WorldWideScience

Sample records for osoxi1-ospti1a phosphorylation cascade

  1. Carbocyclization cascades of allyl ketenimines via aza-Claisen rearrangements of N-phosphoryl-N-allyl-ynamides.

    Science.gov (United States)

    DeKorver, Kyle A; Wang, Xiao-Na; Walton, Mary C; Hsung, Richard P

    2012-04-06

    A series of carbocyclization cascades of allyl ketenimines initiated through a thermal aza-Claisen rearrangement of N-phosphoryl-N-allyl ynamides is described. Interceptions of the cationic intermediate via Meerwein-Wagner rearrangements and polyene-type cyclizations en route to fused bi- and tricyclic frameworks are featured.

  2. Phosphorylation of paxillin via the ERK mitogen-activated protein kinase cascade in EL4 thymoma cells.

    Science.gov (United States)

    Ku, H; Meier, K E

    2000-04-14

    Intracellular signals can regulate cell adhesion via several mechanisms in a process referred to as "inside-out" signaling. In phorbol ester-sensitive EL4 thymoma cells, phorbol-12-myristate 13-acetate (PMA) induces activation of extracellular signal-regulated kinase (ERK) mitogen-activated protein kinases and promotes cell adhesion. In this study, clonal EL4 cell lines with varying abilities to activate ERKs in response to PMA were used to examine signaling events occurring downstream of ERK activation. Paxillin, a multifunctional docking protein involved in cell adhesion, was phosphorylated on serine/threonine residues in response to PMA treatment. This response was correlated with the extent and time course of ERK activation. PMA-induced phosphorylation of paxillin was inhibited by compounds that block the ERK activation pathway in EL4 cells, primary murine thymocytes, and primary murine splenocytes. Paxillin was phosphorylated in vitro by purified active ERK2. Two-dimensional electrophoresis revealed that PMA treatment generated a complex pattern of phosphorylated paxillin species in intact cells, some of which were generated by ERK-mediated phosphorylation in vitro. An ERK pathway inhibitor interfered with PMA-induced adhesion of sensitive EL4 cells to substrate. These findings describe a novel inside-out signaling pathway by which the ERK cascade may regulate events involved in adhesion.

  3. Expression of genes belonging to the interacting TLR cascades, NADPH-oxidase and mitochondrial oxidative phosphorylation in septic patients.

    Directory of Open Access Journals (Sweden)

    Laura A Nucci

    Full Text Available Sepsis is a complex disease that is characterized by activation and inhibition of different cell signaling pathways according to the disease stage. Here, we evaluated genes involved in the TLR signaling pathway, oxidative phosphorylation and oxidative metabolism, aiming to assess their interactions and resulting cell functions and pathways that are disturbed in septic patients.Blood samples were obtained from 16 patients with sepsis secondary to community acquired pneumonia at admission (D0, and after 7 days (D7, N = 10 of therapy. Samples were also collected from 8 healthy volunteers who were matched according to age and gender. Gene expression of 84 genes was performed by real-time polymerase chain reactions. Their expression was considered up- or down-regulated when the fold change was greater than 1.5 compared to the healthy volunteers. A p-value of ≤ 0.05 was considered significant.Twenty-two genes were differently expressed in D0 samples; most of them were down-regulated. When gene expression was analyzed according to the outcomes, higher number of altered genes and a higher intensity in the disturbance was observed in non-survivor than in survivor patients. The canonical pathways altered in D0 samples included interferon and iNOS signaling; the role of JAK1, JAK2 and TYK2 in interferon signaling; mitochondrial dysfunction; and superoxide radical degradation pathways. When analyzed according to outcomes, different pathways were disturbed in surviving and non-surviving patients. Mitochondrial dysfunction, oxidative phosphorylation and superoxide radical degradation pathway were among the most altered in non-surviving patients.Our data show changes in the expression of genes belonging to the interacting TLR cascades, NADPH-oxidase and oxidative phosphorylation. Importantly, distinct patterns are clearly observed in surviving and non-surviving patients. Interferon signaling, marked by changes in JAK-STAT modulation, had prominent changes in

  4. Microtubule Destabilizer KIF2A Undergoes Distinct Site-Specific Phosphorylation Cascades that Differentially Affect Neuronal Morphogenesis

    Directory of Open Access Journals (Sweden)

    Tadayuki Ogawa

    2015-09-01

    Full Text Available Neurons exhibit dynamic structural changes in response to extracellular stimuli. Microtubules (MTs provide rapid and dramatic cytoskeletal changes within the structural framework. However, the molecular mechanisms and signaling networks underlying MT dynamics remain unknown. Here, we have applied a comprehensive and quantitative phospho-analysis of the MT destabilizer KIF2A to elucidate the regulatory mechanisms of MT dynamics within neurons in response to extracellular signals. Interestingly, we identified two different sets of KIF2A phosphorylation profiles that accelerate (A-type and brake (B-type the MT depolymerization activity of KIF2A. Brain-derived neurotrophic factor (BDNF stimulates PAK1 and CDK5 kinases, which decrease the MT depolymerizing activity of KIF2A through B-type phosphorylation, resulting in enhanced outgrowth of neural processes. In contrast, lysophosphatidic acid (LPA induces ROCK2 kinase, which suppresses neurite outgrowth from round cells via A-type phosphorylation. We propose that these two mutually exclusive forms of KIF2A phosphorylation differentially regulate neuronal morphogenesis during development.

  5. Insulin receptor substrate proteins create a link between the tyrosine phosphorylation cascade and the Ca2+-ATPases in muscle and heart.

    Science.gov (United States)

    Algenstaedt, P; Antonetti, D A; Yaffe, M B; Kahn, C R

    1997-09-19

    proteins bind to the Ca2+-ATPase of the sarcoplasmic reticulum in an insulin-regulated fashion, thus creating a potential link between the tyrosine phosphorylation cascade and effects of insulin on calcium.

  6. 3-Monochloro-1,2-propanediol (3-MCPD) induces apoptosis via mitochondrial oxidative phosphorylation system impairment and the caspase cascade pathway

    International Nuclear Information System (INIS)

    Peng, Xiaoli; Gan, Jing; Wang, Qian; Shi, Zhenqiang; Xia, Xiaodong

    2016-01-01

    3-Monochloro-1,2-propanediol (3-MCPD) is the most toxic chloropropanols compounds in foodstuff which mainly generated during thermal processing. Kidney is one of the primary target organs for 3-MCPD. Using human embryonic kidney cell (HEK293FT) as an in vitro model, we found that 3-MCPD caused concentration-dependent increase in cytoxicity as assessed by dye uptake, lactatedehydrogenase (LDH) leakage and MTT assays. HEK293FT cell treated with 3-MCPD suffered the decrease of mitochondrial membrane potential and the impairment of mitochondrial oxidative phosphorylation system, especially the reduced amount of mRNA expression and protein synthesis of electron transport chain complex II, complex IV, and complex III. More importantly, energy release (ATP synthesis) was significantly inhibited by 3-MCPD resulting from the down regulation expressions of ATP synthase (ATP6 and ATP8), as well as the loss of transmembrane potential required for synthesis of ATP. The decreased ratio of mitochondrial apoptogenic factors Bax/Bcl-2 and the cytochrome-c release from mitochondria to cytosol followed by the activation of apoptotic initiators caspase 9 and apoptotic executioners (caspase 3, caspase 6 and caspase 7) leading to apoptosis. The activation of caspase 8 and caspase 2 implied that there were probably other factors to induce the caspase-dependent apoptosis.

  7. 3-Monochloro-1,2-propanediol (3-MCPD) induces apoptosis via mitochondrial oxidative phosphorylation system impairment and the caspase cascade pathway.

    Science.gov (United States)

    Peng, Xiaoli; Gan, Jing; Wang, Qian; Shi, Zhenqiang; Xia, Xiaodong

    2016-11-30

    3-Monochloro-1,2-propanediol (3-MCPD) is the most toxic chloropropanols compounds in foodstuff which mainly generated during thermal processing. Kidney is one of the primary target organs for 3-MCPD. Using human embryonic kidney cell (HEK293FT) as an in vitro model, we found that 3-MCPD caused concentration-dependent increase in cytoxicity as assessed by dye uptake, lactatedehydrogenase (LDH) leakage and MTT assays. HEK293FT cell treated with 3-MCPD suffered the decrease of mitochondrial membrane potential and the impairment of mitochondrial oxidative phosphorylation system, especially the reduced amount of mRNA expression and protein synthesis of electron transport chain complex II, complex IV, and complex III. More importantly, energy release (ATP synthesis) was significantly inhibited by 3-MCPD resulting from the down regulation expressions of ATP synthase (ATP6 and ATP8), as well as the loss of transmembrane potential required for synthesis of ATP. The decreased ratio of mitochondrial apoptogenic factors Bax/Bcl-2 and the cytochrome-c release from mitochondria to cytosol followed by the activation of apoptotic initiators caspase 9 and apoptotic executioners (caspase 3, caspase 6 and caspase 7) leading to apoptosis. The activation of caspase 8 and caspase 2 implied that there were probably other factors to induce the caspase-dependent apoptosis. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  8. Learning Cascading

    CERN Document Server

    Covert, Michael

    2015-01-01

    This book is intended for software developers, system architects and analysts, big data project managers, and data scientists who wish to deploy big data solutions using the Cascading framework. You must have a basic understanding of the big data paradigm and should be familiar with Java development techniques.

  9. Signaling Cascades: Consequences of Varying Substrate and Phosphatase Levels

    DEFF Research Database (Denmark)

    Feliu, Elisenda; Knudsen, Michael; Wiuf, Carsten Henrik

    2012-01-01

    We study signaling cascades with an arbitrary number of layers of one-site phosphorylation cycles. Such cascades are abundant in nature and integrated parts of many pathways. Based on the Michaelis-Menten model of enzyme kinetics and the law of mass-action, we derive explicit analytic expressions...

  10. Gene regulation by MAP kinase cascades

    DEFF Research Database (Denmark)

    Fiil, Berthe Katrine; Petersen, Klaus; Petersen, Morten

    2009-01-01

    Mitogen-activated protein kinase (MAPK) cascades are signaling modules that transduce extracellular stimuli to a range of cellular responses. Research in yeast and metazoans has shown that MAPK-mediated phosphorylation directly or indirectly regulates the activity of transcription factors. Plant ...

  11. Oxidative phosphorylation revisited

    DEFF Research Database (Denmark)

    Nath, Sunil; Villadsen, John

    2015-01-01

    The fundamentals of oxidative phosphorylation and photophosphorylation are revisited. New experimental data on the involvement of succinate and malate anions respectively in oxidative phosphorylation and photophosphorylation are presented. These new data offer a novel molecular mechanistic...

  12. Cascade annealing: an overview

    International Nuclear Information System (INIS)

    Doran, D.G.; Schiffgens, J.O.

    1976-04-01

    Concepts and an overview of radiation displacement damage modeling and annealing kinetics are presented. Short-term annealing methodology is described and results of annealing simulations performed on damage cascades generated using the Marlowe and Cascade programs are included. Observations concerning the inconsistencies and inadequacies of current methods are presented along with simulation of high energy cascades and simulation of longer-term annealing

  13. Cascade quantum teleportation

    Institute of Scientific and Technical Information of China (English)

    ZHOU Nan-run; GONG Li-hua; LIU Ye

    2006-01-01

    In this letter a cascade quantum teleportation scheme is proposed. The proposed scheme needs less local quantum operations than those of quantum multi-teleportation. A quantum teleportation scheme based on entanglement swapping is presented and compared with the cascade quantum teleportation scheme. Those two schemes can effectively teleport quantum information and extend the distance of quantum communication.

  14. Mechanisms of cascade collapse

    International Nuclear Information System (INIS)

    Diaz de la Rubia, T.; Smalinskas, K.; Averback, R.S.; Robertson, I.M.; Hseih, H.; Benedek, R.

    1988-12-01

    The spontaneous collapse of energetic displacement cascades in metals into vacancy dislocation loops has been investigated by molecular dynamics (MD) computer simulation and transmission electron microscopy (TEM). Simulations of 5 keV recoil events in Cu and Ni provide the following scenario of cascade collapse: atoms are ejected from the central region of the cascade by replacement collision sequences; the central region subsequently melts; vacancies are driven to the center of the cascade during resolidification where they may collapse into loops. Whether or not collapse occurs depends critically on the melting temperature of the metal and the energy density and total energy in the cascade. Results of TEM are presented in support of this mechanism. 14 refs., 4 figs., 1 tab

  15. Conjugation of cascades

    International Nuclear Information System (INIS)

    San Martin, Jesus; Rodriguez-Perez, Daniel

    2009-01-01

    Presented in this work are some results relative to sequences found in the logistic equation bifurcation diagram, which is the unimodal quadratic map prototype. All of the different saddle-node bifurcation cascades, associated with every last appearance p-periodic orbit (p=3,4,5,...), can also be generated from the very Feigenbaum cascade. In this way it is evidenced the relationship between both cascades. The orbits of every saddle-node bifurcation cascade, mentioned above, are located in different chaotic bands, and this determines a sequence of orbits converging to every band-merging Misiurewicz point. In turn, these accumulation points form a sequence whose accumulation point is the Myrberg-Feigenbaum point. It is also proven that the first appearance orbits in the n-chaotic band converge to the same point as the last appearance orbits of the (n + 1)-chaotic band. The symbolic sequences of band-merging Misiurewicz points are computed for any window.

  16. Learning optimal embedded cascades.

    Science.gov (United States)

    Saberian, Mohammad Javad; Vasconcelos, Nuno

    2012-10-01

    The problem of automatic and optimal design of embedded object detector cascades is considered. Two main challenges are identified: optimization of the cascade configuration and optimization of individual cascade stages, so as to achieve the best tradeoff between classification accuracy and speed, under a detection rate constraint. Two novel boosting algorithms are proposed to address these problems. The first, RCBoost, formulates boosting as a constrained optimization problem which is solved with a barrier penalty method. The constraint is the target detection rate, which is met at all iterations of the boosting process. This enables the design of embedded cascades of known configuration without extensive cross validation or heuristics. The second, ECBoost, searches over cascade configurations to achieve the optimal tradeoff between classification risk and speed. The two algorithms are combined into an overall boosting procedure, RCECBoost, which optimizes both the cascade configuration and its stages under a detection rate constraint, in a fully automated manner. Extensive experiments in face, car, pedestrian, and panda detection show that the resulting detectors achieve an accuracy versus speed tradeoff superior to those of previous methods.

  17. Muscarinic agonists and phorbol esters increase tyrosine phosphorylation of a 40-kilodalton protein in hippocampal slices

    International Nuclear Information System (INIS)

    Stratton, K.R.; Worley, P.F.; Huganir, R.L.; Baraban, J.M.

    1989-01-01

    The authors have used the hippocampal slice preparation to investigate the regulation of protein tyrosine phosphorylation in brain. After pharmacological treatment of intact slices, proteins were separated by electrophoresis, and levels of protein tyrosine phosphorylation were assessed by immunoblotting with specific anti-phosphotyrosine antibodies. Phorbol esters, activators of the serine- and threonine-phosphorylating enzyme protein kinase C, selectively increase tyrosine phosphorylation of a soluble protein with an apparent molecular mass of approximately 40 kilodaltons. Muscarinic agonists such as carbachol and oxotremorine M that strongly activate the inositol phospholipid system also increase tyrosine phosphorylation of this protein. Neurotransmitter activation of the inositol phospholipid system and protein kinase C appears to trigger a cascade leading to increased tyrosine phosphorylation

  18. Cross-phosphorylation of bacterial serine/threonine and tyrosine protein kinases on key regulatory residues

    Directory of Open Access Journals (Sweden)

    Lei eShi

    2014-09-01

    Full Text Available Bacteria possess protein serine/threonine and tyrosine kinases which resemble eukaryal kinases in their capacity to phosphorylate multiple substrates. We hypothesized that the analogy might extend further, and bacterial kinases may also undergo mutual phosphorylation and activation, which is currently considered as a hallmark of eukaryal kinase networks. In order to test this hypothesis, we explored the capacity of all members of four different classes of serine/threonine and tyrosine kinases present in the firmicute model organism Bacillus subtilis to phosphorylate each other in vitro and interact with each other in vivo. The interactomics data suggested a high degree of connectivity among all types of kinases, while phosphorylation assays revealed equally wide-spread cross-phosphorylation events. Our findings suggest that the Hanks-type kinases PrkC, PrkD and YabT exhibit the highest capacity to phosphorylate other B. subtilis kinases, while the BY-kinase PtkA and the two-component-like kinases RsbW and SpoIIAB show the highest propensity to be phosphorylated by other kinases. Analysis of phosphorylated residues on several selected recipient kinases suggests that most cross-phosphorylation events concern key regulatory residues. Therefore, cross-phosphorylation events are very likely to influence the capacity of recipient kinases to phosphorylate substrates downstream in the signal transduction cascade. We therefore conclude that bacterial serine/threonine and tyrosine kinases probably engage in a network-type behavior previously described only in eukaryal cells.

  19. Cascade Organic Solar Cells

    KAUST Repository

    Schlenker, Cody W.

    2011-09-27

    We demonstrate planar organic solar cells consisting of a series of complementary donor materials with cascading exciton energies, incorporated in the following structure: glass/indium-tin-oxide/donor cascade/C 60/bathocuproine/Al. Using a tetracene layer grown in a descending energy cascade on 5,6-diphenyl-tetracene and capped with 5,6,11,12-tetraphenyl- tetracene, where the accessibility of the π-system in each material is expected to influence the rate of parasitic carrier leakage and charge recombination at the donor/acceptor interface, we observe an increase in open circuit voltage (Voc) of approximately 40% (corresponding to a change of +200 mV) compared to that of a single tetracene donor. Little change is observed in other parameters such as fill factor and short circuit current density (FF = 0.50 ± 0.02 and Jsc = 2.55 ± 0.23 mA/cm2) compared to those of the control tetracene-C60 solar cells (FF = 0.54 ± 0.02 and Jsc = 2.86 ± 0.23 mA/cm2). We demonstrate that this cascade architecture is effective in reducing losses due to polaron pair recombination at donor-acceptor interfaces, while enhancing spectral coverage, resulting in a substantial increase in the power conversion efficiency for cascade organic photovoltaic cells compared to tetracene and pentacene based devices with a single donor layer. © 2011 American Chemical Society.

  20. Energy cascades in Canada

    Energy Technology Data Exchange (ETDEWEB)

    Hayden, A. C.; Brown, T. D.

    1979-03-15

    Combining energy uses in a cascade can result in significant overall reductions in fuel requirements. The simplest applications for a cascade are in the recovery of waste heat from existing processes using special boilers or turbines. Specific applications of more-complex energy cascades for Canada are discussed. A combined-cycle plant at a chemical refinery in Ontario is world leader in energy efficiency. Total-energy systems for commercial buildings, such as one installed in a school in Western Canada, offer attractive energy and operating cost benefits. A cogeneration plant proposed for the National Capital Region, generating electricity as well as steam for district heating, allows the use of a low-grade fossil fuel (coal), greatly improves energy-transformation efficiency, and also utilizes an effectively renewable resource (municipal garbage). Despite the widespread availability of equipment and technology of energy cascades, the sale of steam and electricity across plant boundaries presents a barrier. More widespread use of cascades will require increased cooperation among industry, electric utilities and the various levels of government if Canada is to realize the high levels of energy efficiency potential available.

  1. Cascade Organic Solar Cells

    KAUST Repository

    Schlenker, Cody W.; Barlier, Vincent S.; Chin, Stephanie W.; Whited, Matthew T.; McAnally, R. Eric; Forrest, Stephen R.; Thompson, Mark E.

    2011-01-01

    We demonstrate planar organic solar cells consisting of a series of complementary donor materials with cascading exciton energies, incorporated in the following structure: glass/indium-tin-oxide/donor cascade/C 60/bathocuproine/Al. Using a tetracene layer grown in a descending energy cascade on 5,6-diphenyl-tetracene and capped with 5,6,11,12-tetraphenyl- tetracene, where the accessibility of the π-system in each material is expected to influence the rate of parasitic carrier leakage and charge recombination at the donor/acceptor interface, we observe an increase in open circuit voltage (Voc) of approximately 40% (corresponding to a change of +200 mV) compared to that of a single tetracene donor. Little change is observed in other parameters such as fill factor and short circuit current density (FF = 0.50 ± 0.02 and Jsc = 2.55 ± 0.23 mA/cm2) compared to those of the control tetracene-C60 solar cells (FF = 0.54 ± 0.02 and Jsc = 2.86 ± 0.23 mA/cm2). We demonstrate that this cascade architecture is effective in reducing losses due to polaron pair recombination at donor-acceptor interfaces, while enhancing spectral coverage, resulting in a substantial increase in the power conversion efficiency for cascade organic photovoltaic cells compared to tetracene and pentacene based devices with a single donor layer. © 2011 American Chemical Society.

  2. About phosphorylation of lappaconitine

    International Nuclear Information System (INIS)

    Burdelnaya, E.V.; Turmukhambetov, A.Zh.

    2005-01-01

    In the article chemical modifications of alkaloid lappaconitine are investigated. It was shown that synthesis of the phosphorylated derivatives are the ways to create new biologically active compounds. Interaction of lappaconitine with phosphorus pentachloride was used to obtain new phosphoric derivatives of alkaloid. The composition and structure of the new phosphorus-containing compounds were confirmed by elemental analysis: IR, UV and 13 C, 1 H, 31 P NMR -spectroscopy

  3. Hadron cascades produced by electromagnetic cascades

    International Nuclear Information System (INIS)

    Nelson, W.R.; Jenkins, T.M.; Ranft, J.

    1986-12-01

    A method for calculating high energy hadron cascades induced by multi-GeV electron and photon beams is described. Using the EGS4 computer program, high energy photons in the EM shower are allowed to interact hadronically according to the vector meson dominance (VMD) model, facilitated by a Monte Carlo version of the dual multistring fragmentation model which is used in the hadron cascade code FLUKA. The results of this calculation compare very favorably with experimental data on hadron production in photon-proton collisions and on the hadron production by electron beams on targets (i.e., yields in secondary particle beam lines). Electron beam induced hadron star density contours are also presented and are compared with those produced by proton beams. This FLUKA-EGS4 coupling technique could find use in the design of secondary beams, in the determination high energy hadron source terms for shielding purposes, and in the estimation of induced radioactivity in targets, collimators and beam dumps

  4. Cascade reactor: introduction

    International Nuclear Information System (INIS)

    Pitts, J.H.

    1985-01-01

    Cascade is a concept for an ultrasafe, highly efficient, easily built reactor to convert inertial-confinement fusion energy into electrical power. The Cascade design includes a rotating double-cone-shaped chamber in which a moving, 1-m-thick ceramic granular blanket is held against the reactor wall by centrifugal action. The granular material absorbs energy from the fusion reactions. Accomplishments this year associated with Cascade included improvements to simplify chamber design and lower activation. The authors switched from a steel chamber wall to one made from silicon-carbide (SiC) panels held in compression by SiC-fiber/Al-composite tendons that gird the chamber both circumferentially and axially. The authors studies a number of heat-exchanger designs and selected a gravity-flow cascade design with a vacuum on the primary side. This design allows granules leaving the chamber to be transported to the heat exchangers using their own peripheral speed. The granules transfer their thermal energy and return to the chamber gravitationally: no vacuum locks or conveyors are needed

  5. Stability of cascade search

    Energy Technology Data Exchange (ETDEWEB)

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

    2010-10-22

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

  6. Hadronic cascade processes

    International Nuclear Information System (INIS)

    Ilgenfritz, E.M.; Kripfganz, J.; Moehring, H.J.

    1977-01-01

    The analytical treatment of hadronic decay cascades within the framework of the statistical bootstrap model is demonstrated on the basis of a simple variant. Selected problems for a more comprehensive formulation of the model such as angular momentum conservation, quantum statistical effects, and the immediate applicability to particle production processes at high energies are discussed in detail

  7. Integrated Broadband Quantum Cascade Laser

    Science.gov (United States)

    Mansour, Kamjou (Inventor); Soibel, Alexander (Inventor)

    2016-01-01

    A broadband, integrated quantum cascade laser is disclosed, comprising ridge waveguide quantum cascade lasers formed by applying standard semiconductor process techniques to a monolithic structure of alternating layers of claddings and active region layers. The resulting ridge waveguide quantum cascade lasers may be individually controlled by independent voltage potentials, resulting in control of the overall spectrum of the integrated quantum cascade laser source. Other embodiments are described and claimed.

  8. Properties of phosphorylated thymidylate synthase

    DEFF Research Database (Denmark)

    Frączyk, Tomasz; Ruman, Tomasz; Wilk, Piotr

    2015-01-01

    by (31)P NMR to be modified only on histidine residues, like potassium phosphoramidate (KPA)-phosphorylated TS proteins. NanoLC-MS/MS, enabling the use of CID and ETD peptide fragmentation methods, identified several phosphohistidine residues, but certain phosphoserine and phosphothreonine residues were...... also implicated. Molecular dynamics studies, based on the mouse TS crystal structure, allowed one to assess potential of several phosphorylated histidine residues to affect catalytic activity, the effect being phosphorylation site dependent....

  9. Information cascade on networks

    Science.gov (United States)

    Hisakado, Masato; Mori, Shintaro

    2016-05-01

    In this paper, we discuss a voting model by considering three different kinds of networks: a random graph, the Barabási-Albert (BA) model, and a fitness model. A voting model represents the way in which public perceptions are conveyed to voters. Our voting model is constructed by using two types of voters-herders and independents-and two candidates. Independents conduct voting based on their fundamental values; on the other hand, herders base their voting on the number of previous votes. Hence, herders vote for the majority candidates and obtain information relating to previous votes from their networks. We discuss the difference between the phases on which the networks depend. Two kinds of phase transitions, an information cascade transition and a super-normal transition, were identified. The first of these is a transition between a state in which most voters make the correct choices and a state in which most of them are wrong. The second is a transition of convergence speed. The information cascade transition prevails when herder effects are stronger than the super-normal transition. In the BA and fitness models, the critical point of the information cascade transition is the same as that of the random network model. However, the critical point of the super-normal transition disappears when these two models are used. In conclusion, the influence of networks is shown to only affect the convergence speed and not the information cascade transition. We are therefore able to conclude that the influence of hubs on voters' perceptions is limited.

  10. Cascade ICF power reactor

    International Nuclear Information System (INIS)

    Hogan, W.J.; Pitts, J.H.

    1986-01-01

    The double-cone-shaped Cascade reaction chamber rotates at 50 rpm to keep a blanket of ceramic granules in place against the wall as they slide from the poles to the exit slots at the equator. The 1 m-thick blanket consists of layers of carbon, beryllium oxide, and lithium aluminate granules about 1 mm in diameter. The x rays and debris are stopped in the carbon granules; the neutrons are multiplied and moderated in the BeO and breed tritium in the LiAlO 2 . The chamber wall is made up of SiO tiles held in compression by a network of composite SiC/Al tendons. Cascade operates at a 5 Hz pulse rate with 300 MJ in each pulse. The temperature in the blanket reaches 1600 K on the inner surface and 1350 K at the outer edge. The granules are automatically thrown into three separate vacuum heat exchangers where they give up their energy to high pressure helium. The helium is used in a Brayton cycle to obtain a thermal-to-electric conversion efficiency of 55%. Studies have been done on neutron activation, debris recovery, vaporization and recondensation of blanket material, tritium control and recovery, fire safety, and cost. These studies indicate that Cascade appears to be a promising ICF reactor candidate from all standpoints. At the 1000 MWe size, electricity could be made for about the same cost as in a future fission reactor

  11. An Arabidopsis kinase cascade influences auxin-responsive cell expansion.

    Science.gov (United States)

    Enders, Tara A; Frick, Elizabeth M; Strader, Lucia C

    2017-10-01

    Mitogen-activated protein kinase (MPK) cascades are conserved mechanisms of signal transduction across eukaryotes. Despite the importance of MPK proteins in signaling events, specific roles for many Arabidopsis MPK proteins remain unknown. Multiple studies have suggested roles for MPK signaling in a variety of auxin-related processes. To identify MPK proteins with roles in auxin response, we screened mpk insertional alleles and identified mpk1-1 as a mutant that displays hypersensitivity in auxin-responsive cell expansion assays. Further, mutants defective in the upstream MAP kinase kinase MKK3 also display hypersensitivity in auxin-responsive cell expansion assays, suggesting that this MPK cascade affects auxin-influenced cell expansion. We found that MPK1 interacts with and phosphorylates ROP BINDING PROTEIN KINASE 1 (RBK1), a protein kinase that interacts with members of the Rho-like GTPases from Plants (ROP) small GTPase family. Similar to mpk1-1 and mkk3-1 mutants, rbk1 insertional mutants display auxin hypersensitivity, consistent with a possible role for RBK1 downstream of MPK1 in influencing auxin-responsive cell expansion. We found that RBK1 directly phosphorylates ROP4 and ROP6, supporting the possibility that RBK1 effects on auxin-responsive cell expansion are mediated through phosphorylation-dependent modulation of ROP activity. Our data suggest a MKK3 • MPK1 • RBK1 phosphorylation cascade that may provide a dynamic module for altering cell expansion. © 2017 The Authors The Plant Journal © 2017 John Wiley & Sons Ltd.

  12. Phosphorylation of chicken growth hormone

    International Nuclear Information System (INIS)

    Aramburo, C.; Montiel, J.L.; Donoghue, D.; Scanes, C.G.; Berghman, L.R.

    1990-01-01

    The possibility that chicken growth hormone (cGH) can be phosphorylated has been examined. Both native and biosynthetic cGH were phosphorylated by cAMP-dependent protein kinase (and γ- 32 P-ATP). The extent of phosphorylation was however less than that observed with ovine prolactin. Under the conditions employed, glycosylated cGH was not phosphorylated. Chicken anterior pituitary cells in primary culture were incubated in the presence of 32 P-phosphate. Radioactive phosphate was incorporated in vitro into the fraction immunoprecipitable with antisera against cGH. Incorporation was increased with cell number and time of incubation. The presence of GH releasing factor (GRF) increased the release of 32 P-phosphate labeled immunoprecipitable GH into the incubation media but not content of immunoprecipitable GH in the cells. The molecular weight of the phosphorylated immunoreactive cGH in the cells corresponded to cGH dimer

  13. Identification of ATM Protein Kinase Phosphorylation Sites by Mass Spectrometry.

    Science.gov (United States)

    Graham, Mark E; Lavin, Martin F; Kozlov, Sergei V

    2017-01-01

    ATM (ataxia-telangiectasia mutated) protein kinase is a key regulator of cellular responses to DNA damage and oxidative stress. DNA damage triggers complex cascade of signaling events leading to numerous posttranslational modification on multitude of proteins. Understanding the regulation of ATM kinase is therefore critical not only for understanding the human genetic disorder ataxia-telangiectasia and potential treatment strategies, but essential for deciphering physiological responses of cells to stress. These responses play an important role in carcinogenesis, neurodegeneration, and aging. We focus here on the identification of DNA damage inducible ATM phosphorylation sites to understand the importance of autophosphorylation in the mechanism of ATM kinase activation. We demonstrate the utility of using immunoprecipitated ATM in quantitative LC-MS/MS workflow with stable isotope dimethyl labeling of ATM peptides for identification of phosphorylation sites.

  14. Insulin increase in MAP kinase phosphorylation is shifted to early time-points by overexpressing APS, while Akt phosphorylation is not influenced.

    Science.gov (United States)

    Onnockx, Sheela; Xie, Jingwei; Degraef, Chantal; Erneux, Christophe; Pirson, Isabelle

    2009-09-10

    Upon insulin stimulation, the adaptor protein APS is recruited to the insulin receptor and tyrosine phosphorylated. APS initiates the insulin-induced TC10 cascade which participates to GLUT4 translocation to the plasma membrane. Nevertheless, the molecular mechanism that governs APS and its SH2 and PH domains action on the insulin transduction cascade is not yet fully understood. Here, we show that APS co-immunoprecipitates with the class I PI 3-kinase regulatory subunit p85, through its SH2 domain but that APS does not modulate neither PtdIns(3,4,5)P3 levels nor Akt phosphorylation provoked by insulin. We have confirmed a previously described positive effect of APS overexpression on insulin-induced MAPK phosphorylation upregulation. Consequently, we analyzed the role of SH2 and PH domains of APS in the APS increased MAPK phosphorylation observed upon insulin stimulation and correlated this with the membrane localization of the protein. The effect observed on MAPK phosphorylation requires the intact PH binding domain of APS as well as its SH2 domain.

  15. Cascading Corruption News

    DEFF Research Database (Denmark)

    Damgaard, Mads

    2018-01-01

    Through a content analysis of 8,800 news items and six months of front pages in three Brazilian newspapers, all dealing with corruption and political transgression, this article documents the remarkable skew of media attention to corruption scandals. The bias is examined as an information...... phenomenon, arising from systemic and commercial factors of Brazil’s news media: An information cascade of news on corruption formed, destabilizing the governing coalition and legitimizing the impeachment process of Dilma Rousseff. As this process gained momentum, questions of accountability were disregarded...

  16. Cascading Corruption News

    DEFF Research Database (Denmark)

    Damgaard, Mads

    2018-01-01

    Through a content analysis of 8,800 news items and six months of front pages in three Brazilian newspapers, all dealing with corruption and political transgression, this article documents the remarkable skew of media attention to corruption scandals. The bias is examined as an information...... phenomenon, arising from systemic and commercial factors of Brazil’s news media: An information cascade of news on corruption formed, destabilizing the governing coalition and legitimizing the impeachment process of Dilma Rousseff. As this process gained momentum, questions of accountability were disregarded...... by the media, with harmful effects on democracy....

  17. Band 3 Erythrocyte Membrane Protein Acts as Redox Stress Sensor Leading to Its Phosphorylation by p72 Syk

    Directory of Open Access Journals (Sweden)

    Antonella Pantaleo

    2016-01-01

    Full Text Available In erythrocytes, the regulation of the redox sensitive Tyr phosphorylation of band 3 and its functions are still partially defined. A role of band 3 oxidation in regulating its own phosphorylation has been previously suggested. The current study provides evidences to support this hypothesis: (i in intact erythrocytes, at 2 mM concentration of GSH, band 3 oxidation, and phosphorylation, Syk translocation to the membrane and Syk phosphorylation responded to the same micromolar concentrations of oxidants showing identical temporal variations; (ii the Cys residues located in the band 3 cytoplasmic domain are 20-fold more reactive than GSH; (iii disulfide linked band 3 cytoplasmic domain docks Syk kinase; (iv protein Tyr phosphatases are poorly inhibited at oxidant concentrations leading to massive band 3 oxidation and phosphorylation. We also observed that hemichromes binding to band 3 determined its irreversible oxidation and phosphorylation, progressive hemolysis, and serine hyperphosphorylation of different cytoskeleton proteins. Syk inhibitor suppressed the phosphorylation of band 3 also preventing serine phosphorylation changes and hemolysis. Our data suggest that band 3 acts as redox sensor regulating its own phosphorylation and that hemichromes leading to the protracted phosphorylation of band 3 may trigger a cascade of events finally leading to hemolysis.

  18. Cascade Error Projection Learning Algorithm

    Science.gov (United States)

    Duong, T. A.; Stubberud, A. R.; Daud, T.

    1995-01-01

    A detailed mathematical analysis is presented for a new learning algorithm termed cascade error projection (CEP) and a general learning frame work. This frame work can be used to obtain the cascade correlation learning algorithm by choosing a particular set of parameters.

  19. Interband cascade lasers

    International Nuclear Information System (INIS)

    Vurgaftman, I; Meyer, J R; Canedy, C L; Kim, C S; Bewley, W W; Merritt, C D; Abell, J; Weih, R; Kamp, M; Kim, M; Höfling, S

    2015-01-01

    We review the current status of interband cascade lasers (ICLs) emitting in the midwave infrared (IR). The ICL may be considered the hybrid of a conventional diode laser that generates photons via electron–hole recombination, and an intersubband-based quantum cascade laser (QCL) that stacks multiple stages for enhanced current efficiency. Following a brief historical overview, we discuss theoretical aspects of the active region and core designs, growth by molecular beam epitaxy, and the processing of broad-area, narrow-ridge, and distributed feedback (DFB) devices. We then review the experimental performance of pulsed broad area ICLs, as well as the continuous-wave (cw) characteristics of narrow ridges having good beam quality and DFBs producing output in a single spectral mode. Because the threshold drive powers are far lower than those of QCLs throughout the λ = 3–6 µm spectral band, ICLs are increasingly viewed as the laser of choice for mid-IR laser spectroscopy applications that do not require high output power but need to be hand-portable and/or battery operated. Demonstrated ICL performance characteristics to date include threshold current densities as low as 106 A cm −2 at room temperature (RT), cw threshold drive powers as low as 29 mW at RT, maximum cw operating temperatures as high as 118 °C, maximum cw output powers exceeding 400 mW at RT, maximum cw wallplug efficiencies as high as 18% at RT, maximum cw single-mode output powers as high as 55 mW at RT, and single-mode output at λ = 5.2 µm with a cw drive power of only 138 mW at RT. (topical review)

  20. Glycogen phosphorylation and Lafora disease.

    Science.gov (United States)

    Roach, Peter J

    2015-12-01

    Covalent phosphorylation of glycogen, first described 35 years ago, was put on firm ground through the work of the Whelan laboratory in the 1990s. But glycogen phosphorylation lay fallow until interest was rekindled in the mid 2000s by the finding that it could be removed by a glycogen-binding phosphatase, laforin, and that mutations in laforin cause a fatal teenage-onset epilepsy, called Lafora disease. Glycogen phosphorylation is due to phosphomonoesters at C2, C3 and C6 of glucose residues. Phosphate is rare, ranging from 1:500 to 1:5000 phosphates/glucose depending on the glycogen source. The mechanisms of glycogen phosphorylation remain under investigation but one hypothesis to explain C2 and perhaps C3 phosphate is that it results from a rare side reaction of the normal synthetic enzyme glycogen synthase. Lafora disease is likely caused by over-accumulation of abnormal glycogen in insoluble deposits termed Lafora bodies in neurons. The abnormality in the glycogen correlates with elevated phosphorylation (at C2, C3 and C6), reduced branching, insolubility and an enhanced tendency to aggregate and become insoluble. Hyperphosphorylation of glycogen is emerging as an important feature of this deadly childhood disease. Copyright © 2015 Elsevier Ltd. All rights reserved.

  1. Inferring network structure from cascades

    Science.gov (United States)

    Ghonge, Sushrut; Vural, Dervis Can

    2017-07-01

    Many physical, biological, and social phenomena can be described by cascades taking place on a network. Often, the activity can be empirically observed, but not the underlying network of interactions. In this paper we offer three topological methods to infer the structure of any directed network given a set of cascade arrival times. Our formulas hold for a very general class of models where the activation probability of a node is a generic function of its degree and the number of its active neighbors. We report high success rates for synthetic and real networks, for several different cascade models.

  2. Cascade energy amplifier

    International Nuclear Information System (INIS)

    Barzilov, A.P.; Gulevich, A.V.; Kukharchuk, O.F.

    2000-01-01

    The technical problem of long-life fission product and minor actinide incineration and production of plutonium fuel in the prospective nuclear systems will arise at significant scales of nuclear power industry development. Subcritical nuclear reactors driven by extemal neutron sources (energy amplifiers) are considered as incinerators of toxicity of complete nuclear industry. In the frames of this concept, the subcritical reactor part consisting of two coupled blanket regions (inner fast neutron spectrum core and outer thermal core) driven by extemal neutron source is discussed. Two types of source are studied: spallation target and 14-MeV fusion bum of micropellets. Liquid metal Pb-Bi is considered as target material and coolant of inner fast core. Thermal core is a heavy-water subcritical reactor of the Candu-type. The fast core is protected from thermal neutrons influence with the boron shield. All reactor technologies used in this concept are tested during years of operation and commercially available. Thus, the cascade energy amplifiers have a set of advantages in comparison with traditional concepts: in energy production, in transmutation efficiency, and in economics. (authors)

  3. Propofol directly increases tau phosphorylation.

    Directory of Open Access Journals (Sweden)

    Robert A Whittington

    2011-01-01

    Full Text Available In Alzheimer's disease (AD and other tauopathies, the microtubule-associated protein tau can undergo aberrant hyperphosphorylation potentially leading to the development of neurofibrillary pathology. Anesthetics have been previously shown to induce tau hyperphosphorylation through a mechanism involving hypothermia-induced inhibition of protein phosphatase 2A (PP2A activity. However, the effects of propofol, a common clinically used intravenous anesthetic, on tau phosphorylation under normothermic conditions are unknown. We investigated the effects of a general anesthetic dose of propofol on levels of phosphorylated tau in the mouse hippocampus and cortex under normothermic conditions. Thirty min following the administration of propofol 250 mg/kg i.p., significant increases in tau phosphorylation were observed at the AT8, CP13, and PHF-1 phosphoepitopes in the hippocampus, as well as at AT8, PHF-1, MC6, pS262, and pS422 epitopes in the cortex. However, we did not detect somatodendritic relocalization of tau. In both brain regions, tau hyperphosphorylation persisted at the AT8 epitope 2 h following propofol, although the sedative effects of the drug were no longer evident at this time point. By 6 h following propofol, levels of phosphorylated tau at AT8 returned to control levels. An initial decrease in the activity and expression of PP2A were observed, suggesting that PP2A inhibition is at least partly responsible for the hyperphosphorylation of tau at multiple sites following 30 min of propofol exposure. We also examined tau phosphorylation in SH-SY5Y cells transfected to overexpress human tau. A 1 h exposure to a clinically relevant concentration of propofol in vitro was also associated with tau hyperphosphorylation. These findings suggest that propofol increases tau phosphorylation both in vivo and in vitro under normothermic conditions, and further studies are warranted to determine the impact of this anesthetic on the acceleration of

  4. Ultrarelativistic cascades and strangeness production

    Energy Technology Data Exchange (ETDEWEB)

    Kahana, D.E. [State Univ. of New York, Stony Brook, NY (United States). Dept. of Physics; Kahana, S.H. [Brookhaven National Lab., Upton, NY (United States). Physics Dept.

    1998-08-24

    A two-phase cascade code, LUCIFER II, developed for the treatment of ultra high energy-ion-ion collisions is applied to the production of strangeness at SPS energies {radical}(s)=17-20. This simulation is able to simultaneously describe both hard processes such as Drell-Yan and slower, soft processes such as the production of light mesons by separating the dynamics into two steps, a fast cascade involving only the nucleons in the original colliding relativistic ions followed, after an appropriate delay, by a normal multiscattering of the resulting excited baryons and mesons produced virtually in the first step. No energy loss can take place in the short time interval over which the first cascade takes place. The chief result is a reconciliation of the important Drell-Yan measurements with the apparent success of standard cascades to describe the nucleon stopping and meson production in heavy-ion experiments at the CERN SPS. (orig.) 26 refs.

  5. Ultrarelativistic cascades and strangeness production

    International Nuclear Information System (INIS)

    Kahana, D.E.; Kahana, S.H.

    1998-01-01

    A two-phase cascade code, LUCIFER II, developed for the treatment of ultra high energy-ion-ion collisions is applied to the production of strangeness at SPS energies √(s)=17-20. This simulation is able to simultaneously describe both hard processes such as Drell-Yan and slower, soft processes such as the production of light mesons by separating the dynamics into two steps, a fast cascade involving only the nucleons in the original colliding relativistic ions followed, after an appropriate delay, by a normal multiscattering of the resulting excited baryons and mesons produced virtually in the first step. No energy loss can take place in the short time interval over which the first cascade takes place. The chief result is a reconciliation of the important Drell-Yan measurements with the apparent success of standard cascades to describe the nucleon stopping and meson production in heavy-ion experiments at the CERN SPS. (orig.)

  6. Ultrarelativistic cascades and strangeness production

    International Nuclear Information System (INIS)

    Kahana, D.E.; Kahana, S.H.

    1998-02-01

    A two phase cascade, LUCIFER II, developed for the treatment of ultra high energy Ion-Ion collisions is applied to the production of strangeness at SPS energies. This simulation is able to simultaneously describe both hard processes such as Drell-Yan and slower, soft processes such as the production of light mesons by separating the dynamics into two steps, a fast cascade involving only the nucleons in the original colliding relativistic ions followed, after an appropriate delay, by a normal multiscattering of the resulting excited baryons and mesons produced virtually in the first step. No energy loss can take place in the short time interval over which the first cascade takes place. The chief result is a reconciliation of the important Drell-Yan measurements with the apparent success of standard cascades to describe the nucleon stopping and meson production in heavy ion experiments at the CERN SPS

  7. Cascade redox flow battery systems

    Science.gov (United States)

    Horne, Craig R.; Kinoshita, Kim; Hickey, Darren B.; Sha, Jay E.; Bose, Deepak

    2014-07-22

    A reduction/oxidation ("redox") flow battery system includes a series of electrochemical cells arranged in a cascade, whereby liquid electrolyte reacts in a first electrochemical cell (or group of cells) before being directed into a second cell (or group of cells) where it reacts before being directed to subsequent cells. The cascade includes 2 to n stages, each stage having one or more electrochemical cells. During a charge reaction, electrolyte entering a first stage will have a lower state-of-charge than electrolyte entering the nth stage. In some embodiments, cell components and/or characteristics may be configured based on a state-of-charge of electrolytes expected at each cascade stage. Such engineered cascades provide redox flow battery systems with higher energy efficiency over a broader range of current density than prior art arrangements.

  8. Stochastic background of atmospheric cascades

    International Nuclear Information System (INIS)

    Wilk, G.; Wlodarczyk, Z.

    1993-01-01

    Fluctuations in the atmospheric cascades developing during the propagation of very high energy cosmic rays through the atmosphere are investigated using stochastic branching model of pure birth process with immigration. In particular, we show that the multiplicity distributions of secondaries emerging from gamma families are much narrower than those resulting from hadronic families. We argue that the strong intermittent like behaviour found recently in atmospheric families results from the fluctuations in the cascades themselves and are insensitive to the details of elementary interactions

  9. Computation of inverse magnetic cascades

    International Nuclear Information System (INIS)

    Montgomery, D.

    1981-10-01

    Inverse cascades of magnetic quantities for turbulent incompressible magnetohydrodynamics are reviewed, for two and three dimensions. The theory is extended to the Strauss equations, a description intermediate between two and three dimensions appropriate to tokamak magnetofluids. Consideration of the absolute equilibrium Gibbs ensemble for the system leads to a prediction of an inverse cascade of magnetic helicity, which may manifest itself as a major disruption. An agenda for computational investigation of this conjecture is proposed

  10. Differential regulation of the transcriptional activity of the glucocorticoid receptor through site-specific phosphorylation

    Directory of Open Access Journals (Sweden)

    Raj Kumar

    2008-08-01

    Full Text Available Raj Kumar1, William J Calhoun21Division of Gastroenterology; 2Division of Allergy, Pulmonary, Immunology, Critical Care, and Sleep (APICS, Department of Internal Medicine, University of Texas Medical Branch, Galveston, TX, USAAbstract: Post-translational modifications such as phosphorylation are known to play an important role in the gene regulation by the transcription factors including the nuclear hormone receptor superfamily of which the glucocorticoid receptor (GR is a member. Protein phosphorylation often switches cellular activity from one state to another. Like many other transcription factors, the GR is a phosphoprotein, and phosphorylation plays an important role in the regulation of GR activity. Cell signaling pathways that regulate phosphorylation of the GR and its associated proteins are important determinants of GR function under various physiological conditions. While the role of many phosphorylation sites in the GR is still not fully understood, the role of others is clearer. Several aspects of transcription factor function, including DNA binding affinity, interaction of transactivation domains with the transcription initiation complex, and shuttling between the cytoplasmic compartments, have all been linked to site-specific phosphorylation. All major phosphorylation sites in the human GR are located in the N-terminal domain including the major transactivation domain, AF1. Available literature clearly indicates that many of these potential phosphorylation sites are substrates for multiple kinases, suggesting the potential for a very complex regulatory network. Phosphorylated GR interacts favorably with critical coregulatory proteins and subsequently enhances transcriptional activity. In addition, the activities and specificities of coregulators may be subject to similar regulation by phosphorylation. Regulation of the GR activity due to phosphorylation appears to be site-specific and dependent upon specific cell signaling cascade

  11. SYMPOSIUM ON PLANT PROTEIN PHOSPHORYLATION

    Energy Technology Data Exchange (ETDEWEB)

    JOHN C WALKER

    2011-11-01

    Protein phosphorylation and dephosphorylation play key roles in many aspects of plant biology, including control of cell division, pathways of carbon and nitrogen metabolism, pattern formation, hormonal responses, and abiotic and biotic responses to environmental signals. A Symposium on Plant Protein Phosphorylation was hosted on the Columbia campus of the University of Missouri from May 26-28, 2010. The symposium provided an interdisciplinary venue at which scholars studying protein modification, as it relates to a broad range of biological questions and using a variety of plant species, presented their research. It also provided a forum where current international challenges in studies related to protein phosphorylation could be examined. The symposium also stimulated research collaborations through interactions and networking among those in the research community and engaged students and early career investigators in studying issues in plant biology from an interdisciplinary perspective. The proposed symposium, which drew 165 researchers from 13 countries and 21 States, facilitated a rapid dissemination of acquired knowledge and technical expertise regarding protein phosphorylation in plants to a broad range of plant biologists worldwide.

  12. Tyrosine phosphorylation in human lymphomas

    NARCIS (Netherlands)

    Haralambieva, E; Jones, M.; Roncador, GM; Cerroni, L; Lamant, L; Ott, G; Rosenwald, A; Sherman, C; Thorner, P; Kusec, R; Wood, KM; Campo, E; Falini, B; Ramsay, A; Marafioti, T; Stein, H; Kluin, PM; Pulford, K; Mason, DY

    2002-01-01

    In a previous study, we showed that the high level of protein tyrosine phosphorylation present in lymphomas containing an anaplastic lymphoma kinase (ALK) can be demonstrated in routinely processed paraffin tissue sections using immunolabelling techniques. In the present study we investigated

  13. IRS-1 serine phosphorylation and insulin resistance in skeletal muscle from pancreas tranplant recipient

    DEFF Research Database (Denmark)

    Bouzakri, K; Karlsson, HRK; Vestergaard, Henrik

    2006-01-01

    Insulin-dependent diabetic recipients of successful pancreas allografts achieve self-regulatory insulin secretion and discontinue exogenous insulin therapy; however, chronic hyperinsulinemia and impaired insulin sensitivity generally develop. To determine whether insulin resistance is accompanied....... In conclusion, peripheral insulin resistance in pancreas-kidney transplant recipients may arise from a negative feedback regulation of the canonical insulin-signaling cascade from excessive serine phosphorylation of IRS-1, possibly as a consequence of immunosuppressive therapy and hyperinsulinemia....... insulin receptor substrate (IRS)-1 Ser (312) and Ser (616) phosphorylation, IRS-1-associated phosphatidylinositol 3-kinase activity, and extracellular signal-regulated kinase (ERK)-1/2 phosphorylation were elevated in pancreas-kidney transplant recipients, coincident with fasting hyperinsulinemia. Basal...

  14. Time structure of cascade showers

    International Nuclear Information System (INIS)

    Nakatsuka, Takao

    1984-01-01

    Interesting results have been reported on the time structure of the electromagnetic components of air showers which have been obtained by using recent fast electronic circuit technology. However, these analyses and explanations seem not very persuasive. One of the reasons is that there is not satisfactory theoretical calculation yet to explain the delay of electromagnetic components in cascade processes which are the object of direct observation. Therefore, Monte Carlo calculation was attempted for examining the relationship between the altitude at which high energy γ-ray is generated up in the air and the time structure of cascade showers at the level of observation. The investigation of a dominant factor over the delay of electromagnetic components indicated that the delay due to the multiple scattering of electrons was essential. The author used the analytical solution found by himself of C. N. Yang's equation for the study on the delay due to multiple scattering. The results were as follows: The average delay time and the spread of distribution of electromagnetic cascades were approximately in linear relationship with the mass of a material having passed in a thin uniform medium; the rise time of arrival time distribution for electromagnetic cascade showers was very steep under the condition that they were generated up in the air and observed on the ground; the subpeaks delayed by tens of ns in arrival time may sometimes appear due to the perturbation in electromagnetic cascade processes. (Wakatsuki, Y.)

  15. MST4 kinase phosphorylates ACAP4 protein to orchestrate apical membrane remodeling during gastric acid secretion.

    Science.gov (United States)

    Yuan, Xiao; Yao, Phil Y; Jiang, Jiying; Zhang, Yin; Su, Zeqi; Yao, Wendy; Wang, Xueying; Gui, Ping; Mullen, McKay; Henry, Calmour; Ward, Tarsha; Wang, Wenwen; Brako, Larry; Tian, Ruijun; Zhao, Xuannv; Wang, Fengsong; Cao, Xinwang; Wang, Dongmei; Liu, Xing; Ding, Xia; Yao, Xuebiao

    2017-09-29

    Digestion in the stomach depends on acidification of the lumen. Histamine-elicited acid secretion is triggered by activation of the PKA cascade, which ultimately results in the insertion of gastric H,K-ATPases into the apical plasma membranes of parietal cells. Our recent study revealed the functional role of PKA-MST4-ezrin signaling axis in histamine-elicited acid secretion. However, it remains uncharacterized how the PKA-MST4-ezrin signaling axis operates the insertion of H,K-ATPases into the apical plasma membranes of gastric parietal cells. Here we show that MST4 phosphorylates ACAP4, an ARF6 GTPase-activating protein, at Thr 545 Histamine stimulation activates MST4 and promotes MST4 interaction with ACAP4. ACAP4 physically interacts with MST4 and is a cognate substrate of MST4 during parietal cell activation. The phosphorylation site of ACAP4 by MST4 was mapped to Thr 545 by mass spectrometric analyses. Importantly, phosphorylation of Thr 545 is essential for acid secretion in parietal cells because either suppression of ACAP4 or overexpression of non-phosphorylatable ACAP4 prevents the apical membrane reorganization and proton pump translocation elicited by histamine stimulation. In addition, persistent overexpression of MST4 phosphorylation-deficient ACAP4 results in inhibition of gastric acid secretion and blockage of tubulovesicle fusion to the apical membranes. Significantly, phosphorylation of Thr 545 enables ACAP4 to interact with ezrin. Given the location of Thr 545 between the GTPase-activating protein domain and the first ankyrin repeat, we reason that MST4 phosphorylation elicits a conformational change that enables ezrin-ACAP4 interaction. Taken together, these results define a novel molecular mechanism linking the PKA-MST4-ACAP4 signaling cascade to polarized acid secretion in gastric parietal cells. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  16. Pervanadate induces Mammalian Ste20 Kinase 3 (MST3) tyrosine phosphorylation but not activation.

    Science.gov (United States)

    Kan, Wei-Chih; Lu, Te-Ling; Ling, Pin; Lee, Te-Hsiu; Cho, Chien-Yu; Huang, Chi-Ying F; Jeng, Wen-Yih; Weng, Yui-Ping; Chiang, Chun-Yen; Wu, Jin Bin; Lu, Te-Jung

    2016-07-01

    The yeast Ste20 (sterile) protein kinase, which is a serine/threonine kinase, responds to the stimulation of the G proteincoupled receptor (GPCR) pheromone receptor. Ste20 protein kinase serves as the critical component that links signaling from the GPCR/G proteins to the mitogen-activated protein kinase (MAPK) cascade in yeast. The yeast Ste20p functions as a MAP kinase kinase kinase kinase (MAP4K) in the pheromone response. Ste20-like kinases are structurally conserved from yeast to mammals. The mechanism by which MAP4K links GPCR to the MAPK pathway is less clearly defined in vertebrates. In addition to MAP4K, the tyrosine kinase cascade bridges G proteins and the MAPK pathway in vertebrate cells. Mammalian Ste20 Kinase 3 (MST3) has been categorized into the Ste20 family and has been reported to function in the regulation of cell polarity and migration. However, whether MST3 tyrosine phosphorylation regulates diverse signaling pathways is unknown. In this study, the tyrosine phosphatase inhibitor pervanadate was found to induce MST3 tyrosine phosphorylation in intact cells, and the activity of tyrosine-phosphorylated MST3 was measured. This tyrosine-directed phosphorylation was independent of MST3 activity. Parameters including protein conformation, Triton concentration and ionic concentration influenced the sensitivity of MST3 activity. Taken together, our data suggests that the serine/threonine kinase MST3 undergoes tyrosinedirected phosphorylation. The tyrosine-phosphorylated MST3 may create a docking site for the structurally conserved SH2/SH3 (Src Homology 2 and 3) domains within the Src oncoprotein. The unusual tyrosinephosphorylated MST3 may recruit MST3 to various signaling components. Copyright © 2016. Published by Elsevier Inc.

  17. Rescuing Ecosystems from Extinction Cascades

    Science.gov (United States)

    Sahasrabudhe, Sagar; Motter, Adilson

    2010-03-01

    Food web perturbations stemming from climate change, overexploitation, invasive species, and natural disasters often cause an initial loss of species that results in a cascade of secondary extinctions. Using a predictive modeling framework, here we will present a systematic network-based approach to reduce the number of secondary extinctions. We will show that the extinction of one species can often be compensated by the concurrent removal of a second specific species, which is a counter-intuitive effect not previously tested in complex food webs. These compensatory perturbations frequently involve long-range interactions that are not a priori evident from local predator-prey relationships. Strikingly, in numerous cases even the early removal of a species that would eventually be extinct by the cascade is found to significantly reduce the number of cascading extinctions. Other nondestructive interventions based on partial removals and growth suppression and/or mortality increase are shown to sometimes prevent all secondary extinctions.

  18. Tyrosine phosphorylation of WW proteins

    Science.gov (United States)

    Reuven, Nina; Shanzer, Matan

    2015-01-01

    A number of key regulatory proteins contain one or two copies of the WW domain known to mediate protein–protein interaction via proline-rich motifs, such as PPxY. The Hippo pathway components take advantage of this module to transduce tumor suppressor signaling. It is becoming evident that tyrosine phosphorylation is a critical regulator of the WW proteins. Here, we review the current knowledge on the involved tyrosine kinases and their roles in regulating the WW proteins. PMID:25627656

  19. MAP Kinase Cascades Regulate the Cold Response by Modulating ICE1 Protein Stability.

    Science.gov (United States)

    Zhao, Chunzhao; Wang, Pengcheng; Si, Tong; Hsu, Chuan-Chih; Wang, Lu; Zayed, Omar; Yu, Zheping; Zhu, Yingfang; Dong, Juan; Tao, W Andy; Zhu, Jian-Kang

    2017-12-04

    Mitogen-activated protein kinase cascades are important signaling modules that convert environmental stimuli into cellular responses. We show that MPK3, MPK4, and MPK6 are rapidly activated after cold treatment. The mpk3 and mpk6 mutants display increased expression of CBF genes and enhanced freezing tolerance, whereas constitutive activation of the MKK4/5-MPK3/6 cascade in plants causes reduced expression of CBF genes and hypersensitivity to freezing, suggesting that the MKK4/5-MPK3/6 cascade negatively regulates the cold response. MPK3 and MPK6 can phosphorylate ICE1, a basic-helix-loop-helix transcription factor that regulates the expression of CBF genes, and the phosphorylation promotes the degradation of ICE1. Interestingly, the MEKK1-MKK2-MPK4 pathway constitutively suppresses MPK3 and MPK6 activities and has a positive role in the cold response. Furthermore, the MAPKKK YDA and two calcium/calmodulin-regulated receptor-like kinases, CRLK1 and CRLK2, negatively modulate the cold activation of MPK3/6. Our results uncover important roles of MAPK cascades in the regulation of plant cold response. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Multiplicity distributions in QCD cascades

    International Nuclear Information System (INIS)

    Gustafson, G.

    1992-03-01

    Multiplicity distributions for hadrons and for jets are studied in QCD parton cascades. The colour dipole formalism is used and earlier results in the double log approximation are generalized to include terms which are suppressed by colour factors or factors of ln s. The result is a set of coupled differential equations, together with appropriate boundary conditions

  1. A comparison of methods for cascade prediction

    OpenAIRE

    Guo, Ruocheng; Shakarian, Paulo

    2016-01-01

    Information cascades exist in a wide variety of platforms on Internet. A very important real-world problem is to identify which information cascades can go viral. A system addressing this problem can be used in a variety of applications including public health, marketing and counter-terrorism. As a cascade can be considered as compound of the social network and the time series. However, in related literature where methods for solving the cascade prediction problem were proposed, the experimen...

  2. Computer simulation of displacement cascades in copper

    International Nuclear Information System (INIS)

    Heinisch, H.L.

    1983-06-01

    More than 500 displacement cascades in copper have been generated with the computer simulation code MARLOWE over an energy range pertinent to both fission and fusion neutron spectra. Three-dimensional graphical depictions of selected cascades, as well as quantitative analysis of cascade shapes and sizes and defect densities, illustrate cascade behavior as a function of energy. With increasing energy, the transition from production of single compact damage regions to widely spaced multiple damage regions is clearly demonstrated

  3. Dynamics robustness of cascading systems.

    Directory of Open Access Journals (Sweden)

    Jonathan T Young

    2017-03-01

    Full Text Available A most important property of biochemical systems is robustness. Static robustness, e.g., homeostasis, is the insensitivity of a state against perturbations, whereas dynamics robustness, e.g., homeorhesis, is the insensitivity of a dynamic process. In contrast to the extensively studied static robustness, dynamics robustness, i.e., how a system creates an invariant temporal profile against perturbations, is little explored despite transient dynamics being crucial for cellular fates and are reported to be robust experimentally. For example, the duration of a stimulus elicits different phenotypic responses, and signaling networks process and encode temporal information. Hence, robustness in time courses will be necessary for functional biochemical networks. Based on dynamical systems theory, we uncovered a general mechanism to achieve dynamics robustness. Using a three-stage linear signaling cascade as an example, we found that the temporal profiles and response duration post-stimulus is robust to perturbations against certain parameters. Then analyzing the linearized model, we elucidated the criteria of when signaling cascades will display dynamics robustness. We found that changes in the upstream modules are masked in the cascade, and that the response duration is mainly controlled by the rate-limiting module and organization of the cascade's kinetics. Specifically, we found two necessary conditions for dynamics robustness in signaling cascades: 1 Constraint on the rate-limiting process: The phosphatase activity in the perturbed module is not the slowest. 2 Constraints on the initial conditions: The kinase activity needs to be fast enough such that each module is saturated even with fast phosphatase activity and upstream changes are attenuated. We discussed the relevance of such robustness to several biological examples and the validity of the above conditions therein. Given the applicability of dynamics robustness to a variety of systems, it

  4. Cascaded Bragg scattering in fiber optics.

    Science.gov (United States)

    Xu, Y Q; Erkintalo, M; Genty, G; Murdoch, S G

    2013-01-15

    We report on a theoretical and experimental study of cascaded Bragg scattering in fiber optics. We show that the usual energy-momentum conservation of Bragg scattering can be considerably relaxed via cascade-induced phase-matching. Experimentally we demonstrate frequency translation over six- and 11-fold cascades, in excellent agreement with derived phase-matching conditions.

  5. Phosphorylation regulates SIRT1 function.

    Directory of Open Access Journals (Sweden)

    Tsutomu Sasaki

    Full Text Available BACKGROUND: SIR2 is an NAD(+-dependent deacetylase [1]-[3] implicated in the regulation of lifespan in species as diverse as yeast [4], worms [5], and flies [6]. We previously reported that the level of SIRT1, the mammalian homologue of SIR2 [7], [8], is coupled to the level of mitotic activity in cells both in vitro and in vivo[9]. Cells from long-lived mice maintained SIRT1 levels of young mice in tissues that undergo continuous cell replacement by proliferating stem cells. Changes in SIRT1 protein level were not associated with changes in mRNA level, suggesting that SIRT1 could be regulated post-transcriptionally. However, other than a recent report on sumoylation [10] and identification of SIRT1 as a nuclear phospho-protein by mass spectrometry [11], post-translational modifications of this important protein have not been reported. METHODOLOGY/PRINCIPAL FINDINGS: We identified 13 residues in SIRT1 that are phosphorylated in vivo using mass spectrometry. Dephosphorylation by phosphatases in vitro resulted in decreased NAD(+-dependent deacetylase activity. We identified cyclinB/Cdk1 as a cell cycle-dependent kinase that forms a complex with and phosphorylates SIRT1. Mutation of two residues phosphorylated by Cyclin B/Cdk1 (threonine 530 and serine 540 disturbs normal cell cycle progression and fails to rescue proliferation defects in SIRT1-deficient cells [12], [13]. CONCLUSIONS/SIGNIFICANCE: Pharmacological manipulation of SIRT1 activity is currently being tested as a means of extending lifespan in mammals. Treatment of obese mice with resveratrol, a pharmacological activator of SIRT1, modestly but significantly improved longevity and, perhaps more importantly, offered some protection against the development of type 2 diabetes mellitus and metabolic syndrome [14]-[16]. Understanding the endogenous mechanisms that regulate the level and activity of SIRT1, therefore, has obvious relevance to human health and disease. Our results identify

  6. Melatonin synthesis in the human ciliary body triggered by TRPV4 activation: Involvement of AANAT phosphorylation.

    Science.gov (United States)

    Alkozi, Hanan Awad; Perez de Lara, María J; Pintor, Jesús

    2017-09-01

    Melatonin is a substance synthesized in the pineal gland as well as in other organs. This substance is involved in many ocular functions, giving its synthesis in numerous eye structures. Melatonin is synthesized from serotonin through two enzymes, the first limiting step into the synthesis of melatonin being aralkylamine N-acetyltransferase (AANAT). In this current study, AANAT phosphorylation after the activation of TRPV4 was studied using human non-pigmented epithelial ciliary body cells. Firstly, it was necessary to determine the adequate time and dose of the TRPV4 agonist GSK1016790A to reach the maximal phosphorylation of AANAT. An increase of 72% was observed after 5 min incubation with 10 nM GSK (**p melatonin synthesis. The involvement of a TRPV4 channel in melatonin synthesis was verified by antagonist and siRNA studies as a previous step to studying intracellular signalling. Studies performed on the second messengers involved in GSK induced AANAT phosphorylation were carried out by inhibiting several pathways. In conclusion, the activation of calmodulin and calmodulin-dependent protein kinase II was confirmed, as shown by the cascade seen in AANAT phosphorylation (***p melatonin levels. In conclusion, the activation of a TRPV4 present in human ciliary body epithelial cells produced an increase in AANAT phosphorylation and a further melatonin increase by a mechanism in which Ca-calmodulin and the calmodulin-dependent protein kinase II are involved. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Detection of phosphorylated mitogen-activated protein kinase in the developing spinal cord of the mouse embryo

    International Nuclear Information System (INIS)

    Teraishi, Toshiya; Miura, Kenji

    2011-01-01

    Highlights: → We detected physiologically phosphorylated MAPKs in developing spinal cord. → We detected physiologically phosphorylated MAPKs by an improved method. → p-ERK1/2 and p-JNK1/2 were detected in the marginal layer and the dorsal horn. → p-ERK1/2 and p-JNK1/2 might play critical roles in the developing spinal cord. → Constructing phosphoprotein atlases will be possible if expanding this work. -- Abstract: Global understanding of the proteome is a major research topic. The comprehensive visualization of the distribution of proteins in vivo or the construction of in situ protein atlases may be a valuable strategy for proteomic researchers. Information about the distribution of various proteins under physiological and pathological conditions should be extremely valuable for the basic and clinical sciences. The mitogen-activated protein kinase (MAPK) cascade plays an essential role in intracellular signaling in organisms. This cascade also regulates biological processes involving development, differentiation, and proliferation. Phosphorylation and dephosphorylation are integral reactions in regulating the activity of MAPKs. Changes in the phosphorylation state of MAPKs are rapid and reversible; therefore, the localizations of physiologically phosphorylated MAPKs in vivo are difficult to accurately detect. Furthermore, phosphorylated MAPKs are likely to change phosphorylated states through commonly used experimental manipulations. In the present study, as a step toward the construction of in situ phosphoprotein atlases, we attempted to detect physiologically phosphorylated MAPKs in vivo in developing spinal cords of mice. We previously reported an improved immunohistochemical method for detecting unstable phosphorylated MAPKs. The distribution patterns of phosphorylated MAPKs in the spinal cords of embryonic mice from embryonic day 13 (E13) to E17 were observed with an improved immunohistochemical method. Phosphorylated extracellular signal

  8. Phosphorylated nano-diamond/ Polyimide Nanocomposites

    International Nuclear Information System (INIS)

    Beyler-Çiǧil, Asli; Çakmakçi, Emrah; Kahraman, Memet Vezir

    2014-01-01

    In this study, a novel route to synthesize polyimide (PI)/phosphorylated nanodiamond films with improved thermal and mechanical properties was developed. Surface phosphorylation of nano-diamond was performed in dichloromethane. Phosphorylation dramatically enhanced the thermal stability of nano-diamond. Poly(amic acid) (PAA), which is the precursor of PI, was successfully synthesized with 3,3',4,4'-Benzophenonetetracarboxylic dianhydride (BTDA) and 4,4'-oxydianiline (4,4'-ODA) in the solution of N,N- dimethylformamide (DMF). Pure BTDA-ODA polyimide films and phosphorylated nanodiamond containing BTDA-ODA PI films were prepared. The PAA displayed good compatibility with phosphorylated nano-diamond. The morphology of the polyimide (PI)/phosphorylated nano-diamond was characterized by scanning electron microscopy (SEM). Chemical structure of polyimide and polyimide (PI)/phosphorylated nano-diamond was characterized by FTIR. SEM and FTIR results showed that the phosphorylated nano-diamond was successfully prepared. Thermal properties of the polyimide (PI)/phosphorylated nanodiamond was characterized by thermogravimetric analysis (TGA). TGA results showed that the thermal stability of (PI)/phosphorylated nano-diamond film was increased

  9. Tyrosine phosphorylation in signal transduction

    International Nuclear Information System (INIS)

    Roberts, T.M.; Kaplan, D.; Morgan, W.; Keller, T.; Mamon, H.; Piwnica-Worms, H.; Druker, B.; Whitman, M.; Morrison, D.; Cohen, B.; Schaffhausen, B.; Cantley, L.; Rapp, U.

