implications for aging and age-related neurodegenerative disorders.

  10. Thermionic photovoltaic energy converter

    Science.gov (United States)

    Chubb, D. L. (Inventor)

    1985-01-01

    A thermionic photovoltaic energy conversion device comprises a thermionic diode mounted within a hollow tubular photovoltaic converter. The thermionic diode maintains a cesium discharge for producing excited atoms that emit line radiation in the wavelength region of 850 nm to 890 nm. The photovoltaic converter is a silicon or gallium arsenide photovoltaic cell having bandgap energies in this same wavelength region for optimum cell efficiency.

  11. Estimation of kinetic parameters related to biochemical interactions between hydrogen peroxide and signal transduction proteins

    Directory of Open Access Journals (Sweden)

    Paula Matos de Brito

    2014-10-01

    Full Text Available The lack of kinetic data concerning the biological effects of reactive oxygen species is slowing down the development of the field of redox signaling. Herein, we deduced and applied equations to estimate kinetic parameters from typical redox signaling experiments. H2O2-sensing mediated by the oxidation of a protein target and the switch-off of this sensor, by being converted back to its reduced form, are the two processes for which kinetic parameters are determined. The experimental data required to apply the equations deduced is the fraction of the H2O2 sensor protein in the reduced or in the oxidized state measured in intact cells or living tissues after exposure to either endogenous or added H2O2. Either non-linear fittings that do not need transformation of the experimental data or linearized plots in which deviations from the equations are easily observed can be used. The equations were shown to be valid by fitting to them virtual time courses simulated with a kinetic model. The good agreement between the kinetic parameters estimated in these fittings and those used to simulate the virtual time courses supported the accuracy of the kinetic equations deduced. Finally, equations were successfully tested with real data taken from published experiments that describe redox signaling mediated by the oxidation of two protein tyrosine phosphatases, PTP1B and SHP-2, which are two of the few H2O2-sensing proteins with known kinetic parameters. Whereas for PTP1B estimated kinetic parameters fitted in general the present knowledge, for SHP-2 results obtained suggest that reactivity towards H2O2 as well as the rate of SHP-2 regeneration back to its reduced form are higher than previously thought. In conclusion, valuable quantitative kinetic data can be estimated from typical redox signaling experiments, thus improving our understanding about the complex processes that underline the interplay between oxidative stress and redox signaling responses.

  12. Estimation of kinetic parameters related to biochemical interactions between hydrogen peroxide and signal transduction proteins

    Science.gov (United States)

    Brito, Paula; Antunes, Fernando

    2014-10-01

    The lack of kinetic data concerning the biological effects of reactive oxygen species is slowing down the development of the field of redox signaling. Herein, we deduced and applied equations to estimate kinetic parameters from typical redox signaling experiments. H2O2-sensing mediated by the oxidation of a protein target and the switch-off of this sensor, by being converted back to its reduced form, are the two processes for which kinetic parameters are determined. The experimental data required to apply the equations deduced is the fraction of the H2O2 sensor protein in the reduced or in the oxidized state measured in intact cells or living tissues after exposure to either endogenous or added H2O2. Either non-linear fittings that do not need transformation of the experimental data or linearized plots in which deviations from the equations are easily observed can be used. The equations were shown to be valid by fitting to them virtual time courses simulated with a kinetic model. The good agreement between the kinetic parameters estimated in these fittings and those used to simulate the virtual time courses supported the accuracy of the kinetic equations deduced. Finally, equations were successfully tested with real data taken from published experiments that describe redox signaling mediated by the oxidation of two protein tyrosine phosphatases, PTP1B and SHP-2, which are two of the few H2O2-sensing proteins with known kinetic parameters. Whereas for PTP1B estimated kinetic parameters fitted in general the present knowledge, for SHP-2 results obtained suggest that reactivity towards H2O2 as well as the rate of SHP-2 regeneration back to its reduced form are higher than previously thought. In conclusion, valuable quantitative kinetic data can be estimated from typical redox signaling experiments, thus improving our understanding about the complex processes that underline the interplay between oxidative stress and redox signaling responses.

  13. Quantitative proteomic characterization of redox-dependent post-translational modifications on protein cysteines

    Energy Technology Data Exchange (ETDEWEB)

    Duan, Jicheng; Gaffrey, Matthew J.; Qian, Wei-Jun

    2017-01-01

    Protein cysteine thiols play a crucial role in redox signaling, regulation of enzymatic activity and protein function, and maintaining redox homeostasis in living systems. The unique chemical reactivity of thiol groups makes cysteine susceptible to oxidative modifications by reactive oxygen and nitrogen species to form a broad array of reversible and irreversible protein post-translational modifications (PTMs). The reversible modifications in particular are one of the major components of redox signaling and are involved in regulation of various cellular processes under physiological and pathological conditions. The biological significance of these redox PTMs in health and diseases has been increasingly recognized. Herein, we review the recent advances of quantitative proteomic approaches for investigating redox PTMs in complex biological systems, including the general considerations of sample processing, various chemical or affinity enrichment strategies, and quantitative approaches. We also highlight a number of redox proteomic approaches that enable effective profiling of redox PTMs for addressing specific biological questions. Although some technological limitations remain, redox proteomics is paving the way towards a better understanding of redox signaling and regulation in human health and diseases.

  14. Thioredoxin/Txnip: Redoxisome, As a Redox Switch for the Pathogenesis of Diseases

    Directory of Open Access Journals (Sweden)

    Eiji eYoshihara

    2014-01-01

    Full Text Available During the past few decades, it has been widely recognized that reducing-oxidizing (Redox responses occurring at the intra- and extra-cellular levels are one of most important biological phenomena and dysregulated redox responses are involved in the initiation and progression of multiple diseases. Thioredoxin 1 (Trx1 and Thioredoxin 2 (Trx2, mainly located in the cytoplasm and mitochondria, respectively, are ubiquitously expressed in variety of cells and control cellular reactive oxygen species (ROS by reducing the disulfides into thiol groups. Thioredoxin interacting protein (Txnip/TBP-2/VDUP1 directly binds to Trx1 & Trx2 (Trx and inhibit the reducing activity of Trx through their disulfide exchange. Recent studies have revealed that Trx1 and Txnip are involved in some critical redox-dependent signal pathways including NLRP3 inflammasome activation in a redox-dependent manner. Therefore, Trx/Txnip, a redox-sensitive signaling complex is a regulator of cellular redox status and has emerged as a key component in the link between redox-regulation and the pathogenesis of diseases. Here, we review the novel functional concept of the redox-related protein complex, named Redoxisome, consisting of Trx/Txnip, as a critical regulator for intra- and extra-cellular redox signaling, involved in the pathogenesis of various diseases such as cancer, autoimmune disease, and diabetes.

  15. Redox theory of aging.

    Science.gov (United States)

    Jones, Dean P

    2015-08-01

    Metazoan genomes encode exposure memory systems to enhance survival and reproductive potential by providing mechanisms for an individual to adjust during lifespan to environmental resources and challenges. These systems are inherently redox networks, arising during evolution of complex systems with O2 as a major determinant of bioenergetics, metabolic and structural organization, defense, and reproduction. The network structure decreases flexibility from conception onward due to differentiation and cumulative responses to environment (exposome). The redox theory of aging is that aging is a decline in plasticity of genome-exposome interaction that occurs as a consequence of execution of differentiation and exposure memory systems. This includes compromised mitochondrial and bioenergetic flexibility, impaired food utilization and metabolic homeostasis, decreased barrier and defense capabilities and loss of reproductive fidelity and fecundity. This theory accounts for hallmarks of aging, including failure to maintain oxidative or xenobiotic defenses, mitochondrial integrity, proteostasis, barrier structures, DNA repair, telomeres, immune function, metabolic regulation and regenerative capacity. Copyright © 2015. Published by Elsevier B.V.

  16. Optical analog-to-digital converter

    Science.gov (United States)

    Evanchuk, Vincent L. (Inventor)

    1984-01-01

    A method and apparatus for converting the intensity of an unknown optical signal (B) into an electrical signal in digital form utilizes two elongated optical attenuators (11, 13), one for the unknown optical signal from a source (10) and one for a known optical signal (A) from a variable source (12), a plurality of photodetectors (e.g., 17, 18) along each attenuator for detecting the intensity of the optical signals, and a plurality of comparators (e.g., 21) connected to the photodetectors in pairs to determine at what points being compared the attenuated known signal equals the attenuated unknown signal. The intensity of the unknown relative to the known is thus determined by the output of a particular comparator. That output is automatically encoded to a relative intensity value in digital form through a balancing feedback control (24) and encoder (23). The digital value may be converted to analog form in a D-to-A converter (27) and used to vary the source of the known signal so that the attenuated intensity of the known signal at a predetermined point (comparator 16) equals the attenuated intensity of the unknown signal at the predetermined point of comparison. If the known signal is then equal to the unknown, there is verification of the analog-to-digital conversion being complete. Otherwise the output of the comparator indicating equality at some other point along the attenuators will provide an output which is encoded and added, through an accumulator comprised of a register (25) and an adder (26), to a previous relative intensity value thereby to further vary the intensity of the known signal source. The steps are repeated until full conversion is verified.

  17. Redox flow batteries: a review

    Energy Technology Data Exchange (ETDEWEB)

    Weber, Adam Z. [Lawrence Berkeley National Laboratory (LBNL); Mench, Matthew M [ORNL; Meyers, Jeremy [University of Texas, Austin; Ross, Philip N. [Lawrence Berkeley National Laboratory (LBNL); Gostick, Jeffrey T. [McGill University, Montreal, Quebec; Liu, Qinghua [University of Tennessee, Knoxville (UTK)

    2011-01-01

    Redox flow batteries (RFBs) are enjoying a renaissance due to their ability to store large amounts of electrical energy relatively cheaply and efficiently. In this review, we examine the components of RFBs with a focus on understanding the underlying physical processes. The various transport and kinetic phenomena are discussed along with the most common redox couples.

  18. Direct electrochemistry of redox proteins.

    NARCIS (Netherlands)

    Heering, H.A.

    1995-01-01

    The goal of the project was to obtain more detailed insight in interactions between redox proteins and solid electrodes and the mechanisms of electron transfer. In addition to this, the influence of the protein environment on the redox properties of the active site and the possible influence of the

  19. A linear temperature-to-frequency converter

    DEFF Research Database (Denmark)

    Løvborg, Leif

    1965-01-01

    The possibility of converting temperature into a frequency signal by means of a thermistor which is part of the frequency-determining network of an RC oscillator is investigated. It is shown that a temperature - frequency characteristic which has a point of inflection may be realized, and that th......The possibility of converting temperature into a frequency signal by means of a thermistor which is part of the frequency-determining network of an RC oscillator is investigated. It is shown that a temperature - frequency characteristic which has a point of inflection may be realized......, and that the maximum value of the temperature-frequency coefficient beta in this point is-1/3 alpha, where a is the temperature coefficient of the thermistor at the corresponding temperature. Curves showing the range in which the converter is expected to be linear to within plusmn0.1 degC are given. A laboratory...

  20. Differential Cyclic Voltammetry - a Novel Technique for Selective and Simultaneous Detection using Redox Cycling Based Sensors

    NARCIS (Netherlands)

    Odijk, M.; Wiedemair, J.; Megen, M.J.J; Olthuis, W.; Berg, van den A.

    2010-01-01

    Redox cycling (RC) is an effect that is used to amplify electrochemical signals. However, traditional techniques such as cyclic voltammetry (CV) do not provide clear insight for a mixture of multiple redox couples while RC is applied. Thus, we have developed a new measurement technique which deliver

  1. Differential Cyclic Voltammetry - a Novel Technique for Selective and Simultaneous Detection using Redox Cycling Based Sensors

    NARCIS (Netherlands)

    Odijk, Mathieu; Wiedemair, Justyna; van Megen, M.J.J.; Olthuis, Wouter; van den Berg, Albert

    2010-01-01

    Redox cycling (RC) is an effect that is used to amplify electrochemical signals. However, traditional techniques such as cyclic voltammetry (CV) do not provide clear insight for a mixture of multiple redox couples while RC is applied. Thus, we have developed a new measurement technique which

  2. Modulation of Chlamydomonas reinhardtii flagellar motility by redox poise

    Science.gov (United States)

    Wakabayashi, Ken-ichi; King, Stephen M.

    2006-01-01

    Redox-based regulatory systems are essential for many cellular activities. Chlamydomonas reinhardtii exhibits alterations in motile behavior in response to different light conditions (photokinesis). We hypothesized that photokinesis is signaled by variations in cytoplasmic redox poise resulting from changes in chloroplast activity. We found that this effect requires photosystem I, which generates reduced NADPH. We also observed that photokinetic changes in beat frequency and duration of the photophobic response could be obtained by altering oxidative/reductive stress. Analysis of reactivated cell models revealed that this redox poise effect is mediated through the outer dynein arms (ODAs). Although the global redox state of the thioredoxin-related ODA light chains LC3 and LC5 and the redox-sensitive Ca2+-binding subunit of the docking complex DC3 did not change upon light/dark transitions, we did observe significant alterations in their interactions with other flagellar components via mixed disulfides. These data indicate that redox poise directly affects ODAs and suggest that it may act in the control of flagellar motility. PMID:16754958

  3. Redox Regulation in Cancer Stem Cells

    Directory of Open Access Journals (Sweden)

    Shijie Ding

    2015-01-01

    Full Text Available Reactive oxygen species (ROS and ROS-dependent (redox regulation signaling pathways and transcriptional activities are thought to be critical in stem cell self-renewal and differentiation during growth and organogenesis. Aberrant ROS burst and dysregulation of those ROS-dependent cellular processes are strongly associated with human diseases including many cancers. ROS levels are elevated in cancer cells partially due to their higher metabolism rate. In the past 15 years, the concept of cancer stem cells (CSCs has been gaining ground as the subpopulation of cancer cells with stem cell-like properties and characteristics have been identified in various cancers. CSCs possess low levels of ROS and are responsible for cancer recurrence after chemotherapy or radiotherapy. Unfortunately, how CSCs control ROS production and scavenging and how ROS-dependent signaling pathways contribute to CSCs function remain poorly understood. This review focuses on the role of redox balance, especially in ROS-dependent cellular processes in cancer stem cells (CSCs. We updated recent advances in our understanding of ROS generation and elimination in CSCs and their effects on CSC self-renewal and differentiation through modulating signaling pathways and transcriptional activities. The review concludes that targeting CSCs by manipulating ROS metabolism/dependent pathways may be an effective approach for improving cancer treatment.

  4. Angiotensin-converting enzyme

    DEFF Research Database (Denmark)

    Sørensen, P G; Rømer, F K; Cortes, D

    1984-01-01

    In order to evaluate bleomycin-associated lung damage in humans, lung function parameters and serum levels of the endothelial-bound angiotensin-converting enzyme (ACE) were determined by serial measurements in 11 patients who were treated for testicular cancer. None developed clinical or radiolog......In order to evaluate bleomycin-associated lung damage in humans, lung function parameters and serum levels of the endothelial-bound angiotensin-converting enzyme (ACE) were determined by serial measurements in 11 patients who were treated for testicular cancer. None developed clinical...

  5. Proteomics of Arabidopsis redox proteins in response to methyl jasmonate.

    Science.gov (United States)

    Alvarez, Sophie; Zhu, Mengmeng; Chen, Sixue

    2009-11-02

    Protein redox regulation is increasingly recognized as an important switch of protein activity in yeast, bacteria, mammals and plants. In this study, we identified proteins with potential thiol switches involved in jasmonate signaling, which is essential for plant defense. Methyl jasmonate (MeJA) treatment led to enhanced production of hydrogen peroxide in Arabidopsis leaves and roots, indicating in vivo oxidative stress. With monobromobimane (mBBr) labeling to capture oxidized sulfhydryl groups and 2D gel separation, a total of 35 protein spots that displayed significant redox and/or total protein expression changes were isolated. Using LC-MS/MS, the proteins in 33 spots were identified in both control and MeJA-treated samples. By comparative analysis of mBBr and SyproRuby gel images, we were able to determine many proteins that were redox responsive and proteins that displayed abundance changes in response to MeJA. Interestingly, stress and defense proteins constitute a large group that responded to MeJA. In addition, many cysteine residues involved in the disulfide dynamics were mapped based on tandem MS data. Identification of redox proteins and their cysteine residues involved in the redox regulation allows for a deeper understanding of the jasmonate signaling networks.

  6. [Experimental and clinical aspects of oxidative stress and redox regulation].

    Science.gov (United States)

    Nakamura, Hajime

    2003-02-01

    Although excess amounts of oxidative stress damage proteins and nucleotides, small amounts of oxidative stress transduce intracellular signals for cellular activation, differentiation and proliferation. Reduction/oxidation(redox) regulation is defined as a biological response to maintain homeostasis against oxidative stress. Thioredoxin, a 12 kD small protein with a redox-active dithiol/disulfide in the conserved active site: -Cys-Gly-Pro-Cys-, is a key molecule for redox regulation as well as glutathione(GSH). Thioredoxin is induced by a variety of oxidative stresses and secreted from cells. Thioredoxin plays crucial roles as a redox-regulator of intracellular signal transduction and as a radical scavenger. Plasma levels of thioredoxin are good biomarkers for oxidative stress. Thioredoxin-transgenic mice are more resistant to cerebral infarction, infection or inflammation and survive longer than control mice. Administration of thioredoxin may have a good potential for anti-aging and anti-stress effects. Redox regulation mechanisms by thioredoxin and other thioredoxin family members will clarify the pathophysiology of oxidative stress-associated disorders.

  7. Converting the reset

    NARCIS (Netherlands)

    Hoogland, J.K.; Neumann, C.D.D.; Bloch, D.

    2001-01-01

    We give a simple algorithm to incorporate the effects of resets in convertible bond prices, without having to add an extra factor to take into account the value of the reset. Furthermore we show that the effect of a notice period, and additional make-whole features, can be treated in a straightforwa

  8. An Electromagnetic Beam Converter

    DEFF Research Database (Denmark)

    2009-01-01

    The present invention relates to an electromagnetic beam converter and a method for conversion of an input beam of electromagnetic radiation having a bell shaped intensity profile a(x,y) into an output beam having a prescribed target intensity profile l(x',y') based on a further development...

  9. Definition of Power Converters

    CERN Document Server

    Bordry, F

    2015-01-01

    The paper is intended to introduce power conversion principles and to define common terms in the domain. The concept s of sources and switches are defined and classified. From the basic laws of source interconnections, a generic method of power converter synthesis is presented. Some examples illustrate this systematic method. Finally, the commutation cell and soft commuta tion are introduced and discussedd.

  10. Convertible Proxy Signcryption Scheme

    Institute of Scientific and Technical Information of China (English)

    李继国; 李建中; 曹珍富; 张亦辰

    2004-01-01

    In 1996, Mambo et al introduced the concept of proxy signature. However, proxy signature can only provide the delegated authenticity and cannot provide confidentiality. Recently, Gamage et al and Chan and Wei proposed different proxy signcryption schemes respectively, which extended the concept of proxy signature.However, only the specified receiver can decrypt and verify the validity of proxy signcryption in their schemes.To protect the receiver' s benefit in case of a later dispute, Wu and Hsu proposed a convertible authenticated encryption scheme, which carn enable the receiver to convert signature into an ordinary one that can be verified by anyone. Based on Wu and Hsu' s scheme and improved Kim' s scheme, we propose a convertible proxy signcryption scheme. The security of the proposed scheme is based on the intractability of reversing the one-way hash function and solving the discrete logarithm problem. The proposed scheme can satisfy all properties of strong proxy signature and withstand the public key substitution attack and does not use secure channel. In addition, the proposed scheme can be extended to convertible threshold proxy signcryption scheme.

  11. The Convertible Arbitrage Strategy Analyzed

    NARCIS (Netherlands)

    Loncarski, I.; Ter Horst, J.R.; Veld, C.H.

    2006-01-01

    This paper analyzes convertible bond arbitrage on the Canadian market for the period 1998 to 2004.Convertible bond arbitrage is the combination of a long position in convertible bonds and a short position in the underlying stocks. Convertible arbitrage has been one of the most successful strategies

  12. MAS receptors mediate vasoprotective and atheroprotective effects of candesartan upon the recovery of vascular angiotensin-converting enzyme 2-angiotensin-(1-7)-MAS axis functionality.

    Science.gov (United States)

    Pernomian, Larissa; do Prado, Alejandro F; Gomes, Mayara S; Pernomian, Laena; da Silva, Carlos H T P; Gerlach, Raquel F; de Oliveira, Ana M

    2015-10-05

    AT1 antagonists effectively prevent atherosclerosis since AT1 upregulation and angiotensin II-induced proinflammatory actions are critical to atherogenesis. Despite the classic mechanisms underlying the vasoprotective and atheroprotective actions of AT1 antagonists, the cross-talk between angiotensin-converting enzyme-angiotensin II-AT1 and angiotensin-converting enzyme 2-angiotensin-(1-7)-MAS axes suggests other mechanisms beyond AT1 blockage in such effects. For instance, angiotensin-converting enzyme 2 activity is inhibited by reactive oxygen species derived from AT1-mediated proinflammatory signaling. Since angiotensin-(1-7) promotes antiatherogenic effects, we hypothesized that the vasoprotective and atheroprotective effects of AT1 antagonists could result from their inhibitory effects on the AT1-mediated negative modulation of vascular angiotensin-converting enzyme 2-angiotensin-(1-7)-MAS axis functionality. Interestingly, our results showed that early atherosclerosis triggered in thoracic aorta from high cholesterol fed-Apolipoprotein E-deficient mice impairs angiotensin-converting enzyme 2-angiotensin-(1-7)-MAS axis functionality by a proinflammatory-redox AT1-mediated pathway. In such mechanism, AT1 activation leads to the aortic release of tumor necrosis factor-α, which stimulates NAD(P)H oxidase/Nox1-driven generation of superoxide and hydrogen peroxide. While hydrogen peroxide inhibits angiotensin-converting enzyme 2 activity, superoxide impairs MAS functionality. Candesartan treatment restored the functionality of angiotensin-converting enzyme 2-angiotensin-(1-7)-MAS axis by inhibiting the proinflammatory-redox AT1-mediated mechanism. Candesartan also promoted vasoprotective and atheroprotective effects that were mediated by MAS since A779 (MAS antagonist) co-treatment inhibited them. The role of MAS receptors as the final mediators of the vasoprotective and atheroprotective effects of candesartan was supported by the vascular actions of angiotensin

  13. Vascular remodeling: A redox-modulated mechanism of vessel caliber regulation.

    Science.gov (United States)

    Tanaka, Leonardo Y; Laurindo, Francisco R M

    2017-01-18

    Vascular remodeling, i.e. whole-vessel structural reshaping, determines lumen caliber in (patho)physiology. Here we review mechanisms underlying vessel remodeling, with emphasis in redox regulation. First, we discuss confusing terminology and focus on strictu sensu remodeling. Second, we propose a mechanobiological remodeling paradigm based on the concept of tensional homeostasis as a setpoint regulator. We first focus on shear-mediated models as prototypes of remodeling closely dominated by highly redox-sensitive endothelial function. More detailed discussions focus on mechanosensors, integrins, extracellular matrix, cytoskeleton and inflammatory pathways as potential of mechanisms potentially coupling tensional homeostasis to redox regulation. Further discussion of remodeling associated with atherosclerosis and injury repair highlights important aspects of redox vascular responses. While neointima formation has not shown consistent responsiveness to antioxidants, vessel remodeling has been more clearly responsive, indicating that despite the multilevel redox signaling pathways, there is a coordinated response of the whole vessel. Among mechanisms that may orchestrate redox pathways, we discuss roles of superoxide dismutase activity and extracellular protein disulfide isomerase. We then discuss redox modulation of aneurysms, a special case of expansive remodeling. We propose that the redox modulation of vascular remodeling may reflect (1) remodeling pathophysiology is dominated by a particularly redox-sensitive cell type, e.g., endothelial cells (2) redox pathways are temporospatially coordinated at an organ level across distinct cellular and acellular structures or (3) the tensional homeostasis setpoint is closely connected to redox signaling. The mechanobiological/redox model discussed here can be a basis for improved understanding of remodeling and helps clarifying mechanisms underlying prevalent hard-to-treat diseases.

  14. Advanced DC/DC converters

    CERN Document Server

    Luo, Fang Lin

    2003-01-01

    INTRODUCTIONHistorical ReviewMultiple Quadrant ChoppersPump CircuitsDevelopment of DC/DC Conversion TechniqueCategorize Prototypes and DC/DC Converters Family TreeVOLTAGE-LIFT CONVERTERSIntroductionSeven Self-Lift ConvertersPositive Output Luo-ConvertersNegative Output Luo-ConvertersModified Positive Output Luo-Converters Double Output Luo-ConvertersPOSITIVE OUTPUT SUPER-LIFT LUO-CONVERTERS IntroductionMain SeriesAdditional SeriesEnhanced Series Re-Enhanced Series Multiple-Enhanced Series Summary of Positive Output

  15. Direct mapping of local redox current density on a monolith electrode by laser scanning.

    Science.gov (United States)

    Lee, Seung-Woo; Lopez, Jeffrey; Saraf, Ravi F

    2013-09-15

    An optical method of mapping local redox reaction over a monolith electrode using simple laser scanning is described. As the optical signal is linearly proportional to the maximum redox current that is measured concomitantly by voltammetry, the optical signal quantitatively maps the local redox current density distribution. The method is demonstrated on two types of reactions: (1) a reversible reaction where the redox moieties are ionic, and (2) an irreversible reaction on two different types of enzymes immobilized on the electrode where the reaction moieties are nonionic. To demonstrate the scanning capability, the local redox behavior on a "V-shaped" electrode is studied where the local length scale and, hence, the local current density, is nonuniform. The ability to measure the current density distribution by this method will pave the way for multianalyte analysis on a monolith electrode using a standard three-electrode configuration. The method is called Scanning Electrometer for Electrical Double-layer (SEED).

