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Sample records for single mapk cascade

  1. 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.

  2. Oscillations in MAPK cascade triggered by two distinct designs of coupled positive and negative feedback loops

    Science.gov (United States)

    2012-01-01

    Background Feedback loops, both positive and negative are embedded in the Mitogen Activated Protein Kinase (MAPK) cascade. In the three layer MAPK cascade, both feedback loops originate from the terminal layer and their sites of action are either of the two upstream layers. Recent studies have shown that the cascade uses coupled positive and negative feedback loops in generating oscillations. Two plausible designs of coupled positive and negative feedback loops can be elucidated from the literature; in one design the positive feedback precedes the negative feedback in the direction of signal flow and vice-versa in another. But it remains unexplored how the two designs contribute towards triggering oscillations in MAPK cascade. Thus it is also not known how amplitude, frequency, robustness or nature (analogous/digital) of the oscillations would be shaped by these two designs. Results We built two models of MAPK cascade that exhibited oscillations as function of two underlying designs of coupled positive and negative feedback loops. Frequency, amplitude and nature (digital/analogous) of oscillations were found to be differentially determined by each design. It was observed that the positive feedback emerging from an oscillating MAPK cascade and functional in an external signal processing module can trigger oscillations in the target module, provided that the target module satisfy certain parametric requirements. The augmentation of the two models was done to incorporate the nuclear-cytoplasmic shuttling of cascade components followed by induction of a nuclear phosphatase. It revealed that the fate of oscillations in the MAPK cascade is governed by the feedback designs. Oscillations were unaffected due to nuclear compartmentalization owing to one design but were completely abolished in the other case. Conclusion The MAPK cascade can utilize two distinct designs of coupled positive and negative feedback loops to trigger oscillations. The amplitude, frequency and

  3. A fungal-responsive MAPK cascade regulates phytoalexin biosynthesis in Arabidopsis.

    Science.gov (United States)

    Ren, Dongtao; Liu, Yidong; Yang, Kwang-Yeol; Han, Ling; Mao, Guohong; Glazebrook, Jane; Zhang, Shuqun

    2008-04-08

    Plant recognition of pathogens leads to rapid activation of MPK3 and MPK6, two Arabidopsis mitogen-activated protein kinases (MAPKs), and their orthologs in other species. Here, we report that synthesis of camalexin, the major phytoalexin in Arabidopsis, is regulated by the MPK3/MPK6 cascade. Activation of MPK3/MPK6 by expression of active upstream MAPK kinase (MAPKK) or MAPKK kinase (MAPKKK) was sufficient to induce camalexin synthesis in the absence of pathogen attack. Induction of camalexin by Botrytis cinerea was preceded by MPK3/MPK6 activation, and compromised in mpk3 and mpk6 mutants. Genetic analysis placed the MPK3/MPK6 cascade upstream of PHYTOALEXIN DEFICIENT 2 (PAD2) and PAD3, but independent or downstream of PAD1 and PAD4. Camalexin induction after MPK3/MPK6 activation was preceded by rapid and coordinated up-regulation of multiple genes encoding enzymes in the tryptophan (Trp) biosynthetic pathway, in the conversion of Trp to indole-3-acetaldoxime (IAOx, a branch point between primary and secondary metabolism), and in the camalexin biosynthetic pathway downstream of IAOx. These results indicate that the MPK3/MPK6 cascade regulates camalexin synthesis through transcriptional regulation of the biosynthetic genes after pathogen infection.

  4. p38 MAPK-SKN-1/Nrf signaling cascade is required for intestinal barrier against graphene oxide toxicity in Caenorhabditis elegans.

    Science.gov (United States)

    Zhao, Yunli; Zhi, Lingtong; Wu, Qiuli; Yu, Yonglin; Sun, Qiqing; Wang, Dayong

    2016-12-01

    Biological barrier plays a crucial role for organisms against the possible toxicity from engineered nanomaterials (ENMs). Graphene oxide (GO) has been proven to cause potential toxicity on organisms. However, the molecular mechanisms for intestinal barrier of animals against GO toxicity are largely unclear. Using in vivo assay system of Caenorhabditis elegans, we found that mutation of genes encoding core p38 mitogen-activated protein kinase (MAPK) signaling pathway caused susceptible property to GO toxicity and enhanced translocation of GO into the body of nematodes. Genetic assays indicated that SKN-1/Nrf functioned downstream of p38 MAPK signaling pathway to regulate GO toxicity and translocation. Transcription factor of SKN-1 could regulate GO toxicity and translocation at least through function of its targeted gene of gst-4 encoding one of phase II detoxification proteins. Moreover, intestine-specific RNA interference (RNAi) assay demonstrated that the p38 MAPK-SKN-1/Nrf signaling cascade could function in intestine to regulate GO toxicity and intestinal permeability in GO exposed nematodes. Therefore, p38 MAPK-SKN-1/Nrf signaling cascade may act as an important molecular basis for intestinal barrier against GO toxicity in organisms. Exposure to GO induced significantly increased expression of genes encoding p38 MAPK-SKN-1/Nrf signaling cascade, which further implies that the identified p38 MAPK-SKN-1/Nrf signaling cascade may encode a protection mechanism for nematodes in intestine to be against GO toxicity.

  5. In silico analysis reveals widespread presence of three gene families, MAPK, MAPKK and MAPKKK, of the MAPK cascade from crop plants of Solanaceae in comparison to the distantly-related syntenic species from Rubiaceae, coffee

    Directory of Open Access Journals (Sweden)

    Hira Iftikhar

    2017-06-01

    Full Text Available Mitogen-activated protein kinases (MAPKs are an important family of genes which play roles in vital plant processes, and they also help in coping against various kinds of environmental stresses including abiotic as well as biotic factors. The advancement of genomics calls for the annotation, identification, and detailed processing of the essential gene families in plants in order to provide insights into the importance of their central roles as well as for providing the basis for making their growth vigorous even under stressed conditions and, ultimately, to benefit from them by foreseeing the potential threats to their growth. In the current study, MAPK, MAPKK, and MAPKKK families of the MAPK cascade were identified and reported from five different agriculturally and economically important crop species of the Solanaceae and Rubiaceae families based on conserved signature motifs aligned throughout the members of the families under this gene superfamily. Genes reported from the species after strict filtering were: 89, tomato; 108, potato; 63, eggplant; 79, pepper; 64, coffee. These MAPKs were found to be randomly distributed throughout the genome on the chromosomes of the respective species. Various characteristics of the identified genes were studied including gene structure, gene and coding sequence length, protein length, isoelectric point, molecular weight, and subcellular localization. Moreover, maximum likelihood test of phylogeny was conducted on the retrieved sequences for the three MAPK cascade families to determine their homologous relationships which were also analyzed quantitatively by heat plots.

  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. Single phase cascaded H5 inverter with leakage current elimination for transformerless photovoltaic system

    DEFF Research Database (Denmark)

    Guo, Xiaoqiang; Jia, X.; Lu, Z.

    2016-01-01

    Leakage current reduction is one of the important issues for the transformelress PV systems. In this paper, the transformerless single-phase cascaded H-bridge PV inverter is investigated. The common mode model for the cascaded H4 inverter is analyzed. And the reason why the conventional cascade H...

  8. Single-Mode, Distributed Feedback Interband Cascade Lasers

    Science.gov (United States)

    Frez, Clifford F. (Inventor); Borgentun, Carl E. (Inventor); Briggs, Ryan M. (Inventor); Bagheri, Mahmood (Inventor); Forouhar, Siamak (Inventor)

    2016-01-01

    Single-mode, distributed feedback interband cascade lasers (ICLs) using distributed-feedback gratings (e.g., lateral Bragg gratings) and methods of fabricating such ICLs are provided. The ICLs incorporate distributed-feedback gratings that are formed above the laser active region and adjacent the ridge waveguide (RWG) of the ICL. The ICLs may incorporate a double-ridge system comprising an optical confinement structure (e.g., a RWG) disposed above the laser active region that comprises the first ridge of the double ridge system, a DFB grating (e.g., lateral Bragg grating) disposed above the laser active region and adjacent the optical confinement structure, and an electric confinement structure that passes at least partially through the laser active region and that defines the boundary of the second ridge comprises and the termination of the DFB grating.

  9. 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.

  10. Mechanisms for type-II vitellogenesis-inhibiting hormone suppression of vitellogenin transcription in shrimp hepatopancreas: Crosstalk of GC/cGMP pathway with different MAPK-dependent cascades.

    Science.gov (United States)

    Chen, Ting; Ren, Chunhua; Jiang, Xiao; Zhang, Lvping; Li, Hongmei; Huang, Wen; Hu, Chaoqun

    2018-01-01

    Vitellogenesis is the process of yolk formation via accumulating vitellin (Vn) with nutrients in the oocytes. Expression of vitellogenin (Vg), the precursor of Vn, is one of the indicators for the start of vitellogenesis. In Pacific white shrimp (Litopenaeus vannamei), the type-II vitellogenesis-inhibiting hormone (VIH-2) effectively suppresses hepatopancreatic Vg mRNA expression. In this study, we demonstrate the increasing transcript levels of hepatopancreatic Vg during L. vannamei ovarian development, suggesting that the hepatopancreas-derived Vg/Vn may also contribute to vitellogenesis in this species. Using a combination of in vivo injections and in vitro primary cell cultures, we provide evidences that the inhibition of VIH-2 on hepatopancreatic Vg gene expression is mediated through a functional coupling of the GC/cGMP pathway with different MAPK-dependent cascades in female shrimp. In VIH-2 signaling, the NO-independent GC/cGMP/PKG cascades were upstream of the MAPKs. Activations of the MAPK signal by VIH-2 include the phosphorylation of JNK and the mRNA/protein expression of P38MAPK. Additionally, the cAMP/PKA pathway is another positive intracellular signal for hepatopancreatic Vg mRNA expression but is independent of its VIH-2 regulation. Our findings establish a model for the signal transduction mechanism of Vg regulation by VIH and shed light on the biological functions and signaling of the CHH family in crustaceans.

  11. Atomistic simulations of displacement cascades in Y2O3 single crystal

    International Nuclear Information System (INIS)

    Dholakia, Manan; Chandra, Sharat; Valsakumar, M.C.; Mathi Jaya, S.

    2014-01-01

    Graphical abstract: (a) The averaged distortion index and the Y–O bond length of the Y 2 O 3 octahedra as a function of the simulation time for 5 keV PKA. (b) Shows the nearest neighbourhood of one of the Y ions as a function of simulation time, showing the destruction and the recovery of the YO 6 octahedron during the cascade corresponding to 5 keV Y PKA. - Highlights: • Qualitative difference in displacement cascades exists for Y and O PKA. • Nearest neighbour correlation between Y and O ions exists even at cascade peak. • Cascade core in Y 2 O 3 does not undergo melting. • Topological connectivity of YO 6 polyhedra plays important role in stability of Y 2 O 3 . - Abstract: We study the characteristics of displacement cascades in single crystal Y 2 O 3 using classical molecular dynamics. There are two possible ways to generate the cascades in yttria, using either the Y or the O atoms as the primary knock-on (PKA) atom. It is shown that there is a qualitative difference in the characteristics of the cascades obtained in these two cases. Even though the crystal is seen to be in a highly disordered state in the cascade volume, as seen from the plots of radial distribution function, the correlation between the Y and O atoms is not completely lost. This facilitates a quick recovery of the system during the annealing phase. Topological connectivity of the YO 6 polyhedral units plays an important role in imparting stability to the Y 2 O 3 crystal. These characteristics of the cascades can help explain the stability of the yttria nanoparticles when they are dispersed in oxide dispersion strengthened steels

  12. Galangin ameliorates cisplatin induced nephrotoxicity in vivo by modulation of oxidative stress, apoptosis and inflammation through interplay of MAPK signaling cascade.

    Science.gov (United States)

    Tomar, Ameesha; Vasisth, Swati; Khan, Sana Irfan; Malik, Salma; Nag, Tapas Chandra; Arya, Dharamveer Singh; Bhatia, Jagriti

    2017-10-15

    Cisplatin is a widely used chemotherapeutic agent but now-a-days its usage is limited in clinical chemotherapy because of its severe nephrotoxic effect on renal tissues. Galangin, a flavonoid obtained from ginger family has been demonstrated to have antioxidant, anti-apoptotic and anti-inflammatory properties. This study is aimed to investigate the possible ameliorative effect of galangin in a rodent model of cisplatin-induced nephrotoxicity. Adult male albino wistar rats were divided into six groups (n=6) viz normal, cisplatin-control, galangin (25, 50 and 100mg/kg p.o.) and per se (100mg/kg galangin, p.o.). Galangin was administrated orally to the rats for a period of 10 days. On the 7th day of the treatment, nephrotoxicity was induced in all the groups by a single dose of cisplatin (8mg/kg, i.p.) (except normal and per se group). On the 11th day, the rats were anaesthetized and blood was withdrawn via direct heart puncture for biochemical estimation. Rats were sacrificed and kidneys were isolated and preserved for evaluation of histopathological, ultra structural immunohistochemical studies and western blot analysis. Cisplatin significantly impaired renal function and increased oxidative stress and inflammation. It also increased expression of pro-apoptotic proteins Bax and caspase-3 and decreased the expression of the anti-apoptotic protein Bcl-2. Histological and ultrastructural findings were also supportive of renal tubular damage. Pretreatment with galangin (100mg/kg p.o.) preserved renal function, morphology, suppressed oxidative stress, inflammation and the activation of apoptotic pathways. TUNEL assay showed decreased DNA fragmentation on galangin pre-treatment. Furthermore, galangin (100mg/kg) pre-treatment also reduced the expression of NFκB along with proteins MAPK pathway i.e. p38, JNK and ERK1/2. In conclusion, Galangin (100mg/kg, p.o.) significantly ameliorated cisplatin induced nephrotoxicity by suppressing MAPK induced inflammation and apoptosis

  13. Photon Cascade from a Single Crystal Phase Nanowire Quantum Dot

    DEFF Research Database (Denmark)

    Bouwes Bavinck, Maaike; Jöns, Klaus D; Zieliński, Michal

    2016-01-01

    We report the first comprehensive experimental and theoretical study of the optical properties of single crystal phase quantum dots in InP nanowires. Crystal phase quantum dots are defined by a transition in the crystallographic lattice between zinc blende and wurtzite segments and therefore offe...

  14. 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 ...

  15. Single-mode quantum cascade lasers employing a candy-cane shaped monolithic coupled cavity

    Science.gov (United States)

    Liu, Peter Q.; Sladek, Kamil; Wang, Xiaojun; Fan, Jen-Yu; Gmachl, Claire F.

    2011-12-01

    We demonstrate single-mode quantum cascade lasers emitting at ˜4.5 μm by employing a monolithic "candy-cane" shaped coupled-cavity consisting of a straight section connecting at one end to a spiral section. The fabrication process is identical to those for simple Fabry-Perot-type ridge lasers. Continuously tunable single-mode emission across ˜8 cm-1 with side mode suppression ratio up to ˜25 dB and a single-mode operating current range of more than 70% above the threshold current is achieved when the lasers are operated in pulsed-mode from 80 K to 155 K.

  16. Nano-optical observation of cascade switching in a parallel superconducting nanowire single photon detector

    International Nuclear Information System (INIS)

    Heath, Robert M.; Tanner, Michael G.; Casaburi, Alessandro; Hadfield, Robert H.; Webster, Mark G.; San Emeterio Alvarez, Lara; Jiang, Weitao; Barber, Zoe H.; Warburton, Richard J.

    2014-01-01

    The device physics of parallel-wire superconducting nanowire single photon detectors is based on a cascade process. Using nano-optical techniques and a parallel wire device with spatially separate pixels, we explicitly demonstrate the single- and multi-photon triggering regimes. We develop a model for describing efficiency of a detector operating in the arm-trigger regime. We investigate the timing response of the detector when illuminating a single pixel and two pixels. We see a change in the active area of the detector between the two regimes and find the two-pixel trigger regime to have a faster timing response than the one-pixel regime

  17. Highly efficient single-pass sum frequency generation by cascaded nonlinear crystals

    DEFF Research Database (Denmark)

    Hansen, Anders Kragh; Andersen, Peter E.; Jensen, Ole Bjarlin

    2015-01-01

    The cascading of nonlinear crystals has been established as a simple method to greatly increase the conversion efficiency of single-pass second-harmonic generation compared to a single-crystal scheme. Here, we show for the first time that the technique can be extended to sum frequency generation......, despite differences in the phase relations of the involved fields. An unprecedented 5.5 W of continuous-wave diffraction-limited green light is generated from the single-pass sum frequency mixing of two diode lasers in two periodically poled nonlinear crystals (conversion efficiency 50%). The technique...

  18. A Novel Hydroxamate-Based Compound WMJ-J-09 Causes Head and Neck Squamous Cell Carcinoma Cell Death via LKB1-AMPK-p38MAPK-p63-Survivin Cascade.

    Science.gov (United States)

    Yen, Chia-Sheng; Choy, Cheuk-Sing; Huang, Wei-Jan; Huang, Shiu-Wen; Lai, Pin-Ye; Yu, Meng-Chieh; Shiue, Ching; Hsu, Ya-Fen; Hsu, Ming-Jen

    2018-01-01

    Growing evidence shows that hydroxamate-based compounds exhibit broad-spectrum pharmacological properties including anti-tumor activity. However, the precise mechanisms underlying hydroxamate derivative-induced cancer cell death remain incomplete understood. In this study, we explored the anti-tumor mechanisms of a novel aliphatic hydroxamate-based compound, WMJ-J-09, in FaDu head and neck squamous cell carcinoma (HNSCC) cells. WMJ-J-09 induced G2/M cell cycle arrest and apoptosis in FaDu cells. These actions were associated with liver kinase B1 (LKB1), AMP-activated protein kinase (AMPK) and p38 mitogen-activated protein kinase (p38MAPK) activation, transcription factor p63 phosphorylation, as well as modulation of p21 and survivin. LKB1-AMPK-p38MAPK signaling blockade reduced WMJ-J-09's enhancing effects in p63 phosphorylation, p21 elevation and survivin reduction. Moreover, WMJ-J-09 caused an increase in α-tubulin acetylation and interfered with microtubule assembly. Furthermore, WMJ-J-09 suppressed the growth of subcutaneous FaDu xenografts in vivo . Taken together, WMJ-J-09-induced FaDu cell death may involve LKB1-AMPK-p38MAPK-p63-survivin signaling cascade. HDACs inhibition and disruption of microtubule assembly may also contribute to WMJ-J-09's actions in FaDu cells. This study suggests that WMJ-J-09 may be a potential lead compound and warrant the clinical development in the treatment of HNSCC.

  19. Plasticity of the MAPK signaling network in response to mechanical stress.

    Directory of Open Access Journals (Sweden)

    Andrea M Pereira

    Full Text Available Cells display versatile responses to mechanical inputs and recent studies have identified the mitogen-activated protein kinase (MAPK cascades mediating the biological effects observed upon mechanical stimulation. Although, MAPK pathways can act insulated from each other, several mechanisms facilitate the crosstalk between the components of these cascades. Yet, the combinatorial complexity of potential molecular interactions between these elements have prevented the understanding of their concerted functions. To analyze the plasticity of the MAPK signaling network in response to mechanical stress we performed a non-saturating epistatic screen in resting and stretched conditions employing as readout a JNK responsive dJun-FRET biosensor. By knocking down MAPKs, and JNK pathway regulators, singly or in pairs in Drosophila S2R+ cells, we have uncovered unexpected regulatory links between JNK cascade kinases, Rho GTPases, MAPKs and the JNK phosphatase Puc. These relationships have been integrated in a system network model at equilibrium accounting for all experimentally validated interactions. This model allows predicting the global reaction of the network to its modulation in response to mechanical stress. It also highlights its context-dependent sensitivity.

  20. Strong coupling and stimulated emission in single parabolic quantum well microcavity for terahertz cascade

    International Nuclear Information System (INIS)

    Tzimis, A.; Savvidis, P. G.; Trifonov, A. V.; Ignatiev, I. V.; Christmann, G.; Tsintzos, S. I.; Hatzopoulos, Z.; Kavokin, A. V.

    2015-01-01

    We report observation of strong light-matter coupling in an AlGaAs microcavity (MC) with an embedded single parabolic quantum well. The parabolic potential is achieved by varying aluminum concentration along the growth direction providing equally spaced energy levels, as confirmed by Brewster angle reflectivity from a reference sample without MC. It acts as an active region of the structure which potentially allows cascaded emission of terahertz (THz) light. Spectrally and time resolved pump-probe spectroscopy reveals characteristic quantum beats whose frequencies range from 0.9 to 4.5 THz, corresponding to energy separation between relevant excitonic levels. The structure exhibits strong stimulated nonlinear emission with simultaneous transition to weak coupling regime. The present study highlights the potential of such devices for creating cascaded relaxation of bosons, which could be utilized for THz emission

  1. High frequency modulation capabilities and quasi single-sideband emission from a quantum cascade laser.

    Science.gov (United States)

    Hangauer, Andreas; Spinner, Georg; Nikodem, Michal; Wysocki, Gerard

    2014-09-22

    Both intensity- (IM) and frequency-modulation (FM) behavior of a directly modulated quantum cascade laser (QCL) are measured from 300 Hz to 1.7 GHz. Quantitative measurements of tuning coefficients has been performed and the transition from thermal- to electronic-tuning is clearly observed. A very specific FM behavior of QCLs has been identified which allows for optical quasi single sideband (SSB) modulation through current injection and has not been observed in directly modulated semiconductor lasers before. This predestines QCLs in applications where SSB is required, such as telecommunication or high speed spectroscopy. The experimental procedure and theoretical modeling for data extraction is discussed.

  2. NONLINEAR SYSTEM MODELING USING SINGLE NEURON CASCADED NEURAL NETWORK FOR REAL-TIME APPLICATIONS

    Directory of Open Access Journals (Sweden)

    S. Himavathi

    2012-04-01

    Full Text Available Neural Networks (NN have proved its efficacy for nonlinear system modeling. NN based controllers and estimators for nonlinear systems provide promising alternatives to the conventional counterpart. However, NN models have to meet the stringent requirements on execution time for its effective use in real time applications. This requires the NN model to be structurally compact and computationally less complex. In this paper a parametric method of analysis is adopted to determine the compact and faster NN model among various neural network architectures. This work proves through analysis and examples that the Single Neuron Cascaded (SNC architecture is distinct in providing compact and simpler models requiring lower execution time. The unique structural growth of SNC architecture enables automation in design. The SNC Network is shown to combine the advantages of both single and multilayer neural network architectures. Extensive analysis on selected architectures and their models for four benchmark nonlinear theoretical plants and a practical application are tested. A performance comparison of the NN models is presented to demonstrate the superiority of the single neuron cascaded architecture for online real time applications.