    1988-01-01

    Recent work has focused on the elucidation of the mechanisms by which membrane-bound tyrosine kinases transmit signals within the cell. To examine the role of tyrosine phosphorylation the authors have employed the following strategy. First, they have utilized antibodies to phosphotyrosine (anti-P.Tyr) to identify candidate substrates of various tyrosine kinases, such as pp60 c-src , the CSF- receptor, or the platelet-derived growth factor (PDGF) receptor. Second, they have attempted to characterize the biochemical properties of the putative substrates and to determine in what manner these properties are modified by phosphorylation on tyrosine residues. In this endeavor, they are recapitulating the classic biochemical analysis used to study the effect of kinases on metabolism. The final portion of our work consists of using modern molecular biological strategies to clone the genes or cDNAs for the substrates and overproduce the relevant proteins for studies in vitro in defined systems. This paper describes the first and second aspects of this strategy, the identification and characterization of novel substrate molecules

  10. Conformational Clusters of Phosphorylated Tyrosine.

    Science.gov (United States)

    Abdelrasoul, Maha; Ponniah, Komala; Mao, Alice; Warden, Meghan S; Elhefnawy, Wessam; Li, Yaohang; Pascal, Steven M

    2017-12-06

    Tyrosine phosphorylation plays an important role in many cellular and intercellular processes including signal transduction, subcellular localization, and regulation of enzymatic activity. In 1999, Blom et al., using the limited number of protein data bank (PDB) structures available at that time, reported that the side chain structures of phosphorylated tyrosine (pY) are partitioned into two conserved conformational clusters ( Blom, N.; Gammeltoft, S.; Brunak, S. J. Mol. Biol. 1999 , 294 , 1351 - 1362 ). We have used the spectral clustering algorithm to cluster the increasingly growing number of protein structures with pY sites, and have found that the pY residues cluster into three distinct side chain conformations. Two of these pY conformational clusters associate strongly with a narrow range of tyrosine backbone conformation. The novel cluster also highly correlates with the identity of the n + 1 residue, and is strongly associated with a sequential pYpY conformation which places two adjacent pY side chains in a specific relative orientation. Further analysis shows that the three pY clusters are associated with distinct distributions of cognate protein kinases.

  11. A Large-Scale Quantitative Proteomic Approach to Identifying Sulfur Mustard-Induced Protein Phosphorylation Cascades

    Science.gov (United States)

    2010-01-01

    snapshot of SM-induced toxicity. Over the past few years, innovations in systems biology and biotechnology have led to important advances in our under...perturbations. SILAC has been used to study tumor metastasis (3, 4), focal adhesion- associated proteins, growth factor signaling, and insulin regula- tion (5...stained with colloidal Coomassie blue. After it was destained, the gel lane was excised into six regions, and each region was cut into 1 mm cubes

  12. Threonine phosphorylation of rat liver glycogen synthase

    International Nuclear Information System (INIS)

    Arino, J.; Arro, M.; Guinovart, J.J.

    1985-01-01

    32 P-labeled glycogen synthase specifically immunoprecipitated from 32 P-phosphate incubated rat hepatocytes contains, in addition to [ 32 P] phosphoserine, significant levels of [ 32 P] phosphothreonine. When the 32 P-immunoprecipitate was cleaved with CNBr, the [ 32 P] phosphothreonine was recovered in the large CNBr fragment (CB-2, Mapp 28 Kd). Homogeneous rat liver glycogen synthase was phosphorylated by all the protein kinases able to phosphorylate CB-2 in vitro. After analysis of the immunoprecipitated enzyme for phosphoaminoacids, it was observed that only casein kinase II was able to phosphorylate on threonine and 32 P-phosphate was only found in CB-2. These results demonstrate that rat liver glycogen synthase is phosphorylated at threonine site(s) contained in CB-2 and strongly indicate that casein kinase II may play a role in the ''in vivo'' phosphorylation of liver glycogen synthase. This is the first protein kinase reported to phosphorylate threonine residues in liver glycogen synthase

  13. Phosphoinositolphosphate (PIP) cascade induction by hypertonic stress of plant tissue

    International Nuclear Information System (INIS)

    Srivastava, A.; Jacoby, B.

    1989-01-01

    Inositol 1,4,5-trisphosphate (IP 3 ) was determined by competition with [ 3 H]-IP 3 for binding to an IP 3 specific protein. A hypertonic mannitol, sorbitol or lactose shock induced an increase in the rate of K + uptake and raised the IP 3 content of Beta vulgaris slices, excised Vigna mungo and Sorghum bicolor roots, as well as attached V. mungo roots. Increased K + uptake could also be induced by compounds that artificially induce the PIP cascade, or mimic it's products. A hypertonic shock, administered to intact B. vulgaris slices, further enhanced the phosphorylation of a 20 kD protein in the plasmalemma. Maximal IP 3 content was found 10 min after hypertonic induction and maximal K + uptake was obtained 10 min later. The effect of a continuous hypertonic treatment on IP 3 content, but not on K + uptake, was transient. Li + decreased the rate of IP 3 metabolism

  14. Atom-atom collision cascades localization

    International Nuclear Information System (INIS)

    Kirsanov, V.V.

    1980-01-01

    The presence of an impurity and thermal vibration influence on the atom-atom collision cascade development is analysed by the computer simulation method (the modificated dynamic model). It is discovered that the relatively low energetic cascades are localized with the temperature increase of an irradiated crystal. On the basis of the given effect the mechanism of splitting of the high energetic cascades into subcascades is proposed. It accounts for two factors: the primary knocked atom energy and the irradiated crystal temperature. Introduction of an impurity also localizes the cascades independently from the impurity atom mass. The cascades localization leads to intensification of the process of annealing in the cascades and reduction of the post-cascade vacancy cluster sizes. (author)

  15. Cascade Chaotic System With Applications.

    Science.gov (United States)

    Zhou, Yicong; Hua, Zhongyun; Pun, Chi-Man; Chen, C L Philip

    2015-09-01

    Chaotic maps are widely used in different applications. Motivated by the cascade structure in electronic circuits, this paper introduces a general chaotic framework called the cascade chaotic system (CCS). Using two 1-D chaotic maps as seed maps, CCS is able to generate a huge number of new chaotic maps. Examples and evaluations show the CCS's robustness. Compared with corresponding seed maps, newly generated chaotic maps are more unpredictable and have better chaotic performance, more parameters, and complex chaotic properties. To investigate applications of CCS, we introduce a pseudo-random number generator (PRNG) and a data encryption system using a chaotic map generated by CCS. Simulation and analysis demonstrate that the proposed PRNG has high quality of randomness and that the data encryption system is able to protect different types of data with a high-security level.

  16. Cascade reactor: granule fabrication processes

    International Nuclear Information System (INIS)

    Erlandson, O.D.; Winkler, E.O.; Maya, I.; Pitts, J.H.

    1985-01-01

    A key feature of Cascade is the granular blanket. Of the many blanket material options open to Cascade, fabrication of Li 2 O granules was felt to offer the greatest challenge. The authors explored available methods for initial Li 2 O granule fabrication. They identified three cost-effective processes for fabricating Li 2 O granules: the VSM drop-melt furnace process, which is based on melting and spheroidizing irregularly shaped Li 2 O feed granules; the LiOH process, which spheroidizes liquefied LiOH and uses GA Technologies' sphere-forming procedures; and the Li 2 CO 3 sol-gel process, used for making spherical fuel particles for the high-temperature gas-cooled reactor (HTGR). Each process is described below

  17. Bankruptcy cascades in interbank markets.

    Directory of Open Access Journals (Sweden)

    Gabriele Tedeschi

    Full Text Available We study a credit network and, in particular, an interbank system with an agent-based model. To understand the relationship between business cycles and cascades of bankruptcies, we model a three-sector economy with goods, credit and interbank market. In the interbank market, the participating banks share the risk of bad debits, which may potentially spread a bank's liquidity problems through the network of banks. Our agent-based model sheds light on the correlation between bankruptcy cascades and the endogenous economic cycle of booms and recessions. It also demonstrates the serious trade-off between, on the one hand, reducing risks of individual banks by sharing them and, on the other hand, creating systemic risks through credit-related interlinkages of banks. As a result of our study, the dynamics underlying the meltdown of financial markets in 2008 becomes much better understandable.

  18. Lens Coupled Quantum Cascade Laser

    Science.gov (United States)

    Hu, Qing (Inventor); Lee, Alan Wei Min (Inventor)

    2013-01-01

    Terahertz quantum cascade (QC) devices are disclosed that can operate, e.g., in a range of about 1 THz to about 10 THz. In some embodiments, QC lasers are disclosed in which an optical element (e.g., a lens) is coupled to an output facet of the laser's active region to enhance coupling of the lasing radiation from the active region to an external environment. In other embodiments, terahertz amplifier and tunable terahertz QC lasers are disclosed.

  19. Mapping of p140Cap phosphorylation sites

    DEFF Research Database (Denmark)

    Repetto, Daniele; Aramu, Simona; Boeri Erba, Elisabetta

    2013-01-01

    phosphorylation and tunes its interactions with other regulatory molecules via post-translation modification. In this work, using mass spectrometry, we found that p140Cap is in vivo phosphorylated on tyrosine (Y) within the peptide GEGLpYADPYGLLHEGR (from now on referred to as EGLYA) as well as on three serine...... residues. Consistently, EGLYA has the highest score of in silico prediction of p140Cap phosphorylation. To further investigate the p140Cap function, we performed site specific mutagenesis on tyrosines inserted in EGLYA and EPLYA, a second sequence with the same highest score of phosphorylation. The mutant...

  20. Phosphorylation of human link proteins

    International Nuclear Information System (INIS)

    Oester, D.A.; Caterson, B.; Schwartz, E.R.

    1986-01-01

    Three link proteins of 48, 44 and 40 kDa were purified from human articular cartilage and identified with monoclonal anti-link protein antibody 8-A-4. Two sets of lower molecular weight proteins of 30-31 kDa and 24-26 kDa also contained link protein epitopes recognized by the monoclonal antibody and were most likely degradative products of the intact link proteins. The link proteins of 48 and 40 kDa were identified as phosphoproteins while the 44 kDa link protein did not contain 32 P. The phosphorylated 48 and 40 kDa link proteins contained approximately 2 moles PO 4 /mole link protein

  1. SIMAC - A phosphoproteomic strategy for the rapid separation of mono-phosphorylated from multiply phosphorylated peptides

    DEFF Research Database (Denmark)

    Thingholm, Tine E; Jensen, Ole N; Robinson, Phillip J

    2008-01-01

    spectrometric analysis, such as immobilized metal affinity chromatography or titanium dioxide the coverage of the phosphoproteome of a given sample is limited. Here we report a simple and rapid strategy - SIMAC - for sequential separation of mono-phosphorylated peptides and multiply phosphorylated peptides from...... and an optimized titanium dioxide chromatographic method. More than double the total number of identified phosphorylation sites was obtained with SIMAC, primarily from a three-fold increase in recovery of multiply phosphorylated peptides....

  2. Stabilization of Microtubule-Unbound Tau via Tau Phosphorylation at Ser262/356 by Par-1/MARK Contributes to Augmentation of AD-Related Phosphorylation and Aβ42-Induced Tau Toxicity.

    Directory of Open Access Journals (Sweden)

    Kanae Ando

    2016-03-01

    Full Text Available Abnormal accumulation of the microtubule-interacting protein tau is associated with neurodegenerative diseases including Alzheimer's disease (AD. β-amyloid (Aβ lies upstream of abnormal tau behavior, including detachment from microtubules, phosphorylation at several disease-specific sites, and self-aggregation into toxic tau species in AD brains. To prevent the cascade of events leading to neurodegeneration in AD, it is essential to elucidate the mechanisms underlying the initial events of tau mismetabolism. Currently, however, these mechanisms remain unclear. In this study, using transgenic Drosophila co-expressing human tau and Aβ, we found that tau phosphorylation at AD-related Ser262/356 stabilized microtubule-unbound tau in the early phase of tau mismetabolism, leading to neurodegeneration. Aβ increased the level of tau detached from microtubules, independent of the phosphorylation status at GSK3-targeted SP/TP sites. Such mislocalized tau proteins, especially the less phosphorylated species, were stabilized by phosphorylation at Ser262/356 via PAR-1/MARK. Levels of Ser262 phosphorylation were increased by Aβ42, and blocking this stabilization of tau suppressed Aβ42-mediated augmentation of tau toxicity and an increase in the levels of tau phosphorylation at the SP/TP site Thr231, suggesting that this process may be involved in AD pathogenesis. In contrast to PAR-1/MARK, blocking tau phosphorylation at SP/TP sites by knockdown of Sgg/GSK3 did not reduce tau levels, suppress tau mislocalization to the cytosol, or diminish Aβ-mediated augmentation of tau toxicity. These results suggest that stabilization of microtubule-unbound tau by phosphorylation at Ser262/356 via the PAR-1/MARK may act in the initial steps of tau mismetabolism in AD pathogenesis, and that such tau species may represent a potential therapeutic target for AD.

  3. Abnormal cascading failure spreading on complex networks

    International Nuclear Information System (INIS)

    Wang, Jianwei; Sun, Enhui; Xu, Bo; Li, Peng; Ni, Chengzhang

    2016-01-01

    Applying the mechanism of the preferential selection of the flow destination, we develop a new method to quantify the initial load on an edge, of which the flow is transported along the path with the shortest edge weight between two nodes. Considering the node weight, we propose a cascading model on the edge and investigate cascading dynamics induced by the removal of the edge with the largest load. We perform simulated attacks on four types of constructed networks and two actual networks and observe an interesting and counterintuitive phenomenon of the cascading spreading, i.e., gradually improving the capacity of nodes does not lead to the monotonous increase in the robustness of these networks against cascading failures. The non monotonous behavior of cascading dynamics is well explained by the analysis on a simple graph. We additionally study the effect of the parameter of the node weight on cascading dynamics and evaluate the network robustness by a new metric.

  4. Combined 15N-Labeling and TandemMOAC Quantifies Phosphorylation of MAP Kinase Substrates Downstream of MKK7 in Arabidopsis

    Directory of Open Access Journals (Sweden)

    Nicola V. Huck

    2017-12-01

    Full Text Available Reversible protein phosphorylation is a widespread posttranslational modification that plays a key role in eukaryotic signal transduction. Due to the dynamics of protein abundance, low stoichiometry and transient nature of protein phosphorylation, the detection and accurate quantification of substrate phosphorylation by protein kinases remains a challenge in phosphoproteome research. Here, we combine tandem metal-oxide affinity chromatography (tandemMOAC with stable isotope 15N metabolic labeling for the measurement and accurate quantification of low abundant, transiently phosphorylated peptides by mass spectrometry. Since tandemMOAC is not biased toward the enrichment of acidophilic, basophilic, or proline-directed kinase substrates, the method is applicable to identify targets of all these three types of protein kinases. The MKK7-MPK3/6 module, for example, is involved in the regulation of plant development and plant basal and systemic immune responses, but little is known about downstream cascade components. Using our here described phosphoproteomics approach we identified several MPK substrates downstream of the MKK7-MPK3/6 phosphorylation cascade in Arabidopsis. The identification and validation of dynamin-related protein 2 as a novel phosphorylation substrate of the MKK7-MPK3/6 module establishes a novel link between MPK signaling and clathrin-mediated vesicle trafficking.

  5. Identification of Tyrosine Phosphorylated Proteins by SH2 Domain Affinity Purification and Mass Spectrometry.

    Science.gov (United States)

    Buhs, Sophia; Gerull, Helwe; Nollau, Peter

    2017-01-01

    Phosphotyrosine signaling plays a major role in the control of many important biological functions such as cell proliferation and apoptosis. Deciphering of phosphotyrosine-dependent signaling is therefore of great interest paving the way for the understanding of physiological and pathological processes of signal transduction. On the basis of the specific binding of SH2 domains to phosphotyrosine residues, we here present an experimental workflow for affinity purification and subsequent identification of tyrosine phosphorylated proteins by mass spectrometry. In combination with SH2 profiling, a broadly applicable platform for the characterization of phosphotyrosine profiles in cell extracts, our pull down strategy enables researchers by now to identify proteins in signaling cascades which are differentially phosphorylated and selectively recognized by distinct SH2 domains.

  6. ATF3 activates Stat3 phosphorylation through inhibition of p53 expression in skin cancer cells.

    Science.gov (United States)

    Hao, Zhen-Feng; Ao, Jun-Hong; Zhang, Jie; Su, You-Ming; Yang, Rong-Ya

    2013-01-01

    ATF3, a member of the ATF/CREB family of transcription factors, has been found to be selectively induced by calcineurin/NFAT inhibition and to enhance keratinocyte tumor formation, although the precise role of ATF3 in human skin cancer and possible mechanisms remain unknown. In this study, clinical analysis of 30 skin cancer patients and 30 normal donors revealed that ATF3 was accumulated in skin cancer tissues. Functional assays demonstrated that ATF3 significantly promoted skin cancer cell proliferation. Mechanically, ATF3 activated Stat3 phosphorylation in skin cancer cell through regulation of p53 expression. Moreover, the promotion effect of ATF3 on skin cancer cell proliferation was dependent on the p53-Stat3 signaling cascade. Together, the results indicate that ATF3 might promote skin cancer cell proliferation and enhance skin keratinocyte tumor development through inhibiting p53 expression and then activating Stat3 phosphorylation.

  7. Cofilin phosphorylation is elevated after F-actin disassembly induced by Rac1 depletion

    DEFF Research Database (Denmark)

    Liu, Linna; Li, Jing; Zhang, Liwang

    2015-01-01

    Cytoskeletal reorganization is essential to keratinocyte function. Rac1 regulates cytoskeletal reorganization through signaling pathways such as the cofilin cascade. Cofilin severs actin filaments after activation by dephosphorylation. Rac1 was knocked out in mouse keratinocytes and it was found...... that actin filaments disassembled. In the epidermis of mice in which Rac1 was knocked out only in keratinocytes, cofilin phosphorylation was aberrantly elevated, corresponding to repression of the phosphatase slingshot1 (SSH1). These effects were independent of the signaling pathways for p21-activated kinase....../LIM kinase (Pak/LIMK), protein kinase C, or protein kinase D or generation of reactive oxygen species. Similarly, when actin polymerization was specifically inhibited or Rac1 was knocked down, cofilin phosphorylation was enhanced and SSH1 was repressed. Repression of SSH1 partially blocked actin...

  8. Disaster Mythology and Availability Cascades

    Directory of Open Access Journals (Sweden)

    Lisa Grow Sun

    2013-04-01

    Full Text Available Sociological research conducted in the aftermath of natural disasters has uncovered a number of “disaster myths” – widely shared misconceptions about typical post-disaster human behavior. This paper discusses the possibility that perpetuation of disaster mythology reflects an “availability cascade,” defined in prior scholarship as a “self-reinforcing process of collective belief formation by which an expressed perception triggers a chain reaction that gives the perception increasing plausibility through its rising availability in public discourse.” (Kuran and Sunstein 1999. Framing the spread of disaster mythology as an availability cascade suggests that certain tools may be useful in halting the myths’ continued perpetuation. These tools include changing the legal and social incentives of so-called “availability entrepreneurs” – those principally responsible for beginning and perpetuating the cascade, as well as insulating decision-makers from political pressures generated by the availability cascade. This paper evaluates the potential effectiveness of these and other solutions for countering disaster mythology. Las investigaciones sociológicas realizadas tras los desastres naturales han hecho evidentes una serie de “mitos del desastre”, conceptos erróneos ampliamente compartidos sobre el comportamiento humano típico tras un desastre. Este artículo analiza la posibilidad de que la perpetuación de los mitos del desastre refleje una “cascada de disponibilidad”, definida en estudios anteriores como un “proceso de auto-refuerzo de la formación de una creencia colectiva, a través del que una percepción expresada produce una reacción en cadena que hace que la percepción sea cada vez más verosímil, a través de una mayor presencia en el discurso público” (Kuran y Sunstein 1999. Enmarcar la propagación de los mitos del desastre como una cascada de disponibilidad sugiere que ciertas herramientas pueden ser

  9. Ion-implantation dense cascade data

    International Nuclear Information System (INIS)

    Winterbon, K.B.

    1983-04-01

    A tabulation is given of data useful in estimating various aspects of ion-implantation cascades in the nuclear stopping regime, particularly with respect to nonlinearity of the cascade at high energy densities. The tabulation is restricted to self-ion implantation. Besides power-cross-section cascade dimensions, various material properties are included. Scaling of derived quantities with input data is noted, so one is not limited to the values assumed by the author

  10. A non-conventional isotope separation cascade without any mixing: net cascade

    International Nuclear Information System (INIS)

    Zeng Shi; Jiang Dongjun; Ying Zhengen

    2012-01-01

    A component has different concentrations in the incoming flows at a confluent point in all existing isotope separations cascades for multi-component isotope separation and mixing is inevitable, which results in deterioration of separation performance of the separation cascade. However, realization of no-mixing at a confluent point is impossible with a conventional cascade. A non-conventional isotope separation cascade, net cascade, is found to be able to realize no mixings for all components at confluent points, and its concept is further developed here. No-mixing is fulfilled by requiring symmetrical separation of two specified key components at every stage, and the procedure of realizing no-mixing is presented in detail. Some properties of net cascade are investigated preliminarily, and the results demonstrated the no-mixing property is indeed realized. Net cascade is the only separation cascade that so far possesses the no-mixing property. (authors)

  11. Contingency Analysis of Cascading Line Outage Events

    Energy Technology Data Exchange (ETDEWEB)

    Thomas L Baldwin; Magdy S Tawfik; Miles McQueen

    2011-03-01

    As the US power systems continue to increase in size and complexity, including the growth of smart grids, larger blackouts due to cascading outages become more likely. Grid congestion is often associated with a cascading collapse leading to a major blackout. Such a collapse is characterized by a self-sustaining sequence of line outages followed by a topology breakup of the network. This paper addresses the implementation and testing of a process for N-k contingency analysis and sequential cascading outage simulation in order to identify potential cascading modes. A modeling approach described in this paper offers a unique capability to identify initiating events that may lead to cascading outages. It predicts the development of cascading events by identifying and visualizing potential cascading tiers. The proposed approach was implemented using a 328-bus simplified SERC power system network. The results of the study indicate that initiating events and possible cascading chains may be identified, ranked and visualized. This approach may be used to improve the reliability of a transmission grid and reduce its vulnerability to cascading outages.

  12. A Semisupervised Cascade Classification Algorithm

    Directory of Open Access Journals (Sweden)

    Stamatis Karlos

    2016-01-01

    Full Text Available Classification is one of the most important tasks of data mining techniques, which have been adopted by several modern applications. The shortage of enough labeled data in the majority of these applications has shifted the interest towards using semisupervised methods. Under such schemes, the use of collected unlabeled data combined with a clearly smaller set of labeled examples leads to similar or even better classification accuracy against supervised algorithms, which use labeled examples exclusively during the training phase. A novel approach for increasing semisupervised classification using Cascade Classifier technique is presented in this paper. The main characteristic of Cascade Classifier strategy is the use of a base classifier for increasing the feature space by adding either the predicted class or the probability class distribution of the initial data. The classifier of the second level is supplied with the new dataset and extracts the decision for each instance. In this work, a self-trained NB∇C4.5 classifier algorithm is presented, which combines the characteristics of Naive Bayes as a base classifier and the speed of C4.5 for final classification. We performed an in-depth comparison with other well-known semisupervised classification methods on standard benchmark datasets and we finally reached to the point that the presented technique has better accuracy in most cases.

  13. Multiple phosphorylation sites at the C-terminus regulate nuclear import of HCMV DNA polymerase processivity factor ppUL44

    International Nuclear Information System (INIS)

    Alvisi, Gualtiero; Marin, Oriano; Pari, Gregory; Mancini, Manuela; Avanzi, Simone; Loregian, Arianna; Jans, David A.; Ripalti, Alessandro

    2011-01-01

    The processivity factor of human cytomegalovirus DNA polymerase, phosphoprotein ppUL44, is essential for viral replication. During viral infection ppUL44 is phosphorylated by the viral kinase pUL97, but neither the target residues on ppUL44 nor the effect of phosphorylation on ppUL44's activity are known. We report here that ppUL44 is phosphorylated when transiently expressed in mammalian cells and coimmunoprecipitates with cellular kinases. Of three potential phosphorylation sites (S413, S415, S418) located upstream of ppUL44's nuclear localization signal (NLS) and one (T427) within the NLS itself, protein kinase CK2 (CK2) specifically phosphorylates S413, to trigger a cascade of phosphorylation of S418 and S415 by CK1 and CK2, respectively. Negative charge at the CK2/CK1 target serine residues facilitates optimal nuclear accumulation of ppUL44, whereas negative charge on T427, a potential cyclin-dependent 1 phosphorylation site, strongly decreases nuclear accumulation. Thus, nuclear transport of ppUL44 is finely tuned during viral infection through complex phosphorylation events.

  14. Autocrine motility factor (neuroleukin, phosphohexose isomerase) induces cell movement through 12-lipoxygenase-dependent tyrosine phosphorylation and serine dephosphorylation events.

    Science.gov (United States)

    Timár, J; Tóth, S; Tóvári, J; Paku, S; Raz, A

    1999-01-01

    Autocrine motility factor (AMF) is one of the motility cytokines regulating tumor cell migration, therefore identification of the signaling pathway coupled with it has critical importance. Previous studies revealed several elements of this pathway predominated by lipoxygenase-PKC activations but the role for tyrosine kinases remained questionable. Motility cytokines frequently have mitogenic effect as well, producing activation of overlapping signaling pathways therefore we have used B16a melanoma cells as models where AMF has exclusive motility effect. Our studies revealed that in B16a cells AMF initiated rapid (1-5 min) activation of the protein tyrosine kinase (PTK) cascade inducing phosphorylation of 179, 125, 95 and 40/37 kD proteins which was mediated by upstream cyclo- and lipoxygenases. The phosphorylated proteins were localized to the cortical actin-stress fiber attachment zones in situ by confocal microscopy. On the other hand, AMF receptor activation induced significant decrease in overall serine-phosphorylation level of cellular proteins accompanied by serine phosphorylation of 200, 90, 78 and 65 kd proteins. The decrease in serine phosphorylation was independent of PTKs, PKC as well as cyclo- and lipoxygenases. However, AMF induced robust translocation of PKCalpha to the stress fibers and cortical actin suggesting a critical role for this kinase in the generation of the motility signal. Based on the significant decrease in serine phosphorylation after AMF stimulus in B16a cells we postulated the involvement of putative serine/threonine phosphatase(s) upstream lipoxygenase and activation of the protein tyrosine kinase cascade downstream cyclo- and lipoxygenase(s) in the previously identified autocrine motility signal.

  15. Membrane phosphorylation and nerve cell function

    International Nuclear Information System (INIS)

    Baer, P.R.

    1982-01-01

    This thesis deals with the phosphorylation of membrane components. In part I a series of experiments is described using the hippocampal slice as a model system. In part II a different model system - cultured hybrid cells - is used to study protein and lipid phosphorylation, influenced by incubation with neuropeptides. In part III in vivo and in vitro studies are combined to study protein phosphorylation after neuroanatomical lesions. In a section of part II (Page 81-90) labelling experiments of the membrane inositol-phospholipids are described. 32 P-ATP was used to label phospholipids in intact hybrid cells, and short incubations were found to be the most favourable. (C.F.)

  16. Protein-Tyrosine Phosphorylation in Bacillus subtilis

    DEFF Research Database (Denmark)

    Mijakovic, Ivan; Petranovic, Dina; Bottini, N.

    2005-01-01

    phosphorylation, indicating that this post-translational modifi cation could regulate physiological processes ranging from stress response and exopolysaccharide synthesis to DNA metabolism. Some interesting work in this fi eld was done in Bacillus subtilis , and we here present the current state of knowledge...... on protein-tyrosine phosphorylation in this gram-positive model organism. With its two kinases, two kinase modulators, three phosphatases and at least four different tyrosine-phosphorylated substrates, B. subtilis is the bacterium with the highest number of presently known participants in the global network...

  17. Insulin treatment promotes tyrosine phosphorylation of PKR and inhibits polyIC induced PKR threonine phosphorylation.

    Science.gov (United States)

    Swetha, Medchalmi; Ramaiah, Kolluru V A

    2015-11-01

    Tyrosine phosphorylation of insulin receptor beta (IRβ) in insulin treated HepG2 cells is inversely correlated to ser(51) phosphorylation in the alpha-subunit of eukaryotic initiation factor 2 (eIF2α) that regulates protein synthesis. Insulin stimulates interaction between IRβ and PKR, double stranded RNA-dependent protein kinase, also known as EIF2AK2, and phosphorylation of tyrosine residues in PKR, as analyzed by immunoprecipitation and pull down assays using anti-IRβ and anti-phosphotyrosine antibodies, recombinant IRβ and immunopurified PKR. Further polyIC or synthetic double stranded RNA-induced threonine phosphorylation or activation of immunopurified and cellular PKR is suppressed in the presence of insulin treated purified IRβ and cell extracts. Acute, but not chronic, insulin treatment enhances tyrosine phosphorylation of IRβ, its interaction with PKR and tyrosine phosphorylation of PKR. In contrast, lipopolysaccharide that stimulates threonine phosphorylation of PKR and eIF2α phosphorylation and AG 1024, an inhibitor of the tyrosine kinase activity of IRβ, reduces PKR association with the receptor, IRβ in HepG2 cells. These findings therefore may suggest that tyrosine phosphorylated PKR plays a role in the regulation of insulin induced protein synthesis and in maintaining insulin sensitivity, whereas, suppression of polyIC-mediated threonine phosphorylation of PKR by insulin compromises its ability to fight against virus infection in host cells. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. Design concept of Hydro cascade control system

    International Nuclear Information System (INIS)

    Fustik, Vangel; Kiteva, Nevenka

    2006-01-01

    In this paper a design concept of the comple hydro cascade scheme is presented with the design parameters of the main technical features. The cascade control system architecture is designed considering up-to-date communication and information technology. The control algorithm is based on Pond Level Control and Economic Load Allocation concepts.

  19. Centrifugal separator cascade connected in zigzag manner

    International Nuclear Information System (INIS)

    Kai, Tsunetoshi; Inoue, Yoshiya; Oya, Akio; Nagakura, Masaaki.

    1974-01-01

    Object: To effectively accommodate centrifugal separators of the entire cascade within the available space in a plant by freely selecting perpendicular direction of connection of the centrifugal separator. Structure: Centrifugal separators are connected in zigzag fashion by using a single header for each stage so that in a rectangular shape the entire cascade is arranged. (Kamimura, M.)

  20. Cascaded impedance networks for NPC inverter

    DEFF Research Database (Denmark)

    Li, Ding; Gao, Feng; Loh, Poh Chiang

    2010-01-01

    they are subject to the renewable sources. To date, three distinct types of impedance networks can be summarized for implementing a hybrid source impedance network, which can in principle be combined and cascaded before connected to a NPC inverter by proposed two ways. The resulting cascaded impedance network NPC...

  1. Cascading costs: an economic nitrogen cycle.

    Science.gov (United States)

    Moomaw, William R; Birch, Melissa B L

    2005-09-01

    The chemical nitrogen cycle is becoming better characterized in terms of fluxes and reservoirs on a variety of scales. Galloway has demonstrated that reactive nitrogen can cascade through multiple ecosystems causing environmental damage at each stage before being denitrified to N(2). We propose to construct a parallel economic nitrogen cascade (ENC) in which economic impacts of nitrogen fluxes can be estimated by the costs associated with each stage of the chemical cascade. Using economic data for the benefits of damage avoided and costs of mitigation in the Chesapeake Bay basin, we have constructed an economic nitrogen cascade for the region. Since a single ton of nitrogen can cascade through the system, the costs also cascade. Therefore evaluating the benefits of mitigating a ton of reactive nitrogen released needs to consider the damage avoided in all of the ecosystems through which that ton would cascade. The analysis reveals that it is most cost effective to remove a ton of nitrogen coming from combustion since it has the greatest impact on human health and creates cascading damage through the atmospheric, terrestrial, aquatic and coastal ecosystems. We will discuss the implications of this analysis for determining the most cost effective policy option for achieving environmental quality goals.

  2. MAPK cascades in guard cell signal transduction

    Directory of Open Access Journals (Sweden)

    Yuree eLee

    2016-02-01

    Full Text Available Guard cells form stomata on the epidermis and continuously respond to endogenous and environmental stimuli to fine-tune the gas exchange and transpirational water loss, processes which involve mitogen-activated protein kinase (MAPK cascades. MAPKs form three-tiered kinase cascades with MAPK kinases and MAPK kinase kinases, by which signals are transduced to the target proteins. MAPK cascade genes are highly conserved in all eukaryotes, and they play crucial roles in myriad developmental and physiological processes. MAPK cascades function during biotic and abiotic stress responses by linking extracellular signals received by receptors to cytosolic events and gene expression. In this review, we highlight recent findings and insights into MAPK-mediated guard cell signaling, including the specificity of MAPK cascades and the remaining questions.

  3. Cascade Error Projection: An Efficient Hardware Learning Algorithm

    Science.gov (United States)

    Duong, T. A.

    1995-01-01

    A new learning algorithm termed cascade error projection (CEP) is presented. CEP is an adaption of a constructive architecture from cascade correlation and the dynamical stepsize of A/D conversion from the cascade back propagation algorithm.

  4. Protein phosphorylation in bcterial signaling and regulation

    KAUST Repository

    Mijakovic, Ivan

    2016-01-01

    . Evolutionary studies based on genome comparison indicate that BY-kinases exist only in bacteria. They are non-essential (present in about 40% bacterial genomes), and their knockouts lead to pleiotropic phenotypes, since they phosphorylate many substrates

  5. Displacement cascades in diatomic materials

    International Nuclear Information System (INIS)

    Parkin, D.M.; Coulter, C.A.

    1981-01-01

    A new function, the specified-projectile displacement function p/sub ijk/ (E), is introduced to describe displacement cascades in polyatomic materials. This function describes the specific collision events that produce displacements and hence adds new information not previously available. Calculations of p/sub ijk/ (E) for MgO, Al 2 O 3 and TaO are presented and discussed. Results show that the parameters that have the largest effect on displacement collision events are the PKA energy and the mass ratio of the atom types in the material. It is further shown that the microscopic nature of the displacement events changes over the entire recoil energy range relevant to fusion neutron spectra and that these changes are different in materials whose mass ratio is near one than in those where it is far from one

  6. The Geant4 Bertini Cascade

    Energy Technology Data Exchange (ETDEWEB)

    Wright, D.H.; Kelsey, M.H.

    2015-12-21

    One of the medium energy hadron–nucleus interaction models in the GEANT4 simulation toolkit is based partly on the Bertini intranuclear cascade model. Since its initial appearance in the toolkit, this model has been largely re-written in order to extend its physics capabilities and to reduce its memory footprint. Physics improvements include extensions in applicable energy range and incident particle types, and improved hadron–nucleon cross-sections and angular distributions. Interfaces have also been developed which allow the model to be coupled with other GEANT4 models at lower and higher energies. The inevitable speed reductions due to enhanced physics have been mitigated by memory and CPU efficiency improvements. Details of these improvements, along with selected comparisons of the model to data, are discussed.

  7. Availability Cascades & the Sharing Economy

    DEFF Research Database (Denmark)

    Netter, Sarah

    2014-01-01

    attention. This conceptual paper attempts to explain the emergent focus on the sharing economy and associated business and consumption models by applying cascade theory. Risks associated with this behavior will be especially examined with regard to the sustainability claim of collaborative consumption......In search of a new concept that will provide answers to as to how modern societies should not only make sense but also resolve the social and environmental problems linked with our modes of production and consumption, collaborative consumption and the sharing economy are increasingly attracting....... With academics, practitioners, and civil society alike having a shared history in being rather fast in accepting new concepts that will not only provide business opportunities but also a good conscience, this study proposes a critical study of the implications of collaborative consumption, before engaging...

  8. Cardiovascular Protective Effect of Metformin and Telmisartan: Reduction of PARP1 Activity via the AMPK-PARP1 Cascade.

    Directory of Open Access Journals (Sweden)

    Fenqing Shang

    Full Text Available Hyperglycemia and hypertension impair endothelial function in part through oxidative stress-activated poly (ADP-ribose polymerase 1 (PARP1. Biguanides and angiotensin II receptor blockers (ARBs such as metformin and telmisartan have a vascular protective effect. We used cultured vascular endothelial cells (ECs, diabetic and hypertensive rodent models, and AMPKα2-knockout mice to investigate whether metformin and telmisartan have a beneficial effect on the endothelium via AMP-activated protein kinase (AMPK phosphorylation of PARP1 and thus inhibition of PARP1 activity. The results showed that metformin and telmisartan, but not glipizide and metoprolol, activated AMPK, which phosphorylated PARP1 Ser-177 in cultured ECs and the vascular wall of rodent models. Experiments using phosphorylated/de-phosphorylated PARP1 mutants show that AMPK phosphorylation of PARP1 leads to decreased PARP1 activity and attenuated protein poly(ADP-ribosylation (PARylation, but increased endothelial nitric oxide synthase (eNOS activity and silent mating type information regulation 2 homolog 1 (SIRT1 expression. Taken together, the data presented here suggest biguanides and ARBs have a beneficial effect on the vasculature by the cascade of AMPK phosphorylation of PARP1 to inhibit PARP1 activity and protein PARylation in ECs, thereby mitigating endothelial dysfunction.

  9. Experimental study of flow through compressor Cascade

    Directory of Open Access Journals (Sweden)

    Satyam Panchal

    2017-09-01

    Full Text Available The objective of this research work is to study the behaviour of flow at the inlet, within the blade passage and at the exit of a compressor cascade. For this purpose, a cascade with six numbers of aerofoil blades was designed and constructed. The cascade was fitted on the cascade test tunnel. Out of six blades two were instrumented for measuring the pressure distribution on the pressure and suction surface. The blades had a parabolic camber line, with a maximum camber position at 40% of the chord from the leading edge of the blade. The profile of the blade was C4, height of the blade was 160 mm, chord length was 80 mm, camber angle was 45° and stagger angle was 30°. Similarly, the length of the cascade was 300 mm, span was 160 mm, pitch was 60 mm, the actual chord of the cascade was 80 mm, the axial chord of the cascade was 70 mm, the stagger angle of the cascade was 30° and the pitch-chord ratio was 0.75. The data was taken and analyzed at −500% of the axial chord before the cascade, −25% of the axial chord before the leading edge, 25%, 50%, 75% and 150% of the axial chord from the leading edge of the blade. The readings were taken from the cascade wall to the mid span position along the pitch wise direction. The angle of incidence was also changed during the experiment and varied from i=−50°, −30°, −10° to 5°.

  10. Fibronectin phosphorylation by ecto-protein kinase

    International Nuclear Information System (INIS)

    Imada, Sumi; Sugiyama, Yayoi; Imada, Masaru

    1988-01-01

    The presence of membrane-associated, extracellular protein kinase (ecto-protein kinase) and its substrate proteins was examined with serum-free cultures of Swiss 3T3 fibroblast. When cells were incubated with [γ- 32 ]ATP for 10 min at 37 degree C, four proteins with apparent molecular weights between 150 and 220 kDa were prominently phosphorylated. These proteins were also radiolabeled by lactoperoxidase catalyzed iodination and were sensitive to mild tryptic digestion, suggesting that they localized on the cell surface or in the extracellular matrix. Phosphorylation of extracellular proteins with [γ- 32 P]ATP in intact cell culture is consistent with the existence of ecto-protein kinase. Anti-fibronectin antibody immunoprecipitated one of the phosphoproteins which comigrated with a monomer and a dimer form of fibronectin under reducing and nonreducing conditions of electrophoresis, respectively. The protein had affinity for gelatin as demonstrated by retention with gelatin-conjugated agarose. This protein substrate of ecto-protein kinase was thus concluded to be fibronectin. The sites of phosphorylation by ecto-protein kinase were compared with those of intracellularly phosphorylated fibronectin by the analysis of radiolabeled amino acids and peptides. Ecto-protein kinase phosphorylated fibronectin at serine and threonine residues which were distinct from the sites of intracellular fibronectin phosphorylation

  11. Phosphorylation of human skeletal muscle myosin

    International Nuclear Information System (INIS)

    Houston, M.E.; Lingley, M.D.; Stuart, D.S.; Hoffman-Goetz, L.

    1986-01-01

    Phosphorylation of the P-light chains (phosphorylatable light chains) in human skeletal muscle myosin was studied in vitro and in vivo under resting an d contracted conditions. biopsy samples from rested vastus lateralis muscle of male and female subjects were incubated in oxygenated physiological solution at 30 0 C. Samples frozen following a quiescent period showed the presence of only unphosphorylated P-light chains designated LC2f (light chain two of fast myosin) CL2s and LC2s'(light chains two of slow myosin). Treatment with caffeine (10 mM) or direct electrical stimulation resulted in the appearance of three additional bands which were identified as the phosphorylated forms of the P-light chains i.e. LC2f-P, LC2s-P and LC2s'-P. The presence of phosphate was confirmed by prior incubation with ( 30 P) orthophosphate. Muscle samples rapidly frozen from resting vastus lateralis muscle revealed the presence of unphosphorylated and phosphorylated P-light chains in approximately equal ratios. Muscle samples rapidly frozen following a maximal 10 second isometric contraction showed virtually only phosphorylated fast and slow P-light chains. These results reveal that the P-light chains in human fast and slow myosin may be rapidly phosphorylated, but the basal level of phosphorylation in rested human muscle considerably exceeds that observed in animal muscles studied in vitro or in situ

  12. Protein phosphorylation during coconut zygotic embryo development

    International Nuclear Information System (INIS)

    Islas-Flores, I.; Oropeza, C.; Hernandez-Sotomayor, S.M.T.

    1998-01-01

    Evidence was obtained on the occurrence of protein threonine, serine, and tyrosine (Tyr) kinases in developing coconut (Cocos nucifera L.) zygotic embryos, based on in vitro phosphorylation of proteins in the presence of [gamma-32P]ATP, alkaline treatment, and thin-layer chromatography analysis, which showed the presence of [32P]phosphoserine, [32P]phosphothreonine, and [32P]phosphotyrosine in [32P]-labeled protein hydrolyzates. Tyr kinase activity was further confirmed in extracts of embryos at different stages of development using antiphosphotyrosine monoclonal antibodies and the synthetic peptide derived from the amino acid sequence surrounding the phosphorylation site in pp60src (RR-SRC), which is specific for Tyr kinases. Anti-phosphotyrosine western blotting revealed a changing profile of Tyr-phosphorylated proteins during embryo development. Tyr kinase activity, as assayed using RR-SRC, also changed during embryo development, showing two peaks of activity, one during early and another during late embryo development. In addition, the use of genistein, a Tyr kinase inhibitor, diminished the ability of extracts to phosphorylate RR-SRC. Results presented here show the occurrence of threonine, serine, and Tyr kinases in developing coconut zygotic embryos, and suggest that protein phosphorylation, and the possible inference of Tyr phosphorylation in particular, may play a role in the coordination of the development of embryos in this species

  13. PKA regulates calcineurin function through the phosphorylation of RCAN1: Identification of a novel phosphorylation site

    International Nuclear Information System (INIS)

    Kim, Seon Sook; Lee, Eun Hye; Lee, Kooyeon; Jo, Su-Hyun; Seo, Su Ryeon

    2015-01-01

    Calcineurin is a calcium/calmodulin-dependent phosphatase that has been implicated in T cell activation through the induction of nuclear factors of activated T cells (NFAT). We have previously suggested that endogenous regulator of calcineurin (RCAN1, also known as DSCR1) is targeted by protein kinase A (PKA) for the control of calcineurin activity. In the present study, we characterized the PKA-mediated phosphorylation site in RCAN1 by mass spectrometric analysis and revealed that PKA directly phosphorylated RCAN1 at the Ser 93. PKA-induced phosphorylation and the increase in the half-life of the RCAN1 protein were prevented by the substitution of Ser 93 with Ala (S93A). Furthermore, the PKA-mediated phosphorylation of RCAN1 at Ser 93 potentiated the inhibition of calcineurin-dependent pro-inflammatory cytokine gene expression by RCAN1. Our results suggest the presence of a novel phosphorylation site in RCAN1 and that its phosphorylation influences calcineurin-dependent inflammatory target gene expression. - Highlights: • We identify novel phosphorylation sites in RCAN1 by LC-MS/MS analysis. • PKA-dependent phosphorylation of RCAN1 at Ser 93 inhibits calcineurin-mediated intracellular signaling. • We show the immunosuppressive function of RCAN1 phosphorylation at Ser 93 in suppressing cytokine expression

  14. Reconstruction and analysis of nutrient-induced phosphorylation networks in Arabidopsis thaliana.

    Directory of Open Access Journals (Sweden)

    Guangyou eDuan

    2013-12-01

    Full Text Available Elucidating the dynamics of molecular processes in living organisms in response to external perturbations is a central goal in modern systems biology. We investigated the dynamics of protein phosphorylation events in Arabidopsis thaliana exposed to changing nutrient conditions. Phosphopeptide expression levels were detected at five consecutive time points over a time interval of 30 minutes after nutrient resupply following prior starvation. The three tested inorganic, ionic nutrients NH4+, NO3-, PO43- elicited similar phosphosignaling responses that were distinguishable from those invoked by the sugars mannitol, sucrose. When embedded in the protein-protein interaction network of Arabidopsis thaliana, phosphoproteins were found to exhibit a higher degree compared to average proteins. Based on the time-series data, we reconstructed a network of regulatory interactions mediated by phosphorylation. The performance of different network inference methods was evaluated by the observed likelihood of physical interactions within and across different subcellular compartments and based on gene ontology semantic similarity. The dynamic phosphorylation network was then reconstructed using a Pearson correlation method with added directionality based on partial variance differences. The topology of the inferred integrated network corresponds to an information dissemination architecture, in which the phosphorylation signal is passed on to an increasing number of phosphoproteins stratified into an initiation, processing, and effector layer. Specific phosphorylation peptide motifs associated with the distinct layers were identified indicating the action of layer-specific kinases. Despite the limited temporal resolution, combined with information on subcellular location, the available time-series data proved useful for reconstructing the dynamics of the molecular signaling cascade in response to nutrient stress conditions in the plant Arabidopsis thaliana.

  15. Protein kinases mediate increment of the phosphorylation of cyclic AMP -responsive element binding protein in spinal cord of rats following capsaicin injection

    Directory of Open Access Journals (Sweden)

    Li Junfa

    2005-09-01

    Full Text Available Abstract Background Strong noxious stimuli cause plastic changes in spinal nociceptive neurons. Intracellular signal transduction pathways from cellular membrane to nucleus, which may further regulate gene expression by critical transcription factors, convey peripheral stimulation. Cyclic AMP-responsive element binding protein (CREB is a well-characterized stimulus-induced transcription factor whose activation requires phosphorylation of the Serine-133 residue. Phospho-CREB can further induce gene transcription and strengthen synaptic transmission by the activation of the protein kinase cascades. However, little is known about the mechanisms by which CREB phosphorylation is regulated by protein kinases during nociception. This study was designed to use Western blot analysis to investigate the role of mitogen-activated protein (MAP/extracellular signal-regulated kinase (ERK kinase (MEK 1/2, PKA and PKC in regulating the phosphorylation of CREB in the spinal cord of rats following intraplantar capsaicin injection. Results We found that capsaicin injection significantly increased the phosphorylation level of CREB in the ipsilateral side of the spinal cord. Pharmacological manipulation of MEK 1/2, PKA and PKC with their inhibitors (U0126, H89 and NPC 15473, respectively significantly blocked this increment of CREB phosphorylation. However, the expression of CREB itself showed no change in any group. Conclusion These findings suggest that the activation of intracellular MAP kinase, PKA and PKC cascades may contribute to the regulation of phospho-CREB in central nociceptive neurons following peripheral painful stimuli.

  16. Genetic algorithm based separation cascade optimization

    International Nuclear Information System (INIS)

    Mahendra, A.K.; Sanyal, A.; Gouthaman, G.; Bera, T.K.

    2008-01-01

    The conventional separation cascade design procedure does not give an optimum design because of squaring-off, variation of flow rates and separation factor of the element with respect to stage location. Multi-component isotope separation further complicates the design procedure. Cascade design can be stated as a constrained multi-objective optimization. Cascade's expectation from the separating element is multi-objective i.e. overall separation factor, cut, optimum feed and separative power. Decision maker may aspire for more comprehensive multi-objective goals where optimization of cascade is coupled with the exploration of separating element optimization vector space. In real life there are many issues which make it important to understand the decision maker's perception of cost-quality-speed trade-off and consistency of preferences. Genetic algorithm (GA) is one such evolutionary technique that can be used for cascade design optimization. This paper addresses various issues involved in the GA based multi-objective optimization of the separation cascade. Reference point based optimization methodology with GA based Pareto optimality concept for separation cascade was found pragmatic and promising. This method should be explored, tested, examined and further developed for binary as well as multi-component separations. (author)

  17. Raf Kinase Inhibitory Protein Function Is Regulated via a Flexible Pocket and Novel Phosphorylation-Dependent Mechanism▿ †

    Science.gov (United States)

    Granovsky, Alexey E.; Clark, Matthew C.; McElheny, Dan; Heil, Gary; Hong, Jia; Liu, Xuedong; Kim, Youngchang; Joachimiak, Grazyna; Joachimiak, Andrzej; Koide, Shohei; Rosner, Marsha Rich

    2009-01-01

    Raf kinase inhibitory protein (RKIP/PEBP1), a member of the phosphatidylethanolamine binding protein family that possesses a conserved ligand-binding pocket, negatively regulates the mammalian mitogen-activated protein kinase (MAPK) signaling cascade. Mutation of a conserved site (P74L) within the pocket leads to a loss or switch in the function of yeast or plant RKIP homologues. However, the mechanism by which the pocket influences RKIP function is unknown. Here we show that the pocket integrates two regulatory signals, phosphorylation and ligand binding, to control RKIP inhibition of Raf-1. RKIP association with Raf-1 is prevented by RKIP phosphorylation at S153. The P74L mutation increases kinase interaction and RKIP phosphorylation, enhancing Raf-1/MAPK signaling. Conversely, ligand binding to the RKIP pocket inhibits kinase interaction and RKIP phosphorylation by a noncompetitive mechanism. Additionally, ligand binding blocks RKIP association with Raf-1. Nuclear magnetic resonance studies reveal that the pocket is highly dynamic, rationalizing its capacity to interact with distinct partners and be involved in allosteric regulation. Our results show that RKIP uses a flexible pocket to integrate ligand binding- and phosphorylation-dependent interactions and to modulate the MAPK signaling pathway. This mechanism is an example of an emerging theme involving the regulation of signaling proteins and their interaction with effectors at the level of protein dynamics. PMID:19103740

  18. Raf kinase inhibitory protein function is regulated via a flexible pocket and novel phosphorylation-dependent mechanism.

    Science.gov (United States)

    Granovsky, Alexey E; Clark, Matthew C; McElheny, Dan; Heil, Gary; Hong, Jia; Liu, Xuedong; Kim, Youngchang; Joachimiak, Grazyna; Joachimiak, Andrzej; Koide, Shohei; Rosner, Marsha Rich

    2009-03-01

    Raf kinase inhibitory protein (RKIP/PEBP1), a member of the phosphatidylethanolamine binding protein family that possesses a conserved ligand-binding pocket, negatively regulates the mammalian mitogen-activated protein kinase (MAPK) signaling cascade. Mutation of a conserved site (P74L) within the pocket leads to a loss or switch in the function of yeast or plant RKIP homologues. However, the mechanism by which the pocket influences RKIP function is unknown. Here we show that the pocket integrates two regulatory signals, phosphorylation and ligand binding, to control RKIP inhibition of Raf-1. RKIP association with Raf-1 is prevented by RKIP phosphorylation at S153. The P74L mutation increases kinase interaction and RKIP phosphorylation, enhancing Raf-1/MAPK signaling. Conversely, ligand binding to the RKIP pocket inhibits kinase interaction and RKIP phosphorylation by a noncompetitive mechanism. Additionally, ligand binding blocks RKIP association with Raf-1. Nuclear magnetic resonance studies reveal that the pocket is highly dynamic, rationalizing its capacity to interact with distinct partners and be involved in allosteric regulation. Our results show that RKIP uses a flexible pocket to integrate ligand binding- and phosphorylation-dependent interactions and to modulate the MAPK signaling pathway. This mechanism is an example of an emerging theme involving the regulation of signaling proteins and their interaction with effectors at the level of protein dynamics.

  19. Identification of novel PAMP-triggered phosphorylation and dephosphorylation events in arabidopsis thaliana by quantitative phosphoproteomic analysis

    KAUST Repository

    Rayapuram, Naganand; Bonhomme, Ludovic; Bigeard, Jean; Haddadou, Kahina; Przybylski, Cé dric; Hirt, Heribert; Pflieger, Delphine

    2014-01-01

    Signaling cascades rely strongly on protein kinase-mediated substrate phosphorylation. Currently a major challenge in signal transduction research is to obtain high confidence substrate phosphorylation sites and assign them to specific kinases. In response to bacterial flagellin, a pathogen-associated molecular pattern (PAMP), we searched for rapidly phosphorylated proteins in Arabidopsis thaliana by combining multistage activation (MSA) and electron transfer dissociation (ETD) fragmentation modes, which generate complementary spectra and identify phosphopeptide sites with increased reliability. Of a total of 825 phosphopeptides, we identified 58 to be differentially phosphorylated. These peptides harbor kinase motifs of mitogen-activated protein kinases (MAPKs) and calcium-dependent protein kinases (CDPKs), as well as yet unknown protein kinases. Importantly, 12 of the phosphopeptides show reduced phosphorylation upon flagellin treatment. Since protein abundance levels did not change, these results indicate that flagellin induces not only various protein kinases but also protein phosphatases, even though a scenario of inhibited kinase activity may also be possible. © 2014 American Chemical Society.

  20. Identification of novel PAMP-triggered phosphorylation and dephosphorylation events in arabidopsis thaliana by quantitative phosphoproteomic analysis

    KAUST Repository

    Rayapuram, Naganand

    2014-04-04

    Signaling cascades rely strongly on protein kinase-mediated substrate phosphorylation. Currently a major challenge in signal transduction research is to obtain high confidence substrate phosphorylation sites and assign them to specific kinases. In response to bacterial flagellin, a pathogen-associated molecular pattern (PAMP), we searched for rapidly phosphorylated proteins in Arabidopsis thaliana by combining multistage activation (MSA) and electron transfer dissociation (ETD) fragmentation modes, which generate complementary spectra and identify phosphopeptide sites with increased reliability. Of a total of 825 phosphopeptides, we identified 58 to be differentially phosphorylated. These peptides harbor kinase motifs of mitogen-activated protein kinases (MAPKs) and calcium-dependent protein kinases (CDPKs), as well as yet unknown protein kinases. Importantly, 12 of the phosphopeptides show reduced phosphorylation upon flagellin treatment. Since protein abundance levels did not change, these results indicate that flagellin induces not only various protein kinases but also protein phosphatases, even though a scenario of inhibited kinase activity may also be possible. © 2014 American Chemical Society.

  1. Protein phosphorylation systems in postmortem human brain

    International Nuclear Information System (INIS)

    Walaas, S.I.; Perdahl-Wallace, E.; Winblad, B.; Greengard, P.

    1989-01-01

    Protein phosphorylation systems regulated by cyclic adenosine 3',5'-monophosphate (cyclic AMP), or calcium in conjunction with calmodulin or phospholipid/diacylglycerol, have been studied by phosphorylation in vitro of particulate and soluble fractions from human postmortem brain samples. One-dimensional or two-dimensional gel electrophoretic protein separations were used for analysis. Protein phosphorylation catalyzed by cyclic AMP-dependent protein kinase was found to be highly active in both particulate and soluble preparations throughout the human CNS, with groups of both widely distributed and region-specific substrates being observed in different brain nuclei. Dopamine-innervated parts of the basal ganglia and cerebral cortex contained the phosphoproteins previously observed in rodent basal ganglia. In contrast, calcium/phospholipid-dependent and calcium/calmodulin-dependent protein phosphorylation systems were less prominent in human postmortem brain than in rodent brain, and only a few widely distributed substrates for these protein kinases were found. Protein staining indicated that postmortem proteolysis, particularly of high-molecular-mass proteins, was prominent in deeply located, subcortical regions in the human brain. Our results indicate that it is feasible to use human postmortem brain samples, when obtained under carefully controlled conditions, for qualitative studies on brain protein phosphorylation. Such studies should be of value in studies on human neurological and/or psychiatric disorders

  2. Aspects of the QCD cascade

    International Nuclear Information System (INIS)

    Olsson, Magnus.

    1993-02-01

    A model is proposed for the production of transverse jets from diffractively excited protons. We propose that transverse jets can be obtained from gluonic bremsstrahlung in a way similar to the emission in DIS. Qualitative agreement is obtained between the model and the uncorrected data published by the UA8 collaboration. Perturbative QCD in the MLLA approximation is applied to multiple jet production in e + e - -annihilation. We propose modified evolution equations for deriving the jet cross sections, defined in the 'k t ' or 'Durham' algorithm. The mean number of jets as a function of the jet resolution is studied, and analytical predictions are compared to the results of MC simulations. We also study a set of differential-difference equations for multiplicity distributions in e + e - -annihilations, supplemented with appropriate boundary conditions. These equations take into account nonsingular terms in the GLAP splitting functions as well as kinematical constraints related to recoil effects. The presence of retarded terms imply that the cascade develops more slowly and reduces the fluctuations. The solutions agree well with MC simulations and experimental data. (authors)

  3. A stable aspirin-triggered lipoxin A4 analog blocks phosphorylation of leukocyte-specific protein 1 in human neutrophils.

    Science.gov (United States)

    Ohira, Taisuke; Bannenberg, Gerard; Arita, Makoto; Takahashi, Minoru; Ge, Qingyuan; Van Dyke, Thomas E; Stahl, Gregory L; Serhan, Charles N; Badwey, John A

    2004-08-01

    Lipoxins and their aspirin-triggered 15-epimers are endogenous anti-inflammatory agents that block neutrophil chemotaxis in vitro and inhibit neutrophil influx in several models of acute inflammation. In this study, we examined the effects of 15-epi-16-(p-fluoro)-phenoxy-lipoxin A(4) methyl ester, an aspirin-triggered lipoxin A(4)-stable analog (ATLa), on the protein phosphorylation pattern of human neutrophils. Neutrophils stimulated with the chemoattractant fMLP were found to exhibit intense phosphorylation of a 55-kDa protein that was blocked by ATLa (10-50 nM). This 55-kDa protein was identified as leukocyte-specific protein 1, a downstream component of the p38-MAPK cascade in neutrophils, by mass spectrometry, Western blotting, and immunoprecipitation experiments. ATLa (50 nM) also reduced phosphorylation/activation of several components of the p38-MAPK pathway in these cells (MAPK kinase 3/MAPK kinase 6, p38-MAPK, MAPK-activated protein kinase-2). These results indicate that ATLa exerts its anti-inflammatory effects, at least in part, by blocking activation of the p38-MAPK cascade in neutrophils, which is known to promote chemotaxis and other proinflammatory responses by these cells.

  4. Bursting behaviours in cascaded stimulated Brillouin scattering

    International Nuclear Information System (INIS)

    Liu Zhan-Jun; He Xian-Tu; Zheng Chun-Yang; Wang Yu-Gang

    2012-01-01

    Stimulated Brillouin scattering is studied by numerically solving the Vlasov—Maxwell system. A cascade of stimulated Brillouin scattering can occur when a linearly polarized laser pulse propagates in a plasma. It is found that a stimulated Brillouin scattering cascade can reduce the scattering and increase the transmission of light, as well as introduce a bursting behaviour in the evolution of the laser-plasma interaction. The bursting time in the reflectivity is found to be less than half the ion acoustic period. The ion temperature can affect the stimulated Brillouin scattering cascade, which can repeat several times at low ion temperatures and can be completely eliminated at high ion temperatures. For stimulated Brillouin scattering saturation, higher-harmonic generation and wave—wave interaction of the excited ion acoustic waves can restrict the amplitude of the latter. In addition, stimulated Brillouin scattering cascade can restrict the amplitude of the scattered light. (physics of gases, plasmas, and electric discharges)

  5. Defect accumulation under cascade damage conditions

    DEFF Research Database (Denmark)

    Trinkaus, H.; Singh, B.N.; Woo, C.H.

    1994-01-01

    in terms of this reaction kinetics taking into account cluster production, dissociation, migration and annihilation at extended sinks. Microstructural features which are characteristic of cascade damage and cannot be explained in terms of the conventional single defect reaction kinetics are emphasized......There is now ample evidence from both experimental and computer simulation studies that in displacement cascades not only intense recombination takes place but also efficient clustering of both self-interstitial atoms (SIAs) and vacancies. The size distributions of the two types of defects produced...... reactions kinetics associated with the specific features of cascade damage is described, with emphasis on asymmetries between SIA and vacancy type defects concerning their production, stability, mobility and interactions with other defects. Defect accumulation under cascade damage conditions is discussed...

  6. Cascade theory in isotopic separation processes

    International Nuclear Information System (INIS)

    Agostini, J.P.

    1994-06-01

    Three main areas are developed within the scope of this work: - the first one is devoted to fundamentals: separative power, value function, ideal cascade and square cascade. Applications to two main cases are carried out, namely: Study of binary isotopic mix, Study of processes with a small enrichment coefficient. - The second one is devoted to cascade coupling -high-flux coupling (more widely used and better known) as well as low-flux coupling are presented and compared to one another. - The third one is an outlook on problems linked to cascade transients. Those problem are somewhat intricate and their interest lies mainly into two areas: economics where the start-up time may have a large influence on the interests paid during the construction and start-up period, military productions where the start-up time has a direct bearing on the production schedule. (author). 50 figs. 3 annexes. 12 refs. 6 tabs

  7. τ polarization in SUSY cascade decays

    International Nuclear Information System (INIS)

    Choi, S.Y.; Hagiwara, K.; Kim, Y.G.

    2006-12-01

    τ leptons emitted in cascade decays of supersymmetric particles are polarized. The polarization may be exploited to determine spin and mixing properties of the neutralinos and stau particles involved. (orig.)

  8. MAP kinase cascades in Arabidopsis innate immunity

    DEFF Research Database (Denmark)

    Rasmussen, Magnus Wohlfahrt; Roux, Milena Edna; Petersen, Morten

    2012-01-01

    Plant mitogen-activated protein kinase (MAPK) cascades generally transduce extracellular stimuli into cellular responses. These stimuli include the perception of pathogen-associated molecular patterns (PAMPs) by host transmembrane pattern recognition receptors which trigger MAPK-dependent innate ...

  9. Cascade processes in kaonic and muonic atoms

    International Nuclear Information System (INIS)

    Faifman, M.P.; Men'shikov, L.I.

    2003-01-01

    Cascade processes in exotic (kaonic and muonic) hydrogen/deuterium have been studied with the quantum-classical Monte Carlo code (QCMC) developed for 'ab initio' - calculations. It has been shown that the majority of kaonic hydrogen atoms during cascade are accelerated to high energies E ∼ 100 eV, which leads to a much lower value for the calculated yields Y of x-rays than predicted by the 'standard cascade model'. The modified QCMC scheme has been applied to the study of the cascade in μp and μd muonic atoms. A comparison of the calculated yields for K-series x-rays with experimental data directly indicates that the molecular structure of the hydrogen target and new types of non-radiative transitions are essential for the light muonic atoms, while they are negligible for heavy (kaonic) atoms. These processes have been considered and estimates of their probabilities are presented. (author)

  10. Cascade Error Projection: A New Learning Algorithm

    Science.gov (United States)

    Duong, T. A.; Stubberud, A. R.; Daud, T.; Thakoor, A. P.

    1995-01-01

    A new neural network architecture and a hardware implementable learning algorithm is proposed. The algorithm, called cascade error projection (CEP), handles lack of precision and circuit noise better than existing algorithms.

  11. Simulation of concentration spikes in cascades

    International Nuclear Information System (INIS)

    Wood, H.G.

    2006-01-01

    Research has been conducted to investigate the maximum possible enrichment that might be temporarily achieved in a facility that is producing enriched uranium for fuel for nuclear power reactors. The purpose is to provide information to evaluate if uranium enrichment facilities are producing 235 U enriched within declared limits appropriate for power reactors or if the facilities are actually producing more highly enriched uranium. The correlation between feed rate and separation factor in a gas centrifuge cascade shows that as flow decreases, the separation factor increases, thereby, creating small amounts of higher enriched uranium than would be found under optimum design operating conditions. The research uses a number of cascade enrichment programs to model the phenomenon and determine the maximum enrichment possible during the time transient of a gas centrifuge cascade. During cascade start-up, the flow through the centrifuges begins at lower than centrifuge design stage flow rates. Steady-state cascade models have been used to study the maximum 235 U concentrations that would be predicted in the cascade. These calculations should produce an upper bound of product concentrations expected during the transient phase of start-up. Due to the fact that there are different ways in which to start a cascade, several methods are used to determine the maximum enrichment during the time transient. Model cascades were created for gas centrifuges with several product to .feed assay separation factors. With this information, the models were defined and the equilibrium programs were used to determine the maximum enrichment level during the time transient. The calculations predict in a cascade with separation factor 1.254 designed to produce enriched uranium for the purpose of supplying reactor fuel, it would not be unreasonable to see some 235 U in the range of 12-15%. Higher assays produced during the start-up period might lead inspectors to believe the cascade is being

  12. Cofilin phosphorylation is elevated after F-actin disassembly induced by Rac1 depletion.

    Science.gov (United States)

    Liu, Linna; Li, Jing; Zhang, Liwang; Zhang, Feng; Zhang, Rong; Chen, Xiang; Brakebusch, Cord; Wang, Zhipeng; Liu, Xinyou

    2015-01-01

    Cytoskeletal reorganization is essential to keratinocyte function. Rac1 regulates cytoskeletal reorganization through signaling pathways such as the cofilin cascade. Cofilin severs actin filaments after activation by dephosphorylation. Rac1 was knocked out in mouse keratinocytes and it was found that actin filaments disassembled. In the epidermis of mice in which Rac1 was knocked out only in keratinocytes, cofilin phosphorylation was aberrantly elevated, corresponding to repression of the phosphatase slingshot1 (SSH1). These effects were independent of the signaling pathways for p21-activated kinase/LIM kinase (Pak/LIMK), protein kinase C, or protein kinase D or generation of reactive oxygen species. Similarly, when actin polymerization was specifically inhibited or Rac1 was knocked down, cofilin phosphorylation was enhanced and SSH1 was repressed. Repression of SSH1 partially blocked actin depolymerization induced by Rac1 depletion. Therefore, aberrant cofilin phosphorylation that induces actin polymerization might be a consequence of actin disassembly induced by the absence of Rac1. © 2015 International Union of Biochemistry and Molecular Biology.

  13. mTORC1 directly phosphorylates and regulates human MAF1.

    Science.gov (United States)

    Michels, Annemieke A; Robitaille, Aaron M; Buczynski-Ruchonnet, Diane; Hodroj, Wassim; Reina, Jaime H; Hall, Michael N; Hernandez, Nouria

    2010-08-01

    mTORC1 is a central regulator of growth in response to nutrient availability, but few direct targets have been identified. RNA polymerase (pol) III produces a number of essential RNA molecules involved in protein synthesis, RNA maturation, and other processes. Its activity is highly regulated, and deregulation can lead to cell transformation. The human phosphoprotein MAF1 becomes dephosphorylated and represses pol III transcription after various stresses, but neither the significance of the phosphorylations nor the kinase involved is known. We find that human MAF1 is absolutely required for pol III repression in response to serum starvation or TORC1 inhibition by rapamycin or Torin1. The protein is phosphorylated mainly on residues S60, S68, and S75, and this inhibits its pol III repression function. The responsible kinase is mTORC1, which phosphorylates MAF1 directly. Our results describe molecular mechanisms by which mTORC1 controls human MAF1, a key repressor of RNA polymerase III transcription, and add a new branch to the signal transduction cascade immediately downstream of TORC1.