  16. Compact self-contained electrical-to-optical converter/transmitter

    Energy Technology Data Exchange (ETDEWEB)

    Seligmann, D.A.; Moss, W.C.; Valk, T.C.; Conder, A.D.

    1992-12-31

    An electrical-to-optical converter/transmitter is disclosed. A first optical receiver and a second optical receiver are provided for receiving a calibrate command and a power switching signal, respectively, from a remote processor. A third receiver is provided for receiving an analog electrical signal from a transducer. A calibrator generates a reference signal in response to the calibrate command. A combiner mixes the electrical signal with the reference signal to form a calibrated signal. A converter converts the calibrated signal to an optical signal. A transmitter transmits the optical signal to the remote processor. A primary battery supplies power to the calibrator, the combiner, the converter, and the transmitter. An optically-activated switch supplies power to the calibrator, the combiner, the converter, and the transmitter in response to the power switching signal. An auxiliary battery supplies power continuously to the switch means.

  17. FPGA implementation of digital down converter using CORDIC algorithm

    Science.gov (United States)

    Agarwal, Ashok; Lakshmi, Boppana

    2013-01-01

    In radio receivers, Digital Down Converters (DDC) are used to translate the signal from Intermediate Frequency level to baseband. It also decimates the oversampled signal to a lower sample rate, eliminating the need of a high end digital signal processors. In this paper we have implemented architecture for DDC employing CORDIC algorithm, which down converts an IF signal of 70MHz (3G) to 200 KHz baseband GSM signal, with an SFDR greater than 100dB. The implemented architecture reduces the hardware resource requirements by 15 percent when compared with other architecture available in the literature due to elimination of explicit multipliers and a quadrature phase shifter for mixing.

  18. Redox Properties of Free Radicals.

    Science.gov (United States)

    Neta, P.

    1981-01-01

    Describes pulse radiolysis as a useful means in studing one-electron redox potentials. This method allows the production of radicals and the determination of their concentration and rates of reaction. (CS)

  19. Bifunctional redox flow battery

    Energy Technology Data Exchange (ETDEWEB)

    Wen, Y.H. [Research Institute of Chemical Defense, Beijing 100083 (China)], E-mail: wen_yuehua@126.com; Cheng, J. [Research Institute of Chemical Defense, Beijing 100083 (China); Beijing Science and Technology University, Beijing 100083 (China); Xun, Y. [Research Institute of Chemical Defense, Beijing 100083 (China); Ma, P.H. [Full Cell R and D Center, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, Liaoning 116023 (China); Yang, Y.S. [Research Institute of Chemical Defense, Beijing 100083 (China); Beijing Science and Technology University, Beijing 100083 (China)

    2008-08-20

    A new bifunctional redox flow battery (BRFB) system, V(III)/V(II)-L-cystine(O{sub 2}), was systematically investigated by using different separators. It is shown that during charge, water transfer is significantly restricted with increasing the concentration of HBr when the Nafion 115 cation exchange membrane is employed. The same result can be obtained when the gas diffusion layer (GDL) hot-pressed separator is used. The organic electro-synthesis is directly correlated with the crossover of vanadium. When employing the anion exchange membrane, the electro-synthesis efficiency is over 96% due to a minimal crossover of vanadium. When the GDL hot-pressed separator is applied, the crossover of vanadium and water transfer are noticeably prevented and the electro-synthesis efficiency of over 99% is obtained. Those impurities such as vanadium ions and bromine can be eliminated through the purification of organic electro-synthesized products. The purified product is identified to be L-cysteic acid by IR spectrum. The BRFB shows a favorable discharge performance at a current density of 20 mA cm{sup -2}. Best discharge performance is achieved by using the GDL hot-pressed separator. The coulombic efficiency of 87% and energy efficiency of about 58% can be obtained. The cause of major energy losses is mainly associated with the cross-contamination of anodic and cathodic active electrolytes.

  20. Pilot tones in WDM networks with wavelength converters

    DEFF Research Database (Denmark)

    Kloch, Allan; Mikkelsen, Benny; Stubkjær, Kristian

    1997-01-01

    Here we investigate the transmission of a pilot tone through an interferometric wavelength converter (IWC) in conjunction with a 2.5 Gbit/s experiment. The pilot tone is added by sinusoidal modulation of the bias current to the signal laser. After the IWC (Michelson interferometer) the converted...

  1. Intelligent dc-dc Converter Technology Developed and Tested

    Science.gov (United States)

    Button, Robert M.

    2001-01-01

    The NASA Glenn Research Center and the Cleveland State University have developed a digitally controlled dc-dc converter to research the benefits of flexible, digital control on power electronics and systems. Initial research and testing has shown that conventional dc-dc converters can benefit from improved performance by using digital-signal processors and nonlinear control algorithms.

  2. Three-channel integrating analog-to-digital converter

    Science.gov (United States)

    Stevens, G. L.

    1978-01-01

    A three-channel integrating analog-to-digital converter was added to the complex mixer system to accept the baseband, complex signals generated by the complex mixers and output binary data to the digital demodulator for further processing and recording. The converter was first used for processing multistation data in radar experiments in the spring of 1977.

  3. Characterisation of the Redox Sensitive NMDA Receptor

    KAUST Repository

    Alzahrani, Ohood

    2016-05-01

    Glucose entry into the brain and its subsequent metabolism to L-lactate, regulated by astrocytes, plays a major role in synaptic plasticity and memory formation. A recent study has shown that L-lactate produced by the brain upon stimulation of glycolysis, and glycogen-derived L-lactate from astrocytes and its transport into neurons, is crucial for memory formation. A recent study revealed the molecular mechanisms that underlie the role of L-lactate in neuronal plasticity and long-term memory formation. L-lactate was shown to induce a cascade of molecular events via modulation of redox-sensitive N-Methyl-D-aspartate (NMDA) receptor activity that was mimicked by nicotinamide adenine dinucleotide hydride (NADH) co-enzyme. This indicated that changes in cellular redox state, following L-lactate transport inside the cells and its subsequent metabolism, production of NADH, and favouring a reduced state are the key effects of L-lactate. Therefore, we are investigating the role of L-lactate in modulating NMDA receptor function via redox modulatory sites. Accordingly, crucial redox-sensitive cysteine residues, Cys320 and Cys87, of the NR2A NMDA receptor subunit are mutated using site-directed mutation, transfected, and expressed in HEK293 cells. This cellular system will then be used to characterise and monitor its activity upon Llactate stimulation, compared to the wild type. This will be achieved by calcium imaging, using fluorescent microscopy. Our data shows that L-lactate potentiated NMDA receptor activity and increased intracellular calcium influx in NR1/NR2A wild type compared to the control condition (WT NR1/NR2A perfused with (1μM) glutamate and (1μM) glycine agonist only), showing faster response initiation and slower decay rate of the calcium signal to the baseline. Additionally, stimulating with L-lactate associated with greater numbers of cells having high fluorescent intensity (peak amplitude) compared to the control. Furthermore, L-lactate rescued the

  4. Redox regulation of mammalian sperm capacitation

    Directory of Open Access Journals (Sweden)

    Cristian O′Flaherty

    2015-01-01

    Full Text Available Capacitation is a series of morphological and metabolic changes necessary for the spermatozoon to achieve fertilizing ability. One of the earlier happenings during mammalian sperm capacitation is the production of reactive oxygen species (ROS that will trigger and regulate a series of events including protein phosphorylation, in a time-dependent fashion. The identity of the sperm oxidase responsible for the production of ROS involved in capacitation is still elusive, and several candidates are discussed in this review. Interestingly, ROS-induced ROS formation has been described during human sperm capacitation. Redox signaling during capacitation is associated with changes in thiol groups of proteins located on the plasma membrane and subcellular compartments of the spermatozoon. Both, oxidation of thiols forming disulfide bridges and the increase on thiol content are necessary to regulate different sperm proteins associated with capacitation. Reducing equivalents such as NADH and NADPH are necessary to support capacitation in many species including humans. Lactate dehydrogenase, glucose-6-phospohate dehydrogenase, and isocitrate dehydrogenase are responsible in supplying NAD (P H for sperm capacitation. Peroxiredoxins (PRDXs are newly described enzymes with antioxidant properties that can protect mammalian spermatozoa; however, they are also candidates for assuring the regulation of redox signaling required for sperm capacitation. The dysregulation of PRDXs and of enzymes needed for their reactivation such as thioredoxin/thioredoxin reductase system and glutathione-S-transferases impairs sperm motility, capacitation, and promotes DNA damage in spermatozoa leading to male infertility.

  5. Redox regulation of protein damage in plasma

    Directory of Open Access Journals (Sweden)

    Helen R. Griffiths

    2014-01-01

    In this review, we focus on redox regulatory control of those enzymes and processes which control protein maturation during synthesis, produce reactive species, repair and remove damaged plasma proteins. We have highlighted the potential for alterations in the extracellular redox compartment to regulate intracellular redox state and, conversely, for intracellular oxidative stress to alter the cellular secretome and composition of extracellular vesicles. Through secreted, redox-active regulatory molecules, changes in redox state may be transmitted to distant sites.

  6. SSG Wave Energy Converter

    DEFF Research Database (Denmark)

    Margheritini, Lucia; Vicinanza, Diego; Frigaard, Peter

    2008-01-01

    head hydroturbines are converting the potential energy of the stored water into power. A key to success for the SSG will be the low cost of the structure and its robustness. The construction of the pilot plant is scheduled and this paper aims to describe the concept of the SSG wave energy converter...... and the studies behind the process that leads to its construction. The pilot plant is an on-shore full scale module in 3 levels with an expected power production of 320 MWh/y in the North Sea. Location, wave climate and laboratory tests results will be used here to describe the pilot plant and its characteristics.......The SSG (Sea Slot-cone Generator) is a wave energy converter of the overtopping type. The structure consists of a number of reservoirs one on the top of each others above the mean water level, in which the water of incoming waves is stored temporary. In each reservoir, expressively designed low...

  7. A Review of RedOx Cycling of Solid Oxide Fuel Cells Anode

    Directory of Open Access Journals (Sweden)

    Jan Van herle

    2012-08-01

    Full Text Available Solid oxide fuel cells are able to convert fuels, including hydrocarbons, to electricity with an unbeatable efficiency even for small systems. One of the main limitations for long-term utilization is the reduction-oxidation cycling (RedOx cycles of the nickel-based anodes. This paper will review the effects and parameters influencing RedOx cycles of the Ni-ceramic anode. Second, solutions for RedOx instability are reviewed in the patent and open scientific literature. The solutions are described from the point of view of the system, stack design, cell design, new materials and microstructure optimization. Finally, a brief synthesis on RedOx cycling of Ni-based anode supports for standard and optimized microstructures is depicted.

  8. Linking mitochondrial bioenergetics to insulin resistance via redox biology.

    Science.gov (United States)

    Fisher-Wellman, Kelsey H; Neufer, P Darrell

    2012-03-01

    Chronic overnutrition and physical inactivity are major risk factors for insulin resistance and type 2 diabetes. Recent research indicates that overnutrition generates an increase in hydrogen peroxide (H(2)O(2)) emission from mitochondria, serving as a release valve to relieve the reducing pressure created by fuel overload, as well as a primary signal that ultimately decreases insulin sensitivity. H(2)O(2) is a major input to cellular redox circuits that link to cysteine residues throughout the entire proteome to regulate cell function. Here we review the principles of mitochondrial bioenergetics and redox systems biology and offer new insight into how H(2)O(2) emission may be linked via redox biology to the etiology of insulin resistance. Copyright © 2011 Elsevier Ltd. All rights reserved.

  9. Another look at Statics and Dynamics of Switching Power Converters

    Science.gov (United States)

    Sasaki, Seigo; Watanabe, Haruo

    Three types of switching power supply, which are buck, boost, buck/boost converter, are statically and dynamically analysed. A framework of large signal analysis presents characteristics of converters which vary with operating points, and discusses a relationship between statics and dynamics. It is shown that boost and buck/boost converters substantially change their characteristics. There exists the operating points where for low frequencies the phases become -90° or -180° and the gains fall off to low values. The phenomenon is characterized by a zero of transfer function of the converter and also by the statics.

  10. Design of a High Efficiency Boost DC-DC Converter

    Institute of Scientific and Technical Information of China (English)

    GAO Jing; YAO Suying; XU Jiangtao; SHI Zaifeng

    2009-01-01

    An accurate circuit of PWM/PFM mode converting and a circuit of auto-adaptively adjusting dimension of power transistor are described. The duty cycle of the signal when the control mode converts can be gained accu-rately by using ratios of currents and capacitances, and an optimal dimension of power transistor is derived with different loads. The converter is designed by 0.35 μm standard CMOS technology. Simulation results indicate that the converter starts work at 0.8 V input voltage. Combined with synchronized rectification, the transfer efficiency is higher than 90% with full load range, and achieves 97.5% at rating output.

  11. NAD(H) and NADP(H) Redox Couples and Cellular Energy Metabolism.

    Science.gov (United States)

    Xiao, Wusheng; Wang, Rui-Sheng; Handy, Diane E; Loscalzo, Joseph

    2017-07-28

    The nicotinamide adenine dinucleotide (NAD(+))/reduced NAD(+) (NADH) and NADP(+)/reduced NADP(+) (NADPH) redox couples are essential for maintaining cellular redox homeostasis and for modulating numerous biological events, including cellular metabolism. Deficiency or imbalance of these two redox couples has been associated with many pathological disorders. Recent Advances: Newly identified biosynthetic enzymes and newly developed genetically encoded biosensors enable us to understand better how cells maintain compartmentalized NAD(H) and NADP(H) pools. The concept of redox stress (oxidative and reductive stress) reflected by changes in NAD(H)/NADP(H) has increasingly gained attention. The emerging roles of NAD(+)-consuming proteins in regulating cellular redox and metabolic homeostasis are active research topics. The biosynthesis and distribution of cellular NAD(H) and NADP(H) are highly compartmentalized. It is critical to understand how cells maintain the steady levels of these redox couple pools to ensure their normal functions and simultaneously avoid inducing redox stress. In addition, it is essential to understand how NAD(H)- and NADP(H)-utilizing enzymes interact with other signaling pathways, such as those regulated by hypoxia-inducible factor, to maintain cellular redox homeostasis and energy metabolism. Additional studies are needed to investigate the inter-relationships among compartmentalized NAD(H)/NADP(H) pools and how these two dinucleotide redox couples collaboratively regulate cellular redox states and cellular metabolism under normal and pathological conditions. Furthermore, recent studies suggest the utility of using pharmacological interventions or nutrient-based bioactive NAD(+) precursors as therapeutic interventions for metabolic diseases. Thus, a better understanding of the cellular functions of NAD(H) and NADP(H) may facilitate efforts to address a host of pathological disorders effectively. Antioxid. Redox Signal. 00, 000-000.

  12. The Global Redox Responding RegB/RegA Signal Transduction System Regulates the Genes Involved in Ferrous Iron and Inorganic Sulfur Compound Oxidation of the Acidophilic Acidithiobacillus ferrooxidans

    Directory of Open Access Journals (Sweden)

    Danielle Moinier

    2017-07-01

    Full Text Available The chemical attack of ore by ferric iron and/or sulfuric acid releases valuable metals. The products of these reactions are recycled by iron and sulfur oxidizing microorganisms. These acidophilic chemolithotrophic prokaryotes, among which Acidithiobacillus ferrooxidans, grow at the expense of the energy released from the oxidation of ferrous iron and/or inorganic sulfur compounds (ISCs. In At. ferrooxidans, it has been shown that the expression of the genes encoding the proteins involved in these respiratory pathways is dependent on the electron donor and that the genes involved in iron oxidation are expressed before those responsible for ISCs oxidation when both iron and sulfur are present. Since the redox potential increases during iron oxidation but remains stable during sulfur oxidation, we have put forward the hypothesis that the global redox responding two components system RegB/RegA is involved in this regulation. To understand the mechanism of this system and its role in the regulation of the aerobic respiratory pathways in At. ferrooxidans, the binding of different forms of RegA (DNA binding domain, wild-type, unphosphorylated and phosphorylated-like forms of RegA on the regulatory region of different genes/operons involved in ferrous iron and ISC oxidation has been analyzed. We have shown that the four RegA forms are able to bind specifically the upstream region of these genes. Interestingly, the phosphorylation of RegA did not change its affinity for its cognate DNA. The transcriptional start site of these genes/operons has been determined. In most cases, the RegA binding site(s was (were located upstream from the −35 (or −24 box suggesting that RegA does not interfere with the RNA polymerase binding. Based on the results presented in this report, the role of the RegB/RegA system in the regulation of the ferrous iron and ISC oxidation pathways in At. ferrooxidans is discussed.

  13. The Global Redox Responding RegB/RegA Signal Transduction System Regulates the Genes Involved in Ferrous Iron and Inorganic Sulfur Compound Oxidation of the Acidophilic Acidithiobacillus ferrooxidans.

    Science.gov (United States)

    Moinier, Danielle; Byrne, Deborah; Amouric, Agnès; Bonnefoy, Violaine

    2017-01-01

    The chemical attack of ore by ferric iron and/or sulfuric acid releases valuable metals. The products of these reactions are recycled by iron and sulfur oxidizing microorganisms. These acidophilic chemolithotrophic prokaryotes, among which Acidithiobacillus ferrooxidans, grow at the expense of the energy released from the oxidation of ferrous iron and/or inorganic sulfur compounds (ISCs). In At. ferrooxidans, it has been shown that the expression of the genes encoding the proteins involved in these respiratory pathways is dependent on the electron donor and that the genes involved in iron oxidation are expressed before those responsible for ISCs oxidation when both iron and sulfur are present. Since the redox potential increases during iron oxidation but remains stable during sulfur oxidation, we have put forward the hypothesis that the global redox responding two components system RegB/RegA is involved in this regulation. To understand the mechanism of this system and its role in the regulation of the aerobic respiratory pathways in At. ferrooxidans, the binding of different forms of RegA (DNA binding domain, wild-type, unphosphorylated and phosphorylated-like forms of RegA) on the regulatory region of different genes/operons involved in ferrous iron and ISC oxidation has been analyzed. We have shown that the four RegA forms are able to bind specifically the upstream region of these genes. Interestingly, the phosphorylation of RegA did not change its affinity for its cognate DNA. The transcriptional start site of these genes/operons has been determined. In most cases, the RegA binding site(s) was (were) located upstream from the -35 (or -24) box suggesting that RegA does not interfere with the RNA polymerase binding. Based on the results presented in this report, the role of the RegB/RegA system in the regulation of the ferrous iron and ISC oxidation pathways in At. ferrooxidans is discussed.

  14. A Sliding Surface-Regulated Current-Mode Pulse-Width Modulation Controller for a Digital Signal Processor-Based Single Ended Primary Inductor Converter-Type Power Factor Correction Rectifier

    National Research Council Canada - National Science Library

    Hsin-Jang Shieh; Ying-Zuo Chen

    2017-01-01

    To efficiently supply wide-range DC voltage from a pulse-width modulation (PWM) rectifier, this paper presents a single-phase, full-wave, diode-bridge, single-ended primary-inductor converter-type (SEPIC-type...

  15. Redox rhythm reinforces the circadian clock to gate immune response.

    Science.gov (United States)

    Zhou, Mian; Wang, Wei; Karapetyan, Sargis; Mwimba, Musoki; Marqués, Jorge; Buchler, Nicolas E; Dong, Xinnian

    2015-07-23

    Recent studies have shown that in addition to the transcriptional circadian clock, many organisms, including Arabidopsis, have a circadian redox rhythm driven by the organism's metabolic activities. It has been hypothesized that the redox rhythm is linked to the circadian clock, but the mechanism and the biological significance of this link have only begun to be investigated. Here we report that the master immune regulator NPR1 (non-expressor of pathogenesis-related gene 1) of Arabidopsis is a sensor of the plant's redox state and regulates transcription of core circadian clock genes even in the absence of pathogen challenge. Surprisingly, acute perturbation in the redox status triggered by the immune signal salicylic acid does not compromise the circadian clock but rather leads to its reinforcement. Mathematical modelling and subsequent experiments show that NPR1 reinforces the circadian clock without changing the period by regulating both the morning and the evening clock genes. This balanced network architecture helps plants gate their immune responses towards the morning and minimize costs on growth at night. Our study demonstrates how a sensitive redox rhythm interacts with a robust circadian clock to ensure proper responsiveness to environmental stimuli without compromising fitness of the organism.

  16. Understanding delta-sigma data converters

    CERN Document Server

    Pavan, Shanti; Temes, Gabor C

    2017-01-01

    This new edition introduces novel analysis and design techniques for delta-sigma (ΔΣ) converters in physical and conceptual terms, and includes new chapters that explore developments in the field over the last decade. This book explains the principles and operation of delta-sigma analog-to-digital converters (ADCs) in physical and conceptual terms in accordance with the most recent developments in the field. The interest of ΔΣ converter designers has shifted significantly over the past decade, due to many new applications for data converters at the far ends of the frequency spectrum. Continuous-time delta-sigma A/D converters with GHz clocks, of both lowpass and bandpass types, are required for wireless applications. At the other extreme, multiplexed ADCs with very narrow (sometimes 10 Hz wide) signal bandwidths, but very high accuracy are needed in the interfaces of biomedical and environmental sensors. To reflect the changing eeds of designers, the second edition includes significant new material on bo...

  17. Redox control of senescence and age-related disease

    Directory of Open Access Journals (Sweden)

    Akshaya Chandrasekaran

    2017-04-01

    Full Text Available The signaling networks that drive the aging process, associated functional deterioration, and pathologies has captured the scientific community's attention for decades. While many theories exist to explain the aging process, the production of reactive oxygen species (ROS provides a signaling link between engagement of cellular senescence and several age-associated pathologies. Cellular senescence has evolved to restrict tumor progression but the accompanying senescence-associated secretory phenotype (SASP promotes pathogenic pathways. Here, we review known biological theories of aging and how ROS mechanistically control senescence and the aging process. We also describe the redox-regulated signaling networks controlling the SASP and its important role in driving age-related diseases. Finally, we discuss progress in designing therapeutic strategies that manipulate the cellular redox environment to restrict age-associated pathology.

  18. X-Y Converter Family

    DEFF Research Database (Denmark)

    Bhaskar, Mahajan Sagar; Sanjeevikumar, Padmanaban; Wheeler, Patrick

    2016-01-01

    A New breed of a buck boost converter, named as the XY converter family is proposed in this article. In the XY family, 16 topologies are presented which are highly suitable for renewable energy applications which require a high ratio of DC-DC converter; such as a photovoltaic multilevel inverter...... system, high voltage automotive applications and industrial drives. Compared to the traditional boost converter and existing recent converters, the proposed XY converter family has the ability to provide a higher output voltage by using less number of power devices and reactive components. Other distinct...... features of the XY converter family are i) Single control switch ii) Provide negative output voltage iii) Non-isolated topologies iv) High conversion ratio without making the use of high duty cycle and v) modular structure. XY family is compared with the recent high step-up converters and the detailed...

  19. Species-Specific Standard Redox Potential of Thiol-Disulfide Systems: A Key Parameter to Develop Agents against Oxidative Stress

    Science.gov (United States)

    Mirzahosseini, Arash; Noszál, Béla

    2016-11-01

    Microscopic standard redox potential, a new physico-chemical parameter was introduced and determined to quantify thiol-disulfide equilibria of biological significance. The highly composite, codependent acid-base and redox equilibria of thiols could so far be converted into pH-dependent, apparent redox potentials (E’°) only. Since the formation of stable metal-thiolate complexes precludes the direct thiol-disulfide redox potential measurements by usual electrochemical techniques, an indirect method had to be elaborated. In this work, the species-specific, pH-independent standard redox potentials of glutathione were determined primarily by comparing it to 1-methylnicotinamide, the simplest NAD+ analogue. Secondarily, the species-specific standard redox potentials of the two-electron redox transitions of cysteamine, cysteine, homocysteine, penicillamine, and ovothiol were determined using their microscopic redox equilibrium constants with glutathione. The 30 different, microscopic standard redox potential values show close correlation with the respective thiolate basicities and provide sound means for the development of potent agents against oxidative stress.

  20. Weather satellite picture receiving stations, APT digital scan converter

    Science.gov (United States)

    Vermillion, C. H.; Kamowski, J. C.

    1975-01-01

    The automatic picture transmission digital scan converter is used at ground stations to convert signals received from scanning radiometers to data compatible with ground equipment designed to receive signals from vidicons aboard operational meteorological satellites. Information necessary to understand the circuit theory, functional operation, general construction and calibration of the converter is provided. Brief and detailed descriptions of each of the individual circuits are included, accompanied by a schematic diagram contained at the end of each circuit description. Listings of integral parts and testing equipment required as well as an overall wiring diagram are included. This unit will enable the user to readily accept and process weather photographs from the operational meteorological satellites.

  1. Redox electrode materials for supercapatteries

    Science.gov (United States)

    Yu, Linpo; Chen, George Z.

    2016-09-01

    Redox electrode materials, including transition metal oxides and electronically conducting polymers, are capable of faradaic charge transfer reactions, and play important roles in most electrochemical energy storage devices, such as supercapacitor, battery and supercapattery. Batteries are often based on redox materials with low power capability and safety concerns in some cases. Supercapacitors, particularly those based on redox inactive materials, e.g. activated carbon, can offer high power output, but have relatively low energy capacity. Combining the merits of supercapacitor and battery into a hybrid, the supercapattery can possess energy as much as the battery and output a power almost as high as the supercapacitor. Redox electrode materials are essential in the supercapattery design. However, it is hard to utilise these materials easily because of their intrinsic characteristics, such as the low conductivity of metal oxides and the poor mechanical strength of conducting polymers. This article offers a brief introduction of redox electrode materials, the basics of supercapattery and its relationship with pseudocapacitors, and reviews selectively some recent progresses in the relevant research and development.