  3. Plasticity of the MAPK signaling network in response to mechanical stress

    NARCIS (Netherlands)

    Pereira, Andrea M; Tudor, Cicerone; Pouille, Philippe-Alexandre; Shekhar, Shashank; Kanger, Johannes S; Subramaniam, Vinod; Martín-Blanco, Enrique

    2014-01-01

    Cells display versatile responses to mechanical inputs and recent studies have identified the mitogen-activated protein kinase (MAPK) cascades mediating the biological effects observed upon mechanical stimulation. Although, MAPK pathways can act insulated from each other, several mechanisms

  4. Robust cascade control for the horizontal motion of a vehicle with single-wheel actuators

    Science.gov (United States)

    Moseberg, Jan-Erik; Roppenecker, Günter

    2015-12-01

    The article presents a cascade control for the horizontal motion of a vehicle with single-wheel actuators. The outer control loop for the longitudinal and lateral accelerations and the yaw rate ensures a desired vehicle motion. By a combination of state feedback control and observer-based disturbance feedforward the inner control loop robustly stabilises the rotating and steering motions of the wheels in spite of unknown frictions between tyres and ground. Since the three degrees of freedom of the horizontal motion are affected by eight tyre forces, the vehicle considered is an over-actuated system. Thus additional control objectives can be realised besides the desired motion trajectory as, for example, a maximum in driving safety. The corresponding analytical tyre force allocation also guarantees real-time capability because of its relatively low computational effort. Provided suitable fault detection and isolation are available, the proposed cascade control has the potential of fault-tolerance, because the force allocation is adaptable. Another benefit results from the modular control structure, because it allows a stepwise implementation. Besides, it only requires a small number of measurements for control purposes. These measurements are the rotational speeds and steering angles of the wheels, the longitudinal and lateral acceleration and the yaw rate of the vehicle.

  5. Hard-metal (WC-Co) particles trigger a signaling cascade involving p38 MAPK, HIF-1α, HMOX1, and p53 activation in human PBMC.

    Science.gov (United States)

    Lombaert, Noömi; Castrucci, Eleonora; Decordier, Ilse; Van Hummelen, Paul; Kirsch-Volders, Micheline; Cundari, Enrico; Lison, Dominique

    2013-02-01

    Hard-metals are made of tungsten carbide (WC) and metallic cobalt (Co) particles and are important industrial materials produced for their extreme hardness and high wear resistance properties. While occupational exposure to metallic Co alone is apparently not associated with an increased risk of cancer, the WC-Co particle mixture was shown to increase the risk of lung cancer in exposed workers. We have previously shown that WC-Co specifically induces a burst of reactive oxygen species (ROS) and in vitro mutagenic/apoptogenic effects in human peripheral blood mononucleated cells (PBMC) used as a validated experimental model. In the present study, PBMCs were treated during a short period (15 min) to focus on the very rapid ROS burst induced by WC-Co. We investigated by microarray the response to WC-Co versus Co(2+) ions (CoCl(2)) after 15 min exposure and found that the oxidative stress response HMOX1 gene was highly expressed in WC-Co-treated samples. This result was confirmed by qRT-PCR, and western blotting was carried out to analyze translational and post-translational regulation of genes belonging to the HMOX1 pathway. We show here that WC-Co, and metallic Co particles although with slower kinetics, but not CoCl(2) or WC alone, induced a temporally ordered cascade of events. This cascade implies p38/MAP kinase activation, HIF-1α stabilization, HMOX1 transcriptional activation, and ATM-independent p53 stabilization. These events, and in particular HIF-1α stabilization, could contribute to the carcinogenic activity of WC-Co dusts.

  6. Stable Single-Mode Operation of Distributed Feedback Quantum Cascade Laser by Optimized Reflectivity Facet Coatings.

    Science.gov (United States)

    Wang, Dong-Bo; Zhang, Jin-Chuan; Cheng, Feng-Min; Zhao, Yue; Zhuo, Ning; Zhai, Shen-Qiang; Wang, Li-Jun; Liu, Jun-Qi; Liu, Shu-Man; Liu, Feng-Qi; Wang, Zhan-Guo

    2018-02-02

    In this work, quantum cascade lasers (QCLs) based on strain compensation combined with two-phonon resonance design are presented. Distributed feedback (DFB) laser emitting at ~ 4.76 μm was fabricated through a standard buried first-order grating and buried heterostructure (BH) processing. Stable single-mode emission is achieved under all injection currents and temperature conditions without any mode hop by the optimized antireflection (AR) coating on the front facet. The AR coating consists of a double layer dielectric of Al 2 O 3 and Ge. For a 2-mm laser cavity, the maximum output power of the AR-coated DFB-QCL was more than 170 mW at 20 °C with a high wall-plug efficiency (WPE) of 4.7% in a continuous-wave (CW) mode.

  7. Mitogen-activated protein kinase (MAPK) dynamics determine cell fate in the yeast mating response.

    Science.gov (United States)

    Li, Yang; Roberts, Julie; AkhavanAghdam, Zohreh; Hao, Nan

    2017-12-15

    In the yeast Saccharomyces cerevisiae , the exposure to mating pheromone activates a prototypic mitogen-activated protein kinase (MAPK) cascade and triggers a dose-dependent differentiation response. Whereas a high pheromone dose induces growth arrest and formation of a shmoo-like morphology in yeast cells, lower pheromone doses elicit elongated cell growth. Previous population-level analysis has revealed that the MAPK Fus3 plays an important role in mediating this differentiation switch. To further investigate how Fus3 controls the fate decision process at the single-cell level, we developed a specific translocation-based reporter for monitoring Fus3 activity in individual live cells. Using this reporter, we observed strikingly different dynamic patterns of Fus3 activation in single cells differentiated into distinct fates. Cells committed to growth arrest and shmoo formation exhibited sustained Fus3 activation. In contrast, most cells undergoing elongated growth showed either a delayed gradual increase or pulsatile dynamics of Fus3 activity. Furthermore, we found that chemically perturbing Fus3 dynamics with a specific inhibitor could effectively redirect the mating differentiation, confirming the causative role of Fus3 dynamics in driving cell fate decisions. MAPKs mediate proliferation and differentiation signals in mammals and are therapeutic targets in many cancers. Our results highlight the importance of MAPK dynamics in regulating single-cell responses and open up the possibility that MAPK signaling dynamics could be a pharmacological target in therapeutic interventions. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  8. Demonstration of Cascaded In-Line Single-Pump Fiber Optical Parametric Amplifiers in Recirculating Loop Transmission

    DEFF Research Database (Denmark)

    Lali-Dastjerdi, Zohreh; Ozolins, Oskars; An, Yi

    2012-01-01

    The performance of cascaded single-pump fiber optical parametric amplifiers (FOPAs) is experimentally studied for the first time using recirculating loop transmission with 80-km dispersion managed spans. Error-free performance has been achieved over 320 km for 40-Gbit/s CSRZ-OOK and CSRZ...

  9. Live-cell microscopy reveals small molecule inhibitor effects on MAPK pathway dynamics.

    Directory of Open Access Journals (Sweden)

    Daniel J Anderson

    Full Text Available Oncogenic mutations in the mitogen activated protein kinase (MAPK pathway are prevalent in human tumors, making this pathway a target of drug development efforts. Recently, ATP-competitive Raf inhibitors were shown to cause MAPK pathway activation via Raf kinase priming in wild-type BRaf cells and tumors, highlighting the need for a thorough understanding of signaling in the context of small molecule kinase inhibitors. Here, we present critical improvements in cell-line engineering and image analysis coupled with automated image acquisition that allow for the simultaneous identification of cellular localization of multiple MAPK pathway components (KRas, CRaf, Mek1 and Erk2. We use these assays in a systematic study of the effect of small molecule inhibitors across the MAPK cascade either as single agents or in combination. Both Raf inhibitor priming as well as the release from negative feedback induced by Mek and Erk inhibitors cause translocation of CRaf to the plasma membrane via mechanisms that are additive in pathway activation. Analysis of Erk activation and sub-cellular localization upon inhibitor treatments reveals differential inhibition and activation with the Raf inhibitors AZD628 and GDC0879 respectively. Since both single agent and combination studies of Raf and Mek inhibitors are currently in the clinic, our assays provide valuable insight into their effects on MAPK signaling in live cells.

  10. The Role of MAPK in Drug-Induced Kidney Injury

    Directory of Open Access Journals (Sweden)

    Hilary Cassidy

    2012-01-01

    Full Text Available This paper focuses on the role that mitogen-activated protein kinases (MAPKs play in drug-induced kidney injury. The MAPKs, of which there are four major classes (ERK, p38, JNK, and ERK5/BMK, are signalling cascades which have been found to be broadly conserved across a wide variety of organisms. MAPKs allow effective transmission of information from the cell surface to the cytosolic or nuclear compartments. Cross talk between the MAPKs themselves and with other signalling pathways allows the cell to modulate responses to a wide variety of external stimuli. The MAPKs have been shown to play key roles in both mediating and ameliorating cellular responses to stress including xenobiotic-induced toxicity. Therefore, this paper will discuss the specific role of the MAPKs in the kidney in response to injury by a variety of xenobiotics and the potential for therapeutic intervention at the level of MAPK signalling across different types of kidney disease.

  11. MAP Kinase Cascades in Plant Innate Immunity

    Directory of Open Access Journals (Sweden)

    Magnus Wohlfahrt Rasmussen

    2012-07-01

    Full Text Available 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 (PRRs which trigger MAPK-dependent innate immune responses. In the model Arabidopsis, molecular genetic evidence implicates a number of MAPK cascade components in PAMP signaling, and in responses to immunity-related phytohormones such as ethylene, jasmonate and salicylate. In a few cases, cascade components have been directly linked to the transcription of target genes or to the regulation of phytohormone synthesis. Thus MAPKs are obvious targets for bacterial effector proteins and are likely guardees of resistance (R proteins, which mediate defense signaling in response to the action of effectors, or effector-triggered immunity (ETI. This mini-review discusses recent progress in this field with a focus on the Arabidopsis MAPKs MPK3, 4, 6 and 11 in their apparent pathways.

  12. 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 ...

  13. Conservation of Chitin-Induced MAPK Signaling Pathways in Rice and Arabidopsis.

    Science.gov (United States)

    Yamada, Kenta; Yamaguchi, Koji; Yoshimura, Satomi; Terauchi, Akira; Kawasaki, Tsutomu

    2017-06-01

    Perception of microbe-associated molecular patterns (MAMPs) including chitin by pattern recognition receptors (PRRs) rapidly induces activation of mitogen-activated protein kinase (MAPK) cascades. However, how PRRs transmit immune signals to the MAPK cascade is largely unknown. Recently, Arabidopsis receptor-like cytoplasmic kinase PBL27 has been reported to activate MAPKs through phosphorylation of AtMAPKKK5 in the chitin signaling pathway. In this study, we found that OsRLCK185, a rice ortholog of PBL27, regulates chitin-induced MAPK activation in a similar fashion to PBL27 in rice. Upon chitin perception, OsRLCK185 is phosphorylated by OsCERK1, a component of the chitin receptor complex. OsRLCK185 interacted with OsMAPKKK11 and OsMAPKKK18, rice orthologs of AtMAPKKK5, in yeast two-hybrid assays. Silencing of both OsMAPKKK11 and OsMAPKKK18 significantly reduced chitin-induced activation of OsMPK3 and OsMPK6. Expression levels of OsMAPKKK18 were much higher than that of OsMAPKKK11 in rice cells, which was consistent with the fact that the Osmapkkk11 single mutation did not affect MAPK activation. This result suggested that OsMAPKKK18 plays a more important role than OsMAPKKK11 in the chitin-induced activation of OsMPK3 and OsMPK6. The bimolecular fluorescence complementation (BiFC) experiment indicated that OsRLCK185 interacted with OsMAPKKK18 at the plasma membrane in planta. In vitro phosphorylation experiments showed that OsRLCK185 directly phosphorylates OsMAPKKK18. Furthermore, OsMAPKKK18 interacted with the MAPKK OsMKK4, the upstream component of OsMPK3/6. These results suggested that OsRLCK185 connects the chitin receptor to the MAPK cascade consisting of OsMAPKKK18-OsMKK4-OsMPK3/6. Our data revealed that chitin-induced MAPK activation in rice and Arabidopsis is regulated by common homologous elements. © The Author 2017. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please

  14. Single-mode interband cascade laser sources for mid-infrared spectroscopic applications

    Science.gov (United States)

    Scheuermann, J.; von Edlinger, M.; Weih, R.; Becker, S.; Nähle, L.; Fischer, M.; Koeth, J.; Kamp, M.; Höfling, S.

    2016-05-01

    Compared to the near infrared, many technologically and industrially relevant gas species have more than an order of magnitude higher absorption features in the mid-infrared (MIR) wavelength range. These species include for example important hydrocarbons (methane, acetylene), nitrogen oxides and sulfur oxides. Tunable laser absorption spectroscopy (TLAS) has proven to be a versatile tool for gas sensing applications with significant advantages compared to other techniques. These advantages include real time measurement, standoff detection and ruggedness of the sensor. We present interband cascade lasers (ICLs), which have evolved into important laser sources for the MIR spectral range from 3 to 7 μm. ICLs achieve high efficiency by cascading optically active zones whilst using interband transitions, so they combine common diode laser as well as quantum cascade laser based technologies. Our application grade singlemode distributed feedback devices operate continuous wave at room temperature and are offering several features especially useful for high performance TLAS applications like: side mode suppression ratio of > 30 dB, continuous tuning ranges up to 30 nm, low threshold power densities and low overall power consumption. The devices are typically integrated in a thermoelectrically cooled TO-style package, hermetically sealed using a cap with anti-reflection coated window. This low power consumption as well as the compact size and ruggedness of the fabricated laser sources makes them perfectly suited for battery powered portable solutions for in field spectroscopy applications.

  15. A Five-Level Cascade Multilevel Inverter Three-Phase Motor Drive Using a Single DC Source

    Energy Technology Data Exchange (ETDEWEB)

    Chiasson, J. N. [University of Tennessee, Knoxville (UTK)

    2006-10-01

    A method is presented showing that a 5-level cascade multilevel inverter for a three-phase permanent magnet sychronous motor drive can be implemented using only a single DC link to supply a standard 3-leg inverter along with three full H-bridges supplied by capacitors. It is shown that the capacitor voltages can be regulated while achieving an output voltage waveform that is 20% greater than that obained using the standard 3-leg inverter alone. Finally conditions are given in terms of the power factor and modulation index that determine when the capacitor voltage can regulated.

  16. A Five-Level Cascade Multilever Invertor Three-Phase Motor Drive Using a Single DC Source

    Energy Technology Data Exchange (ETDEWEB)

    Chiasson, J.N. (Univ. Tennessee-Knoxville)

    2006-09-15

    A method is presented showing that a 5-level cascade multilevel inverter for a three-phase permanent magnet synchronous motor drive can be implemented using only a single DC link to supply a standard 3-leg inverter along with three full H-bridges supplied by capacitors. It is shown that the capacitor voltages can be regulated while achieving an output voltage waveform that is 20% greater than that obtained using the standard 3-leg inverter alone. Finally conditions are given in terms of the power factor and modulation index that determine when the capacitor voltage can regulated.

  17. Realization of a Cascaded Quantum System: Heralded Absorption of a Single Photon Qubit by a Single-Electron Charged Quantum Dot.

    Science.gov (United States)

    Delteil, Aymeric; Sun, Zhe; Fält, Stefan; Imamoğlu, Atac

    2017-04-28

    Photonic losses pose a major limitation for the implementation of a quantum state transfer between nodes of a quantum network. A measurement that heralds a successful transfer without revealing any information about the qubit may alleviate this limitation. Here, we demonstrate the heralded absorption of a single photonic qubit, generated by a single neutral quantum dot, by a single-electron charged quantum dot that is located 5 m away. The transfer of quantum information to the spin degree of freedom takes place upon the emission of a photon; for a properly chosen or prepared quantum dot, the detection of this photon yields no information about the qubit. We show that this process can be combined with local operations optically performed on the destination node by measuring classical correlations between the absorbed photon color and the final state of the electron spin. Our work suggests alternative avenues for the realization of quantum information protocols based on cascaded quantum systems.

  18. Investigation on stacked cascade multilevel inverter by employing single-phase transformers

    Directory of Open Access Journals (Sweden)

    Y. Suresh

    2016-06-01

    Full Text Available In the present paper a new version of multilevel inverter is investigated. This new version is based on hybrid association of commutation cells with H-bridge cells. The association allows a significant reduction of the volume of the capacitors. In fact, presented topology allows us to work on higher input voltage levels with the same power switches. This new version is generally called as SCMI (stacked cascade multilevel inverter. The proposed inverter has potential to generate high quality waveforms, reduction in switching frequency, capable to operate at higher voltage levels and finally utilizes minimum number of switching components. The presented version of SCMI is simulated in Matlab-simulink and further, experimental validation is carried out in the laboratory with prototype setup.

  19. Regulation of ERK-MAPK signaling in human epidermis.

    Science.gov (United States)

    Cursons, Joseph; Gao, Jerry; Hurley, Daniel G; Print, Cristin G; Dunbar, P Rod; Jacobs, Marc D; Crampin, Edmund J

    2015-07-25

    The skin is largely comprised of keratinocytes within the interfollicular epidermis. Over approximately two weeks these cells differentiate and traverse the thickness of the skin. The stage of differentiation is therefore reflected in the positions of cells within the tissue, providing a convenient axis along which to study the signaling events that occur in situ during keratinocyte terminal differentiation, over this extended two-week timescale. The canonical ERK-MAPK signaling cascade (Raf-1, MEK-1/2 and ERK-1/2) has been implicated in controlling diverse cellular behaviors, including proliferation and differentiation. While the molecular interactions involved in signal transduction through this cascade have been well characterized in cell culture experiments, our understanding of how this sequence of events unfolds to determine cell fate within a homeostatic tissue environment has not been fully characterized. We measured the abundance of total and phosphorylated ERK-MAPK signaling proteins within interfollicular keratinocytes in transverse cross-sections of human epidermis using immunofluorescence microscopy. To investigate these data we developed a mathematical model of the signaling cascade using a normalized-Hill differential equation formalism. These data show coordinated variation in the abundance of phosphorylated ERK-MAPK components across the epidermis. Statistical analysis of these data shows that associations between phosphorylated ERK-MAPK components which correspond to canonical molecular interactions are dependent upon spatial position within the epidermis. The model demonstrates that the spatial profile of activation for ERK-MAPK signaling components across the epidermis may be maintained in a cell-autonomous fashion by an underlying spatial gradient in calcium signaling. Our data demonstrate an extended phospho-protein profile of ERK-MAPK signaling cascade components across the epidermis in situ, and statistical associations in these data

  20. Effect of single and repeated heat stress on chemical signals of heat shock response cascade in the rat's heart.

    Science.gov (United States)

    Ilievska, Gordana; Dinevska-Kjovkarovska, Suzana; Miova, Biljana

    2017-11-24

    Exposure to sublethal heat stress activates a complex cascade of signaling events, such as activators (NO), signal molecules (PKCε), and mediators (HSP70 and COX-2), leading to implementation of heat preconditioning, an adaptive mechanism which makes the organism more tolerant to additional stress. We investigated the time frame in which these chemical signals are triggered after heat stress (41 ± 0.5°С/45 min), single or repeated (24 or 72 h after the first one) in heart tissue of male Wistar rats. The animals were allowed to recover 24, 48 or 72 h at room temperature. Single heat stress caused a significant increase of the concentration of HSP70, NO, and PKC level and decrease of COX-2 level 24 h after the heat stress, which in the next course of recovery gradually normalized. The second heat stress, 24 h after the first one, caused a significant reduction of the HSP70 levels, concentration of NO and PKCɛ, and significant increase of COX-2 concentration. The second exposure, 72 h after the first heat stress, caused more expressive changes of HSP70 and NO in the 24 h-recovery groups. The level of PKCɛ was not significantly changed, but there was significantly increased COX-2 concentration during recovery. Serum activity of AST, ALT, and CK was reduced after single exposure and increased after repeated exposure to heat stress, in both time intervals. In conclusion, a longer period of recovery (72 h) between two consecutive sessions of heat stress is necessary to achieve more expressive changes in mediators (HSP70) and triggers (NO) of heat preconditioning.

  1. Dynamic optical arbitrary waveform shaping based on cascaded optical modulators of single FBG.

    Science.gov (United States)

    Chen, Jingyuan; Li, Peili

    2015-08-10

    A dynamic optical arbitrary waveform generation (O-AWG) with amplitude and phase independently controlled in optical modulators of single fiber Bragg Grating (FBG) has been proposed. This novel scheme consists of several optical modulators. In the optical modulator (O-MOD), a uniform FBG is used to filter spectral component of the input signal. The amplitude is controlled by fiber stretcher (FS) in Mach-Zehnder interference (MZI) structure through interference of two MZI arms. The phase is manipulated via the second FS in the optical modulator. This scheme is investigated by simulation. Consequently, optical pulse trains with different waveforms as well as pulse trains with nonuniform pulse intensity, pulse spacing and pulse width within each period are obtained through FSs adjustment to alter the phase shifts of signal in each O-MOD.

  2. TaMAPK4 Acts as a Positive Regulator in Defense of Wheat Stripe-Rust Infection

    OpenAIRE

    Bing Wang; Na Song; Qiong Zhang; Ning Wang; Zhensheng Kang

    2018-01-01

    Highly conserved mitogen-activated protein kinase (MAPK) cascades regulate numerous plant processes, including hormonal responses, stress, and innate immunity. In this research, TaMAPK4 was predicted to be a target of tae-miR164. We verified the binding and suppression of TaMAPK4 by co-expression in Nicotiana benthamiana. Moreover, we found TaMAPK4 was localized in the cytoplasm and nucleus using transient expression analyses. TaMAPK4 transcripts increased following salicylic acid (SA) treatm...

  3. Generation of 3.5 W of diffraction-limited green light from SHG of a single tapered diode laser in a cascade of nonlinear crystals

    DEFF Research Database (Denmark)

    Hansen, Anders Kragh; Jensen, Ole Bjarlin; Sumpf, Bernd

    2014-01-01

    frequency conversion of infrared tapered diode lasers. Here, we describe the generation of 3.5 W of diffraction-limited green light from SHG of a single tapered diode laser, itself yielding 10 W at 1063 nm. This SHG is performed in single pass through a cascade of two PPMgO:LN crystals with re...... power of 3.5 W corresponds to a power enhancement greater than 2 compared to SHG in each of the crystals individually and is the highest visible output power generated by frequency conversion of a single diode laser. Such laser sources provide the necessary pump power for biophotonics applications...

  4. Genome-Wide Identification and Analysis of MAPK and MAPKK Gene Families in Bread Wheat (Triticum aestivum L.

    Directory of Open Access Journals (Sweden)

    Haoshuang Zhan

    2017-10-01

    Full Text Available The mitogen-activated protein kinase (MAPK cascade is a universal signal transduction module that plays a vital role in regulating growth and development, as well as environmental stress responses in plants. Wheat is one of the most important crops worldwide. Although the MAPK kinase kinase (MAP3K family in wheat has been investigated, the MAPK and MAPK kinase (MAP2K gene families remain unknown at present. Here, 54 MAPK and 18 MAPKK genes were identified in wheat using recent genomic information. Phylogenetic analysis of Triticum aestivum L. MAPKs and MAPKKs (TaMAPKs and TaMAPKKs together with homologous genes from other species classified them into four groups, and the clustering was consistent with the genomic exon/intron structures. Conserved motif analysis found that MAPK proteins contained a typical TXY phosphorylation site and MAPKK proteins contained an S/T-X5-S/T motif. RNA-seq data mapping analysis showed that MAPK and MAPKK genes in group IV had tissue-specific expression profiles, whereas each group I member showed relatively high expression in all organs. Expression patterns of TaMAPK and TaMAPKK genes under stress conditions were also investigated and stress-responsive candidates were identified. Co-expression network analysis identified 11 TaMAPK genes and 6 TaMAPKK genes involved in the interaction network pathway. Overall, this study provided useful information for evolutionary and functional surveys of MAPK and MAPKK gene families in wheat and beyond.