  14. mTORC1 Directly Phosphorylates and Regulates Human MAF1▿

    Science.gov (United States)

    Michels, Annemieke A.; Robitaille, Aaron M.; Buczynski-Ruchonnet, Diane; Hodroj, Wassim; Reina, Jaime H.; Hall, Michael N.; Hernandez, Nouria

    2010-01-01

    mTORC1 is a central regulator of growth in response to nutrient availability, but few direct targets have been identified. RNA polymerase (pol) III produces a number of essential RNA molecules involved in protein synthesis, RNA maturation, and other processes. Its activity is highly regulated, and deregulation can lead to cell transformation. The human phosphoprotein MAF1 becomes dephosphorylated and represses pol III transcription after various stresses, but neither the significance of the phosphorylations nor the kinase involved is known. We find that human MAF1 is absolutely required for pol III repression in response to serum starvation or TORC1 inhibition by rapamycin or Torin1. The protein is phosphorylated mainly on residues S60, S68, and S75, and this inhibits its pol III repression function. The responsible kinase is mTORC1, which phosphorylates MAF1 directly. Our results describe molecular mechanisms by which mTORC1 controls human MAF1, a key repressor of RNA polymerase III transcription, and add a new branch to the signal transduction cascade immediately downstream of TORC1. PMID:20516213

  15. Designing the Cascade inertial confinement fusion reactor

    International Nuclear Information System (INIS)

    Pitts, J.H.

    1987-01-01

    The primary goal in designing inertial confinement fusion (ICF) reactors is to produce electrical power as inexpensively as possible, with minimum activation and without compromising safety. This paper discusses a method for designing the Cascade rotating ceramic-granule-blanket reactor (Pitts, 1985) and its associated power plant (Pitts and Maya, 1985). Although focus is on the cascade reactor, the design method and issues presented are applicable to most other ICF reactors

  16. High energy evolution of soft gluon cascades

    International Nuclear Information System (INIS)

    Shuvaev, A.; Wallon, S.

    2006-01-01

    In this paper we derive an evolution equation for the gluon density in soft gluon cascades emitted from any colored source, in the leading logarithmic approximation of perturbative QCD. We show that this equation has the same form as the BFKL equation in the forward case. An explicit expression for the total cascade wavefunction involving an arbitrary number of soft gluons is obtained. Renormalization of the colored source wavefunction turns out to be responsible for the reggeization of the source. (orig.)

  17. High energy evolution of soft gluon cascades

    Energy Technology Data Exchange (ETDEWEB)

    Shuvaev, A. [St. Petersburg Nuclear Physics Institute, Gatchina, St. Petersburg district (Russian Federation); Wallon, S. [Universite Paris XI, Laboratoire de Physique Theorique, Orsay Cedex (France)

    2006-04-15

    In this paper we derive an evolution equation for the gluon density in soft gluon cascades emitted from any colored source, in the leading logarithmic approximation of perturbative QCD. We show that this equation has the same form as the BFKL equation in the forward case. An explicit expression for the total cascade wavefunction involving an arbitrary number of soft gluons is obtained. Renormalization of the colored source wavefunction turns out to be responsible for the reggeization of the source. (orig.)

  18. Cascade of links in complex networks

    Energy Technology Data Exchange (ETDEWEB)

    Feng, Yeqian; Sun, Bihui [Department of Management Science, School of Government, Beijing Normal University, 100875 Beijing (China); Zeng, An, E-mail: anzeng@bnu.edu.cn [School of Systems Science, Beijing Normal University, 100875 Beijing (China)

    2017-01-30

    Cascading failure is an important process which has been widely used to model catastrophic events such as blackouts and financial crisis in real systems. However, so far most of the studies in the literature focus on the cascading process on nodes, leaving the possibility of link cascade overlooked. In many real cases, the catastrophic events are actually formed by the successive disappearance of links. Examples exist in the financial systems where the firms and banks (i.e. nodes) still exist but many financial trades (i.e. links) are gone during the crisis, and the air transportation systems where the airports (i.e. nodes) are still functional but many airlines (i.e. links) stop operating during bad weather. In this letter, we develop a link cascade model in complex networks. With this model, we find that both artificial and real networks tend to collapse even if a few links are initially attacked. However, the link cascading process can be effectively terminated by setting a few strong nodes in the network which do not respond to any link reduction. Finally, a simulated annealing algorithm is used to optimize the location of these strong nodes, which significantly improves the robustness of the networks against the link cascade. - Highlights: • We propose a link cascade model in complex networks. • Both artificial and real networks tend to collapse even if a few links are initially attacked. • The link cascading process can be effectively terminated by setting a few strong nodes. • A simulated annealing algorithm is used to optimize the location of these strong nodes.

  19. Cascade of links in complex networks

    International Nuclear Information System (INIS)

    Feng, Yeqian; Sun, Bihui; Zeng, An

    2017-01-01

    Cascading failure is an important process which has been widely used to model catastrophic events such as blackouts and financial crisis in real systems. However, so far most of the studies in the literature focus on the cascading process on nodes, leaving the possibility of link cascade overlooked. In many real cases, the catastrophic events are actually formed by the successive disappearance of links. Examples exist in the financial systems where the firms and banks (i.e. nodes) still exist but many financial trades (i.e. links) are gone during the crisis, and the air transportation systems where the airports (i.e. nodes) are still functional but many airlines (i.e. links) stop operating during bad weather. In this letter, we develop a link cascade model in complex networks. With this model, we find that both artificial and real networks tend to collapse even if a few links are initially attacked. However, the link cascading process can be effectively terminated by setting a few strong nodes in the network which do not respond to any link reduction. Finally, a simulated annealing algorithm is used to optimize the location of these strong nodes, which significantly improves the robustness of the networks against the link cascade. - Highlights: • We propose a link cascade model in complex networks. • Both artificial and real networks tend to collapse even if a few links are initially attacked. • The link cascading process can be effectively terminated by setting a few strong nodes. • A simulated annealing algorithm is used to optimize the location of these strong nodes.

  20. Defect production in simulated cascades: Cascade quenching and short-term annealing

    International Nuclear Information System (INIS)

    Heinisch, H.L.

    1983-01-01

    Defect production in displacement cascades in copper has been modeled using the MARLOWE code to generate cascades and the stochastic annealing code ALSOME to simulate cascade quenching and short-term annealing of isolated cascades. Quenching is accomplished by using exaggerated values for defect mobilities and for critical reaction distances in ALSOME for a very short time. The quenched cascades are then short-term annealed with normal parameter values. The quenching parameter values were empirically determined by comparison with results of resistivity measurements. Throughout the collisional, quenching and short-term annealing phases of cascade development, the high energy cascades continue to behave as a collection of independent lower energy lobes. For recoils above about 30 keV the total number of defects and the numbers of free defects scale with the damage energy. As the energy decreases from 30 keV, defect production varies with the changing nature of the cascade configuration, resulting in more defects per unit damage energy. The simulated annealing of a low fluence of interacting cascades revealed an interstitial shielding effect on depleted zones during Stage I recovery. (orig.)

  1. Src kinase regulation by phosphorylation and dephosphorylation

    International Nuclear Information System (INIS)

    Roskoski, Robert

    2005-01-01

    Src and Src-family protein-tyrosine kinases are regulatory proteins that play key roles in cell differentiation, motility, proliferation, and survival. The initially described phosphorylation sites of Src include an activating phosphotyrosine 416 that results from autophosphorylation, and an inhibiting phosphotyrosine 527 that results from phosphorylation by C-terminal Src kinase (Csk) and Csk homologous kinase. Dephosphorylation of phosphotyrosine 527 increases Src kinase activity. Candidate phosphotyrosine 527 phosphatases include cytoplasmic PTP1B, Shp1 and Shp2, and transmembrane enzymes include CD45, PTPα, PTPε, and PTPλ. Dephosphorylation of phosphotyrosine 416 decreases Src kinase activity. Thus far PTP-BL, the mouse homologue of human PTP-BAS, has been shown to dephosphorylate phosphotyrosine 416 in a regulatory fashion. The platelet-derived growth factor receptor protein-tyrosine kinase mediates the phosphorylation of Src Tyr138; this phosphorylation has no direct effect on Src kinase activity. The platelet-derived growth factor receptor and the ErbB2/HER2 growth factor receptor protein-tyrosine kinases mediate the phosphorylation of Src Tyr213 and activation of Src kinase activity. Src kinase is also a substrate for protein-serine/threonine kinases including protein kinase C (Ser12), protein kinase A (Ser17), and CDK1/cdc2 (Thr34, Thr46, and Ser72). Of the three protein-serine/threonine kinases, only phosphorylation by CDK1/cdc2 has been demonstrated to increase Src kinase activity. Although considerable information on the phosphoprotein phosphatases that catalyze the hydrolysis of Src phosphotyrosine 527 is at hand, the nature of the phosphatases that mediate the hydrolysis of phosphotyrosine 138 and 213, and phosphoserine and phosphothreonine residues has not been determined

  2. Formalism of continual integrals for cascade processes with particle fusion

    International Nuclear Information System (INIS)

    Gedalin, Eh.V.

    1987-01-01

    Formalism of continuous integrals for description of cascade processes, in which besides cascade particle reproduction, their synthesis and coalescence take place, is used. Account of cascade particle coalescence leads to the fact that the development of some cascade branches cannot be independent and main equations of the cascade process become functional instead of integral. The method of continuous intagrals permits to construct in the closed form producing functionals for the cascade process and to obtain the rules of their calculation using diagrams. Analytical expressions in the form of continuous integrals for producing functionals describing cascade development are obtained

  3. Proteasome phosphorylation regulates cocaine-induced sensitization.

    Science.gov (United States)

    Gonzales, Frankie R; Howell, Kristin K; Dozier, Lara E; Anagnostaras, Stephan G; Patrick, Gentry N

    2018-04-01

    Repeated exposure to cocaine produces structural and functional modifications at synapses from neurons in several brain regions including the nucleus accumbens. These changes are thought to underlie cocaine-induced sensitization. The ubiquitin proteasome system plays a crucial role in the remodeling of synapses and has recently been implicated in addiction-related behavior. The ATPase Rpt6 subunit of the 26S proteasome is phosphorylated by Ca 2+ /calmodulin-dependent protein kinases II alpha at ser120 which is thought to regulate proteasome activity and distribution in neurons. Here, we demonstrate that Rpt6 phosphorylation is involved in cocaine-induced locomotor sensitization. Cocaine concomitantly increases proteasome activity and Rpt6 S120 phosphorylation in cultured neurons and in various brain regions of wild type mice including the nucleus accumbens and prefrontal cortex. In contrast, cocaine does not increase proteasome activity in Rpt6 phospho-mimetic (ser120Asp) mice. Strikingly, we found a complete absence of cocaine-induced locomotor sensitization in the Rpt6 ser120Asp mice. Together, these findings suggest a critical role for Rpt6 phosphorylation and proteasome function in the regulation cocaine-induced behavioral plasticity. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Regulation of protein phosphorylation in oat mitochondria

    International Nuclear Information System (INIS)

    Pike, C.; Kopeck, K.; Sceppa, E.

    1989-01-01

    We sought to identify phosphorylated proteins in isolated oat mitocchondria and to characterize the enzymatic and regulatory properties of the protein kinase(s). Mitochondria from oats (Avena sativa L. cv. Garry) were purified on Percoll gradients. Mitochondria were incubated with 32 P-γ-ATP; proteins were separated by SDS-PAGE. A small number of bands was detected on autoradiograms, most prominently at 70 kD and 42 kD; the latter band has been tentatively identified as a subunit of the pyruvate dehydrogenase complex, a well-known phosphoprotein. The protein kinase(s) could also phosphorylate casein, but not histone. Spermine enhanced the phosphorylation of casein and inhibited the phosphorylation of the 42 kD band. These studies were carried out on both intact and burst mitochondria. Control by calcium and other ions was investigated. The question of the action of regulators on protein kinase or protein phosphatase was studied by the use of 35 S-adenosine thiotriphosphate

  5. Tyrosine phosphorylation switching of a G protein.

    Science.gov (United States)

    Li, Bo; Tunc-Ozdemir, Meral; Urano, Daisuke; Jia, Haiyan; Werth, Emily G; Mowrey, David D; Hicks, Leslie M; Dokholyan, Nikolay V; Torres, Matthew P; Jones, Alan M

    2018-03-30

    Heterotrimeric G protein complexes are molecular switches relaying extracellular signals sensed by G protein-coupled receptors (GPCRs) to downstream targets in the cytoplasm, which effect cellular responses. In the plant heterotrimeric GTPase cycle, GTP hydrolysis, rather than nucleotide exchange, is the rate-limiting reaction and is accelerated by a receptor-like regulator of G signaling (RGS) protein. We hypothesized that posttranslational modification of the Gα subunit in the G protein complex regulates the RGS-dependent GTPase cycle. Our structural analyses identified an invariant phosphorylated tyrosine residue (Tyr 166 in the Arabidopsis Gα subunit AtGPA1) located in the intramolecular domain interface where nucleotide binding and hydrolysis occur. We also identified a receptor-like kinase that phosphorylates AtGPA1 in a Tyr 166 -dependent manner. Discrete molecular dynamics simulations predicted that phosphorylated Tyr 166 forms a salt bridge in this interface and potentially affects the RGS protein-accelerated GTPase cycle. Using a Tyr 166 phosphomimetic substitution, we found that the cognate RGS protein binds more tightly to the GDP-bound Gα substrate, consequently reducing its ability to accelerate GTPase activity. In conclusion, we propose that phosphorylation of Tyr 166 in AtGPA1 changes the binding pattern with AtRGS1 and thereby attenuates the steady-state rate of the GTPase cycle. We coin this newly identified mechanism "substrate phosphoswitching." © 2018 by The American Society for Biochemistry and Molecular Biology, Inc.

  6. Defect production in simulated cascades: cascade quenching and short-term annealing

    International Nuclear Information System (INIS)

    Heinisch, H.L.

    1982-01-01

    Defect production in high energy displacement cascades has been modeled using the computer code MARLOWE to generate the cascades and the stochastic computer code ALSOME to simulate the cascade quenching and short-term annealing of isolated cascades. The quenching is accomplished by using ALSOME with exaggerated values for defect mobilities and critical reaction distanes for recombination and clustering, which are in effect until the number of defect pairs is equal to the value determined from resistivity experiments at 4K. Then normal mobilities and reaction distances are used during short-term annealing to a point representative of Stage III recovery. Effects of cascade interactions at low fluences are also being investigated. The quenching parameter values were empirically determined for 30 keV cascades. The results agree well with experimental information throughout the range from 1 keV to 100 keV. Even after quenching and short-term annealing the high energy cascades behave as a collection of lower energy subcascades and lobes. Cascades generated in a crystal having thermal displacements were found to be in better agreement with experiments after quenching and annealing than those generated in a non-thermal crystal

  7. PKCδ-mediated phosphorylation of BAG3 at Ser187 site induces epithelial-mesenchymal transition and enhances invasiveness in thyroid cancer FRO cells.

    Science.gov (United States)

    Li, N; Du, Z-X; Zong, Z-H; Liu, B-Q; Li, C; Zhang, Q; Wang, H-Q

    2013-09-19

    Protein kinase C delta (PKCδ) is a serine (Ser)/threonine kinase, which regulates numerous cellular processes, including proliferation, differentiation, migration and apoptosis. In the current study, Chinese hamster ovary cells were transfected with either a constitutively activated PKCδ or a dominant negative PKCδ, phosphoprotein enrichment, two-dimensional difference gel electrophoresis and mass spectrometry was combined to globally identified candidates of PKCδ cascade. We found that Bcl-2 associated athanogene 3 (BAG3) was one of the targets of PKCδ cascade, and BAG3 interacted with PKCδ in vivo. In addition, we clarified that BAG3 was phosphorylate at Ser187 site in a PKCδ-dependent manner in vivo. BAG3 has been implicated in multiple cellular functions, including proliferation, differentiation, apoptosis, migration, invasion, macroautophagy and so on. We generated wild-type (WT)-, Ser187Ala (S187A)- or Ser187Asp (S187D)-BAG3 stably expressing FRO cells, and noticed that phosphorylation state of BAG3 influenced FRO morphology. Finally, for the first time, we showed that BAG3 was implicated in epithelial-mesenchymal transition (EMT) procedure, and phosphorylation state at Ser187 site had a critical role in EMT regulation by BAG3. Collectively, the current study indicates that BAG3 is a novel substrate of PKCδ, and PKCδ-mediated phosphorylation of BAG3 is implicated in EMT and invasiveness of thyroid cancer cells.

  8. Assigning Quantitative Function to Post-Translational Modifications Reveals Multiple Sites of Phosphorylation That Tune Yeast Pheromone Signaling Output

    Energy Technology Data Exchange (ETDEWEB)

    Pincus, David; Ryan, Christopher J.; Smith, Richard D.; Brent, Roger; Resnekov, Orna; Hakimi, Mohamed Ali

    2013-03-12

    Cell signaling systems transmit information by post-­translationally modifying signaling proteins, often via phosphorylation. While thousands of sites of phosphorylation have been identified in proteomic studies, the vast majority of sites have no known function. Assigning functional roles to the catalog of uncharacterized phosphorylation sites is a key research challenge. Here we present a general approach to address this challenge and apply it to a prototypical signaling pathway, the pheromone response pathway in Saccharomyces cerevisiae. The pheromone pathway includes a mitogen activated protein kinase (MAPK) cascade activated by a G-­protein coupled receptor (GPCR). We used mass spectrometry-based proteomics to identify sites whose phosphorylation changed when the system was active, and evolutionary conservation to assign priority to a list of candidate MAPK regulatory sites. We made targeted alterations in those sites, and measured the effects of the mutations on pheromone pathway output in single cells. Our work identified six new sites that quantitatively tuned system output. We developed simple computational models to find system architectures that recapitulated the quantitative phenotypes of the mutants. Our results identify a number of regulated phosphorylation events that contribute to adjust the input-­output relationship of this model eukaryotic signaling system. We believe this combined approach constitutes a general means not only to reveal modification sites required to turn a pathway on and off, but also those required for more subtle quantitative effects that tune pathway output. Our results further suggest that relatively small quantitative influences from individual regulatory phosphorylation events endow signaling systems with plasticity that evolution may exploit to quantitatively tailor signaling outcomes.

  9. Protein phosphorylation in isolated human adipocytes - Adrenergic control of the phosphorylation of hormone-sensitive lipase

    International Nuclear Information System (INIS)

    Smiley, R.M.; Paul, S.; Browning, M.D.; Leibel, R.L.; Hirsch, J.

    1990-01-01

    The effect of adrenergic agents on protein phosphorylation in human adipocytes was examined. Freshly isolated human fat cells were incubated with 32 PO 4 in order to label intracellular ATP, then treated with a variety of adrenergic and other pharmacologic agents. Treatment with the β-adrenergic agonist isoproterenol led to a significant increase in phosphate content of at least five protein bands (M r 52, 53, 63, 67, 84 kDa). The increase in phosphorylation was partially inhibited by the α-2 agonist clonidine. Epinephrine, a combined α and β agonist, was less effective at increasing phosphate content of the proteins than was isoproterenol. Neither insulin nor the α-1 agonist phenylephrine had any discernible effect on the pattern of protein phosphorylation. The 84 kDa phosphorylated peptide band appears to contain hormone-sensitive lipase, a key enzyme in the lipolytic pathway which is activated by phosphorylation. These results are somewhat different than previously reported results for rat adipocytes, and represent the first report of overall pattern and adrenergic modulation of protein phosphorylation in human adipocytes

  10. Conserved phosphoryl transfer mechanisms within kinase families and the role of the C8 proton of ATP in the activation of phosphoryl transfer

    Directory of Open Access Journals (Sweden)

    Kenyon Colin P

    2012-03-01

    Full Text Available Abstract Background The kinome is made up of a large number of functionally diverse enzymes, with the classification indicating very little about the extent of the conserved kinetic mechanisms associated with phosphoryl transfer. It has been demonstrated that C8-H of ATP plays a critical role in the activity of a range of kinase and synthetase enzymes. Results A number of conserved mechanisms within the prescribed kinase fold families have been identified directly utilizing the C8-H of ATP in the initiation of phosphoryl transfer. These mechanisms are based on structurally conserved amino acid residues that are within hydrogen bonding distance of a co-crystallized nucleotide. On the basis of these conserved mechanisms, the role of the nucleotide C8-H in initiating the formation of a pentavalent intermediate between the γ-phosphate of the ATP and the substrate nucleophile is defined. All reactions can be clustered into two mechanisms by which the C8-H is induced to be labile via the coordination of a backbone carbonyl to C6-NH2 of the adenyl moiety, namely a "push" mechanism, and a "pull" mechanism, based on the protonation of N7. Associated with the "push" mechanism and "pull" mechanisms are a series of proton transfer cascades, initiated from C8-H, via the tri-phosphate backbone, culminating in the formation of the pentavalent transition state between the γ-phosphate of the ATP and the substrate nucleophile. Conclusions The "push" mechanism and a "pull" mechanism are responsible for inducing the C8-H of adenyl moiety to become more labile. These mechanisms and the associated proton transfer cascades achieve the proton transfer via different family-specific conserved sets of amino acids. Each of these mechanisms would allow for the regulation of the rate of formation of the pentavalent intermediate between the ATP and the substrate nucleophile. Phosphoryl transfer within kinases is therefore a specific event mediated and regulated via the

  11. Numerical routine for magnetic heat pump cascading

    DEFF Research Database (Denmark)

    Filonenko, Konstantin; Lei, Tian; Engelbrecht, Kurt

    Heat pumps use low-temperature heat absorbed from the energy source to create temperature gradient (TG) across the energy sink. Magnetic heat pumps (MHP) can perform this function through operating active magnetic regeneration (AMR) cycle. For building heating, TGs of up to a few K might...... and 3 K. Changing the number of MHPs, we optimized input parameters to achieve maximum heating powers. We have found that both maximum heating power and COP decrease together with number of heat pumps, but the TGs and the temperature span can be largely increased. References [1] M. Tahavori et al., “A...... be necessary, which is hardly achievable with a single MHP and such techniques as cascading are required. Series and parallel cascading increase the AMR span and heating power, respectively, but do not change TG. Therefore, the intermediate type of cascading was proposed with individual MHPs separately...

  12. Non-spill control squared cascade

    International Nuclear Information System (INIS)

    Kai, Tsunetoshi; Inoue, Yoshiya; Oya, Akio; Suemori, Nobuo.

    1974-01-01

    Object: To reduce a mixed loss thus enhancing separating efficiency by the provision of a simple arrangement wherein a reflux portion in a conventional spill control squared cascade is replaced by a special stage including centrifugal separators. Structure: Steps in the form of a square cascade, in which a plurality of centrifugal separators are connected by pipe lines, are accumulated in multistage fashion to form a squared cascade. Between the adjoining steps is disposed a special stage including a centrifugal separator which receives both lean flow from the upper step and rich flow from the lower step. The centrifugal separator in the special stage has its rich side connected to the upper step and its lean side connected to the lower step. Special stages are each disposed at the upper side of the uppermost step and at the lower side of the lowermost step. (Kamimura, M.)

  13. Sample Selection for Training Cascade Detectors.

    Science.gov (United States)

    Vállez, Noelia; Deniz, Oscar; Bueno, Gloria

    2015-01-01

    Automatic detection systems usually require large and representative training datasets in order to obtain good detection and false positive rates. Training datasets are such that the positive set has few samples and/or the negative set should represent anything except the object of interest. In this respect, the negative set typically contains orders of magnitude more images than the positive set. However, imbalanced training databases lead to biased classifiers. In this paper, we focus our attention on a negative sample selection method to properly balance the training data for cascade detectors. The method is based on the selection of the most informative false positive samples generated in one stage to feed the next stage. The results show that the proposed cascade detector with sample selection obtains on average better partial AUC and smaller standard deviation than the other compared cascade detectors.

  14. Sample Selection for Training Cascade Detectors.

    Directory of Open Access Journals (Sweden)

    Noelia Vállez

    Full Text Available Automatic detection systems usually require large and representative training datasets in order to obtain good detection and false positive rates. Training datasets are such that the positive set has few samples and/or the negative set should represent anything except the object of interest. In this respect, the negative set typically contains orders of magnitude more images than the positive set. However, imbalanced training databases lead to biased classifiers. In this paper, we focus our attention on a negative sample selection method to properly balance the training data for cascade detectors. The method is based on the selection of the most informative false positive samples generated in one stage to feed the next stage. The results show that the proposed cascade detector with sample selection obtains on average better partial AUC and smaller standard deviation than the other compared cascade detectors.

  15. Multilevel Inverter by Cascading Industrial VSI

    DEFF Research Database (Denmark)

    Teodorescu, Remus; Blaabjerg, Frede; Pedersen, John Kim

    2002-01-01

    In this paper the modularity concept applied to medium-voltage adjustable speed drives is addressed. First, the single-phase cascaded voltage-source inverter that uses series connection of IGBT H-bridge modules with isolated dc-buses is presented. Next, a novel three-phase cascaded voltage......-source inverter that uses three IGBT triphase inverter modules along with an output transformer to obtain a 3 p.u. multilevel output voltage is introduced. The system yields in high-quality multistep voltage with up to 4 levels and low dv/dt, balanced operation of the inverter modules, each supplying a third...... of the motor rated kVA. The concept of using cascaded inverters is further extended to a new modular motor-modular inverter system where the motor winding connections are reconnected into several three-phase groups, either six-lead or 12-lead connection according to the voltage level, each powered...

  16. Cascade enzymatic reactions for efficient carbon sequestration.

    Science.gov (United States)

    Xia, Shunxiang; Zhao, Xueyan; Frigo-Vaz, Benjamin; Zheng, Wenyun; Kim, Jungbae; Wang, Ping

    2015-04-01

    Thermochemical processes developed for carbon capture and storage (CCS) offer high carbon capture capacities, but are generally hampered by low energy efficiency. Reversible cascade enzyme reactions are examined in this work for energy-efficient carbon sequestration. By integrating the reactions of two key enzymes of RTCA cycle, isocitrate dehydrogenase and aconitase, we demonstrate that intensified carbon capture can be realized through such cascade enzymatic reactions. Experiments show that enhanced thermodynamic driving force for carbon conversion can be attained via pH control under ambient conditions, and that the cascade reactions have the potential to capture 0.5 mol carbon at pH 6 for each mole of substrate applied. Overall it manifests that the carbon capture capacity of biocatalytic reactions, in addition to be energy efficient, can also be ultimately intensified to approach those realized with chemical absorbents such as MEA. Copyright © 2015 Elsevier Ltd. All rights reserved.

  17. Activation of Signaling Cascades by Weak Extremely Low Frequency Electromagnetic Fields

    Directory of Open Access Journals (Sweden)

    Einat Kapri-Pardes

    2017-10-01

    Full Text Available Background/Aims: Results from recent studies suggest that extremely low frequency magnetic fields (ELF-MF interfere with intracellular signaling pathways related to proliferative control. The mitogen-activated protein kinases (MAPKs, central signaling components that regulate essentially all stimulated cellular processes, include the extracellular signal-regulated kinases 1/2 (ERK1/2 that are extremely sensitive to extracellular cues. Anti-phospho-ERK antibodies serve as a readout for ERK1/2 activation and are able to detect minute changes in ERK stimulation. The objective of this study was to explore whether activation of ERK1/2 and other signaling cascades can be used as a readout for responses of a variety of cell types, both transformed and non-transformed, to ELF-MF. Methods: We applied ELF-MF at various field strengths and time periods to eight different cell types with an exposure system housed in a tissue culture incubator and followed the phosphorylation of MAPKs and Akt by western blotting. Results: We found that the phosphorylation of ERK1/2 is increased in response to ELF-MF. However, the phosphorylation of ERK1/2 is likely too low to induce ELF-MF-dependent proliferation or oncogenic transformation. The p38 MAPK was very slightly phosphorylated, but JNK or Akt were not. The effect on ERK1/2 was detected for exposures to ELF-MF strengths as low as 0.15 µT and was maximal at ∼10 µT. We also show that ERK1/2 phosphorylation is blocked by the flavoprotein inhibitor diphenyleneiodonium, indicating that the response to ELF-MF may be exerted via NADP oxidase similar to the phosphorylation of ERK1/2 in response to microwave radiation. Conclusions: Our results further indicate that cells are responsive to ELF-MF at field strengths much lower than previously suspected and that the effect may be mediated by NADP oxidase. However, the small increase in ERK1/2 phosphorylation is probably insufficient to affect proliferation and oncogenic

  18. Cascade Processes in Muonic Hydrogen Atoms

    International Nuclear Information System (INIS)

    Faifman, M. P.; Men'Shikov, L. I.

    2001-01-01

    The QCMC scheme created earlier for cascade calculations in heavy hadronic atoms of hydrogen isotopes has been modified and applied to the study of cascade processes in the μp muonic hydrogen atoms. The distribution of μp atoms over kinetic energies has been obtained and the yields of K-series X-rays per one stopped muon have been calculated.Comparison with experimental data indicated directly that for muonic and pionic atoms new types of non-radiative transitions are essential, while they are negligible for heavy (kaonic, antiprotonic, etc.) atoms. These processes have been considered and their probabilities have been estimated.

  19. Volcano geodesy in the Cascade arc, USA

    Science.gov (United States)

    Poland, Michael; Lisowski, Michael; Dzurisin, Daniel; Kramer, Rebecca; McLay, Megan; Pauk, Benjamin

    2017-01-01

    Experience during historical time throughout the Cascade arc and the lack of deep-seated deformation prior to the two most recent eruptions of Mount St. Helens might lead one to infer that Cascade volcanoes are generally quiescent and, specifically, show no signs of geodetic change until they are about to erupt. Several decades of geodetic data, however, tell a different story. Ground- and space-based deformation studies have identified surface displacements at five of the 13 major Cascade arc volcanoes that lie in the USA (Mount Baker, Mount St. Helens, South Sister, Medicine Lake, and Lassen volcanic center). No deformation has been detected at five volcanoes (Mount Rainier, Mount Hood, Newberry Volcano, Crater Lake, and Mount Shasta), and there are not sufficient data at the remaining three (Glacier Peak, Mount Adams, and Mount Jefferson) for a rigorous assessment. In addition, gravity change has been measured at two of the three locations where surveys have been repeated (Mount St. Helens and Mount Baker show changes, while South Sister does not). Broad deformation patterns associated with heavily forested and ice-clad Cascade volcanoes are generally characterized by low displacement rates, in the range of millimeters to a few centimeters per year, and are overprinted by larger tectonic motions of several centimeters per year. Continuous GPS is therefore the best means of tracking temporal changes in deformation of Cascade volcanoes and also for characterizing tectonic signals so that they may be distinguished from volcanic sources. Better spatial resolution of volcano deformation can be obtained through the use of campaign GPS, semipermanent GPS, and interferometric synthetic aperture radar observations, which leverage the accumulation of displacements over time to improve signal to noise. Deformation source mechanisms in the Cascades are diverse and include magma accumulation and withdrawal, post-emplacement cooling of recent volcanic deposits, magmatic

  20. Volcano geodesy in the Cascade arc, USA

    Science.gov (United States)

    Poland, Michael P.; Lisowski, Michael; Dzurisin, Daniel; Kramer, Rebecca; McLay, Megan; Pauk, Ben

    2017-08-01

    Experience during historical time throughout the Cascade arc and the lack of deep-seated deformation prior to the two most recent eruptions of Mount St. Helens might lead one to infer that Cascade volcanoes are generally quiescent and, specifically, show no signs of geodetic change until they are about to erupt. Several decades of geodetic data, however, tell a different story. Ground- and space-based deformation studies have identified surface displacements at five of the 13 major Cascade arc volcanoes that lie in the USA (Mount Baker, Mount St. Helens, South Sister, Medicine Lake, and Lassen volcanic center). No deformation has been detected at five volcanoes (Mount Rainier, Mount Hood, Newberry Volcano, Crater Lake, and Mount Shasta), and there are not sufficient data at the remaining three (Glacier Peak, Mount Adams, and Mount Jefferson) for a rigorous assessment. In addition, gravity change has been measured at two of the three locations where surveys have been repeated (Mount St. Helens and Mount Baker show changes, while South Sister does not). Broad deformation patterns associated with heavily forested and ice-clad Cascade volcanoes are generally characterized by low displacement rates, in the range of millimeters to a few centimeters per year, and are overprinted by larger tectonic motions of several centimeters per year. Continuous GPS is therefore the best means of tracking temporal changes in deformation of Cascade volcanoes and also for characterizing tectonic signals so that they may be distinguished from volcanic sources. Better spatial resolution of volcano deformation can be obtained through the use of campaign GPS, semipermanent GPS, and interferometric synthetic aperture radar observations, which leverage the accumulation of displacements over time to improve signal to noise. Deformation source mechanisms in the Cascades are diverse and include magma accumulation and withdrawal, post-emplacement cooling of recent volcanic deposits, magmatic

  1. Interferometric modulation of quantum cascade interactions

    Science.gov (United States)

    Cusumano, Stefano; Mari, Andrea; Giovannetti, Vittorio

    2018-05-01

    We consider many-body quantum systems dissipatively coupled by a cascade network, i.e., a setup in which interactions are mediated by unidirectional environmental modes propagating through a linear optical interferometer. In particular we are interested in the possibility of inducing different effective interactions by properly engineering an external dissipative network of beam splitters and phase shifters. In this work we first derive the general structure of the master equation for a symmetric class of translation-invariant cascade networks. Then we show how, by tuning the parameters of the interferometer, one can exploit interference effects to tailor a large variety of many-body interactions.

  2. Flux control through protein phosphorylation in yeast

    DEFF Research Database (Denmark)

    Chen, Yu; Nielsen, Jens

    2016-01-01

    Protein phosphorylation is one of the most important mechanisms regulating metabolism as it can directly modify metabolic enzymes by the addition of phosphate groups. Attributed to such a rapid and reversible mechanism, cells can adjust metabolism rapidly in response to temporal changes. The yeast...... as well as identify mechanisms underlying human metabolic diseases. Here we collect functional phosphorylation events of 41 enzymes involved in yeast metabolism and demonstrate functional mechanisms and the application of this information in metabolic engineering. From a systems biology perspective, we...... describe the development of phosphoproteomics in yeast as well as approaches to analysing the phosphoproteomics data. Finally, we focus on integrated analyses with other omics data sets and genome-scale metabolic models. Despite the advances, future studies improving both experimental technologies...

  3. Solid polymer electrolyte from phosphorylated chitosan

    Energy Technology Data Exchange (ETDEWEB)

    Fauzi, Iqbal, E-mail: arcana@chem.itb.ac.id; Arcana, I Made, E-mail: arcana@chem.itb.ac.id [Inorganic and Physical Chemistry Research Groups, Faculty of Mathematics and Natural Sciences, Institut Teknologi Bandung, Jl. Ganesha 10, Bandung 40132 (Indonesia)

    2014-03-24

    Recently, the need of secondary battery application continues to increase. The secondary battery which using a liquid electrolyte was indicated had some weakness. A solid polymer electrolyte is an alternative electrolytes membrane which developed in order to replace the liquid electrolyte type. In the present study, the effect of phosphorylation on to polymer electrolyte membrane which synthesized from chitosan and lithium perchlorate salts was investigated. The effect of the component’s composition respectively on the properties of polymer electrolyte, was carried out by analyzed of it’s characterization such as functional groups, ion conductivity, and thermal properties. The mechanical properties i.e tensile resistance and the morphology structure of membrane surface were determined. The phosphorylation processing of polymer electrolyte membrane of chitosan and lithium perchlorate was conducted by immersing with phosphoric acid for 2 hours, and then irradiated on a microwave for 60 seconds. The degree of deacetylation of chitosan derived from shrimp shells was obtained around 75.4%. Relative molecular mass of chitosan was obtained by viscometry method is 796,792 g/mol. The ionic conductivity of chitosan membrane was increase from 6.33 × 10{sup −6} S/cm up to 6.01 × 10{sup −4} S/cm after adding by 15 % solution of lithium perchlorate. After phosphorylation, the ionic conductivity of phosphorylated lithium chitosan membrane was observed 1.37 × 10{sup −3} S/cm, while the tensile resistance of 40.2 MPa with a better thermal resistance. On the strength of electrolyte membrane properties, this polymer electrolyte membrane was suggested had one potential used for polymer electrolyte in field of lithium battery applications.

  4. Protein phosphorylation in bcterial signaling and regulation

    KAUST Repository

    Mijakovic, Ivan

    2016-01-26

    In 2003, it was demonstrated for the first time that bacteria possess protein-tyrosine kinases (BY-kinases), capable of phosphorylating other cellular proteins and regulating their activity. It soon became apparent that these kinases phosphorylate a number of protein substrates, involved in different cellular processes. More recently, we found out that BY-kinases can be activated by several distinct protein interactants, and are capable of engaging in cross-phosphorylation with other kinases. Evolutionary studies based on genome comparison indicate that BY-kinases exist only in bacteria. They are non-essential (present in about 40% bacterial genomes), and their knockouts lead to pleiotropic phenotypes, since they phosphorylate many substrates. Surprisingly, BY-kinase genes accumulate mutations at an increased rate (non-synonymous substitution rate significantly higher than other bacterial genes). One direct consequence of this phenomenon is no detectable co-evolution between kinases and their substrates. Their promiscuity towards substrates thus seems to be “hard-wired”, but why would bacteria maintain such promiscuous regulatory devices? One explanation is the maintenance of BY-kinases as rapidly evolving regulators, which can readily adopt new substrates when environmental changes impose selective pressure for quick evolution of new regulatory modules. Their role is clearly not to act as master regulators, dedicated to triggering a single response, but they might rather be employed to contribute to fine-tuning and improving robustness of various cellular responses. This unique feature makes BY-kinases a potentially useful tool in synthetic biology. While other bacterial kinases are very specific and their signaling pathways insulated, BY-kinase can relatively easily be engineered to adopt new substrates and control new biosynthetic processes. Since they are absent in humans, and regulate some key functions in pathogenic bacteria, they are also very promising

  5. Peroxides and radiation impairment of oxidative phosphorylation

    Energy Technology Data Exchange (ETDEWEB)

    Dovgii, I E; Akoev, I G

    1975-09-01

    An increase in the peroxidase activity of the mitochondria and a simultaneous rise in the amount of peroxide compounds, which are half lipid-like substances, are detected within the first 10 minutes after irradiation (1000 r). A mechanism of radiation impairment of oxidative phosphorylation is connected with the penetration of its inhibitors to the mitochondria due to the disturbed permeability of membranes affected by peroxides.

  6. Phosphorylation of proteins in Clostridium thermohydrosulfuricum

    International Nuclear Information System (INIS)

    Londesborough, J.

    1986-01-01

    Cell extracts of the thermophile Clostridium thermohydrosulfuricum catalyzed the phosphorylation by (γ- 32 P)ATP of several endogenous proteins with M/sub r/s between 13,000 and 100,000. Serine and tyrosine were the main acceptors. Distinct substrate proteins were found in the soluble (e.g., proteins p66, p63, and p53 of M/sub r/s 66,000, 63,000, and 53,000, respectively) and particulate (p76 and p30) fractions, both of which contained protein kinase and phosphatase activity. The soluble fraction suppressed the phosphorylation of particulate proteins and contained a protein kinase inhibitor. Phosphorylation of p53 was promoted by 10μM fructose 1,6-bisphosphate or glucose 1,6-bisphosphate and suppressed by hexose monophosphates, whereas p30 and p13 were suppressed by 5 μM brain (but not spinach) calmodulin. Polyamines, including the odd polyamines characteristic of thermophiles, modulated the labeling of most of the phosphoproteins. Apart from p66, all the proteins labeled in vitro were also rapidly labeled in intact cells by 32 P/sub i/. Several proteins strongly labeled in vivo were labeled slowly or not at all in vitro

  7. Unraveling a phosphorylation event in a folded protein by NMR spectroscopy: phosphorylation of the Pin1 WW domain by PKA

    Energy Technology Data Exchange (ETDEWEB)

    Smet-Nocca, Caroline, E-mail: caroline.smet@univ-lille1.fr; Launay, Helene; Wieruszeski, Jean-Michel; Lippens, Guy; Landrieu, Isabelle, E-mail: isabelle.landrieu@univ-lille1.fr [Universite de Lille-Nord de France, Institut Federatif de Recherches 147, CNRS UMR 8576 (France)

    2013-04-15

    The Pin1 protein plays a critical role in the functional regulation of the hyperphosphorylated neuronal Tau protein in Alzheimer's disease and is by itself regulated by phosphorylation. We have used Nuclear Magnetic Resonance (NMR) spectroscopy to both identify the PKA phosphorylation site in the Pin1 WW domain and investigate the functional consequences of this phosphorylation. Detection and identification of phosphorylation on serine/threonine residues in a globular protein, while mostly occurring in solvent-exposed flexible loops, does not lead to chemical shift changes as obvious as in disordered proteins and hence does not necessarily shift the resonances outside the spectrum of the folded protein. Other complications were encountered to characterize the extent of the phosphorylation, as part of the {sup 1}H,{sup 15}N amide resonances around the phosphorylation site are specifically broadened in the unphosphorylated state. Despite these obstacles, NMR spectroscopy was an efficient tool to confirm phosphorylation on S16 of the WW domain and to quantify the level of phosphorylation. Based on this analytical characterization, we show that WW phosphorylation on S16 abolishes its binding capacity to a phosphorylated Tau peptide. A reduced conformational heterogeneity and flexibility of the phospho-binding loop upon S16 phosphorylation could account for part of the decreased affinity for its phosphorylated partner. Additionally, a structural model of the phospho-WW obtained by molecular dynamics simulation and energy minimization suggests that the phosphate moiety of phospho-S16 could compete with the phospho-substrate.

  8. Unraveling a phosphorylation event in a folded protein by NMR spectroscopy: phosphorylation of the Pin1 WW domain by PKA

    International Nuclear Information System (INIS)

    Smet-Nocca, Caroline; Launay, Hélène; Wieruszeski, Jean-Michel; Lippens, Guy; Landrieu, Isabelle

    2013-01-01

    The Pin1 protein plays a critical role in the functional regulation of the hyperphosphorylated neuronal Tau protein in Alzheimer’s disease and is by itself regulated by phosphorylation. We have used Nuclear Magnetic Resonance (NMR) spectroscopy to both identify the PKA phosphorylation site in the Pin1 WW domain and investigate the functional consequences of this phosphorylation. Detection and identification of phosphorylation on serine/threonine residues in a globular protein, while mostly occurring in solvent-exposed flexible loops, does not lead to chemical shift changes as obvious as in disordered proteins and hence does not necessarily shift the resonances outside the spectrum of the folded protein. Other complications were encountered to characterize the extent of the phosphorylation, as part of the 1 H, 15 N amide resonances around the phosphorylation site are specifically broadened in the unphosphorylated state. Despite these obstacles, NMR spectroscopy was an efficient tool to confirm phosphorylation on S16 of the WW domain and to quantify the level of phosphorylation. Based on this analytical characterization, we show that WW phosphorylation on S16 abolishes its binding capacity to a phosphorylated Tau peptide. A reduced conformational heterogeneity and flexibility of the phospho-binding loop upon S16 phosphorylation could account for part of the decreased affinity for its phosphorylated partner. Additionally, a structural model of the phospho-WW obtained by molecular dynamics simulation and energy minimization suggests that the phosphate moiety of phospho-S16 could compete with the phospho-substrate.

  9. Cascading effects of overfishing marine systems

    NARCIS (Netherlands)

    Scheffer, M.; Carpenter, S.; Young, de B.

    2005-01-01

    Profound indirect ecosystem effects of overfishing have been shown for coastal systems such as coral reefs and kelp forests. A new study from the ecosystem off the Canadian east coast now reveals that the elimination of large predatory fish can also cause marked cascading effects on the pelagic food

  10. Plant MAPK cascades: Just rapid signaling modules?

    KAUST Repository

    Boudsocq, Marie; Danquah, Agyemang; Zé licourt, Axel de; Hirt, Heribert; Colcombet, Jean

    2015-01-01

    rapid MAPK activation, we showed that the activation of the new MAPK module is delayed and relies on the MAP3K protein synthesis. In this addendum, we discuss the role of this original and unexpected activation mechanism of MAPK cascades which suggests

  11. Computer simulation of high energy displacement cascades

    International Nuclear Information System (INIS)

    Heinisch, H.L.

    1990-01-01

    A methodology developed for modeling many aspects of high energy displacement cascades with molecular level computer simulations is reviewed. The initial damage state is modeled in the binary collision approximation (using the MARLOWE computer code), and the subsequent disposition of the defects within a cascade is modeled with a Monte Carlo annealing simulation (the ALSOME code). There are few adjustable parameters, and none are set to physically unreasonable values. The basic configurations of the simulated high energy cascades in copper, i.e., the number, size and shape of damage regions, compare well with observations, as do the measured numbers of residual defects and the fractions of freely migrating defects. The success of these simulations is somewhat remarkable, given the relatively simple models of defects and their interactions that are employed. The reason for this success is that the behavior of the defects is very strongly influenced by their initial spatial distributions, which the binary collision approximation adequately models. The MARLOWE/ALSOME system, with input from molecular dynamics and experiments, provides a framework for investigating the influence of high energy cascades on microstructure evolution. (author)

  12. Energy Cascade in Fermi-Pasta Models

    Science.gov (United States)

    Ponno, A.; Bambusi, D.

    We show that, for long-wavelength initial conditions, the FPU dynamics is described, up to a certain time, by two KdV-like equations, which represent the resonant Hamiltonian normal form of the system. The energy cascade taking place in the system is then quantitatively characterized by arguments of dimensional analysis based on such equations.

  13. Molecular dynamics studies of displacement cascades

    International Nuclear Information System (INIS)

    Averback, R.S.; Hsieh, Horngming; Diaz de la Rubia, T.

    1990-02-01

    Molecular-dynamics simulations of cascades in Cu and Ni with primary-knock-on energies up to 5 keV and lattice temperatures in the range 0 K--700 K are described. Interatomic forces were represented by either the Gibson II (Cu) or Johnson-Erginsoy (Ni) potentials in most of this work, although some simulations using ''Embedded Atom Method'' potentials, e.g., for threshold events in Ni 3 Al, are also presented. The results indicate that the primary state of damage produced by displacement cascades is controlled by two phenomena, replacement collision sequences during the collisional phase of the cascade and local melting during the thermal spike. As expected, the collisional phase is rather similar in Cu and Ni, however, the thermal spike is of longer duration and has a more pronounced influence in Cu than Ni. When the ambient temperature of the lattice is increased, the melt zones are observed to both increase in size and cool more slowly. This has the effect of reducing defect production and enhancing atomic mixing and disordering. The implications of these results for defect production, cascade collapse, atomic disordering will be discussed. 34 refs., 7 figs., 2 tabs

  14. Impedance interactions in bidirectional cascaded converter

    DEFF Research Database (Denmark)

    Tian, Yanjun; Loh, Poh Chiang; Chen, Zhe

    2016-01-01

    A cascaded converter is built by connecting one elementary converter to another. Output impedance of one converter will therefore interact with input impedance of the other converter. This interaction will change when power flow reverses. To compare this difference, an investigation is performed...

  15. Forecasting Social Unrest Using Activity Cascades.

    Science.gov (United States)

    Cadena, Jose; Korkmaz, Gizem; Kuhlman, Chris J; Marathe, Achla; Ramakrishnan, Naren; Vullikanti, Anil

    2015-01-01

    Social unrest is endemic in many societies, and recent news has drawn attention to happenings in Latin America, the Middle East, and Eastern Europe. Civilian populations mobilize, sometimes spontaneously and sometimes in an organized manner, to raise awareness of key issues or to demand changes in governing or other organizational structures. It is of key interest to social scientists and policy makers to forecast civil unrest using indicators observed on media such as Twitter, news, and blogs. We present an event forecasting model using a notion of activity cascades in Twitter (proposed by Gonzalez-Bailon et al., 2011) to predict the occurrence of protests in three countries of Latin America: Brazil, Mexico, and Venezuela. The basic assumption is that the emergence of a suitably detected activity cascade is a precursor or a surrogate to a real protest event that will happen "on the ground." Our model supports the theoretical characterization of large cascades using spectral properties and uses properties of detected cascades to forecast events. Experimental results on many datasets, including the recent June 2013 protests in Brazil, demonstrate the effectiveness of our approach.

  16. Forecasting Social Unrest Using Activity Cascades.

    Directory of Open Access Journals (Sweden)

    Jose Cadena

    Full Text Available Social unrest is endemic in many societies, and recent news has drawn attention to happenings in Latin America, the Middle East, and Eastern Europe. Civilian populations mobilize, sometimes spontaneously and sometimes in an organized manner, to raise awareness of key issues or to demand changes in governing or other organizational structures. It is of key interest to social scientists and policy makers to forecast civil unrest using indicators observed on media such as Twitter, news, and blogs. We present an event forecasting model using a notion of activity cascades in Twitter (proposed by Gonzalez-Bailon et al., 2011 to predict the occurrence of protests in three countries of Latin America: Brazil, Mexico, and Venezuela. The basic assumption is that the emergence of a suitably detected activity cascade is a precursor or a surrogate to a real protest event that will happen "on the ground." Our model supports the theoretical characterization of large cascades using spectral properties and uses properties of detected cascades to forecast events. Experimental results on many datasets, including the recent June 2013 protests in Brazil, demonstrate the effectiveness of our approach.

  17. The Attention Cascade Model and Attentional Blink

    Science.gov (United States)

    Shih, Shui-I

    2008-01-01

    An attention cascade model is proposed to account for attentional blinks in rapid serial visual presentation (RSVP) of stimuli. Data were collected using single characters in a single RSVP stream at 10 Hz [Shih, S., & Reeves, A. (2007). "Attentional capture in rapid serial visual presentation." "Spatial Vision", 20(4), 301-315], and single words,…

  18. Cascaded FSO-VLC Communication System

    KAUST Repository

    Gupta, Akash; Sharma, Nikhil; Garg, Parul; Alouini, Mohamed-Slim

    2017-01-01

    The proposed cascaded free space optics (FSO)-visible light communication (VLC) system consists of multiple VLC access points which caters the end users connected via a decode and forward (DF) relay to the FSO backhaul link. The FSO link is assumed

  19. A simple method for potential flow simulation of cascades

    Indian Academy of Sciences (India)

    vortex panel method to simulate potential flow in cascades is presented. The cascade ... The fluid loading on the blades, such as the normal force and pitching moment, may ... of such discrete infinite array singularities along the blade surface.

  20. Cascade theory in isotopic separation processes; Theorie des cascades en separation isotopique

    Energy Technology Data Exchange (ETDEWEB)

    Agostini, J P

    1994-06-01

    Three main areas are developed within the scope of this work: - the first one is devoted to fundamentals: separative power, value function, ideal cascade and square cascade. Applications to two main cases are carried out, namely: Study of binary isotopic mix, Study of processes with a small enrichment coefficient. - The second one is devoted to cascade coupling -high-flux coupling (more widely used and better known) as well as low-flux coupling are presented and compared to one another. - The third one is an outlook on problems linked to cascade transients. Those problem are somewhat intricate and their interest lies mainly into two areas: economics where the start-up time may have a large influence on the interests paid during the construction and start-up period, military productions where the start-up time has a direct bearing on the production schedule. (author). 50 figs. 3 annexes. 12 refs. 6 tabs.

  1. Particle fluxes in atomic collision cascades

    International Nuclear Information System (INIS)

    Sckerl, B.W.; Sigmund, P.; Vicanek, M.

    1996-01-01

    The flux of recoil atoms in atomic collision cascades induced by an ion beam or another source of energetic particles in a material is known to approach isotropy at kinetic energies far below the beam energy. A variety of irradiation effects can be explained satisfactorily on the basis of an isotropic particle flux, but significant deviations from this simple behavior are known to exist. While numerous examples have been studied by numerical simulation of cascade processes, the systematics is, by and large, unknown. The present study aims at general scaling properties and estimates of the magnitude of moderate deviations from isotropy and their spatial dependence for a wide range of beam and material parameters. Anisotropies introduced by crystal structure are ignored. Although it is well established that cascade anisotropy is related to the momentum of beam particles, previous attempts to quantify this relation have failed. We have found that there are two leading correction terms to the isotropic particle flux, a well-known term centered around the beam direction as a symmetry axis and a new term proportional to the gradient of the deposited-energy density. As a general rule the two contributions are either both significant or both negligible. Specific situations in which the gradient term dominates are, however, of considerable interest in applications. The parameters which characterize the anisotropy of collision cascades also determine the deposition of momentum, but the connection is less straightforward than asserted hitherto. General principles are first illustrated on the specific case of elastic-collision cascades under self-bombardment which contains the essentials. Thereafter several generalizations are made, including atomic binding forces and inelasticity as well as allowance for multicomponent materials. Application areas in mixing and sputtering are outlined. (au) 58 refs

  2. Cascading Generative Adversarial Networks for Targeted

    KAUST Repository

    Hamdi, Abdullah

    2018-01-01

    Abundance of labelled data played a crucial role in the recent developments in computer vision, but that faces problems like scalability and transferability to the wild. One alternative approach is to utilize the data without labels, i.e. unsupervised learning, in learning valuable information and put it in use to tackle vision problems. Generative Adversarial Networks (GANs) have gained momentum for their ability to model image distributions in unsupervised manner. They learn to emulate the training set and that enables sampling from that domain and using the knowledge learned for useful applications. Several methods proposed enhancing GANs, including regularizing the loss with some feature matching. We seek to push GANs beyond the data in the training and try to explore unseen territory in the image manifold. We first propose a new regularizer for GAN based on K-Nearest Neighbor (K-NN) selective feature matching to a target set Y in high-level feature space, during the adversarial training of GAN on the base set X, and we call this novel model K-GAN. We show that minimizing the added term follows from cross-entropy minimization between the distributions of GAN and set Y. Then, we introduce a cascaded framework for GANs that try to address the task of imagining a new distribution that combines the base set X and target set Y by cascading sampling GANs with translation GANs, and we dub the cascade of such GANs as the Imaginative Adversarial Network (IAN). Several cascades are trained on a collected dataset Zoo-Faces and generated innovative samples are shown, including from K-GAN cascade. We conduct an objective and subjective evaluation for different IAN setups in the addressed task of generating innovative samples and we show the effect of regularizing GAN on different scores. We conclude with some useful applications for these IANs, like multi-domain manifold traversing.

  3. Cascading Generative Adversarial Networks for Targeted

    KAUST Repository

    Hamdi, Abdullah

    2018-04-09

    Abundance of labelled data played a crucial role in the recent developments in computer vision, but that faces problems like scalability and transferability to the wild. One alternative approach is to utilize the data without labels, i.e. unsupervised learning, in learning valuable information and put it in use to tackle vision problems. Generative Adversarial Networks (GANs) have gained momentum for their ability to model image distributions in unsupervised manner. They learn to emulate the training set and that enables sampling from that domain and using the knowledge learned for useful applications. Several methods proposed enhancing GANs, including regularizing the loss with some feature matching. We seek to push GANs beyond the data in the training and try to explore unseen territory in the image manifold. We first propose a new regularizer for GAN based on K-Nearest Neighbor (K-NN) selective feature matching to a target set Y in high-level feature space, during the adversarial training of GAN on the base set X, and we call this novel model K-GAN. We show that minimizing the added term follows from cross-entropy minimization between the distributions of GAN and set Y. Then, we introduce a cascaded framework for GANs that try to address the task of imagining a new distribution that combines the base set X and target set Y by cascading sampling GANs with translation GANs, and we dub the cascade of such GANs as the Imaginative Adversarial Network (IAN). Several cascades are trained on a collected dataset Zoo-Faces and generated innovative samples are shown, including from K-GAN cascade. We conduct an objective and subjective evaluation for different IAN setups in the addressed task of generating innovative samples and we show the effect of regularizing GAN on different scores. We conclude with some useful applications for these IANs, like multi-domain manifold traversing.

  4. Identification of the protein kinase C phosphorylation site in neuromodulin

    International Nuclear Information System (INIS)

    Apel, E.D.; Byford, M.F.; Au, D.; Walsh, K.A.; Storm, D.R.

    1990-01-01

    Neuromodulin (P-57, GAP-43, B-50, F-1) is a neurospecific calmodulin binding protein that is phosphorylated by protein kinase C. Phosphorylation by protein kinase C has been shown to abolish the affinity of neuromodulin for calmodulin and the authors have proposed that the concentration of free CaM in neurons may be regulated by phosphorylation and dephosphorylation of neuromodulin. The purpose of this study was to identify the protein kinase C phosphorylation site(s) in neuromodulin using recombinant neuromodulin as a substrate. Toward this end, it was demonstrated that recombinant neuromodulin purified from Escherichia coli and bovine neuromodulin were phosphorylated with similar K m values and stoichiometries and that protein kinase C mediated phosphorylation of both proteins abolished binding to calmodulin-Sepharose. Recombinant neuromodulin was phosphorylated by using protein kinase C and [γ- 32 P]ATP and digested with trypsin, and the resulting peptides were separated by HPLC. Only one 32 P-labeled tryptic peptide was generated from phosphorylated neuromodulin. They conclude that serine-41 is the protein kinase C phosphorylation site of neuromodulin and that phosphorylation of this amino acid residue blocks binding of calmoculin to neuromodulin. The proximity of serine-41 to the calmodulin binding domain in neuromodulin very likely explains the effect of phosphorylation on the affinity of neuromodulin for calmodulin

  5. Akt phosphorylates Prohibitin 1 to mediate its mitochondrial localization and promote proliferation of bladder cancer cells

    Science.gov (United States)

    Jiang, L; Dong, P; Zhang, Z; Li, C; Li, Y; Liao, Y; Li, X; Wu, Z; Guo, S; Mai, S; Xie, D; Liu, Z; Zhou, F

    2015-01-01

    Bladder cancer (BC) is very common and associated with significant morbidity and mortality, though the molecular underpinnings of its origination and progression remain poorly understood. In this study, we demonstrate that Prohibitin 1 (PHB) was overexpressed in human BC tissues and that PHB upregulation was associated with poor prognosis. We also found that PHB was necessary and sufficient for BC cell proliferation. Interestingly, the overexpressed PHB was primarily found within mitochondria, and we provide the first direct evidence that phosphorylation by Akt at Thr258 of PHB induces this mitochondrial localization. Inhibiton of Akt reverses these effects and inhibited the proliferation of BC cells. Finally, the phosphorylation of PHB was required for BC cell proliferation, further implicating the importance of the Akt in BC. Taken together, these findings identify the Akt/PHB signaling cascade as a novel mechanism of cancer cell proliferation and provide the scientific basis for the establishment of PHB as a new prognostic marker and treatment target for BC. PMID:25719244

  6. Phosphoryl functionalized mesoporous silica for uranium adsorption

    International Nuclear Information System (INIS)

    Xue, Guo; Yurun, Feng; Li, Ma; Dezhi, Gao; Jie, Jing; Jincheng, Yu; Haibin, Sun; Hongyu, Gong; Yujun, Zhang

    2017-01-01

    Highlights: • Phosphoryl functionalized mesoporous silica (TBP-SBA-15) is synthesized. • The amino and phosphoryl groups are successfully grafted on SBA-15. • TBP-SBA-15 has high and rapid uranium adsorption capacity in broad pH range. • The U(VI) adsorption of TBP-SBA-15 is spontaneous and belongs to chemical adsorption. - Abstract: Phosphoryl functionalized mesoporous silica (TBP-SBA-15) was synthesized by modified mesoporous silica with γ-amino propyl triethoxy silane and tributyl phosphate. The obtained samples were characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), small angle X-ray diffraction (SAXRD), thermo-gravimetric/differential thermalanalyzer (TG/DTA), N_2 adsorption–desorption (BET) and Fourier transform infrared spectroscopy (FT-IR) techniques. Results showed that TBP-SBA-15 had large surface areas with ordered channel structure. Moreover, the effects of adsorption time, sorbent dose, solution pH, initial uranium concentration and temperature on the uranium adsorption behaviors were investigated. TBP-SBA-15 showed a high uranium adsorption capacity in a broad range of pH values. The U(VI) adsorption rate of TBP-SBA-15 was fast and nearly achieved completion in 10 min with the sorbent dose of 1 g/L. The U(VI) adsorption of TBP-SBA-15 followed the pseudo-second-order kinetic model and Freundlich isotherm model, indicating that the process was belonged to chemical adsorption. Furthermore, the thermodynamic parameters (ΔG"0, ΔH"0 and ΔS"0) confirmed that the adsorption process was endothermic and spontaneous.

  7. Phosphoryl functionalized mesoporous silica for uranium adsorption

    Energy Technology Data Exchange (ETDEWEB)

    Xue, Guo; Yurun, Feng; Li, Ma; Dezhi, Gao; Jie, Jing; Jincheng, Yu; Haibin, Sun [Key Laboratory for Liquid-Solid Structural Evolution & Processing of Materials of Ministry of Education, Shandong University, Jinan 250061 (China); Key Laboratory of Special Functional Aggregated Materials, Ministry of Education, Shandong University, Jinan 250061 (China); Hongyu, Gong, E-mail: gong_hongyu@163.com [Key Laboratory for Liquid-Solid Structural Evolution & Processing of Materials of Ministry of Education, Shandong University, Jinan 250061 (China); Key Laboratory of Special Functional Aggregated Materials, Ministry of Education, Shandong University, Jinan 250061 (China); Yujun, Zhang, E-mail: yujunzhangcn@163.com [Key Laboratory for Liquid-Solid Structural Evolution & Processing of Materials of Ministry of Education, Shandong University, Jinan 250061 (China); Key Laboratory of Special Functional Aggregated Materials, Ministry of Education, Shandong University, Jinan 250061 (China)

    2017-04-30

    Highlights: • Phosphoryl functionalized mesoporous silica (TBP-SBA-15) is synthesized. • The amino and phosphoryl groups are successfully grafted on SBA-15. • TBP-SBA-15 has high and rapid uranium adsorption capacity in broad pH range. • The U(VI) adsorption of TBP-SBA-15 is spontaneous and belongs to chemical adsorption. - Abstract: Phosphoryl functionalized mesoporous silica (TBP-SBA-15) was synthesized by modified mesoporous silica with γ-amino propyl triethoxy silane and tributyl phosphate. The obtained samples were characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), small angle X-ray diffraction (SAXRD), thermo-gravimetric/differential thermalanalyzer (TG/DTA), N{sub 2} adsorption–desorption (BET) and Fourier transform infrared spectroscopy (FT-IR) techniques. Results showed that TBP-SBA-15 had large surface areas with ordered channel structure. Moreover, the effects of adsorption time, sorbent dose, solution pH, initial uranium concentration and temperature on the uranium adsorption behaviors were investigated. TBP-SBA-15 showed a high uranium adsorption capacity in a broad range of pH values. The U(VI) adsorption rate of TBP-SBA-15 was fast and nearly achieved completion in 10 min with the sorbent dose of 1 g/L. The U(VI) adsorption of TBP-SBA-15 followed the pseudo-second-order kinetic model and Freundlich isotherm model, indicating that the process was belonged to chemical adsorption. Furthermore, the thermodynamic parameters (ΔG{sup 0}, ΔH{sup 0} and ΔS{sup 0}) confirmed that the adsorption process was endothermic and spontaneous.

  8. Monitoring HPV-16 E7 phosphorylation events

    Energy Technology Data Exchange (ETDEWEB)

    Nogueira, Marcela O.; Hošek, Tomáš; Calçada, Eduardo O.; Castiglia, Francesca [Magnetic Resonance Center (CERM) and Department of Chemistry “Ugo Schiff”, University of Florence, via Luigi Sacconi 6, Sesto Fiorentino (Italy); Massimi, Paola; Banks, Lawrence [International Centre for Genetic Engineering and Biotechnology (ICGEB), Padriciano 99, Trieste (Italy); Felli, Isabella C., E-mail: felli@cerm.unifi.it [Magnetic Resonance Center (CERM) and Department of Chemistry “Ugo Schiff”, University of Florence, via Luigi Sacconi 6, Sesto Fiorentino (Italy); Pierattelli, Roberta, E-mail: pierattelli@cerm.unifi.it [Magnetic Resonance Center (CERM) and Department of Chemistry “Ugo Schiff”, University of Florence, via Luigi Sacconi 6, Sesto Fiorentino (Italy)

    2017-03-15

    HPV-16 E7 is one of the key proteins that, by interfering with the host metabolism through many protein-protein interactions, hijacks cell regulation and contributes to malignancy. Here we report the high resolution investigation of the CR3 region of HPV-16 E7, both as an isolated domain and in the full-length protein. This opens the way to the atomic level study of the many interactions in which HPV-16 E7 is involved. Along these lines we show here the effect of one of the key post-translational modifications of HPV-16 E7, the phosphorylation by casein kinase II.

  9. Quantum Cascade Lasers Modulation and Applications

    Science.gov (United States)

    Luzhansky, Edward

    The mid-wave IR (MWIR) spectral band, extending from 3 to 5 microns, is considered to be a low loss atmospheric window. There are several spectral sub-bands with relatively low atmospheric attenuation in this region making it popular for various commercial and military applications. Relatively low thermal and solar background emissions, effective penetration through the natural and anthropogenic obscurants and eye safety add to the long list of advantages of MWIR wavelengths. Quantum Cascade Lasers are compact semiconductor devices capable of operating in MWIR spectrum. They are based on inter-subband transitions in a multiple-quantum-well (QW) hetero-structure, designed by means of band-structure engineering. The inter-subband nature of the optical transition has several key advantages. First, the emission wavelength is primarily a function of the QW thickness. This characteristic allows choosing well-understood and reliable semiconductors for the generation of light in a wavelength range of interest. Second, a cascade process in which tens of photons are generated per injected electron. This cascading process is behind the intrinsic high-power capabilities of QCLs. This dissertation is focused on modulation properties of Quantum Cascade Lasers. Both amplitude and phase/frequency modulations were studied including modulation bandwidth, modulation efficiency and chirp linearity. Research was consisted of the two major parts. In the first part we describe the theory of frequency modulation (FM) response of Distributed Feedback Quantum Cascade Lasers (DFB QCL). It includes cascading effect on the QCL's maximum modulation frequency. The "gain levering" effect for the maximum FM response of the two section QCLs was studied as well. In the second part of research we concentrated on the Pulse Position Amplitude Modulation of a single section QCL. The low complexity, low size, weight and power Mid-Wavelength Infra-Red optical communications transceiver concept is

  10. Ghrelin upregulates the phosphorylation of the GluN2B subunit of the NMDA receptor by activating GHSR1a and Fyn in the rat hippocampus.

    Science.gov (United States)

    Berrout, Liza; Isokawa, Masako

    2018-01-01

    Ghrelin and its receptor GHSR1a have been shown to exert numerous physiological functions in the brain, in addition to the well-established orexigenic role in the hypothalamus. Earlier work indicated that ghrelin stimulated the phosphorylation of the GluN1 subunit of the NMDA receptor (NMDAR) and enhanced synaptic transmission in the hippocampus. In the present study, we report that the exogenous application of ghrelin increased GluN2B phosphorylation. This increase was independent of GluN2B subunit activity or NMDAR channel activity. However, it depended on the activation of GHSR1a and Fyn as it was blocked by D-Lys3-GHRP-6 and PP2, respectively. Inhibitors for G-protein-regulated second messengers, such as Rp-cAMP, H89, TBB, ryanodine, and thapsigargin, unexpectedly enhanced GluN2B phosphorylation, suggesting that cAMP, PKA, casein kinase II, and cytosolic calcium signaling may oppose to the effect of ghrelin on the phosphorylation of GluN2B. Our findings suggest that 1) GluN2B is likely a molecular target of ghrelin and GHSR1a-driven signaling cascades, and 2) the ghrelin-mediated phosphorylation of GluN2B depends on Fyn activation under complex negative regulation by other second messengers. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Suppression of adhesion-induced protein tyrosine phosphorylation decreases invasive and metastatic potentials of B16-BL6 melanoma cells by protein tyrosine kinase inhibitor genistein.

    Science.gov (United States)

    Yan, C; Han, R

    1997-01-01

    Protein tyrosine kinase (PTK) appears to be involved in the activation of signaling during cell attachment to and spreading on extracellular matrix (ECM) in the metastatic cascade. To verify the assumption that PTK inhibitors might impair ECM signaling and prevent cancer metastasis, the highly metastatic B16-BL6 mouse melanoma cells were exposed to the PTK inhibitor genistein for 3 days. The ability of the cells to invade through reconstituted basement membrane (Matrigel) and to establish experimental pulmonary metastatic foci in C57BL/6 mice decreased after genistein exposure. The genistein-treated cells were also prevented from attaching to Matrigel and spread extremely poorly on the ECM substratum. Immunoblot analysis showed that tyrosine phosphorylation of a 125-kD protein in response to cell spreading on Matrigel was suppressed in the genistein-treated cells. Adhesion-induced protein tyrosine phosphorylation represents the earlier and specific event in the activation of ECM signaling, so this result implied ECM signaling was impaired in the treated cells. With immunofluorescence microscopy, the adhesion-induced tyrosine phosphorylated proteins were located at the pericytoplasms of well-spread cells, but not at the periphery of poorly spread genistein-treated cells. Therefore, this paper suggests that genistein might impair ECM signaling and subsequently prevent cancer cells from spreading well and invading or establishing metastasis through the suppression of adhesion-induced protein tyrosine phosphorylation. PTKs and adhesion-induced protein tyrosine phosphorylation might play a role in the control of invasion and metastasis.