  2. Resonant power converters

    CERN Document Server

    Kazimierczuk, Marian K

    2012-01-01

    This book is devoted to resonant energy conversion in power electronics. It is a practical, systematic guide to the analysis and design of various dc-dc resonant inverters, high-frequency rectifiers, and dc-dc resonant converters that are building blocks of many of today's high-frequency energy processors. Designed to function as both a superior senior-to-graduate level textbook for electrical engineering courses and a valuable professional reference for practicing engineers, it provides students and engineers with a solid grasp of existing high-frequency technology, while acquainting them wit

  3. Cycloidal Wave Energy Converter

    Energy Technology Data Exchange (ETDEWEB)

    Stefan G. Siegel, Ph.D.

    2012-11-30

    This program allowed further advancing the development of a novel type of wave energy converter, a Cycloidal Wave Energy Converter or CycWEC. A CycWEC consists of one or more hydrofoils rotating around a central shaft, and operates fully submerged beneath the water surface. It operates under feedback control sensing the incoming waves, and converts wave power to shaft power directly without any intermediate power take off system. Previous research consisting of numerical simulations and two dimensional small 1:300 scale wave flume experiments had indicated wave cancellation efficiencies beyond 95%. The present work was centered on construction and testing of a 1:10 scale model and conducting two testing campaigns in a three dimensional wave basin. These experiments allowed for the first time for direct measurement of electrical power generated as well as the interaction of the CycWEC in a three dimensional environment. The Atargis team successfully conducted two testing campaigns at the Texas A&M Offshore Technology Research Center and was able to demonstrate electricity generation. In addition, three dimensional wave diffraction results show the ability to achieve wave focusing, thus increasing the amount of wave power that can be extracted beyond what was expected from earlier two dimensional investigations. Numerical results showed wave cancellation efficiencies for irregular waves to be on par with results for regular waves over a wide range of wave lengths. Using the results from previous simulations and experiments a full scale prototype was designed and its performance in a North Atlantic wave climate of average 30kW/m of wave crest was estimated. A full scale WEC with a blade span of 150m will deliver a design power of 5MW at an estimated levelized cost of energy (LCOE) in the range of 10-17 US cents per kWh. Based on the new results achieved in the 1:10 scale experiments these estimates appear conservative and the likely performance at full scale will

  4. Redox regulation of antioxidants, autophagy, and the response to stress: implications for electrophile therapeutics.

    Science.gov (United States)

    Levonen, Anna-Liisa; Hill, Bradford G; Kansanen, Emilia; Zhang, Jianhua; Darley-Usmar, Victor M

    2014-06-01

    Redox networks in the cell integrate signaling pathways that control metabolism, energetics, cell survival, and death. The physiological second messengers that modulate these pathways include nitric oxide, hydrogen peroxide, and electrophiles. Electrophiles are produced in the cell via both enzymatic and nonenzymatic lipid peroxidation and are also relatively abundant constituents of the diet. These compounds bind covalently to families of cysteine-containing, redox-sensing proteins that constitute the electrophile-responsive proteome, the subproteomes of which are found in localized intracellular domains. These include those proteins controlling responses to oxidative stress in the cytosol-notably the Keap1-Nrf2 pathway, the autophagy-lysosomal pathway, and proteins in other compartments including mitochondria and endoplasmic reticulum. The signaling pathways through which electrophiles function have unique characteristics that could be exploited for novel therapeutic interventions; however, development of such therapeutic strategies has been challenging due to a lack of basic understanding of the mechanisms controlling this form of redox signaling. In this review, we discuss current knowledge of the basic mechanisms of thiol-electrophile signaling and its potential impact on the translation of this important field of redox biology to the clinic. Emerging understanding of thiol-electrophile interactions and redox signaling suggests replacement of the oxidative stress hypothesis with a new redox biology paradigm, which provides an exciting and influential framework for guiding translational research.

  5. Bidirectional buck boost converter

    Science.gov (United States)

    Esser, Albert Andreas Maria

    1998-03-31

    A bidirectional buck boost converter and method of operating the same allows regulation of power flow between first and second voltage sources in which the voltage level at each source is subject to change and power flow is independent of relative voltage levels. In one embodiment, the converter is designed for hard switching while another embodiment implements soft switching of the switching devices. In both embodiments, first and second switching devices are serially coupled between a relatively positive terminal and a relatively negative terminal of a first voltage source with third and fourth switching devices serially coupled between a relatively positive terminal and a relatively negative terminal of a second voltage source. A free-wheeling diode is coupled, respectively, in parallel opposition with respective ones of the switching devices. An inductor is coupled between a junction of the first and second switching devices and a junction of the third and fourth switching devices. Gating pulses supplied by a gating circuit selectively enable operation of the switching devices for transferring power between the voltage sources. In the second embodiment, each switching device is shunted by a capacitor and the switching devices are operated when voltage across the device is substantially zero.

  6. Gallium phosphide energy converters

    Energy Technology Data Exchange (ETDEWEB)

    Sims, P.E.; Dinetta, L.C.; Goetz, M.A.

    1995-10-01

    Gallium phosphide (GaP) energy converters may be successfully deployed to provide new mission capabilities for spacecraft. Betavoltaic power supplies based on the conversion of tritium beta decay to electricity using GaP energy converters can supply long term low-level power with high reliability. High temperature solar cells, also based on GaP, can be used in inward-bound missions greatly reducing the need for thermal dissipation. Results are presented for GaP direct conversion devices powered by Ni-63 and compared to the conversion of light emitted by tritiarated phosphors. Leakage currents as low as 1.2 x 10(exp {minus}17) A/sq cm have been measured and the temperature dependence of the reverse saturation current is found to have ideal behavior. Temperature dependent IV, QE, R(sub sh), and V(sub oc) results are also presented. These data are used to predict the high-temperature solar cell and betacell performance of GaP devices and suggest appropriate applications for the deployment of this technology.

  7. Roles of oxidative stress and redox regulation in atherosclerosis.

    Science.gov (United States)

    Kondo, Takahito; Hirose, Makoto; Kageyama, Kan

    2009-10-01

    Oxidative stress is believed to be a cause of aging and cardiovascular disorders. In response to inflam-mation or endothelial cell injury, production of reactive oxygen species (ROS) is enhanced in vascular cells. These changes contribute to the initiation of atherosclerosis. Vascular cells possess anti-oxidant systems to protect against oxidative stress, in addition to the redox system. The redox status of pro-tein thiols is important for cellular functions. The Akt signaling pathway exerts effects on survival and apoptosis, and is regulated by the glutathione (GSH)/glutaredoxin (GRX)-dependent redox sys-tem. Sex hormones such as estrogens protect against oxidative stress by protecting the Akt signaling pathway but the physiological role of the extracellular GSH/GRX system has not been clarified, although found an increase in the levels of S-glutathionylated serum proteins in patients with athero-sclerosis obliterans. The results suggested that impaired serum redox potential is a marker of the development vascular dysfunction and estrogen has a possible role in the prevention of atherosclerosis.

  8. Thermal heat-balance mode flow-to-frequency converter

    Science.gov (United States)

    Pawlowski, Eligiusz

    2016-11-01

    This paper presents new type of thermal flow converter with the pulse frequency output. The integrating properties of the temperature sensor have been used, which allowed for realization of pulse frequency modulator with thermal feedback loop, stabilizing temperature of sensor placed in the flowing medium. The system assures balancing of heat amount supplied in impulses to the sensor and heat given up by the sensor in a continuous way to the flowing medium. Therefore the frequency of output impulses is proportional to the heat transfer coefficient from sensor to environment. According to the King's law, the frequency of those impulses is a function of medium flow velocity around the sensor. The special feature of presented solution is total integration of thermal sensor with the measurement signal conditioning system. Sensor and conditioning system are not the separate elements of the measurement circuit, but constitute a whole in form of thermal heat-balance mode flow-to-frequency converter. The advantage of such system is easiness of converting the frequency signal to the digital form, without using any additional analogue-to-digital converters. The frequency signal from the converter may be directly connected to the microprocessor input, which with use of standard built-in counters may convert the frequency into numerical value of high precision. Moreover, the frequency signal has higher resistance to interference than the voltage signal and may be transmitted to remote locations without the information loss.

  9. Redox Couples with Unequal Diffusion Coefficients: Effect on Redox Cycling

    NARCIS (Netherlands)

    Mampallil Augustine, Dileep; Mathwig, Klaus; Kang, Shuo; Lemay, Serge G.

    2013-01-01

    Redox cycling between two electrodes separated by a narrow gap allows dramatic amplification of the faradaic current. Unlike conventional electrochemistry at a single electrode, however, the mass-transport-limited current is controlled by the diffusion coefficient of both the reduced and oxidized fo

  10. EMI filter techniques in power electronic converters

    Directory of Open Access Journals (Sweden)

    Fredy Edimer Hoyos Velasco

    2012-04-01

    Full Text Available This paper presents the results of EMI reduction techniques applied to power electronic converters. The techniques applied included shielding control and power signals, separating power system references regarding reference for instrumentation and measurement signals, implementing analog filters and configuring an appropriate switch trigger system for electronic power to decrease shifting EMI emissions to the maximum. This paper presents the results before and after applying the techniques to reduce interference. The results were also veryfied by using two real time control strategies rapid control prototyping (RCP.

  11. Manufacturing method of photoelectric converter

    Energy Technology Data Exchange (ETDEWEB)

    Yamazaki, Shunpei; Suzuki, Kunio; Fukada, Takeshi; Kanehana, Mikio

    1987-06-25

    This is a photoelectric converter wherein a photoelectromotive force is generated by utilizing the shorter wavelength side by the 1st converter and by utilizing the longer wavelength side by the 2nd converter; as a whole, wider wavelength range of light can be converted into electricity. In the 1st. converter, an electrode on the side of semi-incident surface is made transparent as well as an electrode equipped on the back of a non-mono-crystalline semiconductor. Light which passed this is introduced into the 2nd converter to generate an electromotive force. This invention especially relates with a method of forming this 2nd converter. In preparing I-type non-mono-crystalline semiconductor among the semiconductors having PIN junction, PCVD method is used by means of ECR (Electron Cyclotron Resonance) by using a hydrogen- or halogen- added Si-semiconductor instead of using expensive Ge, etc, which are common in the conventional method. (3 figs)

  12. Electromagnetic wave energy converter

    Science.gov (United States)

    Bailey, R. L. (Inventor)

    1973-01-01

    Electromagnetic wave energy is converted into electric power with an array of mutually insulated electromagnetic wave absorber elements each responsive to an electric field component of the wave as it impinges thereon. Each element includes a portion tapered in the direction of wave propagation to provide a relatively wideband response spectrum. Each element includes an output for deriving a voltage replica of the electric field variations intercepted by it. Adjacent elements are positioned relative to each other so that an electric field subsists between adjacent elements in response to the impinging wave. The electric field results in a voltage difference between adjacent elements that is fed to a rectifier to derive dc output power.

  13. Nitric oxide and zinc-mediated protein assemblies involved in mu opioid receptor signaling.

    Science.gov (United States)

    Rodríguez-Muñoz, María; Garzón, Javier

    2013-12-01

    Opioids are among the most effective analgesics in controlling the perception of intense pain, although their continuous use decreases their potency due to the development of tolerance. The glutamate N-methyl-D-aspartate (NMDA) receptor system is currently considered to be the most relevant functional antagonist of morphine analgesia. In the postsynapse of different brain regions the C terminus of the mu-opioid receptor (MOR) associates with NR1 subunits of NMDARs, as well as with a series of signaling proteins, such as neural nitric oxide synthase (nNOS)/nitric oxide (NO), protein kinase C (PKC), calcium and calmodulin-dependent kinase II (CaMKII) and the mitogen-activated protein kinases (MAPKs). NO is implicated in redox signaling and PKC falls under the regulation of zinc metabolism, suggesting that these signaling elements might participate in the regulation of MOR activity by the NMDAR. In this review, we discuss the influence of redox signaling in the mechanisms whose plasticity triggers opioid tolerance. Thus, the MOR C terminus assembles a series of signaling proteins around the homodimeric histidine triad nucleotide-binding protein 1 (HINT1). The NMDAR NR1 subunit and the regulator of G protein signaling RGSZ2 bind HINT1 in a zinc-independent manner, with RGSZ2 associating with nNOS and regulating MOR-induced production of NO. This NO acts on the RGSZ2 zinc finger, providing the zinc ions that are required for PKC/Raf-1 cysteine-rich domains to simultaneously bind to the histidines present in the HINT1 homodimer. The MOR-induced activation of phospholipase β (PLCβ) regulates PKC, which increases the reactive oxygen species (ROS) by acting on NOX/NADPH, consolidating the long-term PKC activation required to regulate the Raf-1/MAPK cascade and enhancing NMDAR function. Thus, RGSZ2 serves as a Redox Zinc Switch that converts NO signals into Zinc signals, thereby modulating Redox Sensor Proteins like PKCγ and Raf-1. Accordingly, redox-dependent and

  14. Integrated power electronic converters and digital control

    CERN Document Server

    Emadi, Ali; Nie, Zhong

    2009-01-01

    Non-isolated DC-DC ConvertersBuck ConverterBoost ConverterBuck-Boost ConverterIsolated DC-DC ConvertersFlyback ConverterForward ConverterPush-Pull ConverterFull-Bridge ConverterHalf-Bridge ConverterPower Factor CorrectionConcept of PFCGeneral Classification of PFC CircuitsHigh Switching Frequency Topologies for PFCApplication of PFC in Advanced Motor DrivesIntegrated Switched-Mode Power ConvertersSwitched-Mode Power SuppliesThe Concept of Integrated ConverterDefinition of Integrated Switched-Mode Power Supplies (ISMPS)Boost-Type Integrated TopologiesGeneral Structure of Boost-Type Integrated T

  15. Advanced power electronics converters PWM converters processing AC voltages

    CERN Document Server

    dos Santos, Euzeli

    2014-01-01

    This book covers power electronics, in depth, by presenting the basic principles and application details, which can be used both as a textbook and reference book.  Introduces a new method to present power electronics converters called Power Blocks Geometry. Applicable for courses focusing on power electronics, power electronics converters, and advanced power converters. Offers a comprehensive set of simulation results to help understand the circuits presented throughout the book

  16. Nanostructure Neutron Converter Layer Development

    Science.gov (United States)

    Park, Cheol (Inventor); Sauti, Godfrey (Inventor); Kang, Jin Ho (Inventor); Lowther, Sharon E. (Inventor); Thibeault, Sheila A. (Inventor); Bryant, Robert G. (Inventor)

    2016-01-01

    Methods for making a neutron converter layer are provided. The various embodiment methods enable the formation of a single layer neutron converter material. The single layer neutron converter material formed according to the various embodiments may have a high neutron absorption cross section, tailored resistivity providing a good electric field penetration with submicron particles, and a high secondary electron emission coefficient. In an embodiment method a neutron converter layer may be formed by sequential supercritical fluid metallization of a porous nanostructure aerogel or polyimide film. In another embodiment method a neutron converter layer may be formed by simultaneous supercritical fluid metallization of a porous nanostructure aerogel or polyimide film. In a further embodiment method a neutron converter layer may be formed by in-situ metalized aerogel nanostructure development.

  17. Impedance source power electronic converters

    CERN Document Server

    Liu, Yushan; Ge, Baoming; Blaabjerg, Frede; Ellabban, Omar; Loh, Poh Chiang

    2016-01-01

    Impedance Source Power Electronic Converters brings together state of the art knowledge and cutting edge techniques in various stages of research related to the ever more popular impedance source converters/inverters. Significant research efforts are underway to develop commercially viable and technically feasible, efficient and reliable power converters for renewable energy, electric transportation and for various industrial applications. This book provides a detailed understanding of the concepts, designs, controls, and application demonstrations of the impedance source converters/inverters. Key features: Comprehensive analysis of the impedance source converter/inverter topologies, including typical topologies and derived topologies. Fully explains the design and control techniques of impedance source converters/inverters, including hardware design and control parameter design for corresponding control methods. Presents the latest power conversion solutions that aim to advance the role of pow...

  18. Linking mitochondrial bioenergetics to insulin resistance via redox biology

    OpenAIRE

    Fisher-Wellman, Kelsey H.; Neufer, P. Darrell

    2012-01-01

    Chronic overnutrition and physical inactivity are major risk factors for insulin resistance and type 2 diabetes. Recent research indicates that overnutrition generates an increase in hydrogen peroxide (H2O2) emission from mitochondria, serving as a release valve to relieve the reducing pressure created by fuel overload, as well as a primary signal to ultimately decrease insulin sensitivity. H2O2 is a major input to cellular redox circuits that link to cysteine residues throughout the entire p...

  19. Novel Design for High Speed and Resolution Delta-sigma A/D Converter

    Institute of Scientific and Technical Information of China (English)

    TANG Sheng-xue; HE Yi-gang; GUO Jie-rong; LI Hong-min

    2007-01-01

    The delta-sigma converter is one of the high speed and resolution analog-to-digital modulators. Its implementation needs the low oversampling technique and the multi-bit D/A converter. The noise induced by the multi-bit D/A converter becomes one of the key factors deteriorating the signal-to-noise rate of the delta-sigma A/D converter. A novel structure with signal unity transfunction, dynamic element matching(DEM) and noise-shaping is discussed. The method is investigated to design converter based on the proposed structure. The behavior simulation indicates that the structure and the design method are feasible.

  20. Scaling behavior in mitochondrial redox fluctuations.

    Science.gov (United States)

    Ramanujan, V Krishnan; Biener, Gabriel; Herman, Brian A

    2006-05-15

    Scale-invariant long-range correlations have been reported in fluctuations of time-series signals originating from diverse processes such as heart beat dynamics, earthquakes, and stock market data. The common denominator of these apparently different processes is a highly nonlinear dynamics with competing forces and distinct feedback species. We report for the first time an experimental evidence for scaling behavior in NAD(P)H signal fluctuations in isolated mitochondria and intact cells isolated from the liver of a young (5-month-old) mouse. Time-series data were collected by two-photon imaging of mitochondrial NAD(P)H fluorescence and signal fluctuations were quantitatively analyzed for statistical correlations by detrended fluctuation analysis and spectral power analysis. Redox [NAD(P)H / NAD(P)(+)] fluctuations in isolated mitochondria and intact liver cells were found to display nonrandom, long-range correlations. These correlations are interpreted as arising due to the regulatory dynamics operative in Krebs' cycle enzyme network and electron transport chain in the mitochondria. This finding may provide a novel basis for understanding similar regulatory networks that govern the nonequilibrium properties of living cells.

  1. A thermochemical energy converter

    Energy Technology Data Exchange (ETDEWEB)

    Toyeguti, K.; Indzima, T.

    1982-08-09

    Mercury is used as the active mass of the anode in the converter and 0/sub 2/ is used as the active cathode material. The reaction of Mercury + 1/2 0/sub 2/-Hg0 occurs with a discharge. With heating to 500/sup 0/C the regeneration of the Mercury, Hg0 yields Mercury + 1/2 0/sub 2/, occurs. The device for performing the thermochenical conversion of energy contains an element body, an oxygen chamber, an oxygen electrode, a chamber with an alkaline liquid electrolyte, a separator, an auxiliary separator, an electrode and a chamber with the Mercury. The thermochemical reaction occurs in the reactor to which the Hg0 is transported along a pipe which has a refrigerator and a valve. The Mercury is fed into the element from a reservoir. The Mercury reduced in the reactor and in a reaction tower is fed into it through a closed cycle. The bellows is connected with the reactor by a pipe with a refrigerator. Through it the 0/sub 2/ goes in a closed cycle to the chamber. The current forming reactions are Hg + 20H-anion yields Hg0 + H/sub 2/0 + 2e and 1/2 0/sub 2/ + H/sub 2/0 + 2e yields 20H-anion. The voltage on the outleads of the element is approximately 0.3 volts.

  2. DC to DC converters: operation; Hacheurs: fonctionnement

    Energy Technology Data Exchange (ETDEWEB)

    Bernot, F. [Ecole d' Ingenieurs de Tours, 37 (France)

    2002-05-01

    This article deals with pulse width modulation (PWM) and pulse position modulation (PPM) DC to DC converters. A tri-phase PWM converter is made of 6 simple DC/DC converters grouped together into 3 reversible converters of the same type: 1 - single-quadrant voltage lowering converters (hydraulic analogy, study with ideal elements, full scheme with input and output filters); 2 - single-quadrant voltage raising converters (hydraulic analogy, operation); 3 - two quadrants reversible converters (structure construction, quadrants of operation, reversible converter connected to a DC motor); 4 - four-quadrants reversible converters; 5 - other converters structure (current converters and converters with intermediate storage, asymmetrical converters, converters with capacitive storage, insulated converters, resonating converters, status); 6 - conclusion. (J.S.)

  3. CIECA - Application to current programmed switching Dc-Dc converters

    Science.gov (United States)

    Chetty, P. R. K.

    1982-09-01

    The current injection equivalent circuit approach (CIECA) to modeling switching converter power stages is extended to model the current programmed converter power stages operating in fixed frequency, continuous inductor conduction mode. To demonstrate the method, modeling is carried out for the buck, boost, and buckboost converters to obtain small-signal linear equivalent circuit models which represent both input and output properties. The results of these analyses are presented in the form of linear equivalent circuit models as well as transfer functions. Though current programmed converters exhibit single-pole response, the addition of artificial ramp changes converters to exhibit well damped two-pole response. This has been investigated for the first time using CIECA. The results of these analyses are presented in the form of linear equivalent circuit models as well as transfer functions.

  4. Role of redox status in development of glioblastoma

    Directory of Open Access Journals (Sweden)

    Aleli eSalazar-Ramiro

    2016-04-01

    Full Text Available Glioblastoma (GBM is a highly aggressive neoplasia, prognosis remains dismal and current therapy is mostly palliative. There are no known risk factors associated with gliomagenesis; however, it is well established that chronic inflammation in brain tissue induces oxidative stress in astrocytes and microglia. High quantities of reactive species of oxygen into the cells can react with several macromolecules, including chromosomal and mitochondrial DNA, leading to damage and malfunction of DNA repair enzymes. These changes bring genetic instability and abnormal metabolic processes favoring oxidative environment and increase rate of cell proliferation. In GBM, a high metabolic rate and increased basal levels of ROS play an important role as chemical mediators in the regulation of signal transduction, protecting malignant cells from apoptosis, thus creating an immunosuppressive environment. New redox therapeutics could reduce oxidative stress preventing cellular damage and high mutation rate accompanied by chromosomal instability, reducing the immunosuppressive environment. In addition, therapies directed to modulate redox rate reduce resistance and moderate the high rate of cell proliferation, favoring apoptosis of tumoral cells. This review describes the redox status in GBM and how this imbalance could promote gliomagenesis through genomic and mitochondrial DNA damage, inducing the pro-oxidant and pro-inflammatory environment involved in tumor cell proliferation, resistance and immune scape. In addition, are described some therapeutic agents that modulate redox status and might be advantageous in therapy against GBM.

  5. Parametric algorithms for frequency estimation in PWM converter systems

    Energy Technology Data Exchange (ETDEWEB)

    Lobos, T.; Hejke, I.; Rezmer, J.; Sikorski, T.; Kostyla, P. [Dept. of Electrical Engineering, Wroclaw University of Technology, Wyb. Wyspianskiego 27, 50-370 Wroclaw (Poland)

    2009-11-15

    Proper estimation of voltage parameters has a significant meaning for power converters control systems. One of the measured parameter, directly associated with control process, is frequency of the basic voltage component at the converter output. Unfortunately, power converters generate a wide spectrum of harmonics as well as interharmonics, that makes difficulties in estimation this frequency. Measurement carried out in industrial applications exhibits complex nature of investigated signals often corrupted by resonances or overvoltages phenomena. It entails searching a new digital algorithms for frequency measurement. This work presents algorithm using modification of high-resolution Prony method connected with digital filtering. The investigations was based on simulations and real measured signals recorded in two different commercial PWM converters. Obtained results indicate accuracy of the method as well as its fast response. (author)

  6. Microbial population heterogeneity versus bioreactor heterogeneity: evaluation of Redox Sensor Green as an exogenous metabolic biosensor

    DEFF Research Database (Denmark)

    Baert, Jonathan; Delepierre, Anissa; Telek, Samuel

    2016-01-01

    performances (i.e. microbial population heterogeneity). In this work, we have evaluated the relevance of Redox Sensor Green (RSG) as an exogenous biosensor of metabolic activity at the single cell level. RSG signal is proportional to the activity of the electron transport chain and its signal is strongly...

  7. Acupuncture Mechanism and Redox Equilibrium

    OpenAIRE

    Xiang-Hong Zeng; Qian-Qian Li; Qian Xu; Fang Li; Cun-Zhi Liu

    2014-01-01

    Oxidative stress participates in the pathological process of various diseases. Acupuncture is a component of the health care system in China that can be traced back for at least 3000 years. Recently, increased evidences indicate that acupuncture stimulation could reduce oxidative damage in organisms under pathological state, but the exact mechanism remains unclear. This review focuses on the emerging links between acupuncture and redox modulation in various disorders, such as vascular dementi...

  8. Time-interleaved analog-to-digital converters

    CERN Document Server

    Louwsma, Simon; Nauta, Bram

    2010-01-01

    ""Time-interleaved Analog-to-Digital Converters"" describes the research performed on low-power time-interleaved ADCs. A detailed theoretical analysis is made of the time-interleaved Track & Hold, since it must be capable of handling signals in the GHz range with little distortion, and minimal power consumption. Timing calibration is not attractive, therefore design techniques are presented which do not require timing calibration. The design of power efficient sub-ADCs is addressed with a theoretical analysis of a successive approximation converter and a pipeline converter. It turns out that t

  9. Proposed electromagnetic wave energy converter

    Science.gov (United States)

    Bailey, R. L.