  5. Cascaded automatic target recognition (Cascaded ATR)

    Science.gov (United States)

    Walls, Bradley

    2010-04-01

    The global war on terror has plunged US and coalition forces into a battle space requiring the continuous adaptation of tactics and technologies to cope with an elusive enemy. As a result, technologies that enhance the intelligence, surveillance, and reconnaissance (ISR) mission making the warfighter more effective are experiencing increased interest. In this paper we show how a new generation of smart cameras built around foveated sensing makes possible a powerful ISR technique termed Cascaded ATR. Foveated sensing is an innovative optical concept in which a single aperture captures two distinct fields of view. In Cascaded ATR, foveated sensing is used to provide a coarse resolution, persistent surveillance, wide field of view (WFOV) detector to accomplish detection level perception. At the same time, within the foveated sensor, these detection locations are passed as a cue to a steerable, high fidelity, narrow field of view (NFOV) detector to perform recognition level perception. Two new ISR mission scenarios, utilizing Cascaded ATR, are proposed.

  6. Arrestin orchestrates crosstalk between G protein-coupled receptors to modulate the spatiotemporal activation of ERK MAPK.

    Science.gov (United States)

    Cervantes, David; Crosby, Catherine; Xiang, Yang

    2010-01-08

    G protein-coupled receptors (GPCRs) respond to diversified extracellular stimuli to modulate cellular function. Despite extensive studies investigating the regulation of single GPCR signaling cascades, the effects of concomitant GPCR activation on downstream signaling and cellular function remain unclear. We aimed to characterize the cellular mechanism by which GPCR crosstalk regulates mitogen-activated protein kinase (MAPK) activation. Adrenergic receptors on cardiac fibroblasts were manipulated to examine the role of arrestin in the spatiotemporal regulation of extracellular signal-regulated kinase (ERK)1/2 MAPK signaling. We show a general mechanism in which arrestin activation by one GPCR is capable of regulating signaling originating from another GPCR. Activation of Gq coupled-receptor signaling leads to prolonged ERK1/2 MAPK phosphorylation, nuclear accumulation, and cellular proliferation. Interestingly, coactivation of these receptors with the beta-adrenergic receptors induced transient ERK signaling localized within the cytosol, which attenuated cell proliferation. Further studies revealed that recruitment of arrestin3 to the beta2-adrenergic receptor orchestrates the sequestration of Gq-coupled receptor-induced ERK to the cytosol through direct binding of ERK to arrestin. This is the first evidence showing that arrestin3 acts as a coordinator to integrate signals from multiple GPCRs. Our studies not only provide a novel mechanism explaining the integration of mitogenic signaling elicited by different GPCRs, but also underscore the critical role of signaling crosstalk among GPCRs in vivo.

  7. Watt-level widely tunable single-mode emission by injection-locking of a multimode Fabry-Perot quantum cascade laser

    Science.gov (United States)

    Chevalier, Paul; Piccardo, Marco; Anand, Sajant; Mejia, Enrique A.; Wang, Yongrui; Mansuripur, Tobias S.; Xie, Feng; Lascola, Kevin; Belyanin, Alexey; Capasso, Federico

    2018-02-01

    Free-running Fabry-Perot lasers normally operate in a single-mode regime until the pumping current is increased beyond the single-mode instability threshold, above which they evolve into a multimode state. As a result of this instability, the single-mode operation of these lasers is typically constrained to few percents of their output power range, this being an undesired limitation in spectroscopy applications. In order to expand the span of single-mode operation, we use an optical injection seed generated by an external-cavity single-mode laser source to force the Fabry-Perot quantum cascade laser into a single-mode state in the high current range, where it would otherwise operate in a multimode regime. Utilizing this approach, we achieve single-mode emission at room temperature with a tuning range of 36 cm-1 and stable continuous-wave output power exceeding 1 W at 4.5 μm. Far-field measurements show that a single transverse mode is emitted up to the highest optical power, indicating that the beam properties of the seeded Fabry-Perot laser remain unchanged as compared to free-running operation.

  8. Wavelet cascades

    Science.gov (United States)

    Giesemann, Jens; Greiner, Martin; Lipa, Peter

    1997-02-01

    The generators of binary multiplicative cascade models with a non-overlapping branching structure are given by the Haar wavelets. We construct specific generalizations of these models for which any given wavelet represents the generators of the local cascade branchings. Such “wavelet cascades”, for which we calculate spatial correlation functions, have spatially overlapping branches and are therefore useful for modeling recombination effects in hierarchical branching processes.

  9. The Drosophila Arf GEF Steppke controls MAPK activation in EGFR signaling.

    Science.gov (United States)

    Hahn, Ines; Fuss, Bernhard; Peters, Annika; Werner, Tamara; Sieberg, Andrea; Gosejacob, Dominic; Hoch, Michael

    2013-06-01

    Guanine nucleotide exchange factors (GEFs) of the cytohesin protein family are regulators of GDP/GTP exchange for members of the ADP ribosylation factor (Arf) of small GTPases. They have been identified as modulators of various receptor tyrosine kinase signaling pathways including the insulin, the vascular epidermal growth factor (VEGF) and the epidermal growth factor (EGF) pathways. These pathways control many cellular functions, including cell proliferation and differentiation, and their misregulation is often associated with cancerogenesis. In vivo studies on cytohesins using genetic loss of function alleles are lacking, however, since knockout mouse models are not available yet. We have recently identified mutants for the single cytohesin Steppke (Step) in Drosophila and we could demonstrate an essential role of Step in the insulin signaling cascade. In the present study, we provide in vivo evidence for a role of Step in EGFR signaling during wing and eye development. By analyzing step mutants, transgenic RNA interference (RNAi) and overexpression lines for tissue specific as well as clonal analysis, we found that Step acts downstream of the EGFR and is required for the activation of mitogen-activated protein kinase (MAPK) and the induction of EGFR target genes. We further demonstrate that step transcription is induced by EGFR signaling whereas it is negatively regulated by insulin signaling. Furthermore, genetic studies and biochemical analysis show that Step interacts with the Connector Enhancer of KSR (CNK). We propose that Step may be part of a larger signaling scaffold coordinating receptor tyrosine kinase-dependent MAPK activation.

  10. 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.

  11. Stable single-mode distributed feedback quantum cascade lasers at λ ∼ 4.25 μm with low power consumption

    Science.gov (United States)

    Jia, Zhiwei; Wang, Lijun; Zhang, Jinchuan; Liu, Fengqi; Zhuo, Ning; Zhai, Shenqiang; Liu, Junqi; Wang, Zhanguo

    2016-10-01

    Short-wavelength (4.25 μm) distributed-feedback quantum cascade laser operating in continuous wave (cw) mode at room temperature with low power consumption was presented. Stable single-mode operation with a side-mode-suppression-ratio above 25 dB was maintained for the whole measured current and temperature range by enlarging gain difference and strong grating coupling. Because of the strong coupling, very low threshold current and power consumption were achieved. For a device of 9-μm-wide and 2-mm-long, the cw threshold current and power consumption at 293 K were as low as 126 mA and 1.45 W, respectively. All results above were from the device without using buried heterostructure geometry.

  12. 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

  13. 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.

  14. Effect of zeatin on the infection process and expression of MAPK-4 ...

    African Journals Online (AJOL)

    HP

    2013-04-24

    Apr 24, 2013 ... signaling modules in eukaryotic cells. In this paper, an attempt was made to study the .... A number of studies have been identified where MAPK4 is component of pathogen signalling cascade .... were subjected to RNA isolation using RNEasy plant minikit. (Himedia Laboratories Private Limited India) as per ...

  15. High temperature, single mode, long infrared (λ = 17.8 μm) InAs-based quantum cascade lasers

    Energy Technology Data Exchange (ETDEWEB)

    Chastanet, D.; Bousseksou, A., E-mail: adel.bousseksou@u-psud.fr; Julien, F. H.; Colombelli, R., E-mail: raffaele.colombelli@u-psud.fr [Institut d' Electronique Fondamentale, Univ. Paris Sud, UMR 8622 CNRS, 91405 Orsay (France); Lollia, G.; Bahriz, M.; Baranov, A. N.; Teissier, R., E-mail: roland.teissier@ies.univ-montp2.fr [Institut d' Electronique du Sud, Univ. Montpellier 2, UMR 5214 CNRS, 34095 Montpellier (France)

    2014-09-15

    We demonstrate quantum cascade lasers in the InAs/AlSb material system which operate up to 333 K (in pulsed regime) at λ = 17.8 μm. They employ metal-metal optical waveguides and the threshold current density is 1.6 kA/cm{sup 2} at 78 K. We also report distributed-feedback devices obtained using the same laser material via a 1{sup st}-order Bragg grating inscribed in the sole top metallic contact. Spectral single mode operation with more than 20 dB side mode suppression ratio is achieved at a temperature of 300 K. Large wavelength tuning rates, of the order of 1.5 nm/K, are demonstrated. A wavelength coverage of 0.38 μm is achieved in single-mode regime over a temperature range of 255 K.

  16. Single-Electrical-Port Control of Cascaded Doubly-Fed Induction Machine for EV/HEV Applications

    DEFF Research Database (Denmark)

    Han, Peng; Cheng, Ming; Chen, Zhe

    2017-01-01

    as a master/slave architecture, that is, the power winding is supplied with a constant-voltage constant-frequency inverter, termed as the master inverter, in an open-loop way, while the control winding is fed by a closed-loop field-oriented-controlled (FOC) variable-voltage variable-frequency inverter, termed...... as slave inverter. With this configuration, the control emphasis is placed on the slave inverter, yielding reduced control complexity and cost, and the inaccuracy of flux estimation in conventional FOC for singly-fed induction machines is avoided at very low or even zero speed. It is found that the doubly...

  17. Wavefront measurement of single-mode quantum cascade laser beam for seed application in laser-produced plasma extreme ultraviolet system.

    Science.gov (United States)

    Nowak, Krzysztof M; Ohta, Takeshi; Suganuma, Takashi; Yokotsuka, Toshio; Fujimoto, Junichi; Mizoguchi, Hakaru

    2012-12-01

    Quantum cascade laser (QCL) is a very attractive seed source for a multikilowatt pulsed CO2 lasers applied for driving extreme ultraviolet emitting plasmas. In this Letter, we investigate output beam properties of a QCL designed to address P18 and P20 lines of 10.6 micron band of CO2 molecule. In particular, output beam quality and stability are investigated for the first time. A well-defined linear polarization and a single-mode operation enabled a use of phase retrieval method for full description of QCL output beam. A direct, multi-image numerical phase retrieval technique was developed and successfully applied to the measured intensity patterns of a QCL beam. Very good agreement between the measured and reconstructed beam profiles was observed at distances ranging from QCL aperture to infinity, proving a good understanding of the beam propagation. The results also confirm a high spatial coherence and high stability of the beam parameters, the features expected from an excellent seed source.

  18. Genome-Wide Survey and Expression Profile Analysis of the Mitogen-Activated Protein Kinase (MAPK) Gene Family in Brassica rapa.

    Science.gov (United States)

    Lu, Kun; Guo, Wenjin; Lu, Junxing; Yu, Hao; Qu, Cunmin; Tang, Zhanglin; Li, Jiana; Chai, Yourong; Liang, Ying

    2015-01-01

    Mitogen-activated protein kinase (MAPK) cascades are fundamental signal transduction modules in plants, controlling cell division, development, hormone signaling, and biotic and abiotic stress responses. Although MAPKs have been investigated in several plant species, a comprehensive analysis of the MAPK gene family has hitherto not been performed in Brassica rapa. In this study, we identified 32 MAPKs in the B. rapa genome by conducting BLASTP and syntenic block analyses, and screening for the essential signature motif (TDY or TEY) of plant MAPK proteins. Of the 32 BraMAPK genes retrieved from the Brassica Database, 13 exhibited exon splicing errors, excessive splicing of the 5' sequence, excessive retention of the 5' sequence, and sequencing errors of the 3' end. Phylogenetic trees of the 32 corrected MAPKs from B. rapa and of MAPKs from other plants generated by the neighbor-joining and maximum likelihood methods suggested that BraMAPKs could be divided into four groups (groups A, B, C, and D). Gene number expansion was observed for BraMAPK genes in groups A and D, which may have been caused by the tandem duplication and genome triplication of the ancestral genome of the Brassica progenitor. Except for five members of the BraMAPK10 subfamily, the identified BraMAPKs were expressed in most of the tissues examined, including callus, root, stem, leaf, flower, and silique. Quantitative real-time PCR demonstrated that at least six and five BraMAPKs were induced or repressed by various abiotic stresses and hormone treatments, respectively, suggesting their potential roles in the abiotic stress response and various hormone signal transduction pathways in B. rapa. This study provides valuable insight into the putative physiological and biochemical functions of MAPK genes in B. rapa.

  19. Deoxynivalenol induced mouse skin cell proliferation and inflammation via MAPK pathway

    International Nuclear Information System (INIS)

    Mishra, Sakshi; Tripathi, Anurag; Chaudhari, Bhushan P.; Dwivedi, Premendra D.; Pandey, Haushila P.; Das, Mukul

    2014-01-01

    Several toxicological manifestations of deoxynivalenol (DON), a mycotoxin, are well documented; however, dermal toxicity is not yet explored. The effect of topical application of DON to mice was studied using markers of skin proliferation, inflammation and tumor promotion. Single topical application of DON (84–672 nmol/mouse) significantly enhanced dermal hyperplasia and skin edema. DON (336 and 672 nmol) caused significant enhancement in [ 3 H]-thymidine uptake in DNA along with increased myeloperoxidase and ornithine decarboxylase activities, suggesting tissue inflammation and cell proliferation. Furthermore, DON (168 nmol) caused enhanced expression of RAS, and phosphorylation of PI3K/Akt, ERK, JNK and p38 MAPKs. DON exposure also showed activation of transcription factors, c-fos, c-jun and NF-κB along with phosphorylation of IkBα. Enhanced phosphorylation of NF-κB by DON caused over expression of target proteins, COX-2, cyclin D1 and iNOS in skin. Though a single topical application of DMBA followed by twice weekly application of DON (84 and 168 nmol) showed no tumorigenesis after 24 weeks, however, histopathological studies suggested hyperplasia of the epidermis and hypertrophy of hair follicles. Interestingly, intestine was also found to be affected as enlarged Peyer's patches were observed, suggesting inflammatory effects which were supported by elevation of inflammatory cytokines after 24 weeks of topical application of DON. These results suggest that DON induced cell proliferation in mouse skin is through the activation of MAPK signaling pathway involving transcription factors NFκB and AP-1, further leading to transcriptional activation of downstream target proteins c-fos, c-jun, cyclin D1, iNOS and COX-2 which might be responsible for its inflammatory potential. - Highlights: • Topical application of DON enhanced epidermal inflammation and cell proliferation. • DON follows PI3K/Akt/MAPK signaling cascade, with activation of AP-1 and NF

  20. Deoxynivalenol induced mouse skin cell proliferation and inflammation via MAPK pathway

    Energy Technology Data Exchange (ETDEWEB)

    Mishra, Sakshi [Food Drug and Chemical Toxicology, CSIR-Indian Institute of Toxicology Research (CSIR-IITR), P.O. Box No. 80, Mahatma Gandhi Marg, Lucknow 226 001 (India); Department of Biochemistry, Banaras Hindu University (BHU), Varanasi (India); Tripathi, Anurag [Food Drug and Chemical Toxicology, CSIR-Indian Institute of Toxicology Research (CSIR-IITR), P.O. Box No. 80, Mahatma Gandhi Marg, Lucknow 226 001 (India); Chaudhari, Bhushan P. [Pathology Laboratory, CSIR-Indian Institute of Toxicology Research (CSIR-IITR), Mahatma Gandhi Marg, PO Box 80, Lucknow 226001, Uttar Pradesh (India); Dwivedi, Premendra D. [Food Drug and Chemical Toxicology, CSIR-Indian Institute of Toxicology Research (CSIR-IITR), P.O. Box No. 80, Mahatma Gandhi Marg, Lucknow 226 001 (India); Pandey, Haushila P. [Department of Biochemistry, Banaras Hindu University (BHU), Varanasi (India); Das, Mukul, E-mail: mditrc@rediffmail.com [Food Drug and Chemical Toxicology, CSIR-Indian Institute of Toxicology Research (CSIR-IITR), P.O. Box No. 80, Mahatma Gandhi Marg, Lucknow 226 001 (India)

    2014-09-01

    Several toxicological manifestations of deoxynivalenol (DON), a mycotoxin, are well documented; however, dermal toxicity is not yet explored. The effect of topical application of DON to mice was studied using markers of skin proliferation, inflammation and tumor promotion. Single topical application of DON (84–672 nmol/mouse) significantly enhanced dermal hyperplasia and skin edema. DON (336 and 672 nmol) caused significant enhancement in [{sup 3}H]-thymidine uptake in DNA along with increased myeloperoxidase and ornithine decarboxylase activities, suggesting tissue inflammation and cell proliferation. Furthermore, DON (168 nmol) caused enhanced expression of RAS, and phosphorylation of PI3K/Akt, ERK, JNK and p38 MAPKs. DON exposure also showed activation of transcription factors, c-fos, c-jun and NF-κB along with phosphorylation of IkBα. Enhanced phosphorylation of NF-κB by DON caused over expression of target proteins, COX-2, cyclin D1 and iNOS in skin. Though a single topical application of DMBA followed by twice weekly application of DON (84 and 168 nmol) showed no tumorigenesis after 24 weeks, however, histopathological studies suggested hyperplasia of the epidermis and hypertrophy of hair follicles. Interestingly, intestine was also found to be affected as enlarged Peyer's patches were observed, suggesting inflammatory effects which were supported by elevation of inflammatory cytokines after 24 weeks of topical application of DON. These results suggest that DON induced cell proliferation in mouse skin is through the activation of MAPK signaling pathway involving transcription factors NFκB and AP-1, further leading to transcriptional activation of downstream target proteins c-fos, c-jun, cyclin D1, iNOS and COX-2 which might be responsible for its inflammatory potential. - Highlights: • Topical application of DON enhanced epidermal inflammation and cell proliferation. • DON follows PI3K/Akt/MAPK signaling cascade, with activation of AP-1 and NF

  1. Control of the cell cycle progression by the MAPK Hog1

    Directory of Open Access Journals (Sweden)

    Josep Clotet

    2013-02-01

    Full Text Available Eukaryotic cells coordinate various intracellular activities in response to environmental stresses, activating an adaptive program to maximize the probability of survival and proliferation. Cells transduce diverse cellular stimuli by multiple mitogen-activated protein kinase (MAPK cascades. MAPK are key signal transduction kinases required to respond to stress. A prototypical member of the MAPK family is the yeast high osmolarity glycerol (Hog1. Activation of Hog1 results in the generation of a set of adaptive responses that leads to the modulation of several aspects of cell physiology that are essential for cell survival, such as gene expression, translation, and morphogenesis. This review focuses on the control of cell cycle progression by Hog1 which is critical for cell survival in response to stress conditions.

  2. Detection of MAPK3/6 Phosphorylation During Hypersensitive Response (HR)-Associated Programmed Cell Death in Plants.

    Science.gov (United States)

    Wu, Qingyu; Jackson, David

    2018-01-01

    Programmed cell death (PCD) is an essential component of development, biotic and abiotic responses. Hypersensitive response (HR)-associated cell death activated under pathogen attack is one of the most dramatic manifestations of PCD in plants. Signal transduction through mitogen-activated protein kinase (MAPK) cascades, a very conserved signaling pathway across eukaryotes, is a core mediator for HR-associated PCD. Therefore, monitoring MAPK activation enables the mechanisms underlying HR-associated PCD to be elucidated. Here, we describe the use of a phosphorylation-specific MAPK3/6 antibody to monitor the activation of MAPK3/6 during HR-associated PCD. The technique may be adapted for use in other types of PCD.

  3. Genome-wide genetic analyses highlight mitogen-activated protein kinase (MAPK) signaling in the pathogenesis of endometriosis.

    Science.gov (United States)

    Uimari, Outi; Rahmioglu, Nilufer; Nyholt, Dale R; Vincent, Katy; Missmer, Stacey A; Becker, Christian; Morris, Andrew P; Montgomery, Grant W; Zondervan, Krina T

    2017-04-01

    Do genome-wide association study (GWAS) data for endometriosis provide insight into novel biological pathways associated with its pathogenesis? GWAS analysis uncovered multiple pathways that are statistically enriched for genetic association signals, analysis of Stage A disease highlighted a novel variant in MAP3K4, while top pathways significantly associated with all endometriosis and Stage A disease included several mitogen-activated protein kinase (MAPK)-related pathways. Endometriosis is a complex disease with an estimated heritability of 50%. To date, GWAS revealed 10 genomic regions associated with endometriosis, explaining endometriosis cases and 7060 controls of European ancestry with genotype data imputed up to 1000 Genomes Phase three reference panel. GWAS was performed for all endometriosis cases and for Stage A (revised American Fertility Society (rAFS) I/II, n = 1686) and B (rAFS III/IV, n = 1364) cases separately. The identified significant pathways were compared with pathways previously investigated in the literature through candidate association studies. The most comprehensive biological pathway databases, MSigDB (including BioCarta, KEGG, PID, SA, SIG, ST and GO) and PANTHER were utilized to test for enrichment of genetic variants associated with endometriosis. Statistical enrichment analysis was performed using the MAGENTA (Meta-Analysis Gene-set Enrichment of variaNT Associations) software. The first genome-wide association analysis for Stage A endometriosis revealed a novel locus, rs144240142 (P = 6.45 × 10-8, OR = 1.71, 95% CI = 1.23-2.37), an intronic single-nucleotide polymorphism (SNP) within MAP3K4. This SNP was not associated with Stage B disease (P = 0.086). MAP3K4 was also shown to be differentially expressed in eutopic endometrium between Stage A endometriosis cases and controls (P = 3.8 × 10-4), but not with Stage B disease (P = 0.26). A total of 14 pathways enriched with genetic endometriosis associations were identified (false

  4. 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.)

  5. The Drosophila secreted protein Argos regulates signal transduction in the Ras/MAPK pathway.

    Science.gov (United States)

    Sawamoto, K; Okabe, M; Tanimura, T; Mikoshiba, K; Nishida, Y; Okano, H

    1996-08-25

    The Drosophila argos gene encodes a secreted protein with an EGF motif which acts as an inhibitor of cellular differentiation in multiple developmental processes. To investigate the cellular pathways regulated by Argos, we screened for mutations which could modify the phenotype caused by overexpression of argos. We show that the effects of argos overexpression on the eye and wing vein development are suppressed by gain-of-function mutations of the MAPKK/D-MEK gene (Dsor1/D-mek) and the MAPK/ERK-A gene (rolled) and were enhanced by loss-of-function mutations of Star. Loss-of-function mutations in components of the Ras/MAPK signaling cascade act as dominant suppressors of the phenotype caused by the argos null mutations. A loss-of-function argos mutation enhanced the overproduction of R7 neurons caused by gain-of-function alleles of Son of sevenless and Dsor1. Conversely, overexpression of argos inhibited formation of the extra R7 cells that was caused by high-level MAPK/ERK-A activity. A phenotype of the sev; argos double mutants revealed that sev is epistatic to argos. These results provide evidence that Argos negatively regulates signal transduction events in the Ras/MAPK cascade.