  12. SH3 domain tyrosine phosphorylation--sites, role and evolution.

    Directory of Open Access Journals (Sweden)

    Zuzana Tatárová

    Full Text Available BACKGROUND: SH3 domains are eukaryotic protein domains that participate in a plethora of cellular processes including signal transduction, proliferation, and cellular movement. Several studies indicate that tyrosine phosphorylation could play a significant role in the regulation of SH3 domains. RESULTS: To explore the incidence of the tyrosine phosphorylation within SH3 domains we queried the PhosphoSite Plus database of phosphorylation sites. Over 100 tyrosine phosphorylations occurring on 20 different SH3 domain positions were identified. The tyrosine corresponding to c-Src Tyr-90 was by far the most frequently identified SH3 domain phosphorylation site. A comparison of sequences around this tyrosine led to delineation of a preferred sequence motif ALYD(Y/F. This motif is present in about 15% of human SH3 domains and is structurally well conserved. We further observed that tyrosine phosphorylation is more abundant than serine or threonine phosphorylation within SH3 domains and other adaptor domains, such as SH2 or WW domains. Tyrosine phosphorylation could represent an important regulatory mechanism of adaptor domains. CONCLUSIONS: While tyrosine phosphorylation typically promotes signaling protein interactions via SH2 or PTB domains, its role in SH3 domains is the opposite - it blocks or prevents interactions. The regulatory function of tyrosine phosphorylation is most likely achieved by the phosphate moiety and its charge interfering with binding of polyproline helices of SH3 domain interacting partners.

  13. Systematic inference of functional phosphorylation events in yeast metabolism.

    Science.gov (United States)

    Chen, Yu; Wang, Yonghong; Nielsen, Jens

    2017-07-01

    Protein phosphorylation is a post-translational modification that affects proteins by changing their structure and conformation in a rapid and reversible way, and it is an important mechanism for metabolic regulation in cells. Phosphoproteomics enables high-throughput identification of phosphorylation events on metabolic enzymes, but identifying functional phosphorylation events still requires more detailed biochemical characterization. Therefore, development of computational methods for investigating unknown functions of a large number of phosphorylation events identified by phosphoproteomics has received increased attention. We developed a mathematical framework that describes the relationship between phosphorylation level of a metabolic enzyme and the corresponding flux through the enzyme. Using this framework, it is possible to quantitatively estimate contribution of phosphorylation events to flux changes. We showed that phosphorylation regulation analysis, combined with a systematic workflow and correlation analysis, can be used for inference of functional phosphorylation events in steady and dynamic conditions, respectively. Using this analysis, we assigned functionality to phosphorylation events of 17 metabolic enzymes in the yeast Saccharomyces cerevisiae , among which 10 are novel. Phosphorylation regulation analysis cannot only be extended for inference of other functional post-translational modifications but also be a promising scaffold for multi-omics data integration in systems biology. Matlab codes for flux balance analysis in this study are available in Supplementary material. yhwang@ecust.edu.cn or nielsenj@chalmers.se. Supplementary data are available at Bioinformatics online. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

  14. Cascading failure in the wireless sensor scale-free networks

    Science.gov (United States)

    Liu, Hao-Ran; Dong, Ming-Ru; Yin, Rong-Rong; Han, Li

    2015-05-01

    In the practical wireless sensor networks (WSNs), the cascading failure caused by a failure node has serious impact on the network performance. In this paper, we deeply research the cascading failure of scale-free topology in WSNs. Firstly, a cascading failure model for scale-free topology in WSNs is studied. Through analyzing the influence of the node load on cascading failure, the critical load triggering large-scale cascading failure is obtained. Then based on the critical load, a control method for cascading failure is presented. In addition, the simulation experiments are performed to validate the effectiveness of the control method. The results show that the control method can effectively prevent cascading failure. Project supported by the Natural Science Foundation of Hebei Province, China (Grant No. F2014203239), the Autonomous Research Fund of Young Teacher in Yanshan University (Grant No. 14LGB017) and Yanshan University Doctoral Foundation, China (Grant No. B867).

  15. Phenobarbital Meets Phosphorylation of Nuclear Receptors.

    Science.gov (United States)

    Negishi, Masahiko

    2017-05-01

    Phenobarbital was the first therapeutic drug to be characterized for its induction of hepatic drug metabolism. Essentially at the same time, cytochrome P450, an enzyme that metabolizes drugs, was discovered. After nearly 50 years of investigation, the molecular target of phenobarbital induction has now been delineated to phosphorylation at threonine 38 of the constitutive androstane receptor (NR1I3), a member of the nuclear receptor superfamily. Determining this mechanism has provided us with the molecular basis to understand drug induction of drug metabolism and disposition. Threonine 38 is conserved as a phosphorylation motif in the majority of both mouse and human nuclear receptors, providing us with an opportunity to integrate diverse functions of nuclear receptors. Here, I review the works and accomplishments of my laboratory at the National Institutes of Health National Institute of Environmental Health Sciences and the future research directions of where our study of the constitutive androstane receptor might take us. U.S. Government work not protected by U.S. copyright.

  16. Regulation of cardiac C-protein phosphorylation

    International Nuclear Information System (INIS)

    Titus, F.L.

    1985-01-01

    Molecular mechanisms of cardiac sympathetic and parasympathetic responses were addressed by studying subcellular changes in protein phosphorylation, cAMP-dependent protein kinase activity and protein phosphatase activity in frog hearts. B-adrenergic agonists increased and muscarinic cholinergic agonists decreased [ 32 P]phosphate incorporation into C-protein, a thick filament component. Regulation of protein phosphatase activity by Iso and methacholine (MCh) was assayed using extracts of drug treated frog hearts and [ 32 P]phospho-C-protein as substrate. Total phosphatase activity decreased 21% in extracts from hearts perfused with 0.1 μM Iso and 17% in hearts exposed to Iso plus 1 μM methacholine. This decrease reflected decreased phosphatase-2A activity. No changes in total phosphatase activity were measurable in broken cells treated with Iso or MCh. The results suggest adrenergic stimulation changes contractile activity in frog hearts by activating cAMP-dependent protein kinase associated with particulate cellular elements and inactivating soluble protein phosphatase-2A. This is the first demonstration of coordinated regulation of these enzymes by B-adrenergic agonists favoring phosphorylation of effector proteins. Coordinated regulation by methacholine in the presence of Iso was not observed

  17. Modelling the Krebs cycle and oxidative phosphorylation.

    Science.gov (United States)

    Korla, Kalyani; Mitra, Chanchal K

    2014-01-01

    The Krebs cycle and oxidative phosphorylation are the two most important sets of reactions in a eukaryotic cell that meet the major part of the total energy demands of a cell. In this paper, we present a computer simulation of the coupled reactions using open source tools for simulation. We also show that it is possible to model the Krebs cycle with a simple black box with a few inputs and outputs. However, the kinetics of the internal processes has been modelled using numerical tools. We also show that the Krebs cycle and oxidative phosphorylation together can be combined in a similar fashion - a black box with a few inputs and outputs. The Octave script is flexible and customisable for any chosen set-up for this model. In several cases, we had no explicit idea of the underlying reaction mechanism and the rate determining steps involved, and we have used the stoichiometric equations that can be easily changed as and when more detailed information is obtained. The script includes the feedback regulation of the various enzymes of the Krebs cycle. For the electron transport chain, the pH gradient across the membrane is an essential regulator of the kinetics and this has been modelled empirically but fully consistent with experimental results. The initial conditions can be very easily changed and the simulation is potentially very useful in a number of cases of clinical importance.

  18. Invariant mass distributions in cascade decays

    CERN Document Server

    Miller, D J; Raklev, A R

    2006-01-01

    We derive analytical expressions for the shape of the invariant mass distributions of massless Standard Model endproducts in cascade decays involving massive New Physics (NP) particles, D -> Cc -> Bbc -> Aabc, where the final NP particle A in the cascade is unobserved and where two of the particles a, b, c may be indistinguishable. Knowledge of these expressions can improve the determination of NP parameters at the LHC. The shape formulas are composite, but contain nothing more complicated than logarithms of simple expressions. We study the effects of cuts, final state radiation and detector effects on the distributions through Monte Carlo simulations, using a supersymmetric model as an example. We also consider how one can deal with the width of NP particles and with combinatorics from the misidentification of final state particles. The possible mismeasurements of NP masses through `feet' in the distributions are discussed. Finally, we demonstrate how the effects of different spin configurations can be inclu...

  19. Invariant mass distributions in cascade decays

    International Nuclear Information System (INIS)

    Miller, David J.; Osland, Per; Raklev, Are R.

    2006-01-01

    We derive analytical expressions for the shape of the invariant mass distributions of massless Standard Model endproducts in cascade decays involving massive New Physics (NP) particles, D→Cc→Bbc→Aabc, where the final NP particle A in the cascade is unobserved and where two of the particles a, b, c may be indistinguishable. Knowledge of these expressions can improve the determination of NP parameters at the LHC. The shape formulas are composite, but contain nothing more complicated than logarithms of simple expressions. We study the effects of cuts, final state radiation and detector effects on the distributions through Monte Carlo simulations, using a supersymmetric model as an example. We also consider how one can deal with the width of NP particles and with combinatorics from the misidentification of final state particles. The possible mismeasurements of NP masses through 'feet' in the distributions are discussed. Finally, we demonstrate how the effects of different spin configurations can be included in the distributions

  20. Cascade-based attacks on complex networks

    Science.gov (United States)

    Motter, Adilson E.; Lai, Ying-Cheng

    2002-12-01

    We live in a modern world supported by large, complex networks. Examples range from financial markets to communication and transportation systems. In many realistic situations the flow of physical quantities in the network, as characterized by the loads on nodes, is important. We show that for such networks where loads can redistribute among the nodes, intentional attacks can lead to a cascade of overload failures, which can in turn cause the entire or a substantial part of the network to collapse. This is relevant for real-world networks that possess a highly heterogeneous distribution of loads, such as the Internet and power grids. We demonstrate that the heterogeneity of these networks makes them particularly vulnerable to attacks in that a large-scale cascade may be triggered by disabling a single key node. This brings obvious concerns on the security of such systems.

  1. Cascade Apartments: Deep Energy Multifamily Retrofit

    Energy Technology Data Exchange (ETDEWEB)

    Gordon, A. [National Renewable Energy Lab. (NREL), Golden, CO (United States); Mattheis, L. [National Renewable Energy Lab. (NREL), Golden, CO (United States); Kunkle, R. [National Renewable Energy Lab. (NREL), Golden, CO (United States); Howard, L. [National Renewable Energy Lab. (NREL), Golden, CO (United States); Lubliner, M. [National Renewable Energy Lab. (NREL), Golden, CO (United States)

    2014-02-01

    In December of 2009-10, King County Housing Authority (KCHA) implemented energy retrofit improvements in the Cascade multifamily community, located in Kent, Washington (marine climate.)This research effort involved significant coordination from stakeholders KCHA, WA State Department of Commerce, utility Puget Sound Energy, and Cascade tenants. This report focuses on the following three primary BA research questions : 1. What are the modeled energy savings using DOE low income weatherization approved TREAT software? 2. How did the modeled energy savings compare with measured energy savings from aggregate utility billing analysis? 3. What is the Savings to Investment Ratio (SIR) of the retrofit package after considering utility window incentives and KCHA capitol improvement funding.

  2. Output Control Using Feedforward And Cascade Controllers

    Science.gov (United States)

    Seraji, Homayoun

    1990-01-01

    Report presents theoretical study of open-loop control elements in single-input, single-output linear system. Focus on output-control (servomechanism) problem, in which objective is to find control scheme that causes output to track certain command inputs and to reject certain disturbance inputs in steady state. Report closes with brief discussion of characteristics and relative merits of feedforward, cascade, and feedback controllers and combinations thereof.

  3. Modeling techniques for quantum cascade lasers

    Energy Technology Data Exchange (ETDEWEB)

    Jirauschek, Christian [Institute for Nanoelectronics, Technische Universität München, D-80333 Munich (Germany); Kubis, Tillmann [Network for Computational Nanotechnology, Purdue University, 207 S Martin Jischke Drive, West Lafayette, Indiana 47907 (United States)

    2014-03-15

    Quantum cascade lasers are unipolar semiconductor lasers covering a wide range of the infrared and terahertz spectrum. Lasing action is achieved by using optical intersubband transitions between quantized states in specifically designed multiple-quantum-well heterostructures. A systematic improvement of quantum cascade lasers with respect to operating temperature, efficiency, and spectral range requires detailed modeling of the underlying physical processes in these structures. Moreover, the quantum cascade laser constitutes a versatile model device for the development and improvement of simulation techniques in nano- and optoelectronics. This review provides a comprehensive survey and discussion of the modeling techniques used for the simulation of quantum cascade lasers. The main focus is on the modeling of carrier transport in the nanostructured gain medium, while the simulation of the optical cavity is covered at a more basic level. Specifically, the transfer matrix and finite difference methods for solving the one-dimensional Schrödinger equation and Schrödinger-Poisson system are discussed, providing the quantized states in the multiple-quantum-well active region. The modeling of the optical cavity is covered with a focus on basic waveguide resonator structures. Furthermore, various carrier transport simulation methods are discussed, ranging from basic empirical approaches to advanced self-consistent techniques. The methods include empirical rate equation and related Maxwell-Bloch equation approaches, self-consistent rate equation and ensemble Monte Carlo methods, as well as quantum transport approaches, in particular the density matrix and non-equilibrium Green's function formalism. The derived scattering rates and self-energies are generally valid for n-type devices based on one-dimensional quantum confinement, such as quantum well structures.

  4. Modeling techniques for quantum cascade lasers

    Science.gov (United States)

    Jirauschek, Christian; Kubis, Tillmann

    2014-03-01

    Quantum cascade lasers are unipolar semiconductor lasers covering a wide range of the infrared and terahertz spectrum. Lasing action is achieved by using optical intersubband transitions between quantized states in specifically designed multiple-quantum-well heterostructures. A systematic improvement of quantum cascade lasers with respect to operating temperature, efficiency, and spectral range requires detailed modeling of the underlying physical processes in these structures. Moreover, the quantum cascade laser constitutes a versatile model device for the development and improvement of simulation techniques in nano- and optoelectronics. This review provides a comprehensive survey and discussion of the modeling techniques used for the simulation of quantum cascade lasers. The main focus is on the modeling of carrier transport in the nanostructured gain medium, while the simulation of the optical cavity is covered at a more basic level. Specifically, the transfer matrix and finite difference methods for solving the one-dimensional Schrödinger equation and Schrödinger-Poisson system are discussed, providing the quantized states in the multiple-quantum-well active region. The modeling of the optical cavity is covered with a focus on basic waveguide resonator structures. Furthermore, various carrier transport simulation methods are discussed, ranging from basic empirical approaches to advanced self-consistent techniques. The methods include empirical rate equation and related Maxwell-Bloch equation approaches, self-consistent rate equation and ensemble Monte Carlo methods, as well as quantum transport approaches, in particular the density matrix and non-equilibrium Green's function formalism. The derived scattering rates and self-energies are generally valid for n-type devices based on one-dimensional quantum confinement, such as quantum well structures.

  5. How periodic are terahertz quantum cascade lasers?

    International Nuclear Information System (INIS)

    Kubis, T; Vogl, P

    2009-01-01

    We apply a novel non-equilibrium Green's function method for open quantum devices to analyze quantum cascade lasers. We find the carrier distribution in typical resonant phonon THz-QCLs to develop a periodicity that differs from the geometric periodicity of the QCL. We propose a design improvement that thermalizes electrons at threshold bias and thereby pins the electron density to the QCL periodicity.

  6. How periodic are terahertz quantum cascade lasers?

    Energy Technology Data Exchange (ETDEWEB)

    Kubis, T; Vogl, P, E-mail: tillmann.kubis@wsi.tum.d [Walter Schottky Institute, Technische Universitaet Muenchen, Am Coulombwall 3, 85748 Garching (Germany)

    2009-11-15

    We apply a novel non-equilibrium Green's function method for open quantum devices to analyze quantum cascade lasers. We find the carrier distribution in typical resonant phonon THz-QCLs to develop a periodicity that differs from the geometric periodicity of the QCL. We propose a design improvement that thermalizes electrons at threshold bias and thereby pins the electron density to the QCL periodicity.

  7. Cascade of circulations in fluid turbulence.

    Science.gov (United States)

    Eyink, Gregory L

    2006-12-01

    Kelvin's theorem on conservation of circulations is an essential ingredient of Taylor's theory of turbulent energy dissipation by the process of vortex-line stretching. In previous work, we have proposed a nonlinear mechanism for the breakdown of Kelvin's theorem in ideal turbulence at infinite Reynolds number. We develop here a detailed physical theory of this cascade of circulations. Our analysis is based upon an effective equation for large-scale coarse-grained velocity, which contains a turbulent-induced vortex force that can violate Kelvin's theorem. We show that singularities of sufficient strength, which are observed to exist in turbulent flow, can lead to nonvanishing dissipation of circulation for an arbitrarily small coarse-graining length in the effective equations. This result is an analog for circulation of Onsager's theorem on energy dissipation for singular Euler solutions. The physical mechanism of the breakdown of Kelvin's theorem is diffusion of lines of large-scale vorticity out of the advected loop. This phenomenon can be viewed as a classical analog of the Josephson-Anderson phase-slip phenomenon in superfluids due to quantized vortex lines. We show that the circulation cascade is local in scale and use this locality to develop concrete expressions for the turbulent vortex force by a multiscale gradient expansion. We discuss implications for Taylor's theory of turbulent dissipation and we point out some related cascade phenomena, in particular for magnetic flux in magnetohydrodynamic turbulence.

  8. Cascade laser applications: trends and challenges

    Science.gov (United States)

    d'Humières, B.; Margoto, Éric; Fazilleau, Yves

    2016-03-01

    When analyses need rapid measurements, cost effective monitoring and miniaturization, tunable semiconductor lasers can be very good sources. Indeed, applications like on-field environmental gas analysis or in-line industrial process control are becoming available thanks to the advantage of tunable semiconductor lasers. Advances in cascade lasers (CL) are revolutionizing Mid-IR spectroscopy with two alternatives: interband cascade lasers (ICL) in the 3-6μm spectrum and quantum cascade lasers (QCL), with more power from 3 to 300μm. The market is getting mature with strong players for driving applications like industry, environment, life science or transports. CL are not the only Mid-IR laser source. In fact, a strong competition is now taking place with other technologies like: OPO, VCSEL, Solid State lasers, Gas, SC Infrared or fiber lasers. In other words, CL have to conquer a share of the Mid-IR application market. Our study is a market analysis of CL technologies and their applications. It shows that improvements of components performance, along with the progress of infrared laser spectroscopy will drive the CL market growth. We compare CL technologies with other Mid-IR sources and estimate their share in each application market.

  9. CDK2 and PKA mediated-sequential phosphorylation is critical for p19INK4d function in the DNA damage response.

    Directory of Open Access Journals (Sweden)

    Mariela C Marazita

    Full Text Available DNA damage triggers a phosphorylation-based signaling cascade known as the DNA damage response. p19INK4d, a member of the INK4 family of CDK4/6 inhibitors, has been reported to participate in the DNA damage response promoting DNA repair and cell survival. Here, we provide mechanistic insight into the activation mechanism of p19INK4d linked to the response to DNA damage. Results showed that p19INK4d becomes phosphorylated following UV radiation, β-amyloid peptide and cisplatin treatments. ATM-Chk2/ATR-Chk1 signaling pathways were found to be differentially involved in p19INK4d phosphorylation depending on the type of DNA damage. Two sequential phosphorylation events at serine 76 and threonine 141 were identified using p19INK4d single-point mutants in metabolic labeling assays with (32P-orthophosphate. CDK2 and PKA were found to participate in p19INK4d phosphorylation process and that they would mediate serine 76 and threonine 141 modifications respectively. Nuclear translocation of p19INK4d induced by DNA damage was shown to be dependent on serine 76 phosphorylation. Most importantly, both phosphorylation sites were found to be crucial for p19INK4d function in DNA repair and cell survival. In contrast, serine 76 and threonine 141 were dispensable for CDK4/6 inhibition highlighting the independence of p19INK4d functions, in agreement with our previous findings. These results constitute the first description of the activation mechanism of p19INK4d in response to genotoxic stress and demonstrate the functional relevance of this activation following DNA damage.

  10. Phosphorylation of Histone H2A.X in Peripheral Blood Mononuclear Cells May Be a Useful Marker for Monitoring Cardiometabolic Risk in Nondiabetic Individuals

    Directory of Open Access Journals (Sweden)

    So Ra Yoon

    2017-01-01

    Full Text Available Phosphorylation of H2A.X (serine 139 in the histone H2A family located in the downstream of the DNA damage kinase signaling cascade is an important indicator of DNA damage. Recently, phosphorylation of H2A.X was proposed as a sensitive biomarker of aging. This study investigated if phosphorylation of H2A.X in peripheral blood mononuclear cells (PBMCs is associated with cardiometabolic risk in nondiabetic individuals. Basic parameters and oxidative stress/inflammatory markers were measured in nondiabetic healthy Koreans (n=119. Phosphorylation of H2A.X was measured randomly among the study subjects using a flow cytometer. According to the number of metabolic syndrome risk factor (MetS-RF, the study subjects were subdivided into “super healthy” (MetS−RF=0, n=71 and “MetS-risk” (MetS−RF≥1, n=48 groups. Phosphorylation of H2A.X in PBMCs (percentages and mean fluorescence intensity was significantly higher in the MetS-risk group than in the super healthy group after adjusting for age, sex, cigarette smoking, and alcohol consumption. Phosphorylated H2A.X was positively correlated with the number of MetS-RF as well as waist circumference, blood pressures, triglyceride, HbA1C, oxidized LDL, high sensitivity C-reactive protein, tumor necrosis factor-alpha, and alanine aminotransferase after the adjustment. The present study suggested that phosphorylated H2A.X in circulating PBMCs measured by flow cytometer may be a useful marker for monitoring cardiometabolic risk in nondiabetic individuals.

  11. Chemoselective synthesis and analysis of naturally occurring phosphorylated cysteine peptides

    Science.gov (United States)

    Bertran-Vicente, Jordi; Penkert, Martin; Nieto-Garcia, Olaia; Jeckelmann, Jean-Marc; Schmieder, Peter; Krause, Eberhard; Hackenberger, Christian P. R.

    2016-09-01

    In contrast to protein O-phosphorylation, studying the function of the less frequent N- and S-phosphorylation events have lagged behind because they have chemical features that prevent their manipulation through standard synthetic and analytical methods. Here we report on the development of a chemoselective synthetic method to phosphorylate Cys side-chains in unprotected peptides. This approach makes use of a reaction between nucleophilic phosphites and electrophilic disulfides accessible by standard methods. We achieve the stereochemically defined phosphorylation of a Cys residue and verify the modification using electron-transfer higher-energy dissociation (EThcD) mass spectrometry. To demonstrate the use of the approach in resolving biological questions, we identify an endogenous Cys phosphorylation site in IICBGlc, which is known to be involved in the carbohydrate uptake from the bacterial phosphotransferase system (PTS). This new chemical and analytical approach finally allows further investigating the functions and significance of Cys phosphorylation in a wide range of crucial cellular processes.

  12. Phosphorylation of mouse serine racemase regulates D-serine synthesis

    DEFF Research Database (Denmark)

    Foltyn, Veronika N; Zehl, Martin; Dikopoltsev, Elena

    2010-01-01

    Serine racemase (SR) catalyses the synthesis of the transmitter/neuromodulator D-serine, which plays a major role in synaptic plasticity and N-methyl D-aspartate receptor neurotoxicity. We now report that SR is phosphorylated at Thr71 and Thr227 as revealed by mass spectrometric analysis and in v...... with a phosphorylation-deficient SR mutant indicate that Thr71 phosphorylation increases SR activity, suggesting a novel mechanism for regulating D-serine production....

  13. Nitric oxide generated by ionizing radiation and EGF is implicated in EGF receptor phosphorylation in A549 lung carcinoma cells

    International Nuclear Information System (INIS)

    Park, In Chul; Lee, Hyung Chahn; Rhee, Chang Hun; Hong, Seok Il

    2004-01-01

    Although it has been demonstrated that ionizing radiation (IR) control various cell functions in a different cell types, the mechanisms of its action via NO are not well understood. NO may potentially affect every type of mammalian cells, owing to its ubiquitous production and participate in the control of cell proliferation in a great variety of cell types. The epidermal growth factor (EGF) receptor is a transmembrane glycoprotein of Mr 170,000. When EGF binds to its receptor, the receptor is dimerized and autophosphorylated at the carboxyl-terminal tyrosine 992, 1608, 1086, 1148 and 1173. This phosphorylated receptor initiates a series of signal tranduction events through interacting proteins of SH2 family including Shc, Grb2 and Sos, which in turn trigger ativation of MAPK cascades. Although the number of signaling events mediated by IR-induced NO is growing, it is still unclear how NO activate cellular signaling events. Thus, we examined the effect of NO on cellular phosphorylation and found that NO was produced by ionizing radiation in A549 lung adenocarcinoma cells and enhances the unique tyrosine phosphorylation on EGF receptor

  14. Modeling of cascade and sub-cascade formation at high pka energies in irradiated fusion structural materials

    International Nuclear Information System (INIS)

    Ryazanov, A.; Metelkin, E.V.; Semenov, E.A.

    2007-01-01

    Full text of publication follows: A new theoretical model is developed for the investigations of cascade and sub-cascade formation in fusion structural materials under fast neutron irradiation at high primary knock atom (PKA) energies. Under 14 MeV neutron irradiation especially of light fusion structural materials such as Be, C, SiC materials PKA will have the energies up to 1 MeV. At such high energies it is very difficult to use the Monte Carlo or molecular dynamic simulations. The developed model is based on the analytical consideration of elastic collisions between displaced moving atoms into atomic cascades produced by a PKAs with the some kinetic energy obtained from fast neutrons. The Tomas-Fermy interaction potential is used for the describing of elastic collisions between moving atoms. The suggested model takes into account also the electronic losses for moving atoms between elastic collisions. The self consistent criterion for sub-cascade formation is suggested here which is based on the comparison of mean distance between two consequent PKA collisions and size of sub-cascade produced by PKA. The analytical relations for the most important characteristics of cascades and sub-cascade are determined including the average number of sub-cascades per one PKA in the dependence on PKA energy, the distance between sub-cascades and the average cascade and sub-cascade sizes as a function of PKA energy. The developed model allows determining the total numbers, distribution functions of cascades and sub-cascades in dependence on their sizes and generation rate of cascades and sub-cascades for different fusion neutron energy spectra. Based on the developed model the numerical calculations for main characteristics of cascades and sub-cascades in different fusion structural materials are performed using the neutron flux and PKA energy spectra for fusion reactors: ITER and DEMO. The main characteristics for cascade and sub-cascade formation are calculated here for the

  15. The in vivo phosphorylation sites of rat brain dynamin I

    DEFF Research Database (Denmark)

    Graham, Mark E; Anggono, Victor; Bache, Nicolai

    2007-01-01

    -824). To resolve the discrepancy and to better understand the biological roles of dynI phosphorylation, we undertook a systematic identification of all phosphorylation sites in rat brain nerve terminal dynI. Using phosphoamino acid analysis, exclusively phospho-serine residues were found. Thr(780) phosphorylation...... of their relative abundance and relative responses to depolarization. The multiple phospho-sites suggest subtle regulation of synaptic vesicle endocytosis by new protein kinases and new protein-protein interactions. The homologous dynI and dynIII phosphorylation indicates a high mechanistic similarity. The results...

  16. Altered phosphorylation of rhodopsin in retinal dystrophic Irish Setters

    International Nuclear Information System (INIS)

    Cunnick, J.; Takemoto, D.J.; Takemoto, L.J.

    1986-01-01

    The carboxyl-terminus of rhodopsin in retinal dystrophic (rd) Irish Setters is altered near a possible phosphorylation site. To determine if this alteration affects ATP-mediated phosphorylation they compared the phosphorylation of rhodopsin from rd affected Irish Setters and normal unaffected dogs. Retinas from 8-week-old Irish Setters were phosphorylated with γ- 32 P-ATP and separated on SDS-PAGE. Compared to unaffected normal retinas, equalized for rhodopsin content, phosphorylation of rd rhodopsin was drastically reduced. When rd retinas were mixed with normal dog retinas, phosphorylation of the latter was inhibited. Inhibition also occurred when bovine retinas were mixed with rd retinas. The rd-mediated inhibition of phosphorylation was prevented by including 1mM NaF in the reaction mixture. Likewise, 1mM NaF restored phosphorylation of rd rhodopsin to normal levels. Phosphopeptide maps of rd and normal rhodopsin were identical and indicated 5 phosphopeptides present in each. Results suggest that one cause of the depressed rd rhodopsin phosphorylation is an increased phosphatase activity

  17. Cisplatinum and Taxol Induce Different Patterns of p53 Phosphorylation

    Directory of Open Access Journals (Sweden)

    Giovanna Damia

    2001-01-01

    Full Text Available Posttranslational modifications of p53 induced by two widely used anticancer agents, cisplatinum (DDP and taxol were investigated in two human cancer cell lines. Although both drugs were able to induce phosphorylation at serine 20 (Ser20, only DDP treatment induced p53 phosphorylation at serine 15 (Ser15. Moreover, both drug treatments were able to increase p53 levels and consequently the transcription of waf1 and mdm-2 genes, although DDP treatment resulted in a stronger inducer of both genes. Using two ataxia telangiectasia mutated (ATM cell lines, the role of ATM in druginduced p53 phosphorylations was investigated. No differences in drug-induced p53 phosphorylation could be observed, indicating that ATM is not the kinase involved in these phosphorylation events. In addition, inhibition of DNA-dependent protein kinase activity by wortmannin did not abolish p53 phosphorylation at Ser15 and Ser20, again indicating that DNA-PK is unlikely to be the kinase involved. After both taxol and DDP treatments, an activation of hCHK2 was found and this is likely to be responsible for phosphorylation at Ser20. In contrast, only DDP was able to activate ATR, which is the candidate kinase for phosphorylation of Ser15 by this drug. This data clearly suggests that differential mechanisms are involved in phosphorylation and activation of p53 depending on the drug type.

  18. Tyrosine phosphorylation of Grb14 by Tie2

    Directory of Open Access Journals (Sweden)

    Dumont Daniel J

    2010-10-01

    Full Text Available Abstract Background Growth factor receptor bound (Grb proteins 7, 10 and 14 are a family of structurally related multi-domain adaptor proteins involved in a variety of biological processes. Grb7, 10 and 14 are known to become serine and/or threonine phosphorylated in response to growth factor (GF stimulation. Grb7 and 10 have also been shown to become tyrosine phosphorylated under certain conditions. Under experimental conditions Grb7 is tyrosine phosphorylated by the Tie2/Tie-2/Tek angiogenic receptor tyrosine kinase (RTK. Furthermore, Grb14 has also been shown to interact with Tie2, however tyrosine phosphorylation of this Grb family member has yet to be reported. Results Here we report for the first time tyrosine phosphorylation of Grb14. This phosphorylation requires a kinase competent Tie2 as well as intact tyrosines 1100 and 1106 (Y1100 and Y1106 on the receptor. Furthermore, a complete SH2 domain on Grb14 is required for Grb14 tyrosine phosphorylation by Tie2. Grb14 was also able to become tyrosine phosphorylated in primary endothelial cells when treated with a soluble and potent variant of the Tie2 ligand, cartilage oligomeric matrix protein (COMP Ang1. Conclusion Our results show that Grb14, like its family members Grb7 and Grb10, is able to be tyrosine phosphorylated. Furthermore, our data indicate a role for Grb14 in endothelial signaling downstream of the Tie2 receptor.

  19. Dioscin inhibits osteoclast differentiation and bone resorption though down-regulating the Akt signaling cascades

    Energy Technology Data Exchange (ETDEWEB)

    Qu, Xinhua; Zhai, Zanjing; Liu, Xuqiang; Li, Haowei [Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedics, Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai (China); Ouyang, Zhengxiao [Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedics, Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai (China); Department of Orthopaedics, Hunan Provincial Tumor Hospital and Tumor Hospital of Xiangya School of Medicine, Central South University, Changsha (China); Wu, Chuanlong [Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedics, Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai (China); Liu, Guangwang [Department of Orthopaedic Surgery, The Central Hospital of Xuzhou, Affiliated Hospital of Medical Collage of Southeast University, Xuzhou (China); Fan, Qiming; Tang, Tingting [Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedics, Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai (China); Qin, An, E-mail: dr.qinan@gmail.com [Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedics, Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai (China); Dai, Kerong, E-mail: krdai@163.com [Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedics, Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai (China)

    2014-01-10

    Highlights: •A natural-derived compound, dioscin, suppresses osteoclast formation and bone resorption. •Dioscin inhibits osteolytic bone loss in vivo. •Dioscin impairs the Akt signaling cascades pathways during osteoclastogenesis. •Dioscin have therapeutic value in treating osteoclast-related diseases. -- Abstract: Bone resorption is the unique function of osteoclasts (OCs) and is critical for both bone homeostasis and pathologic bone diseases including osteoporosis, rheumatoid arthritis and tumor bone metastasis. Thus, searching for natural compounds that may suppress osteoclast formation and/or function is promising for the treatment of osteoclast-related diseases. In this study, we for the first time demonstrated that dioscin suppressed RANKL-mediated osteoclast differentiation and bone resorption in vitro in a dose-dependent manner. The suppressive effect of dioscin is supported by the reduced expression of osteoclast-specific markers. Further molecular analysis revealed that dioscin abrogated AKT phosphorylation, which subsequently impaired RANKL-induced nuclear factor-kappaB (NF-κB) signaling pathway and inhibited NFATc1 transcriptional activity. Moreover, in vivo studies further verified the bone protection activity of dioscin in osteolytic animal model. Together our data demonstrate that dioscin suppressed RANKL-induced osteoclast formation and function through Akt signaling cascades. Therefore, dioscin is a potential natural agent for the treatment of osteoclast-related diseases.

  20. Dioscin inhibits osteoclast differentiation and bone resorption though down-regulating the Akt signaling cascades

    International Nuclear Information System (INIS)

    Qu, Xinhua; Zhai, Zanjing; Liu, Xuqiang; Li, Haowei; Ouyang, Zhengxiao; Wu, Chuanlong; Liu, Guangwang; Fan, Qiming; Tang, Tingting; Qin, An; Dai, Kerong

    2014-01-01

    Highlights: •A natural-derived compound, dioscin, suppresses osteoclast formation and bone resorption. •Dioscin inhibits osteolytic bone loss in vivo. •Dioscin impairs the Akt signaling cascades pathways during osteoclastogenesis. •Dioscin have therapeutic value in treating osteoclast-related diseases. -- Abstract: Bone resorption is the unique function of osteoclasts (OCs) and is critical for both bone homeostasis and pathologic bone diseases including osteoporosis, rheumatoid arthritis and tumor bone metastasis. Thus, searching for natural compounds that may suppress osteoclast formation and/or function is promising for the treatment of osteoclast-related diseases. In this study, we for the first time demonstrated that dioscin suppressed RANKL-mediated osteoclast differentiation and bone resorption in vitro in a dose-dependent manner. The suppressive effect of dioscin is supported by the reduced expression of osteoclast-specific markers. Further molecular analysis revealed that dioscin abrogated AKT phosphorylation, which subsequently impaired RANKL-induced nuclear factor-kappaB (NF-κB) signaling pathway and inhibited NFATc1 transcriptional activity. Moreover, in vivo studies further verified the bone protection activity of dioscin in osteolytic animal model. Together our data demonstrate that dioscin suppressed RANKL-induced osteoclast formation and function through Akt signaling cascades. Therefore, dioscin is a potential natural agent for the treatment of osteoclast-related diseases

  1. Parkinson's disease associated with impaired oxidative phosphorylation

    International Nuclear Information System (INIS)

    Finsterer, J.; Jarius, C.; Baumgartner, M.

    2001-01-01

    Parkinson's disease may be due to primary or secondary oxidative phosphorylation (OXPHOS) defects. In a 76-year-old man with Parkinson's disease since 1992, slightly but recurrently elevated creatine phosphokinase, recurrently elevated blood glucose, thickening of the left ventricular myocardium, bifascicular block and hypacusis were found. Cerebral MRI showed atrophy, periventricular demyelination, multiple, disseminated, supra- and infratentorial lacunas, and haemosiderin deposits in both posterior horns. Muscle biopsy showed typical features of an OXPHOS defect. Whether the association of Parkinson's disease and impaired OXPHOS was causative or coincidental remains unknown. Possibly, the mitochondrial defect acted as an additional risk factor for Parkinson's disease or the OXPHOS defect worsened the preexisting neurological impairments by a cumulative or synergistic mechanism. In conclusion, this case shows that Parkinson's disease may be associated with a mitochondrially or nuclearly encoded OXPHOS defect, manifesting as hypacusis, myopathy, axonal polyneuropathy, cardiomyopathy and recurrent subclinical ischaemic strokes and haemorrhages. (orig.)

  2. Andrographolide inhibits nuclear factor-κB activation through JNK-Akt-p65 signaling cascade in tumor necrosis factor-α-stimulated vascular smooth muscle cells.

    Science.gov (United States)

    Chen, Yu-Ying; Hsu, Ming-Jen; Hsieh, Cheng-Ying; Lee, Lin-Wen; Chen, Zhih-Cherng; Sheu, Joen-Rong

    2014-01-01

    Critical vascular inflammation leads to vascular dysfunction and cardiovascular diseases, including abdominal aortic aneurysms, hypertension, and atherosclerosis. Andrographolide is the most active and critical constituent isolated from the leaves of Andrographis paniculata, a herbal medicine widely used for treating anti-inflammation in Asia. In this study, we investigated the mechanisms of the inhibitory effects of andrographolide in vascular smooth muscle cells (VSMCs) exposed to a proinflammatory stimulus, tumor necrosis factor-α (TNF-α). Treating TNF-α-stimulated VSMCs with andrographolide suppressed the expression of inducible nitric oxide synthase in a concentration-dependent manner. A reduction in TNF-α-induced c-Jun N-terminal kinase (JNK), Akt, and p65 phosphorylation was observed in andrographolide-treated VSMCs. However, andrographolide affected neither IκBα degradation nor p38 mitogen-activated protein kinase or extracellular signal-regulated kinase 1/2 phosphorylation under these conditions. Both treatment with LY294002, a phosphatidylinositol 3-kinase/Akt inhibitor, and treatment with SP600125, a JNK inhibitor, markedly reversed the andrographolide-mediated inhibition of p65 phosphorylation. In addition, LY294002 and SP600125 both diminished Akt phosphorylation, whereas LY294002 had no effects on JNK phosphorylation. These results collectively suggest that therapeutic interventions using andrographolide can benefit the treatment of vascular inflammatory diseases, and andrographolide-mediated inhibition of NF-κB activity in TNF-α-stimulated VSMCs occurs through the JNK-Akt-p65 signaling cascade, an IκBα-independent mechanism.

  3. A grammar inference approach for predicting kinase specific phosphorylation sites.

    Science.gov (United States)

    Datta, Sutapa; Mukhopadhyay, Subhasis

    2015-01-01

    Kinase mediated phosphorylation site detection is the key mechanism of post translational mechanism that plays an important role in regulating various cellular processes and phenotypes. Many diseases, like cancer are related with the signaling defects which are associated with protein phosphorylation. Characterizing the protein kinases and their substrates enhances our ability to understand the mechanism of protein phosphorylation and extends our knowledge of signaling network; thereby helping us to treat such diseases. Experimental methods for predicting phosphorylation sites are labour intensive and expensive. Also, manifold increase of protein sequences in the databanks over the years necessitates the improvement of high speed and accurate computational methods for predicting phosphorylation sites in protein sequences. Till date, a number of computational methods have been proposed by various researchers in predicting phosphorylation sites, but there remains much scope of improvement. In this communication, we present a simple and novel method based on Grammatical Inference (GI) approach to automate the prediction of kinase specific phosphorylation sites. In this regard, we have used a popular GI algorithm Alergia to infer Deterministic Stochastic Finite State Automata (DSFA) which equally represents the regular grammar corresponding to the phosphorylation sites. Extensive experiments on several datasets generated by us reveal that, our inferred grammar successfully predicts phosphorylation sites in a kinase specific manner. It performs significantly better when compared with the other existing phosphorylation site prediction methods. We have also compared our inferred DSFA with two other GI inference algorithms. The DSFA generated by our method performs superior which indicates that our method is robust and has a potential for predicting the phosphorylation sites in a kinase specific manner.

  4. A Grammar Inference Approach for Predicting Kinase Specific Phosphorylation Sites

    Science.gov (United States)

    Datta, Sutapa; Mukhopadhyay, Subhasis

    2015-01-01

    Kinase mediated phosphorylation site detection is the key mechanism of post translational mechanism that plays an important role in regulating various cellular processes and phenotypes. Many diseases, like cancer are related with the signaling defects which are associated with protein phosphorylation. Characterizing the protein kinases and their substrates enhances our ability to understand the mechanism of protein phosphorylation and extends our knowledge of signaling network; thereby helping us to treat such diseases. Experimental methods for predicting phosphorylation sites are labour intensive and expensive. Also, manifold increase of protein sequences in the databanks over the years necessitates the improvement of high speed and accurate computational methods for predicting phosphorylation sites in protein sequences. Till date, a number of computational methods have been proposed by various researchers in predicting phosphorylation sites, but there remains much scope of improvement. In this communication, we present a simple and novel method based on Grammatical Inference (GI) approach to automate the prediction of kinase specific phosphorylation sites. In this regard, we have used a popular GI algorithm Alergia to infer Deterministic Stochastic Finite State Automata (DSFA) which equally represents the regular grammar corresponding to the phosphorylation sites. Extensive experiments on several datasets generated by us reveal that, our inferred grammar successfully predicts phosphorylation sites in a kinase specific manner. It performs significantly better when compared with the other existing phosphorylation site prediction methods. We have also compared our inferred DSFA with two other GI inference algorithms. The DSFA generated by our method performs superior which indicates that our method is robust and has a potential for predicting the phosphorylation sites in a kinase specific manner. PMID:25886273

  5. PAK6 Phosphorylates 14-3-3γ to Regulate Steady State Phosphorylation of LRRK2

    Directory of Open Access Journals (Sweden)

    Laura Civiero

    2017-12-01

    Full Text Available Mutations in Leucine-rich repeat kinase 2 (LRRK2 are associated with Parkinson's disease (PD and, as such, LRRK2 is considered a promising therapeutic target for age-related neurodegeneration. Although the cellular functions of LRRK2 in health and disease are incompletely understood, robust evidence indicates that PD-associated mutations alter LRRK2 kinase and GTPase activities with consequent deregulation of the downstream signaling pathways. We have previously demonstrated that one LRRK2 binding partner is P21 (RAC1 Activated Kinase 6 (PAK6. Here, we interrogate the PAK6 interactome and find that PAK6 binds a subset of 14-3-3 proteins in a kinase dependent manner. Furthermore, PAK6 efficiently phosphorylates 14-3-3γ at Ser59 and this phosphorylation serves as a switch to dissociate the chaperone from client proteins including LRRK2, a well-established 14-3-3 binding partner. We found that 14-3-3γ phosphorylated by PAK6 is no longer competent to bind LRRK2 at phospho-Ser935, causing LRRK2 dephosphorylation. To address whether these interactions are relevant in a neuronal context, we demonstrate that a constitutively active form of PAK6 rescues the G2019S LRRK2-associated neurite shortening through phosphorylation of 14-3-3γ. Our results identify PAK6 as the kinase for 14-3-3γ and reveal a novel regulatory mechanism of 14-3-3/LRRK2 complex in the brain.

  6. Phosphorylated benzimedazoles. 8. Synthesis of phosphorylated with /sup 32/P benzimidazoles

    Energy Technology Data Exchange (ETDEWEB)

    Makarov, A M; Matevosyan, G L; Zavlin, P M [Leningradskij Sel' skokhozyajstvennyj Inst. (USSR)

    1983-03-01

    Accessible methods of synthesis and identification of phosphorylated benzimidazoles with specific activity close to the maximum permissible with labelled /sup 32/P are developed. These methods permit to determine the permissible residual amounts of the above preparations in nutrition products and the maximum permissible amounts of growth regulators in different objects of the environment, because it is impossible to detect, for example, tri(1-benzimidazolido)phosphate with other physico-chemical methods with the existing concentration of 10/sup -9/%.

  7. Zinc promotes proliferation and activation of myogenic cells via the PI3K/Akt and ERK signaling cascade

    Energy Technology Data Exchange (ETDEWEB)

    Ohashi, Kazuya, E-mail: asuno10k@yahoo.co.jp [Department of Life Sciences, Graduate School of Arts and Sciences, The University of Tokyo (Japan); Nagata, Yosuke, E-mail: cynagata@mail.ecc.u-tokyo.ac.jp [Department of Life Sciences, Graduate School of Arts and Sciences, The University of Tokyo (Japan); Wada, Eiji, E-mail: gacchu1@yahoo.co.jp [Department of Life Sciences, Graduate School of Arts and Sciences, The University of Tokyo (Japan); Zammit, Peter S., E-mail: peter.zammit@kcl.ac.uk [Randall Division of Cell and Molecular Biophysics, King' s College London, London SE1 1UL (United Kingdom); Shiozuka, Masataka, E-mail: cmuscle@mail.ecc.u-tokyo.ac.jp [Department of Life Sciences, Graduate School of Arts and Sciences, The University of Tokyo (Japan); Matsuda, Ryoichi, E-mail: cmatsuda@mail.ecc.u-tokyo.ac.jp [Department of Life Sciences, Graduate School of Arts and Sciences, The University of Tokyo (Japan)

    2015-05-01

    Skeletal muscle stem cells named muscle satellite cells are normally quiescent but are activated in response to various stimuli, such as injury and overload. Activated satellite cells enter the cell cycle and proliferate to produce a large number of myogenic progenitor cells, and these cells then differentiate and fuse to form myofibers. Zinc is one of the essential elements in the human body, and has multiple roles, including cell growth and DNA synthesis. However, the role of zinc in myogenic cells is not well understood, and is the focus of this study. We first examined the effects of zinc on differentiation of murine C2C12 myoblasts and found that zinc promoted proliferation, with an increased number of cells incorporating EdU, but inhibited differentiation with reduced myogenin expression and myotube formation. Furthermore, we used the C2C12 reserve cell model of myogenic quiescence to investigate the role of zinc on activation of myogenic cells. The number of reserve cells incorporating BrdU was increased by zinc in a dose dependent manner, with the number dramatically further increased using a combination of zinc and insulin. Akt and extracellular signal-regulated kinase (ERK) are downstream of insulin signaling, and both were phosphorylated after zinc treatment. The zinc/insulin combination-induced activation involved the phosphoinositide 3-kinase (PI3K)/Akt and ERK cascade. We conclude that zinc promotes activation and proliferation of myogenic cells, and this activation requires phosphorylation of PI3K/Akt and ERK as part of the signaling cascade. - Highlights: • Zinc has roles for promoting proliferation and inhibition differentiation of C2C12. • Zinc promotes activation of reserve cells. • Insulin and zinc synergize activation of reserve cells. • PI3K/Akt and ERK cascade affect zinc/insulin-mediated activation of reserve cells.

  8. Heat cascading regenerative sorption heat pump

    Science.gov (United States)

    Jones, Jack A. (Inventor)

    1995-01-01

    A simple heat cascading regenerative sorption heat pump process with rejected or waste heat from a higher temperature chemisorption circuit (HTCC) powering a lower temperature physisorption circuit (LTPC) which provides a 30% total improvement over simple regenerative physisorption compression heat pumps when ammonia is both the chemisorbate and physisorbate, and a total improvement of 50% or more for LTPC having two pressure stages. The HTCC contains ammonia and a chemisorbent therefor contained in a plurality of canisters, a condenser-evaporator-radiator system, and a heater, operatively connected together. The LTPC contains ammonia and a physisorbent therefor contained in a plurality of compressors, a condenser-evaporator-radiator system, operatively connected together. A closed heat transfer circuit (CHTC) is provided which contains a flowing heat transfer liquid (FHTL) in thermal communication with each canister and each compressor for cascading heat from the HTCC to the LTPC. Heat is regenerated within the LTPC by transferring heat from one compressor to another. In one embodiment the regeneration is performed by another CHTC containing another FHTL in thermal communication with each compressor. In another embodiment the HTCC powers a lower temperature ammonia water absorption circuit (LTAWAC) which contains a generator-absorber system containing the absorbent, and a condenser-evaporator-radiator system, operatively connected together. The absorbent is water or an absorbent aqueous solution. A CHTC is provided which contains a FHTL in thermal communication with the generator for cascading heat from the HTCC to the LTAWAC. Heat is regenerated within the LTAWAC by transferring heat from the generator to the absorber. The chemical composition of the chemisorbent is different than the chemical composition of the physisorbent, and the absorbent. The chemical composition of the FHTL is different than the chemisorbent, the physisorbent, the absorbent, and ammonia.

  9. Cascade plant control by timer method

    International Nuclear Information System (INIS)

    Kiguchi, Takashi; Inoue, Kotaro; Kawai, Toshio; Senoo, Makoto.

    1970-01-01

    The present invention relates to a method of controlling uranium flow rate through a cascaded centrifuge plant for the purpose of enriching uranium 235. Such a cascade includes multiple gas separation stage each of which consists of a plurality of centrifuges. The product gas usually includes a large amount of He gas, and a cold trap is used to eliminate the He from UF 6 . The cold trap is operated periodically in such a way that the mixed gas of He and UF 6 is cooled to solidify only UF 6 and then warmed to obtain UF 6 by gasification. In order to operate the plant continuously, parallel multiple cold traps are operated alternatively. The operating conditions in such a complex cascade system are difficult to alter by conventional control methods. The present invention provides a rapid method of controlling the system when a certain percentage of the centrifuges in one stage malfunction. The control system consists of timers which are provided one for each cold trap to control the operational period of the trap. For example, if 20% of the centrifuges in a particular stage malfunction, the timer period of the cold traps attached to the normally operating centrifuge within the stage is maintained, and the period of all the other centrifuges are changed to 10/8 times that of the initial value. In this way the flow volume through all centrifuges except that in the particular stage is reduced to 80% of the initial value and the operation of the system can be continued with reduced efficiency. (Masui, R.)

  10. Energy cascading in large district heating systems

    International Nuclear Information System (INIS)

    Mayer, F.W.

    1978-01-01

    District heat transfer is the most economical utilization of the waste heat of power plants. Optimum utilization and heat transfer over large distances are possible because of a new energy distribution system, the ''energy cascading system,'' in which heat is transferred to several consumer regions at different temperature ranges. It is made more profitable by the use of heat pumps. The optimum flow-line temperature is 368 0 K, and the optimum return-line temperature is 288 0 K, resulting in an approximately 50% reduction of electric power loss at the power plant

  11. The identification of a cascade hypernucleus

    CERN Document Server

    Mondal, A S; Husain, A; Kasim, M M

    1979-01-01

    In a systematic search for rare hypernuclear species in nuclear emulsion exposed to 3.0 GeV/c K/sup -/-mesons at the CERN PS, an event with three connecting stars has been observed. The two secondary stars are most probably due to the decay of a cascade hypernucleus according to the following channel: /sub Xi //sup -13/-C to /sub Lambda //sup 8 /Be+/sub Lambda //sup 5/He+Q. The binding energy of the Xi - hypernucleus is B/sub Xi /-(/sub Xi //sup 13/-C)=(18.1+or-3.2) MeV. (11 refs).

  12. Cascaded recompression closed brayton cycle system

    Energy Technology Data Exchange (ETDEWEB)

    Pasch, James J.

    2018-01-02

    The present disclosure is directed to a cascaded recompression closed Brayton cycle (CRCBC) system and method of operation thereof, where the CRCBC system includes a compressor for compressing the system fluid, a separator for generating fluid feed streams for each of the system's turbines, and separate segments of a heater that heat the fluid feed streams to different feed temperatures for the system's turbines. Fluid exiting each turbine is used to preheat the fluid to the turbine. In an embodiment, the amount of heat extracted is determined by operational costs.

  13. Tracking Control for Switched Cascade Nonlinear Systems

    Directory of Open Access Journals (Sweden)

    Xiaoxiao Dong

    2015-01-01

    Full Text Available The issue of H∞ output tracking for switched cascade nonlinear systems is discussed in this paper, where not all the linear parts of subsystems are stabilizable. The conditions of the solvability for the issue are given by virtue of the structural characteristics of the systems and the average dwell time method, in which the total activation time for stabilizable subsystems is longer than that for the unstabilizable subsystems. At last, a simulation example is used to demonstrate the validity and advantages of the proposed approach.

  14. Cascaded Quadratic Soliton Compression in Waveguide Structures

    DEFF Research Database (Denmark)

    Guo, Hairun

    between the Kerr nonlinear effects and the dispersive effects in the medium. A Kerr-like nonlinearity is produced through the cascaded phase mismatched quadratic process, e.g. the second harmonic generation process, which can be flexibly tuned in both the sign and the amplitude, making possible a strong......-phase-matching technology is not necessarily needed. In large-RI-changed waveguides, CQSC is extended to the mid-infrared range to generate single-cycle pulses with purely nonlinear interactions, since an all-normal dispersion profile could be achieved within the guidance band. We believe that CQSC in quadratic waveguides...

  15. Quadrotor trajectory tracking using PID cascade control

    Science.gov (United States)

    Idres, M.; Mustapha, O.; Okasha, M.

    2017-12-01

    Quadrotors have been applied to collect information for traffic, weather monitoring, surveillance and aerial photography. In order to accomplish their mission, quadrotors have to follow specific trajectories. This paper presents proportional-integral-derivative (PID) cascade control of a quadrotor for path tracking problem when velocity and acceleration are small. It is based on near hover controller for small attitude angles. The integral of time-weighted absolute error (ITAE) criterion is used to determine the PID gains as a function of quadrotor modeling parameters. The controller is evaluated in three-dimensional environment in Simulink. Overall, the tracking performance is found to be excellent for small velocity condition.

  16. Plant MAPK cascades: Just rapid signaling modules?

    KAUST Repository

    Boudsocq, Marie

    2015-08-27

    © 2015 Taylor & Francis Group, LLC. Abscisic acid (ABA) is a major phytohormone mediating important stress-related processes. We recently unveiled an ABA-activated MAPK signaling module constituted of MAP3K17/18-MKK3-MPK1/2/7/14. Unlike classical rapid MAPK activation, we showed that the activation of the new MAPK module is delayed and relies on the MAP3K protein synthesis. In this addendum, we discuss the role of this original and unexpected activation mechanism of MAPK cascades which suggests that MAPKs can regulate both early and longterm plant stress responses.

  17. Atom localization with double-cascade configuration

    International Nuclear Information System (INIS)

    Gordeev, Maksim Yu; Rozhdestvensky, Yuri V; Efremova, Ekaterina A

    2016-01-01

    We investigate the one-dimensional (1D) and two-dimensional (2D) atom localization of a four-level system in a double-cascade configuration. We demonstrate the possibility of 1D localization in the field of a standing wave, 2D localization in the field of two standing waves and 2D localization only in the field of running waves by using different configurations of driven waves on transitions. In addition, for each configuration we reached a high-precision atom localization in one of the states at scales much smaller than the wavelength of the incident optical radiation. (paper)

  18. Cascaded recompression closed brayton cycle system

    Science.gov (United States)

    Pasch, James J.

    2018-01-02

    The present disclosure is directed to a cascaded recompression closed Brayton cycle (CRCBC) system and method of operation thereof, where the CRCBC system includes a compressor for compressing the system fluid, a separator for generating fluid feed streams for each of the system's turbines, and separate segments of a heater that heat the fluid feed streams to different feed temperatures for the system's turbines. Fluid exiting each turbine is used to preheat the fluid to the turbine. In an embodiment, the amount of heat extracted is determined by operational costs.

  19. Influence of non-binary effects on intranuclear cascade method

    International Nuclear Information System (INIS)

    Gomes, E.H.C.

    1985-01-01

    The importance of non binary process effects in the intranuclear cascade method is analysed. It is shown that, in the higher density steps, the non binary collisions lead to baryon density distribution and rapidity differents from the one obtained using the usual intranuclear cascade method (limited to purely binary collisions). The validity of the applications of binary intranuclear cascade method to the simulation of the thermal equilibrium, nuclear transparency and particle production, is discussed. (M.C.K.) [pt

  20. Separation Options for Phosphorylated Osteopontin from Transgenic Microalgae Chlamydomonas reinhardtii

    Directory of Open Access Journals (Sweden)

    Ayswarya Ravi

    2018-02-01

    Full Text Available Correct folding and post-translational modifications are vital for therapeutic proteins to elicit their biological functions. Osteopontin (OPN, a bone regenerative protein present in a range of mammalian cells, is an acidic phosphoprotein with multiple potential phosphorylation sites. In this study, the ability of unicellular microalgae, Chlamydomonas reinhardtii, to produce phosphorylated recombinant OPN in its chloroplast is investigated. This study further explores the impact of phosphorylation and expression from a “plant-like” algae on separation of OPN. Chromatography resins ceramic hydroxyapatite (CHT and Gallium-immobilized metal affinity chromatography (Ga-IMAC were assessed for their binding specificity to phosphoproteins. Non-phosphorylated recombinant OPN expressed in E. coli was used to compare the specificity of interaction of the resins to phosphorylated OPN. We observed that CHT binds OPN by multimodal interactions and was better able to distinguish phosphorylated proteins in the presence of 250 mM NaCl. Ga-IMAC interaction with OPN was not selective to phosphorylation, irrespective of salt, as the resin bound OPN from both algal and bacterial sources. Anion exchange chromatography proved an efficient capture method to partially separate major phosphorylated host cell protein impurities such as Rubisco from OPN.

  1. Distribution pattern of histone H3 phosphorylation at serine 10

    Indian Academy of Sciences (India)

    We evaluated the pattern of H3 phosphorylation using immunodetection during mitosis and meiosis in both diploid and tetraploid genotypes of Brachiaria species. Results revealed differences in chromosome distribution of H3S10ph when mitosis and meiosis were compared. Whole chromosomes were phosphorylated ...

  2. Phosphorylation of eukaryotic aminoacyl-tRNA synthetases

    International Nuclear Information System (INIS)

    Pendergast, A.M.

    1986-01-01

    The phosphorylation of the highly purified aminoacyl-tRNA synthetase complex from rabbit reticulocytes was examined. The synthetase complex contained, in addition to eight aminoacyl-tRNA synthetases, three unidentified proteins and was free of endogenous protein kinase activity. Incubation of the complex with casein kinase I in the presence of ATP resulted in the phosphorylation of four synthetases, the glutamyl-, isoleucyl-, methionyl-, and lysyl-tRNA synthetases. Phosphorylation by casein kinase I altered binding to tRNA-Sepharose such that the phosphorylated complex eluted at 190 mM NaCl instead of the 275 mM salt observed for the nonphosphorylated form. Phosphorylation by casein kinase I resulted in a significant inhibition of aminoacylation with the four synthetases; the activities of the nonphosphorylated synthetases were unchanged. One of the unidentified proteins in the complex (M/sub r/ 37,000) was also an excellent substrate for casein kinase I. A comparison of the properties and two-dimensional phosphopeptide pattern of this protein with that of casein kinase I suggest that the 37,000 dalton protein in the synthetase complex is an inactive form of casein kinase I. Two other protein kinases were shown to phosphorylate aminoacyl-tRNA synthetases in the complex. The phosphorylation of threonyl-tRNA synthetase was also investigated. Five aminoacyl-tRNA synthetases in the high molecular weight complex were shown to be phosphorylated in rabbit reticulocytes following labeling with ( 32 P)orthophosphate

  3. Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis

    DEFF Research Database (Denmark)

    Miller, Martin Lee; Brunak, Søren; Olsen, JV

    2010-01-01

    and phosphorylation sites were grouped according to their cell cycle kinetics and compared to publicly available messenger RNA microarray data. Most detected phosphorylation sites and more than 20% of all quantified proteins showed substantial regulation, mainly in mitotic cells. Kinase-motif analysis revealed global...

  4. Myosin light chain kinase phosphorylation in tracheal smooth muscle

    International Nuclear Information System (INIS)

    Stull, J.T.; Hsu, L.C.; Tansey, M.G.; Kamm, K.E.

    1990-01-01

    Purified myosin light chain kinase from smooth muscle is phosphorylated by cyclic AMP-dependent protein kinase, protein kinase C, and the multifunctional calmodulin-dependent protein kinase II. Because phosphorylation in a specific site (site A) by any one of these kinases desensitizes myosin light chain kinase to activation by Ca2+/calmodulin, kinase phosphorylation could play an important role in regulating smooth muscle contractility. This possibility was investigated in 32 P-labeled bovine tracheal smooth muscle. Treatment of tissues with carbachol, KCl, isoproterenol, or phorbol 12,13-dibutyrate increased the extent of kinase phosphorylation. Six primary phosphopeptides (A-F) of myosin light chain kinase were identified. Site A was phosphorylated to an appreciable extent only with carbachol or KCl, agents which contract tracheal smooth muscle. The extent of site A phosphorylation correlated to increases in the concentration of Ca2+/calmodulin required for activation. These results show that cyclic AMP-dependent protein kinase and protein kinase C do not affect smooth muscle contractility by phosphorylating site A in myosin light chain kinase. It is proposed that phosphorylation of myosin light chain kinase in site A in contracting tracheal smooth muscle may play a role in the reported desensitization of contractile elements to activation by Ca2+

  5. Novel Role of Src in Priming Pyk2 Phosphorylation.

    Directory of Open Access Journals (Sweden)

    Ming Zhao

    Full Text Available Proline-rich tyrosine kinase 2 (Pyk2 is a member of the focal adhesion kinase (FAK family of non-receptor tyrosine kinases and plays an important role in diverse cellular events downstream of the integrin-family of receptors, including cell migration, proliferation and survival. Here, we have identified a novel role for Src kinase in priming Pyk2 phosphorylation and subsequent activation upon cell attachment on the integrin-ligand fibronectin. By using complementary methods, we show that Src activity is indispensable for the initial Pyk2 phosphorylation on the Y402 site observed in response to cell attachment. In contrast, the initial fibronectin-induced autophosphorylation of FAK in the homologous Y397 site occurs in a Src-independent manner. We demonstrate that the SH2-domain of Src is required for Src binding to Pyk2 and for Pyk2 phosphorylation at sites Y402 and Y579. Moreover, Y402 phosphorylation is a prerequisite for the subsequent Y579 phosphorylation. While this initial phosphorylation of Pyk2 by Src is independent of Pyk2 kinase activity, subsequent autophosphorylation of Pyk2 in trans is required for full Pyk2 phosphorylation and activation. Collectively, our studies reveal a novel function of Src in priming Pyk2 (but not FAK phosphorylation and subsequent activation downstream of integrins, and shed light on the signaling events that regulate the function of Pyk2.

  6. Identification of ASK1, MKK4, JNK, c-Jun, and caspase-3 as a signaling cascade involved in cadmium-induced neuronal cell apoptosis

    International Nuclear Information System (INIS)

    Kim, Sun Don; Moon, Chang Kyu; Eun, Su-Yong; Ryu, Pan Dong; Jo, Sangmee Ahn

    2005-01-01

    Cd induces oxidative stress and apoptosis in various cells by activating mitogen-activated protein kinases (MAPKs), but the precise signaling components of the MAPK cascade and their role in neuronal apoptosis are still unclear. Here, we report that Cd treatment of SH-SY5Y cells caused apoptosis through sequential phosphorylation of the apoptosis signal regulating kinase 1, MAPK kinase 4, c-Jun N-terminal kinase (JNK), and c-Jun as determined by overexpression of dominant negative (DN) constructs of these genes or using a specific JNK inhibitor SP600125. Both Cd-induced JNK and c-Jun phosphorylation and apoptosis were inhibited dramatically by N-acetyl-L-cysteine, a free radical scavenger. In addition, caspase inhibitors, zDEVD and zVAD, reduced apoptosis but not JNK and c-Jun phosphorylation induced by Cd, while overexpression of DN JNK1 inhibited caspase-3 activity. Taken together, our data suggested that the JNK/c-Jun signaling cascade plays a crucial role in Cd-induced neuronal cell apoptosis and provides a molecular linkage between oxidative stress and neuronal apoptosis

  7. The comparison of extraction of energy in two-cascade and one-cascade targets

    Energy Technology Data Exchange (ETDEWEB)

    Dolgoleva, G. V., E-mail: dolgg@list.ru [National Research Tomsk State University, 36, Lenin Ave., 634050, Tomsk (Russian Federation); Ponomarev, I. V., E-mail: wingof17@mail.ru [Moscow State University, Department of Mechanics and Mathematics, 1, Vorobyovy Gory, Moscow,119961 (Russian Federation)

    2016-01-15

    The paper is devoted to numerical designing of cylindrical microtargets on the basis of shock-free compression. When designing microtargets for the controlled thermonuclear fusion, the core tasks are to select geometry and make-up of layers, and the law of energy embedding as well, which allow receiving of “burning” of deuterium- tritium mix, that is, the existence of thermonuclear reactions of working area. Yet, the energy yield as a result of thermonuclear reactions has to be more than the embedded energy (the coefficient of amplification is more than a unit). So, an important issue is the value of the embedded energy. The purpose of the present paper is to study the extraction of energy by working DT area in one-cascade and two-cascade targets. A bigger extraction of energy will contribute to a better burning of DT mix and a bigger energy yield as a result of thermonuclear reactions. The comparison of analytical results to numerical calculations is carried out. The received results show advantages of a two-cascade target compared to a one-cascade one.

  8. Optimization of the cascade with gas centrifuges for uranium enrichment

    International Nuclear Information System (INIS)

    Ozaki, N.; Harada, I.

    1976-01-01

    Computer programs to optimize the step and tapered-step cascades with gas centrifuges are developed. The 'Complex Method', one of the direct search method, is employed to find the optimum of the nonlinear function of several variables within a constrained region. The separation characteristics of the optimized step and tapered-step cascades are discussed in comparison with that of the ideal cascade. The local optima of the cascade profile, the convergence of the object function, and the stopping criterion for the optimization trial are also discussed. (author)

  9. Noise propagation in two-step series MAPK cascade.

    Directory of Open Access Journals (Sweden)

    Venkata Dhananjaneyulu

    Full Text Available Series MAPK enzymatic cascades, ubiquitously found in signaling networks, act as signal amplifiers and play a key role in processing information during signal transduction in cells. In activated cascades, cell-to-cell variability or noise is bound to occur and thereby strongly affects the cellular response. Commonly used linearization method (LM applied to Langevin type stochastic model of the MAPK cascade fails to accurately predict intrinsic noise propagation in the cascade. We prove this by using extensive stochastic simulations for various ranges of biochemical parameters. This failure is due to the fact that the LM ignores the nonlinear effects on the noise. However, LM provides a good estimate of the extrinsic noise propagation. We show that the correct estimate of intrinsic noise propagation in signaling networks that contain at least one enzymatic step can be obtained only through stochastic simulations. Noise propagation in the cascade depends on the underlying biochemical parameters which are often unavailable. Based on a combination of global sensitivity analysis (GSA and stochastic simulations, we developed a systematic methodology to characterize noise propagation in the cascade. GSA predicts that noise propagation in MAPK cascade is sensitive to the total number of upstream enzyme molecules and the total number of molecules of the two substrates involved in the cascade. We argue that the general systematic approach proposed and demonstrated on MAPK cascade must accompany noise propagation studies in biological networks.

  10. All passive architecture for high efficiency cascaded Raman conversion

    Science.gov (United States)

    Balaswamy, V.; Arun, S.; Chayran, G.; Supradeepa, V. R.

    2018-02-01

    Cascaded Raman fiber lasers have offered a convenient method to obtain scalable, high-power sources at various wavelength regions inaccessible with rare-earth doped fiber lasers. A limitation previously was the reduced efficiency of these lasers. Recently, new architectures have been proposed to enhance efficiency, but this came at the cost of enhanced complexity, requiring an additional low-power, cascaded Raman laser. In this work, we overcome this with a new, all-passive architecture for high-efficiency cascaded Raman conversion. We demonstrate our architecture with a fifth-order cascaded Raman converter from 1117nm to 1480nm with output power of ~64W and efficiency of 60%.