    1973-01-01

    Device converts wave energy into electric power through array of insulated absorber elements responsive to field of impinging electromagnetic radiation. Device could also serve as solar energy converter that is potentially less expensive and fragile than solar cells, yet substantially more efficient.

  10. The Design Points of RS232 -RS422/RS485/TLL Signal Converter%RS232-RS422/RS485/TLL信号转换器设计

    Institute of Scientific and Technical Information of China (English)

    苏燕; 周士龙

    2012-01-01

    主要介绍了RS232-RS422/485信号转换器在窃电电路、自动方向转换电路、RS232信号补偿电路的设计要点,提出了将RS422接口与TLL接口兼容使用的方法。%This article mainly introduces design points of the RS232 -RS422/485 signal converter's getting power supply from signal pins circuit, automatic direction of transform circuit and RS232 signal compensation circuit. It puts forward the RS422 interface and TLL interface compatibility methods

  11. Impedance Source Power Electronic Converters

    DEFF Research Database (Denmark)

    Liu, Yushan; Abu-Rub, Haitham; Ge, Baoming

    Impedance Source Power Electronic Converters brings together state of the art knowledge and cutting edge techniques in various stages of research related to the ever more popular impedance source converters/inverters. Significant research efforts are underway to develop commercially viable...... and technically feasible, efficient and reliable power converters for renewable energy, electric transportation and for various industrial applications. This book provides a detailed understanding of the concepts, designs, controls, and application demonstrations of the impedance source converters/inverters. Key...... control methods. Presents the latest power conversion solutions that aim to advance the role of power electronics into industries and sustainable energy conversion systems. Compares impedance source converter/inverter applications in renewable energy power generation and electric vehicles as well...

  12. Nitroso-redox status and vascular function in marginal and severe ascorbate deficiency.

    Science.gov (United States)

    Garcia-Saura, Maria-Francisca; Saijo, Fumito; Bryan, Nathan S; Bauer, Selena; Rodriguez, Juan; Feelisch, Martin

    2012-10-01

    Marginal vitamin C (ascorbic acid) deficiency is a prevalent yet underappreciated risk factor for cardiovascular disease. Along with glutathione, ascorbate plays important roles in antioxidant defense and redox signaling. Production of nitric oxide (NO) and reactive oxygen species and their interaction, giving rise to nitroso and nitrosyl product formation, are key components of the redox regulation/signaling network. Numerous in vitro studies have demonstrated that these systems are interconnected via multiple chemical transformation reactions, but little is known about their dynamics and significance in vivo. We sought to investigate the time-course of changes in NO/redox status and vascular function during ascorbate depletion in rats unable to synthesize vitamin C. We here show that both redox and protein nitros(yl)ation status in blood and vital organs vary dynamically during development of ascorbate deficiency. Prolonged marginal ascorbate deficiency is associated with cell/tissue-specific perturbations in ascorbate and glutathione redox and NO status. Scurvy develops earlier in marginally deficient compared to adequately supplemented animals, with blunted compensatory NO production and a dissociation of biochemistry from clinical symptomology in the former. Paradoxically, aortic endothelial reactivity is enhanced rather than impaired, irrespective of ascorbate status. Innovation/Conclusion: Enhanced NO production and protein nitros(yl)ation are integral responses to the redox stress of acute ascorbate deprivation. The elevated cardiovascular risk in marginal ascorbate deficiency is likely to be associated with perturbations of NO/redox-sensitive signaling nodes unrelated to the regulation of vascular tone. This new model may have merit for the future study of redox-sensitive events in marginal ascorbate deficiency.

  13. Lung extracellular matrix and redox regulation.

    Science.gov (United States)

    Watson, Walter H; Ritzenthaler, Jeffrey D; Roman, Jesse

    2016-08-01

    Pulmonary fibrosis affects millions worldwide and, even though there has been a significant investment in understanding the processes involved in wound healing and maladaptive repair, a complete understanding of the mechanisms responsible for lung fibrogenesis eludes us, and interventions capable of reversing or halting disease progression are not available. Pulmonary fibrosis is characterized by the excessive expression and uncontrolled deposition of extracellular matrix (ECM) proteins resulting in erosion of the tissue structure. Initially considered an 'end-stage' process elicited after injury, these events are now considered pathogenic and are believed to contribute to the course of the disease. By interacting with integrins capable of signal transduction and by influencing tissue mechanics, ECM proteins modulate processes ranging from cell adhesion and migration to differentiation and growth factor expression. In doing so, ECM proteins help orchestrate complex developmental processes and maintain tissue homeostasis. However, poorly controlled deposition of ECM proteins promotes inflammation, fibroproliferation, and aberrant differentiation of cells, and has been implicated in the pathogenesis of pulmonary fibrosis, atherosclerosis and cancer. Considering their vital functions, ECM proteins are the target of investigation, and oxidation-reduction (redox) reactions have emerged as important regulators of the ECM. Oxidative stress invariably accompanies lung disease and promotes ECM expression directly or through the overproduction of pro-fibrotic growth factors, while affecting integrin binding and activation. In vitro and in vivo investigations point to redox reactions as targets for intervention in pulmonary fibrosis and related disorders, but studies in humans have been disappointing probably due to the narrow impact of the interventions tested, and our poor understanding of the factors that regulate these complex reactions. This review is not meant to

  14. Redox control of 20S proteasome gating.

    Science.gov (United States)

    Silva, Gustavo M; Netto, Luis E S; Simões, Vanessa; Santos, Luiz F A; Gozzo, Fabio C; Demasi, Marcos A A; Oliveira, Cristiano L P; Bicev, Renata N; Klitzke, Clécio F; Sogayar, Mari C; Demasi, Marilene

    2012-06-01

    The proteasome is the primary contributor in intracellular proteolysis. Oxidized or unstructured proteins can be degraded via a ubiquitin- and ATP-independent process by the free 20S proteasome (20SPT). The mechanism by which these proteins enter the catalytic chamber is not understood thus far, although the 20SPT gating conformation is considered to be an important barrier to allowing proteins free entrance. We have previously shown that S-glutathiolation of the 20SPT is a post-translational modification affecting the proteasomal activities. The goal of this work was to investigate the mechanism that regulates 20SPT activity, which includes the identification of the Cys residues prone to S-glutathiolation. Modulation of 20SPT activity by proteasome gating is at least partially due to the S-glutathiolation of specific Cys residues. The gate was open when the 20SPT was S-glutathiolated, whereas following treatment with high concentrations of dithiothreitol, the gate was closed. S-glutathiolated 20SPT was more effective at degrading both oxidized and partially unfolded proteins than its reduced form. Only 2 out of 28 Cys were observed to be S-glutathiolated in the proteasomal α5 subunit of yeast cells grown to the stationary phase in glucose-containing medium. We demonstrate a redox post-translational regulatory mechanism controlling 20SPT activity. S-glutathiolation is a post-translational modification that triggers gate opening and thereby activates the proteolytic activities of free 20SPT. This process appears to be an important regulatory mechanism to intensify the removal of oxidized or unstructured proteins in stressful situations by a process independent of ubiquitination and ATP consumption. Antioxid. Redox Signal. 16, 1183-1194.

  15. Lung extracellular matrix and redox regulation

    Directory of Open Access Journals (Sweden)

    Walter H. Watson

    2016-08-01

    Full Text Available Pulmonary fibrosis affects millions worldwide and, even though there has been a significant investment in understanding the processes involved in wound healing and maladaptive repair, a complete understanding of the mechanisms responsible for lung fibrogenesis eludes us, and interventions capable of reversing or halting disease progression are not available. Pulmonary fibrosis is characterized by the excessive expression and uncontrolled deposition of extracellular matrix (ECM proteins resulting in erosion of the tissue structure. Initially considered an ‘end-stage’ process elicited after injury, these events are now considered pathogenic and are believed to contribute to the course of the disease. By interacting with integrins capable of signal transduction and by influencing tissue mechanics, ECM proteins modulate processes ranging from cell adhesion and migration to differentiation and growth factor expression. In doing so, ECM proteins help orchestrate complex developmental processes and maintain tissue homeostasis. However, poorly controlled deposition of ECM proteins promotes inflammation, fibroproliferation, and aberrant differentiation of cells, and has been implicated in the pathogenesis of pulmonary fibrosis, atherosclerosis and cancer. Considering their vital functions, ECM proteins are the target of investigation, and oxidation–reduction (redox reactions have emerged as important regulators of the ECM. Oxidative stress invariably accompanies lung disease and promotes ECM expression directly or through the overproduction of pro-fibrotic growth factors, while affecting integrin binding and activation. In vitro and in vivo investigations point to redox reactions as targets for intervention in pulmonary fibrosis and related disorders, but studies in humans have been disappointing probably due to the narrow impact of the interventions tested, and our poor understanding of the factors that regulate these complex reactions. This

  16. Redox regulation, gene expression and longevity.

    Science.gov (United States)

    Honda, Yoko; Tanaka, Masashi; Honda, Shuji

    2010-07-01

    Lifespan can be lengthened by genetic and environmental modifications. Study of these might provide valuable insights into the mechanism of aging. Low doses of radiation and short-term exposure to heat and high concentrations of oxygen prolong the lifespan of the nematode Caenorhabditis elegans. These might be caused by adaptive responses to harmful environmental conditions. Single-gene mutations have been found to extend lifespan in C. elegans, Drosophila and mice. So far, the best-characterized system is the C. elegans mutant in the daf-2, insulin/IGF-I receptor gene that is the component of the insulin/IGF-I signaling pathway. The mutant animals live twice as long as the wild type. The insulin/IGF-I signaling pathway regulates the activity of DAF-16, a FOXO transcription factor. However, the unified explanation for the function of DAF-16 transcription targets in the lifespan extension is not yet fully established. As both of the Mn superoxide dismutase (MnSOD) isoforms (sod-2 and sod-3) are found to be targets of DAF-16, we attempted to assess their functions in regulating lifespan and oxidative stress responsivity. We show that the double deletions of sod-2 and sod-3 genes induced oxidative-stress sensitivity but do not shorten lifespan in the daf-2 mutant background, indicating that oxidative stress is not necessarily a limiting factor for longevity. Furthermore, the deletion in the sod-3 gene lengthens lifespan in the daf-2 mutant. We conclude that the MnSOD systems in C. elegans fine-tune the insulin/IGF-I-signaling based regulation of longevity by acting not as anti-oxidants but as physiological-redox-signaling modulators.

  17. Redox regulation of autophagy in healthy brain and neurodegeneration.

    Science.gov (United States)

    Hensley, Kenneth; Harris-White, Marni E

    2015-12-01

    Autophagy and redox biochemistry are two major sub disciplines of cell biology which are both coming to be appreciated for their paramount importance in the etiology of neurodegenerative diseases including Alzheimer's disease (AD). Thus far, however, there has been relatively little exploration of the interface between autophagy and redox biology. Autophagy normally recycles macro-molecular aggregates produced through oxidative-stress mediated pathways, and also may reduce the mitochondrial production of reactive oxygen species through recycling of old and damaged mitochondria. Conversely, dysfunction in autophagy initiation, progression or clearance is evidenced to increase aggregation-prone proteins in neural and extraneural tissues. Redox mechanisms of autophagy regulation have been documented at the level of cross-talk between the Nrf2/Keap1 oxidant and electrophilic defense pathway and p62/sequestosome-1 (SQSTM1)-associated autophagy, at least in extraneural tissue; but other mechanisms of redox autophagy regulation doubtless remain to be discovered and the relevance of such processes to maintenance of neural homeostasis remains to be determined. This review summarizes current knowledge regarding the relationship of redox signaling, autophagy control, and oxidative stress as these phenomena relate to neurodegenerative disease. AD is specifically addressed as an example of the theme and as a promising indication for new therapies that act through engagement of autophagy pathways. To exemplify one such novel therapeutic entity, data is presented that the antioxidant and neurotrophic agent lanthionine ketimine-ethyl ester (LKE) affects autophagy pathway proteins including beclin-1 in the 3xTg-AD model of Alzheimer's disease where the compound has been shown to reduce pathological features and cognitive dysfunction.

  18. Redox regulation in plant programmed cell death.

    Science.gov (United States)

    De Pinto, M C; Locato, V; De Gara, L

    2012-02-01

    Programmed cell death (PCD) is a genetically controlled process described both in eukaryotic and prokaryotic organisms. Even if it is clear that PCD occurs in plants, in response to various developmental and environmental stimuli, the signalling pathways involved in the triggering of this cell suicide remain to be characterized. In this review, the main similarities and differences in the players involved in plant and animal PCD are outlined. Particular attention is paid to the role of reactive oxygen species (ROS) as key inducers of PCD in plants. The involvement of different kinds of ROS, different sites of ROS production, as well as their interaction with other molecules, is crucial in activating PCD in response to specific stimuli. Moreover, the importance is stressed on the balance between ROS production and scavenging, in various cell compartments, for the activation of specific steps in the signalling pathways triggering this cell suicide process. The review focuses on the complexity of the interplay between ROS and antioxidant molecules and enzymes in determining the most suitable redox environment required for the occurrence of different forms of PCD. © 2011 Blackwell Publishing Ltd.

  19. Redox regulation of the Calvin-Benson cycle: something old, something new.

    Science.gov (United States)

    Michelet, Laure; Zaffagnini, Mirko; Morisse, Samuel; Sparla, Francesca; Pérez-Pérez, María Esther; Francia, Francesco; Danon, Antoine; Marchand, Christophe H; Fermani, Simona; Trost, Paolo; Lemaire, Stéphane D

    2013-11-25

    Reversible redox post-translational modifications such as oxido-reduction of disulfide bonds, S-nitrosylation, and S-glutathionylation, play a prominent role in the regulation of cell metabolism and signaling in all organisms. These modifications are mainly controlled by members of the thioredoxin and glutaredoxin families. Early studies in photosynthetic organisms have identified the Calvin-Benson cycle, the photosynthetic pathway responsible for carbon assimilation, as a redox regulated process. Indeed, 4 out of 11 enzymes of the cycle were shown to have a low activity in the dark and to be activated in the light through thioredoxin-dependent reduction of regulatory disulfide bonds. The underlying molecular mechanisms were extensively studied at the biochemical and structural level. Unexpectedly, recent biochemical and proteomic studies have suggested that all enzymes of the cycle and several associated regulatory proteins may undergo redox regulation through multiple redox post-translational modifications including glutathionylation and nitrosylation. The aim of this review is to detail the well-established mechanisms of redox regulation of Calvin-Benson cycle enzymes as well as the most recent reports indicating that this pathway is tightly controlled by multiple interconnected redox post-translational modifications. This redox control is likely allowing fine tuning of the Calvin-Benson cycle required for adaptation to varying environmental conditions, especially during responses to biotic and abiotic stresses.

  20. Redox Changes During the Cell Cycle in the Embryonic Root Meristem of Arabidopsis thaliana.

    Science.gov (United States)

    de Simone, Ambra; Hubbard, Rachel; Viñegra de la Torre, Natanael; Velappan, Yazhini; Wilson, Michael; Considine, Michael J; Soppe, Wim J J; Foyer, Christine H

    2017-05-30

    The aim of this study was to characterize redox changes in the nuclei and cytosol occurring during the mitotic cell cycle in the embryonic roots of germinating Arabidopsis seedlings, and to determine how redox cycling was modified in mutants with a decreased capacity for ascorbate synthesis. Using an in vivo reduction-oxidation (redox) reporter (roGFP2), we show that transient oxidation of the cytosol and the nuclei occurred at G1 in the synchronized dividing cells of the Arabidopsis root apical meristem, with reduction at G2 and mitosis. This redox cycle was absent from low ascorbate mutants in which nuclei were significantly more oxidized than controls. The cell cycle-dependent increase in nuclear size was impaired in the ascorbate-deficient mutants, which had fewer cells per unit area in the root proliferation zone. The transcript profile of the dry seeds and size of the imbibed seeds was strongly influenced by low ascorbate but germination, dormancy release and seed aging characteristics were unaffected. These data demonstrate the presence of a redox cycle within the plant cell cycle and that the redox state of the nuclei is an important factor in cell cycle progression. Controlled oxidation is a key feature of the early stages of the plant cell cycle. However, sustained mild oxidation restricts nuclear functions and impairs progression through the cell cycle leading to fewer cells in the root apical meristem. Antioxid. Redox Signal. 00, 000-000.

  1. Red light-induced redox reactions in cells observed with TEMPO.

    Science.gov (United States)

    Eichler, Maor; Lavi, Ronit; Friedmann, Harry; Shainberg, Asher; Lubart, Rachel

    2007-06-01

    The aim of this study was to determine the wavelength dependence of light-induced redox reactions in cells, particularly whether there is any contribution by red wavelengths. An additional aim was to assess the potential of 2,2,6,6-tetramethyl piperidine-N-oxyl (TEMPO) as a tool for measuring these redox reactions. Visible light has been shown to affect cells, and redox reactions, which have been detected previously using spin traps, have been proposed as a mechanism. However, there is little evidence that red light, which is used in most such experiments, is redox active in cells. Redox activity was observed by measuring the decay of the electron paramagnetic resonance signal of TEMPO that occurs in the presence of illuminated cells. Color filters were used to generate blue, green, and red light, and the decay resulting from these wavelengths was compared to the decay caused by white light. Shorter wavelengths have a considerably stronger effect than longer wavelengths, although red light has some effect. Creation of reactive oxygen species by red light was confirmed with the spin trap 5,5-dimethyl-1-pyrroline-N-oxide (DMPO). Red light can induce redox reactions in illuminated cells. However, shorter wavelengths are more efficient in this regard. In addition, TEMPO was found to be a more sensitive probe than DMPO for detecting light-induced cellular redox reactions.

  2. Radiation tolerant power converter controls

    CERN Document Server

    Todd, B; King, Q; Uznanski, S

    2012-01-01

    The Large Hadron Collider (LHC) at the European Organisation for Nuclear Research (CERN) is the world's most powerful particle collider. The LHC has several thousand magnets, both warm and super-conducting, which are supplied with current by power converters. Each converter is controlled by a purpose-built electronic module called a Function Generator Controller (FGC). The FGC allows remote control of the power converter and forms the central part of a closed-loop control system where the power converter voltage is set, based on the converter output current and magnet-circuit characteristics. Some power converters and FGCs are located in areas which are exposed to beam-induced radiation. There are numerous radiation induced effects, some of which lead to a loss of control of the power converter, having a direct impact upon the accelerator's availability. Following the first long shut down (LS1), the LHC will be able to run with higher intensity beams and higher beam energy. This is expected to lead to signifi...

  3. Power converter simulation and analysis

    Energy Technology Data Exchange (ETDEWEB)

    Ghazy, M.A.

    1989-01-01

    There has been a great deal of progress made in computer aided design and analysis in the power electronic field. Many of the simulation packages are inefficient and time consuming in simulating switching converters. This thesis proposes an efficient, simple, general simulation approach to simulate any power converter with less computation time and space requirements on computer. In this approach the equations of power converters are formulated using network topology. In this thesis several procedures have been explained for the steady-state computation of power electronic circuits. Also, the steady-state analyses have been accomplished by a new technique called Fourier series method. For a complete system consisting of converters, filters, and electric machines, the simulation is complicated if a frequency domain technique is used. This thesis introduces a better technique which decouples the system into subsystems and simulates it in the time domain. The design of power converters using optimization techniques is presented in this thesis. Finally, the theory of Variable Structured Systems has been applied to power converters. Sliding mode control for DC-DC and DC-AC power converters is introduced as a tool to accomplish desired characteristics.

  4. Monolithically integrated optoelectronic down-converter (MIOD)

    Science.gov (United States)

    Portnoi, Efrim L.; Venus, G. B.; Khazan, A. A.; Gorfinkel, Vera B.; Kompa, Guenter; Avrutin, Evgenii A.; Thayne, Iain G.; Barrow, David A.; Marsh, John H.

    1995-06-01

    Optoelectronic down-conversion of very high-frequency amplitude-modulated signals using a semiconductor laser simultaneously as a local oscillator and a mixer is proposed. Three possible constructions of a monolithically integrated down-converter are considered theoretically: a four-terminal semiconductor laser with dual pumping current/modal gain control, and both a passively mode-locked and a passively Q-switched semiconductor laser monolithically integrated with an electroabsorption or pumping current modulator. Experimental verification of the feasibility of the concept of down conversion in a laser diode is presented.

  5. Electrochemical aptasensor of cellular prion protein based on modified polypyrrole with redox dendrimers.

    Science.gov (United States)

    Miodek, A; Castillo, G; Hianik, T; Korri-Youssoufi, H

    2014-06-15

    This work consists of the development of an electrochemical aptasensor based on polyprrole modified with redox dendrimers, able to detect human cellular prions PrP(C) with high sensitivity. The gold surface was modified by conductive polypyrrole film coupled to polyamidoamine dendrimers of fourth generation (PAMAM G4) and ferrocenyl group as redox marker. The aptamers were immobilized on the surface via biotin/streptavidin chemistry. Electrochemical signal was detected by ferrocenyl group incorporated between dendrimers and aptamers layers. We demonstrated that the interaction between aptamer and prion protein led to variation in electrochemical signal of the ferrocenyl group. The kinetics parameters (diffusion coefficient D and heterogeneous constant transfer ket) calculated from electrochemical signals demonstrate that the variation in redox signal results from the lower diffusion process of ions during redox reaction after prion interaction due to bulk effect of larger protein. The association of redox dendrimers with conducting polypyrrole leads to high sensitivity of PrP(C) determination with detection limit of 0.8 pM, which is three orders of magnitude lower, compared to flat ferrocene-functionalized polypyrrole. Detection of PrP(C) in spiked blood plasma has been achieved and demonstrated a recovery up to 90%. Copyright © 2013 Elsevier B.V. All rights reserved.

  6. PWM DC/DC Converter

    OpenAIRE

    Chen, Juan

    2008-01-01

    This report is the result of a Master Thesis work done at Seaward Electronics Inc. in Beijing, China from June to December in 2007. The main goal for this thesis is to verify and improve the performance of Honey-PWM DC-DC converter, which has been fabricated by a standard 0.6um CMOS processes. The project was started with studying of Buck converter structure. After the understanding of the converter structure, the project goes in to the analyses phase for each sub-cells, including the theory,...

  7. Mouse redox histology using genetically encoded probes.

    Science.gov (United States)

    Fujikawa, Yuuta; Roma, Leticia P; Sobotta, Mirko C; Rose, Adam J; Diaz, Mauricio Berriel; Locatelli, Giuseppe; Breckwoldt, Michael O; Misgeld, Thomas; Kerschensteiner, Martin; Herzig, Stephan; Müller-Decker, Karin; Dick, Tobias P

    2016-03-15

    Mapping the in vivo distribution of endogenous oxidants in animal tissues is of substantial biomedical interest. Numerous health-related factors, including diet, physical activity, infection, aging, toxins, or pharmacological intervention, may cause redox changes. Tools are needed to pinpoint redox state changes to particular organs, tissues, cell types, and subcellular organelles. We describe a procedure that preserves the in vivo redox state of genetically encoded redox biosensors within histological tissue sections, thus providing "redox maps" for any tissue and comparison of interest. We demonstrate the utility of the technique by visualizing endogenous redox differences and changes in the context of tumor growth, inflammation, embryonic development, and nutrient starvation. Copyright © 2016, American Association for the Advancement of Science.

  8. Glutathione Redox Control of Asthma: From Molecular Mechanisms to Therapeutic Opportunities

    Science.gov (United States)

    Jones, Dean P.; Brown, Lou Ann S.

    2012-01-01

    Abstract Asthma is a chronic inflammatory disorder of the airways associated with airway hyper-responsiveness and airflow limitation in response to specific triggers. Whereas inflammation is important for tissue regeneration and wound healing, the profound and sustained inflammatory response associated with asthma may result in airway remodeling that involves smooth muscle hypertrophy, epithelial goblet-cell hyperplasia, and permanent deposition of airway extracellular matrix proteins. Although the specific mechanisms responsible for asthma are still being unraveled, free radicals such as reactive oxygen species and reactive nitrogen species are important mediators of airway tissue damage that are increased in subjects with asthma. There is also a growing body of literature implicating disturbances in oxidation/reduction (redox) reactions and impaired antioxidant defenses as a risk factor for asthma development and asthma severity. Ultimately, these redox-related perturbations result in a vicious cycle of airway inflammation and injury that is not always amenable to current asthma therapy, particularly in cases of severe asthma. This review will discuss disruptions of redox signaling and control in asthma with a focus on the thiol, glutathione, and reduced (thiol) form (GSH). First, GSH synthesis, GSH distribution, and GSH function and homeostasis are discussed. We then review the literature related to GSH redox balance in health and asthma, with an emphasis on human studies. Finally, therapeutic opportunities to restore the GSH redox balance in subjects with asthma are discussed. Antioxid. Redox Signal. 17, 375–408. PMID:22304503

  9. In Vivo Detection of Reactive Oxygen Species and Redox Status in Caenorhabditis elegans.

    Science.gov (United States)

    Braeckman, Bart P; Smolders, Arne; Back, Patricia; De Henau, Sasha

    2016-10-01

    Due to its large families of redox-active enzymes, genetic amenability, and complete transparency, the nematode Caenorhabditis elegans has the potential to become an important model for the in vivo study of redox biology. The recent development of several genetically encoded ratiometric reactive oxygen species (ROS) and redox sensors has revolutionized the quantification and precise localization of ROS and redox signals in living organisms. Only few exploratory studies have applied these sensors in C. elegans and undoubtedly much remains to be discovered in this model. As a follow-up to our recent findings that the C. elegans somatic gonad uses superoxide and hydrogen peroxide (H2O2) signals to communicate with the germline, we here analyze the patterns of H2O2 inside the C. elegans germline. Despite the advantages of genetically encoded ROS and redox sensors over classic chemical sensors, still several general as well as C. elegans-specific issues need to be addressed. The major concerns for the application of these sensors in C. elegans are (i) decreased vitality of some reporter strains, (ii) interference of autofluorescent compartments with the sensor signal, and (iii) the use of immobilization methods that do not influence the worm's redox physiology. We propose that several of the current issues may be solved by designing reporter strains carrying single copies of codon-optimized sensors. Preferably, these sensors should have their emission wavelengths in the red region, where autofluorescence is absent. Worm analysis could be optimized using four-dimensional ratiometric fluorescence microscopy of worms immobilized in microfluidic chips. Antioxid. Redox Signal. 25, 577-592.