  6. Tunable All-Optical Wavelength Conversion Based on Cascaded SHG/DFG in a Ti:PPLN Waveguide Using a Single CW Control Laser

    DEFF Research Database (Denmark)

    Hu, Hao; Nouroozi, Rahman; Wang, Wenrui

    2012-01-01

    Tunable all-optical wavelength conversion (AOWC) of a 40-Gb/s RZ-OOK data signal based on cascaded second-harmonic generation (SHG) and difference-frequency generation (DFG) in a Ti:PPLN waveguide is demonstrated. Error-free performances with negligible power penalty are achieved for the wavelength...

  7. A simple method for potential flow simulation of cascades

    Indian Academy of Sciences (India)

    Keywords. Cascade; turbo-machinery; aerodynamics; conformal mapping. Abstract. A simple method using a combination of conformal mapping and vortex panel method to simulate potential flow in cascades is presented. The cascade is first transformed to a single body using a conformal mapping, and the potential flow ...

  8. Identification and characterization of an ABA-activated MAP kinase cascade in Arabidopsis thaliana

    KAUST Repository

    Danquah, Agyemang

    2015-04-01

    Summary Abscisic acid (ABA) is a major phytohormone involved in important stress-related and developmental plant processes. Recent phosphoproteomic analyses revealed a large set of ABA-triggered phosphoproteins as putative mitogen-activated protein kinase (MAPK) targets, although the evidence for MAPKs involved in ABA signalling is still scarce. Here, we identified and reconstituted in vivo a complete ABA-activated MAPK cascade, composed of the MAP3Ks MAP3K17/18, the MAP2K MKK3 and the four C group MAPKs MPK1/2/7/14. In planta, we show that ABA activation of MPK7 is blocked in mkk3-1 and map3k17mapk3k18 plants. Coherently, both mutants exhibit hypersensitivity to ABA and altered expression of a set of ABA-dependent genes. A genetic analysis further reveals that this MAPK cascade is activated by the PYR/PYL/RCAR-SnRK2-PP2C ABA core signalling module through protein synthesis of the MAP3Ks, unveiling an atypical mechanism for MAPK activation in eukaryotes. Our work provides evidence for a role of an ABA-induced MAPK pathway in plant stress signalling. Significance Statement We report in this article the identification of a complete MAPK module, composed of MAP3K17/18, MKK3 and MPK1/2/7/14, which is activated by ABA through the ABA core signalling complex. We showed that the activation of this module requires the MAP3K protein synthesis which occurs after hours of stress treatment, suggesting that the pathway is involved in a delayed wave of cellular responses to ABA and drought. © 2015 The Authors The Plant Journal © 2015 John Wiley & Sons Ltd.

  9. A functional screen reveals an extensive layer of transcriptional and splicing control underlying RAS/MAPK signaling in Drosophila.

    Directory of Open Access Journals (Sweden)

    Dariel Ashton-Beaucage

    2014-03-01

    Full Text Available The small GTPase RAS is among the most prevalent oncogenes. The evolutionarily conserved RAF-MEK-MAPK module that lies downstream of RAS is one of the main conduits through which RAS transmits proliferative signals in normal and cancer cells. Genetic and biochemical studies conducted over the last two decades uncovered a small set of factors regulating RAS/MAPK signaling. Interestingly, most of these were found to control RAF activation, thus suggesting a central regulatory role for this event. Whether additional factors are required at this level or further downstream remains an open question. To obtain a comprehensive view of the elements functionally linked to the RAS/MAPK cascade, we used a quantitative assay in Drosophila S2 cells to conduct a genome-wide RNAi screen for factors impacting RAS-mediated MAPK activation. The screen led to the identification of 101 validated hits, including most of the previously known factors associated to this pathway. Epistasis experiments were then carried out on individual candidates to determine their position relative to core pathway components. While this revealed several new factors acting at different steps along the pathway--including a new protein complex modulating RAF activation--we found that most hits unexpectedly work downstream of MEK and specifically influence MAPK expression. These hits mainly consist of constitutive splicing factors and thereby suggest that splicing plays a specific role in establishing MAPK levels. We further characterized two representative members of this group and surprisingly found that they act by regulating mapk alternative splicing. This study provides an unprecedented assessment of the factors modulating RAS/MAPK signaling in Drosophila. In addition, it suggests that pathway output does not solely rely on classical signaling events, such as those controlling RAF activation, but also on the regulation of MAPK levels. Finally, it indicates that core splicing

  10. 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)

  11. Interband cascade lasers

    Science.gov (United States)

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

    2015-04-01

    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.

  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. Nicotiana benthamiana MAPK-WRKY pathway confers resistance to a necrotrophic pathogen Botrytis cinerea.

    Science.gov (United States)

    Adachi, Hiroaki; Ishihama, Nobuaki; Nakano, Takaaki; Yoshioka, Miki; Yoshioka, Hirofumi

    2016-06-02

    MEK2-SIPK/WIPK cascade, a Nicotiana benthamiana mitogen-activated protein kinase (MAPK) cascade, is an essential signaling pathway for plant immunity and involved in hypersensitive response (HR) accompanied by cell death. WRKY transcription factors as substrates of SIPK and WIPK have been isolated and implicated in HR cell death. Here, we show virus-induced gene silencing of WRKY genes compromised constitutively active MEK2-triggered cell death in N. benthamiana leaves. In general, HR cell death enhances susceptibility to necrotrophic pathogens such as Botrytis cinerea. However, the WRKY gene silencing elevated susceptibility to B. cinerea. These findings suggest that downstream WRKYs of MEK2-SIPK/WIPK cascade are required for cell death-dependent and -independent immunities in N. benthamiana.

  14. Spatial focalization of pheromone/MAPK signaling triggers commitment to cell–cell fusion

    Science.gov (United States)

    Merlini, Laura

    2016-01-01

    Cell fusion is universal in eukaryotes for fertilization and development, but what signals this process is unknown. Here, we show in Schizosaccharomyces pombe that fusion does not require a dedicated signal but is triggered by spatial focalization of the same pheromone–GPCR (G-protein-coupled receptor)–MAPK signaling cascade that drives earlier mating events. Autocrine cells expressing the receptor for their own pheromone trigger fusion attempts independently of cell–cell contact by concentrating pheromone release at the fusion focus, a dynamic actin aster underlying the secretion of cell wall hydrolases. Pheromone receptor and MAPK cascade are similarly enriched at the fusion focus, concomitant with fusion commitment in wild-type mating pairs. This focalization promotes cell fusion by immobilizing the fusion focus, thus driving local cell wall dissolution. We propose that fusion commitment is imposed by a local increase in MAPK concentration at the fusion focus, driven by a positive feedback between fusion focus formation and focalization of pheromone release and perception. PMID:27798845

  15. Deep cascade learning

    OpenAIRE

    Marquez, Enrique, Salvador; Hare, Jonathon; Niranjan, Mahesan

    2018-01-01

    In this paper, we propose a novel approach for efficient training of deep neural networks in a bottom-up fashion using a layered structure. Our algorithm, which we refer to as Deep Cascade Learning, is motivated by the Cascade Correlation approach of Fahlman who introduced it in the context of perceptrons. We demonstrate our algorithm on networks of convolutional layers, though its applicability is more general. Such training of deep networks in a cascade, directly circumvents the well-know...

  16. Cholinergic Transactivation of the EGFR in HaCaT Keratinocytes Stimulates a Flotillin-1 Dependent MAPK-Mediated Transcriptional Response

    Directory of Open Access Journals (Sweden)

    Sina Kühne

    2015-03-01

    Full Text Available Acetylcholine and its receptors regulate numerous cellular processes in keratinocytes and other non-neuronal cells. Muscarinic acetylcholine receptors are capable of transactivating the epidermal growth factor receptor (EGFR and, downstream thereof, the mitogen-activated protein kinase (MAPK cascade, which in turn regulates transcription of genes involved in cell proliferation and migration. We here show that cholinergic stimulation of human HaCaT keratinocytes results in increased transcription of matrix metalloproteinase MMP-3 as well as several ligands of the epidermal growth factor family. Since both metalloproteinases and the said ligands are involved in the transactivation of the EGFR, this transcriptional upregulation may provide a positive feed-forward loop for EGFR/MAPK activation. We here also show that the cholinergic EGFR and MAPK activation and the upregulation of MMP-3 and EGF-like ligands are dependent on the expression of flotillin-1 which we have previously shown to be a regulator of MAPK signaling.

  17. Anopheles stephensi p38 MAPK signaling regulates innate immunity and bioenergetics during Plasmodium falciparum infection.

    Science.gov (United States)

    Wang, Bo; Pakpour, Nazzy; Napoli, Eleonora; Drexler, Anna; Glennon, Elizabeth K K; Surachetpong, Win; Cheung, Kong; Aguirre, Alejandro; Klyver, John M; Lewis, Edwin E; Eigenheer, Richard; Phinney, Brett S; Giulivi, Cecilia; Luckhart, Shirley

    2015-08-19

    Fruit flies and mammals protect themselves against infection by mounting immune and metabolic responses that must be balanced against the metabolic needs of the pathogens. In this context, p38 mitogen-activated protein kinase (MAPK)-dependent signaling is critical to regulating both innate immunity and metabolism during infection. Accordingly, we asked to what extent the Asian malaria mosquito Anopheles stephensi utilizes p38 MAPK signaling during infection with the human malaria parasite Plasmodium falciparum. A. stephensi p38 MAPK (AsP38 MAPK) was identified and patterns of signaling in vitro and in vivo (midgut) were analyzed using phospho-specific antibodies and small molecule inhibitors. Functional effects of AsP38 MAPK inhibition were assessed using P. falciparum infection, quantitative real-time PCR, assays for reactive oxygen species and survivorship under oxidative stress, proteomics, and biochemical analyses. The genome of A. stephensi encodes a single p38 MAPK that is activated in the midgut in response to parasite infection. Inhibition of AsP38 MAPK signaling significantly reduced P. falciparum sporogonic development. This phenotype was associated with AsP38 MAPK regulation of mitochondrial physiology and stress responses in the midgut epithelium, a tissue critical for parasite development. Specifically, inhibition of AsP38 MAPK resulted in reduction in mosquito protein synthesis machinery, a shift in glucose metabolism, reduced mitochondrial metabolism, enhanced production of mitochondrial reactive oxygen species, induction of an array of anti-parasite effector genes, and decreased resistance to oxidative stress-mediated damage. Hence, P. falciparum-induced activation of AsP38 MAPK in the midgut facilitates parasite infection through a combination of reduced anti-parasite immune defenses and enhanced host protein synthesis and bioenergetics to minimize the impact of infection on the host and to maximize parasite survival, and ultimately, transmission

  18. Skb5, an SH3 adaptor protein, regulates Pmk1 MAPK signaling by controlling the intracellular localization of the MAPKKK Mkh1.

    Science.gov (United States)

    Kanda, Yuki; Satoh, Ryosuke; Matsumoto, Saki; Ikeda, Chisato; Inutsuka, Natsumi; Hagihara, Kanako; Matzno, Sumio; Tsujimoto, Sho; Kita, Ayako; Sugiura, Reiko

    2016-08-15

    The mitogen-activated protein kinase (MAPK) cascade is a highly conserved signaling module composed of MAPK kinase kinases (MAPKKKs), MAPK kinases (MAPKK) and MAPKs. The MAPKKK Mkh1 is an initiating kinase in Pmk1 MAPK signaling, which regulates cell integrity in fission yeast (Schizosaccharomyces pombe). Our genetic screen for regulators of Pmk1 signaling identified Shk1 kinase binding protein 5 (Skb5), an SH3-domain-containing adaptor protein. Here, we show that Skb5 serves as an inhibitor of Pmk1 MAPK signaling activation by downregulating Mkh1 localization to cell tips through its interaction with the SH3 domain. Consistent with this, the Mkh1(3PA) mutant protein, with impaired Skb5 binding, remained in the cell tips, even when Skb5 was overproduced. Intriguingly, Skb5 needs Mkh1 to localize to the growing ends as Mkh1 deletion and disruption of Mkh1 binding impairs Skb5 localization. Deletion of Pck2, an upstream activator of Mkh1, impaired the cell tip localization of Mkh1 and Skb5 as well as the Mkh1-Skb5 interaction. Interestingly, both Pck2 and Mkh1 localized to the cell tips at the G1/S phase, which coincided with Pmk1 MAPK activation. Taken together, Mkh1 localization to cell tips is important for transmitting upstream signaling to Pmk1, and Skb5 spatially regulates this process. © 2016. Published by The Company of Biologists Ltd.

  19. HER2+ Cancer Cell Dependence on PI3K vs. MAPK Signaling Axes Is Determined by Expression of EGFR, ERBB3 and CDKN1B.

    Directory of Open Access Journals (Sweden)

    Daniel C Kirouac

    2016-04-01

    Full Text Available Understanding the molecular pathways by which oncogenes drive cancerous cell growth, and how dependence on such pathways varies between tumors could be highly valuable for the design of anti-cancer treatment strategies. In this work we study how dependence upon the canonical PI3K and MAPK cascades varies across HER2+ cancers, and define biomarkers predictive of pathway dependencies. A panel of 18 HER2+ (ERBB2-amplified cell lines representing a variety of indications was used to characterize the functional and molecular diversity within this oncogene-defined cancer. PI3K and MAPK-pathway dependencies were quantified by measuring in vitro cell growth responses to combinations of AKT (MK2206 and MEK (GSK1120212; trametinib inhibitors, in the presence and absence of the ERBB3 ligand heregulin (NRG1. A combination of three protein measurements comprising the receptors EGFR, ERBB3 (HER3, and the cyclin-dependent kinase inhibitor p27 (CDKN1B was found to accurately predict dependence on PI3K/AKT vs. MAPK/ERK signaling axes. Notably, this multivariate classifier outperformed the more intuitive and clinically employed metrics, such as expression of phospho-AKT and phospho-ERK, and PI3K pathway mutations (PIK3CA, PTEN, and PIK3R1. In both cell lines and primary patient samples, we observed consistent expression patterns of these biomarkers varies by cancer indication, such that ERBB3 and CDKN1B expression are relatively high in breast tumors while EGFR expression is relatively high in other indications. The predictability of the three protein biomarkers for differentiating PI3K/AKT vs. MAPK dependence in HER2+ cancers was confirmed using external datasets (Project Achilles and GDSC, again out-performing clinically used genetic markers. Measurement of this minimal set of three protein biomarkers could thus inform treatment, and predict mechanisms of drug resistance in HER2+ cancers. More generally, our results show a single oncogenic transformation can

  20. 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

  1. Extending the wavelength range of single-emitter diode lasers for medical and sensing applications: 12xx-nm quantum dots, 2000-nm wells, > 5000-nm cascade lasers

    Science.gov (United States)

    Crump, Paul; Patterson, Steve; Elim, Sandrio; Zhang, Shiguo; Bougher, Mike; Patterson, Jason; Das, Suhit; Dong, Weimin; Grimshaw, Mike; Wang, Jun; Wise, Damian; DeFranza, Mark; Bell, Jake; Farmer, Jason; DeVito, Mark; Martinsen, Rob; Kovsh, Alexey; Toor, Fatima; Gmachl, Claire F.

    2007-02-01

    Diode lasers supply high power densities at wavelengths from 635-nm to 2000-nm, with different applications enabled by providing this power at different wavelengths. As the range of available wavelengths broadens, many novel medical and atmospheric applications are enabled. Traditional quantum well lasers provide high performance in the range 635- nm to 1100-nm range for GaAs-based devices and 1280-nm to 2000-nm for InP, leaving a notable gap in the 1100 to 1280-nm range. There are many important medical and sensing applications in this range and quantum dots produced using Stranski-Krastanow self-organized MBE growth on GaAs substrates provide an alternative high performance solution. We present results confirming broad area quantum dot lasers can deliver high optical powers of 16-W per emitter and high power conversion efficiency of 35% in this wavelength range. In addition, there are growing applications for high power sources in wavelengths > 1500-nm. We present a brief review of our current performance status in this wavelength range, both with conventional quantum wells in the 1500-nm to 2500-nm range and MOCVD grown quantum cascade lasers for wavelengths > 4000-nm. At each wavelength, we review the designs that deliver this performance, prospects for increased performance and the potential for further broadening the availability of novel wavelengths for high power applications.

  2. Collision cascades in Zr3Fe

    International Nuclear Information System (INIS)

    Howe, L.M.; Rainville, M.H.; Phillips, D.; Plattner, H.H.; Bonnett, J.D.

    1994-11-01

    The objective of the present research is to understand better the processes that control irradiation-induced phase changes and solute segregation in zirconium alloys. Previously, it was found that 0.5 - 1.5 MeV 40 Ar ion irradiations resulted in the conversion of the crystalline Zr 3 Fe orthorhombic phase to the amorphous state. In the present investigation, 15 - 1500 keV 209 Bi ion irradiations (10 11 - 10 14 ions cm -2 ) were performed to provide more detailed information on collision cascades in Zr 3 Fe. Consecutive ion bombardments with 1.5, 1.0 and 0.5 MeV 209 Bi ions showed that complete amorphization occurred from 35 K to at least 600 K. Low fluence (10 11 - 101 12 ions cm -2 ) irradiations performed at 35 - 40 K with 15 - 350 keV 209 Bi ions provided information on the nature of the damage produced within individual damage cascades. At high values for the average deposited-energy density θυ in the cascade, which correspond to low-energy heavy-ion implants (e.g., 15-30 keV in Zr 3 Fe), the visible damage produced in a cascade consisted of single damaged region. With decreasing values of θυ (i.e., increasing ion implant energies), there was an increasing tendency for multiple damaged regions (subcascades) to form within a main cascade. The visible damaged regions appeared to be amorphous. It was also found that as the Bi ion energy increased (θυ decreased), the fraction of the theoretical collision-cascade volume that was occupied by the visible damage regions within a cascade decreased rapidly. The crystalline-to-amorphous transformation appeared to be the result of direct amorphization within the collision cascades and a critical defect concentration being reached in the cascade overlap regions, thus producing additional amorphous regions. (author). 30 refs., 2 tabs., 3 figs

  3. MAPK phosphatase AP2C3 induces ectopic proliferation of epidermal cells leading to stomata development in Arabidopsis.

    Directory of Open Access Journals (Sweden)

    Julija Umbrasaite

    2010-12-01

    Full Text Available In plant post-embryonic epidermis mitogen-activated protein kinase (MAPK signaling promotes differentiation of pavement cells and inhibits initiation of stomata. Stomata are cells specialized to modulate gas exchange and water loss. Arabidopsis MAPKs MPK3 and MPK6 are at the core of the signaling cascade; however, it is not well understood how the activity of these pleiotropic MAPKs is constrained spatially so that pavement cell differentiation is promoted only outside the stomata lineage. Here we identified a PP2C-type phosphatase termed AP2C3 (Arabidopsis protein phosphatase 2C that is expressed distinctively during stomata development as well as interacts and inactivates MPK3, MPK4 and MPK6. AP2C3 co-localizes with MAPKs within the nucleus and this localization depends on its N-terminal extension. We show that other closely related phosphatases AP2C2 and AP2C4 are also MAPK phosphatases acting on MPK6, but have a distinct expression pattern from AP2C3. In accordance with this, only AP2C3 ectopic expression is able to stimulate cell proliferation leading to excess stomata development. This function of AP2C3 relies on the domains required for MAPK docking and intracellular localization. Concomitantly, the constitutive and inducible AP2C3 expression deregulates E2F-RB pathway, promotes the abundance and activity of CDKA, as well as changes of CDKB1;1 forms. We suggest that AP2C3 downregulates the MAPK signaling activity to help maintain the balance between differentiation of stomata and pavement cells.

  4. Cascade orificial resistive device

    Science.gov (United States)

    Bitsakis, Nicholas; Cassidy, James

    1994-07-01

    A cascade orificial resistive device for throttling fluid flow which minimizes acoustic noise and internal vibrations is described herein. The device has a hollow body defining a fluid passageway, a plurality of perforated plates mounted within the passageway, a fixed end ring adjacent one end of the perforated plates, and a threadable end ring adjacent an opposite end of the perforated plates to place the plates in compression. Each of the perforated plates is a single piece molded plate having an integral outer ring and an integrally formed center keying mechanism as well as a plurality of orifices. The keying mechanism formed on each plate is designed so that adjacent ones of the plates have their orifices misaligned. In this manner, a pressure drop across each plate is created and the fluid flow through the device is throttled. The device of the present invention has utility in a number of onboard marine vessel systems wherein reduced acoustic noise and internal vibrations are particularly desirable.

  5. MAPK activation by radio waves.

    Science.gov (United States)

    Arthur, J Simon C

    2007-08-01

    In this issue of the Biochemical Journal, Freidman et al. report the findings of a study to look at the potential of mobile phones to activate intracellular signalling cascades. They found that radio waves corresponding to the frequency commonly used by mobile phones are able to activate ERK1/2 (extracellular-signal-regulated kinases 1 and 2). This effect was observed even at intensities lower than those emitted by mobile phones that are unable to cause any measurable heating effects. This study provides evidence that radio waves induce ERK1/2 activation downstream of the EGF (epidermal growth factor) receptor, which is in turn activated by the release of reactive oxygen species.

  6. Biocatalysis: Chiral cascades

    Science.gov (United States)

    Wang, Jian-Bo; Reetz, Manfred T.

    2015-12-01

    Racemic or enantiomerically pure alcohols can be converted with high yield into enantiopure chiral amines in a one-pot redox-neutral cascade process by the clever combination of an alcohol dehydrogenase and an appropriate amine dehydrogenase.

  7. 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.

  8. Activation of MAPK Is Necessary for Long-Term Memory Consolidation Following Food-Reward Conditioning

    Science.gov (United States)

    Ribeiro, Maria J.; Schofield, Michael G.; Kemenes, Ildiko; O'Shea, Michael; Kemenes, Gyorgy; Benjamin, Paul R.

    2005-01-01

    Although an important role for the mitogen-activated protein kinase (MAPK) has been established for memory consolidation in a variety of learning paradigms, it is not known if this pathway is also involved in appetitive classical conditioning. We address this question by using a single-trial food-reward conditioning paradigm in the freshwater…

  9. 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.

  10. 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.

  11. Identification of putative MAPK kinases in Oryza minuta and O. sativa responsive to biotic stresses.

    Science.gov (United States)

    You, Min Kyoung; Oh, Seung-Ick; Ok, Sung Han; Cho, Sung Ki; Shin, Hyun Young; Jeung, Ji Ung; Shin, Jeong Sheop

    2007-02-28

    The mitogen-activated protein kinase (MAPK) signaling cascade is critical for regulating plant defense systems against various kinds of pathogen and environmental stresses. One component of this cascade, the MAP kinase kinases (MAPKK), has not yet been shown to be induced in plants following biotic attacks, such as those by insects and fungi. We describe here a gene coding for a blast (Magnaporthe grisea)- and insect (Nilaparvata lugens)-responsive putative MAPK kinase, OmMKK1 (Oryza minuta MAPKK 1), which was identified in a library of O. minuta expressed sequence tags (ESTs). Two copies of OmMKK1 are present in the O. minuta genome. They encode a predicted protein with molecular mass 39 kDa and pI of 6.2. Transcript patterns following imbibition of plant hormones such as methyl jasmonic acid (MeJA), ethephone, salicylic acid (SA) and abscisic acid (ABA), as well as exposure to methyl viologen (MV), revealed that the expression of OmMKK1 is related to defense response signaling pathways. A comparative analysis of OmMKK1 and its O. sativa ortholog OsMKK1 showed that both were induced by stress-related hormones and biotic stresses, but that the kinetics of their responses differed despite their high amino acid sequence identity (96%).