  11. Gas separation performance of tapered cascade with membrane

    International Nuclear Information System (INIS)

    Ohno, Masayoshi; Morisue, Tetsuo; Ozaki, Osamu; Miyauchi, Terukatsu.

    1978-01-01

    Membrane gas separation cascades are analyzed at steady state. The method of calculating the flow rate and concentration profiles in the cascade are examined, using formulas expressing the various membrane separation cell characteristics. The method adopted is applicable to relatively high concentrations and separation factors. Considerations are further given on the steady state performance of four theoretical forms of cascade: (a) with common value of cut for all stages, (b) with symmetric separation cells, (c) with no mixing at the junction at each stage, and (d) ideal cascade. The analysis showed that, with membrane cells, the ideal cascade would have a pressure ratio varying from stage to stage. The symmetric separation cascade would provide a separation performance lower than the ideal cascade on account of the mixing at the junctions of streams possessing different concentrations, whereas the cut and separation factor of the no-mixing cascade requiring minimum membrane area exhibits zig-zag curves when plotted against stage number. Both these circumstances contribute to the lower separation performance obtained with these two forms as compared with the ideal cascade, and results in larger total membrane area; but these semi-ideal forms retain the advantage of easy practical treatment with their pressure ratio common to all stages. (auth.)

  12. Effects of protein phosphorylation on color stability of ground meat.

    Science.gov (United States)

    Li, Meng; Li, Xin; Xin, Jianzeng; Li, Zheng; Li, Guixia; Zhang, Yan; Du, Manting; Shen, Qingwu W; Zhang, Dequan

    2017-03-15

    The influence of protein phosphorylation on meat color stability was investigated in this study. Phosphatase and protein kinase inhibitors were added to minced ovine Longissimus thoracis et lumborum (LTL) muscle to manipulate the global phosphorylation of sarcoplasmic proteins. The data obtained show that the rate and extent of pH decline, along with lactate accumulation in postmortem muscle, were related to protein phosphorylation. Analysis of meat color and the relative content of myoglobin redox forms revealed that meat color stability was inversely related to the phosphorylation of sarcoplasmic proteins. Thus, this study suggests that protein phosphorylation may be involved in meat color development by regulating glycolysis and the redox stability of myoglobin. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. Interaction of butylated hydroxyanisole with mitochondrial oxidative phosphorylation.

    Science.gov (United States)

    Fusi, F; Sgaragli, G; Murphy, M P

    1992-03-17

    The antioxidant, butylated hydroxyanisole (BHA), has a number of effects on mitochondrial oxidative phosphorylation. In this study we apply the novel approach developed by Brand (Brand MD, Biochim Biophys Acta 1018: 128-133, 1990) to investigate the site of action of BHA on oxidative phosphorylation in rat liver mitochondria. Using this approach we show that BHA increases the proton leak through the mitochondrial inner membrane and that it also inhibits the delta p (proton motive force across the mitochondrial inner membrane) generating system, but has no effect on the phosphorylation system. This demonstrates that compounds having pleiotypic effects on mitochondrial oxidative phosphorylation in vitro can be analysed and their many effects distinguished. This approach is of general use in analysing many other compounds of pharmacological interest which interact with mitochondria. The implications of these results for the mechanism of interaction of BHA with mitochondrial oxidative phosphorylation are discussed.

  14. Importance of tyrosine phosphorylation in receptor kinase complexes.

    Science.gov (United States)

    Macho, Alberto P; Lozano-Durán, Rosa; Zipfel, Cyril

    2015-05-01

    Tyrosine phosphorylation is an important post-translational modification that is known to regulate receptor kinase (RK)-mediated signaling in animals. Plant RKs are annotated as serine/threonine kinases, but recent work has revealed that tyrosine phosphorylation is also crucial for the activation of RK-mediated signaling in plants. These initial observations have paved the way for subsequent detailed studies on the mechanism of activation of plant RKs and the biological relevance of tyrosine phosphorylation for plant growth and immunity. In this Opinion article we review recent reports on the contribution of RK tyrosine phosphorylation in plant growth and immunity; we propose that tyrosine phosphorylation plays a major regulatory role in the initiation and transduction of RK-mediated signaling in plants. Copyright © 2015 Elsevier Ltd. All rights reserved.

  15. Phosphorylation of the Epstein-Barr virus nuclear antigen 2

    DEFF Research Database (Denmark)

    Grässer, F A; Göttel, S; Haiss, P

    1992-01-01

    A major in vivo phosphorylation site of the Epstein-Barr virus nuclear antigen 2 (EBNA-2) was found to be localized at the C-terminus of the protein. In vitro phosphorylation studies using casein kinase 1 (CK-1) and casein kinase 2 (CK-2) revealed that EBNA-2 is a substrate for CK-2, but not for CK......-1. The CK-2 specific phosphorylation site was localized in the 140 C-terminal amino acids using a recombinant trpE-C-terminal fusion protein. In a similar experiment, the 58 N-terminal amino acids expressed as a recombinant trpE-fusion protein were not phosphorylated. Phosphorylation of a synthetic...

  16. Sequential phosphorylation of GRASP65 during mitotic Golgi disassembly

    Directory of Open Access Journals (Sweden)

    Danming Tang

    2012-09-01

    GRASP65 phosphorylation during mitosis and dephosphorylation after mitosis are required for Golgi disassembly and reassembly during the cell cycle. At least eight phosphorylation sites on GRASP65 have been identified, but whether they are modified in a coordinated fashion during mitosis is so far unknown. In this study, we raised phospho-specific antibodies that recognize phosphorylated T220/T224, S277 and S376 residues of GRASP65, respectively. Biochemical analysis showed that cdc2 phosphorylates all three sites, while plk1 enhances the phosphorylation. Microscopic studies using these antibodies for double and triple labeling demonstrate sequential phosphorylation and dephosphorylation during the cell cycle. S277 and S376 are phosphorylated from late G2 phase through metaphase until telophase when the new Golgi is reassembled. T220/224 is not modified until prophase, but is highly modified from prometaphase to anaphase. In metaphase, phospho-T220/224 signal localizes on both Golgi haze and mitotic Golgi clusters that represent dispersed Golgi vesicles and Golgi remnants, respectively, while phospho-S277 and S376 labeling is more concentrated on mitotic Golgi clusters. Expression of a phosphorylation-resistant GRASP65 mutant T220A/T224A inhibited mitotic Golgi fragmentation to a much larger extent than the expression of the S277A and S376A mutants. In cytokinesis, T220/224 dephosphorylation occurs prior to that of S277, but after S376. This study provides evidence that GRASP65 is sequentially phosphorylated and dephosphorylated during mitosis at different sites to orchestrate Golgi disassembly and reassembly during cell division, with phosphorylation of the T220/224 site being most critical in the process.

  17. Cascading walks model for human mobility patterns.

    Science.gov (United States)

    Han, Xiao-Pu; Wang, Xiang-Wen; Yan, Xiao-Yong; Wang, Bing-Hong

    2015-01-01

    Uncovering the mechanism behind the scaling laws and series of anomalies in human trajectories is of fundamental significance in understanding many spatio-temporal phenomena. Recently, several models, e.g. the explorations-returns model (Song et al., 2010) and the radiation model for intercity travels (Simini et al., 2012), have been proposed to study the origin of these anomalies and the prediction of human movements. However, an agent-based model that could reproduce most of empirical observations without priori is still lacking. In this paper, considering the empirical findings on the correlations of move-lengths and staying time in human trips, we propose a simple model which is mainly based on the cascading processes to capture the human mobility patterns. In this model, each long-range movement activates series of shorter movements that are organized by the law of localized explorations and preferential returns in prescribed region. Based on the numerical simulations and analytical studies, we show more than five statistical characters that are well consistent with the empirical observations, including several types of scaling anomalies and the ultraslow diffusion properties, implying the cascading processes associated with the localized exploration and preferential returns are indeed a key in the understanding of human mobility activities. Moreover, the model shows both of the diverse individual mobility and aggregated scaling displacements, bridging the micro and macro patterns in human mobility. In summary, our model successfully explains most of empirical findings and provides deeper understandings on the emergence of human mobility patterns.

  18. The cascad spent fuel dry storage facility

    International Nuclear Information System (INIS)

    Guay, P.; Bonnet, C.

    1991-01-01

    France has a wide variety of experimental spent fuels different from LWR spent fuel discharged from commercial reactors. Reprocessing such fuels would thus require the development and construction of special facilities. The French Atomic Energy Commission (CEA) has consequently opted for long-term interim storage of these spent fuels over a period of 50 years. Comparative studies of different storage concepts have been conducted on the basis of safety (mainly containment barriers and cooling), economic, modular design and operating flexibility criteria. These studies have shown that dry storage in a concrete vault cooled by natural convection is the best solution. A research and development program including theoretical investigations and mock-up tests confirmed the feasibility of cooling by natural convection and the validity of design rules applied for fuel storage. A facility called CASCAD was built at the CEA's Cadarache Nuclear Research Center, where it has been operational since mid-1990. This paper describes the CASCAD facility and indicates how its concept can be applied to storage of LWR fuel assemblies

  19. Frequency division using a micromechanical resonance cascade

    Energy Technology Data Exchange (ETDEWEB)

    Qalandar, K. R., E-mail: kamala@engineering.ucsb.edu; Gibson, B.; Sharma, M.; Ma, A.; Turner, K. L. [Department of Mechanical Engineering, University of California at Santa Barbara, Santa Barbara, California 93106 (United States); Strachan, B. S. [Department of Mechanical Engineering, Michigan State University, East Lansing, Michigan 48823 (United States); Department of Electrical Engineering, Michigan State University, East Lansing, Michigan 48823 (United States); Shaw, S. W. [Department of Mechanical Engineering, Michigan State University, East Lansing, Michigan 48823 (United States); Department of Physics and Astronomy, Michigan State University, East Lansing, Michigan 48823 (United States)

    2014-12-15

    A coupled micromechanical resonator array demonstrates a mechanical realization of multi-stage frequency division. The mechanical structure consists of a set of N sequentially perpendicular microbeams that are connected by relatively weak elastic elements such that the system vibration modes are localized to individual microbeams and have natural frequencies with ratios close to 1:2:⋯:2{sup N}. Conservative (passive) nonlinear inter-modal coupling provides the required energy transfer between modes and is achieved by finite deformation kinematics. When the highest frequency beam is excited, this arrangement promotes a cascade of subharmonic resonances that achieve frequency division of 2{sup j} at microbeam j for j = 1, …, N. Results are shown for a capacitively driven three-stage divider in which an input signal of 824 kHz is passively divided through three modal stages, producing signals at 412 kHz, 206 kHz, and 103 kHz. The system modes are characterized and used to delineate the range of AC input voltages and frequencies over which the cascade occurs. This narrow band frequency divider has simple design rules that are scalable to higher frequencies and can be extended to a larger number of modal stages.

  20. Turbulent cascades in foreign exchange markets

    Science.gov (United States)

    Ghashghaie, S.; Breymann, W.; Peinke, J.; Talkner, P.; Dodge, Y.

    1996-06-01

    THE availability of high-frequency data for financial markets has made it possible to study market dynamics on timescales of less than a day1. For foreign exchange (FX) rates Müller et al.2 have shown that there is a net flow of information from long to short timescales: the behaviour of long-term traders (who watch the markets only from time to time) influences the behaviour of short-term traders (who watch the markets continuously). Motivated by this hierarchical feature, we have studied FX market dynamics in more detail, and report here an analogy between these dynamics and hydrodynamic turbulence3-8. Specifically, the relationship between the probability density of FX price changes (δx) and the time delay (δt) (Fig. la) is much the same as the relationship between the probability density of the velocity differences (δv) of two points in a turbulent flow and their spatial separation δr (Fig. 1b). Guided by this similarity we claim that there is an information cascade in FX market dynamics that corresponds to the energy cascade in hydrodynamic turbulence. On the basis of this analogy we can now rationalize the statistics of FX price differences at different time delays, which is important for, for example, option pricing. The analogy also provides a conceptual framework for understanding the short-term dynamics of speculative markets.

  1. Cascade Distiller System Performance Testing Interim Results

    Science.gov (United States)

    Callahan, Michael R.; Pensinger, Stuart; Sargusingh, Miriam J.

    2014-01-01

    The Cascade Distillation System (CDS) is a rotary distillation system with potential for greater reliability and lower energy costs than existing distillation systems. Based upon the results of the 2009 distillation comparison test (DCT) and recommendations of the expert panel, the Advanced Exploration Systems (AES) Water Recovery Project (WRP) project advanced the technology by increasing reliability of the system through redesign of bearing assemblies and improved rotor dynamics. In addition, the project improved the CDS power efficiency by optimizing the thermoelectric heat pump (TeHP) and heat exchanger design. Testing at the NASA-JSC Advanced Exploration System Water Laboratory (AES Water Lab) using a prototype Cascade Distillation Subsystem (CDS) wastewater processor (Honeywell d International, Torrance, Calif.) with test support equipment and control system developed by Johnson Space Center was performed to evaluate performance of the system with the upgrades as compared to previous system performance. The system was challenged with Solution 1 from the NASA Exploration Life Support (ELS) distillation comparison testing performed in 2009. Solution 1 consisted of a mixed stream containing human-generated urine and humidity condensate. A secondary objective of this testing is to evaluate the performance of the CDS as compared to the state of the art Distillation Assembly (DA) used in the ISS Urine Processor Assembly (UPA). This was done by challenging the system with ISS analog waste streams. This paper details the results of the AES WRP CDS performance testing.

  2. Quaternary Magmatism in the Cascades - Geologic Perspectives

    Science.gov (United States)

    Hildreth, Wes

    2007-01-01

    Foreward The Cascade magmatic arc is a belt of Quaternary volcanoes that extends 1,250 km from Lassen Peak in northern California to Meager Mountain in Canada, above the subduction zone where the Juan de Fuca Plate plunges beneath the North American Plate. This Professional Paper presents a synthesis of the entire volcanic arc, addressing all 2,300 known Quaternary volcanoes, not just the 30 or so visually prominent peaks that comprise the volcanic skyline. Study of Cascade volcanoes goes back to the geological explorers of the late 19th century and the seminal investigations of Howel Williams in the 1920s and 1930s. However, major progress and application of modern scientific methods and instrumentation began only in the 1970s with the advent of systematic geological, geophysical, and geochemical studies of the entire arc. Initial stimulus from the USGS Geothermal Research Program was enhanced by the USGS Volcano Hazards Program following the 1980 eruption of Mount St. Helens. Together, these two USGS Programs have provided more than three decades of stable funding, staffing, and analytical support. This Professional Paper summarizes the resultant USGS data sets and integrates them with the parallel contributions of other investigators. The product is based upon an all-encompassing and definitive geological database, including chemical and isotopic analyses to characterize the rocks and geochronology to provide the critical time constraints. Until now, this massive amount of data has not been summarized, and a systematic and uniform interpretation firmly grounded in geological fact has been lacking. Herein lies the primary utility of this Cascade volume. It not only will be the mandatory starting point for new workers, but also will provide essential geological context to broaden the perspectives of current investigators of specific Cascade volcanoes. Wes Hildreth's insightful understanding of volcanic processes and his uncompromising scientific integrity make him

  3. Modeling of cascade and sub-cascade formation at high PKA energies in irradiated fusion structural materials

    International Nuclear Information System (INIS)

    Ryazanov, A.I.; Metelkin, E.V.; Semenov, E.V.

    2009-01-01

    A new theoretical model is developed for the investigations of cascade and sub-cascade formation in fusion structural materials under fast neutron irradiation at high primary knock-on atom energies. Light fusion structural materials: such as Be, C and SiC under 14 MeV neutron irradiation in fusion reactor will have the primary knock-on atoms with the energies up to 1 MeV. It is very difficult to use at such high energies the Monte-Carlo or molecular dynamic simulations [H.L. Heinisch, B.N. Singh, Philos. Mag. A67 (1993) 407; H.L. Heinisch, B.N. Singh, J. Nucl. Mater. 251 (1997) 77]. The developed model is based on the analytical consideration of elastic collisions between displaced moving atoms produced by primary knock-on atoms with some kinetic energies obtained from fast neutrons and crystal lattice atoms. The Thomas-Fermi interaction potential is used here for the description of these elastic atomic collisions. The suggested model takes into account also the electronic losses for moving atoms between elastic collisions. The self-consistent criterion for sub-cascade formation is suggested here which is based on the comparison of mean distance of primary knock-on atoms between consequent collisions of them with the target atoms and a size of sub-cascade produced by moving secondary knock-on atoms produced in such collisions. The analytical relations for the most important characteristics of cascades and sub-cascades are determined including the average number of sub-cascades per one primary knock-on atom in the dependence on its energy, the distance between sub-cascades and the average cascade and sub-cascade sizes. The developed model allows determining the total numbers, distribution functions of cascades and sub-cascades in dependence on their sizes and generation rate of cascades and sub-cascades for the different fusion neutron energy spectra. On the basis of this developed model the numerical calculations for main characteristics of cascades and sub-cascades

  4. Measuring brain glucose phosphorylation with labeled glucose

    International Nuclear Information System (INIS)

    Brondsted, H.E.; Gjedde, A.

    1988-01-01

    This study tested whether glucose labeled at the C-6 position generates metabolites that leave brain so rapidly that C-6-labeled glucose cannot be used to measure brain glucose phosphorylation (CMRGlc). In pentobarbital-anesthetized rats, the parietal cortex uptake of [ 14 C]glucose labeled in the C-6 position was followed for times ranging from 10 s to 60 min. We subtracted the observed radioactivity from the radioactivity expected with no loss of labeled metabolites from brain by extrapolation of glucose uptake in an initial period when loss was negligible. The observed radioactivity was a monoexponentially declining function of the total radioactivity expected in the absence of metabolite loss. The constant of decline was 0.0077.min-1 for parietal cortex. Metabolites were lost from the beginning of the experiment. However, with correction for the loss of labeled metabolites, it was possible to determine an average CMRGlc between 4 and 60 min of circulation of 64 +/- 4 (SE; n = 49) mumol.hg-1.min-1

  5. Phosphorylation site on yeast pyruvate dehydrogenase complex

    International Nuclear Information System (INIS)

    Uhlinger, D.J.

    1986-01-01

    The pyruvate dehydrogenase complex was purified to homogeneity from baker's yeast (Saccharomyces cerevisiae). Yeast cells were disrupted in a Manton-Gaulin laboratory homogenizer. The pyruvate dehydrogenase complex was purified by fractionation with polyethylene glycol, isoelectric precipitation, ultracentrifugation and chromatography on hydroxylapatite. Final purification of the yeast pyruvate dehydrogenase complex was achieved by cation-exchange high pressure liquid chromatography (HPLC). No endogenous pyruvate dehydrogenase kinase activity was detected during the purification. However, the yeast pyruvate dehydrogenase complex was phosphorylated and inactivated with purified pyruvate dehydrogenase kinase from bovine kidney. Tryptic digestion of the 32 P-labeled complex yielded a single phosphopeptide which was purified to homogeniety. The tryptic digest was subjected to chromatography on a C-18 reverse phase HPLC column with a linear gradient of acetonitrile. Radioactive fractions were pooled, concentrated, and subjected to anion-exchange HPLC. The column was developed with a linear gradient of ammonium acetate. Final purification of the phosphopeptide was achieved by chromatography on a C-18 reverse phase HPLC column developed with a linear gradient of acetonitrile. The amino acid sequence of the homogeneous peptide was determined by manual modified Edman degradation

  6. Inositol pyrophosphates mediate the DNA-PK/ATM-p53 cell death pathway by regulating CK2 phosphorylation of Tti1/Tel2

    Science.gov (United States)

    Rao, Feng; Cha, Jiyoung; Xu, Jing; Xu, Risheng; Vandiver, M. Scott; Tyagi, Richa; Tokhunts, Robert; Koldobskiy, Michael A.; Fu, Chenglai; Barrow, Roxanne; Wu, Mingxuan; Fiedler, Dorothea; Barrow, James C.; Snyder, Solomon H.

    2014-01-01

    The apoptotic actions of p53 require its phosphorylation by a family of phosphoinositide-3-kinase-related-kinases (PIKKs), which include DNA-PKcs and ATM. These kinases are stabilized by the TTT (Tel2, Tti1, Tti2) co-chaperone family, whose actions are mediated by CK2 phosphorylation. The inositol pyrophosphates, such as 5-diphosphoinositol pentakisphosphate (IP7), are generated by a family of inositol hexakisphosphate kinases (IP6Ks) of which IP6K2 has been implicated in p53-associated cell death. In the present study we report a novel apoptotic signaling cascade linking CK2, TTT, the PIKKs, and p53. We demonstrate that IP7, formed by IP6K2, binds CK2 to enhance its phosphorylation of the TTT complex thereby stabilizing DNA-PKcs and ATM. This process stimulates p53 phosphorylation at serine-15 to activate the cell death program in human cancer cells and in murine B cells. PMID:24657168

  7. ERK-GluR1 phosphorylation in trigeminal spinal subnucleus caudalis neurons is involved in pain associated with dry tongue.

    Science.gov (United States)

    Nakaya, Yuka; Tsuboi, Yoshiyuki; Okada-Ogawa, Akiko; Shinoda, Masamichi; Kubo, Asako; Chen, Jui Yen; Noma, Noboru; Batbold, Dulguun; Imamura, Yoshiki; Sessle, Barry J; Iwata, Koichi

    2016-01-01

    Dry mouth is known to cause severe pain in the intraoral structures, and many dry mouth patients have been suffering from intraoral pain. In development of an appropriate treatment, it is crucial to study the mechanisms underlying intraoral pain associated with dry mouth, yet the detailed mechanisms are not fully understood. To evaluate the mechanisms underlying pain related to dry mouth, the dry-tongue rat model was developed. Hence, the mechanical or heat nocifensive reflex, the phosphorylated extracellular signal-regulated kinase and phosphorylated GluR1-IR immunohistochemistries, and the single neuronal activity were examined in the trigeminal spinal subnucleus caudalis of dry-tongue rats. The head-withdrawal reflex threshold to mechanical, but not heat, stimulation of the tongue was significantly decreased on day 7 after tongue drying. The mechanical, but not heat, responses of trigeminal spinal subnucleus caudalis nociceptive neurons were significantly enhanced in dry-tongue rats compared to sham rats on day 7. The number of phosphorylated extracellular signal-regulated kinase-immunoreactive cells was also significantly increased in the trigeminal spinal subnucleus caudalis following noxious stimulation of the tongue in dry-tongue rats compared to sham rats on day 7. The decrement of the mechanical head-withdrawal reflex threshold (HWT) was reversed during intracisternal administration of the mitogen-activated protein kinase kinase 1 inhibitor, PD98059. The trigeminal spinal subnucleus caudalis neuronal activities and the number of phosphorylated extracellular signal-regulated kinase-immunoreactive cells following noxious mechanical stimulation of dried tongue were also significantly decreased following intracisternal administration of PD98059 compared to vehicle-administrated rats. Increased number of the phosphorylated GluR1-IR cells was observed in the trigeminal spinal subnucleus caudalis of dry-tongue rats, and the number of phosphorylated GluR1-IR cells

  8. Systematic analysis of phosphotyrosine antibodies recognizing single phosphorylated EPIYA-motifs in CagA of Western-type Helicobacter pylori strains.

    Directory of Open Access Journals (Sweden)

    Judith Lind

    Full Text Available The clinical outcome of Helicobacter pylori infections is determined by multiple host-pathogen interactions that may develop to chronic gastritis, and sometimes peptic ulcers or gastric cancer. Highly virulent strains encode a type IV secretion system (T4SS that delivers the effector protein CagA into gastric epithelial cells. Translocated CagA undergoes tyrosine phosphorylation at EPIYA-sequence motifs, called A, B and C in Western-type strains, by members of the oncogenic Src and Abl host kinases. Phosphorylated EPIYA-motifs mediate interactions of CagA with host signaling factors--in particular various SH2-domain containing human proteins--thereby hijacking multiple downstream signaling cascades. Observations of tyrosine-phosphorylated CagA are mainly based on the use of commercial phosphotyrosine antibodies, which originally were selected to detect phosphotyrosines in mammalian proteins. Systematic studies of phosphorylated EPIYA-motif detection by the different antibodies would be very useful, but are not yet available. To address this issue, we synthesized phospho- and non-phosphopeptides representing each predominant Western CagA EPIYA-motif, and determined the recognition patterns of seven different phosphotyrosine antibodies in Western blots, and also performed infection studies with diverse representative Western H. pylori strains. Our results show that a total of 9-11 amino acids containing the phosphorylated EPIYA-motifs are necessary and sufficient for specific detection by these antibodies, but revealed great variability in sequence recognition. Three of the antibodies recognized phosphorylated EPIYA-motifs A, B and C similarly well; whereas preferential binding to phosphorylated motif A and motifs A and C was found with two and one antibodies, respectively, and the seventh anti-phosphotyrosine antibody did not recognize any phosphorylated EPIYA-motif. Controls showed that none of the antibodies recognized the corresponding non

  9. Prion protein induced signaling cascades in monocytes

    International Nuclear Information System (INIS)

    Krebs, Bjarne; Dorner-Ciossek, Cornelia; Schmalzbauer, Ruediger; Vassallo, Neville; Herms, Jochen; Kretzschmar, Hans A.

    2006-01-01

    Prion proteins play a central role in transmission and pathogenesis of transmissible spongiform encephalopathies. The cellular prion protein (PrP C ), whose physiological function remains elusive, is anchored to the surface of a variety of cell types including neurons and cells of the lymphoreticular system. In this study, we investigated the response of a mouse monocyte/macrophage cell line to exposure with PrP C fusion proteins synthesized with a human Fc-tag. PrP C fusion proteins showed an attachment to the surface of monocyte/macrophages in nanomolar concentrations. This was accompanied by an increase of cellular tyrosine phosphorylation as a result of activated signaling pathways. Detailed investigations exhibited activation of downstream pathways through a stimulation with PrP fusion proteins, which include phosphorylation of ERK 1,2 and Akt kinase. Macrophages opsonize and present antigenic structures, contact lymphocytes, and deliver cytokines. The findings reported here may become the basis of understanding the molecular function of PrP C in monocytes and macrophages

  10. Phosphorylation sites of Arabidopsis MAP Kinase Substrate 1 (MKS1)

    DEFF Research Database (Denmark)

    Caspersen, M.B.; Qiu, J.-L.; Zhang, X.

    2007-01-01

    The Arabidopsis MAP kinase 4 (MPK4) substrate MKS1 was expressed in Escherichia coli and purified, full-length, 6x histidine (His)-tagged MKS1 was phosphorylated in vitro by hemagglutinin (HA)-tagged MPK4 immuno-precipitated from plants. MKS1 phosphorylation was initially verified by electrophore......The Arabidopsis MAP kinase 4 (MPK4) substrate MKS1 was expressed in Escherichia coli and purified, full-length, 6x histidine (His)-tagged MKS1 was phosphorylated in vitro by hemagglutinin (HA)-tagged MPK4 immuno-precipitated from plants. MKS1 phosphorylation was initially verified...... phosphopeptide detection. As MAP kinases generally phosphorylate serine or threonine followed by proline (Ser/Thr-Pro), theoretical masses of potentially phosphorylated peptides were calculated and mass spectrometric peaks matching these masses were fragmented and searched for a neutral-loss signal...... at approximately 98 Da indicative of phosphorylation. Additionally, mass spectrometric peaks present in the MPK4-treated MKS1, but not in the control peptide map of untreated MKS1, were fragmented. Fragmentation spectra were subjected to a MASCOT database search which identified three of the twelve Ser-Pro serine...

  11. Cytochrome C is tyrosine 97 phosphorylated by neuroprotective insulin treatment.

    Directory of Open Access Journals (Sweden)

    Thomas H Sanderson

    Full Text Available Recent advancements in isolation techniques for cytochrome c (Cytc have allowed us to discover post-translational modifications of this protein. We previously identified two distinct tyrosine phosphorylated residues on Cytc in mammalian liver and heart that alter its electron transfer kinetics and the ability to induce apoptosis. Here we investigated the phosphorylation status of Cytc in ischemic brain and sought to determine if insulin-induced neuroprotection and inhibition of Cytc release was associated with phosphorylation of Cytc. Using an animal model of global brain ischemia, we found a ∼50% decrease in neuronal death in the CA1 hippocampal region with post-ischemic insulin administration. This insulin-mediated increase in neuronal survival was associated with inhibition of Cytc release at 24 hours of reperfusion. To investigate possible changes in the phosphorylation state of Cytc we first isolated the protein from ischemic pig brain and brain that was treated with insulin. Ischemic brains demonstrated no detectable tyrosine phosphorylation. In contrast Cytc isolated from brains treated with insulin showed robust phosphorylation of Cytc, and the phosphorylation site was unambiguously identified as Tyr97 by immobilized metal affinity chromatography/nano-liquid chromatography/electrospray ionization mass spectrometry. We next confirmed these results in rats by in vivo application of insulin in the absence or presence of global brain ischemia and determined that Cytc Tyr97-phosphorylation is strongly induced under both conditions but cannot be detected in untreated controls. These data suggest a mechanism whereby Cytc is targeted for phosphorylation by insulin signaling, which may prevent its release from the mitochondria and the induction of apoptosis.

  12. The critical care cascade: a systems approach.

    Science.gov (United States)

    Ghosh, Rishi; Pepe, Paul

    2009-08-01

    To emphasize the evolving body of evidence that supports the need for a more seamless and interconnected continuum of patient care for a growing compendium of critical care conditions, starting in the prehospital and emergency department (ED) phases of management and continuing through ICU and rehabilitation services. The care of critically ill and injured patients has become increasingly complex. It now has been demonstrated that, for a number of such critical care conditions, optimal management not only relies heavily on the talents of highly coordinated, multidisciplinary teams, but it also may require shared responsibilities across a continuum of longitudinal care involving numerous specialties and departments. This continuum usually needs to begin in the prehospital and ED settings with management extending through specialized in-hospital diagnostic and interventional suites to traditional ICU and rehabilitation programs. In recent years, examples of these conditions have included the development of systems of care for trauma, cardiac arrest, myocardial infarction, stroke, sepsis syndromes, toxicology and other critical illnesses. Although the widespread implementation of such multidisciplinary, multispecialty critical care cascades of care has been achieved most commonly in trauma care, current healthcare delivery systems generally tend to employ compartmentalized organization for the majority of other critical care patients. Accordingly, optimal systematic care often breaks down in the management of these complex patients due to barriers such as lack of interoperable communication between teams, disjointed transfers between services, unnecessary time-consuming, re-evaluations and transitional pauses in time-dependent circumstances, deficiencies in cross-disciplinary education and quality assurance loops, and significant variability in patient care practices. Such barriers can lead to adverse outcomes in this fragile patient population. This article discusses

  13. Eruptive history of South Sister, Oregon Cascades

    Science.gov (United States)

    Fierstein, J.; Hildreth, W.; Calvert, A.T.

    2011-01-01

    South Sister is southernmost and highest of the Three Sisters, three geologically dissimilar stratovolcanoes that together form a spectacular 20km reach along the Cascade crest in Oregon. North Sister is a monotonously mafic edifice as old as middle Pleistocene, Middle Sister a basalt-andesite-dacite cone built between 48 and 14ka, and South Sister is a basalt-free edifice that alternated rhyolitic and intermediate modes from 50ka to 2ka (largely contemporaneous with Middle Sister). Detailed mapping, 330 chemical analyses, and 42 radioisotopic ages show that the oldest exposed South Sister lavas were initially rhyolitic ~50ka. By ~37ka, rhyolitic lava flows and domes (72-74% SiO2) began alternating with radially emplaced dacite (63-68% SiO2) and andesite (59-63% SiO2) lava flows. Construction of a broad cone of silicic andesite-dacite (61-64% SiO2) culminated ~30ka in a dominantly explosive sequence that began with crater-forming andesitic eruptions that left fragmental deposits at least 200m thick. This was followed at ~27ka by growth of a steeply dipping summit cone of agglutinate-dominated andesite (56-60.5% SiO2) and formation of a summit crater ~800m wide. This crater was soon filled and overtopped by a thick dacite lava flow and then by >150m of dacitic pyroclastic ejecta. Small-volume dacite lavas (63-67% SiO2) locally cap the pyroclastic pile. A final sheet of mafic agglutinate (54-56% SiO2) - the most mafic product of South Sister - erupted from and drapes the small (300-m-wide) present-day summit crater, ending a summit-building sequence that lasted until ~22ka. A 20kyr-long-hiatus was broken by rhyolite eruptions that produced (1) the Rock Mesa coulee, tephra, and satellite domelets (73.5% SiO2) and (2) the Devils Chain of ~20 domes and short coulees (72.3-72.8% SiO2) from N-S vent alignments on South Sister's flanks. The compositional reversal from mafic summit agglutinate to recent rhyolites epitomizes the frequently changing compositional modes of the

  14. Energy cascading in the beat-wave accelerator

    International Nuclear Information System (INIS)

    McKinstrie, C.J.; Batha, S.H.

    1987-01-01

    A review is given of energy cascading in the beat-wave accelerator. The properties of the electromagnetic cascade and the corresponding plasma-wave evolution are well understood within the framework of an approximate analytic model. Based on this model, idealized laser-plasma coupling efficiencies of the order of 10% do not seem unreasonable. 28 refs

  15. Time development of cascades by the binary collision approximation code

    International Nuclear Information System (INIS)

    Fukumura, A.; Ishino, S.; Sekimura, N.

    1991-01-01

    To link a molecular dynamic calculation to binary collision approximation codes to explore high energy cascade damage, time between consecutive collisions is introduced into the binary collision MARLOWE code. Calculated results for gold by the modified code show formation of sub-cascades and their spatial and time overlapping, which can affect formation of defect clusters. (orig.)

  16. Cascades for hydrogen isotope separation using metal hydrides

    International Nuclear Information System (INIS)

    Hill, F.B.; Grzetic, V.

    1982-01-01

    Designs are presented for continuous countercurrent hydrogen isotope separation cascades based on the use of metal hydrides. The cascades are made up of pressure swing adsorption (PSA) or temperature swing adsorption (TSA) stages. The designs were evolved from consideration of previously conducted studies of the separation performance of four types of PSA and TSA processes

  17. Hybrid Modulation Scheme for Cascaded H-Bridge Inverter Cells ...

    African Journals Online (AJOL)

    This work proposes a switching technique for cascaded H-Bridge (CHB) cells. Single carrier Sinusoidal PWM (SCSPWM) scheme is employed in the generation of the gating signals. A sequential switching and base PWM circulation schemes are presented for this fundamental cascaded multilevel inverter topology.

  18. A simple model of global cascades on random networks

    Science.gov (United States)

    Watts, Duncan J.

    2002-04-01

    The origin of large but rare cascades that are triggered by small initial shocks is a phenomenon that manifests itself as diversely as cultural fads, collective action, the diffusion of norms and innovations, and cascading failures in infrastructure and organizational networks. This paper presents a possible explanation of this phenomenon in terms of a sparse, random network of interacting agents whose decisions are determined by the actions of their neighbors according to a simple threshold rule. Two regimes are identified in which the network is susceptible to very large cascadesherein called global cascadesthat occur very rarely. When cascade propagation is limited by the connectivity of the network, a power law distribution of cascade sizes is observed, analogous to the cluster size distribution in standard percolation theory and avalanches in self-organized criticality. But when the network is highly connected, cascade propagation is limited instead by the local stability of the nodes themselves, and the size distribution of cascades is bimodal, implying a more extreme kind of instability that is correspondingly harder to anticipate. In the first regime, where the distribution of network neighbors is highly skewed, it is found that the most connected nodes are far more likely than average nodes to trigger cascades, but not in the second regime. Finally, it is shown that heterogeneity plays an ambiguous role in determining a system's stability: increasingly heterogeneous thresholds make the system more vulnerable to global cascades; but an increasingly heterogeneous degree distribution makes it less vulnerable.

  19. Cascade in muonic and pionic atoms with Z = 1

    International Nuclear Information System (INIS)

    Markushin, V.E.

    1999-01-01

    Recent theoretical and experimental studies of the exotic atoms with Z = 1 are reviewed. An interplay between the atomic internal and external degrees of freedom is essential for a good description of the atomic cascade. The perspective of ab initio cascade calculations is outlined

  20. Intermittent Flow Regimes in a Transonic Fan Airfoil Cascade

    Directory of Open Access Journals (Sweden)

    J. Lepicovsky

    2004-01-01

    velocity.To date, this flow behavior has only been observed in a linear transonic cascade. Further research is necessary to confirm this phenomenon occurs in actual transonic fans and is not the by-product of an endwall restricted linear cascade.

  1. A cascaded online uninterruptible power supply using reduced semiconductor

    DEFF Research Database (Denmark)

    Zhang, Lei; Loh, Poh Chiang; Gao, Feng

    2011-01-01

    A cascaded online uninterruptible power supply (UPS) is proposed here that uses 25% lesser semiconductor, as compared to its traditional H-bridge cascaded precedence. Unlike other component-saving configurations where compromises are unavoidable, almost no performance degradations and constraints...

  2. Cascades for hydrogen isotope separation using metal hydrides

    Energy Technology Data Exchange (ETDEWEB)

    Hill, F B; Grzetic, V [Brookhaven National Lab., Upton, NY (USA)

    1983-02-01

    Designs are presented for continuous countercurrent hydrogen isotope separation cascades based on the use of metal hydrides. The cascades are made up of pressure swing adsorption (PSA) or temperature swing adsorption (TSA) stages. The designs were evolved from consideration of previously conducted studies of the separation performance of four types of PSA and TSA processes.

  3. Participant intimacy: A cluster analysis of the intranuclear cascade

    International Nuclear Information System (INIS)

    Cugnon, J.; Knoll, J.; Randrup, J.

    1981-01-01

    The intranuclear cascade for relativistic nuclear collisions is analyzed in terms of clusters consisting of groups of nucleons which are dynamically linked to each other by violent interactions. The formation cross sections for the different cluster types as well as their intrinsic dynamics are studied and compared with the predictions of the linear cascade model ( rows-on-rows ). (orig.)

  4. Climate Change and Baleen Whale Trophic Cascades in Greenland

    Science.gov (United States)

    2009-09-30

    DISTRIBUTION STATEMENT A: Approved for public release; distribution is unlimited. Climate Change and Baleen Whale Trophic Cascades in Greenland...SUBTITLE Climate Change And Baleen Whale Trophic Cascades In Greenland 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S

  5. Amino acid chirality breaking by N-phosphorylation

    International Nuclear Information System (INIS)

    Zhao Yufen; Yan Qingjin.

    1995-01-01

    The chirality breaking of amino acid is a focus issue in the origin of life. For chemists, there are some interesting chemical approaches to solve the symmetry breaking problem. Our previous experiments indicated that when amino acids were phosphorylated, there were many bio-mimic reactions happened. In this paper, it was found that there had significant difference between the N-phosphoryl L- and D- amino acids such as serine and threonine. The optical rotation tracing experiments of the racemic N-phosphoamino acids also showed the similar results. The chirality breaking of amino acids by N-phosphorylation was a novel phenomena. (author). 3 refs, 1 fig. Abstract only

  6. Rat1p maintains RNA polymerase II CTD phosphorylation balance

    DEFF Research Database (Denmark)

    Jimeno-González, Silvia; Schmid, Manfred; Malagon, Francisco

    2014-01-01

    . Here we describe a function of Rat1p in regulating phosphorylation levels of the C-terminal domain (CTD) of the largest RNAPII subunit, Rpb1p, during transcription elongation. The rat1-1 mutant exhibits highly elevated levels of CTD phosphorylation as well as RNAPII distribution and transcription...... termination defects. These phenotypes are all rescued by overexpression of the CTD phosphatase Fcp1p, suggesting a functional relationship between the absence of Rat1p activity, elevated CTD phosphorylation, and transcription defects. We also demonstrate that rat1-1 cells display increased RNAPII...

  7. Rosamines targeting the cancer oxidative phosphorylation pathway.

    Directory of Open Access Journals (Sweden)

    Siang Hui Lim

    Full Text Available Reprogramming of energy metabolism is pivotal to cancer, so mitochondria are potential targets for anticancer therapy. A prior study has demonstrated the anti-proliferative activity of a new class of mitochondria-targeting rosamines. This present study describes in vitro cytotoxicity of second-generation rosamine analogs, their mode of action, and their in vivo efficacies in a tumor allografted mouse model. Here, we showed that these compounds exhibited potent cytotoxicity (average IC50<0.5 µM, inhibited Complex II and ATP synthase activities of the mitochondrial oxidative phosphorylation pathway and induced loss of mitochondrial transmembrane potential. A NCI-60 cell lines screen further indicated that rosamine analogs 4 and 5 exhibited potent antiproliferative effects with Log10GI50 = -7 (GI50 = 0.1 µM and were more effective against a colorectal cancer sub-panel than other cell lines. Preliminary in vivo studies on 4T1 murine breast cancer-bearing female BALB/c mice indicated that treatment with analog 5 in a single dosing of 5 mg/kg or a schedule dosing of 3 mg/kg once every 2 days for 6 times (q2d×6 exhibited only minimal induction of tumor growth delay. Our results suggest that rosamine analogs may be further developed as mitochondrial targeting agents. Without a doubt proper strategies need to be devised to enhance tumor uptake of rosamines, i.e. by integration to carrier molecules for better therapeutic outcome.

  8. Ion-irradiation studies of cascade damage in metals

    International Nuclear Information System (INIS)

    Averback, R.S.

    1982-03-01

    Ion-irradiation studies of the fundamental aspects of cascade damage in metals are reviewed. The emphasis of these studies has been the determination of the primary state of damage (i.e. the arrangement of atoms in the cascade region prior to thermal migration of defects). Progress has been made towards understanding the damage function (i.e. the number of Frenkel pairs produced as a function of primary recoil atom energy), the spatial configuration of vacancies and interstitials in the cascade and the cascade-induced mixing of atoms. It is concluded for these studies that the agitation of the lattice in the vicinity of energetic displacement cascades stimulates the defect motion and that such thermal spike motion induces recombination and clustering of Frenkel defects. 9 figures

  9. Geothermal segmentation of the Cascade Range in the USA

    Science.gov (United States)

    Guffanti, Marianne; Muffler, L.J.; Mariner, R.H.; Sherrod, D.R.; Smith, James G.; Blackwell, D.D.; Weaver, C.S.

    1990-01-01

    Characteristics of the crustal thermal regime of the Quaternary Cascades vary systematically along the range. Spatially congruent changes in volcanic vent distribution, volcanic extrusion rate, hydrothermal discharge rate, and regional conductive heat flow define 5 geothermal segments. These segments are, from north to south: (1) the Washington Cascades north of Mount Rainier, (2) the Cascades from Mount Rainier to Mount Hood, (3) the Oregon Cascades from south of Mount Hood to the California border, (4) northernmost California, including Mount Shasta and Medicine Lake volcano, and (5) the Lassen region of northern California. This segmentation indicates that geothermal resource potential is not uniform in the Cascade Range. Potential varies from high in parts of Oregon to low in Washington north of Mount Rainier.

  10. Cascaded Amplitude Modulations in Sound Texture Perception

    DEFF Research Database (Denmark)

    McWalter, Richard Ian; Dau, Torsten

    2017-01-01

    . In this study, we investigated the perception of sound textures that contain rhythmic structure, specifically second-order amplitude modulations that arise from the interaction of different modulation rates, previously described as "beating" in the envelope-frequency domain. We developed an auditory texture...... model that utilizes a cascade of modulation filterbanks that capture the structure of simple rhythmic patterns. The model was examined in a series of psychophysical listening experiments using synthetic sound textures-stimuli generated using time-averaged statistics measured from real-world textures....... In a texture identification task, our results indicated that second-order amplitude modulation sensitivity enhanced recognition. Next, we examined the contribution of the second-order modulation analysis in a preference task, where the proposed auditory texture model was preferred over a range of model...

  11. RG cascades in hyperbolic quiver gauge theories

    International Nuclear Information System (INIS)

    Ahl Laamara, R.; Ait Ben Haddou, M.; Belhaj, A.; Drissi, L.B.; Saidi, E.H.

    2004-01-01

    In this paper, we provide a general classification of supersymmatric QFT4s into three basic sets: ordinary, affine and indefinite classes. The last class, which has not been enough explored in literature, is shown to share most of properties of ordinary and affine super-QFT4s. This includes, amongst others, its embedding in type II string on local Calabi-Yau threefolds. We give realizations of these supersymmetric QFT4s as D-brane world volume gauge theories. A special interest is devoted to hyperbolic subset for its peculiar features and for the role it plays in type IIB background with non-zero axion. We also study RG flows and duality cascades in case of hyperbolic quiver theories. Comments regarding the full indefinite sector are made

  12. Cascaded FSO-VLC Communication System

    KAUST Repository

    Gupta, Akash

    2017-08-28

    The proposed cascaded free space optics (FSO)-visible light communication (VLC) system consists of multiple VLC access points which caters the end users connected via a decode and forward (DF) relay to the FSO backhaul link. The FSO link is assumed to be affected by path-loss, pointing error and atmospheric turbulence while the end-to-end signal-to-noise ratio (SNR) of VLC downlinks are statistically characterized considering the randomness of users position. In this study, the novel closed form expressions of the statistics like probability density function (PDF) and cumulative distribution function (CDF) of the equivalent SNR are derived. Capitalizing on these, the closed form expressions for various performance metrics such as outage probability and error probability are provided. The simulation results are provided to verify the functional curves of mathematical analysis.

  13. Congestion and cascades in payment systems

    Science.gov (United States)

    Beyeler, Walter E.; Glass, Robert J.; Bech, Morten L.; Soramäki, Kimmo

    2007-10-01

    We develop a parsimonious model of the interbank payment system. The model incorporates an endogenous instruction arrival process, a scale-free topology of payments between banks, a fixed total liquidity which limits banks’ capacity to process arriving instructions, and a global market that distributes liquidity. We find that at low liquidity the system becomes congested and payment settlement loses correlation with payment instruction arrival, becoming coupled across the network. The onset of congestion is evidently related to the relative values of three characteristic times: the time for banks’ net position to return to 0, the time for a bank to exhaust its liquidity endowment, and the liquidity market relaxation time. In the congested regime settlement takes place in cascades having a characteristic length scale. A global liquidity market substantially attenuates congestion, requiring only a small fraction of the payment-induced liquidity flow to achieve strong beneficial effects.

  14. Prolate yrast cascade in 183Tl

    International Nuclear Information System (INIS)

    Reviol, W.; Carpenter, M. P.; Janssens, R. V. F.; Jenkins, D.; Toth, K. S.; Bingham, C. R.; Riedinger, L. L.; Weintraub, W.; Cizewski, J. A.; Lauritsen, T.

    2000-01-01

    The yrast sequence in 183 Tl has been studied for the first time in recoil-mass selected γ-ray spectroscopic measurements. A rotational-like cascade of seven transitions is established down to the band head with probable spin and parity (13/2 + ). Unlike in the adjacent odd-mass Tl nuclei, prompt γ decay from the yrast band to a lower lying weakly deformed (oblate) structure is not observed. These features are consistent with the predicted drop of the prolate band head in 183 Tl compared to 185 Tl. The implications for the prolate energy minimum in odd-mass Tl nuclei at the neutron i 13/2 midshell (N=103) are discussed. (c) 2000 The American Physical Society

  15. Hadron cascade by the method of characteristics

    Energy Technology Data Exchange (ETDEWEB)

    Tsui, K.H.; Portella, H.M.; Navia, C.E.; Shigueoka, H. [Universidade Federal Fluminense, Niteroi, RJ (Brazil). Inst. de Fisica]. E-mails: tsui@if.uff.br; hmport@if.uff.br; gficnoj@if.uff.br; hisa@if.uff.br; Oliveira, L.C.S. de [Centro Brasileiro de Pesquisas Fisicas (CBPF), Rio de Janeiro, RJ (Brazil)]. E-mail: oliveira@cbpf.br

    2005-02-01

    Hadron diffusion equations with energy-dependent interaction mean free paths and inelasticities are solved using the Mellin transform. Instead of using operators on the finite difference terms, the Mellin transformed equations are Taylor expanded into a first order partial differential equation in atmospheric depth t and in the transform parameter s. Then, these equations are solved by the method of residues. For the case of a regularized power law primary spectrum these hadron fluxes are given by simple residues and one, never before mentioned, essential singularities. A comparison of our solutions with the nucleon flux measured at sea level and with the hadron fluxes measured at t = 840 g/cm{sup 2} and at sea level are made. The agreement between them is in general very good, greater than 90%. In order to check the accuracy of our calculations, a comparison between our solution and the simulated nucleon cascades is also made. (author)

  16. Cascaded face alignment via intimacy definition feature

    Science.gov (United States)

    Li, Hailiang; Lam, Kin-Man; Chiu, Man-Yau; Wu, Kangheng; Lei, Zhibin

    2017-09-01

    Recent years have witnessed the emerging popularity of regression-based face aligners, which directly learn mappings between facial appearance and shape-increment manifolds. We propose a random-forest based, cascaded regression model for face alignment by using a locally lightweight feature, namely intimacy definition feature. This feature is more discriminative than the pose-indexed feature, more efficient than the histogram of oriented gradients feature and the scale-invariant feature transform feature, and more compact than the local binary feature (LBF). Experimental validation of our algorithm shows that our approach achieves state-of-the-art performance when testing on some challenging datasets. Compared with the LBF-based algorithm, our method achieves about twice the speed, 20% improvement in terms of alignment accuracy and saves an order of magnitude on memory requirement.

  17. Seeking heavy Higgs bosons through cascade decays

    Science.gov (United States)

    Coleppa, Baradhwaj; Fuks, Benjamin; Poulose, P.; Sahoo, Shibananda

    2018-04-01

    We investigate the LHC discovery prospects for a heavy Higgs boson decaying into the standard model Higgs boson and additional weak bosons. We consider a generic model-independent new physics configuration where this decay proceeds via a cascade involving other intermediate scalar bosons and focus on an LHC final-state signature comprised either of four b -jets and two charged leptons or of four charged leptons and two b -jets. We design two analyses of the corresponding signals, and demonstrate that a 5 σ discovery at the 14 TeV LHC is possible for various combinations of the parent and daughter Higgs-boson masses. We moreover find that the standard model backgrounds can be sufficiently rejected to guarantee the reconstruction of the parent Higgs boson mass. We apply our analyses to the Type-II two-Higgs-doublet model and identify the regions of the parameter space to which the LHC is sensitive.

  18. Cascade generation in Al laser induced plasma

    Science.gov (United States)

    Nagli, Lev; Gaft, Michael; Raichlin, Yosef; Gornushkin, Igor

    2018-05-01

    We found cascade IR generation in Al laser induced plasma. This generation includes doublet transitions 3s 25s 2S1/2 → 3s24p 2P1/2,3/2 → 3s24s 2S1/2; corresponding to strong lines at 2110 and 2117 nm, and much weaker lines at 1312-1315 nm. The 3s25s2S 1/2 starting IR generation level is directly pumped from the 3s23p 2P3/2 ground level. The starting level for UV generation at 396.2 nm (transitions 3s24s 2S1/2 → 4p 2P3/2) is populated due to the fast collisional processes in the plasma plume. These differences led to different time and special dependences on the lasing in the IR and UV spectral range within the aluminum laser induced plasma.

  19. Cascade DNA nanomachine and exponential amplification biosensing.

    Science.gov (United States)

    Xu, Jianguo; Wu, Zai-Sheng; Shen, Weiyu; Xu, Huo; Li, Hongling; Jia, Lee

    2015-11-15

    DNA is a versatile scaffold for the assembly of multifunctional nanostructures, and potential applications of various DNA nanodevices have been recently demonstrated for disease diagnosis and treatment. In the current study, a powerful cascade DNA nanomachine was developed that can execute the exponential amplification of p53 tumor suppressor gene. During the operation of the newly-proposed DNA nanomachine, dual-cyclical nucleic acid strand-displacement polymerization (dual-CNDP) was ingeniously introduced, where the target trigger is repeatedly used as the fuel molecule and the nicked fragments are dramatically accumulated. Moreover, each displaced nicked fragment is able to activate the another type of cyclical strand-displacement amplification, increasing exponentially the value of fluorescence intensity. Essentially, one target binding event can induce considerable number of subsequent reactions, and the nanodevice was called cascade DNA nanomachine. It can implement several functions, including recognition element, signaling probe, polymerization primer and template. Using the developed autonomous operation of DNA nanomachine, the p53 gene can be quantified in the wide concentration range from 0.05 to 150 nM with the detection limit of 50 pM. If taking into account the final volume of mixture, the detection limit is calculated as lower as 6.2 pM, achieving an desirable assay ability. More strikingly, the mutant gene can be easily distinguished from the wild-type one. The proof-of-concept demonstrations reported herein is expected to promote the development and application of DNA nanomachine, showing great potential value in basic biology and medical diagnosis. Copyright © 2015 Elsevier B.V. All rights reserved.

  20. A minor role of WNK3 in regulating phosphorylation of renal NKCC2 and NCC co-transporters in vivo

    Directory of Open Access Journals (Sweden)

    Katsuyuki Oi

    2012-02-01

    Mutations in WNK1 and WNK4 kinase genes have been shown to cause a human hereditary hypertensive disease, pseudohypoaldosteronism type II (PHAII. We previously discovered that WNK kinases phosphorylate and activate OSR1/SPAK kinases that regulate renal SLC12A family transporters such as NKCC2 and NCC, and clarified that the constitutive activation of this cascade causes PHAII. WNK3, another member of the WNK kinase family, was reported to be a strong activator of NCC/NKCC2 when assayed in Xenopus oocytes, suggesting that WNK3 also plays a major role in regulating blood pressure and sodium reabsorption in the kidney. However, it remains to be determined whether WNK3 is in fact involved in the regulation of these transporters in vivo. To clarify this issue, we generated and analyzed WNK3 knockout mice. Surprisingly, phosphorylation and expression of OSR1, SPAK, NKCC2 and NCC did not decrease in knockout mouse kidney under normal and low-salt diets. Similarly, expression of epithelial Na channel and Na/H exchanger 3 were not affected in knockout mice. Na+ and K+ excretion in urine in WNK3 knockout mice was not affected under different salt diets. Blood pressure in WNK3 knockout mice was not lower under normal diet. However, lower blood pressure was observed in WNK3 knockout mice fed low-salt diet. WNK4 and WNK1 expression was slightly elevated in the knockout mice under low-salt diet, suggesting compensation for WNK3 knockout by these WNKs. Thus, WNK3 may have some role in the WNK-OSR1/SPAK-NCC/NKCC2 signal cascade in the kidney, but its contribution to total WNK kinase activity may be minimal.

  1. Simulated annealing of displacement cascades in FCC metals. 1. Beeler cascades

    International Nuclear Information System (INIS)

    Doran, D.G.; Burnett, R.A.

    1974-09-01

    An important source of damage to structural materials in fast reactors is the displacement of atoms from normal lattice sites. A high energy neutron may impart sufficient energy to an atom to initiate a displacement cascade consisting of a localized high density of hundreds of interstitials and vacancies. These defects subsequently interact to form clusters and to reduce their density by mutual annihilation. This short term annealing of an isolated cascade has been simulated at high and low temperatures using a correlated random walk model. The cascade representations used were developed by Beeler and the point defect properties were based on the model of γ-iron by Johnson. Low temperature anneals, characterized by no vacancy migration and a 104 site annihilation region (AR), resulted in 49 defect pairs at 20 keV and 11 pairs at 5 keV. High temperature anneals, characterized by both interstitial and vacancy migration and a 32 site AR, resulted in 68 pairs at 20 keV and 18 pairs at 5 keV when no cluster dissociation was permitted; most of the vacancies were in immobile clusters. These high temperature values dropped to 40 and 14 upon dissolution of the vacancy clusters. Parameter studies showed that, at a given temperature, the large AR resulted in about one-half as many defects as the small AR. Cluster size distributions and examples of spatial configurations are included. (U.S.)

  2. Cytochrome c Is Tyrosine 97 Phosphorylated by Neuroprotective Insulin Treatment

    Czech Academy of Sciences Publication Activity Database

    Sanderson, T. H.; Mahapatra, G.; Pecina, Petr; Ji, Q.; Yu, K.; Sinkler, Ch.; Varughese, A.; Kumar, R.; Bukowski, M. J.; Tousignant, R. N.; Salomon, A. R.; Lee, I.; Hüttemann, M.

    2013-01-01

    Roč. 8, č. 11 (2013), e78627 E-ISSN 1932-6203 Institutional support: RVO:67985823 Keywords : cytochrome c * tyrosine phosphorylation * brain ischemia * insulin Subject RIV: ED - Physiology Impact factor: 3.534, year: 2013

  3. Bad phosphorylation as a target of inhibition in oncology.

    Science.gov (United States)

    Bui, Ngoc-Linh-Chi; Pandey, Vijay; Zhu, Tao; Ma, Lan; Basappa; Lobie, Peter E

    2018-02-28

    Bcl-2 agonist of cell death (BAD) is a BH3-only member of the Bcl-2 family which possesses important regulatory function in apoptosis. BAD has also been shown to possess many non-apoptotic functions closely linked to cancer including regulation of glycolysis, autophagy, cell cycle progression and immune system development. Interestingly, BAD can be either pro-apoptotic or pro-survival depending on the phosphorylation state of three specific serine residues (human S75, S99 and S118). Expression of BAD and BAD phosphorylation patterns have been shown to influence tumor initiation and progression and play a predictive role in disease prognosis, drug response and chemosensitivity in various cancers. This review aims to summarize the current evidence on the functional role of BAD phosphorylation in human cancer and evaluate the potential utility of modulating BAD phosphorylation in cancer. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Genetics Home Reference: combined oxidative phosphorylation deficiency 1

    Science.gov (United States)

    ... a severe condition that primarily impairs neurological and liver function. Most people with combined oxidative phosphorylation deficiency 1 have severe brain dysfunction (encephalopathy) that worsens over time; they also have difficulty ...

  5. In vivo phosphorylation of a peptide tag for protein purification.

    Science.gov (United States)

    Goux, Marine; Fateh, Amina; Defontaine, Alain; Cinier, Mathieu; Tellier, Charles

    2016-05-01

    To design a new system for the in vivo phosphorylation of proteins in Escherichia coli using the co-expression of the α-subunit of casein kinase II (CKIIα) and a target protein, (Nanofitin) fused with a phosphorylatable tag. The level of the co-expressed CKIIα was controlled by the arabinose promoter and optimal phosphorylation was obtained with 2 % (w/v) arabinose as inductor. The effectiveness of the phosphorylation system was demonstrated by electrophoretic mobility shift assay (NUT-PAGE) and staining with a specific phosphoprotein-staining gel. The resulting phosphorylated tag was also used to purify the phosphoprotein by immobilized metal affinity chromatography, which relies on the specific interaction of phosphate moieties with Fe(III). The use of a single tag for both the purification and protein array anchoring provides a simple and straightforward system for protein analysis.

  6. PhosphoBase: a database of phosphorylation sites

    DEFF Research Database (Denmark)

    Blom, Nikolaj; Kreegipuu, Andres; Brunak, Søren

    1998-01-01

    PhosphoBase is a database of experimentally verified phosphorylation sites. Version 1.0 contains 156 entries and 398 experimentally determined phosphorylation sites. Entries are compiled and revised from the literature and from major protein sequence databases such as SwissProt and PIR. The entries...... provide information about the phosphoprotein and the exact position of its phosphorylation sites. Furthermore, part of the entries contain information about kinetic data obtained from enzyme assays on specific peptides. To illustrate the use of data extracted from PhosphoBase we present a sequence logo...... displaying the overall conservation of positions around serines phosphorylated by protein kinase A (PKA). PhosphoBase is available on the WWW at http://www.cbs.dtu.dk/databases/PhosphoBase/....

  7. Annealing properties of potato starches with different degrees of phosphorylation

    DEFF Research Database (Denmark)

    Muhrbeck, Per; Svensson, E

    1996-01-01

    Changes in the gelatinization temperature interval and gelatinization enthalpy with annealing time at 50 degrees C were followed for a number of potato starch samples, with different degrees of phosphorylation, using differential scanning calorimetry. The gelatinization temperature increased...

  8. Exploring the diversity of protein modifications: special bacterial phosphorylation systems

    DEFF Research Database (Denmark)

    Mijakovic, Ivan; Grangeasse, Christophe; Turgay, Kürşad

    2016-01-01

    Protein modifications not only affect protein homeostasis but can also establish new cellular protein functions and are important components of complex cellular signal sensing and transduction networks. Among these post-translational modifications, protein phosphorylation represents the one that ...

  9. CAPS Activity in Priming Vesicle Exocytosis Requires CK2 Phosphorylation*

    OpenAIRE

    Nojiri, Mari; Loyet, Kelly M.; Klenchin, Vadim A.; Kabachinski, Gregory; Martin, Thomas F. J.

    2009-01-01

    CAPS (Ca2+-dependent activator protein for secretion) functions in priming Ca2+-dependent vesicle exocytosis, but the regulation of CAPS activity has not been characterized. Here we show that phosphorylation by protein kinase CK2 is required for CAPS activity. Dephosphorylation eliminated CAPS activity in reconstituting Ca2+-dependent vesicle exocytosis in permeable and intact PC12 cells. Ser-5, -6, and -7 and Ser-1281 were identified by mass spectrometry as the major phosphorylation sites in...

  10. LRRK2 mediated Rab8a phosphorylation promotes lipid storage.

    Science.gov (United States)

    Yu, Miao; Arshad, Muhammad; Wang, Wenmin; Zhao, Dongyu; Xu, Li; Zhou, Linkang

    2018-02-27

    Several mutations in leucine rich repeat kinase 2 (LRRK2) gene have been associated with pathogenesis of Parkinson's disease (PD), a neurodegenerative disorder marked by resting tremors, and rigidity, leading to Postural instability. It has been revealed that mutations that lead to an increase of kinase activity of LRRK2 protein are significantly associated with PD pathogenesis. Recent studies have shown that some Rab GTPases, especially Rab8, serve as substrates of LRRK2 and undergo phosphorylation in its switch II domain upon interaction. Current study was performed in order to find out the effects of the phosphorylation of Rab8 and its mutants on lipid metabolism and lipid droplets growth. The phosphorylation status of Rab8a was checked by phos-tag gel. Point mutant construct were generated to investigate the function of Rab8a. 3T3L1 cells were transfected with indicated plasmids and the lipid droplets were stained with Bodipy. Fluorescent microscopy experiments were performed to examine the sizes of lipid droplets. The interactions between Rab8a and Optineurin were determined by immunoprecipitation and western blot. Our assays demonstrated that Rab8a was phosphorylated by mutated LRRK2 that exhibits high kinase activity. Phosphorylation of Rab8a on amino acid residue T72 promoted the formation of large lipid droplets. T72D mutant of Rab8a had higher activity to promote the formation of large lipid droplets compared with wild type Rab8a, with increase in average diameter of lipid droplets from 2.10 μm to 2.46 μm. Moreover, phosphorylation of Rab8a weakened the interaction with its effector Optineurin. Y1699C mutated LRRK2 was able to phosphorylate Rab8a and phosphorylation of Rab8a on site 72 plays important role in the fusion and enlargement of lipid droplets. Taken together, our study suggests an indirect relationship between enhanced lipid storage capacity and PD pathogenesis.

  11. Cortactin Tyrosine Phosphorylation Promotes Its Deacetylation and Inhibits Cell Spreading

    Science.gov (United States)

    Meiler, Eugenia; Nieto-Pelegrín, Elvira; Martinez-Quiles, Narcisa

    2012-01-01

    Background Cortactin is a classical Src kinase substrate that participates in actin cytoskeletal dynamics by activating the Arp2/3 complex and interacting with other regulatory proteins, including FAK. Cortactin has various domains that may contribute to the assembly of different protein platforms to achieve process specificity. Though the protein is known to be regulated by post-translational modifications such as phosphorylation and acetylation, how tyrosine phosphorylation regulates cortactin activity is poorly understood. Since the basal level of tyrosine phosphorylation is low, this question must be studied using stimulated cell cultures, which are physiologically relevant but unreliable and difficult to work with. In fact, their unreliability may be the cause of some contradictory findings about the dynamics of tyrosine phosphorylation of cortactin in different processes. Methodology/Principal Findings In the present study, we try to overcome these problems by using a Functional Interaction Trap (FIT) system, which involves cotransfecting cells with a kinase (Src) and a target protein (cortactin), both of which are fused to complementary leucine-zipper domains. The FIT system allowed us to control precisely the tyrosine phosphorylation of cortactin and explore its relationship with cortactin acetylation. Conclusions/Significance Using this system, we provide definitive evidence that a competition exists between acetylation and tyrosine phosphorylation of cortactin and that phosphorylation inhibits cell spreading. We confirmed the results from the FIT system by examining endogenous cortactin in different cell types. Furthermore, we demonstrate that cell spreading promotes the association of cortactin and FAK and that tyrosine phosphorylation of cortactin disrupts this interaction, which may explain how it inhibits cell spreading. PMID:22479425

  12. Protein S blocks the extrinsic apoptotic cascade in tissue plasminogen activator/N-methyl D-aspartate-treated neurons via Tyro3-Akt-FKHRL1 signaling pathway

    Directory of Open Access Journals (Sweden)

    Freeman Robert S

    2011-02-01

    Full Text Available Abstract Background Thrombolytic therapy with tissue plasminogen activator (tPA benefits patients with acute ischemic stroke. However, tPA increases the risk for intracerebral bleeding and enhances post-ischemic neuronal injury if administered 3-4 hours after stroke. Therefore, combination therapies with tPA and neuroprotective agents have been considered to increase tPA's therapeutic window and reduce toxicity. The anticoagulant factor protein S (PS protects neurons from hypoxic/ischemic injury. PS also inhibits N-methyl-D-aspartate (NMDA excitotoxicity by phosphorylating Bad and Mdm2 which blocks the downstream steps in the intrinsic apoptotic cascade. To test whether PS can protect neurons from tPA toxicity we studied its effects on tPA/NMDA combined injury which in contrast to NMDA alone kills neurons by activating the extrinsic apoptotic pathway. Neither Bad nor Mdm2 which are PS's targets and control the intrinsic apoptotic pathway can influence the extrinsic cascade. Thus, based on published data one cannot predict whether PS can protect neurons from tPA/NMDA injury by blocking the extrinsic pathway. Neurons express all three TAM (Tyro3, Axl, Mer receptors that can potentially interact with PS. Therefore, we studied whether PS can activate TAM receptors during a tPA/NMDA insult. Results We show that PS protects neurons from tPA/NMDA-induced apoptosis by suppressing Fas-ligand (FasL production and FasL-dependent caspase-8 activation within the extrinsic apoptotic pathway. By transducing neurons with adenoviral vectors expressing the kinase-deficient Akt mutant AktK179A and a triple FKHRL1 Akt phosphorylation site mutant (FKHRL1-TM, we show that Akt activation and Akt-mediated phosphorylation of FKHRL1, a member of the Forkhead family of transcription factors, are critical for FasL down-regulation and caspase-8 inhibition. Using cultured neurons from Tyro3, Axl and Mer mutants, we show that Tyro3, but not Axl and Mer, mediates

  13. Protein phosphorylation in isolated hepatocytes of septic and endotoxemic rats

    International Nuclear Information System (INIS)

    Deaciuc, I.V.; Spitzer, J.A.

    1989-01-01

    The purpose of this study was to investigate possible alterations induced by sepsis and endotoxicosis in the late phase of Ca2+-dependent signaling in rat liver. Hepatocytes isolated from septic or chronically endotoxin (ET)-treated rats were labeled with [32P]H3PO4 and stimulated with various agents. Proteins were resolved by one-dimensional polyacrylamide gel electrophoresis and autoradiographed. Vasopressin (VP)- and phenylephrine (PE)-induced responses were attenuated in both septic and ET-treated rats for cytosolic and membrane proteins compared with their respective controls. Glucagon and 12-O-myristate phorbol-13-acetate (TPA) affected only the phosphorylation of membrane proteins. Glucagon-induced changes in the phosphorylation of membrane proteins were affected by both sepsis and endotoxicosis, whereas TPA-stimulated phosphorylation was lowered only in endotoxicosis. Response to the Ca2+ ionophore A23187 was depressed in septic rats for cytosolic proteins. The phosphorylation of two cytosolic proteins, i.e., 93 and 61 kDa (previously identified as glycogen phosphorylase and pyruvate kinase, respectively), in response to VP, PE, and A23187 was severely impaired by endotoxicosis and sepsis. TPA did not affect the phosphorylation state of these two proteins. The results show that sepsis and endotoxicosis produce perturbations of the phosphorylation step in Ca2+ transmembrane signaling. Such changes can explain alterations of glycogenolysis and gluconeogenesis associated with sepsis and endotoxicosis

  14. Characterisation and properties of homo- and heterogenously phosphorylated nanocellulose.

    Science.gov (United States)

    Kokol, Vanja; Božič, Mojca; Vogrinčič, Robert; Mathew, Aji P

    2015-07-10

    Nano-sized cellulose ester derivatives having phosphoryl side groups were synthesised by phosphorylation of nanofibrilated cellulose (NFC) and nanocrystaline cellulose (NCC), using different heterogeneous (in water) and homogeneous (in molten urea) processes with phosphoric acid as phosphoryl donor. The phosphorylation mechanism, efficacy, stability, as well as its influence on the NC crystallinity and thermal properties, were evaluated using ATR-FTIR and (13)C NMR spectroscopies, potentiometric titration, capillary electrophoresis, X-ray diffraction, colorimetry, thermogravimmetry and SEM. Phosphorylation under both processes created dibasic phosphate and monobasic tautomeric phosphite groups at C6 and C3 positioned hydroxyls of cellulose, yielded 60-fold (∼1,173 mmol/kg) and 2-fold (∼1.038 mmol/kg) higher surface charge density for p-NFC and p-NCC, respectively, under homogenous conditions. None of the phosphorylations affected neither the NC crystallinity degree nor the structure, and noticeably preventing the derivatives from weight loss during the pyrolysis process. The p-NC showed high hydrolytic stability to water at all pH mediums. Reusing of the treatment bath was examined after the heterogeneous process. Copyright © 2015 Elsevier Ltd. All rights reserved.