  10. Engineering an NADPH/NADP+ Redox Biosensor in Yeast

    DEFF Research Database (Denmark)

    Zhang, Jie; Sonnenschein, Nikolaus; Pihl, Thomas Peter Boye

    2016-01-01

    and biotechnology. Still, there is a need for bioprospecting and engineering of more biosensors to enable real-time monitoring of specific cellular states and controlling downstream actuation. In this study, we report the engineering and application of a transcription factor-based NADPH/NADP+ redox biosensor...... NADPH deficiency by activation of NADPH regeneration. Finally, we couple the biosensor with an expression of dosage-sensitive genes (DSGs) and thereby create a novel tunable sensor-selector useful for synthetic selection of cells with higher NADPH/NADP+ ratios from mixed cell populations. We show...... that the combination of exploitation and rational engineering of native signaling components is applicable for diagnosis, regulation, and selection of cellular redox states....

  11. Membranes for Redox Flow Battery Applications

    OpenAIRE

    Maria Skyllas-Kazacos; Aishwarya Parasuraman; Tuti Mariana Lim; Suminto Winardi; Helen Prifti

    2012-01-01

    The need for large scale energy storage has become a priority to integrate renewable energy sources into the electricity grid. Redox flow batteries are considered the best option to store electricity from medium to large scale applications. However, the current high cost of redox flow batteries impedes the wide spread adoption of this technology. The membrane is a critical component of redox flow batteries as it determines the performance as well as the economic viability of the batteries. Th...

  12. Modelling and analysis of current-programmed ac/dc converters

    Science.gov (United States)

    Tymerski, R. P. E.; Daly, K. C.

    1985-03-01

    Current-programmed dc/dc converters operating at a fixed switching frequency are analyzed using state-space averaged modeling. For converters operating in the continuous conduction mode, general closed form expressions that describe the dynamic ac small signal characteristics of the converter are obtained. A reduced order model is used to derive the control current input-to-output voltage, audio susceptibility and output impedance small signal ac transfer functions for the ideal buck, boost, and buck-boost converters operating in the continuous conduction model. It is shown that state-space averaging can correctly predict instability on the buck converter. Current-programmed converters operating in the discontinuous conduction mode are addressed, showing that the transfer functions are represented by a finite pole and a zero at infinity. Instability is predicted for the buck converter when an external ramp is omitted and the output-to-input voltage ratio is greater than or equal to two-thirds.

  13. Redox conditions for mantle plumes

    Science.gov (United States)

    Heister, L. E.; Lesher, C. E.

    2005-12-01

    The vanadium to scandium ratio (V/Sc) for basalts from mid-ocean ridge (MOR) and arc environments has been proposed as a proxy for fO2 conditions during partial melting (e.g. [1] and [2]). Contrary to barometric measurements of the fO2 of primitive lavas, the V/Sc ratio of the upper mantle at mid-ocean ridges and arcs is similar, leading previous authors to propose that the upper mantle has uniform redox potential and is well-buffered. We have attempted to broaden the applicability of the V/Sc parameter to plume-influenced localities (both oceanic and continental), where mantle heterogeneities associated with recycled sediments, mafic crust, and metasomatized mantle, whether of shallow or deep origin, exist. We find that primitive basalts from the North Atlantic Igneous Province (NAIP), Hawaii (both the Loa and Kea trends), Deccan, Columbia River, and Siberian Traps show a range of V/Sc ratios that are generally higher (average ~9) than those for MOR (average ~ 6.7) or arc (average ~7) lavas. Based on forward polybaric decompression modeling, we attribute these differences to polybaric melting and melt segregation within the garnet stability field rather than the presence of a more oxidized mantle in plume-influenced settings. Like MORB, the V/Sc ratios for plume-influenced basalts can be accounted for by an oxidation state approximately one log unit below the Ni-NiO buffer (NNO-1). Our analysis suggests that source heterogeneities have little, if any, resolvable influence on mantle redox conditions, although they have significant influence on the trace element and isotopic composition of mantle-derived melts. We suggest that variations in the redox of erupted lavas is largely a function of shallow lithospheric processes rather than intrinsic to the mantle source, regardless of tectonic setting. [1] Li and Lee (2004) EPSL, [2] Lee et al. (2005) J. of Petrology

  14. Laser system with wavelength converter

    DEFF Research Database (Denmark)

    2012-01-01

    The present invention relates to an apparatus comprising a diode laser (10) providing radiation in a first wavelength interval, a radiation conversion unit (12) having an input and an output, the radiation converter configured to receive the radiation in the first wavelength interval from the diode...... laser at the input, the radiation conversion unit configured to convert the radiation in the first wavelength interval to radiation in a second wavelength interval and the output configured to output the converted radiation, the second wavelength interval having one end point outside the first...... wavelength interval. Further, the invention relates to a method of optically pumping a target laser (14) in a laser system, the laser system comprising a laser source providing radiation at a first frequency, the laser source being optically connected to an input of a frequency converter, the frequency...

  15. Time-to-digital converters

    CERN Document Server

    Henzler, Stephan

    2010-01-01

    This text covers the fundamentals of time-to-digital converters on analog and digital conversion principles. It includes a theoretical investigation into quantization, linearity, noise and variability, and it details a range of advanced TDC architectures.

  16. Optical Wavelength Converters Based on Four Wave Mixing in SOA-MZI Configuration

    Directory of Open Access Journals (Sweden)

    Rajni

    2016-01-01

    Full Text Available Wavelength converter plays an important role for increasing the capacity and flexibility of future broadcast network. This paper investigates the performance of a 10Gb/s the SOA based FWM wavelength converter. All performances are analyzed in terms of its shifted wavelength conversion efficiency, Q-factors and converted signal powers. The converters are modeled and simulated using Optisystem7 Software, by varying the probe signal wavelength and power. It was found that conversion efficiency and OSNR of the converted signal both decreased at large detuning wavelengths. Similarly, higher total SOA input powers worsened the conversion efficiency, but steadily improved the OSNR. FWM wavelength converter had the lowest conversion efficiency for CW sources.

  17. Supersymmetric mode converters

    Science.gov (United States)

    Heinrich, Matthias; Miri, Mohammad-Ali; Stützer, Simon; Nolte, Stefan; Szameit, Alexander; Christodoulides, Demetrios N.

    2015-08-01

    In recent years, the ever-increasing demand for high-capacity transmission systems has driven remarkable advances in technologies that encode information on an optical signal. Mode-division multiplexing makes use of individual modes supported by an optical waveguide as mutually orthogonal channels. The key requirement in this approach is the capability to selectively populate and extract specific modes. Optical supersymmetry (SUSY) has recently been proposed as a particularly elegant way to resolve this design challenge in a manner that is inherently scalable, and at the same time maintains compatibility with existing multiplexing strategies. Supersymmetric partners of multimode waveguides are characterized by the fact that they share all of their effective indices with the original waveguide. The crucial exception is the fundamental mode, which is absent from the spectrum of the partner waveguide. Here, we demonstrate experimentally how this global phase-matching property can be exploited for efficient mode conversion. Multimode structures and their superpartners are experimentally realized in coupled networks of femtosecond laser-written waveguides, and the corresponding light dynamics are directly observed by means of fluorescence microscopy. We show that SUSY transformations can readily facilitate the removal of the fundamental mode from multimode optical structures. In turn, hierarchical sequences of such SUSY partners naturally implement the conversion between modes of adjacent order. Our experiments illustrate just one of the many possibilities of how SUSY may serve as a building block for integrated mode-division multiplexing arrangements. Supersymmetric notions may enrich and expand integrated photonics by versatile optical components and desirable, yet previously unattainable, functionalities.

  18. Boron nitride converted carbon fiber

    Science.gov (United States)

    Rousseas, Michael; Mickelson, William; Zettl, Alexander K.

    2016-04-05

    This disclosure provides systems, methods, and apparatus related to boron nitride converted carbon fiber. In one aspect, a method may include the operations of providing boron oxide and carbon fiber, heating the boron oxide to melt the boron oxide and heating the carbon fiber, mixing a nitrogen-containing gas with boron oxide vapor from molten boron oxide, and converting at least a portion of the carbon fiber to boron nitride.

  19. Photoelectric converters with quantum coherence

    OpenAIRE

    Su, Shan-He; Sun, Chang-Pu; Li, Sheng-Wen; Chen, Jin-Can

    2016-01-01

    Photon impingement is capable of liberating electrons in electronic devices and driving the electron flux from the lower chemical potential to higher chemical potential. Previous studies hinted that the thermodynamic efficiency of a nano-sized photoelectric converter at maximum power is bounded by the Curzon-Ahlborn efficiency. In this study, we apply quantum effects to design a photoelectric converter based on a three-level quantum dot (QD) interacting with fermionic baths and photons. We sh...

  20. Radiation tolerant power converter controls

    Science.gov (United States)

    Todd, B.; Dinius, A.; King, Q.; Uznanski, S.

    2012-11-01

    The Large Hadron Collider (LHC) at the European Organisation for Nuclear Research (CERN) is the world's most powerful particle collider. The LHC has several thousand magnets, both warm and super-conducting, which are supplied with current by power converters. Each converter is controlled by a purpose-built electronic module called a Function Generator Controller (FGC). The FGC allows remote control of the power converter and forms the central part of a closed-loop control system where the power converter voltage is set, based on the converter output current and magnet-circuit characteristics. Some power converters and FGCs are located in areas which are exposed to beam-induced radiation. There are numerous radiation induced effects, some of which lead to a loss of control of the power converter, having a direct impact upon the accelerator's availability. Following the first long shut down (LS1), the LHC will be able to run with higher intensity beams and higher beam energy. This is expected to lead to significantly increased radiation induced effects in materials close to the accelerator, including the FGC. Recent radiation tests indicate that the current FGC would not be sufficiently reliable. A so-called FGClite is being designed to work reliably in the radiation environment in the post-LS1 era. This paper outlines the concepts of power converter controls for machines such as the LHC, introduces the risks related to radiation and a radiation tolerant project flow. The FGClite is then described, with its key concepts and challenges: aiming for high reliability in a radiation field.

  1. Transformerless dc-Isolated Converter

    Science.gov (United States)

    Rippel, Wally E.

    1987-01-01

    Efficient voltage converter employs capacitive instead of transformer coupling to provide dc isolation. Offers buck/boost operation, minimal filtering, and low parts count, with possible application in photovoltaic power inverters, power supplies and battery charges. In photovoltaic inverter circuit with transformerless converter, Q2, Q3, Q4, and Q5 form line-commutated inverter. Switching losses and stresses nil because switching performed when current is zero.

  2. Wave energy converter test application

    OpenAIRE

    Hottola, Niko

    2016-01-01

    This thesis was made for wave energy company Wello Oy. Given assignment was to find the suitable generator and frequency converter for a wave energy converter test application. The primary objective was to find a suitable generator for direct drive, in order to avoid the weight of the test application rising too high. In this thesis the possible machine types for test application are presented and what are their advenatages and disadvantages. In addition, the operation of the frequency co...

  3. Silencing of nicotinamide nucleotide transhydrogenase impairs cellular redox homeostasis and energy metabolism in PC12 cells.

    Science.gov (United States)

    Yin, Fei; Sancheti, Harsh; Cadenas, Enrique

    2012-03-01

    Mitochondrial NADPH generation is largely dependent on the inner-membrane nicotinamide nucleotide transhydrogenase (NNT), which catalyzes the reduction of NADP(+) to NADPH utilizing the proton gradient as the driving force and NADH as the electron donor. Small interfering RNA (siRNA) silencing of NNT in PC12 cells results in decreased cellular NADPH levels, altered redox status of the cell in terms of decreased GSH/GSSG ratios and increased H(2)O(2) levels, thus leading to an increased redox potential (a more oxidized redox state). NNT knockdown results in a decrease of oxidative phosphorylation while anaerobic glycolysis levels remain unchanged. Decreased oxidative phosphorylation was associated with a) inhibition of mitochondrial pyruvate dehydrogenase (PDH) and succinyl-CoA:3-oxoacid CoA transferase (SCOT) activity; b) reduction of NADH availability, c) decline of mitochondrial membrane potential, and d) decrease of ATP levels. Moreover, the alteration of redox status actually precedes the impairment of mitochondrial bioenergetics. A possible mechanism could be that the activation of the redox-sensitive c-Jun N-terminal kinase (JNK) and its translocation to the mitochondrion leads to the inhibition of PDH (upon phosphorylation) and induction of intrinsic apoptosis, resulting in decreased cell viability. This study supports the notion that oxidized cellular redox state and decline in cellular bioenergetics - as a consequence of NNT knockdown - cannot be viewed as independent events, but rather as an interdependent relationship coordinated by the mitochondrial energy-redox axis. Disruption of electron flux from fuel substrates to redox components due to NNT suppression induces not only mitochondrial dysfunction but also cellular disorders through redox-sensitive signaling.

  4. A redox-sensitive yellow fluorescent protein sensor for monitoring nuclear glutathione redox dynamics.

    Science.gov (United States)

    Banach-Latapy, Agata; Dardalhon, Michèle; Huang, Meng-Er

    2015-01-01

    Intracellular redox homeostasis is crucial for many cellular functions, but accurate measurements of cellular compartment-specific redox states remain technically challenging. Genetically encoded biosensors, including the glutathione-specific redox-sensitive yellow fluorescent protein (rxYFP), provide an alternative approach to overcome the limitations of conventional glutathione/glutathione disulfide (GSH/GSSG) redox measurements. In this chapter we describe methods to measure the nuclear rxYFP redox state in human cells by a redox Western blot technique. A nucleus-targeted rxYFP sensor can be used to sense nuclear steady-state and dynamic redox changes in response to oxidative stress. Complementary to existing redox sensors and conventional redox measurements, nucleus-targeted rxYFP sensors provide a novel tool for examining nuclear redox homeostasis in mammalian cells, permitting high-resolution readout of steady glutathione state and dynamics of redox changes. The technique described may be used with minimal variations to study the effects of stress conditions which lead to glutathione redox changes.

  5. BRIEF COMMUNICATIONS: Parametric noise in a nonlinear frequency up-converter of infrared signals by two-photon pumping of 3S-3D and 3S-5S transitions in sodium vapor

    Science.gov (United States)

    Galaĭchuk, Yu A.; Kudryashov, V. A.; Strizhevskiĭ, V. L.; Fontaniĭ, V. A.; Yashkir, Yu N.

    1985-07-01

    A systematic analysis was made of the spectral characteristics of resonance four-photon parametric conversion of infrared radiation as a result of two-photon resonance pumping of the 3S-3D and 3S-5S transitions in sodium and the influence of these characteristics on the threshold sensitivity of a parametric conversion detector was investigated. An experimental study was made of the characteristics of the noise radiation generated as a result of hyperparametric scattering. The results obtained can be used to select the optimal parameters of high-sensitivity detectors of weak infrared signals by parametric conversion in alkali metal vapors.

  6. Simplifying the circuit of Josephson parametric converters

    Science.gov (United States)

    Abdo, Baleegh; Brink, Markus; Chavez-Garcia, Jose; Keefe, George

    Josephson parametric converters (JPCs) are quantum-limited three-wave mixing devices that can play various important roles in quantum information processing in the microwave domain, including amplification of quantum signals, transduction of quantum information, remote entanglement of qubits, nonreciprocal amplification, and circulation of signals. However, the input-output and biasing circuit of a state-of-the-art JPC consists of bulky components, i.e. two commercial off-chip broadband 180-degree hybrids, four phase-matched short coax cables, and one superconducting magnetic coil. Such bulky hardware significantly hinders the integration of JPCs in scalable quantum computing architectures. In my talk, I will present ideas on how to simplify the JPC circuit and show preliminary experimental results

  7. The redox biology network in cancer pathophysiology and therapeutics

    Directory of Open Access Journals (Sweden)

    Gina Manda

    2015-08-01

    Full Text Available The review pinpoints operational concepts related to the redox biology network applied to the pathophysiology and therapeutics of solid tumors. A sophisticated network of intrinsic and extrinsic cues, integrated in the tumor niche, drives tumorigenesis and tumor progression. Critical mutations and distorted redox signaling pathways orchestrate pathologic events inside cancer cells, resulting in resistance to stress and death signals, aberrant proliferation and efficient repair mechanisms. Additionally, the complex inter-cellular crosstalk within the tumor niche, mediated by cytokines, redox-sensitive danger signals (HMGB1 and exosomes, under the pressure of multiple stresses (oxidative, inflammatory, metabolic, greatly contributes to the malignant phenotype. The tumor-associated inflammatory stress and its suppressive action on the anti-tumor immune response are highlighted. We further emphasize that ROS may act either as supporter or enemy of cancer cells, depending on the context. Oxidative stress-based therapies, such as radiotherapy and photodynamic therapy, take advantage of the cytotoxic face of ROS for killing tumor cells by a non-physiologically sudden, localized and intense oxidative burst. The type of tumor cell death elicited by these therapies is discussed. Therapy outcome depends on the differential sensitivity to oxidative stress of particular tumor cells, such as cancer stem cells, and therefore co-therapies that transiently down-regulate their intrinsic antioxidant system hold great promise. We draw attention on the consequences of the damage signals delivered by oxidative stress-injured cells to neighboring and distant cells, and emphasize the benefits of therapeutically triggered immunologic cell death in metastatic cancer. An integrative approach should be applied when designing therapeutic strategies in cancer, taking into consideration the mutational, metabolic, inflammatory and oxidative status of tumor cells, cellular

  8. Early Oscillation Detection Technique for Hybrid DC/DC Converters

    Science.gov (United States)

    Wang, Bright L.

    2011-01-01

    Oscillation or instability is a situation that must be avoided for reliable hybrid DC/DC converters. A real-time electronics measurement technique was developed to detect catastrophic oscillations at early stages for hybrid DC/DC converters. It is capable of identifying low-level oscillation and determining the degree of the oscillation at a unique frequency for every individual model of the converters without disturbing their normal operations. This technique is specially developed for space-used hybrid DC/DC converters, but it is also suitable for most of commercial and military switching-mode power supplies. This is a weak-electronic-signal detection technique to detect hybrid DC/DC converter oscillation presented as a specific noise signal at power input pins. It is based on principles of feedback control loop oscillation and RF signal modulations, and is realized by using signal power spectral analysis. On the power spectrum, a channel power amplitude at characteristic frequency (CPcf) and a channel power amplitude at switching frequency (CPsw) are chosen as oscillation level indicators. If the converter is stable, the CPcf is a very small pulse and the CPsw is a larger, clear, single pulse. At early stage of oscillation, the CPcf increases to a certain level and the CPsw shows a small pair of sideband pulses around it. If the converter oscillates, the CPcf reaches to a higher level and the CPsw shows more high-level sideband pulses. A comprehensive stability index (CSI) is adopted as a quantitative measure to accurately assign a degree of stability to a specific DC/DC converter. The CSI is a ratio of normal and abnormal power spectral density, and can be calculated using specified and measured CPcf and CPsw data. The novel and unique feature of this technique is the use of power channel amplitudes at characteristic frequency and switching frequency to evaluate stability and identify oscillations at an early stage without interfering with a DC/DC converter s

  9. Applied signal processing concepts, circuits, and systems

    CERN Document Server

    Hamdy, Nadder

    2008-01-01

    Introduction What are Signals? Signal parameters Why Signal processing? Analog vs. Digital Signal processing Practical Signal processing Systems Analog Signal Processing Amplitude Shaping Frequency Spectrum Shaping Phase Errors Correction Waveform Generation Analog Filter Design Describing Equations Design Procedures Filter Specifications Approximations to the Ideal Response Realization Practical RC-Filters Design Switched Capacitor Filter Realization Design examples Data Converters Introduction A typical DSP System Specifications of Data Converters Sampling Samp

  10. Forback DC-to-DC converter

    Science.gov (United States)

    Lukemire, Alan T.

    1995-05-01

    A pulse-width modulated DC-to-DC power converter including a first inductor, i.e. a transformer or an equivalent fixed inductor equal to the inductance of the secondary winding of the transformer, coupled across a source of DC input voltage via a transistor switch which is rendered alternately conductive (ON) and nonconductive (OFF) in accordance with a signal from a feedback control circuit is described. A first capacitor capacitively couples one side of the first inductor to a second inductor which is connected to a second capacitor which is coupled to the other side of the first inductor. A circuit load shunts the second capacitor. A semiconductor diode is additionally coupled from a common circuit connection between the first capacitor and the second inductor to the other side of the first inductor. A current sense transformer generating a current feedback signal for the switch control circuit is directly coupled in series with the other side of the first inductor so that the first capacitor, the second inductor and the current sense transformer are connected in series through the first inductor. The inductance values of the first and second inductors, moreover, are made identical. Such a converter topology results in a simultaneous voltsecond balance in the first inductance and ampere-second balance in the current sense transformer.

  11. Forback DC-to-DC converter

    Science.gov (United States)

    Lukemire, Alan T. (Inventor)

    1993-01-01

    A pulse-width modulated DC-to-DC power converter including a first inductor, i.e. a transformer or an equivalent fixed inductor equal to the inductance of the secondary winding of the transformer, coupled across a source of DC input voltage via a transistor switch which is rendered alternately conductive (ON) and nonconductive (OFF) in accordance with a signal from a feedback control circuit is described. A first capacitor capacitively couples one side of the first inductor to a second inductor which is connected to a second capacitor which is coupled to the other side of the first inductor. A circuit load shunts the second capacitor. A semiconductor diode is additionally coupled from a common circuit connection between the first capacitor and the second inductor to the other side of the first inductor. A current sense transformer generating a current feedback signal for the switch control circuit is directly coupled in series with the other side of the first inductor so that the first capacitor, the second inductor and the current sense transformer are connected in series through the first inductor. The inductance values of the first and second inductors, moreover, are made identical. Such a converter topology results in a simultaneous voltsecond balance in the first inductance and ampere-second balance in the current sense transformer.

  12. Redox pioneer: professor Barry Halliwell.

    Science.gov (United States)

    Pervaiz, Shazib

    2011-05-01

    Professor Barry Halliwell is recognized as a Redox Pioneer because he has published eight articles on redox biology that have been each cited more than 1000 times, and 158 articles that have been each cited more than 100 times. His contributions go back as far as 1976, when he was involved in elucidation of the Foyer-Halliwell-Asada cycle, an efficient mechanism for preventing oxidative damage to chloroplasts. His subsequent work established the important role of iron and zinc in free radical reactions and their relevance to human pathologies. Professor Halliwell is also a leader in developing novel methodology for detecting free radical intermediates in vivo, and his contributions to our knowledge of reactive nitrogen species are highly significant. His sustained excellence won him the top-cited scientist award in the United Kingdom in biomedical sciences in 1999, and in 2003 he was recognized as a highly cited scientist by Institute of Scientific Information (ISI) for work on plant antioxidants, and the same year ranked 28 out of 5494 biochemists/biologists for scientific impact. Two pieces of his scholarly work have been listed as Citation Classics by ISI, and in 2007 his laboratory was ranked number 1 worldwide based on highest citation score in research on free radicals.

  13. Systematic risk variations (beta convertible debenture brazilian companies

    Directory of Open Access Journals (Sweden)

    Renata Drumond Pinto Coelho Antonino

    2010-01-01

    Full Text Available purpose of this article is to analyze the impact of issuing convertible debentures on the systematic risk of Brazilian companies. Some applied researches in the U.S. capital market (STEIN, 1992; LEWIS et al, 2002; RAI, 2005 indicate that convertible debentures may be used as an alternative financing source when adverse selection problem makes stock issuing unattractive financing source. The analysis of Brazilian companies that issued convertible debentures recorded in the period from 1998 to 2006 and that presented liquidity on the market indicated that variation in beta, on average, is positive. These results are coherent with the signaling hypothesis and with the absence of convertible debenture issuing in 2005 and 2006 on the Brazilian market. They also may be related to the precarious financial situation of issuing companies, observed by the analysis of some financial indicators in year of issue and in two pre- e post-issuing years.

  14. Step-Up DC-DC Power Converter

    DEFF Research Database (Denmark)

    2015-01-01

    The present invention relates to a step-up DC-DC power converter which comprises a primary side circuit and a secondary side circuit coupled through a galvanic isolation barrier. The primary side circuit comprises a positive and a negative input terminal for receipt of an input voltage and an input...... being charged from the input voltage and discharged to the output capacitor through the galvanic isolation barrier in accordance with a switch control signal to produce the converter output voltage. The step-up DC-DC power converter comprises an electrical short-circuit connection across the galvanic...... capacitor coupled between the positive and negative input terminals and the secondary side circuit comprises an output capacitor chargeable to a converter output voltage between a first positive electrode and a second negative electrode. A switched energy storage network is configured for alternatingly...