  12. Interaction of LRRK2 with kinase and GTPase signaling cascades

    Directory of Open Access Journals (Sweden)

    Joon Y Boon

    2014-07-01

    Full Text Available LRRK2 is a protein that interacts with a plethora of signaling molecules, but the complexity of LRRK2 function presents a challenge for understanding the role of LRRK2 in the pathophysiology of Parkinson’s disease. Studies of LRRK2 using over-expression in transgenic mice have been disappointing, however studies using invertebrate systems have yielded a much clearer picture, with clear effects of LRRK2 expression, knockdown or deletion in C. elegans and Drosophila on modulation of survival of dopaminergic neurons. Recent studies have begun to focus attention on particular signaling cascades that are a target of LRRK2 function. LRRK2 interacts with members of the MAPK pathway and might regulate the pathway action by acting as a scaffold that directs the location of MAPK pathway activity, without strongly affecting the amount of MAPK pathway activity. Binding to GTPases, GAPs and GEFs are another strong theme in LRRK2 biology, with LRRK2 binding to Rac1, cdc42, rab5, rab7L1, endoA, RGS2, ArfGAP1 and ArhGEF7. All of these molecules appear to feed into a function output for LRRK2 that modulates cytoskeletal outgrowth and vesicular dynamics, including autophagy. These functions likely impact modulation of α-synuclein aggregation and associated toxicity eliciting the disease processes that we term Parkinson’s disease.

  13. 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

  14. Mitogen-Activated Protein Kinase (MAPK) Pathway Regulates Branching by Remodeling Epithelial Cell Adhesion

    Science.gov (United States)

    Ihermann-Hella, Anneliis; Lume, Maria; Miinalainen, Ilkka J.; Pirttiniemi, Anniina; Gui, Yujuan; Peränen, Johan; Charron, Jean; Saarma, Mart; Costantini, Frank; Kuure, Satu

    2014-01-01

    Although the growth factor (GF) signaling guiding renal branching is well characterized, the intracellular cascades mediating GF functions are poorly understood. We studied mitogen-activated protein kinase (MAPK) pathway specifically in the branching epithelia of developing kidney by genetically abrogating the pathway activity in mice lacking simultaneously dual-specificity protein kinases Mek1 and Mek2. Our data show that MAPK pathway is heterogeneously activated in the subset of G1- and S-phase epithelial cells, and its tissue-specific deletion results in severe renal hypodysplasia. Consequently to the deletion of Mek1/2, the activation of ERK1/2 in the epithelium is lost and normal branching pattern in mutant kidneys is substituted with elongation-only phenotype, in which the epithelium is largely unable to form novel branches and complex three-dimensional patterns, but able to grow without primary defects in mitosis. Cellular characterization of double mutant epithelium showed increased E-cadherin at the cell surfaces with its particular accumulation at baso-lateral locations. This indicates changes in cellular adhesion, which were revealed by electron microscopic analysis demonstrating intercellular gaps and increased extracellular space in double mutant epithelium. When challenged to form monolayer cultures, the mutant epithelial cells were impaired in spreading and displayed strong focal adhesions in addition to spiky E-cadherin. Inhibition of MAPK activity reduced paxillin phosphorylation on serine 83 while remnants of phospho-paxillin, together with another focal adhesion (FA) protein vinculin, were augmented at cell surface contacts. We show that MAPK activity is required for branching morphogenesis, and propose that it promotes cell cycle progression and higher cellular motility through remodeling of cellular adhesions. PMID:24603431

  15. Mitogen-activated protein kinase (MAPK pathway regulates branching by remodeling epithelial cell adhesion.

    Directory of Open Access Journals (Sweden)

    Anneliis Ihermann-Hella

    2014-03-01

    Full Text Available Although the growth factor (GF signaling guiding renal branching is well characterized, the intracellular cascades mediating GF functions are poorly understood. We studied mitogen-activated protein kinase (MAPK pathway specifically in the branching epithelia of developing kidney by genetically abrogating the pathway activity in mice lacking simultaneously dual-specificity protein kinases Mek1 and Mek2. Our data show that MAPK pathway is heterogeneously activated in the subset of G1- and S-phase epithelial cells, and its tissue-specific deletion results in severe renal hypodysplasia. Consequently to the deletion of Mek1/2, the activation of ERK1/2 in the epithelium is lost and normal branching pattern in mutant kidneys is substituted with elongation-only phenotype, in which the epithelium is largely unable to form novel branches and complex three-dimensional patterns, but able to grow without primary defects in mitosis. Cellular characterization of double mutant epithelium showed increased E-cadherin at the cell surfaces with its particular accumulation at baso-lateral locations. This indicates changes in cellular adhesion, which were revealed by electron microscopic analysis demonstrating intercellular gaps and increased extracellular space in double mutant epithelium. When challenged to form monolayer cultures, the mutant epithelial cells were impaired in spreading and displayed strong focal adhesions in addition to spiky E-cadherin. Inhibition of MAPK activity reduced paxillin phosphorylation on serine 83 while remnants of phospho-paxillin, together with another focal adhesion (FA protein vinculin, were augmented at cell surface contacts. We show that MAPK activity is required for branching morphogenesis, and propose that it promotes cell cycle progression and higher cellular motility through remodeling of cellular adhesions.

  16. Integrative modelling of the influence of MAPK network on cancer cell fate decision.

    Directory of Open Access Journals (Sweden)

    Luca Grieco

    2013-10-01

    Full Text Available The Mitogen-Activated Protein Kinase (MAPK network consists of tightly interconnected signalling pathways involved in diverse cellular processes, such as cell cycle, survival, apoptosis and differentiation. Although several studies reported the involvement of these signalling cascades in cancer deregulations, the precise mechanisms underlying their influence on the balance between cell proliferation and cell death (cell fate decision in pathological circumstances remain elusive. Based on an extensive analysis of published data, we have built a comprehensive and generic reaction map for the MAPK signalling network, using CellDesigner software. In order to explore the MAPK responses to different stimuli and better understand their contributions to cell fate decision, we have considered the most crucial components and interactions and encoded them into a logical model, using the software GINsim. Our logical model analysis particularly focuses on urinary bladder cancer, where MAPK network deregulations have often been associated with specific phenotypes. To cope with the combinatorial explosion of the number of states, we have applied novel algorithms for model reduction and for the compression of state transition graphs, both implemented into the software GINsim. The results of systematic simulations for different signal combinations and network perturbations were found globally coherent with published data. In silico experiments further enabled us to delineate the roles of specific components, cross-talks and regulatory feedbacks in cell fate decision. Finally, tentative proliferative or anti-proliferative mechanisms can be connected with established bladder cancer deregulations, namely Epidermal Growth Factor Receptor (EGFR over-expression and Fibroblast Growth Factor Receptor 3 (FGFR3 activating mutations.

  17. The potential impact of membrane cascading on downstream processing of oligosaccharides

    NARCIS (Netherlands)

    Patil, N.V.; Janssen, A.E.M.; Boom, R.M.

    2014-01-01

    To assess the potential use of ideal nanofiltration cascades for the industrial fractionation of oligosac- charides, simulations of single, three and five stage NF cascades were carried out.Three and five stage ideal cascades show significant improvement in separation with diafiltration compared to

  18. Terahertz Quantum Cascade Laser Based 3D Imaging Project

    Data.gov (United States)

    National Aeronautics and Space Administration — LongWave Photonics proposes a terahertz quantum-cascade laser based swept-source optical coherence tomography (THz SS-OCT) system for single-sided, 3D,...

  19. Neuroprotective Effects of Bioactive Compounds and MAPK Pathway Modulation in “Ischemia”—Stressed PC12 Pheochromocytoma Cells

    Science.gov (United States)

    Lahiani, Adi; Brand-Yavin, Annette; Yavin, Ephraim

    2018-01-01

    This review surveys the efforts taken to investigate in vitro neuroprotective features of synthetic compounds and cell-released growth factors on PC12 clonal cell line temporarily deprived of oxygen and glucose followed by reoxygenation (OGD/R). These cells have been used previously to mimic some of the properties of in vivo brain ischemia-reperfusion-injury (IRI) and have been instrumental in identifying common mechanisms such as calcium overload, redox potential, lipid peroxidation and MAPKs modulation. In addition, they were useful for establishing the role of certain membrane penetrable cocktails of antioxidants as well as potential growth factors which may act in neuroprotection. Pharmacological mechanisms of neuroprotection addressing modulation of the MAPK cascade and increased redox potential by natural products, drugs and growth factors secreted by stem cells, in either undifferentiated or nerve growth factor-differentiated PC12 cells exposed to ischemic conditions are discussed for future prospects in neuroprotection studies. PMID:29419806

  20. Growth factor-dependent activation of the Ras-Raf-MEK-MAPK pathway in the human pancreatic carcinoma cell line PANC-1 carrying activated K-ras: implications for cell proliferation and cell migration.

    Science.gov (United States)

    Giehl, K; Skripczynski, B; Mansard, A; Menke, A; Gierschik, P

    2000-06-08

    Human ductal adenocarcinoma of the pancreas frequently carry activating point mutations in the K-ras protooncogene. We have analysed the activity of the Ras-Raf-MEK-MAPK cascade in the human pancreatic carcinoma cell line PANC-1 carrying an activating K-ras mutation. Serum-starved cells and cells grown in medium with serum did not show constitutively activated c-Raf, MEK-1, or p42 MAPK. Stimulation of cells with epidermal growth factor (EGF) or fetal calf serum (FCS) resulted in activation of N-Ras, but not K-Ras, as well as activation of c-Raf, MEK-1, and p42 MAPK. Preincubation of serum-starved cells with MEK-1 inhibitor PD98059 abolished EGF- and FCS-induced MAPK activation, identifying MEK as the upstream activator of MAPK. PANC-1 cells exhibited marked serum-dependence of anchorage-dependent and -independent cell growth as well as cell migration. EGF, alone or in combination with insulin and transferrin, did not induce cell proliferation of serum-starved PANC-1 cells, indicating that activation of MAPK alone was not sufficient to induce cell proliferation. FCS-induced DNA synthesis was inhibited by 40% by the MEK-1 inhibitor. On the other hand, treatment with either FCS or EGF alone resulted in marked, MEK-dependent increase of directed cell migration. Collectively, our results show that the activating K-ras mutation in PANC-1 cells does not result in constitutively increased Raf-MEK-MAPK signaling. Signal transduction via the Ras-Raf-MEK-MAPK cascade is maintained in these cells and is required for growth factor-induced cell proliferation and directed cell migration. Oncogene (2000).

  1. Stress activated protein kinases, JNKs and p38 MAPK, are differentially activated in ganglia and heart of land snail Helix lucorum (L.) during seasonal hibernation and arousal.

    Science.gov (United States)

    Michaelidis, Basile; Hatzikamari, Maria; Antoniou, Vassiliki; Anestis, Andreas; Lazou, Antigone

    2009-06-01

    The present work aimed to investigate the phosphorylation and hence activation of stress activated protein kinases, p38 MAPK and JNKs in the tissues of the snail Helix lucorum during seasonal hibernation. Snails were put in large glass boxes, which were placed outdoors so that they were exposed to natural conditions of light and temperature. Phosphorylation and hence activation of JNKs and p38 MAPK was determined in both heart and ganglia. Deep hibernation caused significant increases in the levels of the phosphorylated form of JNK and p38-MAPK in both heart and ganglia. Phosphorylation of JNK remained elevated in the ganglia or increased after a transient drop in the heart, when the snails were prepared for arousal. In addition, phosphorylation of p38-MAPK was further increased in the heart during this period. These data support the conclusion that MAPK signalling cascade might contribute in the physiological and biochemical remodelling in the tissues of land snails during hibernation and upon preparation for arousal.

  2. Quantum-engineered interband cascade photovoltaic devices

    Energy Technology Data Exchange (ETDEWEB)

    Razeghi, Manijeh; Tournié, Eric; Brown, Gail J.; Yang, Rui Q.; Lotfi, Hossein; Li, Lu; Hinkey, Robert T.; Ye, Hao; Klem, John F.; Lei, L.; Mishima, T. D.; Keay, J. C.; Santos, M. B.; Johnson, M. B.

    2013-12-18

    Quantum-engineered multiple stage photovoltaic (PV) devices are explored based on InAs/GaSb/AlSb interband cascade (IC) structures. These ICPV devices employ multiple discrete absorbers that are connected in series by widebandgap unipolar barriers using type-II heterostructure interfaces for facilitating carrier transport between cascade stages similar to IC lasers. The discrete architecture is beneficial for improving the collection efficiency and for spectral splitting by utilizing absorbers with different bandgaps. As such, the photo-voltages from each individual cascade stage in an ICPV device add together, creating a high overall open-circuit voltage, similar to conventional multi-junction tandem solar cells. Furthermore, photo-generated carriers can be collected with nearly 100% efficiency in each stage. This is because the carriers travel over only a single cascade stage, designed to be shorter than a typical diffusion length. The approach is of significant importance for operation at high temperatures where the diffusion length is reduced. Here, we will present our recent progress in the study of ICPV devices, which includes the demonstration of ICPV devices at room temperature and above with narrow bandgaps (e.g. 0.23 eV) and high open-circuit voltages. © (2013) COPYRIGHT Society of Photo-Optical Instrumentation Engineers (SPIE). Downloading of the abstract is permitted for personal use only.

  3. 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....

  4. 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...

  5. A new NFIA:RAF1 fusion activating the MAPK pathway in pilocytic astrocytoma

    DEFF Research Database (Denmark)

    Yde, Christina Westmose; Sehested, Astrid; Regué, Àngels Mateu

    2016-01-01

    are more rarely found. However, in some cases, no apparent cancer driver events can be identified. Here, we describe a novel fusion between the transcription factor nuclear factor 1A (NFIA) and Raf-1 proto-oncogene (RAF1) in a 5-year old boy with PA. The novel fusion was identified as part......Pilocytic astrocytoma (PA) is one of the most common brain cancers among children and activation of the Mitogen-Activated Protein Kinase (MAPK) pathway is considered the hallmark. In the majority of cases, oncogenic BRAF fusions or BRAF V600E mutations are observed, while RAF1 or NF1 alterations...... of a comprehensive genomic tumor profiling. We show that the NFIA:RAF1 fusion results in constitutive Raf1 kinase activity, leading to activation of downstream MEK1/2 cascade and increased proliferation of cancer cells. The NFIA:RAF1 fusion displayed distinct subcellular localization towards the plasma membrane...

  6. p38 mitogen-activated protein kinase (p38MAPK) upregulates catalase levels in response to low dose H2O2 treatment through enhancement of mRNA stability.

    Science.gov (United States)

    Sen, Prosenjit; Chakraborty, Prabir Kumar; Raha, Sanghamitra

    2005-08-15

    V79 fibroblasts were repetitively stressed through multiple exposures to a low dose (30 microM) H2O2 in culture for 4 weeks. Catalase activity, protein levels and mRNA levels increased markedly (5-6-fold) during this time and these augmentations were inhibited by the simultaneous presence of SB203580, an inhibitor of p38 mitogen-activated protein kinase (p38MAPK). p38MAPK became dually phosphorylated and ATF-2, a p38MAPK substrate also became increasingly phosphorylated over the repetitive stress period. Short interfering RNA that induced effective silencing of p38MAPK, was used to silence p38MAPK in V79 fibroblasts. Silencing of p38MAPK drastically hindered the elevation in catalase (protein and mRNA) levels observed after a single low dose (50 microM) of H2O. The rise in catalase mRNA levels induced by low concentration (single and multiple dose) H2O2 treatment was established to be unconnected with transcriptional upregulation but was brought forth primarily by an enhancement in catalase mRNA stability through the action of p38MAPK. Therefore, our data strongly indicate that activation of p38MAPK is a key controlling step in the upregulation of catalase levels by low dose H2O2 treatment.

  7. p38 MAPK mediated in compressive stress-induced chondrogenesis of rat bone marrow MSCs in 3D alginate scaffolds.

    Science.gov (United States)

    Li, Juan; Zhao, Zhihe; Yang, Jingyuan; Liu, Jun; Wang, Jun; Li, Xiaoyu; Liu, Yurong

    2009-12-01

    Mesenchymal stem cells (MSCs) are well known to have the capability to form bone and cartilage, and chondrogenesis derived from MSCs is reported to be affected by mechanical stimuli. This research was aimed to study the effects of cyclic compressive stress on the chondrogenic differentiation of rat bone marrow-derived MSCs (BMSCs) which were encapsulated in alginate scaffolds and cultured with or without chondrogenic medium, and to investigate the role of p38 MAPK phospho-relay cascade in this process. The results show that the gene expression of chondrocyte-specific markers of Col2alpha1, aggrecan, Sox9, Runx2, and Ihh was upregulated by dynamic compressive stress introduced at the 8th day of chondrogenic differentiation in vitro. The p38 MAPK was activated by chondrogenic cytokines in a slow and lagged way, but activated by cyclic compressive stimulation in a rapid and transient manner. And inhibition of p38 activity with SB203580 suppressed gene expression of chondrocyte-specific genes stimulated by chondrogenic medium and (or) cyclic compressive stress. These findings suggest that p38 MAPK signal acts as an essential mediator in the mechano-biochemical transduction and subsequent transcriptional regulation in the process of chondrogenesis.

  8. Blockage of NOX2/MAPK/NF-κB Pathway Protects Photoreceptors against Glucose Deprivation-Induced Cell Death

    Directory of Open Access Journals (Sweden)

    Bin Fan

    2017-01-01

    Full Text Available Acute energy failure is one of the critical factors contributing to the pathogenic mechanisms of retinal ischemia. Our previous study demonstrated that glucose deprivation can lead to a caspase-dependent cell death of photoreceptors. The aim of this study was to decipher the upstream signal pathway in glucose deprivation- (GD- induced cell death. We mimicked acute energy failure by using glucose deprivation in photoreceptor cells (661W cells. GD-induced oxidative stress was evaluated by measuring ROS with the DCFH-DA assay and HO-1 expression by Western blot analysis. The activation of NOX2/MAPK/NF-κB signal was assessed by Western blot and immunohistochemical assays. The roles of these signals in GD-induced cell death were measured by using their specific inhibitors. Inhibition of Rac-1 and NOX2 suppressed GD-induced oxidative stress and protected photoreceptors against GD-induced cell death. NOX2 was an upstream signal in the caspase-dependent cell death cascade, yet the downstream MAPK pathways were activated and blocking MAPK signals rescued 661W cells from GD-induced death. In addition, GD caused the activation of NF-κB signal and inhibiting NF-κB significantly protected 661W cells. These observations may provide insights for treating retinal ischemic diseases and protecting retinal neurons from ischemia-induced cell death.

  9. Bounded Target Cascading in Hierarchical Design Optimization

    Directory of Open Access Journals (Sweden)

    Xiaoling Zhang

    2014-06-01

    Full Text Available For large scale systems, as a hierarchical multilevel decomposed design optimization method, analytical target cascading coordinates the inconsistency between the assigned targets and response in each level by a weighted-sum formulation. To avoid the problems associated with the weighting coefficients, single objective functions in the hierarchical design optimization are formulated by a bounded target cascading method in this paper. In the BTC method, a single objective optimization problem is formulated in the system level, and two kinds of coordination constraints are added: one is bound constraint for the design points based on the response from each subsystem level and the other is linear equality constraint for the common variables based on their sensitivities with respect to each subsystem. In each subsystem level, the deviation with target for design point is minimized in the objective function, and the common variables are constrained by target bounds. Therefore, in the BTC method, the targets are coordinated based on the optimization iteration information in the hierarchical design problem and the performance of the subsystems, and BTC method will converge to the global optimum efficiently. Finally, comparisons of the results from BTC method and the weighted-sum analytical target cascading method are presented and discussed.

  10. Novel crosstalk between ERK MAPK and p38 MAPK leads to homocysteine-NMDA receptor mediated neuronal cell death

    Science.gov (United States)

    Poddar, Ranjana; Paul, Surojit

    2012-01-01

    Hyperhomocysteinemia is an independent risk factor for both acute and chronic neurological disorders but little is known about the underlying mechanisms by which elevated homocysteine can promote neuronal cell death. We recently established a role for NMDA receptor mediated activation of extracellular signal-regulated kinase-mitogen activated protein kinase (ERK-MAPK) in homocysteine-induced neuronal cell death. In the present study we examined the involvement of the stress-induced MAPK, p38 in homocysteine-induced neuronal cell death and further explored the relationship between the two MAPKs, ERK and p38, in triggering cell death. Homocysteine mediated NMDA receptor stimulation and subsequent Ca2+ influx led to a biphasic activation of p38 MAPK characterized by an initial rapid but transient activation followed by a delayed and more prolonged response. Selective inhibition of the delayed p38 MAPK activity was sufficient to attenuate homocysteine-induced neuronal cell death. Using pharmacological and RNAi approaches we further demonstrated that both the initial and delayed activation of p38 MAPK is downstream of, and dependent on activation of ERK MAPK. Our findings highlight a novel interplay between ERK and p38 MAPK in homocysteine-NMDA receptor induced neuronal cell death. PMID:23176034

  11. Cascaded impedance networks for NPC inverter

    DEFF Research Database (Denmark)

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

    2010-01-01

    Multilevel inverters are getting more and more attracted because they have better output waveform quality and lower semiconductor voltage stress. The Z-source NPC is a kind of single stage multilevel inverter which has the ability of voltage boost. But the boost capability is relatively low when...... 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...... would have a higher output voltage gain. It is anticipated that it would help the formed inverters find applications in photovoltaic and other renewable systems, where a high voltage gain is usually requested. Experimental testing has already been conducted and verifies the theory....

  12. Cascaded Multicell Trans-Z-Source Inverters

    DEFF Research Database (Denmark)

    Li, Ding; Chiang Loh, Poh; Zhu, Miao

    2013-01-01

    Inverters with high-output voltage gain usually face the problem of high-input current flowing through their components. The problem might further be exaggerated if the inverters use high-frequency magnetic devices like transformers or coupled inductors. Leakage inductances of these devices must...... strictly be small to prevent overvoltages caused by switching of their winding currents. To avoid these related problems, cascaded trans-Z-source inverters are proposed. They use multiple magnetic cells in an alternately cascading pattern rather than a single magnetic cell with large turns ratio....... Simulation and experimental results have shown that the multicell inverters can produce the same high-voltage gain, while keeping currents and voltages of the components low. The inverters can also step down their output voltages like a traditional voltage-source inverter without compromising waveform...

  13. 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.