  15. Protein phosphorylation and its role in archaeal signal transduction

    Science.gov (United States)

    Esser, Dominik; Hoffmann, Lena; Pham, Trong Khoa; Bräsen, Christopher; Qiu, Wen; Wright, Phillip C.; Albers, Sonja-Verena; Siebers, Bettina

    2016-01-01

    Reversible protein phosphorylation is the main mechanism of signal transduction that enables cells to rapidly respond to environmental changes by controlling the functional properties of proteins in response to external stimuli. However, whereas signal transduction is well studied in Eukaryotes and Bacteria, the knowledge in Archaea is still rather scarce. Archaea are special with regard to protein phosphorylation, due to the fact that the two best studied phyla, the Euryarchaeota and Crenarchaeaota, seem to exhibit fundamental differences in regulatory systems. Euryarchaeota (e.g. halophiles, methanogens, thermophiles), like Bacteria and Eukaryotes, rely on bacterial-type two-component signal transduction systems (phosphorylation on His and Asp), as well as on the protein phosphorylation on Ser, Thr and Tyr by Hanks-type protein kinases. Instead, Crenarchaeota (e.g. acidophiles and (hyper)thermophiles) only depend on Hanks-type protein phosphorylation. In this review, the current knowledge of reversible protein phosphorylation in Archaea is presented. It combines results from identified phosphoproteins, biochemical characterization of protein kinases and protein phosphatases as well as target enzymes and first insights into archaeal signal transduction by biochemical, genetic and polyomic studies. PMID:27476079

  16. ZDHHC3 Tyrosine Phosphorylation Regulates Neural Cell Adhesion Molecule Palmitoylation

    Science.gov (United States)

    Lievens, Patricia Marie-Jeanne; Kuznetsova, Tatiana; Kochlamazashvili, Gaga; Cesca, Fabrizia; Gorinski, Natalya; Galil, Dalia Abdel; Cherkas, Volodimir; Ronkina, Natalia; Lafera, Juri; Gaestel, Matthias

    2016-01-01

    The neural cell adhesion molecule (NCAM) mediates cell-cell and cell-matrix adhesion. It is broadly expressed in the nervous system and regulates neurite outgrowth, synaptogenesis, and synaptic plasticity. Previous in vitro studies revealed that palmitoylation of NCAM is required for fibroblast growth factor 2 (FGF2)-stimulated neurite outgrowth and identified the zinc finger DHHC (Asp-His-His-Cys)-containing proteins ZDHHC3 and ZDHHC7 as specific NCAM-palmitoylating enzymes. Here, we verified that FGF2 controlled NCAM palmitoylation in vivo and investigated molecular mechanisms regulating NCAM palmitoylation by ZDHHC3. Experiments with overexpression and pharmacological inhibition of FGF receptor (FGFR) and Src revealed that these kinases control tyrosine phosphorylation of ZDHHC3 and that ZDHHC3 is phosphorylated by endogenously expressed FGFR and Src proteins. By site-directed mutagenesis, we found that Tyr18 is an FGFR1-specific ZDHHC3 phosphorylation site, while Tyr295 and Tyr297 are specifically phosphorylated by Src kinase in cell-based and cell-free assays. Abrogation of tyrosine phosphorylation increased ZDHHC3 autopalmitoylation, enhanced interaction with NCAM, and upregulated NCAM palmitoylation. Expression of ZDHHC3 with tyrosine mutated in cultured hippocampal neurons promoted neurite outgrowth. Our findings for the first time highlight that FGFR- and Src-mediated tyrosine phosphorylation of ZDHHC3 modulates ZDHHC3 enzymatic activity and plays a role in neuronal morphogenesis. PMID:27247265

  17. Cholinergic regulation of protein phosphorylation in bovine adrenal chromaffin cells

    International Nuclear Information System (INIS)

    Haycock, J.W.; Browning, M.D.; Greengard, P.

    1988-01-01

    Chromaffin cells were isolated from bovine adrenal medullae and maintained in primary culture. After prelabeling with 32 PO 4 , exposure of the chromaffin cells to acetylcholine increased the phosphorylation of a M/sub r/ ≅ 100,000 protein and a M/sub r/ ≅ 60,000 protein (tyrosine hydroxylase), visualized after separation of total cellular proteins in NaDodSO 4 /polyacrylamide gels. Immunoprecipitation with antibodies to three known phosphoproteins (100-kDa, 87-kDa, and protein III) revealed an acetylcholine-dependent phosphorylation of these proteins. These three proteins were also shown to be present in bovine adrenal chromaffin cells by immunolabeling techniques. 100-kDa is a M/sub r/ ≅ 100,000 protein selectively phosphorylated by calcium/calmodulin-dependent protein kinase III, 87-kDa is a M/sub r/ ≅ 87,000 protein selectively phosphorylated by protein kinase C, and protein III is a phosphoprotein doublet of M/sub r/ ≅ 74,000 (IIIa) and M/sub r/ ≅ 55,000 (IIIb) phosphorylated by cAMP-dependent protein kinase and calcium/calmodulin-dependent protein kinase I. The data demonstrate that cholinergic activation of chromaffin cells increases the phosphorylation of several proteins and that several protein kinase systems may be involved in these effects

  18. Energy and carbon balances of wood cascade chains

    Energy Technology Data Exchange (ETDEWEB)

    Sathre, Roger; Gustavsson, Leif [Ecotechnology, Mid Sweden University, SE-831 25 OEstersund (Sweden)

    2006-07-15

    In this study we analyze the energy and carbon balances of various cascade chains for recovered wood lumber. Post-recovery options include reuse as lumber, reprocessing as particleboard, pulping to form paper products, and burning for energy recovery. We compare energy and carbon balances of chains of cascaded products to the balances of products obtained from virgin wood fiber or from non-wood material. We describe and quantify several mechanisms through which cascading can affect the energy and carbon balances: direct cascade effects due to different properties and logistics of virgin and recovered materials, substitution effects due to the reduced demand for non-wood materials when wood is cascaded, and land use effects due to alternative possible land uses when less timber harvest is needed because of wood cascading. In some analyses we assume the forest is a limiting resource, and in others we include a fixed amount of forest land from which biomass can be harvested for use as material or biofuel. Energy and carbon balances take into account manufacturing processes, recovery and transportation energy, material recovery losses, and forest processes. We find that land use effects have the greatest impact on energy and carbon balances, followed by substitution effects, while direct cascade effects are relatively minor. (author)

  19. A thermal modelling of displacement cascades in uranium dioxide

    Energy Technology Data Exchange (ETDEWEB)

    Martin, G., E-mail: guillaume.martin@cea.fr [CEA – DEN/DEC/SESC/LLCC, Bât. 352, 13108 Saint-Paul-Lez-Durance Cedex (France); Garcia, P.; Sabathier, C. [CEA – DEN/DEC/SESC/LLCC, Bât. 352, 13108 Saint-Paul-Lez-Durance Cedex (France); Devynck, F.; Krack, M. [Laboratory for Reactor Physics and Systems Behaviour, Paul Scherrer Institute, CH-5232 Villigen PSI (Switzerland); Maillard, S. [CEA – DEN/DEC/SESC/LLCC, Bât. 352, 13108 Saint-Paul-Lez-Durance Cedex (France)

    2014-05-01

    The space and time dependent temperature distribution was studied in uranium dioxide during displacement cascades simulated by classical molecular dynamics (MD). The energy for each simulated radiation event ranged between 0.2 keV and 20 keV in cells at initial temperatures of 700 K or 1400 K. Spheres into which atomic velocities were rescaled (thermal spikes) have also been simulated by MD to simulate the thermal excitation induced by displacement cascades. Equipartition of energy was shown to occur in displacement cascades, half of the kinetic energy of the primary knock-on atom being converted after a few tenths of picoseconds into potential energy. The kinetic and potential parts of the system energy are however subjected to little variations during dedicated thermal spike simulations. This is probably due to the velocity rescaling process, which impacts a large number of atoms in this case and would drive the system away from a dynamical equilibrium. This result makes questionable MD simulations of thermal spikes carried out up to now (early 2014). The thermal history of cascades was compared to the heat equation solution of a punctual thermal excitation in UO{sub 2}. The maximum volume brought to a temperature above the melting temperature during the simulated cascade events is well reproduced by this simple model. This volume eventually constitutes a relevant estimate of the volume affected by a displacement cascade in UO{sub 2}. This definition of the cascade volume could also make sense in other materials, like iron.

  20. Cascade fuzzy control for gas engine driven heat pump

    International Nuclear Information System (INIS)

    Li Shuze; Zhang Wugao; Zhang Rongrong; Lv Dexu; Huang Zhen

    2005-01-01

    In addition to absorption chillers, today's gas cooling technology includes gas engine driven heat pump systems (GEHP) in a range of capacities and temperature capacities suitable for most commercial air conditioning and refrigeration applications. Much is expected from GEHPs as a product that would help satisfy the air conditioning system demand from medium and small sized buildings, restrict electric power demand peaks in summer and save energy in general. This article describes a kind of control strategy for a GEHP, a cascade fuzzy control. GEHPs have large and varying time constants and their dynamic modeling cannot be easily achieved. A cascade control strategy is effective for systems that have large time constants and disturbances, and a fuzzy control strategy is fit for a system that lacks an accurate model. This cascade fuzzy control structure brings together the best merits of fuzzy control and cascade control structures. The performance of the cascade fuzzy control is compared to that of a cascade PI (proportional and integral) control strategy, and it is shown by example that the cascade fuzzy control strategy gives a better performance, reduced reaction time and smaller overshoot temperature

  1. Network analysis of epidermal growth factor signaling using integrated genomic, proteomic and phosphorylation data.

    Directory of Open Access Journals (Sweden)

    Katrina M Waters

    Full Text Available To understand how integration of multiple data types can help decipher cellular responses at the systems level, we analyzed the mitogenic response of human mammary epithelial cells to epidermal growth factor (EGF using whole genome microarrays, mass spectrometry-based proteomics and large-scale western blots with over 1000 antibodies. A time course analysis revealed significant differences in the expression of 3172 genes and 596 proteins, including protein phosphorylation changes measured by western blot. Integration of these disparate data types showed that each contributed qualitatively different components to the observed cell response to EGF and that varying degrees of concordance in gene expression and protein abundance measurements could be linked to specific biological processes. Networks inferred from individual data types were relatively limited, whereas networks derived from the integrated data recapitulated the known major cellular responses to EGF and exhibited more highly connected signaling nodes than networks derived from any individual dataset. While cell cycle regulatory pathways were altered as anticipated, we found the most robust response to mitogenic concentrations of EGF was induction of matrix metalloprotease cascades, highlighting the importance of the EGFR system as a regulator of the extracellular environment. These results demonstrate the value of integrating multiple levels of biological information to more accurately reconstruct networks of cellular response.

  2. Network Analysis of Epidermal Growth Factor Signaling using Integrated Genomic, Proteomic and Phosphorylation Data

    Energy Technology Data Exchange (ETDEWEB)

    Waters, Katrina M.; Liu, Tao; Quesenberry, Ryan D.; Willse, Alan R.; Bandyopadhyay, Somnath; Kathmann, Loel E.; Weber, Thomas J.; Smith, Richard D.; Wiley, H. S.; Thrall, Brian D.

    2012-03-29

    To understand how integration of multiple data types can help decipher cellular responses at the systems level, we analyzed the mitogenic response of human mammary epithelial cells to epidermal growth factor (EGF) using whole genome microarrays, mass spectrometry-based proteomics and large-scale western blots with over 1000 antibodies. A time course analysis revealed significant differences in the expression of 3172 genes and 596 proteins, including protein phosphorylation changes measured by western blot. Integration of these disparate data types showed that each contributed qualitatively different components to the observed cell response to EGF and that varying degrees of concordance in gene expression and protein abundance measurements could be linked to specific biological processes. Networks inferred from individual data types were relatively limited, whereas networks derived from the integrated data recapitulated the known major cellular responses to EGF and exhibited more highly connected signaling nodes than networks derived from any individual dataset. While cell cycle regulatory pathways were altered as anticipated, we found the most robust response to mitogenic concentrations of EGF was induction of matrix metalloprotease cascades, highlighting the importance of the EGFR system as a regulator of the extracellular environment. These results demonstrate the value of integrating multiple levels of biological information to more accurately reconstruct networks of cellular response.

  3. Cascade multiplicity inside deuteron in Π d high energy collisions

    International Nuclear Information System (INIS)

    Kisielewska, D.

    1983-01-01

    Multiplicity distribution of double scattering events is analysed using the additive quark model including the cascading effect. The mean multiplicity of particles produced in the process of cascading estimated for Π d experiments at 100, 205 and 360 GeV/c is equal to 1.15 ± .31. This value does not depend on the momentum of the incident pion. Some indications are found that the probability of cascading depends on multiplicity of the collision with the first nucleon and is smaller for low multiplicities. (author)

  4. Criticality safety study of shutdown diffusion cascade coolers

    International Nuclear Information System (INIS)

    Paschal, L.S.; Basoglu, B.; Bentley, C.L.; Dunn, M.E.

    1996-01-01

    Gaseous diffusion plants use cascade coolers in the production of highly enriched uranium (HEU) to remove heat from the enriched stream of UF 6 . The cascade coolers operate like shell and tube heat exchangers with the UF 6 on the shell side and Freon on the tube side. Recirculating cooling water (RCW) in condensers is used to cool the Freon. A criticality safety analysis was previously performed for cascade coolers during normal operation. The purpose of this paper is to evaluate several different hypothetical accidents regarding RCW ingress into the cooler to determine whether criticality safety concerns exist

  5. Increasing sensitivity of MOS dosemeters in cascade connection

    International Nuclear Information System (INIS)

    Vychytil, F.; Cechak, T.; Gerndt, J.; Petr, I.

    1978-01-01

    The possibilities of increasing the sensitivity of MOS transistors in their cascade connection were studied theoretically and experimentally. The measurements confirmed the presumption that the instability of cascade-connected MOS transistors increased with the square of the number of transistors in the system. This allows systems to be formed with different sensitivity to ionizing radiation by encasing 10 to 10 4 transistors connected in cascade, which is technologically feasible. The procedure is also acceptable from the point of view of cost. (Z.M.)

  6. Revised tephra volumes for Cascade Range volcanoes

    Science.gov (United States)

    Nathenson, Manuel

    2017-01-01

    Isopach maps from tephra eruptions from Mount St. Helens were reported in Carey et al. (1995) and for tephra eruptions from Glacier Peak in Gardner et al. (1998). For exponential thinning, the isopach data only define a single slope on a log thickness versus square root of area plot. Carey et al. (1995) proposed a model that was used to estimate a second slope, and volumes were presented in both studies using this model. A study by Sulpizio (2005) for estimating the second slope and square root of area where the lines intersect involves a systematic analysis of many eruptions to provide correlation equations. The purpose of this paper is to recalculate the volumes of Cascades eruptions and compare results from the two methods. In order to gain some perspective on the methods for estimating the second slope, we use data for thickness versus distance beyond the last isopach that are available for some of the larger eruptions in the Cascades. The thickness versus square root of area method is extended to thickness versus distance by developing an approximate relation between the two assuming elliptical isopachs with the source at one of the foci. Based on the comparisons made between the Carey et al. (1995) and Sulpizio (2005) methods, it is felt that the later method provides a better estimate of the second slope. For Mount St. Helens, the estimates of total volume using the Sulpizio (2005) method are generally smaller than those using the Carey et al. (1995) method. For the volume estimates of Carey et al. (1995), the volume of the May 18, 1980, eruption of Mount St. Helens is smaller than six of the eight previous eruptions. With the new volumes using the Sulpizio (2005) method, the 1980 eruption is smaller in volume than the upper end of the range for only three of the layers (Wn, Ye, and Yn) and is the same size as layer We. Thus the 1980 eruption becomes representative of the mid-range of volumes rather than being in the lower range.

  7. KSR1 is a functional protein kinase capable of serine autophosphorylation and direct phosphorylation of MEK1

    International Nuclear Information System (INIS)

    Goettel, Jeremy A.; Liang, Dongchun; Hilliard, Valda C.; Edelblum, Karen L.; Broadus, Matthew R.; Gould, Kathleen L.; Hanks, Steven K.; Polk, D. Brent

    2011-01-01

    The extracellular signal-regulated kinase/mitogen-activated protein kinase (ERK/MAPK) pathway is a highly conserved signaling pathway that regulates diverse cellular processes including differentiation, proliferation, and survival. Kinase suppressor of Ras-1 (KSR1) binds each of the three ERK cascade components to facilitate pathway activation. Even though KSR1 contains a C-terminal kinase domain, evidence supporting the catalytic function of KSR1 remains controversial. In this study, we produced recombinant wild-type or kinase-inactive (D683A/D700A) KSR1 proteins in Escherichia coli to test the hypothesis that KSR1 is a functional protein kinase. Recombinant wild-type KSR1, but not recombinant kinase-inactive KSR1, underwent autophosphorylation on serine residue(s), phosphorylated myelin basic protein (MBP) as a generic substrate, and phosphorylated recombinant kinase-inactive MAPK/ERK kinase-1 (MEK1). Furthermore, FLAG immunoprecipitates from KSR1 -/- colon epithelial cells stably expressing FLAG-tagged wild-type KSR1 (+KSR1), but not vector (+vector) or FLAG-tagged kinase-inactive KSR1 (+D683A/D700A), were able to phosphorylate kinase-inactive MEK1. Since TNF activates the ERK pathway in colon epithelial cells, we tested the biological effects of KSR1 in the survival response downstream of TNF. We found that +vector and +D683A/D700A cells underwent apoptosis when treated with TNF, whereas +KSR1 cells were resistant. However, +KSR1 cells were sensitized to TNF-induced cell loss in the absence of MEK kinase activity. These data provide clear evidence that KSR1 is a functional protein kinase, MEK1 is an in vitro substrate of KSR1, and the catalytic activities of both proteins are required for eliciting cell survival responses downstream of TNF.

  8. Raptor is phosphorylated by cdc2 during mitosis.

    Directory of Open Access Journals (Sweden)

    Dana M Gwinn

    2010-02-01

    Full Text Available The appropriate control of mitotic entry and exit is reliant on a series of interlocking signaling events that coordinately drive the biological processes required for accurate cell division. Overlaid onto these signals that promote orchestrated cell division are checkpoints that ensure appropriate mitotic spindle formation, a lack of DNA damage, kinetochore attachment, and that each daughter cell has the appropriate complement of DNA. We recently discovered that AMP-activated protein kinase (AMPK modulates the G2/M phase of cell cycle progression in part through its suppression of mammalian target of rapamycin (mTOR signaling. AMPK directly phosphorylates the critical mTOR binding partner raptor inhibiting mTORC1 (mTOR-raptor rapamycin sensitive mTOR kinase complex 1. As mTOR has been previously tied to mitotic control, we examined further how raptor may contribute to this process.We have discovered that raptor becomes highly phosphorylated in cells in mitosis. Utilizing tandem mass spectrometry, we identified a number of novel phosphorylation sites in raptor, and using phospho-specific antibodies demonstrated that raptor becomes phosphorylated on phospho-serine/threonine-proline sites in mitosis. A combination of site-directed mutagenesis in a tagged raptor cDNA and analysis with a series of new phospho-specific antibodies generated against different sites in raptor revealed that Serine 696 and Threonine 706 represent two key sites in raptor phosphorylated in mitosis. We demonstrate that the mitotic cyclin-dependent kinase cdc2/CDK1 is the kinase responsible for phosphorylating these sites, and its mitotic partner Cyclin B efficiently coimmunoprecipitates with raptor in mitotic cells.This study demonstrates that the key mTOR binding partner raptor is directly phosphorylated during mitosis by cdc2. This reinforces previous studies suggesting that mTOR activity is highly regulated and important for mitotic progression, and points to a direct

  9. Mode structure of a quantum cascade laser

    Science.gov (United States)

    Bogdanov, A. A.; Suris, R. A.

    2011-03-01

    We analyze the mode structure of a quantum cascade laser (QCL) cavity considering the surface plasmon-polariton modes and familiar modes of hollow resonator jointly, within a single model. We present a comprehensive mode structure analysis of the laser cavity, varying its geometric parameters and free electron concentration inside cavity layers within a wide range. Our analysis covers, in particular, the cases of metal-insulator-metal and insulator-metal-insulator waveguides. We discuss the phenomenon of negative dispersion for eigenmodes in detail and explain the nature of this phenomenon. We specify a waveguide parameters domain in which negative dispersion exists. The mode structure of QCL cavity is considered in the case of the anisotropic electrical properties of the waveguide materials. We show that anisotropy of the waveguide core results in propagation of Langmuir modes that are degenerated in the case of the isotropic core. Comparative analysis of optical losses due to free carrier absorption is presented for different modes within the frequency range from terahertz to ultraviolet frequencies.

  10. MCDF calculations of Auger cascade processes

    Science.gov (United States)

    Beerwerth, Randolf; Fritzsche, Stephan

    2017-10-01

    We model the multiple ionization of near-neutral core-excited atoms where a cascade of Auger processes leads to the emission of several electrons. We utilize the multiconfiguration Dirac-Fock (MCDF) method to generate approximate wave functions for all fine-structure levels and to account for all decays between them. This approach allows to compute electron spectra, the population of final-states and ion yields, that are accessible in many experiments. Furthermore, our approach is based on the configuration interaction method. A careful treatment of correlation between electronic configurations enables one to model three-electron processes such as an Auger decay that is accompanied by an additional shake-up transition. Here, this model is applied to the triple ionization of atomic cadmium, where we show that the decay of inner-shell 4p holes to triply-charged final states is purely due to the shake-up transition of valence 5s electrons. Contribution to the Topical Issue "Atomic and Molecular Data and their Applications", edited by Gordon W.F. Drake, Jung-Sik Yoon, Daiji Kato, Grzegorz Karwasz.

  11. Feeding supermassive black holes by collisional cascades

    Science.gov (United States)

    Faber, Christian; Dehnen, Walter

    2018-05-01

    The processes driving gas accretion on to supermassive black holes (SMBHs) are still poorly understood. Angular momentum conservation prevents gas within ˜10 pc of the black hole from reaching radii ˜10-3 pc where viscous accretion becomes efficient. Here we present simulations of the collapse of a clumpy shell of swept-up isothermal gas, which is assumed to have formed as a result of feedback from a previous episode of AGN activity. The gas falls towards the SMBH forming clumps and streams, which intersect, collide, and often form a disc. These collisions promote partial cancellations of angular momenta, resulting in further infall and more collisions. This continued collisional cascade generates a tail of gas with sufficiently small angular momenta and provides a viable route for gas inflow to sub-parsec scales. The efficiency of this process hardly depends on details, such as gas temperature, initial virial ratio and power spectrum of the gas distribution, as long as it is not strongly rotating. Adding star formation to this picture might explain the near-simultaneous formation of the S-stars (from tidally disrupted binaries formed in plunging gas streams) and the sub-parsec young stellar disc around Sgr A⋆.

  12. Depression: An Immuno-Inflammatory Cascade

    Directory of Open Access Journals (Sweden)

    Vivek Sharma

    2016-06-01

    Full Text Available Major depressive disorder also known as clinical depression, unipolar depression or depression is associated with significant morbidity, mortality, high suicidal tendencies and deaths. Preclinical and clinical studies suggest that psychiatric illnesses like MDD, are associated with inflammatory processes. While it is unlikely that major depressive disorder is a primary and lsquo;inflammatory' disorder, there is now evidence to suggest that inflammation play a subtle role in the pathophysiology of major depressive disorder. The inflammation in depression cascade pin points to the origin from immune hyperactivity and thus a new theory that explains role of immune system mediated inflammation has been accepted and researched upon. widely. This theory states that depression is accompanied by altered immune function and activation of the inflammatory response system. This theory is strengthened form the fact that the current therapeutic options which mainly target neurotransmitters, are not effective in many patients and these patients has been found to be associated with elevated levels of inflammatory mediators specifically cytokines. It is reported more recently that other risk factors for depression, including psychosocial stress, psychological trauma, sleep disturbance and pain, also increases inflammatory processes. Thus the intervention in the immune system originated from inflammatory cytokines seems a therapeutically viable option in the field of depression research. [Archives Medical Review Journal 2016; 25(2.000: 223-240

  13. Dissipation range turbulent cascades in plasmas

    International Nuclear Information System (INIS)

    Terry, P. W.; Almagri, A. F.; Forest, C. B.; Nornberg, M. D.; Rahbarnia, K.; Sarff, J. S.; Fiksel, G.; Hatch, D. R.; Jenko, F.; Prager, S. C.; Ren, Y.

    2012-01-01

    Dissipation range cascades in plasma turbulence are described and spectra are formulated from the scaled attenuation in wavenumber space of the spectral energy transfer rate. This yields spectra characterized by the product of a power law and exponential fall-off, applicable to all scales. Spectral indices of the power law and exponential fall-off depend on the scaling of the dissipation, the strength of the nonlinearity, and nonlocal effects when dissipation rates of multiple fluctuation fields are different. The theory is used to derive spectra for MHD turbulence with magnetic Prandtl number greater than unity, extending previous work. The theory is also applied to generic plasma turbulence by considering the spectrum from damping with arbitrary wavenumber scaling. The latter is relevant to ion temperature gradient turbulence modeled by gyrokinetics. The spectrum in this case has an exponential component that becomes weaker at small scale, giving a power law asymptotically. Results from the theory are compared to three very different types of turbulence. These include the magnetic plasma turbulence of the Madison Symmetric Torus, the MHD turbulence of liquid metal in the Madison Dynamo Experiment, and gyrokinetic simulation of ion temperature gradient turbulence.

  14. Cascading reminiscence bumps in popular music.

    Science.gov (United States)

    Krumhansl, Carol Lynne; Zupnick, Justin Adam

    2013-10-01

    Autobiographical memories are disproportionately recalled for events in late adolescence and early adulthood, a phenomenon called the reminiscence bump. Previous studies on music have found autobiographical memories and life-long preferences for music from this period. In the present study, we probed young adults' personal memories associated with top hits over 5-and-a-half decades, as well as the context of their memories and their recognition of, preference for, quality judgments of, and emotional reactions to that music. All these measures showed the typical increase for music released during the two decades of their lives. Unexpectedly, we found that the same measures peaked for the music of participants' parents' generation. This finding points to the impact of music in childhood and suggests that these results reflect the prevalence of music in the home environment. An earlier peak occurred for 1960s music, which may be explained by its quality or by its transmission through two generations. We refer to this pattern of musical cultural transmission over generations as cascading reminiscence bumps.

  15. Chemical sensors based on quantum cascade lasers

    Science.gov (United States)

    Tittel, Frank K.; Kosterev, Anatoliy A.; Rochat, Michel; Beck, Mattias; Faist, Jerome

    2002-09-01

    There is an increasing need in many chemical sensing applications ranging from industrial process control to environmental science and medical diagnostics for fast, sensitive, and selective gas detection based on laser spectroscopy. The recent availability of novel pulsed and cw quantum cascade distributed feedback (QC-DFB) lasers as mid-infrared spectroscopic sources address this need. A number of spectroscopic techniques have been demonstrated. For example, the authors have employed QC-DFB lasers for the monitoring and quantification of several trace gases and isotopic species in ambient air at ppmv and ppbv levels by means of direct absorption, wavelength modulation, cavity enhanced and cavity ringdown spectroscopy. In this work, pulsed thermoelectrically cooled QC-DFB lasers operating at ~15.6 μm were characterized for spectroscopic gas sensing applications. A new method for wavelength scanning based on the repetition rate modulation was developed. A non-wavelength-selective pyroelectric detector was incorporated in the gas sensor giving an advantage of room-temperature operation and low cost. Absorption lines of CO2 and H2O were observed in ambient air providing information about the concentration of these species.

  16. Cascaded Amplitude Modulations in Sound Texture Perception

    Directory of Open Access Journals (Sweden)

    Richard McWalter

    2017-09-01

    Full Text Available Sound textures, such as crackling fire or chirping crickets, represent a broad class of sounds defined by their homogeneous temporal structure. It has been suggested that the perception of texture is mediated by time-averaged summary statistics measured from early auditory representations. In this study, we investigated the perception of sound textures that contain rhythmic structure, specifically second-order amplitude modulations that arise from the interaction of different modulation rates, previously described as “beating” in the envelope-frequency domain. We developed an auditory texture model that utilizes a cascade of modulation filterbanks that capture the structure of simple rhythmic patterns. The model was examined in a series of psychophysical listening experiments using synthetic sound textures—stimuli generated using time-averaged statistics measured from real-world textures. In a texture identification task, our results indicated that second-order amplitude modulation sensitivity enhanced recognition. Next, we examined the contribution of the second-order modulation analysis in a preference task, where the proposed auditory texture model was preferred over a range of model deviants that lacked second-order modulation rate sensitivity. Lastly, the discriminability of textures that included second-order amplitude modulations appeared to be perceived using a time-averaging process. Overall, our results demonstrate that the inclusion of second-order modulation analysis generates improvements in the perceived quality of synthetic textures compared to the first-order modulation analysis considered in previous approaches.

  17. The effect of hydropower on fish stocks: comparison between cascade and non-cascade reservoirs

    Czech Academy of Sciences Publication Activity Database

    Draštík, Vladislav; Kubečka, Jan; Tušer, Michal; Čech, Martin; Frouzová, Jaroslava; Jarolím, Oldřich; Prchalová, Marie

    2008-01-01

    Roč. 609, č. 1 (2008), s. 25-36 ISSN 0018-8158. [EIFAC Symposium on hydropower , flood control and water abstraction: implications for fish and fisheries. Mondsee, 14.06.2006-17.06.2006] R&D Projects: GA ČR(CZ) GA206/06/1371; GA ČR(CZ) GA206/02/0520; GA ČR(CZ) GA206/07/1392; GA AV ČR(CZ) 1QS600170504 Institutional research plan: CEZ:AV0Z60170517 Keywords : abundance * biomass * longitudinal gradient * vertical and horizontal distribution * cascade Subject RIV: EH - Ecology, Behaviour Impact factor: 1.449, year: 2008

  18. Sign epistasis caused by hierarchy within signalling cascades.

    Science.gov (United States)

    Nghe, Philippe; Kogenaru, Manjunatha; Tans, Sander J

    2018-04-13

    Sign epistasis is a central evolutionary constraint, but its causal factors remain difficult to predict. Here we use the notion of parameterised optima to explain epistasis within a signalling cascade, and test these predictions in Escherichia coli. We show that sign epistasis arises from the benefit of tuning phenotypic parameters of cascade genes with respect to each other, rather than from their complex and incompletely known genetic bases. Specifically, sign epistasis requires only that the optimal phenotypic parameters of one gene depend on the phenotypic parameters of another, independent of other details, such as activating or repressing nature, position within the cascade, intra-genic pleiotropy or genotype. Mutational effects change sign more readily in downstream genes, indicating that optimising downstream genes is more constrained. The findings show that sign epistasis results from the inherent upstream-downstream hierarchy between signalling cascade genes, and can be addressed without exhaustive genotypic mapping.

  19. Damped trophic cascades driven by fishing in model marine ecosystems

    DEFF Research Database (Denmark)

    Andersen, Ken Haste; Pedersen, Martin

    2010-01-01

    The largest perturbation on upper trophic levels of many marine ecosystems stems from fishing. The reaction of the ecosystem goes beyond the trophic levels directly targeted by the fishery. This reaction has been described either as a change in slope of the overall size spectrum or as a trophic...... cascade triggered by the removal of top predators. Here we use a novel size- and trait-based model to explore how marine ecosystems might react to perturbations from different types of fishing pressure. The model explicitly resolves the whole life history of fish, from larvae to adults. The results show...... that fishing does not change the overall slope of the size spectrum, but depletes the largest individuals and induces trophic cascades. A trophic cascade can propagate both up and down in trophic levels driven by a combination of changes in predation mortality and food limitation. The cascade is damped...

  20. A cascading failure model for analyzing railway accident causation

    Science.gov (United States)

    Liu, Jin-Tao; Li, Ke-Ping

    2018-01-01

    In this paper, a new cascading failure model is proposed for quantitatively analyzing the railway accident causation. In the model, the loads of nodes are redistributed according to the strength of the causal relationships between the nodes. By analyzing the actual situation of the existing prevention measures, a critical threshold of the load parameter in the model is obtained. To verify the effectiveness of the proposed cascading model, simulation experiments of a train collision accident are performed. The results show that the cascading failure model can describe the cascading process of the railway accident more accurately than the previous models, and can quantitatively analyze the sensitivities and the influence of the causes. In conclusion, this model can assist us to reveal the latent rules of accident causation to reduce the occurrence of railway accidents.

  1. Numerical optimization of a transcritical CO2/propylene cascaded ...

    Indian Academy of Sciences (India)

    transcritical CO2/propylene cascade system with parallel compression ... specific volumes, low solidification temperature, low operating pressure of the ...... Kim M, Pettersen J and Bullard C W 2004 Fundamental process and system design ...

  2. A multivariate approach to heavy flavour tagging with cascade training

    International Nuclear Information System (INIS)

    Bastos, J; Liu, Y

    2007-01-01

    This paper compares the performance of artificial neural networks and boosted decision trees, with and without cascade training, for tagging b-jets in a collider experiment. It is shown, using a Monte Carlo simulation of WH→lνq q-bar events, that for a b-tagging efficiency of 50%, the light jet rejection power given by boosted decision trees without cascade training is about 55% higher than that given by artificial neural networks. The cascade training technique can improve the performance of boosted decision trees and artificial neural networks at this b-tagging efficiency level by about 35% and 80% respectively. We conclude that the cascade trained boosted decision trees method is the most promising technique for tagging heavy flavours at collider experiments

  3. Tunable signal processing in synthetic MAP kinase cascades.

    Science.gov (United States)

    O'Shaughnessy, Ellen C; Palani, Santhosh; Collins, James J; Sarkar, Casim A

    2011-01-07

    The flexibility of MAPK cascade responses enables regulation of a vast array of cell fate decisions, but elucidating the mechanisms underlying this plasticity is difficult in endogenous signaling networks. We constructed insulated mammalian MAPK cascades in yeast to explore how intrinsic and extrinsic perturbations affect the flexibility of these synthetic signaling modules. Contrary to biphasic dependence on scaffold concentration, we observe monotonic decreases in signal strength as scaffold concentration increases. We find that augmenting the concentration of sequential kinases can enhance ultrasensitivity and lower the activation threshold. Further, integrating negative regulation and concentration variation can decouple ultrasensitivity and threshold from the strength of the response. Computational analyses show that cascading can generate ultrasensitivity and that natural cascades with different kinase concentrations are innately biased toward their distinct activation profiles. This work demonstrates that tunable signal processing is inherent to minimal MAPK modules and elucidates principles for rational design of synthetic signaling systems. Copyright © 2011 Elsevier Inc. All rights reserved.

  4. Cascade Structure of Digital Predistorter for Power Amplifier Linearization

    Directory of Open Access Journals (Sweden)

    E. B. Solovyeva

    2015-12-01

    Full Text Available In this paper, a cascade structure of nonlinear digital predistorter (DPD synthesized by the direct learning adaptive algorithm is represented. DPD is used for linearization of power amplifier (PA characteristic, namely for compensation of PA nonlinear distortion. Blocks of the cascade DPD are described by different models: the functional link artificial neural network (FLANN, the polynomial perceptron network (PPN and the radially pruned Volterra model (RPVM. At synthesis of the cascade DPD there is possibility to overcome the ill conditionality problem due to reducing the dimension of DPD nonlinear operator approximation. Results of compensating nonlinear distortion in Wiener–Hammerstein model of PA at the GSM–signal with four carriers are shown. The highest accuracy of PA linearization is produced by the cascade DPD containing PPN and RPVM.

  5. Minimum Entropy-Based Cascade Control for Governing Hydroelectric Turbines

    Directory of Open Access Journals (Sweden)

    Mifeng Ren

    2014-06-01

    Full Text Available In this paper, an improved cascade control strategy is presented for hydroturbine speed governors. Different from traditional proportional-integral-derivative (PID control and model predictive control (MPC strategies, the performance index of the outer controller is constructed by integrating the entropy and mean value of the tracking error with the constraints on control energy. The inner controller is implemented by a proportional controller. Compared with the conventional PID-P and MPC-P cascade control methods, the proposed cascade control strategy can effectively decrease fluctuations of hydro-turbine speed under non-Gaussian disturbance conditions in practical hydropower plants. Simulation results show the advantages of the proposed cascade control method.

  6. On peculiarities of the cascade γ decay of heavy nuclei

    International Nuclear Information System (INIS)

    Boneva, S.T.; Khitrov, V.A.; Popov, Yu.P.; Sukhovoj, A.M.; Vasil'eva, E.V.; Yazvitskij, Yu.S.

    1987-01-01

    Comparison of measured and calculated by statistical theory sums of two-quanta cascade intensities in compound-nuclei 163 ≤ A ≤ 183 points to the dependence of cascade intensity on the structure of initial and intermediate levels. The dependence of two-quanta cascade intensity sum on reduced neutron widths of compound states of even-even nuclei-targets of rare earth regions is detected. In 175 Yb and 179 Hf nuclei a considerable increase in the intensity of two-quanta cascades at the energy of their intermediate level in the range of the calculated position of one-quasiparticle states of the Saxon-Woods deformed potential is observed

  7. Quantum cascade laser infrared spectroscopy of single cancer cells

    KAUST Repository

    Patel, Imran

    2017-03-27

    Quantum cascade laser infrared spectroscopy is a next generation novel imaging technique allowing high resolution spectral imaging of cells. We show after spectral pre-processing, identification of different cancer cell populations within minutes.

  8. SCC: Semantic Context Cascade for Efficient Action Detection

    KAUST Repository

    Heilbron, Fabian Caba; Barrios, Wayner; Escorcia, Victor; Ghanem, Bernard

    2017-01-01

    in videos. Existing approaches have mitigated the computational cost, but still, these methods lack rich high-level semantics that helps them to localize the actions quickly. In this paper, we introduce a Semantic Cascade Context (SCC) model that aims

  9. Quantum cascade laser infrared spectroscopy of single cancer cells

    KAUST Repository

    Patel, Imran; Rajamanickam, Vijayakumar Palanisamy; Bertoncini, Andrea; Pagliari, Francesca; Tirinato, Luca; Laptenok, Sergey P.; Liberale, Carlo

    2017-01-01

    Quantum cascade laser infrared spectroscopy is a next generation novel imaging technique allowing high resolution spectral imaging of cells. We show after spectral pre-processing, identification of different cancer cell populations within minutes.

  10. On periodic orbits in discrete-time cascade systems

    Directory of Open Access Journals (Sweden)

    Huimin Li

    2006-01-01

    Full Text Available We present some results on existence, minimum period, number of periodic orbits, and stability of periodic orbits in discrete-time cascade systems. Some examples are presented to illustrate these results.

  11. The flow analysis of supercavitating cascade by linear theory

    Energy Technology Data Exchange (ETDEWEB)

    Park, E.T. [Sung Kyun Kwan Univ., Seoul (Korea, Republic of); Hwang, Y. [Seoul National Univ., Seoul (Korea, Republic of)

    1996-06-01

    In order to reduce damages due to cavitation effects and to improve performance of fluid machinery, supercavitation around the cascade and the hydraulic characteristics of supercavitating cascade must be analyzed accurately. And the study on the effects of cavitation on fluid machinery and analysis on the performances of supercavitating hydrofoil through various elements governing flow field are critically important. In this study comparison of experiment results with the computed results of linear theory using singularity method was obtainable. Specially singularity points like sources and vortexes on hydrofoil and freestreamline were distributed to analyze two dimensional flow field of supercavitating cascade, and governing equations of flow field were derived and hydraulic characteristics of cascade were calculated by numerical analysis of the governing equations. 7 refs., 6 figs.

  12. Saw palmetto extract suppresses insulin-like growth factor-I signaling and induces stress-activated protein kinase/c-Jun N-terminal kinase phosphorylation in human prostate epithelial cells.

    Science.gov (United States)

    Wadsworth, Teri L; Carroll, Julie M; Mallinson, Rebecca A; Roberts, Charles T; Roselli, Charles E

    2004-07-01

    A common alternative therapy for benign prostatic hyperplasia (BPH) is the extract from the fruit of saw palmetto (SPE). BPH is caused by nonmalignant growth of epithelial and stromal elements of the prostate. IGF action is important for prostate growth and development, and changes in the IGF system have been documented in BPH tissues. The main signaling pathways activated by the binding of IGF-I to the IGF-I receptor (IGF-IR) are the ERK arm of the MAPK cascade and the phosphoinositol-3-kinase (PI3K)/protein kinase B (PKB/Akt) cascade. We tested the hypothesis that SPE suppresses growth and induces apoptosis in the P69 prostate epithelial cell line by inhibiting IGF-I signaling. Treatment with 150 microg/ml SPE for 24 h decreased IGF-I-induced proliferation of P69 cells and induced cleavage of the enzyme poly(ADP-ribose)polymerase (PARP), an index of apoptosis. Treatment of serum-starved P69 cells with 150 microg/ml SPE for 6 h reduced IGF-I-induced phosphorylation of Akt (assessed by Western blot) and Akt activity (assessed by an Akt kinase assay). Western blot analysis showed that SPE reduced IGF-I-induced phosphorylation of the adapter protein insulin receptor substrate-1 and decreased downstream effects of Akt activation, including increased cyclin D1 levels and phosphorylation of glycogen synthase kinase-3 and p70(s6k). There was no effect on IGF-I-induced phosphorylation of MAPK, IGF-IR, or Shc. Treatment of starved cells with SPE alone induced phosphorylation the proapoptotic protein JNK. SPE treatment may relieve symptoms of BPH, in part, by inhibiting specific components of the IGF-I signaling pathway and inducing JNK activation, thus mediating antiproliferative and proapoptotic effects on prostate epithelia.

  13. Laminar shear flow increases hydrogen sulfide and activates a nitric oxide producing signaling cascade in endothelial cells.

    Science.gov (United States)

    Huang, Bin; Chen, Chang-Ting; Chen, Chi-Shia; Wang, Yun-Ming; Hsieh, Hsyue-Jen; Wang, Danny Ling

    2015-09-04

    Laminar shear flow triggers a signaling cascade that maintains the integrity of endothelial cells (ECs). Hydrogen sulfide (H2S), a new gasotransmitter is regarded as an upstream regulator of nitric oxide (NO). Whether the H2S-generating enzymes are correlated to the enzymes involved in NO production under shear flow conditions remains unclear as yet. In the present study, the cultured ECs were subjected to a constant shear flow (12 dyn/cm(2)) in a parallel flow chamber system. We investigated the expression of three key enzymes for H2S biosynthesis, cystathionine-γ-lyase (CSE), cystathionine-β-synthase (CBS), and 3-mercapto-sulfurtransferase (3-MST). Shear flow markedly increased the level of 3-MST. Shear flow enhanced the production of H2S was determined by NBD-SCN reagent that can bind to cysteine/homocystein. Exogenous treatment of NaHS that can release gaseous H2S, ECs showed an increase of phosphorylation in Akt(S473), ERK(T202/Y204) and eNOS(S1177). This indicated that H2S can trigger the NO-production signaling cascade. Silencing of CSE, CBS and 3-MST genes by siRNA separately attenuated the phosphorylation levels of Akt(S473) and eNOS(S1177) under shear flow conditions. The particular mode of shear flow increased H2S production. The interplay between H2S and NO-generating enzymes were discussed in the present study. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. Phosphorylation of the Yeast Choline Kinase by Protein Kinase C

    Science.gov (United States)

    Choi, Mal-Gi; Kurnov, Vladlen; Kersting, Michael C.; Sreenivas, Avula; Carman, George M.

    2005-01-01

    The Saccharomyces cerevisiae CKI1-encoded choline kinase catalyzes the committed step in phosphatidylcholine synthesis via the Kennedy pathway. The enzyme is phosphorylated on multiple serine residues, and some of this phosphorylation is mediated by protein kinase A. In this work, we examined the hypothesis that choline kinase is also phosphorylated by protein kinase C. Using choline kinase as a substrate, protein kinase C activity was dose- and time-dependent, and dependent on the concentrations of choline kinase (Km = 27 μg/ml) and ATP (Km = 15 μM). This phosphorylation, which occurred on a serine residue, was accompanied by a 1.6-fold stimulation of choline kinase activity. The synthetic peptide SRSSS25QRRHS (Vmax/Km = 17.5 mM-1 μmol min-1 mg-1) that contains the protein kinase C motif for Ser25 was a substrate for protein kinase C. A Ser25 to Ala (S25A) mutation in choline kinase resulted in a 60% decrease in protein kinase C phosphorylation of the enzyme. Phosphopeptide mapping analysis of the S25A mutant enzyme confirmed that Ser25 was a protein kinase C target site. In vivo, the S25A mutation correlated with a decrease (55%) in phosphatidylcholine synthesis via the Kennedy pathway whereas an S25D phosphorylation site mimic correlated with an increase (44%) in phosphatidylcholine synthesis. Whereas the S25A (protein kinase C site) mutation did not affect the phosphorylation of choline kinase by protein kinase A, the S30A (protein kinase A site) mutation caused a 46% reduction in enzyme phosphorylation by protein kinase C. A choline kinase synthetic peptide (SQRRHS30LTRQ) containing Ser30 was a substrate (Vmax/Km = 3.0 mM−1 μmol min−1 mg−1) for protein kinase C. Comparison of phosphopeptide maps of the wild type and S30A mutant choline kinase enzymes phosphorylated by protein kinase C confirmed that Ser30 was also a target site for protein kinase C. PMID:15919656

  15. Neurofilament subunit (NFL) head domain phosphorylation regulates axonal transport of neurofilaments.

    LENUS (Irish Health Repository)

    Yates, Darran M

    2009-04-01

    Neurofilaments are the intermediate filaments of neurons and are synthesised in neuronal cell bodies and then transported through axons. Neurofilament light chain (NFL) is a principal component of neurofilaments, and phosphorylation of NFL head domain is believed to regulate the assembly of neurofilaments. However, the role that NFL phosphorylation has on transport of neurofilaments is poorly understood. To address this issue, we monitored axonal transport of phosphorylation mutants of NFL. We mutated four known phosphorylation sites in NFL head domain to either preclude phosphorylation, or mimic permanent phosphorylation. Mutation to preclude phosphorylation had no effect on transport but mutation of three sites to mimic permanent phosphorylation inhibited transport. Mutation of all four sites together to mimic permanent phosphorylation proved especially potent at inhibiting transport and also disrupted neurofilament assembly. Our results suggest that NFL head domain phosphorylation is a regulator of neurofilament axonal transport.

  16. Multi Agent System Based Wide Area Protection against Cascading Events

    DEFF Research Database (Denmark)

    Liu, Zhou; Chen, Zhe; Liu, Leo

    2012-01-01

    In this paper, a multi-agent system based wide area protection scheme is proposed in order to prevent long term voltage instability induced cascading events. The distributed relays and controllers work as a device agent which not only executes the normal function automatically but also can...... the effectiveness of proposed protection strategy. The simulation results indicate that the proposed multi agent control system can effectively coordinate the distributed relays and controllers to prevent the long term voltage instability induced cascading events....

  17. Molecular dynamics simulation of displacement cascades in iron-alpha

    International Nuclear Information System (INIS)

    Vascon, R.

    1997-01-01

    Radiation damage by neutrons or ions in bcc iron has been investigated by molecular dynamics simulations using an embedded atom type many-body potential (EAM). Displacement cascades with energies of 1 to 30 keV were generated in the microcanonical system where the number of atoms (up to 1.5 million) is chosen high enough to compensate the fact that the dissipation of energy is not taken into account in our model. The defect number at the end of cascade lifetime was found to be 60 percent of the NRT standard value. This tendency is in good agreement with experimental data. However, compared with other simulations in iron, we found significant differences in the defect production and distribution. The comparison with results obtained form simulations of cascades in other metals, leads on the one hand to a higher value of the defect number in bcc iron than in fcc metals like copper or nickel, and on the other hand to a ratio, between the number of replacements and the number of defects, lower in iron ( 100). We observed the transient melting of the core of the cascade during simulations. We showed that a higher value of the initial iron crystal temperature, as the mass difference between the components of an artificial binary alloy Fe-X(X=Al,Sb,Au,U) both produce a 'cascade effect': a decrease of the number of defects and an increase of the number of replacements. We also showed up the quasi-channeling of some atoms in high energy cascades. They are at the origin of sub-cascades formation; as a result they induce an opposite effect to the 'cascade effect'. (author)

  18. Linewidth and tuning characteristics of terahertz quantum cascade lasers.

    Science.gov (United States)

    Barkan, A; Tittel, F K; Mittleman, D M; Dengler, R; Siegel, P H; Scalari, G; Ajili, L; Faist, J; Beere, H E; Linfield, E H; Davies, A G; Ritchie, D A

    2004-03-15

    We have measured the spectral linewidths of three continuous-wave quantum cascade lasers operating at terahertz frequencies by heterodyning the free-running quantum cascade laser with two far-infrared gas lasers. Beat notes are detected with a GaAs diode mixer and a microwave spectrum analyzer, permitting very precise frequency measurements and giving instantaneous linewidths of less than -30 kHz. Characteristics are also reported for frequency tuning as the injection current is varied.

  19. Noise properties and cascadability of SOA-EA regenerators

    DEFF Research Database (Denmark)

    Öhman, Filip; Bischoff, Svend; Tromborg, Bjarne

    2002-01-01

    We suggest and analyse a new device containing concatenated pairs of semiconductor optical amplifiers (SOAs) and electroabsorption modulators (EAs). The device has regenerative properties and improves the cascadability of optical fibre links.......We suggest and analyse a new device containing concatenated pairs of semiconductor optical amplifiers (SOAs) and electroabsorption modulators (EAs). The device has regenerative properties and improves the cascadability of optical fibre links....

  20. Molecular dynamics simulation of cascade damage in gold

    International Nuclear Information System (INIS)

    Alonso, E.; Caturla, M.J.; Tang, M.; Huang, H.; Diaz de la Rubia, T.

    1997-01-01

    High-energy cascades have been simulated in gold using molecular dynamics with a modified embedded atom method potential. The results show that both vacancy and interstitial clusters form with high probability as a result of intracascade processes. The formation of clusters has been interpreted in terms of the high pressures generated in the core of the cascade during the early stages. The authors provide evidence that correlation between interstitial and vacancy clustering exists

  1. Parton-hadron cascade approach at SPS and RHIC

    Energy Technology Data Exchange (ETDEWEB)

    Nara, Yasushi [Japan Atomic Energy Research Inst., Tokai, Ibaraki (Japan). Tokai Research Establishment

    1998-07-01

    A parton-hadron cascade model which is the extension of hadronic cascade model incorporating hard partonic scattering based on HIJING is presented to describe the space-time evolution of parton/hadron system produced by ultra-relativistic nuclear collisions. Hadron yield, baryon stopping and transverse momentum distribution are calculated and compared with HIJING and VNI. Baryon density, energy density and temperature for RHIC are calculated within this model. (author)

  2. beta2-adaptin is constitutively de-phosphorylated by serine/threonine protein phosphatase PP2A and phosphorylated by a staurosporine-sensitive kinase

    DEFF Research Database (Denmark)

    Lauritsen, Jens Peter Holst; Menné, C; Kastrup, J

    2000-01-01

    Clathrin-mediated endocytosis includes cycles of assembly and disassembly of the clathrin-coated vesicle constituents. How these cycles are regulated is still not fully known but previous studies have indicated that phosphorylation of coat subunits may play a role. Here we describe that beta2-ada...... the hypothesis that phosphorylation/de-phosphorylation of coat proteins plays a regulatory role in the assembly/disassembly cycle of clathrin-coated vesicles.......Clathrin-mediated endocytosis includes cycles of assembly and disassembly of the clathrin-coated vesicle constituents. How these cycles are regulated is still not fully known but previous studies have indicated that phosphorylation of coat subunits may play a role. Here we describe that beta2......-adaptin undergoes cycles of phosphorylation/de-phosphorylation in intact cells. Thus, beta2-adaptin was constitutively de-phosphorylated by serine/threonine protein phosphatase 2A and phosphorylated by a staurosporine-sensitive kinase in vivo. Confocal laser scanning microscopy demonstrated...

  3. Inhibition of peptide aggregation by means of enzymatic phosphorylation

    Directory of Open Access Journals (Sweden)

    Kristin Folmert

    2016-11-01

    Full Text Available As is the case in numerous natural processes, enzymatic phosphorylation can be used in the laboratory to influence the conformational populations of proteins. In nature, this information is used for signal transduction or energy transfer, but has also been shown to play an important role in many diseases like tauopathies or diabetes. With the goal of determining the effect of phosphorylation on amyloid fibril formation, we designed a model peptide which combines structural characteristics of α-helical coiled-coils and β-sheets in one sequence. This peptide undergoes a conformational transition from soluble structures into insoluble amyloid fibrils over time and under physiological conditions and contains a recognition motif for PKA (cAMP-dependent protein kinase that enables enzymatic phosphorylation. We have analyzed the pathway of amyloid formation and the influence of enzymatic phosphorylation on the different states along the conformational transition from random-coil to β-sheet-rich oligomers to protofilaments and on to insoluble amyloid fibrils, and we found a remarkable directing effect from β-sheet-rich structures to unfolded structures in the initial growth phase, in which small oligomers and protofilaments prevail if the peptide is phosphorylated.

  4. Stimulation of glucose phosphorylation by fructose in isolated rat hepatocytes.

    Science.gov (United States)

    Van Schaftingen, E; Vandercammen, A

    1989-01-15

    The phosphorylation of glucose was measured by the formation of [3H]H2O from [2-3H]glucose in suspensions of freshly isolated rat hepatocytes. Fructose (0.2 mM) stimulated 2-4-fold the rate of phosphorylation of 5 mM glucose although not of 40 mM glucose, thus increasing the apparent affinity of the glucose phosphorylating system. A half-maximal stimulatory effect was observed at about 50 microM fructose. Stimulation was maximal 5 min after addition of the ketose and was stable for at least 40 min, during which period 60% of the fructose was consumed. The effect of fructose was reversible upon removal of the ketose. Sorbitol and tagatose were as potent as fructose in stimulating the phosphorylation of 5 mM glucose. D-Glyceraldehyde also had a stimulatory effect but at tenfold higher concentrations. In contrast, dihydroxyacetone had no significant effect and glycerol inhibited the detritiation of glucose. Oleate did not affect the phosphorylation of glucose, even in the presence of fructose, although it stimulated the formation of ketone bodies severalfold, indicating that it was converted to its acyl-CoA derivative. These results allow the conclusion that fructose stimulates glucokinase in the intact hepatocyte. They also suggest that this effect is mediated through the formation of fructose 1-phosphate, which presumably interacts with a competitive inhibitor of glucokinase other than long-chain acyl-CoAs.

  5. Tyrosine Phosphorylation in Toll-Like Receptor Signaling

    Science.gov (United States)

    Chattopadhyay, Saurabh; Sen, Ganes C.

    2014-01-01

    There is a wealth of knowledge about how different Ser/Thr protein kinases participate in Toll-like receptor (TLR) signaling. In many cases, we know the identities of the Ser/Thr residues of various components of the TLR-signaling pathways that are phosphorylated, the functional consequences of the phosphorylation and the responsible protein kinases. In contrast, the analysis of Tyr-phosphorylation of TLRs and their signaling proteins is currently incomplete, because several existing analyses are not systematic or they do not rely on robust experimental data. Nevertheless, it is clear that many TLRs require, for signaling, ligand-dependent phosphorylation of specific Tyr residues in their cytoplasmic domains; the list includes TLR2, TLR3, TLR4, TLR5, TLR8 and TLR9. In this article, we discuss the current status of knowledge on the effect of Tyr-phosphorylation of TLRs and their signaling proteins on their biochemical and biological functions, the possible identities of the relevant protein tyrosine kinases (PTKs) and the nature of regulations of PTK-mediated activation of TLR signaling pathways. PMID:25022196

  6. Phosphorylation of Large T Antigen Regulates Merkel Cell Polyomavirus Replication

    International Nuclear Information System (INIS)

    Diaz, Jason; Wang, Xin; Tsang, Sabrina H.; Jiao, Jing; You, Jianxin

    2014-01-01

    Merkel Cell Polyomavirus (MCPyV) was recently discovered as a novel human polyomavirus that is associated with ~80% of Merkel Cell Carcinomas. The Large Tumor antigen (LT) is an early viral protein which has a variety of functions, including manipulation of the cell cycle and initiating viral DNA replication. Phosphorylation plays a critical regulatory role for polyomavirus LT proteins, but no investigation of MCPyV LT phosphorylation has been performed to date. In this report mass spectrometry analysis reveals three unique phosphorylation sites: T271, T297 and T299. In vivo replication assays confirm that phosphorylation of T271 does not play a role in viral replication, while modification at T297 and T299 have dramatic and opposing effects on LT’s ability to initiate replication from the viral origin. We test these mutants for their ability to bind, unwind, and act as a functional helicase at the viral origin. These studies provide a framework for understanding how phosphorylation of LT may dynamically regulate viral replication. Although the natural host cell of MCPyV has not yet been established, this work provides a foundation for understanding how LT activity is regulated and provides tools for better exploring this regulation in both natural host cells and Merkel cells

  7. Phosphorylation of Large T Antigen Regulates Merkel Cell Polyomavirus Replication

    Energy Technology Data Exchange (ETDEWEB)

    Diaz, Jason; Wang, Xin; Tsang, Sabrina H. [Department of Microbiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104 (United States); Jiao, Jing [Department of Pathology and Laboratory Medicine, Children’s Hospital of Philadelphia, Philadelphia, PA 19104 (United States); You, Jianxin, E-mail: jianyou@mail.med.upenn.edu [Department of Microbiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104 (United States)

    2014-07-08

    Merkel Cell Polyomavirus (MCPyV) was recently discovered as a novel human polyomavirus that is associated with ~80% of Merkel Cell Carcinomas. The Large Tumor antigen (LT) is an early viral protein which has a variety of functions, including manipulation of the cell cycle and initiating viral DNA replication. Phosphorylation plays a critical regulatory role for polyomavirus LT proteins, but no investigation of MCPyV LT phosphorylation has been performed to date. In this report mass spectrometry analysis reveals three unique phosphorylation sites: T271, T297 and T299. In vivo replication assays confirm that phosphorylation of T271 does not play a role in viral replication, while modification at T297 and T299 have dramatic and opposing effects on LT’s ability to initiate replication from the viral origin. We test these mutants for their ability to bind, unwind, and act as a functional helicase at the viral origin. These studies provide a framework for understanding how phosphorylation of LT may dynamically regulate viral replication. Although the natural host cell of MCPyV has not yet been established, this work provides a foundation for understanding how LT activity is regulated and provides tools for better exploring this regulation in both natural host cells and Merkel cells.

  8. A cryogenic distillation column cascade for a fusion reactor

    International Nuclear Information System (INIS)

    Kinoshita, M.

    1984-01-01

    A cryogenic distillation column cascade composed of only two columns is proposed. Compared with the Tritium Systems Test Assembly (TSTA) cascade, the tritium inventory is about 1.5 times more and the packed height of the highest column increases by about 40%. However, the number of the columns is halved with the separation performance unchanged. The number of the instruments needed and the number of the process parameters to be monitored are also reduced. Unlike in the case of the TSTA cascade, the performance of the proposed cascade is not subject to the flow rate of the neutral beam injector recycle stream. The high performance can be maintained even if the protium percentage in the raw fuel input increases significantly (e.g., from 1 to 3%), just by adjusting the flow rates of the top, bottom, and side streams. Because of this great flexibility, it is worthwhile to build and study the proposed cascade as a possible alternative to the TSTA cascade

  9. Trophic redundancy reduces vulnerability to extinction cascades.

    Science.gov (United States)

    Sanders, Dirk; Thébault, Elisa; Kehoe, Rachel; Frank van Veen, F J

    2018-03-06

    Current species extinction rates are at unprecedentedly high levels. While human activities can be the direct cause of some extinctions, it is becoming increasingly clear that species extinctions themselves can be the cause of further extinctions, since species affect each other through the network of ecological interactions among them. There is concern that the simplification of ecosystems, due to the loss of species and ecological interactions, increases their vulnerability to such secondary extinctions. It is predicted that more complex food webs will be less vulnerable to secondary extinctions due to greater trophic redundancy that can buffer against the effects of species loss. Here, we demonstrate in a field experiment with replicated plant-insect communities, that the probability of secondary extinctions is indeed smaller in food webs that include trophic redundancy. Harvesting one species of parasitoid wasp led to secondary extinctions of other, indirectly linked, species at the same trophic level. This effect was markedly stronger in simple communities than for the same species within a more complex food web. We show that this is due to functional redundancy in the more complex food webs and confirm this mechanism with a food web simulation model by highlighting the importance of the presence and strength of trophic links providing redundancy to those links that were lost. Our results demonstrate that biodiversity loss, leading to a reduction in redundant interactions, can increase the vulnerability of ecosystems to secondary extinctions, which, when they occur, can then lead to further simplification and run-away extinction cascades. Copyright © 2018 the Author(s). Published by PNAS.

  10. Cascaded processing in written compound word production

    Directory of Open Access Journals (Sweden)

    Raymond eBertram

    2015-04-01

    Full Text Available In this study we investigated the intricate interplay between central linguistic processing and peripheral motor processes during typewriting. Participants had to typewrite two-constituent (noun-noun Finnish compounds in response to picture presentation while their typing behavior was registered. As dependent measures we used writing onset time to assess what processes were completed before writing and inter-key intervals to assess what processes were going on during writing. It was found that writing onset time was determined by whole word frequency rather than constituent frequencies, indicating that compound words are retrieved as whole orthographic units before writing is initiated. In addition, we found that the length of the first syllable also affects writing onset time, indicating that the first syllable is fully prepared before writing commences. The inter-key interval results showed that linguistic planning is not fully ready before writing, but cascades into the motor execution phase. More specifically, inter-key intervals were largest at syllable and morpheme boundaries, supporting the view that additional linguistic planning takes place at these boundaries. Bigram and trigram frequency also affected inter-key intervals with shorter intervals corresponding to higher frequencies. This can be explained by stronger memory traces for frequently co-occurring letter sequences in the motor memory for typewriting. These frequency effects were even larger in the second than in the first constituent, indicating that low-level motor memory starts to become more important during the course of writing compound words. We discuss our results in the light of current models of morphological processing and written word production.

  11. Cascaded processing in written compound word production.

    Science.gov (United States)

    Bertram, Raymond; Tønnessen, Finn Egil; Strömqvist, Sven; Hyönä, Jukka; Niemi, Pekka

    2015-01-01

    In this study we investigated the intricate interplay between central linguistic processing and peripheral motor processes during typewriting. Participants had to typewrite two-constituent (noun-noun) Finnish compounds in response to picture presentation while their typing behavior was registered. As dependent measures we used writing onset time to assess what processes were completed before writing and inter-key intervals to assess what processes were going on during writing. It was found that writing onset time was determined by whole word frequency rather than constituent frequencies, indicating that compound words are retrieved as whole orthographic units before writing is initiated. In addition, we found that the length of the first syllable also affects writing onset time, indicating that the first syllable is fully prepared before writing commences. The inter-key interval results showed that linguistic planning is not fully ready before writing, but cascades into the motor execution phase. More specifically, inter-key intervals were largest at syllable and morpheme boundaries, supporting the view that additional linguistic planning takes place at these boundaries. Bigram and trigram frequency also affected inter-key intervals with shorter intervals corresponding to higher frequencies. This can be explained by stronger memory traces for frequently co-occurring letter sequences in the motor memory for typewriting. These frequency effects were even larger in the second than in the first constituent, indicating that low-level motor memory starts to become more important during the course of writing compound words. We discuss our results in the light of current models of morphological processing and written word production.

  12. Fast lossless compression via cascading Bloom filters.

    Science.gov (United States)

    Rozov, Roye; Shamir, Ron; Halperin, Eran

    2014-01-01

    Data from large Next Generation Sequencing (NGS) experiments present challenges both in terms of costs associated with storage and in time required for file transfer. It is sometimes possible to store only a summary relevant to particular applications, but generally it is desirable to keep all information needed to revisit experimental results in the future. Thus, the need for efficient lossless compression methods for NGS reads arises. It has been shown that NGS-specific compression schemes can improve results over generic compression methods, such as the Lempel-Ziv algorithm, Burrows-Wheeler transform, or Arithmetic Coding. When a reference genome is available, effective compression can be achieved by first aligning the reads to the reference genome, and then encoding each read using the alignment position combined with the differences in the read relative to the reference. These reference-based methods have been shown to compress better than reference-free schemes, but the alignment step they require demands several hours of CPU time on a typical dataset, whereas reference-free methods can usually compress in minutes. We present a new approach that achieves highly efficient compression by using a reference genome, but completely circumvents the need for alignment, affording a great reduction in the time needed to compress. In contrast to reference-based methods that first align reads to the genome, we hash all reads into Bloom filters to encode, and decode by querying the same Bloom filters using read-length subsequences of the reference genome. Further compression is achieved by using a cascade of such filters. Our method, called BARCODE, runs an order of magnitude faster than reference-based methods, while compressing an order of magnitude better than reference-free methods, over a broad range of sequencing coverage. In high coverage (50-100 fold), compared to the best tested compressors, BARCODE saves 80-90% of the running time while only increasing space

  13. Cascade of negative muons in atoms

    International Nuclear Information System (INIS)

    Akylas, V.R.

    1978-01-01

    A study is made of the evolution of a negative muon captured in an atom and the formalism of energy loss associated with the muonic atom. The principal goals are to calculate reliability the muon x-ray intensities, given the initial population of the muonic orbits, to invert the problem and deduce the initial distribution from the x-ray intensities, to provide a reasonably simple and convenient tool to correlate observations, and finally, to systematize some questions of theoretical interest. The early part of the history of the muon in matter, including the atomic capture and classical phase of the atomic cascade are reviewed. In the quantal treatment of the transition rates, both radiative and electron Auger transitions are considered. In general, multipolarities up to E3 and K, L, and M electronic shells are fully investigated. Multipole radiation is treated in the conventinal way and pesents no special problems. Magnetic type transitions between states with different principal quantum numbers are shown to be small. Auger electron ejection rates are more complicated and several approximations have been adopted. The basic results have been computed in terms of elemetary functions. In the Auger transitions we have shown that magnetic multipoles can be safety neglected. The relative sizes of the rates corresponding to different multipoles are systematically studied. A comparison of results is made with atomic photoelectric effect data and with the nuclear internal conversion coefficients. A general agreement is found, except around shell thresholds. The existing data of muonic x-ray intensities in iron and thallium are analyzed in a systematic way. It is found that for Fe the initial l-distribution is almost flat, whereas that for T1 is weighted towards the high l values, sharper than statistical. As a result of the investigations and in order to make our findings usable, a computer program has been developed. 36 references

  14. Human initiated cascading failures in societal infrastructures.

    Directory of Open Access Journals (Sweden)

    Chris Barrett

    Full Text Available In this paper, we conduct a systematic study of human-initiated cascading failures in three critical inter-dependent societal infrastructures due to behavioral adaptations in response to a crisis. We focus on three closely coupled socio-technical networks here: (i cellular and mesh networks, (ii transportation networks and (iii mobile call networks. In crises, changes in individual behaviors lead to altered travel, activity and calling patterns, which influence the transport network and the loads on wireless networks. The interaction between these systems and their co-evolution poses significant technical challenges for representing and reasoning about these systems. In contrast to system dynamics models for studying these interacting infrastructures, we develop interaction-based models in which individuals and infrastructure elements are represented in detail and are placed in a common geographic coordinate system. Using the detailed representation, we study the impact of a chemical plume that has been released in a densely populated urban region. Authorities order evacuation of the affected area, and this leads to individual behavioral adaptation wherein individuals drop their scheduled activities and drive to home or pre-specified evacuation shelters as appropriate. They also revise their calling behavior to communicate and coordinate among family members. These two behavioral adaptations cause flash-congestion in the urban transport network and the wireless network. The problem is exacerbated with a few, already occurring, road closures. We analyze how extended periods of unanticipated road congestion can result in failure of infrastructures, starting with the servicing base stations in the congested area. A sensitivity analysis on the compliance rate of evacuees shows non-intuitive effect on the spatial distribution of people and on the loading of the base stations. For example, an evacuation compliance rate of 70% results in higher number

  15. Cascaded Subpatch Networks for Effective CNNs.

    Science.gov (United States)

    Jiang, Xiaoheng; Pang, Yanwei; Sun, Manli; Li, Xuelong

    2017-05-12

    Conventional convolutional neural networks use either a linear or a nonlinear filter to extract features from an image patch (region) of spatial size Hx W (typically, H is small and is equal to W, e.g., H is 5 or 7 ). Generally, the size of the filter is equal to the size Hx W of the input patch. We argue that the representational ability of equal-size strategy is not strong enough. To overcome the drawback, we propose to use subpatch filter whose spatial size hx w is smaller than Hx W . The proposed subpatch filter consists of two subsequent filters. The first one is a linear filter of spatial size hx w and is aimed at extracting features from spatial domain. The second one is of spatial size 1x 1 and is used for strengthening the connection between different input feature channels and for reducing the number of parameters. The subpatch filter convolves with the input patch and the resulting network is called a subpatch network. Taking the output of one subpatch network as input, we further repeat constructing subpatch networks until the output contains only one neuron in spatial domain. These subpatch networks form a new network called the cascaded subpatch network (CSNet). The feature layer generated by CSNet is called the csconv layer. For the whole input image, we construct a deep neural network by stacking a sequence of csconv layers. Experimental results on five benchmark data sets demonstrate the effectiveness and compactness of the proposed CSNet. For example, our CSNet reaches a test error of 5.68% on the CIFAR10 data set without model averaging. To the best of our knowledge, this is the best result ever obtained on the CIFAR10 data set.