  15. A Novel High Gain DC-DC Step up Converter

    Directory of Open Access Journals (Sweden)

    M. Al Mamun

    2016-07-01

    Full Text Available High gain dc-dc converters are widely used to maximize the energy harvest for renewable energy systems, for example, photovoltaic systems and fuel cell. Conventional boost converters usually operates at extreme duty cycle to obtain high voltage gain. Operation at extreme duty cycle leads to reverse recovery problem at the switches, high conduction loss, electromagnetic interference etc. This paper proposes a very high gain dc-dc step up converter operating at very low duty cycle (i.e. duty cycle <0.5. The additional advantage of the proposed converter is that a single control signal is used for the switches which reduces the operation complexity. The steady-state theoretical analysis described in this paper is finally verified by simulation results

  16. Radiation effects on DC-DC Converters

    Science.gov (United States)

    Zhang, Dexin; Attia, John O.; Kankam, Mark D. (Technical Monitor)

    2000-01-01

    DC-DC switching converters are circuits that can be used to convert a DC voltage of one value to another by switching action. They are increasing being used in space systems. Most of the popular DC-DC switching converters utilize power MOSFETs. However power MOSFETs, when subjected to radiation, are susceptible to degradation of device characteristics or catastrophic failure. This work focuses on the effects of total ionizing dose on converter performance. Four fundamental switching converters (buck converter, buck-boost converter, cuk converter, and flyback converter) were built using Harris IRF250 power MOSFETs. These converters were designed for converting an input of 60 volts to an output of about 12 volts with a switching frequency of 100 kHz. The four converters were irradiated with a Co-60 gamma source at dose rate of 217 rad/min. The performances of the four converters were examined during the exposure to the radiation. The experimental results show that the output voltage of the converters increases as total dose increases. However, the increases of the output voltage were different for the four different converters, with the buck converter and cuk converter the highest and the flyback converter the lowest. We observed significant increases in output voltage for cuk converter at a total dose of 24 krad (si).

  17. Binary/BCD-to-ASCII data converter

    Science.gov (United States)

    Miller, A. J.

    1977-01-01

    Converter inputs multiple precision binary words, converts data to multiple precision binary-coded decimal, and routes data back to computer. Converter base can be readily changed without need for new gate structure for each base changeover.

  18. The application of standardized control and interface circuits to three dc to dc power converters.

    Science.gov (United States)

    Yu, Y.; Biess, J. J.; Schoenfeld, A. D.; Lalli, V. R.

    1973-01-01

    Standardized control and interface circuits were applied to the three most commonly used dc to dc converters: the buck-boost converter, the series-switching buck regulator, and the pulse-modulated parallel inverter. The two-loop ASDTIC regulation control concept was implemented by using a common analog control signal processor and a novel digital control signal processor. This resulted in control circuit standardization and superior static and dynamic performance of the three dc-to-dc converters. Power components stress control, through active peak current limiting and recovery of switching losses, was applied to enhance reliability and converter efficiency.

  19. Modelling and Simulation of Variable Frequency Synchronous DC-DC Buck Converter

    Directory of Open Access Journals (Sweden)

    Jeya Selvan Renius

    2014-10-01

    Full Text Available In this paper, novel small-signal averaged models for dc–dc converter operating at variable switching frequency are derived. This is achieved by separately considering the on-time and the off-time of the switching period. The derivation is shown in detail for a synchronous buck converter. The Enhanced Small Signal (ESSA Model is derived for the synchronous buck converter. The equivalent series inductance (ESL is also considered in this modelling. The buck converter model is also simulated in MATLAB and the result is also presented.

  20. Characterization of redox conditions in pollution plumes

    DEFF Research Database (Denmark)

    Christensen, Thomas Højlund; Bjerg, Poul Løgstrup; Banwart, Steven A.

    2000-01-01

    Evalution of redox conditions in groundwater pollution plumes is often a prerequisite for understanding the behviour of the pollutants in the plume and for selecting remediation approaches. Measuring of redox conditions in pollution plumes is, however, a fairly recent issue and yet relative few...

  1. Redox characteristics of the eukaryotic cytosol

    DEFF Research Database (Denmark)

    López-Mirabal, H Reynaldo; Winther, Jakob R

    2007-01-01

    (ROS) and glutathionylated proteins are maintained at very low levels. In the present review, recent progress in the understanding of the cytosolic thiol-disulfide redox metabolism and novel analytical approaches to studying cytosolic redox properties are discussed. We will focus on the yeast model...

  2. Characterization of redox proteins using electrochemical methods.

    NARCIS (Netherlands)

    Verhagen, M.F.J.M.

    1995-01-01

    The use of electrochemical techniques in combination with proteins started approximately a decade ago and has since then developed into a powerfull technique for the study of small redox proteins. In addition to the determination of redox potentials, electrochemistry can be used to obtain informatio

  3. Characterization of redox conditions in pollution plumes

    DEFF Research Database (Denmark)

    Christensen, Thomas Højlund; Bjerg, Poul Løgstrup; Banwart, Steven A.

    2000-01-01

    Evalution of redox conditions in groundwater pollution plumes is often a prerequisite for understanding the behviour of the pollutants in the plume and for selecting remediation approaches. Measuring of redox conditions in pollution plumes is, however, a fairly recent issue and yet relative few...

  4. General-purpose fuzzy controller for dc-dc converters

    Energy Technology Data Exchange (ETDEWEB)

    Mattavelli, P.; Rossetto, L.; Spiazzi, G.; Tenti, P. [Univ. of Padova (Italy)

    1997-01-01

    In this paper, a general-purpose fuzzy controller for dc-dc converters is investigated. Based on a qualitative description of the system to be controlled, fuzzy controllers are capable of good performances, even for those systems where linear control techniques fail, e.g., when a mathematical description is not available or is in the presence of wide parameter variations. The presented approach is general and can be applied to any dc-dc converter topologies. Controller implementation is relatively simple and can guarantee a small-signal response as fast and stable as other standard regulators and an improved large-signal response. Simulation results of Buck-Boost and Sepic converters show control potentialities.

  5. Design and analysis of electrogas(hydro)dynamic converters with electrohydrodynamic jet turbulization

    Energy Technology Data Exchange (ETDEWEB)

    Nagornyi, V.S.

    1986-09-01

    The principles of the design of electropneumatic and electrohydraulic converters with the turbulization of a submerged jet by a directional ion flux in an electric field are examined. A mathematical model is developed for calculating the static characteristics of electrohydrodynamic (EHD) converters of signal energy. It is shown that the same design base can be used for the EHD conversion of an electric signal to either a pneumatic or a hydraulic signal. 7 references.

  6. PWM Converter Power Density Barriers

    Science.gov (United States)

    Kolar, Johann W.; Drofenik, Uwe; Biela, Juergen; Heldwein, Marcelo; Ertl, Hans; Friedli, Thomas; Round, Simon

    Power density of power electronic converters has roughly doubled every 10 years since 1970. Behind this trajectory is the continuous advancement of power semiconductor devices, which has increased the converter switching frequencies by a factor of 10 every decade. However, today's cooling concepts and passive components are major barriers for a continuation of this trend. To identify such technological barriers, this paper investigates the volume of the cooling system and passive components as a function of the switching frequency for power electronic converters and determines the switching frequency that minimizes the total volume. A power density limit of 28kW/dm3 at 300kHz is calculated for an isolated DC-DC converter, 44kW/dm3 at 820kHz for a three-phase unity power factor PWM rectifier, and 26kW/dm3 at 21kHz for a sparse matrix converter. For single-phase AC-DC conversion a general limit of 35kW/dm3 results from the DC link capacitor. These power density limits highlight the need to broaden the scope of power electronics research to include cooling systems, high frequency electromagnetics, interconnection and packaging technology, and multi-domain modelling and simulation to ensure further advancement along the power density trajectory.

  7. Wine consumption and intestinal redox homeostasis

    Science.gov (United States)

    Biasi, Fiorella; Deiana, Monica; Guina, Tina; Gamba, Paola; Leonarduzzi, Gabriella; Poli, Giuseppe

    2014-01-01

    Regular consumption of moderate doses of wine is an integral part of the Mediterranean diet, which has long been considered to provide remarkable health benefits. Wine׳s beneficial effect has been attributed principally to its non-alcoholic portion, which has antioxidant properties, and contains a wide variety of phenolics, generally called polyphenols. Wine phenolics may prevent or delay the progression of intestinal diseases characterized by oxidative stress and inflammation, especially because they reach higher concentrations in the gut than in other tissues. They act as both free radical scavengers and modulators of specific inflammation-related genes involved in cellular redox signaling. In addition, the importance of wine polyphenols has recently been stressed for their ability to act as prebiotics and antimicrobial agents. Wine components have been proposed as an alternative natural approach to prevent or treat inflammatory bowel diseases. The difficulty remains to distinguish whether these positive properties are due only to polyphenols in wine or also to the alcohol intake, since many studies have reported ethanol to possess various beneficial effects. Our knowledge of the use of wine components in managing human intestinal inflammatory diseases is still quite limited, and further clinical studies may afford more solid evidence of their beneficial effects. PMID:25009781

  8. The Yin and Yang of redox regulation.

    Science.gov (United States)

    Olsen, Lars Folke; Issinger, Olaf-Georg; Guerra, Barbara

    2013-01-01

    Mammalian cells produce reactive oxygen and nitrogen species (ROS/RNOS) in response to an oxidative environment. Powerful antioxidant mechanisms have been developed in order to avoid oxidative stress by contributing to the maintenance of redox homeostasis. Traditionally, accumulation of ROS/RNOS is considered deleterious for cells as it can lead to loss of cellular function, aging, and cell death. Consequently, ROS/RNOS imbalance has been implicated in the etiology and/or progression of numerous pathologies such as cardiovascular diseases, inflammation, and cancer. An interesting concept that has emerged more recently is that not only have cells developed efficient systems to cope with ROS/RNOS accumulation but they have also learned to profit of them under certain circumstances. This notion is supported by data showing that ROS/RNOS can act as signaling molecules affecting the function and activity of a multiplicity of protein kinases and phosphatases controlling cellular homeostasis. This review does not provide an exhaustive overview of molecular mechanisms linked to ROS/RNOS generation and processing but includes relevant examples highlighting the dichotomic nature of these small molecules and the multitude of effects elicited by their accumulation. This aspect of ROS/RNOS ought to be taken into account particularly in novel therapeutic setups that aim to achieve high efficiency and minimal or no side effects.

  9. Wine consumption and intestinal redox homeostasis.

    Science.gov (United States)

    Biasi, Fiorella; Deiana, Monica; Guina, Tina; Gamba, Paola; Leonarduzzi, Gabriella; Poli, Giuseppe

    2014-01-01

    Regular consumption of moderate doses of wine is an integral part of the Mediterranean diet, which has long been considered to provide remarkable health benefits. Wine's beneficial effect has been attributed principally to its non-alcoholic portion, which has antioxidant properties, and contains a wide variety of phenolics, generally called polyphenols. Wine phenolics may prevent or delay the progression of intestinal diseases characterized by oxidative stress and inflammation, especially because they reach higher concentrations in the gut than in other tissues. They act as both free radical scavengers and modulators of specific inflammation-related genes involved in cellular redox signaling. In addition, the importance of wine polyphenols has recently been stressed for their ability to act as prebiotics and antimicrobial agents. Wine components have been proposed as an alternative natural approach to prevent or treat inflammatory bowel diseases. The difficulty remains to distinguish whether these positive properties are due only to polyphenols in wine or also to the alcohol intake, since many studies have reported ethanol to possess various beneficial effects. Our knowledge of the use of wine components in managing human intestinal inflammatory diseases is still quite limited, and further clinical studies may afford more solid evidence of their beneficial effects.

  10. Creation of bioorthogonal redox systems depending on nicotinamide flucytosine dinucleotide.

    Science.gov (United States)

    Ji, Debin; Wang, Lei; Hou, Shuhua; Liu, Wujun; Wang, Jinxia; Wang, Qian; Zhao, Zongbao K

    2011-12-28

    Many enzymes catalyzing biological redox chemistry depend on the omnipresent cofactor, nicotinamide adenine dinucleotide (NAD). NAD is also involved in various nonredox processes. It remains challenging to disconnect one particular NAD-dependent reaction from all others. Here we present a bioorthogonal system that catalyzes the oxidative decarboxylation of l-malate with a dedicated abiotic cofactor, nicotinamide flucytosine dinucleotide (NFCD). By screening the multisite saturated mutagenesis libraries of the NAD-dependent malic enzyme (ME), we identified the mutant ME-L310R/Q401C, which showed excellent activity with NFCD, yet marginal activity with NAD. We found that another synthetic cofactor, nicotinamide cytosine dinucleotide (NCD), also displayed similar activity with the ME mutants. Inspired by these observations, we mutated d-lactate dehydrogenase (DLDH) and malate dehydrogenase (MDH) to DLDH-V152R and MDH-L6R, respectively, and both mutants showed fully active with NFCD. When coupled with DLDH-V152R, ME-L310R/Q401C required only a catalytic amount of NFCD to convert l-malate. Our results opened the window to engineer bioorthogonal redox systems for a wide variety of applications in systems biology and synthetic biology.

  11. Error Models of the Analog to Digital Converters

    OpenAIRE

    Michaeli Linus; Šaliga Ján

    2014-01-01

    Error models of the Analog to Digital Converters describe metrological properties of the signal conversion from analog to digital domain in a concise form using few dominant error parameters. Knowledge of the error models allows the end user to provide fast testing in the crucial points of the full input signal range and to use identified error models for post correction in the digital domain. The imperfections of the internal ADC structure determine the error characteristics represented by t...

  12. Mechanisms for redox-regulation of protein kinase C

    Directory of Open Access Journals (Sweden)

    Susan F. Steinberg

    2015-06-01

    Full Text Available Protein kinase C (PKC is comprised of a family of signal-regulated enzymes that play pleiotropic roles in the control of many physiological and pathological responses. PKC isoforms are traditionally viewed as allosterically-activated enzymes that are recruited to membranes by growth factor receptor-generated lipid cofactors. An inherent assumption of this conventional model of PKC isoform activation is that PKCs act exclusively at membrane-delimited substrates and that PKC catalytic activity is an inherent property of each enzyme that is not altered by the activation process. This traditional model of PKC activation does not adequately explain the many well-documented actions of PKC enzymes in mitochondrial, nuclear, and cardiac sarcomeric (non-sarcolemmal subcellular compartments. Recent studies address this dilemma by identifying stimulus-specific differences in the mechanisms for PKC isoform activation during growth factor activation versus oxidative stress. This review discusses a number of noncanonical redox-triggered mechanisms that can alter the catalytic properties and subcellular compartmentation patterns of PKC enzymes. While some redox-activated mechanisms act at structural determinants that are common to all PKCs, the redox-dependent mechanism for PKCδ activation requires Src-dependent tyrosine phosphorylation of a unique phosphorylation motif on this enzyme and is isoform specific. Since oxidative stress contributes to pathogenesis of a wide range of clinical disorders, these stimulus specific differences in the controls and consequences of PKC activation have important implications for the design and evaluation of PKC-targeted therapeutics.

  13. Oxidative Stress, Redox Regulation and Diseases of Cellular Differentiation

    Science.gov (United States)

    Ye, Zhi-Wei; Zhang, Jie; Townsend, Danyelle M.; Tew, Kenneth D.

    2015-01-01

    Background Within cells, there is a narrow concentration threshold that governs whether reactive oxygen species (ROS) induce toxicity or act as second messengers. Scope of review We discuss current understanding of how ROS arise, facilitate cell signaling, cause toxicities and disease related to abnormal cell differentiation and those (primarily) sulfur based pathways that provide nucleophilicity to offset these effects. Primary conclusions Cellular redox homeostasis mediates a plethora of cellular pathways that determine life and death events. For example, ROS intersect with GSH based enzyme pathways to influence cell differentiation, a process integral to normal hematopoiesis, but also affecting a number of diverse cell differentiation related human diseases. Recent attempts to manage such pathologies have focused on intervening in some of these pathways, with the consequence that differentiation therapy targeting redox homeostasis has provided a platform for drug discovery and development. General Significance The balance between electrophilic oxidative stress and protective biomolecular nucleophiles predisposes the evolution of modern life forms. Imbalances of the two can produce aberrant redox homeostasis with resultant pathologies. Understanding the pathways involved provides opportunities to consider interventional strategies. PMID:25445706

  14. A Novel All-Optical Analog-to-Digital Converter

    Institute of Scientific and Technical Information of China (English)

    Xiaobo; Hou; Afshin; Daryoush; Warren; Rosen

    2003-01-01

    An all-optical analog-to-digital converter capable of sampling at 50GS/s is described. The ADC works in the frequency domain. The RF signal is sampled by electro-optically steerable gratings and quantized by a set of detectors with scalable apertures.

  15. On and off controlled resonant dc-dc power converter

    DEFF Research Database (Denmark)

    2015-01-01

    network in a first switch state and select a second impedance characteristic of the resonant network in a second switch state. An output voltage or current control circuit is configured to adjust the converter output voltage and/or current by activating and interrupting the first switch control signal...

  16. Parallel-to-serial biphase-data converter

    Science.gov (United States)

    Truelove, R. D.

    1968-01-01

    Data converter produces a serial biphase output signal from parallel input data. Alternate bits are loaded into a shift register in complement form so that the bits appear at the end of the shift register in a true-complement form sequence.

  17. Mismatch-Shaping Serial Digital-to-Analog Converter

    DEFF Research Database (Denmark)

    Steensgaard-Madsen, Jesper; Moon, Un-Ku; Temes, Gabor C.

    1999-01-01

    A simple but accurate pseudo-passive mismatch-shaping D/A converter is described. A digital state machine is used to control the switching sequence of a symmetric two-capacitor network that performs the D/A conversion. The error caused by capacitor mismatch is uncorrelated with the input signal a...

  18. Post combustion in converter steelmaking

    Energy Technology Data Exchange (ETDEWEB)

    Oghbasilasie, H.; Holappa, L.

    1997-12-31

    The purpose of this work is to study the fundamentals of post combustion and the effect of different process parameters on the post combustion ratio (PCR) and heat transfer efficiency (HTE) in converter steelmaking process. The PCR and HTE have been determined under normal operating conditions. Trials assessed the effect of lance height, vessel volume, foaming slag and pellet additions on PCR and HTE. Based on enthalpy considerations, post combustion of CO gas is regarded as one of the most effective means of increasing the heat supply to the BOP. The thermodynamic study of gas-metal-slag reactions gives the limiting conditions for post combustion inside the converter reactor. Different process parameters influencing both thermodynamic equilibria and kinetic conditions can greatly affect the post combustion ratio. Different features of converter processes as well smelting reduction processes utilizing post combustion have been reviewed. (orig.) SULA 2 Research Programme; 26 refs.

  19. Stirling Converters For Solar Power

    Science.gov (United States)

    Shaltens, Richard K.; Schreiber, Jeffrey G.

    1993-01-01

    Two designs expected to meet long-term goals for performance and cost. Proposed for advanced systems to convert solar thermal power to electrical power. Each system, designed to operate with 11-m-diameter paraboloidal reflector, includes solar-energy receiver, liquid-metal heat-transport subsystem, free-piston Stirling engine, cooling subsystem, alternator or generator coupled directly or indirectly to commercial electric-power system, and control and power-conditioning circuitry. System converts approximately 75 kW of input solar thermal power falling on collector to about 25 kW of output electrical power.

  20. Simplified design of data converters

    CERN Document Server

    Lenk, John

    1997-01-01

    Simplified Design of Data Converters shows how to design and experiment with data converters, both analog-to-digital and digital to analog. The design approach here is the same one used in all of John Lenk's best-selling books on simplified and practical design. Throughout the book, design problems start with guidelines for selecting all components on a trial-value basis, assuming a specific design goal and set of conditions. Then, using the guideline values in experimental circuits, the desired results are produced by varying the experimental component values, if needed.If you are a w

  1. Redox- and non-redox-metal-induced formation of free radicals and their role in human disease.

    Science.gov (United States)

    Valko, Marian; Jomova, Klaudia; Rhodes, Christopher J; Kuča, Kamil; Musílek, Kamil

    2016-01-01

    -tocopherol, glutathione (GSH), carotenoids, flavonoids and antioxidant enzymes which include SOD, catalase and glutathione peroxidase. This review summarizes current views regarding the role of redox-active/inactive metal-induced formation of ROS, and modifications to biomolecules in human disease such as cancer, cardiovascular disease, metabolic disease, Alzheimer's disease, Parkinson's disease, renal disease, blood disorders and other disease. The involvement of metals in DNA repair mechanisms, tumor suppressor functions and interference with signal transduction pathways are also discussed.

  2. Design and Control for the Buck-Boost Converter Combining 1-Plus-D Converter and Synchronous Rectified Buck Converters

    OpenAIRE

    2015-01-01

    In this paper, a design and control for the buck-boost converter, i.e., 1-plus-D converter with a positive output voltage, is presented, which combines the 1-plus-D converter and the synchronous rectified (SR) buck converter. By doing so, the problem in voltage bucking of the 1-plus-D converter can be solved, thereby increasing the application capability of the 1-plus-D converter. Since such a converter operates in continuous conduction mode inherently, it possesses the nonpulsating output cu...

  3. Thioredoxin-mediated redox regulation of resistance to endocrine therapy in breast cancer.

    Science.gov (United States)

    Penney, Rosalind Brigham; Roy, Deodutta

    2013-08-01

    Resistance to endocrine therapy in breast carcinogenesis due to the redox regulation of the signal transduction system by reactive oxygen species (ROS) is the subject of this review article. Both antiestrogens and aromatase inhibitors are thought to prevent cancer through modulating the estrogen receptor function, but other mechanisms cannot be ruled out as these compounds also block metabolism and redox cycling of estrogen and are free radical scavengers. Endocrine therapeutic agents, such as, tamoxifen and other antiestrogens, and the aromatase inhibitor, exemestane, are capable of producing ROS. Aggressive breast cancer cells have high oxidative stress and chronic treatment with exemestane, fulvestrant or tamoxifen may add additional ROS stress. Breast cancer cells receiving long-term antiestrogen treatment appear to adapt to this increased persistent level of ROS. This, in turn, may lead to the disruption of reversible redox signaling that involves redox-sensitive phosphatases, protein kinases, such as, ERK and AKT, and transcription factors, such as, AP-1, NRF-1 and NF-κB. Thioredoxin modulates the expression of estrogen responsive genes through modulating the production of H2O2 in breast cancer cells. Overexpressing thioredoxine reductase 2 and reducing oxidized thioredoxin restores tamoxifen sensitivity to previously resistant breast cancer cells. In summary, it appears that resistance to endocrine therapy may be mediated, in part, by ROS-mediated dysregulation of both estrogen-dependent and estrogen-independent redox-sensitive signaling pathways. Further studies are needed to define the mechanism of action of thioredoxin modifiers, and their effect on the redox regulation that contributes to restoring the antiestrogen-mediated signal transduction system and growth inhibitory action.

  4. Periodic Exposure of Keratinocytes to Cold Physical Plasma: An In Vitro Model for Redox-Related Diseases of the Skin

    Directory of Open Access Journals (Sweden)

    Anke Schmidt

    2016-01-01

    Full Text Available Oxidative stress illustrates an imbalance between radical formation and removal. Frequent redox stress is critically involved in many human pathologies including cancer, psoriasis, and chronic wounds. However, reactive species pursue a dual role being involved in signaling on the one hand and oxidative damage on the other. Using a HaCaT keratinocyte cell culture model, we investigated redox regulation and inflammation to periodic, low-dose oxidative stress after two, six, eight, ten, and twelve weeks. Chronic redox stress was generated by recurrent incubation with cold physical plasma-treated cell culture medium. Using transcriptome microarray technology, we identified both acute ROS-stress responses as well as numerous adaptions after several weeks of redox challenge. We determined a differential expression (2-fold, FDR < 0.01, p<0.05 of 260 genes that function in inflammation and redox homeostasis, such as cytokines (e.g., IL-6, IL-8, and IL-10, growth factors (e.g., CSF2, FGF, and IGF-2, and antioxidant enzymes (e.g., HMOX, NQO1, GPX, and PRDX. Apoptotic signaling was affected rather modestly, especially in p53 downstream targets (e.g., BCL2, BBC3, and GADD45. Strikingly, the cell-protective heat shock protein HSP27 was strongly upregulated (p<0.001. These results suggested cellular adaptions to frequent redox stress and may help to better understand the inflammatory responses in redox-related diseases.

  5. Signal sampling circuit

    NARCIS (Netherlands)

    Louwsma, S.M.; Vertregt, Maarten

    2010-01-01

    A sampling circuit for sampling a signal is disclosed. The sampling circuit comprises a plurality of sampling channels adapted to sample the signal in time-multiplexed fashion, each sampling channel comprising a respective track-and-hold circuit connected to a respective analogue to digital converte

  6. Signal sampling circuit

    NARCIS (Netherlands)

    Louwsma, S.M.; Vertregt, Maarten

    2011-01-01

    A sampling circuit for sampling a signal is disclosed. The sampling circuit comprises a plurality of sampling channels adapted to sample the signal in time-multiplexed fashion, each sampling channel comprising a respective track-and-hold circuit connected to a respective analogue to digital converte

  7. Signal sampling circuit

    NARCIS (Netherlands)

    Louwsma, Simon Minze; Vertregt, Maarten

    2011-01-01

    A sampling circuit for sampling a signal is disclosed. The sampling circuit comprises a plurality of sampling channels adapted to sample the signal in time-multiplexed fashion, each sampling channel comprising a respective track-and-hold circuit connected to a respective analogue to digital converte

  8. Signal sampling circuit

    NARCIS (Netherlands)

    Louwsma, Simon Minze; Vertregt, Maarten

    2010-01-01

    A sampling circuit for sampling a signal is disclosed. The sampling circuit comprises a plurality of sampling channels adapted to sample the signal in time-multiplexed fashion, each sampling channel comprising a respective track-and-hold circuit connected to a respective analogue to digital converte

  9. AC-DC PFC Converter Using Combination of Flyback Converter and Full-bridge DC-DC Converter

    Directory of Open Access Journals (Sweden)

    Moh. Zaenal Efendi

    2014-06-01

    Full Text Available This paper presents a combination of power factor correction converter using Flyback converter and Full-bridge dc-dc converter in series connection. Flyback converter is operated in discontinuous conduction mode so that it can serve as a power factor correction converter and meanwhile Full-bridge dc-dc converter is used for dc regulator. This converter system is designed to produce a 86 Volt of output voltage and 2 A of output current. Both simulation and experiment results show that the power factor of this converter achieves up to 0.99 and meets harmonic standard of IEC61000-3-2. Keywords: Flyback Converter, Full-bridge DC-DC Converter, Power Factor Correction.