  14. Activation of Erk and JNK MAPK pathways by acute swim stress in rat brain regions

    Directory of Open Access Journals (Sweden)

    Salvadore Christopher

    2004-09-01

    Full Text Available Abstract Background The mitogen-activated protein kinases (MAPKs have been shown to participate in a wide array of cellular functions. A role for some MAPKs (e.g., extracellular signal-regulated kinase, Erk1/2 has been documented in response to certain physiological stimuli, such as ischemia, visceral pain and electroconvulsive shock. We recently demonstrated that restraint stress activates the Erk MAPK pathway, but not c-Jun-N-terminal kinase/stress-activated protein kinase (JNK/SAPK or p38MAPK, in several rat brain regions. In the present study, we investigated the effects of a different stressor, acute forced swim stress, on the phosphorylation (P state of these MAPKs in the hippocampus, neocortex, prefrontal cortex, amygdala and striatum. In addition, effects on the phosphorylation state of the upstream activators of the MAPKs, their respective MAPK kinases (MAPKKs; P-MEK1/2, P-MKK4 and P-MKK3/6, were determined. Finally, because the Erk pathway can activate c-AMP response element (CRE binding (CREB protein, and swim stress has recently been reported to enhance CREB phosphorylation, changes in P-CREB were also examined. Results A single 15 min session of forced swimming increased P-Erk2 levels 2–3-fold in the neocortex, prefrontal cortex and striatum, but not in the hippocampus or amygdala. P-JNK levels (P-JNK1 and/or P-JNK2/3 were increased in all brain regions about 2–5-fold, whereas P-p38MAPK levels remained essentially unchanged. Surprisingly, levels of the phosphorylated MAPKKs, P-MEK1/2 and P-MKK4 (activators of the Erk and JNK pathways, respectively were increased in all five brain regions, and much more dramatically (P-MEK1/2, 4.5 to > 100-fold; P-MKK4, 12 to ~300-fold. Consistent with the lack of forced swim on phosphorylation of p38MAPK, there appeared to be no change in levels of its activator, P-MKK3/6. P-CREB was increased in all but cortical (prefrontal, neocortex areas. Conclusions Swim stress specifically and markedly

  15. Spirulina platensis prevents hyperglycemia in rats by modulating gluconeogenesis and apoptosis via modification of oxidative stress and MAPK-pathways.

    Science.gov (United States)

    Sadek, Kadry M; Lebda, Mohamed A; Nasr, Sherif M; Shoukry, Moustafa

    2017-08-01

    Spirulina platensis (SP) is a microalga with antioxidant, antidiabetic and anti-inflammatory properties. The present study explored the ability and potential mechanism(s) by which SP induced glucose lowering impact in diabetic rat model. Forty rats were allocated into four groups: control; streptozotocin (STZ)-induced diabetes (STZ, 45mg/kg b.w., intraperitoneally); SP (500mg/kg b.w., orally twice weekly for 2 months) and STZ-induced diabetes+SP group. In the STZ-induced diabetic rats, SP significantly decreased (P>0.05) serum glucose, glycated hemoglobin (HbA1c), malondialdehyde (MDA) levels and significantly increased (P>0.05) serum insulin, the activity of antioxidant enzymes and normalized their mRNA gene expression. Furthermore, SP attenuates STZ-induced upregulation of the gluconeogenic enzyme pyruvate carboxylase (PC), the pro-apoptotic Bax and caspase-3 (CASP-3), tumor necrosis factor alpha (TNF-α) gene expression. The Western blot results revealed that, SP induced downregulation of mitogen activated protein kinase pathway (MAPK) protein expression in hepatic tissues of diabetic rats. Additionally, SP reestablished the typical histological structure of the liver and pancreas of diabetic rats. Acute toxicity study further shows that SP is relatively safe. This study demonstrates that SP is rich in antioxidant compounds and has powerful glucose lowering effect through the normalization of increased hepatic PC gene expression. Interestingly, SP induced recovery of damaged hepatocytes and pancreatic β-cells via its anti-inflammatory, antioxidant and anti-apoptotic properties. The MAPK signaling cascade is a pivotal component of the proapoptotic signaling pathway induced by diabetes mellitus. MAPK activation may be dependent from ROS production, since SP which exhibited antioxidant activities did have a significant impact on MAPK activity. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  16. Isolation and Characterization of Activators of ERK/MAPK from Citrus Plants

    Directory of Open Access Journals (Sweden)

    Takashi Yoshida

    2012-02-01

    Full Text Available Extracellular signal-regulated kinases 1/2 (ERK1/2, components of the mitogen-activated protein kinase (MAPK signaling cascade, have been recently shown to be involved in synaptic plasticity and in the development of long-term memory in the central nervous system (CNS. We therefore examined the ability of Citrus compounds to activate ERK1/2 in cultured rat cortical neurons, whose activation might have a protective effect against neurodegenerative neurological disorders. Among the samples tested, extracts prepared from the peels of Citrus grandis (Kawachi bankan were found to have the greatest ability to activate ERK1/2. The active substances were isolated by chromatographic separation, and one of them was identified to be 3,5,6,7,8,3′,4′-heptamethoxyflavone (HMF. HMF significantly induced the phosphorylation of cAMP response element-binding protein (CREB, a downstream target of activated ERK1/2, which appears to be a critical step in the signaling cascade for the structural changes underlying the development of long-term potentiation (LTP. In addition, the administration of HMF into mice treated with NMDA receptor antagonist MK-801 restored the MK-801-induced deterioration of spatial learning performance in the Morris mater-maze task. Taken together, these results suggest that HMF is a neurotrophic agent for treating patients with memory disorders.

  17. 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

  18. Cascade Mountain Range in Oregon

    Science.gov (United States)

    Sherrod, David R.

    2016-01-01

    The Cascade mountain system extends from northern California to central British Columbia. In Oregon, it comprises the Cascade Range, which is 260 miles long and, at greatest breadth, 90 miles wide (fig. 1). Oregon’s Cascade Range covers roughly 17,000 square miles, or about 17 percent of the state, an area larger than each of the smallest nine of the fifty United States. The range is bounded on the east by U.S. Highways 97 and 197. On the west it reaches nearly to Interstate 5, forming the eastern margin of the Willamette Valley and, farther south, abutting the Coast Ranges. 

  19. 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.

  20. Spatially transformed fluorescence image data for ERK-MAPK and selected proteins within human epidermis.

    Science.gov (United States)

    Cursons, Joseph; Angel, Catherine E; Hurley, Daniel G; Print, Cristin G; Dunbar, P Rod; Jacobs, Marc D; Crampin, Edmund J

    2015-01-01

    Phosphoprotein signalling pathways have been intensively studied in vitro, yet their role in regulating tissue homeostasis is not fully understood. In the skin, interfollicular keratinocytes differentiate over approximately 2 weeks as they traverse the epidermis. The extracellular signal-regulated kinase (ERK) branch of the mitogen-activated protein kinase (MAPK) pathway has been implicated in this process. Therefore, we examined ERK-MAPK activity within human epidermal keratinocytes in situ. We used confocal microscopy and immunofluorescence labelling to measure the relative abundances of Raf-1, MEK1/2 and ERK1/2, and their phosphorylated (active) forms within three human skin samples. Additionally, we measured the abundance of selected proteins thought to modulate ERK-MAPK activity, including calmodulin, β1 integrin and stratifin (14-3-3σ); and of transcription factors known to act as effectors of ERK1/2, including the AP-1 components Jun-B, Fra2 and c-Fos. Imaging was performed with sufficient resolution to identify the plasma membrane, cytoplasm and nucleus as distinct domains within cells across the epidermis. The image field of view was also sufficiently large to capture the entire epidermis in cross-section, and thus the full range of keratinocyte differentiation in a single observation. Image processing methods were developed to quantify image data for mathematical and statistical analysis. Here, we provide raw image data and processed outputs. These data indicate coordinated changes in ERK-MAPK signalling activity throughout the depth of the epidermis, with changes in relative phosphorylation-mediated signalling activity occurring along the gradient of cellular differentiation. We believe these data provide unique information about intracellular signalling as they are obtained from a homeostatic human tissue, and they might be useful for investigating intercellular heterogeneity.

  1. 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.)

  2. Ultrarelativistic cascades and strangeness production

    Energy Technology Data Exchange (ETDEWEB)

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

    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.

  3. 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

  4. 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

  5. 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

  6. Correlation Structure of Wavelet Cascades

    Science.gov (United States)

    Greiner, Martin; Giesemann, Jens

    The following sections are included: * Introduction * Some Basics about Wavelets * Multiresolution analysis * Dilation equations * Wavelet transformation * Multiplicative Haar-Wavelet Cascade * Binary random multiplicative branching processes * n-point correlation densities * Haar-wavelet transformed correlation densities * Daubechies-wavelet transformed correlation densities * Multiplicative Daubechies-Wavelet Cascade * Random multiplicative branching processes on a D4-wavelet tree * n-point correlation densities * Wavelet transformed correlation densities * Scaling behavior of moments * Conclusion * REFERENCES

  7. Space partitioning strategies for indoor WLAN positioning with cascade-connected ANN structures.

    Science.gov (United States)

    Borenović, Miloš; Nešković, Aleksandar; Budimir, Djuradj

    2011-02-01

    Position information in indoor environments can be procured using diverse approaches. Due to the ubiquitous presence of WLAN networks, positioning techniques in these environments are the scope of intense research. This paper explores two strategies for space partitioning when utilizing cascade-connected Artificial Neural Networks (ANNs) structures for indoor WLAN positioning. A set of cascade-connected ANN structures with different space partitioning strategies are compared mutually and to the single ANN structure. The benefits of using cascade-connected ANNs structures are shown and discussed in terms of the size of the environment, number of subspaces and partitioning strategy. The optimal cascade-connected ANN structures with space partitioning show up to 50% decrease in median error and up to 12% decrease in the average error with respect to the single ANN model. Finally, the single ANN and the optimal cascade-connected ANN model are compared against other well-known positioning techniques.

  8. Interband Cascade Photovoltaic Cells

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Rui Q. [Univ. of Oklahoma, Norman, OK (United States); Santos, Michael B. [Univ. of Oklahoma, Norman, OK (United States); Johnson, Matthew B. [Univ. of Oklahoma, Norman, OK (United States)

    2014-09-24

    In this project, we are performing basic and applied research to systematically investigate our newly proposed interband cascade (IC) photovoltaic (PV) cells [1]. These cells follow from the great success of infrared IC lasers [2-3] that pioneered the use of quantum-engineered IC structures. This quantum-engineered approach will enable PV cells to efficiently convert infrared radiation from the sun or other heat source, to electricity. Such cells will have important applications for more efficient use of solar energy, waste-heat recovery, and power beaming in combination with mid-infrared lasers. The objectives of our investigations are to: achieve extensive understanding of the fundamental aspects of the proposed PV structures, develop the necessary knowledge for making such IC PV cells, and demonstrate prototype working PV cells. This research will focus on IC PV structures and their segments for utilizing infrared radiation with wavelengths from 2 to 5 μm, a range well suited for emission by heat sources (1,000-2,000 K) that are widely available from combustion systems. The long-term goal of this project is to push PV technology to longer wavelengths, allowing for relatively low-temperature thermal sources. Our investigations address material quality, electrical and optical properties, and their interplay for the different regions of an IC PV structure. The tasks involve: design, modeling and optimization of IC PV structures, molecular beam epitaxial growth of PV structures and relevant segments, material characterization, prototype device fabrication and testing. At the end of this program, we expect to generate new cutting-edge knowledge in the design and understanding of quantum-engineered semiconductor structures, and demonstrate the concepts for IC PV devices with high conversion efficiencies.

  9. CFD analysis of cascade effects in marine propellers with trailing edge modification

    DEFF Research Database (Denmark)

    Shin, Keun Woo; Andersen, Poul

    2015-01-01

    Propeller blades are different from a single hydrofoilin isolation due to cascade effects that blades mutually affect hydrodynamic characteristics of each other in proximity. Propeller design programs based lifting-line theory and blade element momentum theory take into account cascade effect by ...

  10. Multicomponent isotope separation in matched abundance ratio cascades composed of stages with large separation factors

    International Nuclear Information System (INIS)

    Von Halle, E.

    1987-06-01

    The concept of the matched abundance ratio cascade and the system of equations for performing multicomponent productivity calculations upon them has proven extremely useful for analyzing the behavior of gaseous diffusion plants in which the stage separation factors are very nearly equal to unity. Recent interest in the gas centrifuge process, in which the separation factor of a single centrifuge can be relatively large, makes desirable the extension of the theory of the matched abundance ratio cascade to cascades composed of stages with large separation factors. Equations permit the calculation of the productivity for simple cascades composed of stages with large separation factors. The concentration gradient of each of the isotopic species present can be calculated and the cascade description can be determined. An illustrative example dealing with the separation of the isotopes of tungsten in a cascade composed of gas centrifuges is included

  11. Cascading pressure reactor and method for solar-thermochemical reactions

    Science.gov (United States)

    Ermanoski, Ivan

    2017-11-14

    Reactors and methods for solar thermochemical reactions are disclosed. The reactors and methods include a cascade of reduction chambers at successively lower pressures that leads to over an order of magnitude pressure decrease compared to a single-chambered design. The resulting efficiency gains are substantial, and represent an important step toward practical and efficient solar fuel production on a large scale.

  12. Separation of an inulin mixture using cascaded nanofiltration

    NARCIS (Netherlands)

    Patil, N.V.; Feng, Xiaoxia; Sewalt, J.J.W.; Boom, R.M.; Janssen, A.E.M.

    2015-01-01

    This paper examines the use of a pilot-scale spiral wound nanofiltration cascade with regard to separation of mono- and disaccharides from a mixture of inulin of different polymer sizes. The choices of the membrane and operational conditions were based on single stage experiments. Two 3-stage

  13. Effect of field quantization on Rabi oscillation of equidistant cascade ...

    Indian Academy of Sciences (India)

    We have exactly solved a model of equidistant cascade four-level system interacting with a single-mode radiation field both semiclassically and quantum mechanically by exploiting its similarity with Jaynes-Cummings model. For the classical field, it is shown that the Rabi oscillation of the system initially in the first level ...

  14. Dynamics of cascade three-level system interacting with the ...

    Indian Academy of Sciences (India)

    Abstract. We study the exact solutions of the cascade three-level atom interacting with a single mode classical and quantized field with different initial conditions of the atom. For the semiclassical model, it is found that if the atom is initially in the middle level, the time-dependent populations of the upper and lower levels are ...

  15. Cross-talk between cAMP and MAPK pathways in HSD11B2 induction by hCG in placental trophoblasts.

    Directory of Open Access Journals (Sweden)

    Qun Shu

    Full Text Available Overexposure of the fetus to glucocorticoids in gestation is detrimental to fetal development. The passage of maternal glucocorticoids into the fetal circulation is governed by 11beta-Hydroxysteroid Dehydrogenase Type 2 (HSD11B2 in the placental syncytiotrophoblasts. Human chorionic gonadotropin (hCG plays an important role in maintaining placental HSD11B2 expression via activation of the cAMP pathway. In this study, we investigated the relationship between the activation of the cAMP pathway by hCG and subsequent phosphorylation of extracellular signal-regulated kinase1/2 (ERK1/2 or p38 mitogen-activated protein kinase (MAPK pathways in the regulation of placental HSD11B2 expression in human placental syncytiotrophoblasts. We found that treatment of the placental syncytiotrophoblasts with either hCG or dibutyl cAMP (dbcAMP could promote the phosphorylation of p38 and ERK1/2. Inhibition of p38 MAPK with SB203580 not only reduced the basal HSD11B2 mRNA and protein levels but also attenuated HSD11B2 levels induced by either hCG or dbcAMP. By contrast, inhibition of ERK1/2 with PD98059 increased the basal mRNA and protein levels of HSD11B2 and had no effect on HSD11B2 mRNA and protein levels induced by either hCG or dbcAMP. These data suggest that p38 MAPK is involved in both basal and hCG/cAMP-induced expression of HSD11B2, and ERK1/2 may play a role opposite to p38 MAPK at least in the basal expression of HSD11B2 in human placental syncytiotrophoblasts and that there is complicated cross-talk between hCG/cAMP and MAPK cascades in the regulation of placental HSD11B2 expression.

  16. 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.)

  17. 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.

  18. Functional analysis of the MAPK pathways in fungi.

    Science.gov (United States)

    Martínez-Soto, Domingo; Ruiz-Herrera, José

    The Mitogen-Activated Protein Kinase (MAPK) signaling pathways constitute one of the most important and evolutionarily conserved mechanisms for the perception of extracellular information in all the eukaryotic organisms. The MAPK pathways are involved in the transfer to the cell of the information perceived from extracellular stimuli, with the final outcome of activation of different transcription factors that regulate gene expression in response to them. In all species of fungi, the MAPK pathways have important roles in their physiology and development; e.g. cell cycle control, mating, morphogenesis, response to different stresses, resistance to UV radiation and to temperature changes, cell wall assembly and integrity, degradation of cellular organelles, virulence, cell-cell signaling, fungus-plant interaction, and response to damage-associated molecular patterns (DAMPs). Considering the importance of the phylogenetically conserved MAPK pathways in fungi, an updated review of the knowledge on them is discussed in this article. This information reveals their importance, their distribution in fungal species evolutionarily distant and with different lifestyles, their organization and function, and the interactions occurring between different MAPK pathways, and with other signaling pathways, for the regulation of the most complex cellular processes. Copyright © 2017 Asociación Española de Micología. Publicado por Elsevier España, S.L.U. All rights reserved.

  19. A novel p38α MAPK inhibitor suppresses brain proinflammatory cytokine up-regulation and attenuates synaptic dysfunction and behavioral deficits in an Alzheimer's disease mouse model

    Directory of Open Access Journals (Sweden)

    McNamara Laurie K

    2007-09-01

    Full Text Available Abstract Background An accumulating body of evidence is consistent with the hypothesis that excessive or prolonged increases in proinflammatory cytokine production by activated glia is a contributor to the progression of pathophysiology that is causally linked to synaptic dysfunction and hippocampal behavior deficits in neurodegenerative diseases such as Alzheimer's disease (AD. This raises the opportunity for the development of new classes of potentially disease-modifying therapeutics. A logical candidate CNS target is p38α MAPK, a well-established drug discovery molecular target for altering proinflammatory cytokine cascades in peripheral tissue disorders. Activated p38 MAPK is seen in human AD brain tissue and in AD-relevant animal models, and cell culture studies strongly implicate p38 MAPK in the increased production of proinflammatory cytokines by glia activated with human amyloid-beta (Aβ and other disease-relevant stressors. However, the vast majority of small molecule drugs do not have sufficient penetrance of the blood-brain barrier to allow their use as in vivo research tools or as therapeutics for neurodegenerative disorders. The goal of this study was to test the hypothesis that brain p38α MAPK is a potential in vivo target for orally bioavailable, small molecules capable of suppressing excessive cytokine production by activated glia back towards homeostasis, allowing an improvement in neurologic outcomes. Methods A novel synthetic small molecule based on a molecular scaffold used previously was designed, synthesized, and subjected to analyses to demonstrate its potential in vivo bioavailability, metabolic stability, safety and brain uptake. Testing for in vivo efficacy used an AD-relevant mouse model. Results A novel, CNS-penetrant, non-toxic, orally bioavailable, small molecule inhibitor of p38α MAPK (MW01-2-069A-SRM was developed. Oral administration of the compound at a low dose (2.5 mg/kg resulted in attenuation of

  20. 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.

  1. Vortex annihilation and inverse cascades in two dimensional superfluid turbulence

    Science.gov (United States)

    Lucas, Andrew; Chesler, Paul M.

    2015-03-01

    The dynamics of a dilute mixture of vortices and antivortices in a turbulent two-dimensional superfluid at finite temperature is well described by first order Hall-Vinen-Iordanskii equations, or dissipative point vortex dynamics. These equations are governed by a single dimensionless parameter: the ratio of the strength of drag forces to Magnus forces on vortices. When this parameter is small, we demonstrate using numerical simulations that the resulting superfluid enjoys an inverse energy cascade where small scale stirring leads to large scale vortex clustering. We argue analytically and numerically that the vortex annihilation rate in a laminar flow may be parametrically smaller than the rate in a turbulent flow with an inverse cascade. This suggests a new way to detect inverse cascades in experiments on two-dimensional superfluid turbulence using cold atomic gases, where traditional probes of turbulence such as the energy spectrum are not currently accessible.

  2. Topological selections for V0 (K0s, Lambda) and Cascade (Xi, Omega) reconstruction in ALICE

    CERN Multimedia

    Maire, Antonin

    2011-01-01

    The figures are illustrations of topological selections used by ALICE to reconstruct ϕ(1020), V0 particles (K°s and Λ, single-strange particles) and cascades (Ξ- and Ω-, charged multi-strange baryons).

  3. Efficiency criteria for optimization of separation cascades for uranium enrichment

    Directory of Open Access Journals (Sweden)

    Georgy Sulaberidze

    2018-02-01

    Full Text Available As it is known, uranium enrichment is carried out on industrial scale by means of multistage separation facilities, i.e., separation cascades in which gas centrifuges (GCs are connected in series and parallel. Design and construction of these facilities require significant investment. So, the problem of calculation and optimization of cascade working parameters is still relevant today. At the same time, in many cases, the minimum unit cost of a product is related to the cascade having the smallest possible number of separation elements/GCs. Also, in theoretical studies, it is often acceptable to apply as an efficiency criterion the minimum total flow to supply cascade stages instead of the abovementioned minimum unit cost or the number of separation elements. In this article, cascades with working parameter of a single GC changing from stage to stage are optimized by two of the abovementioned performance criteria and are compared. The results obtained allow us to make a conclusion about their differences.

  4. TEC and MAPK Kinase Signalling Pathways in T helper (TH) cell Development, TH2 Differentiation and Allergic Asthma

    Science.gov (United States)

    Kannan, Yashaswini; Wilson, Mark S.

    2013-01-01

    Significant advances in our understanding of the signalling events during T cell development and differentiation have been made in the past few decades. It is clear that ligation of the T cell receptor (TCR) triggers a series of proximal signalling cascades regulated by an array of protein kinases. These orchestrated and highly regulated series of events, with differential requirements of particular kinases, highlight the disparities between αβ+CD4+ T cells. Throughout this review we summarise both new and old studies, highlighting the role of Tec and MAPK in T cell development and differentiation with particular focus on T helper 2 (TH2) cells. Finally, as the allergy epidemic continues, we feature the role played by TH2 cells in the development of allergy and provide a brief update on promising kinase inhibitors that have been tested in vitro, in pre-clinical disease models in vivo and into clinical studies. PMID:24116341

  5. Sequence alignment reveals possible MAPK docking motifs on HIV proteins.

    Directory of Open Access Journals (Sweden)

    Perry Evans

    Full Text Available Over the course of HIV infection, virus replication is facilitated by the phosphorylation of HIV proteins by human ERK1 and ERK2 mitogen-activated protein kinases (MAPKs. MAPKs are known to phosphorylate their substrates by first binding with them at a docking site. Docking site interactions could be viable drug targets because the sequences guiding them are more specific than phosphorylation consensus sites. In this study we use multiple bioinformatics tools to discover candidate MAPK docking site motifs on HIV proteins known to be phosphorylated by MAPKs, and we discuss the possibility of targeting docking sites with drugs. Using sequence alignments of HIV proteins of different subtypes, we show that MAPK docking patterns previously described for human proteins appear on the HIV matrix, Tat, and Vif proteins in a strain dependent manner, but are absent from HIV Rev and appear on all HIV Nef strains. We revise the regular expressions of previously annotated MAPK docking patterns in order to provide a subtype independent motif that annotates all HIV proteins. One revision is based on a documented human variant of one of the substrate docking motifs, and the other reduces the number of required basic amino acids in the standard docking motifs from two to one. The proposed patterns are shown to be consistent with in silico docking between ERK1 and the HIV matrix protein. The motif usage on HIV proteins is sufficiently different from human proteins in amino acid sequence similarity to allow for HIV specific targeting using small-molecule drugs.