  16. Identification and quantitation of signal molecule-dependent protein phosphorylation

    KAUST Repository

    Groen, Arnoud J.

    2013-09-03

    Phosphoproteomics is a fast-growing field that aims at characterizing phosphorylated proteins in a cell or a tissue at a given time. Phosphorylation of proteins is an important regulatory mechanism in many cellular processes. Gel-free phosphoproteome technique involving enrichment of phosphopeptide coupled with mass spectrometry has proven to be invaluable to detect and characterize phosphorylated proteins. In this chapter, a gel-free quantitative approach involving 15N metabolic labelling in combination with phosphopeptide enrichment by titanium dioxide (TiO2) and their identification by MS is described. This workflow can be used to gain insights into the role of signalling molecules such as cyclic nucleotides on regulatory networks through the identification and quantification of responsive phospho(proteins). © Springer Science+Business Media New York 2013.

  17. Study of ATM Phosphorylation by Cdk5 in Neuronal Cells.

    Science.gov (United States)

    She, Hua; Mao, Zixu

    2017-01-01

    The phosphatidylinositol-3-kinase-like kinase ATM (ataxia-telangiectasia mutated) plays a central role in coordinating the DNA damage responses including cell cycle checkpoint control, DNA repair, and apoptosis. Mutations of ATM cause a spectrum of defects ranging from neurodegeneration to cancer predisposition. We previously showed that Cdk5 (cyclin-dependent kinase 5) is activated by DNA damage and directly phosphorylates ATM at serine 794 in postmitotic neurons. Phosphorylation at serine 794 precedes and is required for ATM autophosphorylation at serine 1981, and activates ATM kinase activity. Cdk5-ATM pathway plays a crucial role in DNA damage-induced neuronal injury. This chapter describes protocols used in analyzing ATM phosphorylation by Cdk5 in CGNs (cerebellar granule neurons) and its effects on neuronal survival.

  18. Common extraction of Tc, Pd and Eu by phosphorylated calixarenes

    International Nuclear Information System (INIS)

    Babain, V.; Smirnov, I.; Kvasnitskiy, I.; Karavan, M.; Boiko, V.; Miroshnichenko, V.; Klimchuk, O.; Kalchenko, V.

    2003-01-01

    The present work is aimed at studying the extraction systems based on neutral organophosphorus extractants - phosphorylated calixarenes for recovery of Pd and Tc together with Am and Cm from high-level radioactive wastes. Extraction of Pd, Tc and Eu (Am) was studied for phosphorylated calixarenes in meta-nitrobenzotrifluoride (NBTF). Main results are presented in Table. On the basis of available data one can suggest that type and position of phosphor-organic substituents are not so important for extraction of Tc and Pd, as for Eu and Am extraction. The phosphorylated at upper rim calix[4]arenas with small alkyl substituents at phosphorus atom are of prime interest for joint recovery of europium, americium, technetium and palladium. (authors)

  19. Phosphorylation site dynamics of early T-cell receptor signaling

    DEFF Research Database (Denmark)

    Chylek, Lily A; Akimov, Vyacheslav; Dengjel, Jörn

    2014-01-01

    In adaptive immune responses, T-cell receptor (TCR) signaling impacts multiple cellular processes and results in T-cell differentiation, proliferation, and cytokine production. Although individual protein-protein interactions and phosphorylation events have been studied extensively, we lack...... that diverse dynamic patterns emerge within seconds. We detected phosphorylation dynamics as early as 5 s and observed widespread regulation of key TCR signaling proteins by 30 s. Development of a computational model pointed to the presence of novel regulatory mechanisms controlling phosphorylation of sites...... a systems-level understanding of how these components cooperate to control signaling dynamics, especially during the crucial first seconds of stimulation. Here, we used quantitative proteomics to characterize reshaping of the T-cell phosphoproteome in response to TCR/CD28 co-stimulation, and found...

  20. Histones and their phosphorylation during germination of rice seeds

    International Nuclear Information System (INIS)

    Iqbal Ahmed, C.M.; Padayatti, J.D.

    1980-01-01

    Histones from nuclei of rice embryos were identified by their mobilities on 15% acid-urea polyacrylamide gel electrophoreogram, incorporation of ( 3 H)lysine and ( 14 C) arginine and lack of incorporation of ( 3 H)tryptophan. The ratio of histone to DNA in ungerminated embryos was 2.7 which decreased during germination reaching unity by 48 hr. There was preferential phosphorylation of lysine-rich histones, which paralleled the synthesis of DNA. In the presence of cytosine arabinoside and mitomycin-C, which inhibited the synthesis of DNA to the extend of 75-80% the phosphorylation of lysine-rich histone was reduced by 50-60% suggesting the dependence of phosphorylation on the ongoing synthesis of DNA. (auth.)

  1. Characterization and Prediction of Protein Phosphorylation Hotspots in Arabidopsis thaliana.

    Science.gov (United States)

    Christian, Jan-Ole; Braginets, Rostyslav; Schulze, Waltraud X; Walther, Dirk

    2012-01-01

    The regulation of protein function by modulating the surface charge status via sequence-locally enriched phosphorylation sites (P-sites) in so called phosphorylation "hotspots" has gained increased attention in recent years. We set out to identify P-hotspots in the model plant Arabidopsis thaliana. We analyzed the spacing of experimentally detected P-sites within peptide-covered regions along Arabidopsis protein sequences as available from the PhosPhAt database. Confirming earlier reports (Schweiger and Linial, 2010), we found that, indeed, P-sites tend to cluster and that distributions between serine and threonine P-sites to their respected closest next P-site differ significantly from those for tyrosine P-sites. The ability to predict P-hotspots by applying available computational P-site prediction programs that focus on identifying single P-sites was observed to be severely compromised by the inevitable interference of nearby P-sites. We devised a new approach, named HotSPotter, for the prediction of phosphorylation hotspots. HotSPotter is based primarily on local amino acid compositional preferences rather than sequence position-specific motifs and uses support vector machines as the underlying classification engine. HotSPotter correctly identified experimentally determined phosphorylation hotspots in A. thaliana with high accuracy. Applied to the Arabidopsis proteome, HotSPotter-predicted 13,677 candidate P-hotspots in 9,599 proteins corresponding to 7,847 unique genes. Hotspot containing proteins are involved predominantly in signaling processes confirming the surmised modulating role of hotspots in signaling and interaction events. Our study provides new bioinformatics means to identify phosphorylation hotspots and lays the basis for further investigating novel candidate P-hotspots. All phosphorylation hotspot annotations and predictions have been made available as part of the PhosPhAt database at http://phosphat.mpimp-golm.mpg.de.

  2. Mechanism of APC/CCDC20 activation by mitotic phosphorylation.

    Science.gov (United States)

    Qiao, Renping; Weissmann, Florian; Yamaguchi, Masaya; Brown, Nicholas G; VanderLinden, Ryan; Imre, Richard; Jarvis, Marc A; Brunner, Michael R; Davidson, Iain F; Litos, Gabriele; Haselbach, David; Mechtler, Karl; Stark, Holger; Schulman, Brenda A; Peters, Jan-Michael

    2016-05-10

    Chromosome segregation and mitotic exit are initiated by the 1.2-MDa ubiquitin ligase APC/C (anaphase-promoting complex/cyclosome) and its coactivator CDC20 (cell division cycle 20). To avoid chromosome missegregation, APC/C(CDC20) activation is tightly controlled. CDC20 only associates with APC/C in mitosis when APC/C has become phosphorylated and is further inhibited by a mitotic checkpoint complex until all chromosomes are bioriented on the spindle. APC/C contains 14 different types of subunits, most of which are phosphorylated in mitosis on multiple sites. However, it is unknown which of these phospho-sites enable APC/C(CDC20) activation and by which mechanism. Here we have identified 68 evolutionarily conserved mitotic phospho-sites on human APC/C bound to CDC20 and have used the biGBac technique to generate 47 APC/C mutants in which either all 68 sites or subsets of them were replaced by nonphosphorylatable or phospho-mimicking residues. The characterization of these complexes in substrate ubiquitination and degradation assays indicates that phosphorylation of an N-terminal loop region in APC1 is sufficient for binding and activation of APC/C by CDC20. Deletion of the N-terminal APC1 loop enables APC/C(CDC20) activation in the absence of mitotic phosphorylation or phospho-mimicking mutations. These results indicate that binding of CDC20 to APC/C is normally prevented by an autoinhibitory loop in APC1 and that its mitotic phosphorylation relieves this inhibition. The predicted location of the N-terminal APC1 loop implies that this loop controls interactions between the N-terminal domain of CDC20 and APC1 and APC8. These results reveal how APC/C phosphorylation enables CDC20 to bind and activate the APC/C in mitosis.

  3. Protein phosphatase 2ACα gene knock-out results in cortical atrophy through activating hippo cascade in neuronal progenitor cells.

    Science.gov (United States)

    Liu, Bo; Sun, Li-Hua; Huang, Yan-Fei; Guo, Li-Jun; Luo, Li-Shu

    2018-02-01

    Protein phosphatase 2ACα (PP2ACα), a vital member of the protein phosphatase family, has been studied primarily as a regulator for the development, growth and protein synthesis of a lot of cell types. Dysfunction of PP2ACα protein results in neurodegenerative disease; however, this finding has not been directly confirmed in the mouse model with PP2ACα gene knock-out. Therefore, in this study presented here, we generated the PP2ACα gene knock-out mouse model by the Cre-loxP targeting gene system, with the purpose to directly observe the regulatory role of PP2ACα gene in the development of mouse's cerebral cortex. We observe that knocking-out PP2ACα gene in the central nervous system (CNS) results in cortical neuronal shrinkage, synaptic plasticity impairments, and learning/memory deficits. Further study reveals that PP2ACα gene knock-out initiates Hippo cascade in cortical neuroprogenitor cells (NPCs), which blocks YAP translocation into the nuclei of NPCs. Notably, p73, directly targeted by Hippo cascade, can bind to the promoter of glutaminase2 (GLS2) that plays a dominant role in the enzymatic regulation of glutamate/glutamine cycle. Finally, we find that PP2ACα gene knock-out inhibits the glutamine synthesis through up-regulating the activity of phosphorylated-p73 in cortical NPCs. Taken together, it concludes that PP2ACα critically supports cortical neuronal growth and cognitive function via regulating the signaling transduction of Hippo-p73 cascade. And PP2ACα indirectly modulates the glutamine synthesis of cortical NPCs through targeting p73 that plays a direct transcriptional regulatory role in the gene expression of GLS2. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. Potential Role of Inorganic Confined Environments in Prebiotic Phosphorylation.

    Science.gov (United States)

    Dass, Avinash Vicholous; Jaber, Maguy; Brack, André; Foucher, Frédéric; Kee, Terence P; Georgelin, Thomas; Westall, Frances

    2018-03-05

    A concise outlook on the potential role of confinement in phosphorylation and phosphate condensation pertaining to prebiotic chemistry is presented. Inorganic confinement is a relatively uncharted domain in studies concerning prebiotic chemistry, and even more so in terms of experimentation. However, molecular crowding within confined dimensions is central to the functioning of contemporary biology. There are numerous advantages to confined environments and an attempt to highlight this fact, within this article, has been undertaken, keeping in context the limitations of aqueous phase chemistry in phosphorylation and, to a certain extent, traditional approaches in prebiotic chemistry.

  5. Training-induced adaptation of oxidative phosphorylation in skeletal muscles.

    Science.gov (United States)

    Korzeniewski, Bernard; Zoladz, Jerzy A

    2003-08-15

    Muscle training/conditioning improves the adaptation of oxidative phosphorylation in skeletal muscles to physical exercise. However, the mechanisms underlying this adaptation are still not understood fully. By quantitative analysis of the existing experimental results, we show that training-induced acceleration of oxygen-uptake kinetics at the onset of exercise and improvement of ATP/ADP stability due to physical training are mainly caused by an increase in the amount of mitochondrial proteins and by an intensification of the parallel activation of ATP usage and ATP supply (increase in direct stimulation of oxidative phosphorylation complexes accompanying stimulation of ATP consumption) during exercise.

  6. Tau Phosphorylation by GSK3 in Different Conditions

    Directory of Open Access Journals (Sweden)

    Jesús Avila

    2012-01-01

    Full Text Available Almost a 20% of the residues of tau protein are phosphorylatable amino acids: serine, threonine, and tyrosine. In this paper we comment on the consequences for tau of being a phosphoprotein. We will focus on serine/threonine phosphorylation. It will be discussed that, depending on the modified residue in tau molecule, phosphorylation could be protective, in processes like hibernation, or toxic like in development of those diseases known as tauopathies, which are characterized by an hyperphosphorylation and aggregation of tau.

  7. Andrographolide Inhibits Nuclear Factor-κB Activation through JNK-Akt-p65 Signaling Cascade in Tumor Necrosis Factor-α-Stimulated Vascular Smooth Muscle Cells

    Directory of Open Access Journals (Sweden)

    Yu-Ying Chen

    2014-01-01

    Full Text Available Critical vascular inflammation leads to vascular dysfunction and cardiovascular diseases, including abdominal aortic aneurysms, hypertension, and atherosclerosis. Andrographolide is the most active and critical constituent isolated from the leaves of Andrographis paniculata, a herbal medicine widely used for treating anti-inflammation in Asia. In this study, we investigated the mechanisms of the inhibitory effects of andrographolide in vascular smooth muscle cells (VSMCs exposed to a proinflammatory stimulus, tumor necrosis factor-α (TNF-α. Treating TNF-α-stimulated VSMCs with andrographolide suppressed the expression of inducible nitric oxide synthase in a concentration-dependent manner. A reduction in TNF-α-induced c-Jun N-terminal kinase (JNK, Akt, and p65 phosphorylation was observed in andrographolide-treated VSMCs. However, andrographolide affected neither IκBα degradation nor p38 mitogen-activated protein kinase or extracellular signal-regulated kinase 1/2 phosphorylation under these conditions. Both treatment with LY294002, a phosphatidylinositol 3-kinase/Akt inhibitor, and treatment with SP600125, a JNK inhibitor, markedly reversed the andrographolide-mediated inhibition of p65 phosphorylation. In addition, LY294002 and SP600125 both diminished Akt phosphorylation, whereas LY294002 had no effects on JNK phosphorylation. These results collectively suggest that therapeutic interventions using andrographolide can benefit the treatment of vascular inflammatory diseases, and andrographolide-mediated inhibition of NF-κB activity in TNF-α-stimulated VSMCs occurs through the JNK-Akt-p65 signaling cascade, an IκBα-independent mechanism.

  8. Amino Acid Activation of mTORC1 by a PB1-Domain-Driven Kinase Complex Cascade.

    Science.gov (United States)

    Linares, Juan F; Duran, Angeles; Reina-Campos, Miguel; Aza-Blanc, Pedro; Campos, Alex; Moscat, Jorge; Diaz-Meco, Maria T

    2015-08-25

    The mTORC1 complex is central to the cellular response to changes in nutrient availability. The signaling adaptor p62 contributes to mTORC1 activation in response to amino acids and interacts with TRAF6, which is required for the translocation of mTORC1 to the lysosome and the subsequent K63 polyubiquitination and activation of mTOR. However, the signal initiating these p62-driven processes was previously unknown. Here, we show that p62 is phosphorylated via a cascade that includes MEK3/6 and p38δ and is driven by the PB1-containing kinase MEKK3. This phosphorylation results in the recruitment of TRAF6 to p62, the ubiquitination and activation of mTOR, and the regulation of autophagy and cell proliferation. Genetic inactivation of MEKK3 or p38δ mimics that of p62 in that it leads to inhibited growth of PTEN-deficient prostate organoids. Analysis of human prostate cancer samples showed upregulation of these three components of the pathway, which correlated with enhanced mTORC1 activation. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  9. Amino Acid Activation of mTORC1 by a PB1-Domain-Driven Kinase Complex Cascade

    Directory of Open Access Journals (Sweden)

    Juan F. Linares

    2015-08-01

    Full Text Available The mTORC1 complex is central to the cellular response to changes in nutrient availability. The signaling adaptor p62 contributes to mTORC1 activation in response to amino acids and interacts with TRAF6, which is required for the translocation of mTORC1 to the lysosome and the subsequent K63 polyubiquitination and activation of mTOR. However, the signal initiating these p62-driven processes was previously unknown. Here, we show that p62 is phosphorylated via a cascade that includes MEK3/6 and p38δ and is driven by the PB1-containing kinase MEKK3. This phosphorylation results in the recruitment of TRAF6 to p62, the ubiquitination and activation of mTOR, and the regulation of autophagy and cell proliferation. Genetic inactivation of MEKK3 or p38δ mimics that of p62 in that it leads to inhibited growth of PTEN-deficient prostate organoids. Analysis of human prostate cancer samples showed upregulation of these three components of the pathway, which correlated with enhanced mTORC1 activation.

  10. Cascaded systems analysis of photon counting detectors.

    Science.gov (United States)

    Xu, J; Zbijewski, W; Gang, G; Stayman, J W; Taguchi, K; Lundqvist, M; Fredenberg, E; Carrino, J A; Siewerdsen, J H

    2014-10-01

    Photon counting detectors (PCDs) are an emerging technology with applications in spectral and low-dose radiographic and tomographic imaging. This paper develops an analytical model of PCD imaging performance, including the system gain, modulation transfer function (MTF), noise-power spectrum (NPS), and detective quantum efficiency (DQE). A cascaded systems analysis model describing the propagation of quanta through the imaging chain was developed. The model was validated in comparison to the physical performance of a silicon-strip PCD implemented on an experimental imaging bench. The signal response, MTF, and NPS were measured and compared to theory as a function of exposure conditions (70 kVp, 1-7 mA), detector threshold, and readout mode (i.e., the option for coincidence detection). The model sheds new light on the dependence of spatial resolution, charge sharing, and additive noise effects on threshold selection and was used to investigate the factors governing PCD performance, including the fundamental advantages and limitations of PCDs in comparison to energy-integrating detectors (EIDs) in the linear regime for which pulse pileup can be ignored. The detector exhibited highly linear mean signal response across the system operating range and agreed well with theoretical prediction, as did the system MTF and NPS. The DQE analyzed as a function of kilovolt (peak), exposure, detector threshold, and readout mode revealed important considerations for system optimization. The model also demonstrated the important implications of false counts from both additive electronic noise and charge sharing and highlighted the system design and operational parameters that most affect detector performance in the presence of such factors: for example, increasing the detector threshold from 0 to 100 (arbitrary units of pulse height threshold roughly equivalent to 0.5 and 6 keV energy threshold, respectively), increased the f50 (spatial-frequency at which the MTF falls to a value of

  11. Cascaded systems analysis of photon counting detectors

    International Nuclear Information System (INIS)

    Xu, J.; Zbijewski, W.; Gang, G.; Stayman, J. W.; Taguchi, K.; Carrino, J. A.; Lundqvist, M.; Fredenberg, E.; Siewerdsen, J. H.

    2014-01-01

    Purpose: Photon counting detectors (PCDs) are an emerging technology with applications in spectral and low-dose radiographic and tomographic imaging. This paper develops an analytical model of PCD imaging performance, including the system gain, modulation transfer function (MTF), noise-power spectrum (NPS), and detective quantum efficiency (DQE). Methods: A cascaded systems analysis model describing the propagation of quanta through the imaging chain was developed. The model was validated in comparison to the physical performance of a silicon-strip PCD implemented on an experimental imaging bench. The signal response, MTF, and NPS were measured and compared to theory as a function of exposure conditions (70 kVp, 1–7 mA), detector threshold, and readout mode (i.e., the option for coincidence detection). The model sheds new light on the dependence of spatial resolution, charge sharing, and additive noise effects on threshold selection and was used to investigate the factors governing PCD performance, including the fundamental advantages and limitations of PCDs in comparison to energy-integrating detectors (EIDs) in the linear regime for which pulse pileup can be ignored. Results: The detector exhibited highly linear mean signal response across the system operating range and agreed well with theoretical prediction, as did the system MTF and NPS. The DQE analyzed as a function of kilovolt (peak), exposure, detector threshold, and readout mode revealed important considerations for system optimization. The model also demonstrated the important implications of false counts from both additive electronic noise and charge sharing and highlighted the system design and operational parameters that most affect detector performance in the presence of such factors: for example, increasing the detector threshold from 0 to 100 (arbitrary units of pulse height threshold roughly equivalent to 0.5 and 6 keV energy threshold, respectively), increased the f 50 (spatial-frequency at

  12. Cascaded systems analysis of photon counting detectors

    Energy Technology Data Exchange (ETDEWEB)

    Xu, J.; Zbijewski, W.; Gang, G.; Stayman, J. W. [Department of Biomedical Engineering, Johns Hopkins University, Baltimore, Maryland 21205 (United States); Taguchi, K.; Carrino, J. A. [Russell H. Morgan Department of Radiology, Johns Hopkins University, Baltimore, Maryland 21205 (United States); Lundqvist, M.; Fredenberg, E. [Philips Healthcare, Solna 171 41 (Sweden); Siewerdsen, J. H., E-mail: jeff.siewerdsen@jhu.edu [Department of Biomedical Engineering, Johns Hopkins University, Baltimore, Maryland 21205 (United States); Russell H. Morgan Department of Radiology, Johns Hopkins University, Baltimore, Maryland 21205 (United States)

    2014-10-15

    Purpose: Photon counting detectors (PCDs) are an emerging technology with applications in spectral and low-dose radiographic and tomographic imaging. This paper develops an analytical model of PCD imaging performance, including the system gain, modulation transfer function (MTF), noise-power spectrum (NPS), and detective quantum efficiency (DQE). Methods: A cascaded systems analysis model describing the propagation of quanta through the imaging chain was developed. The model was validated in comparison to the physical performance of a silicon-strip PCD implemented on an experimental imaging bench. The signal response, MTF, and NPS were measured and compared to theory as a function of exposure conditions (70 kVp, 1–7 mA), detector threshold, and readout mode (i.e., the option for coincidence detection). The model sheds new light on the dependence of spatial resolution, charge sharing, and additive noise effects on threshold selection and was used to investigate the factors governing PCD performance, including the fundamental advantages and limitations of PCDs in comparison to energy-integrating detectors (EIDs) in the linear regime for which pulse pileup can be ignored. Results: The detector exhibited highly linear mean signal response across the system operating range and agreed well with theoretical prediction, as did the system MTF and NPS. The DQE analyzed as a function of kilovolt (peak), exposure, detector threshold, and readout mode revealed important considerations for system optimization. The model also demonstrated the important implications of false counts from both additive electronic noise and charge sharing and highlighted the system design and operational parameters that most affect detector performance in the presence of such factors: for example, increasing the detector threshold from 0 to 100 (arbitrary units of pulse height threshold roughly equivalent to 0.5 and 6 keV energy threshold, respectively), increased the f{sub 50} (spatial

  13. Displacement cascades in a borosilicate glass: Influence of the level of polymerization on the cascade morphology

    Energy Technology Data Exchange (ETDEWEB)

    Delaye, J.M. [Commissariata a l`Energie Atomique (CEA), Centre d`Etudes de Saclay, Gif-sur-Yvette (France); Ghaleb, D. [Commissariat a l`Energie Atomique (CEA), Centre d`Etudes de la Vallee du Rhone, BP 171, 30207 Bagnols-sur-Ceze Cedex (France)

    1998-02-01

    We have performed some molecular dynamics calculations of displacement cascades in a simplified nuclear glass (SiO{sub 2} + B{sub 2}O{sub 3} + Na{sub 2}O + Al{sub 2}O{sub 3} + ZrO{sub 2}). We have observed that the damaged volume at the end of the collision sequence can be divided into a so called highly damaged volume and lightly damaged volume. The aim of this paper is to propose an explanation of this phenomenon by considering that some regions are easy to cross by the projectile and others are difficult to cross by the projectile. Regions which are easy to cross correspond to those containing Na atoms with a low level of polymerisation, and regions which are difficult to cross are areas containing Na atoms with a high level of polymerisation. (orig.) 14 refs.

  14. Space-time evolution of electron cascades in diamond

    International Nuclear Information System (INIS)

    Ziaja, Beata; Szoeke, Abraham; Spoel, David van der; Hajdu, Janos

    2002-01-01

    The impact of a primary electron initiates a cascade of secondary electrons in solids, and these cascades play a significant role in the dynamics of ionization. Here we describe model calculations to follow the spatiotemporal evolution of secondary electron cascades in diamond. The band structure of the insulator has been explicitly incorporated into the calculations as it affects ionizations from the valence band. A Monte Carlo model was constructed to describe the path of electrons following the impact of a single electron of energy E∼250 eV. This energy is similar to the energy of an Auger electron from carbon. Two limiting cases were considered: the case in which electrons transmit energy to the lattice, and the case where no such energy transfer is permitted. The results show the evolution of the secondary electron cascades in terms of the number of electrons liberated, the spatial distribution of these electrons, and the energy distribution among the electrons as a function of time. The predicted ionization rates (∼5-13 electrons in 100 fs) lie within the limits given by experiments and phenomenological models. Calculation of the local electron density and the corresponding Debye length shows that the latter is systematically larger than the radius of the electron cloud, and it increases exponentially with the radial size of the cascade. This means that the long-range Coulomb field is not shielded within this cloud, and the electron gas generated does not represent a plasma in a single impact cascade triggered by an electron of E∼250 eV energy. This is important as it justifies the independent-electron approximation used in the model. At 1 fs, the (average) spatial distribution of secondary electrons is anisotropic with the electron cloud elongated in the direction of the primary impact. The maximal radius of the cascade is about 50 A at this time. At 10 fs the cascade has a maximal radius of ∼70 A, and is already dominated by low-energy electrons

  15. The occurrence of a phosphorylated glycosphingolipid in Aspergillus niger.

    Science.gov (United States)

    Brennan, P J; Roe, J

    1975-01-01

    A novel type of water-soluble phosphorylated glycosphingolipid was isolated from Aspergillus niger by a simple procedure involving precipitation, DEAE-cellulose chromatography and preparative t.l.c. Besides ceramide and phosphorus it contains inositol, galactose, mannose and small amounts of glucosamine. Images PLATE 1 PMID:1156383

  16. A mathematical model of phosphorylation AKT in Acute Myeloid Leukemia

    Science.gov (United States)

    Adi, Y. A.; Kusumo, F. A.; Aryati, L.; Hardianti, M. S.

    2016-04-01

    In this paper we consider a mathematical model of PI3K/AKT signaling pathways in phosphorylation AKT. PI3K/AKT pathway is an important mediator of cytokine signaling implicated in regulation of hematopoiesis. Constitutive activation of PI3K/AKT signaling pathway has been observed in Acute Meyloid Leukemia (AML) it caused by the mutation of Fms-like Tyrosine Kinase 3 in internal tandem duplication (FLT3-ITD), the most common molecular abnormality associated with AML. Depending upon its phosphorylation status, protein interaction, substrate availability, and localization, AKT can phosphorylate or inhibite numerous substrates in its downstream pathways that promote protein synthesis, survival, proliferation, and metabolism. Firstly, we present a mass action ordinary differential equation model describing AKT double phosphorylation (AKTpp) in a system with 11 equations. Finally, under the asumtion enzyme catalyst constant and steady state equilibrium, we reduce the system in 4 equation included Michaelis Menten constant. Simulation result suggested that a high concentration of PI3K and/or a low concentration of phospatase increased AKTpp activation. This result also indicates that PI3K is a potential target theraphy in AML.

  17. Activation of purified calcium channels by stoichiometric protein phosphorylation

    Energy Technology Data Exchange (ETDEWEB)

    Nunoki, K.; Florio, V.; Catterall, W.A. (Univ. of Washington, Seattle (USA))

    1989-09-01

    Purified dihydropyridine-sensitive calcium channels from rabbit skeletal muscle were reconstituted into phosphatidylcholine vesicles to evaluate the effect of phosphorylation by cyclic AMP-dependent protein kinase (PK-A) on their function. Both the rate and extent of {sup 45}Ca{sup 2+} uptake into vesicles containing reconstituted calcium channels were increased severalfold after incubation with ATP and PK-A. The degree of stimulation of {sup 45}Ca{sup 2+} uptake was linearly proportional to the extent of phosphorylation of the alpha 1 and beta subunits of the calcium channel up to a stoichiometry of approximately 1 mol of phosphate incorporated into each subunit. The calcium channels activated by phosphorylation were determined to be incorporated into the reconstituted vesicles in the inside-out orientation and were completely inhibited by low concentrations of dihydropyridines, phenylalkylamines, Cd{sup 2+}, Ni{sup 2+}, and Mg{sup 2+}. The results demonstrate a direct relationship between PK-A-catalyzed phosphorylation of the alpha 1 and beta subunits of the purified calcium channel and activation of the ion conductance activity of the dihydropyridine-sensitive calcium channels.

  18. Activation of purified calcium channels by stoichiometric protein phosphorylation

    International Nuclear Information System (INIS)

    Nunoki, K.; Florio, V.; Catterall, W.A.

    1989-01-01

    Purified dihydropyridine-sensitive calcium channels from rabbit skeletal muscle were reconstituted into phosphatidylcholine vesicles to evaluate the effect of phosphorylation by cyclic AMP-dependent protein kinase (PK-A) on their function. Both the rate and extent of 45 Ca 2+ uptake into vesicles containing reconstituted calcium channels were increased severalfold after incubation with ATP and PK-A. The degree of stimulation of 45 Ca 2+ uptake was linearly proportional to the extent of phosphorylation of the alpha 1 and beta subunits of the calcium channel up to a stoichiometry of approximately 1 mol of phosphate incorporated into each subunit. The calcium channels activated by phosphorylation were determined to be incorporated into the reconstituted vesicles in the inside-out orientation and were completely inhibited by low concentrations of dihydropyridines, phenylalkylamines, Cd 2+ , Ni 2+ , and Mg 2+ . The results demonstrate a direct relationship between PK-A-catalyzed phosphorylation of the alpha 1 and beta subunits of the purified calcium channel and activation of the ion conductance activity of the dihydropyridine-sensitive calcium channels

  19. Extraction of rhenium(VII) by phosphorylated podands

    International Nuclear Information System (INIS)

    Turanov, A.N.; Karandashev, V.K.; Baulin, V.E.

    2006-01-01

    Interphase distribution of ReO 4 - between aqueous solutions of H 2 SO 4 and solutions of phosphoryl-containing podands in organic solvents is studied. Stoichiometry of the complexes extracted is determined. Effect of extractant structure and nature of organic solvent on efficiency of rhenium extraction into organic phase is determined [ru

  20. Linear motif atlas for phosphorylation-dependent signaling

    DEFF Research Database (Denmark)

    Miller, Martin Lee; Jensen, LJ; Diella, F

    2008-01-01

    bind to them remains a challenge. NetPhorest is an atlas of consensus sequence motifs that covers 179 kinases and 104 phosphorylation-dependent binding domains [Src homology 2 (SH2), phosphotyrosine binding (PTB), BRCA1 C-terminal (BRCT), WW, and 14-3-3]. The atlas reveals new aspects of signaling...

  1. Genetic defects in the oxidative phosphorylation (OXPHOS) system.

    NARCIS (Netherlands)

    Janssen, R.J.R.J.; Heuvel, L.P.W.J. van den; Smeitink, J.A.M.

    2004-01-01

    The oxidative phosphorylation (OXPHOS) system consists of five multiprotein complexes and two mobile electron carriers embedded in the lipid bilayer of the mitochondrial inner membrane. With the exception of complex II and the mobile carriers, the other parts of the OXPHOS system are under dual

  2. Phosphorylation of intact erythrocytes in human muscular dystrophy

    International Nuclear Information System (INIS)

    Johnson, R.M.; Nigro, M.

    1986-01-01

    The uptake of exogenous 32 Pi into the membrane proteins of intact erythrocytes was measured in 8 patients with Duchenne muscular dystrophy. No abnormalities were noted after autoradiographic analysis. This contrasts with earlier results obtained when isolated membranes were phosphorylated with gamma-[ 32 P]ATP, and suggests a possible reinterpretation of those experiments

  3. Phosphorylation and disassembly of intermediate filaments in mitotic cells

    International Nuclear Information System (INIS)

    Chou, Yinghao; Rosevear, E.; Goldman, R.D.

    1989-01-01

    As baby hamster kidney (BHK-21) cells enter mitosis, networks of intermediate filaments (IFs) are transformed into cytoplasmic aggregates of protofilaments. Coincident with this morphological change, the phosphate content of vimentin increases from 0.3 mol of P i per mol of protein in interphase to 1.9 mol of P i per mol of protein in mitosis. A similar increase in phosphate content is observed with desmin, from 0.5 mol of P i per mol of protein to 1.5 mol of P i per mol of protein. Fractionation of mitotic cell lysates by hydroxylapatite column chromatography reveals the presence of two IF protein kinase activities, designated as IF protein kinase I and IF protein kinase II. Comparison of two-dimensional 32 P-labeled phosphopeptide maps of vimentin and desmin phosphorylated in vivo in mitosis, and in vitro using partially purified kinase fractions, reveals extensive similarity in the two sets of phosphorylation sites. Phosphorylation of in vitro polymerized IFs by IF protein kinase II induces complete disassembly as determined by negative-stain electron microscopy. The results support the idea that the disassembly of IFs in mitosis is regulated by the phosphorylation of its subunit proteins

  4. Phosphorylation of formate dehydrogenase in potato tuber mitochondria

    DEFF Research Database (Denmark)

    Bykova, N.V.; Stensballe, A.; Egsgaard, H.

    2003-01-01

    Two highly phosphorylated proteins were detected after two-dimensional (blue native/SDS-PAGE) gel electrophoretic separation of the matrix fraction isolated from potato tuber mitochondria. These two phosphoproteins were identified by mass spectrometry as formate dehydrogenase (FDH) and the E1alpha...

  5. Syndecan-4 Phosphorylation Is a Control Point for Integrin Recycling

    Science.gov (United States)

    Morgan, Mark R.; Hamidi, Hellyeh; Bass, Mark D.; Warwood, Stacey; Ballestrem, Christoph; Humphries, Martin J.

    2013-01-01

    Summary Precise spatiotemporal coordination of integrin adhesion complex dynamics is essential for efficient cell migration. For cells adherent to fibronectin, differential engagement of α5β1 and αVβ3 integrins is used to elicit changes in adhesion complex stability, mechanosensation, matrix assembly, and migration, but the mechanisms responsible for receptor regulation have remained largely obscure. We identify phosphorylation of the membrane-intercalated proteoglycan syndecan-4 as an essential switch controlling integrin recycling. Src phosphorylates syndecan-4 and, by driving syntenin binding, leads to suppression of Arf6 activity and recycling of αVβ3 to the plasma membrane at the expense of α5β1. The resultant elevation in αVβ3 engagement promotes stabilization of focal adhesions. Conversely, abrogation of syndecan-4 phosphorylation drives surface expression of α5β1, destabilizes adhesion complexes, and disrupts cell migration. These data identify the dynamic spatiotemporal regulation of Src-mediated syndecan-4 phosphorylation as an essential switch controlling integrin trafficking and adhesion dynamics to promote efficient cell migration. PMID:23453597

  6. Systematic inference of functional phosphorylation events in yeast metabolism

    DEFF Research Database (Denmark)

    Chen, Yu; Wang, Yonghong; Nielsen, Jens

    2017-01-01

    Motivation: Protein phosphorylation is a post-translational modification that affects proteins by changing their structure and conformation in a rapid and reversible way, and it is an important mechanism for metabolic regulation in cells. Phosphoproteomics enables high-throughput identification o...

  7. Stress induces pain transition by potentiation of AMPA receptor phosphorylation.

    Science.gov (United States)

    Li, Changsheng; Yang, Ya; Liu, Sufang; Fang, Huaqiang; Zhang, Yong; Furmanski, Orion; Skinner, John; Xing, Ying; Johns, Roger A; Huganir, Richard L; Tao, Feng

    2014-10-08

    Chronic postsurgical pain is a serious issue in clinical practice. After surgery, patients experience ongoing pain or become sensitive to incident, normally nonpainful stimulation. The intensity and duration of postsurgical pain vary. However, it is unclear how the transition from acute to chronic pain occurs. Here we showed that social defeat stress enhanced plantar incision-induced AMPA receptor GluA1 phosphorylation at the Ser831 site in the spinal cord and greatly prolonged plantar incision-induced pain. Interestingly, targeted mutation of the GluA1 phosphorylation site Ser831 significantly inhibited stress-induced prolongation of incisional pain. In addition, stress hormones enhanced GluA1 phosphorylation and AMPA receptor-mediated electrical activity in the spinal cord. Subthreshold stimulation induced spinal long-term potentiation in GluA1 phosphomimetic mutant mice, but not in wild-type mice. Therefore, spinal AMPA receptor phosphorylation contributes to the mechanisms underlying stress-induced pain transition. Copyright © 2014 the authors 0270-6474/14/3413737-10$15.00/0.

  8. Changes in protein composition and protein phosphorylation during ...

    African Journals Online (AJOL)

    Changes in protein profiles and protein phosphorylation were studied in various stages of germinating somatic and zygotic embryos. Many proteins, which were expressed in cotyledonary stage somatic embryos, were also present in the zygotic embryos obtained from mature dry seed. The intensity of 22 kDa protein was ...

  9. A mathematical model of phosphorylation AKT in Acute Myeloid Leukemia

    Energy Technology Data Exchange (ETDEWEB)

    Adi, Y. A., E-mail: yudi.adi@math.uad.ac.id [Department of Mathematic Faculty of MIPA Universitas Ahmad Dahlan (Indonesia); Department of Mathematic Faculty of MIPA Universitas Gadjah Mada (Indonesia); Kusumo, F. A.; Aryati, L. [Department of Mathematic Faculty of MIPA Universitas Gadjah Mada (Indonesia); Hardianti, M. S. [Department of Internal Medicine, Faculty of Medicine, Universitas Gadjah Mada (Indonesia)

    2016-04-06

    In this paper we consider a mathematical model of PI3K/AKT signaling pathways in phosphorylation AKT. PI3K/AKT pathway is an important mediator of cytokine signaling implicated in regulation of hematopoiesis. Constitutive activation of PI3K/AKT signaling pathway has been observed in Acute Meyloid Leukemia (AML) it caused by the mutation of Fms-like Tyrosine Kinase 3 in internal tandem duplication (FLT3-ITD), the most common molecular abnormality associated with AML. Depending upon its phosphorylation status, protein interaction, substrate availability, and localization, AKT can phosphorylate or inhibite numerous substrates in its downstream pathways that promote protein synthesis, survival, proliferation, and metabolism. Firstly, we present a mass action ordinary differential equation model describing AKT double phosphorylation (AKTpp) in a system with 11 equations. Finally, under the asumtion enzyme catalyst constant and steady state equilibrium, we reduce the system in 4 equation included Michaelis Menten constant. Simulation result suggested that a high concentration of PI3K and/or a low concentration of phospatase increased AKTpp activation. This result also indicates that PI3K is a potential target theraphy in AML.

  10. MOLECULAR DYNAMICS SIMULATIONS OF DISPLACEMENT CASCADES IN MOLYBDENUM

    International Nuclear Information System (INIS)

    Smith, Richard Whiting

    2003-01-01

    Molecular dynamics calculations have been employed to simulate displacement cascades in neutron irradiated Mo. A total of 90 simulations were conducted for PKA energies between 1 and 40 keV and temperatures from 298 to 923K. The results suggest very little effect of temperature on final defect count and configuration, but do display a temperature effect on peak defect generation prior to cascade collapse. Cascade efficiency, relative to the NRT model, is computed to lie between 1/4 and 1/3 in agreement with simulations performed on previous systems. There is a tendency for both interstitials and vacancies to cluster together following cascade collapse producing vacancy rich regions surrounded by interstitials. Although coming to rest in close proximity, the point defects comprising the clusters generally do not lie within the nearest neighbor positions of one another, except for the formation of dumbbell di-interstitials. Cascades produced at higher PKA energies (20 or 40 keV) exhibit the formation of subcascades

  11. INCAS: an analytical model to describe displacement cascades

    Energy Technology Data Exchange (ETDEWEB)

    Jumel, Stephanie E-mail: stephanie.jumel@edf.fr; Claude Van-Duysen, Jean E-mail: jean-claude.van-duysen@edf.fr

    2004-07-01

    REVE (REactor for Virtual Experiments) is an international project aimed at developing tools to simulate neutron irradiation effects in Light Water Reactor materials (Fe, Ni or Zr-based alloys). One of the important steps of the project is to characterise the displacement cascades induced by neutrons. Accordingly, the Department of Material Studies of Electricite de France developed an analytical model based on the binary collision approximation. This model, called INCAS (INtegration of CAScades), was devised to be applied on pure elements; however, it can also be used on diluted alloys (reactor pressure vessel steels, etc.) or alloys composed of atoms with close atomic numbers (stainless steels, etc.). INCAS describes displacement cascades by taking into account the nuclear collisions and electronic interactions undergone by the moving atoms. In particular, it enables to determine the mean number of sub-cascades induced by a PKA (depending on its energy) as well as the mean energy dissipated in each of them. The experimental validation of INCAS requires a large effort and could not be carried out in the framework of the study. However, it was verified that INCAS results are in conformity with those obtained from other approaches. As a first application, INCAS was applied to determine the sub-cascade spectrum induced in iron by the neutron spectrum corresponding to the central channel of the High Flux Irradiation Reactor of Oak Ridge National Laboratory.

  12. INCAS: an analytical model to describe displacement cascades

    Science.gov (United States)

    Jumel, Stéphanie; Claude Van-Duysen, Jean

    2004-07-01

    REVE (REactor for Virtual Experiments) is an international project aimed at developing tools to simulate neutron irradiation effects in Light Water Reactor materials (Fe, Ni or Zr-based alloys). One of the important steps of the project is to characterise the displacement cascades induced by neutrons. Accordingly, the Department of Material Studies of Electricité de France developed an analytical model based on the binary collision approximation. This model, called INCAS (INtegration of CAScades), was devised to be applied on pure elements; however, it can also be used on diluted alloys (reactor pressure vessel steels, etc.) or alloys composed of atoms with close atomic numbers (stainless steels, etc.). INCAS describes displacement cascades by taking into account the nuclear collisions and electronic interactions undergone by the moving atoms. In particular, it enables to determine the mean number of sub-cascades induced by a PKA (depending on its energy) as well as the mean energy dissipated in each of them. The experimental validation of INCAS requires a large effort and could not be carried out in the framework of the study. However, it was verified that INCAS results are in conformity with those obtained from other approaches. As a first application, INCAS was applied to determine the sub-cascade spectrum induced in iron by the neutron spectrum corresponding to the central channel of the High Flux Irradiation Reactor of Oak Ridge National Laboratory.

  13. INCAS: an analytical model to describe displacement cascades

    International Nuclear Information System (INIS)

    Jumel, Stephanie; Claude Van-Duysen, Jean

    2004-01-01

    REVE (REactor for Virtual Experiments) is an international project aimed at developing tools to simulate neutron irradiation effects in Light Water Reactor materials (Fe, Ni or Zr-based alloys). One of the important steps of the project is to characterise the displacement cascades induced by neutrons. Accordingly, the Department of Material Studies of Electricite de France developed an analytical model based on the binary collision approximation. This model, called INCAS (INtegration of CAScades), was devised to be applied on pure elements; however, it can also be used on diluted alloys (reactor pressure vessel steels, etc.) or alloys composed of atoms with close atomic numbers (stainless steels, etc.). INCAS describes displacement cascades by taking into account the nuclear collisions and electronic interactions undergone by the moving atoms. In particular, it enables to determine the mean number of sub-cascades induced by a PKA (depending on its energy) as well as the mean energy dissipated in each of them. The experimental validation of INCAS requires a large effort and could not be carried out in the framework of the study. However, it was verified that INCAS results are in conformity with those obtained from other approaches. As a first application, INCAS was applied to determine the sub-cascade spectrum induced in iron by the neutron spectrum corresponding to the central channel of the High Flux Irradiation Reactor of Oak Ridge National Laboratory

  14. Positional information generated by spatially distributed signaling cascades.

    Directory of Open Access Journals (Sweden)

    Javier Muñoz-García

    2009-03-01

    Full Text Available The temporal and stationary behavior of protein modification cascades has been extensively studied, yet little is known about the spatial aspects of signal propagation. We have previously shown that the spatial separation of opposing enzymes, such as a kinase and a phosphatase, creates signaling activity gradients. Here we show under what conditions signals stall in the space or robustly propagate through spatially distributed signaling cascades. Robust signal propagation results in activity gradients with long plateaus, which abruptly decay at successive spatial locations. We derive an approximate analytical solution that relates the maximal amplitude and propagation length of each activation profile with the cascade level, protein diffusivity, and the ratio of the opposing enzyme activities. The control of the spatial signal propagation appears to be very different from the control of transient temporal responses for spatially homogenous cascades. For spatially distributed cascades where activating and deactivating enzymes operate far from saturation, the ratio of the opposing enzyme activities is shown to be a key parameter controlling signal propagation. The signaling gradients characteristic for robust signal propagation exemplify a pattern formation mechanism that generates precise spatial guidance for multiple cellular processes and conveys information about the cell size to the nucleus.

  15. Annealing simulation of cascade damage using MARLOWE-DAIQUIRI codes

    International Nuclear Information System (INIS)

    Muroga, Takeo

    1984-01-01

    The localization effect of the defects generated by the cascade damage on the properties of solids was studied by using a computer code. The code is based on the two-body collision approximation method and the Monte Carlo method. The MARLOWE and DAIQUIRI codes were partly improved to fit the present calculation of the annealing of cascade damage. The purpose of this study is to investigate the behavior of defects under the simulated reactive and irradiation condition. Calculation was made for alpha iron (BCC), and the threshold energy was set at 40 eV. The temperature dependence of annealing and the growth of a cluster were studied. The overlapping effect of cascade was studied. At first, the extreme case of overlapping was studied, then the practical cases were estimated by interpolation. The state of overlapping of cascade corresponded to the irradiation speed. The interaction between cascade and dislocations was studied, and the calculation of the annealing of primary knock-out atoms (PKA) in alpha iron was performed. At low temperature, the effect of dislocations was large, but the growth of vacancy was not seen. At high temperature, the effect of dislocations was small. The evaluation of the simulation of various ion irradiation and the growth efficiency of defects were performed. (Kato, T.)

  16. Framework for cascade size calculations on random networks

    Science.gov (United States)

    Burkholz, Rebekka; Schweitzer, Frank

    2018-04-01

    We present a framework to calculate the cascade size evolution for a large class of cascade models on random network ensembles in the limit of infinite network size. Our method is exact and applies to network ensembles with almost arbitrary degree distribution, degree-degree correlations, and, in case of threshold models, for arbitrary threshold distribution. With our approach, we shift the perspective from the known branching process approximations to the iterative update of suitable probability distributions. Such distributions are key to capture cascade dynamics that involve possibly continuous quantities and that depend on the cascade history, e.g., if load is accumulated over time. As a proof of concept, we provide two examples: (a) Constant load models that cover many of the analytically tractable casacade models, and, as a highlight, (b) a fiber bundle model that was not tractable by branching process approximations before. Our derivations cover the whole cascade dynamics, not only their steady state. This allows us to include interventions in time or further model complexity in the analysis.

  17. Cascades and Dissipative Anomalies in Compressible Fluid Turbulence

    Directory of Open Access Journals (Sweden)

    Gregory L. Eyink

    2018-02-01

    Full Text Available We investigate dissipative anomalies in a turbulent fluid governed by the compressible Navier-Stokes equation. We follow an exact approach pioneered by Onsager, which we explain as a nonperturbative application of the principle of renormalization-group invariance. In the limit of high Reynolds and Péclet numbers, the flow realizations are found to be described as distributional or “coarse-grained” solutions of the compressible Euler equations, with standard conservation laws broken by turbulent anomalies. The anomalous dissipation of kinetic energy is shown to be due not only to local cascade but also to a distinct mechanism called pressure-work defect. Irreversible heating in stationary, planar shocks with an ideal-gas equation of state exemplifies the second mechanism. Entropy conservation anomalies are also found to occur via two mechanisms: an anomalous input of negative entropy (negentropy by pressure work and a cascade of negentropy to small scales. We derive “4/5th-law”-type expressions for the anomalies, which allow us to characterize the singularities (structure-function scaling exponents required to sustain the cascades. We compare our approach with alternative theories and empirical evidence. It is argued that the “Big Power Law in the Sky” observed in electron density scintillations in the interstellar medium is a manifestation of a forward negentropy cascade or an inverse cascade of usual thermodynamic entropy.

  18. Cascades and Dissipative Anomalies in Compressible Fluid Turbulence

    Science.gov (United States)

    Eyink, Gregory L.; Drivas, Theodore D.

    2018-02-01

    We investigate dissipative anomalies in a turbulent fluid governed by the compressible Navier-Stokes equation. We follow an exact approach pioneered by Onsager, which we explain as a nonperturbative application of the principle of renormalization-group invariance. In the limit of high Reynolds and Péclet numbers, the flow realizations are found to be described as distributional or "coarse-grained" solutions of the compressible Euler equations, with standard conservation laws broken by turbulent anomalies. The anomalous dissipation of kinetic energy is shown to be due not only to local cascade but also to a distinct mechanism called pressure-work defect. Irreversible heating in stationary, planar shocks with an ideal-gas equation of state exemplifies the second mechanism. Entropy conservation anomalies are also found to occur via two mechanisms: an anomalous input of negative entropy (negentropy) by pressure work and a cascade of negentropy to small scales. We derive "4 /5 th-law"-type expressions for the anomalies, which allow us to characterize the singularities (structure-function scaling exponents) required to sustain the cascades. We compare our approach with alternative theories and empirical evidence. It is argued that the "Big Power Law in the Sky" observed in electron density scintillations in the interstellar medium is a manifestation of a forward negentropy cascade or an inverse cascade of usual thermodynamic entropy.

  19. Gradients in Catostomid assemblages along a reservoir cascade

    Science.gov (United States)

    Miranda, Leandro E.; Keretz, Kevin R.; Gilliland, Chelsea R.

    2017-01-01

    Serial impoundment of major rivers leads to alterations of natural flow dynamics and disrupts longitudinal connectivity. Catostomid fishes (suckers, family Catostomidae) are typically found in riverine or backwater habitats yet are able to persist in impounded river systems. To the detriment of conservation, there is limited information about distribution of catostomid fishes in impounded rivers. We examined the longitudinal distribution of catostomid fishes over 23 reservoirs of the Tennessee River reservoir cascade, encompassing approximately 1600 km. Our goal was to develop a basin-scale perspective to guide conservation efforts. Catostomid species composition and assemblage structure changed longitudinally along the reservoir cascade. Catostomid species biodiversity was greatest in reservoirs lower in the cascade. Assemblage composition shifted from dominance by spotted sucker Minytrema melanops and buffalos Ictiobus spp. in the lower reservoirs to carpsuckers Carpiodes spp. midway through the cascade and redhorses Moxostoma spp. in the upper reservoirs. Most species did not extend the length of the cascade, and some species were rare, found in low numbers and in few reservoirs. The observed gradients in catostomid assemblages suggest the need for basin-scale conservation measures focusing on three broad areas: (1) conservation and management of the up-lake riverine reaches of the lower reservoirs, (2) maintenance of the access to quality habitat in tributaries to the upper reservoirs and (3) reintroductions into currently unoccupied habitat within species' historic distributions

  20. Critical assessment and ramifications of a purported marine trophic cascade

    Science.gov (United States)

    Grubbs, R. Dean; Carlson, John K; Romine, Jason G.; Curtis, Tobey H; McElroy, W. David; McCandless, Camilla T; Cotton, Charles F; Musick, John A.

    2016-01-01

    When identifying potential trophic cascades, it is important to clearly establish the trophic linkages between predators and prey with respect to temporal abundance, demographics, distribution, and diet. In the northwest Atlantic Ocean, the depletion of large coastal sharks was thought to trigger a trophic cascade whereby predation release resulted in increased cownose ray abundance, which then caused increased predation on and subsequent collapse of commercial bivalve stocks. These claims were used to justify the development of a predator-control fishery for cownose rays, the “Save the Bay, Eat a Ray” fishery, to reduce predation on commercial bivalves. A reexamination of data suggests declines in large coastal sharks did not coincide with purported rapid increases in cownose ray abundance. Likewise, the increase in cownose ray abundance did not coincide with declines in commercial bivalves. The lack of temporal correlations coupled with published diet data suggest the purported trophic cascade is lacking the empirical linkages required of a trophic cascade. Furthermore, the life history parameters of cownose rays suggest they have low reproductive potential and their populations are incapable of rapid increases. Hypothesized trophic cascades should be closely scrutinized as spurious conclusions may negatively influence conservation and management decisions.

  1. A period-doubling cascade precedes chaos for planar maps.

    Science.gov (United States)

    Sander, Evelyn; Yorke, James A

    2013-09-01

    A period-doubling cascade is often seen in numerical studies of those smooth (one-parameter families of) maps for which as the parameter is varied, the map transitions from one without chaos to one with chaos. Our emphasis in this paper is on establishing the existence of such a cascade for many maps with phase space dimension 2. We use continuation methods to show the following: under certain general assumptions, if at one parameter there are only finitely many periodic orbits, and at another parameter value there is chaos, then between those two parameter values there must be a cascade. We investigate only families that are generic in the sense that all periodic orbit bifurcations are generic. Our method of proof in showing there is one cascade is to show there must be infinitely many cascades. We discuss in detail two-dimensional families like those which arise as a time-2π maps for the Duffing equation and the forced damped pendulum equation.

  2. Topographical distribution of phosphorylation sites of phosvitins by mass spectrometry.

    Science.gov (United States)

    Czernick, Drew; Liu, Jess; Serge, Dibart; Salih, Erdjan

    2013-05-27

    Phosvitin, derived from the vitellogenin II gene protein, is a highly phosphorylated protein found in egg yolk. A second hypothetical protein has been predicted based on the vitellogenin I gene, but has not been defined at the protein level. Mass spectrometric analysis was used to identify the phosphopeptide sequences and the precise sites of phosphorylation of two phosvitins, phosvitin 1 and phosvitin 2 derived from vitellogenins I and II, respectively. Samples of native phosvitin were subjected to tryptic digestion followed by mass spectrometric analysis: (i) native phosvitin peptides, (ii) after treatment with NaOH, and (iii) after chemical derivatization of P-Ser/P-Thr residues by dithiothreitol under base-catalyzed conditions. A combination of these approaches led to the identification of 68 and 35 phosphopeptides with 89 (81 P-Ser and 8 P-Thr residues) and 62 (57 P-Ser and 5 P-Thr residues) phosphorylation sites of phosvitin 1 and phosvitin 2, respectively. These data for the first time documented on a large scale the major states and sites of phosphorylation of phosvitins with a total of 151 phosphorylation sites. Importantly, the present work also provided the first direct de novo protein amino-acid sequence data for phosvitin 1 protein and evidence for the full expression of vitellogenin I gene. We have for the first time generated a large number of phosphopeptides (~100) and identified 151 phosphorylation sites of phosvitin 1 and phosvitin 2, respectively. Importantly, this study also led to the discovery of a novel phosvitin 1 and provided the first direct de novo protein amino-acid sequence data for the full expression of vitellogenin I gene. There is considerable interest in naturally occurring phosphopeptides/phosphoproteins and their application in biomedical fields and in the food industry because of their molecular characteristics and non-toxic nature, hence, our work opens new avenues to pursue such endeavors. In addition, the results provide

  3. Phosphorylation of acidic ribosomal proteins from rabbit reticulocytes by a ribosome-associated casein kinase

    DEFF Research Database (Denmark)

    Issinger, O G

    1977-01-01

    Two acidic proteins from 80-S ribosomes were isolated and purified to homogeneity. The purified acidic proteins could be phosphorylated by casein kinase using [gamma-32P]ATP and [gamma-32P]GTP as a phosphoryl donor. The proteins became phosphorylated in situ, too. Sodium dodecyl sulfate polyacryl......Two acidic proteins from 80-S ribosomes were isolated and purified to homogeneity. The purified acidic proteins could be phosphorylated by casein kinase using [gamma-32P]ATP and [gamma-32P]GTP as a phosphoryl donor. The proteins became phosphorylated in situ, too. Sodium dodecyl sulfate...

  4. Proteomic analysis of tyrosine phosphorylation during human liver transplantation

    Directory of Open Access Journals (Sweden)

    Boutros Tarek

    2007-01-01

    Full Text Available Abstract Background Ischemia-reperfusion (I/R causes a dramatic reprogramming of cell metabolism during liver transplantation and can be linked to an alteration of the phosphorylation level of several cellular proteins. Over the past two decades, it became clear that tyrosine phosphorylation plays a pivotal role in a variety of important signalling pathways and was linked to a wide spectrum of diseases. Functional profiling of the tyrosine phosphoproteome during liver transplantation is therefore of great biological significance and is likely to lead to the identification of novel targets for drug discovery and provide a basis for novel therapeutic strategies. Results Using liver biopsies collected during the early phases of organ procurement and transplantation, we aimed at characterizing the global patterns of tyrosine phosphorylation during hepatic I/R. A proteomic approach, based on the purification of tyrosine phosphorylated proteins followed by their identification using mass spectrometry, allowed us to identify Nck-1, a SH2/SH3 adaptor, as a potential regulator of I/R injury. Using immunoblot, cell fractionation and immunohistochemistry, we demonstrate that Nck-1 phosphorylation, expression and localization were affected in liver tissue upon I/R. In addition, mass spectrometry identification of Nck-1 binding partners during the course of the transplantation also suggested a dynamic interaction between Nck-1 and actin during I/R. Conclusion Taken together, our data suggest that Nck-1 may play a role in I/R-induced actin reorganization, which was previously reported to be detrimental for the hepatocytes of the transplanted graft. Nck-1 could therefore represent a target of choice for the design of new organ preservation strategies, which could consequently help to reduce post-reperfusion liver damages and improve transplantation outcomes.

  5. Thymosin-β4 (Tβ4) Blunts PDGF-Dependent Phosphorylation and Binding of AKT to Actin in Hepatic Stellate Cells

    Science.gov (United States)

    Reyes-Gordillo, Karina; Shah, Ruchi; Popratiloff, Anastas; Fu, Sidney; Hindle, Anna; Brody, Frederick; Rojkind, Marcos

    2011-01-01

    Hepatic stellate cell transdifferentiation is a key event in the fibrogenic cascade. Therefore, attempts to prevent and/or revert the myofibroblastic phenotype could result in novel therapeutic approaches to treat liver cirrhosis. The expression of platelet-derived growth factor (PDGF)-β receptor and the proliferative response to platelet-derived growth factor-ββ (PDGF-ββ) are hallmarks of the transdifferentiation of hepatic stellate cells (HSC). In this communication, we investigated whether thymosin-β4 (Tβ4), a chemokine expressed by HSC could prevent PDGF-BB-mediated proliferation and migration of cultured HSC. Using early passages of human HSC, we showed that Tβ4 inhibited cell proliferation and migration and prevented the expression of PDGF-β receptor (PDGF-βr), α-smooth muscle actin and α1(I) collagen mRNAs. Tβ4 also inhibited the reappearance of PDGF-βr after its PDGF-BB-dependent degradation. These PDGF-dependent events were associated with the inhibition of AKT phosphorylation at both T308 and S473 amino acid residues. The lack of AKT phosphorylation was not due to the inhibition of PDGF-βr phosphorylation, the activation of phosphoinositide 3-kinase (PI3K), pyruvate dehydrogenase kinase isozyme 1 (PDK1), and mammalian target of rapamycin (mTOR). We found that PDGF-BB induced AKT binding to actin, and that Tβ4 prevented this effect. Tβ4 also prevented the activation of freshly isolated HSC cultured in the presence of Dulbecco's modified Eagle's medium or Dulbecco's minimal essential medium containing 10% fetal bovine serum. In conclusion, overall, our findings suggest that Tβ4 by sequestering actin prevents binding of AKT, thus inhibiting its phosphorylation. Therefore, Tβ4 has the potential to be an antifibrogenic agent. PMID:21514425

  6. Andrographolide induces vascular smooth muscle cell apoptosis through a SHP-1-PP2A-p38MAPK-p53 cascade.

    Science.gov (United States)

    Chen, Yu-Ying; Hsieh, Cheng-Ying; Jayakumar, Thanasekaran; Lin, Kuan-Hung; Chou, Duen-Suey; Lu, Wan-Jung; Hsu, Ming-Jen; Sheu, Joen-Rong

    2014-07-10

    The abnormal growth of vascular smooth muscle cells (VSMCs) is considered a critical pathogenic process in inflammatory vascular diseases. We have previously demonstrated that protein phosphatase 2 A (PP2A)-mediated NF-κB dephosphorylation contributes to the anti-inflammatory properties of andrographolide, a novel NF-κB inhibitor. In this study, we investigated whether andrographolide causes apoptosis, and characterized its apoptotic mechanisms in rat VSMCs. Andrographolide activated the p38 mitogen-activated protein kinase (p38MAPK), leading to p53 phosphorylation. Phosphorylated p53 subsequently transactivated the expression of Bax, a pro-apoptotic protein. Transfection with pp2a small interfering RNA (siRNA) suppressed andrographolide-induced p38MAPK activation, p53 phosphorylation, and caspase 3 activation. Andrographolide also activated the Src homology 1 domain-containing protein tyrosine phosphatase (SHP-1), and induced PP2A dephosphorylation, both of which were inhibited by the SHP-1 inhibitor sodium stibogluconate (SSG) or shp-1 siRNA. SSG or shp-1 siRNA prevented andrographolide-induced apoptosis. These results suggest that andrographolide activates the PP2A-p38MAPK-p53-Bax cascade, causing mitochondrial dysfunction and VSMC death through an SHP-1-dependent mechanism.

  7. Corticotropin-Releasing Factor Mediates Pain-Induced Anxiety through the ERK1/2 Signaling Cascade in Locus Coeruleus Neurons

    Science.gov (United States)

    Borges, Gisela Patrícia; Micó, Juan Antonio; Neto, Fani Lourença

    2015-01-01

    Background: The corticotropin-releasing factor is a stress-related neuropeptide that modulates locus coeruleus activity. As locus coeruleus has been involved in pain and stress-related patologies, we tested whether the pain-induced anxiety is a result of the corticotropin-releasing factor released in the locus coeruleus. Methods: Complete Freund’s adjuvant-induced monoarthritis was used as inflammatory chronic pain model. α-Helical corticotropin-releasing factor receptor antagonist was microinjected into the contralateral locus coeruleus of 4-week-old monoarthritic animals. The nociceptive and anxiety-like behaviors, as well as phosphorylated extracellular signal-regulated kinases 1/2 and corticotropin-releasing factor receptors expression, were quantified in the paraventricular nucleus and locus coeruleus. Results: Monoarthritic rats manifested anxiety and increased phosphorylated extracellular signal-regulated kinases 1/2 levels in the locus coeruleus and paraventricular nucleus, although the expression of corticotropin-releasing factor receptors was unaltered. α-Helical corticotropin-releasing factor antagonist administration reversed both the anxiogenic-like behavior and the phosphorylated extracellular signal-regulated kinases 1/2 levels in the locus coeruleus. Conclusions: Pain-induced anxiety is mediated by corticotropin-releasing factor neurotransmission in the locus coeruleus through extracellular signal-regulated kinases 1/2 signaling cascade. PMID:25716783

  8. Discrimination between acid and alkali-labile phosphorylated residues on Immobilon: phosphorylation studies of nucleoside diphosphate kinase

    DEFF Research Database (Denmark)

    Biondi, R M; Walz, K; Issinger, O G

    1996-01-01

    of phosphoserine after strong acid hydrolysis of the histidine autophosphorylated enzyme is in fact a nonenzymatic transphosphorylation from phosphohistidine due to the harsh acid treatment. This methodology was also applied to in vivo phosphorylation studies of C. albicans NDP kinase. We believe...

  9. Cascaded Photoenhancement: Implications for Photonic Chemical and Biological Sensors

    Science.gov (United States)

    Fuller, Kirk A.; Smith, David D.

    2006-01-01

    Our analysis shows that coupling of gold nanoparticles to microspheres will evoke a cascading effect from the respective photoenhancement mechanisms. We refer to this amplification process as cascaded photoenhancement, and the resulting cavity amplification of surface-enhanced Raman scattering (SERS) and fluorescence as CASERS and CAF, respectively. Calculations, based on modal analysis of scattering and absorption by compound spheres, presented herein indicate that the absorption cross sections of metal nanoparticles immobilized onto dielectric microspheres can be greatly enhanced by cavity resonances in the microspheres without significant degradation of the resonators. Gain factors associated with CSP of 10(exp 3) - 10(exp 4) are predicted for realistic experimental conditions using homogenous microspheres. Cascaded surface photoenhancement thus has the potential of dramatically increasing the sensitivities of fluorescence and vibrational spectroscopies.

  10. Cascade: a review of heat transport and plant design issues

    International Nuclear Information System (INIS)

    Murray, K.A.; McDowell, M.W.

    1984-01-01

    A conceptual heat transfer loop for Cascade, a centrifugal-action solid-breeder reaction chamber, has been investigated and results are presented. The Cascade concept, a double-cone-shaped reaction chamber, rotates along its horizontal axis. Solid Li 2 O or other lithium-ceramic granules are injected tangentially through each end of the chamber. The granules cascade axially from the smaller radii at the ends to the larger radius at the center, where they are ejected into a stationary granule catcher. Heat and tritium are then removed from the granules and the granules are reinjected into the chamber. A 50% dense Li 2 O granule throughput of 2.8 m 3 /s is transferred from the reaction chamber to the steam generators via continuous bucket elevators. The granules then fall by gravity through 4 vertical steam generators. The entire transport system is maintained at the same vacuum conditions present inside the reaction chamber

  11. Optimization Control of Bidirectional Cascaded DC-AC Converter Systems

    DEFF Research Database (Denmark)

    Tian, Yanjun

    in bidirectional cascaded converter. This research work analyses the control strategies based on the topology of dual active bridges converter cascaded with a three phase inverter. It firstly proposed a dc link voltage and active power coordinative control method for this cascaded topology, and it can reduce dc....... The connections of the renewable energy sources to the power system are mostly through the power electronic converters. Moreover, for high controllability and flexibility, power electronic devices are gradually acting as the interface between different networks in power systems, promoting conventional power...... the bidirectional power flow in the distribution level of power systems. Therefore direct contact of converters introduces significant uncertainties to power system, especially for the stability and reliability. This dissertation studies the optimization control of the two stages directly connected converters...

  12. Bearing-Only Formation Control for Cascade Multirobots

    Directory of Open Access Journals (Sweden)

    Qing Han

    2016-01-01

    Full Text Available A new formation control method is proposed, which is used to queue multirobots in a single-direction cascade structure. In the cascade formation, each robot is a follower for the previous robot and a leader for the next robot, and the robots in the middle act as both leader and follower. The follower robot can only observe the bearing information of the leader robot. The observability of the cascade leader-follower formation is studied, which shows that the bearing-only observation meets the observability conditions required for the nonlinear system. Based on the bearing-only observations, the unscented Kalman filter (UKF is employed for the state estimation of the leader and the follower robots at all levels, which enables the real-time movement control of the follower robots via the input-output feedback control. Simulation results demonstrate that the proposed approach can efficiently control the formation of multirobots as desired.