  10. State space analysis of boost DC/DC converter with voltage mode control

    Science.gov (United States)

    Shenoy, K. Latha; Nayak, C. Gurudas; Mandi, Rajashekar P.

    2017-07-01

    The boost converter belongs to the family of indirect energy transfer converters. The inductor stores energy during switch on and the output capacitor deliver power to the load. During switch off condition, the stored inductive energy appears in series with the input source and supply the output. The paper deals with the small signal analysis of dc-dc boost converter. It is used in modeling the closed loop converter parameters. The boost converter produces an undesirable Right-Half Plane Zero (RHPZ) in the small signal analysis due to which the implementation of voltage mode control needs attention. This requires compensating the regulator such that the crossover frequency occurs well below the frequency of the RHP zero. The paper describes modeling of voltage mode control boost converter operating in continuous conduction mode.

  11. Groundwater redox conditions and conductivity in a contaminant plume from geoelectrical investigations

    Directory of Open Access Journals (Sweden)

    V. Naudet

    2004-01-01

    Full Text Available Accurate mapping of the electrical conductivity and of the redox potential of the groundwater is important in delineating the shape of a contaminant plume. A map of redox potential in an aquifer is indicative of biodegradation of organic matter and of concentrations of redox-active components; a map of electrical conductivity provides information on the mineralisation of the groundwater. Both maps can be used to optimise the position of pumping wells for remediation. The self-potential method (SP and electrical resistivity tomography (ERT have been applied to the contaminant plume associated with the Entressen landfill in south-east France. The self-potential depends on groundwater flow (electrokinetic contribution and redox conditions ('electro-redox' contribution. Using the variation of the piezometric head in the aquifer, the electrokinetic contribution is removed from the SP signals. A good linear correlation (R2=0.85 is obtained between the residual SP data and the redox potential values measured in monitoring wells. This relationship is used to draw a redox potential map of the overall contaminated site. The electrical conductivity of the subsoil is obtained from 3D-ERT analysis. A good linear correlation (R2=0.91 is observed between the electrical conductivity of the aquifer determined from the 3D-ERT image and the conductivity of the groundwater measured in boreholes. This indicates that the formation factor is nearly homogeneous in the shallow aquifer at the scale of the ERT. From this correlation, a map of the pore water conductivity of the aquifer is obtained. Keywords: self-potential, redox potential, electrical resistivity tomography, fluid conductivity, contaminant plume

  12. Organic Redox Species in Aqueous Flow Batteries: Redox Potentials, Chemical Stability and Solubility

    Science.gov (United States)

    Wedege, Kristina; Dražević, Emil; Konya, Denes; Bentien, Anders

    2016-12-01

    Organic molecules are currently investigated as redox species for aqueous low-cost redox flow batteries (RFBs). The envisioned features of using organic redox species are low cost and increased flexibility with respect to tailoring redox potential and solubility from molecular engineering of side groups on the organic redox-active species. In this paper 33, mainly quinone-based, compounds are studied experimentially in terms of pH dependent redox potential, solubility and stability, combined with single cell battery RFB tests on selected redox pairs. Data shows that both the solubility and redox potential are determined by the position of the side groups and only to a small extent by the number of side groups. Additionally, the chemical stability and possible degradation mechanisms leading to capacity loss over time are discussed. The main challenge for the development of all-organic RFBs is to identify a redox pair for the positive side with sufficiently high stability and redox potential that enables battery cell potentials above 1 V.

  13. Controls on the redox potential of rainwater.

    Science.gov (United States)

    Willey, Joan D; Mullaugh, Katherine M; Kieber, Robert J; Avery, G Brooks; Mead, Ralph N

    2012-12-18

    Hydrogen peroxide acting as a reductant affects the redox potential of rainwater collected at the Bermuda Atlantic Time Series Station, the South Island of New Zealand, the contiguous USA, and the primary study site in Wilmington, NC. Analytical measurements of both halves of redox couples for dissolved iron, mercury, and the nitrate-nitrite-ammonium system can predict the rainwater redox potential measured directly by a platinum electrode. Measurements of these redox couples along with the pH in rain yields pe⁻ between 8 and 11; the half reaction for hydrogen peroxide acting as a reductant using typical rainwater conditions of 15 μM H₂O₂ at pH 4.7 gives pe⁻ = 9.12, where pe⁻ = negative log of the activity of hydrated electrons. Of the six rainwater redox systems investigated, only manganese speciation appeared to be controlled by molecular oxygen (pe⁻ = 15.90). Copper redox speciation was consistent with superoxide acting as a reductant (pe⁻ = 2.7). The concentration of H₂O₂ in precipitation has more than doubled over the preceding decade due to a decrease in SO₂ emissions, which suggests the redox chemistry of rainwater is dynamic and changing, potentially altering the speciation of many organic compounds and trace metals in atmospheric waters.

  14. Sub-picosecond Resolution Time-to-Digital Converter

    Energy Technology Data Exchange (ETDEWEB)

    Ph D, Vladimir Bratov; Ph D, Vladimir Katzman; MS EE, Jeb Binkley

    2006-03-30

    Time-to-digital converters with sub-picosecond resolutions are needed to satisfy the requirements of time-on-flight measurements of the next generation of high energy and nuclear physics experiments. The converters must be highly integrated, power effective, low cost, and feature plug-and-play capabilities to handle the increasing number of channels (up to hundreds of millions) in future Department of Energy experiments. Current state-off-the-art time-to-digital converter integrated circuits do not have the sufficient degree of integration and flexibility to fulfill all the described requirements. During Phase I, the Advanced Science and Novel Technology Company in cooperation with the nuclear physics division of the Oak Ridge National Laboratory has developed the architecture of a novel time-to-digital converter with multiple channels connected to an external processor through a special interfacing block and synchronized by clock signals generated by an internal phase-locked loop. The critical blocks of the system including signal delay lines and delay-locked loops with proprietary differential delay cells, as well as the required digital code converter and the clock period counter have been designed and simulated using the advanced SiGe120 BiCMOS technological process. The results of investigations demonstrate a possibility to achieve the digitization accuracy within 1ps. ADSANTEC has demonstrated the feasibility of the proposed concept in computer simulations. The proposed system will be a critical component for the next generation of NEP experiments.

  15. XML Docbook to Mediawiki Converter

    Directory of Open Access Journals (Sweden)

    Maria Chiara Pievatolo

    2013-05-01

    Full Text Available A Perl script, based on the work of Stefano Selleri, to migrate XML-Docbook 4.X documents to Wiki markup. I added some lines to meet my need to convert my Kant translations from Docbook to MediaWiki. A sample of the output can be...

  16. Charge-pump voltage converter

    Science.gov (United States)

    Brainard, John P.; Christenson, Todd R.

    2009-11-03

    A charge-pump voltage converter for converting a low voltage provided by a low-voltage source to a higher voltage. Charge is inductively generated on a transfer rotor electrode during its transit past an inductor stator electrode and subsequently transferred by the rotating rotor to a collector stator electrode for storage or use. Repetition of the charge transfer process leads to a build-up of voltage on a charge-receiving device. Connection of multiple charge-pump voltage converters in series can generate higher voltages, and connection of multiple charge-pump voltage converters in parallel can generate higher currents. Microelectromechanical (MEMS) embodiments of this invention provide a small and compact high-voltage (several hundred V) voltage source starting with a few-V initial voltage source. The microscale size of many embodiments of this invention make it ideally suited for MEMS- and other micro-applications where integration of the voltage or charge source in a small package is highly desirable.

  17. Power electronic converters modeling and control with case studies

    CERN Document Server

    Bacha, Seddik; Bratcu, Antoneta Iuliana

    2014-01-01

    Modern power electronic converters are involved in a very broad spectrum of applications: switched-mode power supplies, electrical-machine-motion-control, active power filters, distributed power generation, flexible AC transmission systems, renewable energy conversion systems and vehicular technology, among them. Power Electronics Converters Modeling and Control teaches the reader how to analyze and model the behavior of converters and so to improve their design and control. Dealing with a set of confirmed algorithms specifically developed for use with power converters, this text is in two parts: models and control methods. The first is a detailed exposition of the most usual power converter models: ·        switched and averaged models; ·        small/large-signal models; and ·        time/frequency models. The second focuses on three groups of control methods: ·        linear control approaches normally associated with power converters; ·        resonant controllers b...

  18. Early Oscillation Detection for DC/DC Converter Fault Diagnosis

    Science.gov (United States)

    Wang, Bright L.

    2011-01-01

    The electrical power system of a spacecraft plays a very critical role for space mission success. Such a modern power system may contain numerous hybrid DC/DC converters both inside the power system electronics (PSE) units and onboard most of the flight electronics modules. One of the faulty conditions for DC/DC converter that poses serious threats to mission safety is the random occurrence of oscillation related to inherent instability characteristics of the DC/DC converters and design deficiency of the power systems. To ensure the highest reliability of the power system, oscillations in any form shall be promptly detected during part level testing, system integration tests, flight health monitoring, and on-board fault diagnosis. The popular gain/phase margin analysis method is capable of predicting stability levels of DC/DC converters, but it is limited only to verification of designs and to part-level testing on some of the models. This method has to inject noise signals into the control loop circuitry as required, thus, interrupts the DC/DC converter's normal operation and increases risks of degrading and damaging the flight unit. A novel technique to detect oscillations at early stage for flight hybrid DC/DC converters was developed.

  19. Selective superoxide generation within mitochondria by the targeted redox cycler MitoParaquat.

    Science.gov (United States)

    Robb, Ellen L; Gawel, Justyna M; Aksentijević, Dunja; Cochemé, Helena M; Stewart, Tessa S; Shchepinova, Maria M; Qiang, He; Prime, Tracy A; Bright, Thomas P; James, Andrew M; Shattock, Michael J; Senn, Hans M; Hartley, Richard C; Murphy, Michael P

    2015-12-01

    Superoxide is the proximal reactive oxygen species (ROS) produced by the mitochondrial respiratory chain and plays a major role in pathological oxidative stress and redox signaling. While there are tools to detect or decrease mitochondrial superoxide, none can rapidly and specifically increase superoxide production within the mitochondrial matrix. This lack impedes progress, making it challenging to assess accurately the roles of mitochondrial superoxide in cells and in vivo. To address this unmet need, we synthesized and characterized a mitochondria-targeted redox cycler, MitoParaquat (MitoPQ) that comprises a triphenylphosphonium lipophilic cation conjugated to the redox cycler paraquat. MitoPQ accumulates selectively in the mitochondrial matrix driven by the membrane potential. Within the matrix, MitoPQ produces superoxide by redox cycling at the flavin site of complex I, selectively increasing superoxide production within mitochondria. MitoPQ increased mitochondrial superoxide in isolated mitochondria and cells in culture ~a thousand-fold more effectively than untargeted paraquat. MitoPQ was also more toxic than paraquat in the isolated perfused heart and in Drosophila in vivo. MitoPQ enables the selective generation of superoxide within mitochondria and is a useful tool to investigate the many roles of mitochondrial superoxide in pathology and redox signaling in cells and in vivo.

  20. Role of glutathione, glutathione transferase, and glutaredoxin in regulation of redox-dependent processes.

    Science.gov (United States)

    Kalinina, E V; Chernov, N N; Novichkova, M D

    2014-12-01

    Over the last decade fundamentally new features have been revealed for the participation of glutathione and glutathione-dependent enzymes (glutathione transferase and glutaredoxin) in cell proliferation, apoptosis, protein folding, and cell signaling. Reduced glutathione (GSH) plays an important role in maintaining cellular redox status by participating in thiol-disulfide exchange, which regulates a number of cell functions including gene expression and the activity of individual enzymes and enzyme systems. Maintaining optimum GSH/GSSG ratio is essential to cell viability. Decrease in the ratio can serve as an indicator of damage to the cell redox status and of changes in redox-dependent gene regulation. Disturbance of intracellular GSH balance is observed in a number of pathologies including cancer. Consequences of inappropriate GSH/GSSG ratio include significant changes in the mechanism of cellular redox-dependent signaling controlled both nonenzymatically and enzymatically with the participation of isoforms of glutathione transferase and glutaredoxin. This review summarizes recent data on the role of glutathione, glutathione transferase, and glutaredoxin in the regulation of cellular redox-dependent processes.

  1. Corynebacterium diphtheriae methionine sulfoxide reductase a exploits a unique mycothiol redox relay mechanism.

    Science.gov (United States)

    Tossounian, Maria-Armineh; Pedre, Brandán; Wahni, Khadija; Erdogan, Huriye; Vertommen, Didier; Van Molle, Inge; Messens, Joris

    2015-05-01

    Methionine sulfoxide reductases are conserved enzymes that reduce oxidized methionines in proteins and play a pivotal role in cellular redox signaling. We have unraveled the redox relay mechanisms of methionine sulfoxide reductase A of the pathogen Corynebacterium diphtheriae (Cd-MsrA) and shown that this enzyme is coupled to two independent redox relay pathways. Steady-state kinetics combined with mass spectrometry of Cd-MsrA mutants give a view of the essential cysteine residues for catalysis. Cd-MsrA combines a nucleophilic cysteine sulfenylation reaction with an intramolecular disulfide bond cascade linked to the thioredoxin pathway. Within this cascade, the oxidative equivalents are transferred to the surface of the protein while releasing the reduced substrate. Alternatively, MsrA catalyzes methionine sulfoxide reduction linked to the mycothiol/mycoredoxin-1 pathway. After the nucleophilic cysteine sulfenylation reaction, MsrA forms a mixed disulfide with mycothiol, which is transferred via a thiol disulfide relay mechanism to a second cysteine for reduction by mycoredoxin-1. With x-ray crystallography, we visualize two essential intermediates of the thioredoxin relay mechanism and a cacodylate molecule mimicking the substrate interactions in the active site. The interplay of both redox pathways in redox signaling regulation forms the basis for further research into the oxidative stress response of this pathogen.

  2. Cysteine-cystine redox cycling in a gold-gold dual-plate generator-collector microtrench sensor.

    Science.gov (United States)

    Hammond, Jules L; Gross, Andrew J; Estrela, Pedro; Iniesta, Jesus; Green, Stephen J; Winlove, C Peter; Winyard, Paul G; Benjamin, Nigel; Marken, Frank

    2014-07-15

    Thiols and disulfides are ubiquitous and important analytical targets. However, their redox properties, in particular on gold sensor electrodes, are complex and obscured by strong adsorption. Here, a gold-gold dual-plate microtrench dual-electrode sensor with feedback signal amplification is demonstrated to give well-defined (but kinetically limited) steady-state voltammetric current responses for the cysteine-cystine redox cycle in nondegassed aqueous buffer media at pH 7 down to micromolar concentration levels.

  3. PRIMARY SIDE DETECTION AND PEAK CURRENT MODE CONTROL IN FLYBACK CONVERTER

    Institute of Scientific and Technical Information of China (English)

    Fang Jian; Lu Zhiping; Yang Jian; Li Zhaoji

    2004-01-01

    A new cycle-by-cycle control flyback converter with primary side detection and peak current mode control is proposed and its dynamic characteristics are analyzed. The flyback converter is verified by the OrCAD simulator. The main advantages of this converter over the conventional one are simplicity, small size, rapid regulating and no sensing control signals over the isolation barrier. The circuit is suitable for digital control implementations.

  4. Synthesis and atomic level in situ redox characterization in ceria and ceria zirconia

    Science.gov (United States)

    Wang, Ruigang

    2007-12-01

    Nanocrystalline ceria-based oxides are widely used in automotive three-way catalytic converters to reduce the emissions of carbon monoxide, nitrogen oxides, and unburned hydrocarbons. The primary function of ceria-based oxides in the catalytic process is to adjust the local oxygen partial pressure and maintain an air-to-fuel ratio near the stoichiometric value (˜14.5) required for the optimal catalyst performance for carbon monoxide, hydrocarbon oxidation, and nitrogen oxides reduction. In this dissertation, a study of the relationship between the nanoscale structure, chemistry, and the redox behavior on high surface area ceria and ceria zirconia is presented. Precipitation and spray freezing methods were used to synthesize nanocrystalline ceria and ceria zirconia solid solution powders respectively. The effect of thermal treatments in oxidizing and reducing atmospheres on the reducibility of the materials has been systematically investigated. X-ray diffraction and thermogravimetric analysis were used to characterize the average structure and reducibility. In situ environmental transmission electron microscope was exploited to visualize the dynamic changes during redox processes at the atomic level. This resulted in the identification of the nanoscale structure and chemistry for the most active nanoparticles in these oxides. The correlation between ex situ macroscopic redox properties and in situ redox behavior of individual nanoparticles is demonstrated. The addition of zirconia to ceria clearly enhances the reducibility and thermal stability of ceria. A fundamental difference between ceria and ceria zirconia during in situ redox processes is related to oxygen vacancy ordering. Ceria showed oxygen vacancy ordering during reduction, whereas ceria zirconia did not. It is suggested that the absence of oxygen vacancy ordering might be a fundamental factor for improved redox properties of ceria zirconia compared with pure ceria. The 50% ceria-50% zirconia solid

  5. The redox interplay between nitrite and nitric oxide: From the gut to the brain

    Directory of Open Access Journals (Sweden)

    Cassilda Pereira

    2013-01-01

    We here discuss the implications of the redox conversion of nitrite to ·NO in the gut, how nitrite-derived ·NO may signal from the digestive to the central nervous system, influencing brain function, as well as a putative ascorbate-driven nitrite/NO pathway occurring in the brain.

  6. Data Converters Performance at Extreme Temperatures

    Science.gov (United States)

    Rejeshuni, Rarnesham; Kumar, Nikil; Mao, James; Keymeulen, Didier; Zebulum, Ricardo S.; Stoica, Adrian

    2006-01-01

    Space missions often require radiation and extreme-temperature hardened electronics to survive the harsh environments beyond earth's atmosphere. Traditional approaches to preserve electronics incorporate shielding, insulation and redundancy at the expense of power and weight. However, a novel way of bypassing these problems is the concept of evolutionary hardware. A reconfgurable device, consisting of several switches interconnected with analog/digital parts, is controlled by an evolutionary processor (EP). When the EP detects degradation in the circuit it sends signals to reconfgure the switches, thus forming a new circuit with the desired output. This concept has been developed since the mid-90s, but one problem remains - the EP cannot degrade substantially. For this reason, extensive testing at extreme temperatures (-180' to 120(deg)C) has been done on devices found on FPGA boards (taking the role of the EP) such as the Analog to Digital and the Digital to Analog Converter. Analysis of the results has shown that FPGA boards implementing EP with some compensation may be a practical solution to evolving circuits. This paper describes results on the tests of data converters at extreme temperatures.

  7. Bidirectional dc-to-dc Power Converter

    Science.gov (United States)

    Griesbach, C. R.

    1986-01-01

    Solid-state, series-resonant converter uses high-voltage thyristors. Converter used either to convert high-voltage, low-current dc power to lowvoltage, high current power or reverse. Taking advantage of newly-available high-voltage thyristors to provide better reliability and efficiency than traditional converters that use vacuum tubes as power switches. New converter essentially maintenance free and provides greatly increased mean time between failures. Attractive in industrial applications whether or not bidirectional capability is required.

  8. Parametric study of laser photovoltaic energy converters

    Science.gov (United States)

    Walker, G. H.; Heinbockel, J. H.

    1987-01-01

    Photovoltaic converters are of interest for converting laser power to electrical power in a space-based laser power system. This paper describes a model for photovoltaic laser converters and the application of this model to a neodymium laser silicon photovoltaic converter system. A parametric study which defines the sensitivity of the photovoltaic parameters is described. An optimized silicon photovoltaic converter has an efficiency greater than 50 percent for 1000 W/sq cm of neodymium laser radiation.

  9. Photonic analog-to-digital converters

    Science.gov (United States)

    Valley, George C.

    2007-03-01

    This paper reviews over 30 years of work on photonic analog-to-digital converters. The review is limited to systems in which the input is a radio-frequency (RF) signal in the electronic domain and the output is a digital version of that signal also in the electronic domain, and thus the review excludes photonic systems directed towards digitizing images or optical communication signals. The state of the art in electronic ADCs, basic properties of ADCs and properties of analog optical links, which are found in many photonic ADCs, are reviewed as background information for understanding photonic ADCs. Then four classes of photonic ADCs are reviewed: 1) photonic assisted ADC in which a photonic device is added to an electronic ADC to improve performance, 2) photonic sampling and electronic quantizing ADC, 3) electronic sampling and photonic quantizing ADC, and 4) photonic sampling and quantizing ADC. It is noted, however, that all 4 classes of “photonic ADC” require some electronic sampling and quantization. After reviewing all known photonic ADCs in the four classes, the review concludes with a discussion of the potential for photonic ADCs in the future.

  10. Increasing the resolution of photoelectric angle-to-code converters

    Energy Technology Data Exchange (ETDEWEB)

    Zakharov, L.P.

    1986-04-01

    The authors describe a circuit for processing the signal of the auxiliary photodetector of a converter of angular shaft displacement to code; it increases the resolution of the converter by two or three orders without increasing the number of code tracks. Ther permissible reading error for all bits of the main code except for the least-significant can be half of the width of a code element of the less-bit track. The auxiliary and main codes are matched and are represented by the output binary code.

  11. Mechanical vibration to electrical energy converter

    Science.gov (United States)

    Kellogg, Rick Allen; Brotz, Jay Kristoffer

    2009-03-03

    Electromechanical devices that generate an electrical signal in response to an external source of mechanical vibrations can operate as a sensor of vibrations and as an energy harvester for converting mechanical vibration to electrical energy. The devices incorporate a magnet that is movable through a gap in a ferromagnetic circuit, wherein a coil is wound around a portion of the ferromagnetic circuit. A flexible coupling is used to attach the magnet to a frame for providing alignment of the magnet as it moves or oscillates through the gap in the ferromagnetic circuit. The motion of the magnet can be constrained to occur within a substantially linear range of magnetostatic force that develops due to the motion of the magnet. The devices can have ferromagnetic circuits with multiple arms, an array of magnets having alternating polarity and, encompass micro-electromechanical (MEM) devices.

  12. Hybrid-free Josephson Parametric Converter

    Science.gov (United States)

    Frattini, N. E.; Narla, A.; Sliwa, K. M.; Shankar, S.; Hatridge, M.; Devoret, M. H.

    A necessary component for any quantum computation architecture is the ability to perform efficient quantum operations. In the microwave regime of superconducting qubits, these quantum-limited operations can be realized with a non-degenerate Josephson junction based three-wave mixer, the Josephson Parametric Converter (JPC). Currently, the quantum signal of interest must pass through a lossy 180 degree hybrid to be presented as a differential drive to the JPC. This hybrid therefore places a limit on the quantum efficiency of the system and also increases the device footprint. We present a new design for the JPC eliminating the need for any external hybrid. We also show that this design has nominally identical performance to the conventional JPC. Work supported by ARO, AFOSR and YINQE.

  13. Redox potential tuning by redox-inactive cations in nature's water oxidizing catalyst and synthetic analogues.

    Science.gov (United States)

    Krewald, Vera; Neese, Frank; Pantazis, Dimitrios A

    2016-04-28

    The redox potential of synthetic oligonuclear transition metal complexes has been shown to correlate with the Lewis acidity of a redox-inactive cation connected to the redox-active transition metals of the cluster via oxo or hydroxo bridges. Such heterometallic clusters are important cofactors in many metalloenzymes, where it is speculated that the redox-inactive constituent ion of the cluster serves to optimize its redox potential for electron transfer or catalysis. A principal example is the oxygen-evolving complex in photosystem II of natural photosynthesis, a Mn4CaO5 cofactor that oxidizes water into dioxygen, protons and electrons. Calcium is critical for catalytic function, but its precise role is not yet established. In analogy to synthetic complexes it has been suggested that Ca(2+) fine-tunes the redox potential of the manganese cluster. Here we evaluate this hypothesis by computing the relative redox potentials of substituted derivatives of the oxygen-evolving complex with the cations Sr(2+), Gd(3+), Cd(2+), Zn(2+), Mg(2+), Sc(3+), Na(+) and Y(3+) for two sequential transitions of its catalytic cycle. The theoretical approach is validated with a series of experimentally well-characterized Mn3AO4 cubane complexes that are structural mimics of the enzymatic cluster. Our results reproduce perfectly the experimentally observed correlation between the redox potential and the Lewis acidities of redox-inactive cations for the synthetic complexes. However, it is conclusively demonstrated that this correlation does not hold for the oxygen evolving complex. In the enzyme the redox potential of the cluster only responds to the charge of the redox-inactive cations and remains otherwise insensitive to their precise identity, precluding redox-tuning of the metal cluster as a primary role for Ca(2+) in biological water oxidation.

  14. An Integrated Inductor For Parallel Interleaved Three-Phase Voltage Source Converters

    DEFF Research Database (Denmark)

    Gohil, Ghanshyamsinh Vijaysinh; Bede, Lorand; Teodorescu, Remus;

    2016-01-01

    Three phase Voltage Source Converters (VSCs) are often connected in parallel to realize high current output converter system. The harmonic quality of the resultant switched output voltage can be improved by interleaving the carrier signals of these parallel connected VSCs. As a result, the line...

  15. Electrochemical reverse engineering: A systems-level tool to probe the redox-based molecular communication of biology.