  6. 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

  7. Azobenzene-functionalized cascade molecules

    DEFF Research Database (Denmark)

    Archut, A.; Vogtle, F.; De Cola, L.

    1998-01-01

    Cascade molecules bearing up to 32 azobenzene groups in the periphery have been prepared from poly(propylene imine) dendrimers and N-hydroxysuccinimide esters. The dendritic azobenzene species show similar isomerization properties as the corresponding azobenzene monomers. The all-E azobenzene...

  8. CASCADE: Introducing AI into CBT.

    Science.gov (United States)

    Hendley, R. J.; Jurascheck, N.

    1992-01-01

    Discusses changes in training requirements of commerce and industry in the United Kingdom and describes a project, CASCADE, that was developed to investigate and implement the introduction of artificial intelligence (AI) techniques into computer-based training (CBT). An overview of pilot projects in higher education settings is provided. (eight…

  9. Cascade Support Vector Machines with Dimensionality Reduction

    Directory of Open Access Journals (Sweden)

    Oliver Kramer

    2015-01-01

    Full Text Available Cascade support vector machines have been introduced as extension of classic support vector machines that allow a fast training on large data sets. In this work, we combine cascade support vector machines with dimensionality reduction based preprocessing. The cascade principle allows fast learning based on the division of the training set into subsets and the union of cascade learning results based on support vectors in each cascade level. The combination with dimensionality reduction as preprocessing results in a significant speedup, often without loss of classifier accuracies, while considering the high-dimensional pendants of the low-dimensional support vectors in each new cascade level. We analyze and compare various instantiations of dimensionality reduction preprocessing and cascade SVMs with principal component analysis, locally linear embedding, and isometric mapping. The experimental analysis on various artificial and real-world benchmark problems includes various cascade specific parameters like intermediate training set sizes and dimensionalities.

  10. p38gamma and p38delta mitogen activated protein kinases (MAPKs, new stars in the MAPK galaxy

    Directory of Open Access Journals (Sweden)

    Alejandra eEscós

    2016-04-01

    Full Text Available The protein kinases p38γ and p38δ belong to the p38 mitogen-activated protein kinase (MAPK family. p38MAPK signalling controls many cellular processes and is one of the most conserved mechanisms in eukaryotes for the cellular response to environmental stress and inflammation. Although p38γ and p38δ are widely expressed, it is likely that they perform specific functions in different tissues. Their involvement in human pathologies such as inflammation-related diseases or cancer is starting to be uncovered. In this article we give a general overview and highlight recent advances made in defining the functions of p38γ and p38δ, focusing in innate immunity and inflammation. We consider the potential of the pharmacological targeting of MAPK pathways to treat autoimmune and inflammatory diseases and cancer

  11. 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.

  12. p38 Mapk signal pathway involved in anti-inflammatory effect of ...

    African Journals Online (AJOL)

    In conclusion, CSS and SLBZS might work as a significant anti-inflammatory effect on hepatocyte of NASH by inhibiting the activation of TLR4, p-p38 MAPK and p38 MAPK involved in p38 MAPK signal pathway. Conclusion: To some extent, CSS and SLBZS may be a potential alternative and complementary medicine to ...

  13. Cascaded Quadratic Soliton Compression in Waveguide Structures

    DEFF Research Database (Denmark)

    Guo, Hairun

    to further push such multi-cycle pulses into few-cycle and even single-cycle. In this thesis, we investigate the high order soliton compression in quadratic nonlinear waveguide structures, which is a one-step pulse compression scheme making use of the soliton regime -- with the spontaneous cancelation...... and self-defocusing Kerr effect so that the soliton is created and the soliton self-compression happens in the normal dispersion region. Meanwhile, the chromatic dispersion in the waveguide is also tunable, understood as the dispersion engineering with structural designs. Therefore, compared to commonly...... used two-step compression scheme with e.g. hollow-core photonic crystal fibers plus a dispersion compensation component, our scheme, called the cascaded quadratic soliton compression (CQSC), provides a simpler setup with larger tunability on the nonlinearity, and could avoid the problem with the self...

  14. Mid infrared DFB interband cascade lasers

    Science.gov (United States)

    Koeth, J.; Weih, R.; Scheuermann, J.; Fischer, M.; Schade, A.; Kamp, M.; Höfling, S.

    2017-08-01

    The mid infrared spectral range (MIR) is of great interest for a variety of industrial, medical and environmental applications since numerous molecules have strong absorption lines therein. Interband cascade lasers (ICLs) have the ability to cover the entire MIR almost independently from the bandgap of the utilized semiconductors. Combined with a DFB technology which is applicable for most kinds of interband transition based semiconductor lasers the spectral range between 2.8 and 5.9 μm could be covered with application grade single mode devices with low power consumption. Recent optimizations regarding the layer design as well as the device processing yielded DFB laser chips with improved performance that will pave the way for a variety of applications that benefit from reasonable output power.

  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. 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.

  17. Bankruptcy cascades in interbank markets.

    Science.gov (United States)

    Tedeschi, Gabriele; Mazloumian, Amin; Gallegati, Mauro; Helbing, Dirk

    2012-01-01

    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. 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)

  19. Simultaneous perturbation of the MAPK and the PI3K/mTOR pathways does not lead to increased radiosensitization

    International Nuclear Information System (INIS)

    Kuger, Sebastian; Flentje, Michael; Djuzenova, Cholpon S.

    2015-01-01

    The mitogen-activated protein kinases (MAPK) and the phosphatidylinositol-3-kinase (PI3K)/mammalian target of rapamycin (mTOR) pathways are intertwined on various levels and simultaneous inhibition reduces tumorsize and prolonges survival synergistically. Furthermore, inhibiting these pathways radiosensitized cancer cells in various studies. To assess, if phenotypic changes after perturbations of this signaling network depend on the genetic background, we integrated a time series of the signaling data with phenotypic data after simultaneous MAPK/ERK kinase (MEK) and PI3K/mTOR inhibition and ionizing radiation (IR). The MEK inhibitor AZD6244 and the dual PI3K/mTOR inhibitor NVP-BEZ235 were tested in glioblastoma and lung carcinoma cells, which differ in their mutational status in the MAPK and the PI3K/mTOR pathways. Effects of AZD6244 and NVP-BEZ235 on the proliferation were assessed using an ATP assay. Drug treatment and IR effects on the signaling network were analyzed in a time-dependent manner along with measurements of phenotypic changes in the colony forming ability, apoptosis, autophagy or cell cycle. Both inhibitors reduced the tumor cell proliferation in a dose-dependent manner, with NVP-BEZ235 revealing the higher anti-proliferative potential. Our Western blot data indicated that AZD6244 and NVP-BEZ235 perturbed the MAPK and PI3K/mTOR signaling cascades, respectively. Additionally, we confirmed crosstalks and feedback loops in the pathways. As shown by colony forming assay, the AZD6244 moderately radiosensitized cancer cells, whereas NVP-BEZ235 caused a stronger radiosensitization. Combining both drugs did not enhance the NVP-BEZ235-mediated radiosensitization. Both inhibitors caused a cell cycle arrest in the G1-phase, whereas concomitant IR and treatment with the inhibitors resulted in cell line- and drug-specific cell cycle alterations. Furthermore, combining both inhibitors synergistically enhanced a G1-phase arrest in sham-irradiated glioblastoma

  20. p38 MAPK Signaling in Postnatal Tendon Growth and Remodeling

    Science.gov (United States)

    Schwartz, Andrew J.; Sarver, Dylan C.; Sugg, Kristoffer B.; Dzierzawski, Justin T.; Gumucio, Jonathan P.; Mendias, Christopher L.

    2015-01-01

    Tendon is a dynamic tissue whose structure and function is influenced by mechanical loading, but little is known about the fundamental mechanisms that regulate tendon growth and remodeling in vivo. Data from cultured tendon fibroblasts indicated that the p38 MAPK pathway plays an important role in tendon fibroblast proliferation and collagen synthesis in vitro. To gain greater insight into the mechanisms of tendon growth, and explore the role of p38 MAPK signaling in this process, we tested the hypotheses that inducing plantaris tendon growth through the ablation of the synergist Achilles tendon would result in rapid expansion of a neotendon matrix surrounding the original tendon, and that treatment with the p38 MAPK inhibitor SB203580 would prevent this growth. Rats were treated with vehicle or SB203580, and subjected to synergist ablation by bilateral tenectomy of the Achilles tendon. Changes in histological and biochemical properties of plantaris tendons were analyzed 3, 7, or 28 days after overload, and comparisons were made to non-overloaded animals. By 28 days after overload, tendon mass had increased by 30% compared to non-overloaded samples, and cross-sectional area (CSA) increased by around 50%, with most of the change occurring in the neotendon. The expansion in CSA initially occurred through the synthesis of a hyaluronic acid rich matrix that was progressively replaced with mature collagen. Pericytes were present in areas of active tendon growth, but never in the original tendon ECM. Inhibition of p38 MAPK resulted in a profound decrease in IL6 expression, and had a modest effect on the expression of other ECM and cell proliferation genes, but had a negligible impact on overall tendon growth. The combined results from this study provided novel insights into tendon mechanobiology, and suggest that p38 MAPK signaling does not appear to be necessary for tendon growth in vivo. PMID:25768932

  1. p38 MAPK signaling in postnatal tendon growth and remodeling.

    Directory of Open Access Journals (Sweden)

    Andrew J Schwartz

    Full Text Available Tendon is a dynamic tissue whose structure and function is influenced by mechanical loading, but little is known about the fundamental mechanisms that regulate tendon growth and remodeling in vivo. Data from cultured tendon fibroblasts indicated that the p38 MAPK pathway plays an important role in tendon fibroblast proliferation and collagen synthesis in vitro. To gain greater insight into the mechanisms of tendon growth, and explore the role of p38 MAPK signaling in this process, we tested the hypotheses that inducing plantaris tendon growth through the ablation of the synergist Achilles tendon would result in rapid expansion of a neotendon matrix surrounding the original tendon, and that treatment with the p38 MAPK inhibitor SB203580 would prevent this growth. Rats were treated with vehicle or SB203580, and subjected to synergist ablation by bilateral tenectomy of the Achilles tendon. Changes in histological and biochemical properties of plantaris tendons were analyzed 3, 7, or 28 days after overload, and comparisons were made to non-overloaded animals. By 28 days after overload, tendon mass had increased by 30% compared to non-overloaded samples, and cross-sectional area (CSA increased by around 50%, with most of the change occurring in the neotendon. The expansion in CSA initially occurred through the synthesis of a hyaluronic acid rich matrix that was progressively replaced with mature collagen. Pericytes were present in areas of active tendon growth, but never in the original tendon ECM. Inhibition of p38 MAPK resulted in a profound decrease in IL6 expression, and had a modest effect on the expression of other ECM and cell proliferation genes, but had a negligible impact on overall tendon growth. The combined results from this study provided novel insights into tendon mechanobiology, and suggest that p38 MAPK signaling does not appear to be necessary for tendon growth in vivo.

  2. Identification of cluster of proteins in the network of MAPK pathways as cancer drug targets

    Directory of Open Access Journals (Sweden)

    V.K. MD Aksam

    2017-01-01

    Full Text Available The quest to develop computational drug target identification methods in complex diseases like cancer is growing in recent years. Feedback, feed-forward loops and cross-talks observed among the MAPK pathways led to the definition of a network of MAPK pathways and considered for single or multiple therapeutic interventions. We developed a computational method to identify clusters of drug targets by analysing the directed network's topological properties and the individual node's functional roles. We aim to identify the primary drug target nodes possessing more cancerous properties and less number of cellular functional roles. For every primary drug targets, we collect the alternate substrate activating nodes for local resistance analysis. Alternate substrate activation free nodes identified as single drug target are SOS, ATF1, BAD, GAB1, LAD, NFAT4, ATF2, MEF2, eEF2K, 4EBP1 and HSP27. Among the remaining identified nodes and their corresponding alternate substrate activating nodes with their cancer retaining and side effects causing properties studied as three different classes-single, multiple and dangerous targets. C-Raf1 and MAPKAP-K observed as a single efficient target due to the absence of resistance mechanism. Due to the resistance mechanism observed among the targeted M3/6, GADD45, and MKK6 multiple target intervention of their corresponding alternate nodes might prove to be the efficient targets. Targeted effect on MLK3, ZAK, DLK and MLTKa/b will impair the network due to intertwined and proximity nature among themselves.

  3. The Skp1 Homologs SKR-1/2 Are Required for the Caenorhabditis elegans SKN-1 Antioxidant/Detoxification Response Independently of p38 MAPK.

    Directory of Open Access Journals (Sweden)

    Cheng-Wei Wu

    2016-10-01

    Full Text Available SKN-1/Nrf are the primary antioxidant/detoxification response transcription factors in animals and they promote health and longevity in many contexts. SKN-1/Nrf are activated by a remarkably broad-range of natural and synthetic compounds and physiological conditions. Defining the signaling mechanisms that regulate SKN-1/Nrf activation provides insights into how cells coordinate responses to stress. Nrf2 in mammals is regulated in part by the redox sensor repressor protein named Keap1. In C. elegans, the p38 MAPK cascade in the intestine activates SKN-1 during oxidative stress by promoting its nuclear accumulation. Interestingly, we find variation in the kinetics of p38 MAPK activation and tissues with SKN-1 nuclear accumulation among different pro-oxidants that all trigger strong induction of SKN-1 target genes. Using genome-wide RNAi screening, we identify new genes that are required for activation of the core SKN-1 target gene gst-4 during exposure to the natural pro-oxidant juglone. Among 10 putative activators identified in this screen was skr-1/2, highly conserved homologs of yeast and mammalian Skp1, which function to assemble protein complexes. Silencing of skr-1/2 inhibits induction of SKN-1 dependent detoxification genes and reduces resistance to pro-oxidants without decreasing p38 MAPK activation. Global transcriptomics revealed strong correlation between genes that are regulated by SKR-1/2 and SKN-1 indicating a high degree of specificity. We also show that SKR-1/2 functions upstream of the WD40 repeat protein WDR-23, which binds to and inhibits SKN-1. Together, these results identify a novel p38 MAPK independent signaling mechanism that activates SKN-1 via SKR-1/2 and involves WDR-23.

  4. The Skp1 Homologs SKR-1/2 Are Required for the Caenorhabditis elegans SKN-1 Antioxidant/Detoxification Response Independently of p38 MAPK

    Science.gov (United States)

    Wu, Cheng-Wei; Deonarine, Andrew; Przybysz, Aaron; Strange, Kevin; Choe, Keith P.

    2016-01-01

    SKN-1/Nrf are the primary antioxidant/detoxification response transcription factors in animals and they promote health and longevity in many contexts. SKN-1/Nrf are activated by a remarkably broad-range of natural and synthetic compounds and physiological conditions. Defining the signaling mechanisms that regulate SKN-1/Nrf activation provides insights into how cells coordinate responses to stress. Nrf2 in mammals is regulated in part by the redox sensor repressor protein named Keap1. In C. elegans, the p38 MAPK cascade in the intestine activates SKN-1 during oxidative stress by promoting its nuclear accumulation. Interestingly, we find variation in the kinetics of p38 MAPK activation and tissues with SKN-1 nuclear accumulation among different pro-oxidants that all trigger strong induction of SKN-1 target genes. Using genome-wide RNAi screening, we identify new genes that are required for activation of the core SKN-1 target gene gst-4 during exposure to the natural pro-oxidant juglone. Among 10 putative activators identified in this screen was skr-1/2, highly conserved homologs of yeast and mammalian Skp1, which function to assemble protein complexes. Silencing of skr-1/2 inhibits induction of SKN-1 dependent detoxification genes and reduces resistance to pro-oxidants without decreasing p38 MAPK activation. Global transcriptomics revealed strong correlation between genes that are regulated by SKR-1/2 and SKN-1 indicating a high degree of specificity. We also show that SKR-1/2 functions upstream of the WD40 repeat protein WDR-23, which binds to and inhibits SKN-1. Together, these results identify a novel p38 MAPK independent signaling mechanism that activates SKN-1 via SKR-1/2 and involves WDR-23. PMID:27776126

  5. Study for Gamma Ray Spectra of Cascading Decay

    International Nuclear Information System (INIS)

    Jassim, F.A.

    2005-01-01

    Relative intensity to the single peaks and true sum peaks to the elements of cascading decay of gamma-rays as 60 Co and 88 Y have been measured for different point source-detector distances by using 3 * 3 N al(Tl) detector into two different methods. These methods give a good information to distinguish between single and true sum peaks especially in analysis a complex pulse height spectrum ; where the relative intensity for true sum peak varies with source - detector distance while it is independent for single peak. The results of two the methods are in fair agreement

  6. Cannabidiol upregulates melanogenesis through CB1 dependent pathway by activating p38 MAPK and p42/44 MAPK.

    Science.gov (United States)

    Hwang, Young Sun; Kim, Youn-Jung; Kim, Mi Ok; Kang, Mingyeong; Oh, Sae Woong; Nho, Youn Hwa; Park, See-Hyoung; Lee, Jongsung

    2017-08-01

    Melanogenesis plays a critical role in the protection of skin against external stresses such as ultraviolet irradiation and oxidative stressors. This study was aimed to investigate the effects of cannabidiol on melanogenesis and its mechanisms of action in human epidermal melanocytes. We found that cannabidiol increased both melanin content and tyrosinase activity. The mRNA levels of microphthalmia-associated transcription factor (MITF), tyrosinase, tyrosinase-related protein (TRP) 1, and TRP2 were increased following cannabidiol treatment. Likewise, cannabidiol increased the protein levels of MITF, TRP 1, TRP 2, and tyrosinase. Mechanistically, we found that cannabidiol regulated melanogenesis by upregulating MITF through phosphorylation of p38 mitogen-activated protein kinase (MAPK) and p42/44 MAPK, independent of cyclic adenosine monophosphate (cAMP)-protein kinase A (PKA) signaling. In addition, the melanogenic effect of cannabidiol was found to be mediated by cannabinoid CB 1 receptor, not by CB 2 receptor. Taken together, these findings indicate that cannabidiol-induced melanogenesis is cannabinoid CB 1 receptor-dependent, and cannabidiol induces melanogenesis through increasing MITF gene expression which is mediated by activation of p38 MAPK and p42/44 MAPK. Our results suggest that cannabidiol might be useful as a protective agent against external stresses. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Multiobjective reservoir operating rules based on cascade reservoir input variable selection method

    Science.gov (United States)

    Yang, Guang; Guo, Shenglian; Liu, Pan; Li, Liping; Xu, Chongyu

    2017-04-01

    The input variable selection in multiobjective cascade reservoir operation is an important and difficult task. To address this problem, this study proposes the cascade reservoir input variable selection (CIS) method that searches for the most valuable input variables for decision making in multiple-objectivity cascade reservoir operations. From a case study of Hanjiang cascade reservoirs in China, we derive reservoir operating rules based on the combination of CIS and Gaussian radial basis functions (RBFs) methods and optimize the rules through Pareto-archived dynamically dimensioned search (PA-DDS) with two objectives: to maximize both power generation and water supply. We select the most effective input variables and evaluate their impacts on cascade reservoir operations. From the simulated trajectories of reservoir water level, power generation, and water supply, we analyze the multiobjective operating rules with several input variables. The results demonstrate that the CIS method performs well in the selection of input variables for the cascade reservoir operation, and the RBFs method can fully express the nonlinear operating rules for cascade reservoirs. We conclude that the CIS method is an effective and stable approach to identifying the most valuable information from a large number of candidate input variables. While the reservoir storage state is the most valuable information for the Hanjiang cascade reservoir multiobjective operation, the reservoir inflow is the most effective input variable for the single-objective operation of Danjiangkou.

  8. Activation of MAPK kinase 9 induces ethylene and camalexin biosynthesis and enhances sensitivity to salt stress in Arabidopsis.

    Science.gov (United States)

    Xu, Juan; Li, Yuan; Wang, Ying; Liu, Hongxia; Lei, Lei; Yang, Hailian; Liu, Guoqin; Ren, Dongtao

    2008-10-03

    Mitogen-activated protein kinase (MAPK) cascades play important roles in regulating plant growth, development, and responses to various environmental stimuli. We demonstrate that MKK9, an MKK, is an upstream activator of the MPKs MPK3 and MPK6 both in vitro and in planta. Expression of active MKK9 protein in transgenic plants induces the synthesis of ethylene and camalexin through the activation of the endogenous MPK3 and MPK6 kinases. As a consequence, transcription of multiple genes responsible for ethylene biosynthesis, ethylene responses, and camalexin biosynthesis is coordinately up-regulated. The activation of MKK9 inhibits hypocotyl elongation in the etiolated seedlings. MKK9-mediated effects on hypocotyl elongation were blocked by the ethylene biosynthesis inhibitor, aminoethoxyvinylglycine, and ethylene receptor antagonist, Ag(+). Expression of active MKK9 protein enhances the sensitivity of transgenic seedlings to salt stress, whereas loss of MKK9 activity reduces salt sensitivity indicating a role for MKK9 in the salt stress response. The results reported here reveal that the MKK9-MPK3/MPK6 cascade participates in the regulation of the biosynthesis of ethylene and camalexin and may be an important axis in the stress responses of Arabidopsis.

  9. Dietary influence on MAPK-signaling pathways and risk of colon and rectal cancer.

    Science.gov (United States)

    Slattery, Martha L; Lundgreen, Abbie; Wolff, Roger K

    2013-01-01

    Mitogen-activated protein kinase (MAPK) pathways regulate cellular functions including cell proliferation, differentiation, migration, and apoptosis. Associations between genes in the DUSP, ERK1/2, JNK, and p38 MAPK-signaling pathways and dietary factors associated with growth factors, inflammation, and oxidative stress and risk of colon and rectal cancer were evaluated. Data include colon cases (n = 1555) and controls (n = 1956) and rectal cases (n = 754) and controls (n = 959). Statistically significant interactions were observed for the MAPK-signaling pathways after adjustment for multiple comparisons. DUSP genes interacted with carbohydrates, mutagen index, calories, calcium, vitamin D, lycopene, dietary fats, folic acid, and selenium. MAPK1, MAPK3, MAPK1, and RAF1 within the ERK1/2 MAPK-signaling pathway interacted with dietary fats and cruciferous vegetables. Within the JNK MAPK-signaling pathway, interactions between MAP3K7 and protein, vitamin C, iron, folic acid, carbohydrates, and cruciferous vegetables; MAP3K10 and folic acid; MAP3K9 and lutein/zeaxanthin; MAPK8 and calcium; MAP3K3 and calcium and lutein; MAP3K1 and cruciferous vegetables. Interaction within the p38-signaling pathway included MAPK14 with calories, carbohydrates saturated fat, selenium, vitamin C; MAP3K2 and carbohydrates, and folic acid. These data suggest that dietary factors involved in inflammation and oxidative stress interact with MAPK-signaling genes to alter risk of colorectal cancer.

  10. LeMAPK1, LeMAPK2, and LeMAPK3 are associated with nitric oxide-induced defense response against Botrytis cinerea in the Lycopersicon esculentum fruit.