  13. Substrate-driven chemotactic assembly in an enzyme cascade

    Science.gov (United States)

    Zhao, Xi; Palacci, Henri; Yadav, Vinita; Spiering, Michelle M.; Gilson, Michael K.; Butler, Peter J.; Hess, Henry; Benkovic, Stephen J.; Sen, Ayusman

    2018-03-01

    Enzymatic catalysis is essential to cell survival. In many instances, enzymes that participate in reaction cascades have been shown to assemble into metabolons in response to the presence of the substrate for the first enzyme. However, what triggers metabolon formation has remained an open question. Through a combination of theory and experiments, we show that enzymes in a cascade can assemble via chemotaxis. We apply microfluidic and fluorescent spectroscopy techniques to study the coordinated movement of the first four enzymes of the glycolysis cascade: hexokinase, phosphoglucose isomerase, phosphofructokinase and aldolase. We show that each enzyme independently follows its own specific substrate gradient, which in turn is produced by the preceding enzymatic reaction. Furthermore, we find that the chemotactic assembly of enzymes occurs even under cytosolic crowding conditions.

  14. Correlation Scales of the Turbulent Cascade at 1 au

    Science.gov (United States)

    Smith, Charles W.; Vasquez, Bernard J.; Coburn, Jesse T.; Forman, Miriam A.; Stawarz, Julia E.

    2018-05-01

    We examine correlation functions of the mixed, third-order expressions that, when ensemble-averaged, describe the cascade of energy in the inertial range of magnetohydrodynamic turbulence. Unlike the correlation function of primitive variables such as the magnetic field, solar wind velocity, temperature, and density, the third-order expressions decorrelate at a scale that is approximately 20% of the lag. This suggests the nonlinear dynamics decorrelate in less than one wavelength. Therefore, each scale can behave differently from one wavelength to the next. In the same manner, different scales within the inertial range can behave independently at any given time or location. With such a cascade that can be strongly patchy and highly variable, it is often possible to obtain negative cascade rates for short periods of time, as reported earlier for individual samples of data.

  15. Investigation of cascade effect failure for tungsten armour

    International Nuclear Information System (INIS)

    Makhankov, A.; Barabash, V.; Berkhov, N.; Divavin, V.; Giniatullin, R.; Grigoriev, S.; Ibbott, C.; Komarov, V.; Labusov, A.; Mazul, I.; McDonald, J.; Tanchuk, V.; Youchison, D.

    2001-01-01

    The glancing angle of incident power on the target of a tokamak divertor results in doubled and highly peaked heat flux onto adjacent downstream tile in the case of lost of tile event (LOTE). As a result downstream tile has higher probability to fail resulting in triple loads to the next downstream tile and so on (cascade effect). This paper devoted to analytical and experimental investigation of the cascade effect failure for the flat tile option of tungsten armoured plasma facing components. Armour geometry resistant to the cascade effect failure was selected on the base of thermal and stress analyses. Experimental investigation of the LOTE has been performed also. Small size W/Cu mock-up withstood not only LOTE simulation load, but also survived afterwards for 1500 cycles at 26-28 MW/m 2 without damage in joint

  16. Cascaded bidirectional recurrent neural networks for protein secondary structure prediction.

    Science.gov (United States)

    Chen, Jinmiao; Chaudhari, Narendra

    2007-01-01

    Protein secondary structure (PSS) prediction is an important topic in bioinformatics. Our study on a large set of non-homologous proteins shows that long-range interactions commonly exist and negatively affect PSS prediction. Besides, we also reveal strong correlations between secondary structure (SS) elements. In order to take into account the long-range interactions and SS-SS correlations, we propose a novel prediction system based on cascaded bidirectional recurrent neural network (BRNN). We compare the cascaded BRNN against another two BRNN architectures, namely the original BRNN architecture used for speech recognition as well as Pollastri's BRNN that was proposed for PSS prediction. Our cascaded BRNN achieves an overall three state accuracy Q3 of 74.38\\%, and reaches a high Segment OVerlap (SOV) of 66.0455. It outperforms the original BRNN and Pollastri's BRNN in both Q3 and SOV. Specifically, it improves the SOV score by 4-6%.

  17. Process Evaluation Tools for Enzymatic Cascades Welcome Message

    DEFF Research Database (Denmark)

    Abu, Rohana

    improvement and implementation. Hence, the goal of this thesis is to evaluate the process concepts in enzymatic cascades in a systematic manner, using tools such as thermodynamic and kinetic analysis. Three relevant case studies have been used to exemplify the approach. In the first case study, thermodynamic......Biocatalysis is attracting significant attention from both academic and industrial scientists due to the excellent capability of enzyme to catalyse selective reactions. Recently, much interest has been shown in the application of enzymatic cascades as a useful tool in organic synthesis......, the kinetics can be controlled in a highly efficient way to achieve a sufficiently favourable conversion to a given target product. This is exemplified in the second case study, in the kinetic modelling of the formation of 2-ketoglutarate from glucoronate, the second case study. This cascade consists of 4...

  18. Electron cascades in sensors for optical detection of ionizing radiation

    International Nuclear Information System (INIS)

    London, Richard A.; Lowry, Mark E.; Vernon, Stephen P.; Stewart, Richard E.

    2013-01-01

    A new class of high-speed detectors, called RadOptic detectors, measures ionizing radiation incident on a transparent semiconductor by sensing changes in the refractive index with an optical probe beam. We describe the role of radiation-initiated electron cascades in setting the sensitivity and the spatial and temporal resolution of RadOptic detectors. We model electron cascades with both analytical and Monte Carlo computational methods. We find that the timescale for the development of an electron cascade is less than of order 100 fs and is not expected to affect the time response of a detector. The characteristic size of the electron cloud is typically less than 2 μm, enabling high spatial resolution in imaging systems. The electron-hole pair density created by single x-rays is much smaller than the saturation density and, therefore, single events should not saturate the detector

  19. Spectrally high performing quantum cascade lasers

    Science.gov (United States)

    Toor, Fatima

    Quantum cascade (QC) lasers are versatile semiconductor light sources that can be engineered to emit light of almost any wavelength in the mid- to far-infrared (IR) and terahertz region from 3 to 300 mum [1-5]. Furthermore QC laser technology in the mid-IR range has great potential for applications in environmental, medical and industrial trace gas sensing [6-10] since several chemical vapors have strong rovibrational frequencies in this range and are uniquely identifiable by their absorption spectra through optical probing of absorption and transmission. Therefore, having a wide range of mid-IR wavelengths in a single QC laser source would greatly increase the specificity of QC laser-based spectroscopic systems, and also make them more compact and field deployable. This thesis presents work on several different approaches to multi-wavelength QC laser sources that take advantage of band-structure engineering and the uni-polar nature of QC lasers. Also, since for chemical sensing, lasers with narrow linewidth are needed, work is presented on a single mode distributed feedback (DFB) QC laser. First, a compact four-wavelength QC laser source, which is based on a 2-by-2 module design, with two waveguides having QC laser stacks for two different emission wavelengths each, one with 7.0 mum/11.2 mum, and the other with 8.7 mum/12.0 mum is presented. This is the first design of a four-wavelength QC laser source with widely different emission wavelengths that uses minimal optics and electronics. Second, since there are still several unknown factors that affect QC laser performance, results on a first ever study conducted to determine the effects of waveguide side-wall roughness on QC laser performance using the two-wavelength waveguides is presented. The results are consistent with Rayleigh scattering effects in the waveguides, with roughness effecting shorter wavelengths more than longer wavelengths. Third, a versatile time-multiplexed multi-wavelength QC laser system that

  20. IL6 induces TAM resistance via kinase-specific phosphorylation of ERα in OVCA cells.

    Science.gov (United States)

    Wang, Yue; Niu, Xiu Long; Guo, Xiao Qin; Yang, Jing; Li, Ling; Qu, Ye; Xiu Hu, Cun; Mao, Li Qun; Wang, Dan

    2015-06-01

    About 40-60% of ovarian cancer (OVCA) cases express ERα, but only a small proportion of patients respond clinically to anti-estrogen treatment with estrogen receptor (ER) antagonist tamoxifen (TAM). The mechanism of TAM resistance in the course of OVCA progression remains unclear. However, IL6 plays a critical role in the development and progression of OVCA. Our recent results indicated that IL6 secreted by OVCA cells may promote the resistance of these cells to TAM via ER isoforms and steroid hormone receptor coactivator-1. Here we demonstrate that both exogenous (a relatively short period of treatment with recombinant IL6) and endogenous IL6 (generated as a result of transfection with a plasmid encoding sense IL6) increases expression of pERα-Ser118 and pERα-Ser167 in non-IL6-expressing A2780 cells, while deleting endogenous IL6 expression in IL6-overexpressing CAOV-3 cells (by transfection with a plasmid encoding antisense IL6) reduces expression of pERα-Ser118 and pERα-Ser167, indicating that IL6-induced TAM resistance may also be associated with increased expression of pERα-Ser118 and pERα-Ser167 in OVCA cells. Results of further investigation indicate that IL6 phosphorylates ERα at Ser118 and Ser167 by triggering activation of MEK/ERK and phosphotidylinositol 3 kinase/Akt signaling, respectively, to activate the ER pathway and thereby induce OVCA cells resistance to TAM. These results indicate that IL6 secreted by OVCA cells may also contribute to the refractoriness of these cells to TAM via the crosstalk between ER and IL6-mediated intracellular signal transduction cascades. Overexpression of IL6 not only plays an important role in OVCA progression but also promotes TAM resistance. Our results indicate that TAM-IL6-targeted adjunctive therapy may lead to a more effective intervention than TAM alone. © 2015 Society for Endocrinology.

  1. Node vulnerability of water distribution networks under cascading failures

    International Nuclear Information System (INIS)

    Shuang, Qing; Zhang, Mingyuan; Yuan, Yongbo

    2014-01-01

    Water distribution networks (WDNs) are important in modern lifeline system. Its stability and reliability are critical for guaranteeing high living quality and continuous operation of urban functions. The aim of this paper is to evaluate the nodal vulnerability of WDNs under cascading failures. Vulnerability is defined to analyze the effects of the consequent failures. A cascading failure is a step-by-step process which is quantitatively investigated by numerical simulation with intentional attack. Monitored pressures in different nodes and flows in different pipes have been used to estimate the network topological structure and the consequences of nodal failure. Based on the connectivity loss of topological structure, the nodal vulnerability has been evaluated. A load variation function is established to record the nodal failure reason and describe the relative differences between the load and the capacity. The proposed method is validated by an illustrative example. The results revealed that the network vulnerability should be evaluated with the consideration of hydraulic analysis and network topology. In the case study, 70.59% of the node failures trigger the cascading failures with different failure processes. It is shown that the cascading failures result in severe consequences in WDNs. - Highlights: • The aim of this paper is to evaluate the nodal vulnerability of water distribution networks under cascading failures. • Monitored pressures and flows have been used to estimate the network topological structure and the consequences of nodal failure. • Based on the connectivity loss of topological structure, the nodal vulnerability has been evaluated. • A load variation function is established to record the failure reason and describe the relative differences between load and capacity. • The results show that 70.59% of the node failures trigger the cascading failures with different failure processes

  2. Haloperidol Regulates the State of Phosphorylation of Ribosomal Protein S6 via Activation of PKA and Phosphorylation of DARPP-32

    Science.gov (United States)

    Valjent, Emmanuel; Bertran-Gonzalez, Jesus; Bowling, Heather; Lopez, Sébastien; Santini, Emanuela; Matamales, Miriam; Bonito-Oliva, Alessandra; Hervé, Denis; Hoeffer, Charles; Klann, Eric; Girault, Jean-Antoine; Fisone, Gilberto

    2011-01-01

    Administration of typical antipsychotic drugs, such as haloperidol, promotes cAMP-dependent signaling in the medium spiny neurons (MSNs) of the striatum. In this study, we have examined the effect of haloperidol on the state of phosphorylation of the ribosomal protein S6 (rpS6), a component of the small 40S ribosomal subunit. We found that haloperidol increases the phosphorylation of rpS6 at the dual site Ser235/236, which is involved in the regulation of mRNA translation. This effect was exerted in the MSNs of the indirect pathway, which express specifically dopamine D2 receptors (D2Rs) and adenosine A2 receptors (A2ARs). The effect of haloperidol was decreased by blockade of A2ARs or by genetic attenuation of the Gαolf protein, which couples A2ARs to activation of adenylyl cyclase. Moreover, stimulation of cAMP-dependent protein kinase A (PKA) increased Ser235/236 phosphorylation in cultured striatal neurons. The ability of haloperidol to promote rpS6 phosphorylation was abolished in knock-in mice deficient for PKA activation of the protein phosphatase-1 inhibitor, dopamine- and cAMP-regulated phosphoprotein of 32 kDa. In contrast, pharmacological or genetic inactivation of p70 rpS6 kinase 1, or extracellular signal-regulated kinases did not affect haloperidol-induced rpS6 phosphorylation. These results identify PKA as a major rpS6 kinase in neuronal cells and suggest that regulation of protein synthesis through rpS6 may be a potential target of antipsychotic drugs. PMID:21814187

  3. Modeling of Bit Error Rate in Cascaded 2R Regenerators

    DEFF Research Database (Denmark)

    Öhman, Filip; Mørk, Jesper

    2006-01-01

    and the regenerating nonlinearity is investigated. It is shown that an increase in nonlinearity can compensate for an increase in noise figure or decrease in signal power. Furthermore, the influence of the improvement in signal extinction ratio along the cascade and the importance of choosing the proper threshold......This paper presents a simple and efficient model for estimating the bit error rate in a cascade of optical 2R-regenerators. The model includes the influences of of amplifier noise, finite extinction ratio and nonlinear reshaping. The interplay between the different signal impairments...

  4. Dirhodium(II Carbenes : The Chiral Product Cascade

    Directory of Open Access Journals (Sweden)

    Gregory H. P. Roos

    2000-12-01

    Full Text Available The last decade has witnessed enormous growth in the spectrum of highly efficient asymmetric synthetic transformations. One prominent example of this progress is the application of dirhodium (II carbenes generated from diazo- precursors. Innovative construction of ‘designer’ catalysts has played a integral role in extending the breadth of the synthetic cascade of non-racemic products now available through the range of cyclopropanation, C-X insertion, aromatic cycloaddition-rearrangement, and ylide-based reaction types. This review deals briefly with an overview of the important catalytic systems and maintains as its primary focus the cascade of diverse optically enriched products that flow from their applications.

  5. Bright, dark and singular optical solitons in a cascaded system

    International Nuclear Information System (INIS)

    Zhou, Qin; Zhu, Qiuping; Yu, Hua; Liu, Yaxian; Wei, Chun; Yao, Ping; Bhrawy, Ali H; Biswas, Anjan

    2015-01-01

    This work studies nonlinear dynamics of optical solitons in a cascaded system with Kerr law nonlinearity and spatio-temporal dispersion. The mathematical model that describes the propagation of optical solitons through a cascaded system is given by the vector-coupled nonlinear Schrödinger equation. It is investigated analytically using three integration algorithms. The Jacobian elliptic equation expansion method, Bernoulli equation expansion approach and Riccati equation expansion scheme are the integration tools of this model that are recruited to extract singular, bright and dark solitons. The restrictions that need to hold for the existence of these solitons are derived. (paper)

  6. Planning of cascade stations on the Maotiao He detailed

    Energy Technology Data Exchange (ETDEWEB)

    Guan, W

    1984-09-20

    Details of the hydroelectric power stations on the Maotiao He cascades and examples of how some problems were resolved begin with a description of the river basin survey for topographical features, hydrometeorological conditions, and geological conditions. The river characteristics survey was the basis for planning the cascade power stations and the selection of installed capacity at each station. The review also covers discharge and flood control planning based on rainfall data and the composition of flood areas. The overall development program emphasizes power generation, but also includes irrigation, industrial water supply, and tourism. 2 figures, 1 table.

  7. Cascade: a high-efficiency ICF power reactor

    International Nuclear Information System (INIS)

    Pitts, J.H.

    1985-01-01

    Cascade attains a net power-plant efficiency of 49% and its cost is competitive with high-temperature gas-cooled reactor, pressurized-water reactor, and coal-fired power plants. The Cascade reactor and blanket are made of ceramic materials and activation is 6 times less than that of the MARS Tandem Mirror Reactor operating at comparable power. Hands-on maintenance of the heat exchangers is possible one day after shutdown. Essentially all tritium is recovered in the vacuum system, with the remainder recovered from the helium power conversion loop. Tritium leakage external to the vacuum system and power conversion loop is only 0.03 Ci/d

  8. Major disruptions, inverse cascades, and the Strauss equations

    International Nuclear Information System (INIS)

    Montgomery, D.

    1982-01-01

    Current-carrying plasmas in a strong dc magnetic field are subject to violent disruptions above certain thresholds. At present difficult to verify, explanations are typically sought in terms of tearing modes. An alternative explanation is in terms of inverse magnetic helicity cascades, generated from a variety of possible sources of small-scale MHD turbulence. Strongly anisotropic MHD plasmas may be described by the Strauss equations. Indications of turbulent inverse cascade behavior for the Strauss equations are sought, in parallel with earlier examples from MHD and fluid mechanics

  9. Primary defect production by high energy displacement cascades in molybdenum

    Energy Technology Data Exchange (ETDEWEB)

    Selby, Aaron P. [Department of Nuclear Engineering, University of Tennessee, Knoxville, TN 37996 (United States); Xu, Donghua, E-mail: xudh@utk.edu [Department of Nuclear Engineering, University of Tennessee, Knoxville, TN 37996 (United States); Juslin, Niklas; Capps, Nathan A. [Department of Nuclear Engineering, University of Tennessee, Knoxville, TN 37996 (United States); Wirth, Brian D. [Department of Nuclear Engineering, University of Tennessee, Knoxville, TN 37996 (United States); Oak Ridge National Laboratory, P.O. Box 2008, MS6003, Oak Ridge, TN 37831 (United States)

    2013-06-15

    We report molecular dynamics simulations of primary damage in molybdenum produced by high energy displacement cascades on the femto- to pico-second and Angstrom to nanometer scales. Clustering directly occurred for both interstitials and vacancies in the 1–50 keV cascade energy range explored. Point defect survival efficiency and partitioning probabilities into different sized clusters were quantified. The results will provide an important reference for kinetic models to describe the microstructural evolution in Mo under ion or neutron irradiations over much longer time and length scales.

  10. Special Issue ;Sediment cascades in cold climate geosystems;

    Science.gov (United States)

    Morche, David; Krautblatter, Michael; Beylich, Achim A.

    2017-06-01

    This Editorial introduces the Special Issue on sediment cascades in cold climate geosystems that evolved from the eighth I.A.G./A.I.G. SEDIBUD (Sediment Budgets in Cold Environments; http://www.geomorph.org/sedibud-working-group/) workshop. The workshop was held from 1st to 4th September 2014 at the Environmental Research Station ;Schneefernerhaus; (http://www.schneefernerhaus.de/en/home.html) located at Mt. Zugspitze, the highest peak of Germany, (2962 m asl). Paper and poster presentations focused on observations, measurements and modeling of geomorphological processes in sediment cascades in cold climate geosystems. This resulting Special Issue brings together ten selected contributions from arctic and alpine environments.

  11. Identification of cascade water tanks using a PWARX model

    Science.gov (United States)

    Mattsson, Per; Zachariah, Dave; Stoica, Petre

    2018-06-01

    In this paper we consider the identification of a discrete-time nonlinear dynamical model for a cascade water tank process. The proposed method starts with a nominal linear dynamical model of the system, and proceeds to model its prediction errors using a model that is piecewise affine in the data. As data is observed, the nominal model is refined into a piecewise ARX model which can capture a wide range of nonlinearities, such as the saturation in the cascade tanks. The proposed method uses a likelihood-based methodology which adaptively penalizes model complexity and directly leads to a computationally efficient implementation.

  12. Common and uncommon pathogenic cascades in lysosomal storage diseases.

    Science.gov (United States)

    Vitner, Einat B; Platt, Frances M; Futerman, Anthony H

    2010-07-02

    Lysosomal storage diseases (LSDs), of which about 50 are known, are caused by the defective activity of lysosomal proteins, resulting in accumulation of unmetabolized substrates. As a result, a variety of pathogenic cascades are activated such as altered calcium homeostasis, oxidative stress, inflammation, altered lipid trafficking, autophagy, endoplasmic reticulum stress, and autoimmune responses. Some of these pathways are common to many LSDs, whereas others are only altered in a subset of LSDs. We now review how these cascades impact upon LSD pathology and suggest how intervention in the pathways may lead to novel therapeutic approaches.

  13. Phosphorylation of the Budding Yeast 9-1-1 Complex Is Required for Dpb11 Function in the Full Activation of the UV-Induced DNA Damage Checkpoint▿ †

    Science.gov (United States)

    Puddu, Fabio; Granata, Magda; Di Nola, Lisa; Balestrini, Alessia; Piergiovanni, Gabriele; Lazzaro, Federico; Giannattasio, Michele; Plevani, Paolo; Muzi-Falconi, Marco

    2008-01-01

    Following genotoxic insults, eukaryotic cells trigger a signal transduction cascade known as the DNA damage checkpoint response, which involves the loading onto DNA of an apical kinase and several downstream factors. Chromatin modifications play an important role in recruiting checkpoint proteins. In budding yeast, methylated H3-K79 is bound by the checkpoint factor Rad9. Loss of Dot1 prevents H3-K79 methylation, leading to a checkpoint defect in the G1 phase of the cell cycle and to a reduction of checkpoint activation in mitosis, suggesting that another pathway contributes to Rad9 recruitment in M phase. We found that the replication factor Dpb11 is the keystone of this second pathway. dot1Δ dpb11-1 mutant cells are sensitive to UV or Zeocin treatment and cannot activate Rad53 if irradiated in M phase. Our data suggest that Dpb11 is held in proximity to damaged DNA through an interaction with the phosphorylated 9-1-1 complex, leading to Mec1-dependent phosphorylation of Rad9. Dpb11 is also phosphorylated after DNA damage, and this modification is lost in a nonphosphorylatable ddc1-T602A mutant. Finally, we show that, in vivo, Dpb11 cooperates with Dot1 in promoting Rad9 phosphorylation but also contributes to the full activation of Mec1 kinase. PMID:18541674

  14. HSP20 phosphorylation and airway smooth muscle relaxation

    Directory of Open Access Journals (Sweden)

    Mariam Ba

    2009-06-01

    Full Text Available Mariam Ba1, Cherie A Singer1, Manoj Tyagi2, Colleen Brophy3, Josh E Baker4, Christine Cremo4, Andrew Halayko5, William T Gerthoffer21Department of Pharmacology, University of Nevada School of Medicine, Reno, NV, USA; 2Department of Biochemistry and Molecular Biology, University of South Alabama, Mobile, AL, USA; 3Harrington Department of Biochemistry, Arizona State University, Tempe, AZ, USA; 4Department of Biochemistry and Molecular Biology, University of Nevada, Reno, NV, USA; 5Departments of Physiology and Internal Medicine, University of Manitoba, Winnipeg, MB, CanadaAbstract: HSP20 (HSPB6 is a small heat shock protein expressed in smooth muscles that is hypothesized to inhibit contraction when phosphorylated by cAMP-dependent protein kinase. To investigate this hypothesis in airway smooth muscle (ASM we showed that HSP20 was constitutively expressed as well as being inducible in cultured hASM cells by treatment with 1 µM isoproterenol or 10 µM salmeterol. In contrast, a mixture of proinflammatory mediators (interleukin-1β, tumor necrosis factor α, and interferon γ inhibited expression of HSP20 by about 50% in 48 hours. To determine whether phosphorylation of HSP20 is sufficient to induce relaxation, canine tracheal smooth muscle was treated with a cell permeant phosphopeptide that mimics the phosphorylation of HSP20. The HSP20 phosphopeptide antagonized carbacholinduced contraction by 60% with no change in myosin light chain phosphorylation. Recombinant full length HSP20 inhibited skeletal actin binding to smooth muscle myosin subfragment 1 (S1, and recombinant cell permeant TAT-HSP20 S16D mutant reduced F-actin filaments in cultured hASM cells. Carbachol stimulation of canine tracheal smooth muscle tissue caused redistribution of HSP20 from large macromolecular complexes (200–500 kDa to smaller complexes (<60 kDa. The results are consistent with HSP20 expression and macromolecular structure being dynamically regulated in airway

  15. Molecular mechanism of APC/C activation by mitotic phosphorylation.

    Science.gov (United States)

    Zhang, Suyang; Chang, Leifu; Alfieri, Claudio; Zhang, Ziguo; Yang, Jing; Maslen, Sarah; Skehel, Mark; Barford, David

    2016-05-12

    In eukaryotes, the anaphase-promoting complex (APC/C, also known as the cyclosome) regulates the ubiquitin-dependent proteolysis of specific cell-cycle proteins to coordinate chromosome segregation in mitosis and entry into the G1 phase. The catalytic activity of the APC/C and its ability to specify the destruction of particular proteins at different phases of the cell cycle are controlled by its interaction with two structurally related coactivator subunits, Cdc20 and Cdh1. Coactivators recognize substrate degrons, and enhance the affinity of the APC/C for its cognate E2 (refs 4-6). During mitosis, cyclin-dependent kinase (Cdk) and polo-like kinase (Plk) control Cdc20- and Cdh1-mediated activation of the APC/C. Hyperphosphorylation of APC/C subunits, notably Apc1 and Apc3, is required for Cdc20 to activate the APC/C, whereas phosphorylation of Cdh1 prevents its association with the APC/C. Since both coactivators associate with the APC/C through their common C-box and Ile-Arg tail motifs, the mechanism underlying this differential regulation is unclear, as is the role of specific APC/C phosphorylation sites. Here, using cryo-electron microscopy and biochemical analysis, we define the molecular basis of how phosphorylation of human APC/C allows for its control by Cdc20. An auto-inhibitory segment of Apc1 acts as a molecular switch that in apo unphosphorylated APC/C interacts with the C-box binding site and obstructs engagement of Cdc20. Phosphorylation of the auto-inhibitory segment displaces it from the C-box-binding site. Efficient phosphorylation of the auto-inhibitory segment, and thus relief of auto-inhibition, requires the recruitment of Cdk-cyclin in complex with a Cdk regulatory subunit (Cks) to a hyperphosphorylated loop of Apc3. We also find that the small-molecule inhibitor, tosyl-l-arginine methyl ester, preferentially suppresses APC/C(Cdc20) rather than APC/C(Cdh1), and interacts with the binding sites of both the C-box and Ile-Arg tail motifs. Our

  16. On the trajectories of CRL...LR...R orbits, their period-doubling cascades and saddle-node bifurcation cascades

    International Nuclear Information System (INIS)

    Cerrada, Lucia; San Martin, Jesus

    2011-01-01

    In this Letter, it is shown that from a two region partition of the phase space of a one-dimensional dynamical system, a p-region partition can be obtained for the CRL...LR...R orbits. That is, permutations associated with symbolic sequences are obtained. As a consequence, the trajectory in phase space is directly deduced from permutation. From this permutation other permutations associated with period-doubling and saddle-node bifurcation cascades are derived, as well as other composite permutations. - Research highlights: → Symbolic sequences are the usual topological approach to dynamical systems. → Permutations bear more physical information than symbolic sequences. → Period-doubling cascade permutations associated with original sequences are obtained. → Saddle-node cascade permutations associated with original sequences are obtained. → Composite permutations are derived.

  17. Displacement cascades and defect annealing in tungsten, Part II: Object kinetic Monte Carlo simulation of tungsten cascade aging

    Energy Technology Data Exchange (ETDEWEB)

    Nandipati, Giridhar, E-mail: giridhar.nandipati@pnnl.gov [Pacific Northwest National Laboratory, Richland, WA (United States); Setyawan, Wahyu; Heinisch, Howard L. [Pacific Northwest National Laboratory, Richland, WA (United States); Roche, Kenneth J. [Pacific Northwest National Laboratory, Richland, WA (United States); Department of Physics, University of Washington, Seattle, WA 98195 (United States); Kurtz, Richard J. [Pacific Northwest National Laboratory, Richland, WA (United States); Wirth, Brian D. [University of Tennessee, Knoxville, TN (United States)

    2015-07-15

    The results of object kinetic Monte Carlo (OKMC) simulations of the annealing of primary cascade damage in bulk tungsten using a comprehensive database of cascades obtained from molecular dynamics (Setyawan et al.) are described as a function of primary knock-on atom (PKA) energy at temperatures of 300, 1025 and 2050 K. An increase in SIA clustering coupled with a decrease in vacancy clustering with increasing temperature, in addition to the disparate mobilities of SIAs versus vacancies, causes an interesting effect of temperature on cascade annealing. The annealing efficiency (the ratio of the number of defects after and before annealing) exhibits an inverse U-shape curve as a function of temperature. The capabilities of the newly developed OKMC code KSOME (kinetic simulations of microstructure evolution) used to carry out these simulations are described.

  18. Displacement cascades and defect annealing in tungsten, Part II: Object kinetic Monte Carlo Simulation of Tungsten Cascade Aging

    Energy Technology Data Exchange (ETDEWEB)

    Nandipati, Giridhar; Setyawan, Wahyu; Heinisch, Howard L.; Roche, Kenneth J.; Kurtz, Richard J.; Wirth, Brian D.

    2015-07-01

    The results of object kinetic Monte Carlo (OKMC) simulations of the annealing of primary cascade damage in bulk tungsten using a comprehensive database of cascades obtained from molecular dynamics (Setyawan et al.) are described as a function of primary knock-on atom (PKA) energy at temperatures of 300, 1025 and 2050 K. An increase in SIA clustering coupled with a decrease in vacancy clustering with increasing temperature, in addition to the disparate mobilities of SIAs versus vacancies, causes an interesting effect of temperature on cascade annealing. The annealing efficiency (the ratio of the number of defects after and before annealing) exhibits an inverse U-shape curve as a function of temperature. The capabilities of the newly developed OKMC code KSOME (kinetic simulations of microstructure evolution) used to carry out these simulations are described.

  19. Large-scale analysis of phosphorylation site occupancy in eukaryotic proteins

    DEFF Research Database (Denmark)

    Rao, R Shyama Prasad; Møller, Ian Max

    2012-01-01

    in proteins is currently lacking. We have therefore analyzed the occurrence and occupancy of phosphorylated sites (~ 100,281) in a large set of eukaryotic proteins (~ 22,995). Phosphorylation probability was found to be much higher in both the  termini of protein sequences and this is much pronounced...... maximum randomness. An analysis of phosphorylation motifs indicated that just 40 motifs and a much lower number of associated kinases might account for nearly 50% of the known phosphorylations in eukaryotic proteins. Our results provide a broad picture of the phosphorylation sites in eukaryotic proteins.......Many recent high throughput technologies have enabled large-scale discoveries of new phosphorylation sites and phosphoproteins. Although they have provided a number of insights into protein phosphorylation and the related processes, an inclusive analysis on the nature of phosphorylated sites...

  20. Prometaphase arrest-dependent phosphorylation of Bcl-2 family proteins and activation of mitochondrial apoptotic pathway are associated with 17α-estradiol-induced apoptosis in human Jurkat T cells.

    Science.gov (United States)

    Han, Cho Rong; Jun, Do Youn; Kim, Yoon Hee; Lee, Ji Young; Kim, Young Ho

    2013-10-01

    In Jurkat T cell clone (JT/Neo), G2/M arrest, apoptotic sub-G1 peak, mitochondrial membrane potential (Δψm) loss, and TUNEL-positive DNA fragmentation were induced following exposure to 17α-estradiol (17α-E2), whereas none of these events (except for G2/M arrest) were induced in Jurkat cells overexpressing Bcl-2 (JT/Bcl-2). Under these conditions, phosphorylation at Thr161 and dephosphorylation at Tyr15 of Cdk1, upregulation of cyclin B1 level, histone H1 phosphorylation, Cdc25C phosphorylation at Thr-48, Bcl-2 phosphorylation at Thr-56 and Ser-70, Mcl-1 phosphorylation, and Bim phosphorylation were detected in the presence of Bcl-2 overexpression. However, the 17α-E2-induced upregulation of Bak levels, activation of Bak, activation of caspase-3, and PARP degradation were abrogated by Bcl-2 overexpression. In the presence of the G1/S blocking agent hydroxyurea, 17α-E2 failed to induce G2/M arrest and all apoptotic events including Cdk1 activation and phosphorylation of Bcl-2, Mcl-1 and Bim. The 17α-E2-induced phosphorylation of Bcl-2 family proteins and mitochondrial apoptotic events were suppressed by a Cdk1 inhibitor but not by aurora A and aurora B kinase inhibitors. Immunofluorescence microscopic analysis showed that an aberrant bipolar microtubule array, incomplete chromosome congression at the metaphase plate, and prometaphase arrest, which was reversible, were the underlying factors for 17α-E2-induced mitotic arrest. The in vitro microtubule polymerization assay showed that 17α-E2 could directly inhibit microtubule formation. These results show that the apoptogenic activity of 17α-E2 was due to the impaired mitotic spindle assembly causing prometaphase arrest and prolonged Cdk1 activation, the phosphorylation of Bcl-2, Mcl-1 and Bim, and the activation of Bak and mitochondria-dependent caspase cascade. Copyright © 2013 Elsevier B.V. All rights reserved.

  1. Identification of tyrosine-phosphorylated proteins associated with metastasis and functional analysis of FER in human hepatocellular carcinoma cells

    International Nuclear Information System (INIS)

    Li, Haiyu; Ren, Zhenggang; Kang, Xiaonan; Zhang, Lan; Li, Xuefei; Wang, Yan; Xue, Tongchun; Shen, Yuefang; Liu, Yinkun

    2009-01-01

    Aberrant activity of tyrosine-phosphorylated proteins is commonly associated with HCC metastasis. Cell signaling events driven by these proteins are implicated in numerous processes that alter cancer cell behavior. Exploring the activities and signaling pathways of these proteins in HCC metastasis may help in identifying new candidate molecules for HCC-targeted therapy. Hep3B (a nonmetastatic HCC cell line) and MHCC97H (a highly metastatic HCC cell line) were used in this study, and the tyrosine-phosphorylated proteins expressed in these cell lines were profiled by a phosphoproteomics technique based on LC-MS/MS. Protein-protein interaction and functional clustering analyses were performed to determine the activities of the identified proteins and the signaling pathways closely related to HCC metastasis. In both cell lines, a total of 247 phosphotyrosine (pTyr) proteins containing 281 pTyr sites were identified without any stimulation. The involvement of almost 30% of these in liver or liver cancer has not been reported previously. Biological process clustering analysis indicated that pTyr proteins involved in cell motility, migration, protein autophosphorylation, cell-cell communication, and antiapoptosis functions were overexpressed during metastasis. Pathway clustering analysis revealed that signaling pathways such as those involved in EGFR signaling, cytokine- and chemokine-mediated signal transduction, and the PI3K and JAK-STAT cascades were significantly activated during HCC metastasis. Moreover, noncanonical regulation of the JNK cascade might also provide new targets for HCC metastasis. After comparing the pTyr proteins that were differentially expressed during HCC cell metastasis, we selected FER, a nonreceptor tyrosine kinase, and validated its role in terms of both expression and function. The data confirmed that FER might play a critical role in the invasion and metastasis of HCC. The identification of pTyr proteins and signaling pathways associated

  2. Interrelation of structure and operational states in cascading failure of overloading lines in power grids

    Science.gov (United States)

    Xue, Fei; Bompard, Ettore; Huang, Tao; Jiang, Lin; Lu, Shaofeng; Zhu, Huaiying

    2017-09-01

    As the modern power system is expected to develop to a more intelligent and efficient version, i.e. the smart grid, or to be the central backbone of energy internet for free energy interactions, security concerns related to cascading failures have been raised with consideration of catastrophic results. The researches of topological analysis based on complex networks have made great contributions in revealing structural vulnerabilities of power grids including cascading failure analysis. However, existing literature with inappropriate assumptions in modeling still cannot distinguish the effects between the structure and operational state to give meaningful guidance for system operation. This paper is to reveal the interrelation between network structure and operational states in cascading failure and give quantitative evaluation by integrating both perspectives. For structure analysis, cascading paths will be identified by extended betweenness and quantitatively described by cascading drop and cascading gradient. Furthermore, the operational state for cascading paths will be described by loading level. Then, the risk of cascading failure along a specific cascading path can be quantitatively evaluated considering these two factors. The maximum cascading gradient of all possible cascading paths can be used as an overall metric to evaluate the entire power grid for its features related to cascading failure. The proposed method is tested and verified on IEEE30-bus system and IEEE118-bus system, simulation evidences presented in this paper suggests that the proposed model can identify the structural causes for cascading failure and is promising to give meaningful guidance for the protection of system operation in the future.

  3. Contraction regulates site-specific phosphorylation of TBC1D1 in skeletal muscle.

    Science.gov (United States)

    Vichaiwong, Kanokwan; Purohit, Suneet; An, Ding; Toyoda, Taro; Jessen, Niels; Hirshman, Michael F; Goodyear, Laurie J

    2010-10-15

    TBC1D1 (tre-2/USP6, BUB2, cdc16 domain family member 1) is a Rab-GAP (GTPase-activating protein) that is highly expressed in skeletal muscle, but little is known about TBC1D1 regulation and function. We studied TBC1D1 phosphorylation on three predicted AMPK (AMP-activated protein kinase) phosphorylation sites (Ser231, Ser660 and Ser700) and one predicted Akt phosphorylation site (Thr590) in control mice, AMPKα2 inactive transgenic mice (AMPKα2i TG) and Akt2-knockout mice (Akt2 KO). Muscle contraction significantly increased TBC1D1 phosphorylation on Ser231 and Ser660, tended to increase Ser700 phosphorylation, but had no effect on Thr590. AICAR (5-aminoimidazole-4-carboxyamide ribonucleoside) also increased phosphorylation on Ser231, Ser660 and Ser700, but not Thr590, whereas insulin only increased Thr590 phosphorylation. Basal and contraction-stimulated TBC1D1 Ser231, Ser660 and Ser700 phosphorylation were greatly reduced in AMPKα2i TG mice, although contraction still elicited a small increase in phosphorylation. Akt2 KO mice had blunted insulin-stimulated TBC1D1 Thr590 phosphorylation. Contraction-stimulated TBC1D1 Ser231 and Ser660 phosphorylation were normal in high-fat-fed mice. Glucose uptake in vivo was significantly decreased in tibialis anterior muscles overexpressing TBC1D1 mutated on four predicted AMPK phosphorylation sites. In conclusion, contraction causes site-specific phosphorylation of TBC1D1 in skeletal muscle, and TBC1D1 phosphorylation on AMPK sites regulates contraction-stimulated glucose uptake. AMPK and Akt regulate TBC1D1 phosphorylation, but there must be additional upstream kinases that mediate TBC1D1 phosphorylation in skeletal muscle.

  4. Involvement of ERK phosphorylation of trigeminal spinal subnucleus caudalis neurons in thermal hypersensitivity in rats with infraorbital nerve injury.

    Directory of Open Access Journals (Sweden)

    Ikuko Suzuki

    Full Text Available To evaluate the involvement of the mitogen-activated protein kinase (MAPK cascade in orofacial neuropathic pain mechanisms, this study assessed nocifensive behavior evoked by mechanical or thermal stimulation of the whisker pad skin, phosphorylation of extracellular signal-regulated kinase (ERK in trigeminal spinal subnucleus caudalis (Vc neurons, and Vc neuronal responses to mechanical or thermal stimulation of the whisker pad skin in rats with the chronic constriction nerve injury of the infraorbital nerve (ION-CCI. The mechanical and thermal nocifensive behavior was significantly enhanced on the side ipsilateral to the ION-CCI compared to the contralateral whisker pad or sham rats. ION-CCI rats had an increased number of phosphorylated ERK immunoreactive (pERK-IR cells which also manifested NeuN-IR but not GFAP-IR and Iba1-IR, and were significantly more in ION-CCI rats compared with sham rats following noxious but not non-noxious mechanical stimulation. After intrathecal administration of the MEK1 inhibitor PD98059 in ION-CCI rats, the number of pERK-IR cells after noxious stimulation and the enhanced thermal nocifensive behavior but not the mechanical nocifensive behavior were significantly reduced in ION-CCI rats. The enhanced background activities, afterdischarges and responses of wide dynamic range neurons to noxious mechanical and thermal stimulation in ION-CCI rats were significantly depressed following i.t. administration of PD98059, whereas responses to non-noxious mechanical and thermal stimulation were not altered. The present findings suggest that pERK-IR neurons in the Vc play a pivotal role in the development of thermal hypersensitivity in the face following trigeminal nerve injury.

  5. Tyrosine 370 phosphorylation of ATM positively regulates DNA damage response

    Science.gov (United States)

    Lee, Hong-Jen; Lan, Li; Peng, Guang; Chang, Wei-Chao; Hsu, Ming-Chuan; Wang, Ying-Nai; Cheng, Chien-Chia; Wei, Leizhen; Nakajima, Satoshi; Chang, Shih-Shin; Liao, Hsin-Wei; Chen, Chung-Hsuan; Lavin, Martin; Ang, K Kian; Lin, Shiaw-Yih; Hung, Mien-Chie

    2015-01-01

    Ataxia telangiectasia mutated (ATM) mediates DNA damage response by controling irradiation-induced foci formation, cell cycle checkpoint, and apoptosis. However, how upstream signaling regulates ATM is not completely understood. Here, we show that upon irradiation stimulation, ATM associates with and is phosphorylated by epidermal growth factor receptor (EGFR) at Tyr370 (Y370) at the site of DNA double-strand breaks. Depletion of endogenous EGFR impairs ATM-mediated foci formation, homologous recombination, and DNA repair. Moreover, pretreatment with an EGFR kinase inhibitor, gefitinib, blocks EGFR and ATM association, hinders CHK2 activation and subsequent foci formation, and increases radiosensitivity. Thus, we reveal a critical mechanism by which EGFR directly regulates ATM activation in DNA damage response, and our results suggest that the status of ATM Y370 phosphorylation has the potential to serve as a biomarker to stratify patients for either radiotherapy alone or in combination with EGFR inhibition. PMID:25601159

  6. Reactions of α-phosphorylated carbonyl compounds with amino alcohols

    International Nuclear Information System (INIS)

    Moskva, V.V.; Sitdikova, T.Sh.; Zykova, T.V.; Alparova, M.V.; Shagvaleev, F.Sh.

    1986-01-01

    2-Aminoethanol reacts with carbonyl compounds with the formation, depending on the structure of the latter, either of a mixture of azomethines and oxazolidines, or of only azomethines. In the development of investigations on the reactivity of α-phosphorylated carbonyl compounds the authors studied the reactions of a number of amino alcohols with phosphorylated acetaldehyde and acetone. In both cases they observed the formation of compounds of enamine structure, oxazolidines and azomethines were not observed. By means of NMR spectroscopy they established clearly the formation of the E-isomeric products. The 1 H, 31 P, and 13 C NMR spectra were recorded on a WP-80 spectrometer. Chemical shifts of protons and 13 C nuclei are given relative to TMS, and phosphorus nuclei relative to orthophosphoric acid

  7. GABAB receptor phosphorylation regulates KCTD12-induced K+ current desensitization

    DEFF Research Database (Denmark)

    Adelfinger, L; Turecek, R; Ivankova, K

    2014-01-01

    released from the G-protein. Receptor-activated K+ currents desensitize in the sustained presence of agonist to avoid excessive effects on neuronal activity. Desensitization of K+ currents integrates distinct mechanistic underpinnings. GABAB receptor activity reduces protein kinase-A activity, which...... reduces phosphorylation of serine-892 in GABAB2 and promotes receptor degradation. This form of desensitization operates on the time scale of several minutes to hours. A faster form of desensitization is induced by the auxiliary subunit KCTD12, which interferes with channel activation by binding to the G......-protein βγ subunits. Here we show that the two mechanisms of desensitization influence each other. Serine-892 phosphorylation in heterologous cells rearranges KCTD12 at the receptor and slows KCTD12-induced desensitization. Likewise, protein kinase-A activation in hippocampal neurons slows fast...

  8. Modulation of repulsive forces between neurofilaments by sidearm phosphorylation

    International Nuclear Information System (INIS)

    Kumar, Sanjay; Hoh, Jan H.

    2004-01-01

    Recent studies have advanced the notion that the axonal organization of neurofilaments (NFs) is based on mutual steric repulsion between the unstructured 'sidearm' domains of adjacent NFs. Here, we present experimental evidence that these repulsive forces are modulated by the degree of sidearm phosphorylation. When NFs are sedimented into a gelatinous pellet, pellet volume falls with increasing ionic strength and enzymatic dephosphorylation; sedimentation of phosphorylated NFs in the presence of divalent cations also dramatically reduces pellet volume. Further, atomic force microscopy imaging of isolated mammalian NFs reveals robust exclusion of colloidal particles from the NF backbone that is reduced at high ionic strength and attenuated when the filaments are enzymatically dephosphorylated. Phosphate-phosphate repulsion on the NF sidearm appears to modulate NF excluded volume in a graded fashion, thereby controlling axonal NF organization through interfilament forces

  9. Investigating quantitation of phosphorylation using MALDI-TOF mass spectrometry.

    Science.gov (United States)

    Parker, Laurie; Engel-Hall, Aaron; Drew, Kevin; Steinhardt, George; Helseth, Donald L; Jabon, David; McMurry, Timothy; Angulo, David S; Kron, Stephen J

    2008-04-01

    Despite advances in methods and instrumentation for analysis of phosphopeptides using mass spectrometry, it is still difficult to quantify the extent of phosphorylation of a substrate because of physiochemical differences between unphosphorylated and phosphorylated peptides. Here we report experiments to investigate those differences using MALDI-TOF mass spectrometry for a set of synthetic peptides by creating calibration curves of known input ratios of peptides/phosphopeptides and analyzing their resulting signal intensity ratios. These calibration curves reveal subtleties in sequence-dependent differences for relative desorption/ionization efficiencies that cannot be seen from single-point calibrations. We found that the behaviors were reproducible with a variability of 5-10% for observed phosphopeptide signal. Although these data allow us to begin addressing the issues related to modeling these properties and predicting relative signal strengths for other peptide sequences, it is clear that this behavior is highly complex and needs to be further explored. John Wiley & Sons, Ltd

  10. ERK phosphorylation regulates sleep and plasticity in Drosophila.

    Directory of Open Access Journals (Sweden)

    William M Vanderheyden

    Full Text Available Given the relationship between sleep and plasticity, we examined the role of Extracellular signal-regulated kinase (ERK in regulating baseline sleep, and modulating the response to waking experience. Both sleep deprivation and social enrichment increase ERK phosphorylation in wild-type flies. The effects of both sleep deprivation and social enrichment on structural plasticity in the LNvs can be recapitulated by expressing an active version of ERK (UAS-ERK(SEM pan-neuronally in the adult fly using GeneSwitch (Gsw Gsw-elav-GAL4. Conversely, disrupting ERK reduces sleep and prevents both the behavioral and structural plasticity normally induced by social enrichment. Finally, using transgenic flies carrying a cAMP response Element (CRE-luciferase reporter we show that activating ERK enhances CRE-Luc activity while disrupting ERK reduces it. These data suggest that ERK phosphorylation is an important mediator in transducing waking experience into sleep.

  11. Novel tyrosine phosphorylation sites in rat skeletal muscle revealed by phosphopeptide enrichment and HPLC-ESI-MS/MS

    DEFF Research Database (Denmark)

    Zhang, Xiangmin; Højlund, Kurt; Luo, Moulun

    2012-01-01

    Tyrosine phosphorylation plays a fundamental role in many cellular processes including differentiation, growth and insulin signaling. In insulin resistant muscle, aberrant tyrosine phosphorylation of several proteins has been detected. However, due to the low abundance of tyrosine phosphorylation (...

  12. Phosphorylation and function of DGAT1 in skeletal muscle cells

    OpenAIRE

    Yu, Jinhai; Li, Yiran; Zou, Fei; Xu, Shimeng; Liu, Pingsheng

    2015-01-01

    Aberrant intramuscular triacylglycerol (TAG) storage in human skeletal muscle is closely related to insulin insensitivity. Excessive lipid storage can induce insulin resistance of skeletal muscle, and under severe conditions, lead to type 2 diabetes. The balance of interconversion between diacylglycerol and TAG greatly influences lipid storage and utilization. Diacylglycerol O-acyltransferase 1 (DGAT1) plays a key role in this process, but its activation and phosphorylation requires further d...

  13. Modulation of P1798 lymphosarcoma proliferation by protein phosphorylation

    International Nuclear Information System (INIS)

    Michnoff, C.A.H.

    1983-01-01

    The role of protein kinases in modulating cell proliferation was examined. Studies characterized the regulation of cell proliferation by adenosine 3':5'-monophosphate-dependent protein kinase (cA-Pk). Calcium/calmodulin-dependent myosin light chain kinase (MLCK) was isolated and examined as a potential substrate regulated by cA-PK in the rapidly proliferating P1798 lymphosarcoma. Modulation of cell proliferation by cA-PK was characterized by quantitating cell division by [methyl- 3 H] thymidine ([ 3 H]-dT) incorporation into DNA, cAMP accumulations, and activation of cA-PK using P1798 lymphosarcoma cells. Epinephrine and prostaglandin E 1 (PGE 1 ) were demonstrated to suppress [ 3 H]-dT incorporation into DNA, to stimulate cAMP accumulation, and to activate cA-PK with dose-dependency. Calcium/calmodulin-dependent MLCK was partially purified from P1798 lymphosarcoma. P1798 MLCK phosphorylated myosin regulatory light chains (P-LC) from thymus, cardiac and skeletal muscles. One mol [ 32 Pi] was transferred into one mol cardiac or skeletal P-LC by P1798 MLCK. Apparent Km values of 65 μM and 51 μM were determined for ATP and cardiac P-LC, respectively. The apparent molecular weight of P1798 MLCK was 135,000. P1798 MLCK was phosphorylated by cA-PK. Phosphorylated MLCK showed a 41% decrease in calcium-dependent activity. Two additional protein kinases from P1798 lymphosarcoma phosphorylated cardiac and skeletal light chains

  14. Phosphorylation Modulates Ameloblastin Self-assembly and Ca2+ Binding

    Czech Academy of Sciences Publication Activity Database

    Stakkestad, O.; Lyngstadaas, S. P.; Thiede, B.; Vondrášek, Jiří; Skalhegg, B. S.; Reseland, J. E.

    2017-01-01

    Roč. 8, Jul 27 (2017), č. článku 531. ISSN 1664-042X Institutional support: RVO:61388963 Keywords : ameloblastin * phosphorylation * self-assembly * Ca2+-binding * enamel * intrinsically disordered proteins Subject RIV: CE - Biochemistry OBOR OECD: Biochemistry and molecular biology Impact factor: 4.134, year: 2016 http://journal.frontiersin.org/article/10.3389/fphys.2017.00531/full

  15. Training-induced adaptation of oxidative phosphorylation in skeletal muscles.

    OpenAIRE

    Korzeniewski, Bernard; Zoladz, Jerzy A

    2003-01-01

    Muscle training/conditioning improves the adaptation of oxidative phosphorylation in skeletal muscles to physical exercise. However, the mechanisms underlying this adaptation are still not understood fully. By quantitative analysis of the existing experimental results, we show that training-induced acceleration of oxygen-uptake kinetics at the onset of exercise and improvement of ATP/ADP stability due to physical training are mainly caused by an increase in the amount of mitochondrial protein...

  16. Cascades on a stochastic pulse-coupled network

    Science.gov (United States)

    Wray, C. M.; Bishop, S. R.

    2014-09-01

    While much recent research has focused on understanding isolated cascades of networks, less attention has been given to dynamical processes on networks exhibiting repeated cascades of opposing influence. An example of this is the dynamic behaviour of financial markets where cascades of buying and selling can occur, even over short timescales. To model these phenomena, a stochastic pulse-coupled oscillator network with upper and lower thresholds is described and analysed. Numerical confirmation of asynchronous and synchronous regimes of the system is presented, along with analytical identification of the fixed point state vector of the asynchronous mean field system. A lower bound for the finite system mean field critical value of network coupling probability is found that separates the asynchronous and synchronous regimes. For the low-dimensional mean field system, a closed-form equation is found for cascade size, in terms of the network coupling probability. Finally, a description of how this model can be applied to interacting agents in a financial market is provided.

  17. Neutron spallation source and the Dubna Cascade Code

    Indian Academy of Sciences (India)

    nuclear cascade and includes all those ... by numerous elastic nuclear collisions up to a very low energy. At the same time in. 470 ..... in table 6 that at low incident energy, major heat contribution comes from the ionization process. For example, it ...

  18. Network protection against worms and cascading failures using modularity partitioning

    NARCIS (Netherlands)

    Omic, J.; Hernandez, J.M.; Van Mieghem, P.

    2010-01-01

    Communication networks are prone to virus and worms spreading and cascading failures. Recently, a number of social networking worms have spread over public Web sites. Another example is error propagation in routing tables, such as in BGP tables. The immunization and error curing applied to these

  19. Plasma flow in a pressure pulsed argon cascade arc

    NARCIS (Netherlands)

    de Haas, J.C.M.; Bol, L.; Kroesen, G.M.W.; Timmermans, C.J.; Timmermans, C.J.

    1985-01-01

    Flowing thermal plasmas are frequently used e . g. in welding, cutting, plasma deposition and testing materials at high temperatures . In most of the applications the geometry is complex . In the cascade arc the argon plasma flows through a straight circular channel with a constant area. The study

  20. Efficient cascade multiple heterojunction organic solar cells with inverted structure

    Science.gov (United States)

    Guo, Tingting; Li, Mingtao; Qiao, Zhenfang; Yu, Leiming; Zhao, Jianhong; Feng, Nianjun; Shi, Peiguang; Wang, Xiaoyan; Pu, Xiaoyun; Wang, Hai

    2018-05-01

    In this work, we demonstrate an efficient cascade multiple heterojunction organic solar cell with inverted structure. By using two donor materials, poly(3-hexylthiosphene) (P3HT) and titanyl phthalocyanine (TiOPc), as well as two acceptor materials, [6,6]-phenyl C61 butyric acid methyl ester (PCBM) and C60, the cascade multiple heterojunctions of P3HT:PCBM/TiOPc:C60/C60 have been constructed. Applying the optimized inverted configuration of FTO/Zinc Tin Oxide (ZTO)/C60 (30 nm)/TiOPc:C60 (1:1.5, 25 nm)/P3HT:PCBM (1:0.8, 100 nm)/MoO3 (4 nm)/Ag, the considerably enhanced open circuit voltage (VOC) and short circuit current (JSC) can be harvested together, and the power conversion efficiency (PCE) is three times higher than that of the control cell with conventional structure. The significant improvements of the inverted cell are mostly due to the broadened spectral absorption and high efficient multi-interface exciton dissociation in the cascade multiple heterojunctions, indicating that the optimized cascade heterojunctions match the inverted structure well.

  1. DNA binding properties of the small cascade subunit Csa5.

    Directory of Open Access Journals (Sweden)

    Michael Daume

    Full Text Available CRISPR-Cas systems provide immunity against viral attacks in archaeal and bacterial cells. Type I systems employ a Cas protein complex termed Cascade, which utilizes small CRISPR RNAs to detect and degrade the exogenic DNA. A small sequence motif, the PAM, marks the foreign substrates. Previously, a recombinant type I-A Cascade complex from the archaeon Thermoproteus tenax was shown to target and degrade DNA in vitro, dependent on a native PAM sequence. Here, we present the biochemical analysis of the small subunit, Csa5, of this Cascade complex. T. tenax Csa5 preferentially bound ssDNA and mutants that showed decreased ssDNA-binding and reduced Cascade-mediated DNA cleavage were identified. Csa5 oligomerization prevented DNA binding. Specific recognition of the PAM sequence was not observed. Phylogenetic analyses identified Csa5 as a universal member of type I-A systems and revealed three distinct groups. A potential role of Csa5 in R-loop stabilization is discussed.

  2. Fire history and pattern in a Cascade Range landscape.

    Science.gov (United States)

    Peter H. Morrison; Frederick J. Swanson

    1990-01-01

    Fire history from years 1150 to 1985 was reconstructed by analyzing forest stands in two 1940-hectare areas in the central-western Cascade Range of Oregon. Serving as records for major fire episodes, these stands revealed a highly variable fire regime. The steeper, more dissected, lower elevation Cook-Quentin study area experienced more frequent fires (natural fire...

  3. Cascaded column generation for scalable predictive demand side management

    NARCIS (Netherlands)

    Toersche, Hermen; Molderink, Albert; Hurink, Johann L.; Smit, Gerardus Johannes Maria

    2014-01-01

    We propose a nested Dantzig-Wolfe decomposition, combined with dynamic programming, for the distributed scheduling of a large heterogeneous fleet of residential appliances with nonlinear behavior. A cascaded column generation approach gives a scalable optimization strategy, provided that the problem

  4. Cascading Constrained 2-D Arrays using Periodic Merging Arrays

    DEFF Research Database (Denmark)

    Forchhammer, Søren; Laursen, Torben Vaarby

    2003-01-01

    We consider a method for designing 2-D constrained codes by cascading finite width arrays using predefined finite width periodic merging arrays. This provides a constructive lower bound on the capacity of the 2-D constrained code. Examples include symmetric RLL and density constrained codes...

  5. Successful Treatment Of Homozygous Familial Hypercholesterolemia Using Cascade Filtration Plasmapheresis

    Directory of Open Access Journals (Sweden)

    Fatih Kardas

    2012-12-01

    Full Text Available OBJECTIVE: The aim of our study is to discuss the efficacy of low-density lipoprotein-cholesterol (LDL-C apheresis procedure using the cascade filtration system for pediatric patients with homozygous familial hypercholesterolemia (FH, and to clarify the adverse effects and difficulties. METHODS: LDL apheresis using the cascade filtration system was performed in 3 pediatric patients with homozygous FH. In total, 120 apheresis sessions were performed for all patients. RESULTS: Cascade filtration therapy significantly reduced the mean LDL-C values from 418 ± 62 mg/dl to 145 ± 43 mg/dl (p<0.05. We determined an acute mean reduction in the plasma levels of total cholesterol (57.9%, LDL cholesterol (70.8%, and high-density lipoprotein (HDL cholesterol (40.7%. Treatments were well tolerated. The most frequent clinical adverse effects were hypotension in 3 sessions (2.5%, chills/feeling cold (1.7% in 2 sessions, and nausea and vomiting in 3 sessions (2.5%. CONCLUSION: Our experience with three patients using the cascade filtration system were, good clinical outcomes, laboratory findings, safety of usage, minor adverse effects and technical problems.

  6. Surface plasmon quantum cascade lasers as terahertz local oscillators

    NARCIS (Netherlands)

    Hajenius, M.; Khosropanah, P.; Hovenier, J. N.; Gao, J. R.; Klapwijk, T. M.; Barbieri, S.; Dhillon, S.; Filloux, P.; Sirtori, C.; Ritchie, D. A.; Beere, H. E.

    2008-01-01

    We characterize a heterodyne receiver based on a surface-plasmon waveguide quantum cascade laser (QCL) emitting at 2.84 THz as a local oscillator, and an NbN hot electron bolometer as a mixer. We find that the envelope of the far-field pattern of the QCL is diffraction-limited and superimposed onto

  7. Processing Interband Cascade Laser for High Temperature CW Operation

    National Research Council Canada - National Science Library

    Tober, Richard

    2004-01-01

    A narrow ridge-waveguide mid-IR interband cascade laser based on Type-II InAs/GaInSh heterostructures processed with a thick gold heat spreading layer operated CW at temperatures ranging from 80 K to 214.4 K...

  8. Evidence for proteins involved in prophenoloxidase cascade Eisenia fetida earthworms

    Czech Academy of Sciences Publication Activity Database

    Kohlerová, Petra; Šilerová, Marcela; Stijlemans, B.; Dieu, M.; Halada, Petr; Josková, Radka; Beschin, A.; De Baetselier, P.; Bilej, Martin

    2006-01-01

    Roč. 176, - (2006), s. 581-587 ISSN 0174-1578 R&D Projects: GA ČR GA310/04/0806; GA AV ČR KJB500200613 Institutional research plan: CEZ:AV0Z50200510 Keywords : protein * prophenoloxidase cascade * eisenia fetida Subject RIV: EE - Microbiology, Virology Impact factor: 1.740, year: 2006

  9. Trophic cascades: the primacy of trait-mediated indirect interactions

    Czech Academy of Sciences Publication Activity Database

    Schmitz, O. J.; Křivan, Vlastimil; Ovadia, O.

    2004-01-01

    Roč. 7, - (2004), s. 153-163 ISSN 1461-023X R&D Projects: GA ČR GA201/03/0091 Institutional research plan: CEZ:AV0Z5007907 Keywords : adaptive foraging * anti-predator behaviour * cascading effects Subject RIV: EH - Ecology, Behaviour Impact factor: 3.914, year: 2004

  10. Sign epistasis caused by hierarchy within signalling cascades

    NARCIS (Netherlands)

    Nghe, Philippe; Kogenaru, Manjunatha; Tans, S.J.

    2018-01-01

    Sign epistasis is a central evolutionary constraint, but its causal factors remain difficult to predict. Here we use the notion of parameterised optima to explain epistasis within a signalling cascade, and test these predictions in Escherichia coli. We show that sign epistasis arises from the

  11. Energy Cascade Analysis: from Subscale Eddies to Mean Flow

    Science.gov (United States)

    Cheikh, Mohamad Ibrahim; Wonnell, Louis; Chen, James

    2017-11-01

    Understanding the energy transfer between eddies and mean flow can provide insights into the energy cascade process. Much work has been done to investigate the energy cascade at the level of the smallest eddies using different numerical techniques derived from the Navier-Stokes equations. These methodologies, however, prove to be computationally inefficient when producing energy spectra for a wide range of length scales. In this regard, Morphing Continuum Theory (MCT) resolves the length-scales issues by assuming the fluid continuum to be composed of inner structures that play the role of subscale eddies. The current study show- cases the capabilities of MCT in capturing the dynamics of energy cascade at the level of subscale eddies, through a supersonic turbulent flow of Mach 2.93 over an 8× compression ramp. Analysis of the results using statistical averaging procedure shows the existence of a statistical coupling of the internal and translational kinetic energy fluctuations with the corresponding rotational kinetic energy of the subscale eddies, indicating a multiscale transfer of energy. The results show that MCT gives a new characterization of the energy cascade within compressible turbulence without the use of excessive computational resources. This material is based upon work supported by the Air Force Office of Scientific Research under Award Number FA9550-17-1-0154.

  12. Low crosstalk Arrayed Waveguide Grating with Cascaded Waveguide Grating Filter

    International Nuclear Information System (INIS)

    Deng Yang; Liu Yuan; Gao Dingshan

    2011-01-01

    We propose a highly compact and low crosstalk arrayed waveguide grating (AWG) with cascaded waveguide grating (CWGF). The side lobes of the silicon nanowire AWG, which are normally introduced by fabrication errors, can be effectively suppressed by the CWGF. And the crosstalk can be improved about 15dB.

  13. 'Cascading participation' and the role of teachers in a collaborative ...

    African Journals Online (AJOL)

    'Cascading participation' and the role of teachers in a collaborative HIV and Aids curriculum development project. D Scott, A Cooper, S Swartz. Abstract. This paper presents findings of four Grade 6 teachers' involvement as facilitators of a participatory action research (PAR) project conducted in three South African primary ...

  14. Effect of field quantization on Rabi oscillation of equidistant cascade ...

    Indian Academy of Sciences (India)

    acting with a single-mode radiation field both semiclassically and quantum ... the equidistant cascade four-level system modeled by the generators of the spin-3. 2 ... (1), hω0 is the equidistant energy gap between the levels, Ω is the frequency.

  15. Exciton management in organic photovoltaic multidonor energy cascades.

    Science.gov (United States)

    Griffith, Olga L; Forrest, Stephen R

    2014-05-14

    Multilayer donor regions in organic photovoltaics show improved power conversion efficiency when arranged in decreasing exciton energy order from the anode to the acceptor interface. These so-called "energy cascades" drive exciton transfer from the anode to the dissociating interface while reducing exciton quenching and allowing improved overlap with the solar spectrum. Here we investigate the relative importance of exciton transfer and blocking in a donor cascade employing diphenyltetracene (D1), rubrene (D2), and tetraphenyldibenzoperiflanthene (D3) whose optical gaps monotonically decrease from D1 to D3. In this structure, D1 blocks excitons from quenching at the anode, D2 accepts transfer of excitons from D1 and blocks excitons at the interface between D2 and D3, and D3 contributes the most to the photocurrent due to its strong absorption at visible wavelengths, while also determining the open circuit voltage. We observe singlet exciton Förster transfer from D1 to D2 to D3 consistent with cascade operation. The power conversion efficiency of the optimized cascade OPV with a C60 acceptor layer is 7.1 ± 0.4%, which is significantly higher than bilayer devices made with only the individual donors. We develop a quantitative model to identify the dominant exciton processes that govern the photocurrent generation in multilayer organic structures.

  16. Multicomponent gas analysis using broadband quantum cascade laser spectroscopy

    NARCIS (Netherlands)

    Reyes Reyes, A.; Hou, Z.; Van Mastrigt, E.; Horsten, R.C.; De Jongste, J.C.; Pijnenburg, M.W.; Urbach, H.P.; Bhattacharya, N.

    2014-01-01

    We present a broadband quantum cascade laser-based spectroscopic system covering the region between 850 and 1250 cm?1. Its robust multipass cavity ensures a constant interaction length over the entire spectral region. The device enables the detection and identification of numerous molecules present

  17. Mid-infrared quantum cascade laser spectroscopy probing of the ...

    Indian Academy of Sciences (India)

    Aparajeo Chattopadhyay

    2018-05-07

    May 7, 2018 ... cm3 molecule. −1 s. −1 ... Quantum cascade laser; time-resolved mid-infrared spectroscopy; transient absorption; peroxy radicals .... peak of the laser emission profile. .... cal with O2 is a termolecular reaction (Eq. 3) and the.

  18. Evolution of the vertebrate phototransduction cascade activation steps.

    Science.gov (United States)

    Lamb, Trevor D; Hunt, David M

    2017-11-01

    We examine the molecular phylogeny of the proteins underlying the activation steps of vertebrate phototransduction, for both agnathan and jawed vertebrate taxa. We expand the number of taxa analysed and we update the alignment and tree building methodology from a previous analysis. For each of the four primary components (the G-protein transducin alpha subunit, Gα T , the cyclic GMP phosphodiesterase, PDE6, and the alpha and beta subunits of the cGMP-gated ion channel, CNGC), the phylogenies appear consistent with expansion from an ancestral proto-vertebrate cascade during two rounds of whole-genome duplication followed by divergence of the agnathan and jawed vertebrate lineages. In each case, we consider possible scenarios for the underlying gene duplications and losses, and we apply relevant constraints to the tree construction. From tests of the topology of the resulting trees, we obtain a scenario for the expansion of each component during 2R that accurately fits the observations. Similar analysis of the visual opsins indicates that the only expansion to have occurred during 2R was the formation of Rh1 and Rh2. Finally, we propose a hypothetical scenario for the conversion of an ancestral chordate cascade into the proto-vertebrate phototransduction cascade, prior to whole-genome duplication. Together, our models provide a plausible account for the origin and expansion of the vertebrate phototransduction cascade. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. ON THE POLAR CAP CASCADE PAIR MULTIPLICITY OF YOUNG PULSARS

    Energy Technology Data Exchange (ETDEWEB)

    Timokhin, A. N.; Harding, A. K., E-mail: andrey.timokhin@nasa.gov [Astrophysics Science Division, NASA/Goddard Space Flight Center, Greenbelt, MD 20771 (United States)

    2015-09-10

    We study the efficiency of pair production in polar caps of young pulsars under a variety of conditions to estimate the maximum possible multiplicity of pair plasma in pulsar magnetospheres. We develop a semi-analytic model for calculation of cascade multiplicity which allows efficient exploration of the parameter space and corroborate it with direct numerical simulations. Pair creation processes are considered separately from particle acceleration in order to assess different factors affecting cascade efficiency, with acceleration of primary particles described by recent self-consistent non-stationary model of pair cascades. We argue that the most efficient cascades operate in the curvature radiation/synchrotron regime, the maximum multiplicity of pair plasma in pulsar magnetospheres is ∼few × 10{sup 5}. The multiplicity of pair plasma in magnetospheres of young energetic pulsars weakly depends on the strength of the magnetic field and the radius of curvature of magnetic field lines and has a stronger dependence on pulsar inclination angle. This result questions assumptions about very high pair plasma multiplicity in theories of pulsar wind nebulae.

  20. Cascade probabilistic function and the Markov's processes. Chapter 1

    International Nuclear Information System (INIS)

    2002-01-01

    In the Chapter 1 the physical and mathematical descriptions of radiation processes are carried out. The relation of the cascade probabilistic functions (CPF) for electrons, protons, alpha-particles and ions with Markov's chain is shown. The algorithms for CPF calculation with accounting energy losses are given