    Science.gov (United States)

    Li, Jinyang; Liu, Yi; Kim, Eunkyoung; March, John C; Bentley, William E; Payne, Gregory F

    2016-12-29

    The intestine is the site of digestion and forms a critical interface between the host and the outside world. This interface is composed of host epithelium and a complex microbiota which is "connected" through an extensive web of chemical and biological interactions that determine the balance between health and disease for the host. This biology and the associated chemical dialogues occur within a context of a steep oxygen gradient that provides the driving force for a variety of reduction and oxidation (redox) reactions. While some redox couples (e.g., catecholics) can spontaneously exchange electrons, many others are kinetically "insulated" (e.g., biothiols) allowing the biology to set and control their redox states far from equilibrium. It is well known that within cells, such non-equilibrated redox couples are poised to transfer electrons to perform reactions essential to immune defense (e.g., transfer from NADH to O2 for reactive oxygen species, ROS, generation) and protection from such oxidative stresses (e.g., glutathione-based reduction of ROS). More recently, it has been recognized that some of these redox-active species (e.g., H2O2) cross membranes and diffuse into the extracellular environment including lumen to transmit redox information that is received by atomically-specific receptors (e.g., cysteine-based sulfur switches) that regulate biological functions. Thus, redox has emerged as an important modality in the chemical signaling that occurs in the intestine and there have been emerging efforts to develop the experimental tools needed to probe this modality. We suggest that electrochemistry provides a unique tool to experimentally probe redox interactions at a systems level. Importantly, electrochemistry offers the potential to enlist the extensive theories established in signal processing in an effort to "reverse engineer" the molecular communication occurring in this complex biological system. Here, we review our efforts to develop this

  16. In vitro susceptibility of thioredoxins and glutathione to redox modification and aging-related changes in skeletal muscle

    Science.gov (United States)

    Dimauro, Ivan; Pearson, Timothy; Caporossi, Daniela; Jackson, Malcolm J.

    2012-01-01

    Thioredoxins (Trx's) regulate redox signaling and are localized to various cellular compartments. Specific redox-regulated pathways for adaptation of skeletal muscle to contractions are attenuated during aging, but little is known about the roles of Trx's in regulating these pathways. This study investigated the susceptibility of Trx1 and Trx2 in skeletal muscle to oxidation and reduction in vitro and the effects of aging and contractions on Trx1, Trx2, and thioredoxin reductase (TrxR) 1 and 2 contents and nuclear and cytosolic Trx1 and mitochondrial Trx2 redox potentials in vivo. The proportions of cytosolic and nuclear Trx1 and mitochondrial Trx2 in the oxidized or reduced forms were analyzed using redox Western blotting. In myotubes, the mean redox potentials were nuclear Trx1, −251 mV; cytosolic Trx1, −242 mV; mitochondrial Trx2, −346 mV, data supporting the occurrence of differing redox potentials between cell compartments. Exogenous treatment of myoblasts and myotubes with hydrogen peroxide or dithiothreitol modified glutathione redox status and nuclear and cytosolic Trx1, but mitochondrial Trx2 was unchanged. Tibialis anterior muscles from young and old mice were exposed to isometric muscle contractions in vivo. Aging increased muscle contents of Trx1, Trx2, and TrxR2, but neither aging nor endogenous ROS generated during contractions modified Trx redox potentials, although oxidation of glutathione and other thiols occurred. We conclude that glutathione redox couples in skeletal muscle are more susceptible to oxidation than Trx and that Trx proteins are upregulated during aging, but do not appear to modulate redox-regulated adaptations to contractions that fail during aging. PMID:23022873

  17. Novel Redox Processes for Carbonaceous Fuel Conversion

    Science.gov (United States)

    He, Feng

    The current study investigates oxygen carrier development, process intensification, and oxygen carrier attrition behaviors for a number of novel, redox-based energy conversion schemes. (Abstract shortened by ProQuest.).

  18. Vibration measurement with nonlinear converter in the presence of noise

    Science.gov (United States)

    Mozuras, Almantas

    2017-10-01

    Conventional vibration measurement methods use the linear properties of physical converters. These methods are strongly influenced by nonlinear distortions, because ideal linear converters are not available. Practically, any converter can be considered as a linear one, when an output signal is very small. However, the influence of noise increases significantly and signal-to-noise ratio decreases at lower signals. When the output signal is increasing, the nonlinear distortions are also augmenting. If the wide spectrum vibration is measured, conventional methods face a harmonic distortion as well as intermodulation effects. Purpose of this research is to develop a measurement method of wide spectrum vibration by using a converter described by a nonlinear function of type f(x), where x =x(t) denotes the dependence of coordinate x on time t due to the vibration. Parameter x(t) describing the vibration is expressed as Fourier series. The spectral components of the converter output f(x(t)) are determined by using Fourier transform. The obtained system of nonlinear equations is solved using the least squares technique that permits to find x(t) in the presence of noise. This method allows one to carry out the absolute or relative vibration measurements. High resistance to noise is typical for the absolute vibration measurement, but it is necessary to know the Taylor expansion coefficients of the function f(x). If the Taylor expansion is not known, the relative measurement of vibration parameters is also possible, but with lower resistance to noise. This method allows one to eliminate the influence of nonlinear distortions to the measurement results, and consequently to eliminate harmonic distortion and intermodulation effects. The use of nonlinear properties of the converter for measurement gives some advantages related to an increased frequency range of the output signal (consequently increasing the number of equations) that allows one to decrease the noise influence on

  19. Assessment of redox markers in cattle

    OpenAIRE

    Burke, Nathaniel Caleb

    2007-01-01

    Metabolic redox status may have important implications to cattle health and production. Antioxidants and biomarkers of oxidative stress were evaluated in cattle under three phases of management. Each phase stood alone as a treatment model, and managerial aspects during the phase were evaluated as potential moderators of redox balance. Yearling heifers were used to assess the impact of fescue toxicosis and heat stress on selected markers in study 1. Intravaginal temperatures, ADG, serum prolac...

  20. Photoelectric converters with quantum coherence

    Science.gov (United States)

    Su, Shan-He; Sun, Chang-Pu; Li, Sheng-Wen; Chen, Jin-Can

    2016-05-01

    Photon impingement is capable of liberating electrons in electronic devices and driving the electron flux from the lower chemical potential to higher chemical potential. Previous studies hinted that the thermodynamic efficiency of a nanosized photoelectric converter at maximum power is bounded by the Curzon-Ahlborn efficiency ηCA. In this study, we apply quantum effects to design a photoelectric converter based on a three-level quantum dot (QD) interacting with fermionic baths and photons. We show that, by adopting a pair of suitable degenerate states, quantum coherences induced by the couplings of QDs to sunlight and fermion baths can coexist steadily in nanoelectronic systems. Our analysis indicates that the efficiency at maximum power is no longer limited to ηCA through manipulation of carefully controlled quantum coherences.

  1. Photoelectric converter; Koden henkan soshi

    Energy Technology Data Exchange (ETDEWEB)

    Sawayama, I.

    1995-04-07

    The conventional solar cell module wherein plural photovoltaic elements formed on a metal substrate are connected and coated by weatherproof and translucent resin has defects such as pinholes, and separation because moisture infiltrating from the outside causes dissolution of such conductive matrix as silver in the collecting electrode. This invention relates to a photoelectric converter which has little decrease in the output under the environment of light irradiation, wherein a photoelectric converting semiconductor, a transparent conductive layer on the above-mentioned semiconductor, and conductive member containing water repellent fine powder grains on this transparent conductive layer are laminated successively. Polytetrafluoroethylene, polydimethyl siloxane, polyethylene, and nylon are desirable to be employed as the water repellent fine powder grains. The fine powder grains are mixed with conductive filler and binder to produce conductive paste, pattern-applied by a screen printing machine, and subjected to thermal treatment to form a conductive member. 3 figs., 1 tab.

  2. Photoelectric converters with quantum coherence.

    Science.gov (United States)

    Su, Shan-He; Sun, Chang-Pu; Li, Sheng-Wen; Chen, Jin-Can

    2016-05-01

    Photon impingement is capable of liberating electrons in electronic devices and driving the electron flux from the lower chemical potential to higher chemical potential. Previous studies hinted that the thermodynamic efficiency of a nanosized photoelectric converter at maximum power is bounded by the Curzon-Ahlborn efficiency η_{CA}. In this study, we apply quantum effects to design a photoelectric converter based on a three-level quantum dot (QD) interacting with fermionic baths and photons. We show that, by adopting a pair of suitable degenerate states, quantum coherences induced by the couplings of QDs to sunlight and fermion baths can coexist steadily in nanoelectronic systems. Our analysis indicates that the efficiency at maximum power is no longer limited to η_{CA} through manipulation of carefully controlled quantum coherences.

  3. Engineering an NADPH/NADP(+) Redox Biosensor in Yeast.

    Science.gov (United States)

    Zhang, Jie; Sonnenschein, Nikolaus; Pihl, Thomas P B; Pedersen, Kasper R; Jensen, Michael K; Keasling, Jay D

    2016-12-16

    Genetically encoded biosensors have emerged as powerful tools for timely and precise in vivo evaluation of cellular metabolism. In particular, biosensors that can couple intercellular cues with downstream signaling responses are currently attracting major attention within health science and biotechnology. Still, there is a need for bioprospecting and engineering of more biosensors to enable real-time monitoring of specific cellular states and controlling downstream actuation. In this study, we report the engineering and application of a transcription factor-based NADPH/NADP(+) redox biosensor in the budding yeast Saccharomyces cerevisiae. Using the biosensor, we are able to monitor the cause of oxidative stress by chemical induction, and changes in NADPH/NADP(+) ratios caused by genetic manipulations. Because of the regulatory potential of the biosensor, we also show that the biosensor can actuate upon NADPH deficiency by activation of NADPH regeneration. Finally, we couple the biosensor with an expression of dosage-sensitive genes (DSGs) and thereby create a novel tunable sensor-selector useful for synthetic selection of cells with higher NADPH/NADP(+) ratios from mixed cell populations. We show that the combination of exploitation and rational engineering of native signaling components is applicable for diagnosis, regulation, and selection of cellular redox states.

  4. Simplified dc to dc converter

    Science.gov (United States)

    Gruber, R. P. (Inventor)

    1984-01-01

    A dc to dc converter which can start with a shorted output and which regulates output voltage and current is described. Voltage controlled switches directed current through the primary of a transformer the secondary of which includes virtual reactance. The switching frequency of the switches is appropriately varied to increase the voltage drop across the virtual reactance in the secondary winding to which there is connected a low impedance load. A starting circuit suitable for voltage switching devices is provided.

  5. Biomass compounds converted to gasoline

    Energy Technology Data Exchange (ETDEWEB)

    1979-10-08

    It is claimed that corn, castor, and jojoba oils as well as Hevea latex can be converted in high yields to gasoline by passage over zeolite catalysts at 450 degrees to 500 degrees centigrade. Gasoline yields are 60% from corn oil (essentially tristearin), compared with 50% yields from methanol. Latex depolymerizes before conversion. Fat and oil molecules adopt conformations that enable them to enter zeolite interstices, resulting in high yields of C6 to C9 aromatics.

  6. Workshop 4 Converter cooling & recuperation

    Science.gov (United States)

    Iles, Peter; Hindman, Don

    1995-01-01

    Cooling the PV converter increases the overall TPV system efficiency, and more than offsets the losses incurred in providing cooling systems. Convective air flow methods may be sufficient, and several standard water cooling systems, including thermo-syphon radiators, capillary pumps or microchannel plates, are available. Recuperation is used to increase system efficiency, rather than to increase the emitter temperature. Recuperators operating at comparable high temperatures, such as in high temperature turbines have worked effectively.

  7. Membranes for Redox Flow Battery Applications

    Directory of Open Access Journals (Sweden)

    Maria Skyllas-Kazacos

    2012-06-01

    Full Text Available The need for large scale energy storage has become a priority to integrate renewable energy sources into the electricity grid. Redox flow batteries are considered the best option to store electricity from medium to large scale applications. However, the current high cost of redox flow batteries impedes the wide spread adoption of this technology. The membrane is a critical component of redox flow batteries as it determines the performance as well as the economic viability of the batteries. The membrane acts as a separator to prevent cross-mixing of the positive and negative electrolytes, while still allowing the transport of ions to complete the circuit during the passage of current. An ideal membrane should have high ionic conductivity, low water intake and excellent chemical and thermal stability as well as good ionic exchange capacity. Developing a low cost, chemically stable membrane for redox flow cell batteries has been a major focus for many groups around the world in recent years. This paper reviews the research work on membranes for redox flow batteries, in particular for the all-vanadium redox flow battery which has received the most attention.

  8. Membranes for redox flow battery applications.

    Science.gov (United States)

    Prifti, Helen; Parasuraman, Aishwarya; Winardi, Suminto; Lim, Tuti Mariana; Skyllas-Kazacos, Maria

    2012-06-19

    The need for large scale energy storage has become a priority to integrate renewable energy sources into the electricity grid. Redox flow batteries are considered the best option to store electricity from medium to large scale applications. However, the current high cost of redox flow batteries impedes the wide spread adoption of this technology. The membrane is a critical component of redox flow batteries as it determines the performance as well as the economic viability of the batteries. The membrane acts as a separator to prevent cross-mixing of the positive and negative electrolytes, while still allowing the transport of ions to complete the circuit during the passage of current. An ideal membrane should have high ionic conductivity, low water intake and excellent chemical and thermal stability as well as good ionic exchange capacity. Developing a low cost, chemically stable membrane for redox flow cell batteries has been a major focus for many groups around the world in recent years. This paper reviews the research work on membranes for redox flow batteries, in particular for the all-vanadium redox flow battery which has received the most attention.

  9. Computerized simulation of converter process

    Energy Technology Data Exchange (ETDEWEB)

    Jalkanen, H.; Suomi, M.L.; Wallgren, M. [Helsinki Univ. of Technology, Otaniemi (Finland). Lab. of Metallurgy

    1996-12-31

    Converter process is essentially an oxidising refining process aiming in addition to (1) the primary refining action, decarburisation of high carbon iron melt, also to (2) maximal elimination of impurity elements, especially silicon, phosphorus and sulphur, (3) melting of substantial amounts of scrap using the extra heat released in oxidation reactions and (4) to exact final steel temperature control, optimal for further treatments. `Quantitative modelling of such a complex non-stationary chemical process as oxygen converting necessitates extensive formulation of chemical and thermal evolution of the process in connection with the technological properties of the reactor and the process control measures. A comprehensive converter simulation program like CONSIM-3. 1 and its preceding versions that is based on the theoretical and practical knowledge on the process can be used for (1) educating specialists and smelter personnel, (2) planning of the blowing programs, (3) developing and testing of process control systems and after some elaboration and restructuring (4) it can be integrated to static or dynamic process control systems. (orig.) SULA 2 Research Programme; 10 refs.

  10. Redox effects on the microbial degradation of refractory organic matter in marine sediments

    Science.gov (United States)

    Reimers, Clare E.; Alleau, Yvan; Bauer, James E.; Delaney, Jennifer; Girguis, Peter R.; Schrader, Paul S.; Stecher, Hilmar A.

    2013-11-01

    enrichment of Deltaproteobacteria on the sediment-hosted anodes over time. Many Deltaproteobacteria are capable of using electrodes as terminal electron acceptors to completely oxidize organic substrates. Notably, Deltaproteobacteria were not measurably enriched in the sediments adjacent to anodes, suggesting that - in these experiments - electron-shuttling bacterial networks did not radiate out away from the electrodes, affecting millimeters or centimeters of sediment. Rather, microbial phylotypes allied to the Clostridia appeared to dominate in the sediment amongst all treatments, and likely played essential roles in converting complex dissolved and particulate sources of OM to simple fermentation products. Thus, we advance that the rate at which fermentation products are generated and migrate to oxidation fronts is what limits the remineralization of OM in many subsurface sediments removed from molecular oxygen. This is a diagenetic scenario that is consistent with the discharging behavior of redox oscillating sediment MFCs. It is also compatible with hypotheses that molecular O2 - and not just the resulting elevated redox potential - may be required to effectively catalyze the degradation of refractory OM. Such decomposition reactions have been suggested to depend on substrate interactions with highly reactive oxygen-containing radicals and/or with specialized extracellular enzymes produced by aerobic prokaryotic or eukaryotic cells.

  11. Design and Control for the Buck-Boost Converter Combining 1-Plus-D Converter and Synchronous Rectified Buck Converters

    Directory of Open Access Journals (Sweden)

    Jeevan Naik

    2015-06-01

    Full Text Available In this paper, a design and control for the buck-boost converter, i.e., 1-plus-D converter with a positive output voltage, is presented, which combines the 1-plus-D converter and the synchronous rectified (SR buck converter. By doing so, the problem in voltage bucking of the 1-plus-D converter can be solved, thereby increasing the application capability of the 1-plus-D converter. Since such a converter operates in continuous conduction mode inherently, it possesses the nonpulsating output current, thereby not only decreasing the current stress on the output capacitor but also reducing the output voltage ripple. Above all, both the 1-plus-D converter and the SR buck converter, combined into a buck–boost converter with no right-half plane zero, use the same power switches, thereby causing the required circuit to be compact and the corresponding cost to be down. Furthermore, during the magnetization period, the input voltage of the 1-plus-D converter comes from the input voltage source, whereas during the demagnetization period, the input voltage of the 1-plus-D converter comes from the output voltage of the SR buck converter.

  12. Three Redox States of Trypanosoma brucei Alternative Oxidase Identified by Infrared Spectroscopy and Electrochemistry

    Science.gov (United States)

    Maréchal, Amandine; Kido, Yasutoshi; Kita, Kiyoshi; Moore, Anthony L.; Rich, Peter R.

    2009-01-01

    Electrochemistry coupled with Fourier transform infrared (IR) spectroscopy was used to investigate the redox properties of recombinant alternative ubiquinol oxidase from Trypanosoma brucei, the organism responsible for African sleeping sickness. Stepwise reduction of the fully oxidized resting state of recombinant alternative ubiquinol oxidase revealed two distinct IR redox difference spectra. The first of these, signal 1, titrates in the reductive direction as an n = 2 Nernstian component with an apparent midpoint potential of 80 mV at pH 7.0. However, reoxidation of signal 1 in the same potential range under anaerobic conditions did not occur and only began with potentials in excess of 500 mV. Reoxidation by introduction of oxygen was also unsuccessful. Signal 1 contained clear features that can be assigned to protonation of at least one carboxylate group, further perturbations of carboxylic and histidine residues, bound ubiquinone, and a negative band at 1554 cm−1 that might arise from a radical in the fully oxidized protein. A second distinct IR redox difference spectrum, signal 2, appeared more slowly once signal 1 had been reduced. This component could be reoxidized with potentials above 100 mV. In addition, when both signals 1 and 2 were reduced, introduction of oxygen caused rapid oxidation of both components. These data are interpreted in terms of the possible active site structure and mechanism of oxygen reduction to water. PMID:19767647

  13. Carbo-quinoids: stability and reversible redox-proaromatic character towards carbo-benzenes.

    Science.gov (United States)

    Cocq, Kévin; Maraval, Valérie; Saffon-Merceron, Nathalie; Saquet, Alix; Poidevin, Corentin; Lepetit, Christine; Chauvin, Remi

    2015-02-23

    The carbo-mer of the para-quinodimethane core is stable within in a bis(9-fluorenylidene) derivative. Oxidation of this carbo-quinoid with MnO2 in the presence of SnCl2 and ethanol affords the corresponding p-bis(9-ethoxy-fluoren-9-yl)-carbo-benzene. The latter can be in turn converted back into the carbo-quinoid by reduction with SnCl2 , thus evidencing a chemical reversibility of the interconversion between a pro-aromatic carbo-quinoid and an aromatic carbo-benzene, and is reminiscent of the behavior of the benzoquinone/hydroquinone redox couple (in the red-ox opposite sense).

  14. Converting signals to knowledge in structural health monitoring systems

    Science.gov (United States)

    Brownjohn, James M. W.; Moyo, Pilate; Omenzetter, Piotr; Chakraboorty, Sushanta

    2005-04-01

    Academic approaches in structural health monitoring (SHM) usually focus on fine detail or on aspects of the technology such as sensors and data collection, and areas that may be less useful to operators than information about the level of performance of their structures. The steps in the process of SHM such as data management, data mining, conversion to knowledge of structural behaviour and integrity are frequently absent, and even the most operationally successful SHM systems may lack the component where deep understanding on the nature of the structure performance is obtained. This paper presents experience gained in a number of SHM exercises where static and dynamic response data have been interpreted, with or without the aid of calibrated structural models, in order to characterise the mechanisms at work and the experiences of the structure.

  15. Cobalt and marine redox evolution

    Science.gov (United States)

    Swanner, Elizabeth D.; Planavsky, Noah J.; Lalonde, Stefan V.; Robbins, Leslie J.; Bekker, Andrey; Rouxel, Olivier J.; Saito, Mak A.; Kappler, Andreas; Mojzsis, Stephen J.; Konhauser, Kurt O.

    2014-03-01

    Cobalt (Co) is a bio-essential trace element and limiting nutrient in some regions of the modern oceans. It has been proposed that Co was more abundant in poorly ventilated Precambrian oceans based on the greater utilization of Co by anaerobic microbes relative to plants and animals. However, there are few empirical or theoretical constraints on the history of seawater Co concentrations. Herein, we present a survey of authigenic Co in marine sediments (iron formations, authigenic pyrite and bulk euxinic shales) with the goal of tracking changes in the marine Co reservoir throughout Earth's history. We further provide an overview of the modern marine Co cycle, which we use as a platform to evaluate how changes in the redox state of Earth's surface were likely to have affected marine Co concentrations. Based on sedimentary Co contents and our understanding of marine Co sources and sinks, we propose that from ca. 2.8 to 1.8 Ga the large volume of hydrothermal fluids circulating through abundant submarine ultramafic rocks along with a predominantly anoxic ocean with a low capacity for Co burial resulted in a large dissolved marine Co reservoir. We tentatively propose that there was a decrease in marine Co concentrations after ca. 1.8 Ga resulting from waning hydrothermal Co sources and the expansion of sulfide Co burial flux. Changes in the Co reservoir due to deep-water ventilation in the Neoproterozoic, if they occurred, are not resolvable with the current dataset. Rather, Co enrichments in Phanerozoic euxinic shales deposited during ocean anoxic events (OAE) indicate Co mobilization from expanded anoxic sediments and enhanced hydrothermal sources. A new record of marine Co concentrations provides a platform from which we can reevaluate the role that environmental Co concentrations played in shaping biological Co utilization throughout Earth's history.

  16. Glutathione redox dynamics and expression of glutathione-related genes in the developing embryo

    Science.gov (United States)

    Timme-Laragy, Alicia R.; Goldstone, Jared V.; Imhoff, Barry R.; Stegeman, John J.; Hahn, Mark E.; Hansen, Jason M.

    2013-01-01

    provides a foundation for understanding the redox regulation of developmental signaling and investigating the effects of oxidative stress during embryogenesis. PMID:23770340

  17. Nrf2 as a key player of redox regulation in cardiovascular diseases.

    Science.gov (United States)

    Barančík, M; Grešová, L; Barteková, M; Dovinová, I

    2016-09-19

    The oxidative stress plays an important role in the development of cardiovascular diseases (CVD). In CVD progression an aberrant redox regulation was observed. In this regulation levels of reactive oxygen species (ROS) play an important role in cellular signaling, where Nrf2 is the key regulator of redox homeostasis. Keap1-Nrf2-ARE system regulates a great set of detoxificant and antioxidant enzymes in cells after ROS and electrophiles exposure. In this review we focus on radical-generating systems in cardiovascular system as well as on Nrf2 as a target against oxidative stress and a key player of redox regulation in cardiovascular diseases. We also summarize the current knowledge about the role of Nrf2 in pathophysiology of several CVD (hypertension, cardiac hypertrophy, cardiomyopathies) as well as in cardioprotection against myocardial ischemia/ reperfusion injury.

  18. Redox Mechanisms in Regulation of Adipocyte Differentiation: Beyond a General Stress Response

    Directory of Open Access Journals (Sweden)

    Fan Jiang

    2012-11-01

    Full Text Available In this review, we summarize advances in our understanding of redox-sensitive mechanisms that regulate adipogenesis. Current evidence indicates that reactive oxygen species may act to promote both the initiation of adipocyte lineage commitment of precursor or stem cells, and the terminal differentiation of preadipocytes to mature adipose cells. These can involve redox regulation of pathways mediated by receptor tyrosine kinases, peroxisome proliferator-activated receptor γ (PPARγ, PPARγ coactivator 1α (PGC-1α, AMP-activated protein kinase (AMPK, and CCAAT/enhancer binding protein β (C/EBPβ. However, the precise roles of ROS in adipogenesis in vivo remain controversial. More studies are needed to delineate the roles of reactive oxygen species and redox signaling mechanisms, which could be either positive or negative, in the pathogenesis of obesity and related metabolic disorders.

  19. The redox-associated adaptive response of brain to physical exercise.

    Science.gov (United States)

    Radak, Z; Ihasz, F; Koltai, E; Goto, S; Taylor, A W; Boldogh, I

    2014-01-01

    Reactive oxygen species (ROS) are continuously generated during metabolism. ROS are involved in redox signaling, but in significant concentrations they can greatly elevate oxidative damage leading to neurodegeneration. Because of the enhanced sensitivity of brain to ROS, it is especially important to maintain a normal redox state in brain and spinal cord cell types. The complex effects of exercise benefit brain function, including functional enhancement as well as its preventive and therapeutic roles. Exercise can induce neurogenesis via neurotrophic factors, increase capillarization, decrease oxidative damage, and enhance repair of oxidative damage. Exercise is also effective in attenuating age-associated loss in brain function, which suggests that physical activity-related complex metabolic and redox changes are important for a healthy neural system.

  20. Si Bule Masuk Islam: Western Converts to Islam in Indonesia - more than just Converts of Convenience?

    OpenAIRE

    M. A. Kevin Brice

    2015-01-01

    In discussing converts to Islam, two different types of converts are often identified based on the reason for conversion: converts of convenience and converts of conviction. The common view is that in most (if not all) cases, conversion to Islam in Indonesia by Westerners is about facilitating marriage and so the converts should be classified as converts of convenience. Evidence of the commonality of this view is considered by reference to advice offered to Westerners about marriage to Indone...