    Science.gov (United States)

    Zheng, Yanyan; Hong, Hui; Chen, Lin; Li, Jingyuan; Sheng, Jiping; Shen, Lin

    2014-02-12

    Nitric oxide (NO) and mitogen-activated protein kinases (MAPKs) are signal molecules involved in the disease resistance of plants. To investigate the role of tomato MAPKs in the NO-mediated defense response, mature green tomatoes (Lycopersicon esculentum Mill. cv. Qian-xi) were treated with a MAPKs inhibitor (1,4-diamino-2,3-dicyano-1,4-bis(o-amino-phenylmercapto) butadiene (U0126)), NO donor sodium nitroprusside (SNP), and SNP plus U0126. Treatment with U0126 increased the incidence of disease and size of lesion areas in the tomato fruits after being inoculated with Botrytis cinerea. NO enhanced the resistance of the tomato fruits against Botrytis cinerea invasion and the activities of nitric oxide synthase, Chitinase, β-1,3-glucanase, polyphenol oxidase, and phenylalanine ammonia-lyase. However, the effects of NO on disease resistance were weakened by the MAPKs inhibitor. Meanwhile, the relative expression of LeMAPK1, LeMAPK2, and LeMAPK3 in the (SNP + U0126)-treated fruits was lower than that in the SNP-treated fruits. The results suggest that LeMAPK1/2/3 are involved in NO-induced disease resistance of tomato fruits against Botrytis cinerea.

  11. Optimized preventive replacement policy for large cascade systems

    International Nuclear Information System (INIS)

    Kretzen, H.H.

    1986-01-01

    The repair-bottleneck problem as a limiting factor for system reliability can be overcome. Design need only cover the steady state, wearout induced accumulations of failures being precluded by preventive replacements with subsequent recycling. As a result, a reliable system appears to be feasible on an economic basis, optimization in detail to be left to more precised cost-benefit studies. As a reference system the radio-frequency-generator cascade of a single-cell linear accelerator is considered. (DG)

  12. A simple method for potential flow simulation of cascades

    Indian Academy of Sciences (India)

    The cascade is first transformed to a single body using a conformal mapping, and the potential flow over this body is solved using a simple higher order vortex panel method. The advantage of this method over existing methodologies is that it enables the use of higher order panel methods, as are used to solve flow past an ...

  13. Scale-separation scheme for simulating superfluid turbulence: Kelvin-Wave cascade

    International Nuclear Information System (INIS)

    Kozik, Evgeny; Svistunov, Boris

    2005-01-01

    A Kolmogorov-type cascade of Kelvin waves--the distortion waves on vortex lines--plays a key part in the relaxation of superfluid turbulence at low temperatures. We propose an efficient numeric scheme for simulating the Kelvin-wave cascade on a single vortex line. This idea is likely to be generalizable for a full-scale simulation of different regimes of superfluid turbulence. With the new scheme, we are able to unambiguously resolve the cascade spectrum exponent, and thus to settle the controversy between recent simulations of Vinen, Tsubota, and Mitani [Phys. Rev. Lett. 91, 135301 (2003)] and recently developed analytic theory [Phys. Rev. Lett. 92, 035301 (2004)

  14. 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.

  15. Interband Cascade Laser Photon Noise

    Science.gov (United States)

    2009-09-01

    separated by an injection region composed of digitally graded Indium Arsenide (InAs)/ Aluminum Indium Antimonide (Al(In)Sb) multi-QWs. The active region...consists of coupled InAs, Gallium Indium Antimonide (GaInSb) and Gallium Antimonide (GaSb) QWs separated by Aluminum Antimonide (AlSb) barriers. Under... Antimonide AlInSb Aluminum Indium Antimonide cw constant wave DC direct current GaSb Gallium Antimonide IC Interband cascade InAs Indium Arsenide InSb

  16. 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....... 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...

  17. Inverse design technique for cascades

    Science.gov (United States)

    Zannetti, L.; Pandolfi, M.

    1984-01-01

    A numerical technique to generate cascades is presented. The basic prescribed parameters are: inlet angle, exit pressure, and distribution of blade thickness and lift along a blade. Other sets of parameters are also discussed. The technique is based on the lambda scheme. The problem of stability of the computation as a function of the prescribed set of parameters and the treatment of boundary conditions is discussed. A one dimensional analysis to indicate a possible way for assuring stability for any two dimensional calculation is provided.

  18. 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

  19. ECR-MAPK Regulation in Liver Early Development

    Directory of Open Access Journals (Sweden)

    Xiu-Ju Zhao

    2014-01-01

    Full Text Available Early growth is connected to a key link between embryonic development and aging. In this paper, liver gene expression profiles were assayed at postnatal day 22 and week 16 of age. Meanwhile another independent animal experiment and cell culture were carried out for validation. Significance analysis of microarrays, qPCR verification, drug induction/inhibition assays, and metabonomics indicated that alpha-2u globulin (extracellular region-socs2 (-SH2-containing signals/receptor tyrosine kinases-ppp2r2a/pik3c3 (MAPK signaling-hsd3b5/cav2 (metabolism/organization plays a vital role in early development. Taken together, early development of male rats is ECR and MAPK-mediated coordination of cancer-like growth and negative regulations. Our data represent the first comprehensive description of early individual development, which could be a valuable basis for understanding the functioning of the gene interaction network of infant development.

  20. 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

  1. The Roles of MAPK Cascades in Synaptic Plasticity and Memory in "Aplysia": Facilitatory Effects and Inhibitory Constraints

    Science.gov (United States)

    Sharma, Shiv K.; Carew, Thomas J.

    2004-01-01

    Synaptic plasticity is thought to contribute to memory formation. Serotonin-induced facilitation of sensory-motor (SN-MN) synapses in "Aplysia" is an extensively studied cellular analog of memory for sensitization. Serotonin, a modulatory neurotransmitter, is released in the CNS during sensitization training, and induces three temporally and…

  2. MAPK signaling correlates with the antidepressant effects of ketamine.

    Science.gov (United States)

    Réus, Gislaine Z; Vieira, Flavio Geraldo; Abelaira, Helena M; Michels, Monique; Tomaz, Débora B; dos Santos, Maria Augusta B; Carlessi, Anelise S; Neotti, Morgana V; Matias, Beatriz I; Luz, Jaíne R; Dal-Pizzol, Felipe; Quevedo, João

    2014-08-01

    Studies have pointed to a relationship between MAPK kinase (MEK) signaling and the behavioral effects of antidepressant drugs. So, in the present study we examined the behavioral and molecular effects of ketamine, an antagonist of the N-methyl-d-aspartate receptor (NMDA), which has been shown to have an antidepressant effect after the inhibition of MEK signaling in Wistar rats. Our results showed that acute administration of the MEK inhibitor PD184161, produced depressive-like behavior and stopped antidepressant-like effects of ketamine in the forced swimming test. The phosphorylation of extracellular signal-regulated kinase 1/2 (pERK 1/2) was decreased by PD184161 in the amygdala and nucleus accumbens, and the effects of ketamine on pERK 1/2 in the prefrontal cortex and hippocampus were inhibited by PD184161. The ERK 2 levels were decreased by PD184161 in the nucleus accumbens; and the effects of ketamine were blocked in this brain area. The p38 protein kinase (p38MAPK) and proBDNF were inhibited by PD184161, and the MEK inhibitor prevented the effects of ketamine in the nucleus accumbens. In addition, ketamine increased pro-BDNF levels in the hippocampus. In conclusion, our findings demonstrated that an acute blockade of MAPK signaling lead to depressive-like behavior and stopped the antidepressant response of ketamine, suggesting that the effects of ketamine could be mediated, at least in part, by the regulation of MAPK signaling in these specific brain areas. Copyright © 2014 Elsevier Ltd. All rights reserved.

  3. Evidence for the Involvement of p38 MAPK Activation in Barnacle Larval Settlement

    KAUST Repository

    He, Li-Sheng

    2012-10-24

    The barnacle Balanus ( = Amphibalanus) amphitrite is a major marine fouling animal. Understanding the molecular mechanism of larval settlement in this species is critical for anti-fouling research. In this study, we cloned one isoform of p38 MAPK (Bar-p38 MAPK) from this species, which shares the significant characteristic of containing a TGY motif with other species such as yeast, Drosophila and humans. The activation of p38 MAPK was detected by an antibody that recognizes the conserved dual phosphorylation sites of TGY. The results showed that phospho-p38 MAPK (pp38 MAPK) was more highly expressed at the cyprid stage, particularly in aged cyprids, in comparison to other stages, including the nauplius and juvenile stages. Immunostaining showed that Bar-p38 MAPK and pp38 MAPK were mainly located at the cyprid antennules, and especially the third and fourth segments, which are responsible for substratum exploration during settlement. The expression and localization patterns of Bar-p38 MAPK suggest its involvement in larval settlement. This postulation was also supported by the larval settlement bioassay with the p38 MAPK inhibitor SB203580. Behavioral analysis by live imaging revealed that the larvae were still capable of exploring the surface of the substratum after SB203580 treatment. This shows that the effect of p38 MAPK on larval settlement might be by regulating the secretion of permanent proteinaceous substances. Furthermore, the level of pp38 MAPK dramatically decreased after full settlement, suggesting that Bar-p38 MAPK maybe plays a role in larval settlement rather than metamorphosis. Finally, we found that Bar-p38 MAPK was highly activated when larvae confronted extracts of adult barnacle containing settlement cues, whereas larvae pre-treated with SB203580 failed to respond to the crude adult extracts.

  4. 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)

  5. 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.

  6. Analysis of Stomatal Patterning in Selected Mutants of MAPK Pathways

    KAUST Repository

    Felemban, Abrar

    2016-05-01

    Stomata are cellular valves in plants that play an essential role in the regulation of gas exchange and are distributed in the epidermis of aerial organs. In Arabidopsis thaliana, stomatal production and development are coordinated by the mitogen-activated protein kinase (MAPK) signalling pathway, which modulates a variety of other processes, including cell proliferation, regulation of cytokinesis, programed cell death, and response to abiotic and biotic stress. The environment also plays a role in stomatal development, by influencing the frequency at which stomata develop in leaves. This thesis presents an analysis of stomatal development in Arabidopsis mutants in two MAPK pathways: MEKK1-MKK1/MKK2-MPK4, and MAP3K17/18-MKK3. Obtained results demonstrate the effect of stress conditions on stomatal development and specify the involvement of analysed MAPK in stomatal patterning. First, both analysed pathways modulate stomatal patterning in Arabidopsis cotyledons. Second, plant growth-promoting bacteria tested enhance stomatal density and affect guard cell morphology. Third, the sucrose or mannitol treatment increases defects in stomatal patterning. Finally, salt stress or high temperature can suppress stomatal defects in mutants of the MEKK1-MKK1/MKK2-MPK4 pathway.

  7. Lifespans of Cascade Arc volcanoes

    Science.gov (United States)

    Calvert, A. T.

    2015-12-01

    Compiled argon ages reveal inception, eruptive episodes, ages, and durations of Cascade stratovolcanoes and their ancestral predecessors. Geologic mapping and geochronology show that most Cascade volcanoes grew episodically on multiple scales with periods of elevated behavior lasting hundreds of years to ca. 100 kyr. Notable examples include the paleomag-constrained, few-hundred-year-long building of the entire 15-20 km3 Shastina edifice at Mt. Shasta, the 100 kyr-long episode that produced half of Mt. Rainier's output, and the 30 kyr-long episode responsible for all of South and Middle Sister. Despite significant differences in timing and rates of construction, total durations of active and ancestral volcanoes at discrete central-vent locations are similar. Glacier Peak, Mt. Rainier, Mt. Adams, Mt. Hood, and Mt. Mazama all have inception ages of 400-600 ka. Mt. St. Helens, Mt. Jefferson, Newberry Volcano, Mt. Shasta and Lassen Domefield have more recent inception ages of 200-300 ka. Only the Sisters cluster and Mt. Baker have established eruptive histories spanning less than 50 kyr. Ancestral volcanoes centered 5-20 km from active stratocones appear to have similar total durations (200-600 kyr), but are less well exposed and dated. The underlying mechanisms governing volcano lifecycles are cryptic, presumably involving tectonic and plumbing changes and perhaps circulation cycles in the mantle wedge, but are remarkably consistent along the arc.

  8. LCA-based optimization of wood utilization under special consideration of a cascading use of wood.

    Science.gov (United States)

    Höglmeier, Karin; Steubing, Bernhard; Weber-Blaschke, Gabriele; Richter, Klaus

    2015-04-01

    Cascading, the use of the same unit of a resource in multiple successional applications, is considered as a viable means to improve the efficiency of resource utilization and to decrease environmental impacts. Wood, as a regrowing but nevertheless limited and increasingly in demand resource, can be used in cascades, thereby increasing the potential efficiency per unit of wood. This study aims to assess the influence of cascading wood utilization on optimizing the overall environmental impact of wood utilization. By combining a material flow model of existing wood applications - both for materials provision and energy production - with an algebraic optimization tool, the effects of the use of wood in cascades can be modelled and quantified based on life cycle impact assessment results for all production processes. To identify the most efficient wood allocation, the effects of a potential substitution of non-wood products were taken into account in a part of the model runs. The considered environmental indicators were global warming potential, particulate matter formation, land occupation and an aggregated single score indicator. We found that optimizing either the overall global warming potential or the value of the single score indicator of the system leads to a simultaneous relative decrease of all other considered environmental impacts. The relative differences between the impacts of the model run with and without the possibility of a cascading use of wood were 7% for global warming potential and the single score indicator, despite cascading only influencing a small part of the overall system, namely wood panel production. Cascading led to savings of up to 14% of the annual primary wood supply of the study area. We conclude that cascading can improve the overall performance of a wood utilization system. Copyright © 2015 Elsevier Ltd. All rights reserved.

  9. Simvastatin-induced breast cancer cell death and deactivation of PI3K/Akt and MAPK/ERK signalling are reversed by metabolic products of the mevalonate pathway.

    Science.gov (United States)

    Wang, Tingting; Seah, Serena; Loh, Xinyi; Chan, Ching-Wan; Hartman, Mikael; Goh, Boon-Cher; Lee, Soo-Chin

    2016-01-19

    Statins purportedly exert anti-tumoral effects on breast cancer. However, the biologic mechanisms for these actions are not fully elucidated. The aims of this study were 1) to explore the effects of simvastatin on apoptosis, proliferation as well as PI3K/Akt/mTOR and MAPK/ERK pathway in a window-of-opportunity breast cancer trial; 2) to further confirm findings from the clinical trial by functional studies; 3) to explore the regulatory role of mevalonate pathway on the anti-tumoral effects of simvastatin. In clinical samples, simvastatin led to increase in cleaved caspase-3 (p = 0.002) and decreased trend for Ki67 (p = 0.245). Simvastatin markedly suppressed PI3K/Akt/mTOR signalling by activating PTEN (p = 0.005) and by dephosphorylating Akt (p = 0.002) and S6RP (p = 0.033); it also inhibited MAPK/ERK pathway by dephosphorylating c-Raf (p = 0.018) and ERK1/2 (p = 0.002). In ER-positive (MCF-7, T47D) and ER-negative (MDA-MB-231, BT-549) breast cancer cells, simvastatin treatment consistently induced apoptosis and inhibited proliferation by deregulating caspase cascades and cell cycle proteins in a dose dependent manner. Concordantly, simvastatin strongly suppressed PI3K/Akt/mTOR pathway by enhancing PTEN expression and by further sequentially dephosphorylating downstream cascades including Akt, mTOR, p70S6K, S6RP and 4E-BP1. Furthermore, simvastatin significantly inhibited MAPK/ERK pathway by dephosphorylating sequential cascades such as c-Raf, MEK1/2 and ERK1/2. These simvastatin anti-tumoral effects were reversed by metabolic products of the mevalonate pathway, including mevalonate, farnesyl pyrophosphate and geranylgeranyl pyrophosphate. These findings shed light on the biological and potential anti-tumoral effects of simvastatin in breast cancer.

  10. A cascaded three-phase symmetrical multistage voltage multiplier

    International Nuclear Information System (INIS)

    Iqbal, Shahid; Singh, G K; Besar, R; Muhammad, G

    2006-01-01

    A cascaded three-phase symmetrical multistage Cockcroft-Walton voltage multiplier (CW-VM) is proposed in this report. It consists of three single-phase symmetrical voltage multipliers, which are connected in series at their smoothing columns like string of batteries and are driven by three-phase ac power source. The smoothing column of each voltage multiplier is charged twice every cycle independently by respective oscillating columns and discharged in series through load. The charging discharging process completes six times a cycle and therefore the output voltage ripple's frequency is of sixth order of the drive signal frequency. Thus the proposed approach eliminates the first five harmonic components of load generated voltage ripples and sixth harmonic is the major ripple component. The proposed cascaded three-phase symmetrical voltage multiplier has less than half the voltage ripple, and three times larger output voltage and output power than the conventional single-phase symmetrical CW-VM. Experimental and simulation results of the laboratory prototype are given to show the feasibility of proposed cascaded three-phase symmetrical CW-VM

  11. Damage production in atomic displacement cascades in beryllium

    Directory of Open Access Journals (Sweden)

    V.A. Borodin

    2016-12-01

    Full Text Available The paper presents the results of a molecular dynamics simulation of cascade damage production in beryllium caused by self-ion recoils in the energy range of 0.5–3keV. It is demonstrated that point defects are produced in Be preferentially in well-separated subcascades generated by secondary and higher order recoils. A linear dependence of the point defect number on the primary recoil energy is obtained with the slope that corresponds to formal atom displacement energy of ∼21eV. Most of the damage is created as single defects and the relatively high part of created point defects (∼50% survives the correlated recombination following the ballistic cascade stage and becomes freely-migrating.

  12. Hybrid-source impedance network and its generalized cascading concepts

    DEFF Research Database (Denmark)

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

    2009-01-01

    for current-type inverters. These impedance networks can in principle be combined into a single generic network entity, before generalized cascading concepts are proposed for connecting multiple of them together to form energy converters with a higher output voltage gain and other unique advantages....... It is anticipated that these concepts and their formed inverters can find applications in photovoltaic and other renewable systems, which in turn motivate the investigation initiated here on two-level and three-level generalized cascading concepts. In addition to their theoretical performance merits, practical...... shortcomings and relevant transient phenomena exhibited by the generalized concepts are discussed to provide a comprehensive knowledge base needed for weighing relevant tradeoffs before deciding on a particular application....

  13. Delay time calculation for dual-wavelength quantum cascade lasers

    Energy Technology Data Exchange (ETDEWEB)

    Hamadou, A., E-mail: abd-hamado@yahoo.fr [Département des Sciences et Techniques, Faculté des Sciences et de la Technologie, Université de Bordj Bou Arreridj 34000 (Algeria); Laboratoire d’étude des surfaces et interfaces des matériaux solides (LESIMS), Sétif 19000 (Algeria); Lamari, S. [Laboratoire d’étude des surfaces et interfaces des matériaux solides (LESIMS), Sétif 19000 (Algeria); Département de Physique, Faculté des Sciences, Université Sétif 1, 19000 (Algeria); Thobel, J.-L. [Institut d' Electronique, de Microélectronique et de Nanotechnologie (IEMN), UMR 8520, Université Lille1, Avenue Poincaré, BP 60069, 59652 Villeneuve d' Ascq Cédex (France)

    2013-11-28

    In this paper, we calculate the turn-on delay (t{sub th}) and buildup (Δt) times of a midinfrared quantum cascade laser operating simultaneously on two laser lines having a common upper level. The approach is based on the four-level rate equations model describing the variation of the electron number in the states and the photon number present within the cavity. We obtain simple analytical formulae for the turn-on delay and buildup times that determine the delay times and numerically apply our results to both the single and bimode states of a quantum cascade laser, in addition the effects of current injection on t{sub th} and Δt are explored.

  14. Abnormal circadian oscillation of hippocampal MAPK activity and power spectrums in NF1 mutant mice

    OpenAIRE

    Chen, Lei; Serdyuk, Tatiana; Yang, Beimeng; Wang, Shuai; Chen, Shiqing; Chu, Xixia; Zhang, Xu; Song, Jinjing; Bao, Hechen; Zhou, Chengbin; Wang, Xiang; Dong, Shuangle; Song, Lulu; Chen, Fujun; He, Guang

    2017-01-01

    Studies have implied that the circadian oscillation of mitogen-activated protein kinase (MAPK) signal pathways is crucial for hippocampus-dependent memory. NF1 mouse models (Nf1 heterozygous null mutants; Nf1 +/?) displayed enhanced MAPK activity in the hippocampus and resulted in memory deficits. We assumed a link between MAPK pathways and hippocampal rhythmic oscillations, which have never been explored in Nf1 +/? mice. We demonstrated that the level of extracellular signal?regulated kinase...

  15. Cascade Harvest’ red raspberry

    Science.gov (United States)

    Cascade Harvest’ is a new floricane fruiting raspberry cultivar (Rubus idaeus L.) jointly released by Washington State University (WSU), Oregon State University (OSU) and the U.S. Department of Agriculture (USDA). ‘Cascade Harvest’ produces a high yield of large, firm fruit suited to machine harves...

  16. Characterization, expression patterns and functional analysis of the MAPK and MAPKK genes in watermelon (Citrullus lanatus).

    Science.gov (United States)

    Song, Qiuming; Li, Dayong; Dai, Yi; Liu, Shixia; Huang, Lei; Hong, Yongbo; Zhang, Huijuan; Song, Fengming

    2015-12-23

    Mitogen-activated protein kinase (MAPK) cascades, which consist of three functionally associated protein kinases, namely MEKKs, MKKs and MPKs, are universal signaling modules in all eukaryotes and have been shown to play critical roles in many physiological and biochemical processes in plants. However, little or nothing is known about the MPK and MKK families in watermelon. In the present study, we performed a systematic characterization of the ClMPK and ClMKK families including the identification and nomenclature, chromosomal localization, phylogenetic relationships, ClMPK-ClMKK interactions, expression patterns in different tissues and in response to abiotic and biotic stress and transient expression-based functional analysis for their roles in disease resistance. Genome-wide survey identified fifteen ClMPK and six ClMKK genes in watermelon genome and phylogenetic analysis revealed that both of the ClMPK and ClMKK families can be classified into four distinct groups. Yeast two-hybrid assays demonstrated significant interactions between members of the ClMPK and ClMKK families, defining putative ClMKK2-1/ClMKK6-ClMPK4-1/ClMPK4-2/ClMPK13 and ClMKK5-ClMPK6 cascades. Most of the members in the ClMPK and ClMKK families showed differential expression patterns in different tissues and in response to abiotic (e.g. drought, salt, cold and heat treatments) and biotic (e.g. infection of Fusarium oxysporum f. sp. niveum) stresses. Transient expression of ClMPK1, ClMPK4-2 and ClMPK7 in Nicotiana benthamiana resulted in enhanced resistance to Botrytis cinerea and upregulated expression of defense genes while transient expression of ClMPK6 and ClMKK2-2 led to increased susceptibility to B. cinerea. Furthermore, transient expression of ClMPK7 also led to hypersensitive response (HR)-like cell death and significant accumulation of H2O2 in N. benthamiana. We identified fifteen ClMPK and six ClMKK genes from watermelon and analyzed their phylogenetic relationships, expression

  17. Availability Cascades & the Sharing Economy

    DEFF Research Database (Denmark)

    Netter, Sarah

    2014-01-01

    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...... 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....... 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...

  18. Time-dependent intranuclear cascade model

    International Nuclear Information System (INIS)

    Barashenkov, V.S.; Kostenko, B.F.; Zadorogny, A.M.

    1980-01-01

    An intranuclear cascade model with explicit consideration of the time coordinate in the Monte Carlo simulation of the development of a cascade particle shower has been considered. Calculations have been performed using a diffuse nuclear boundary without any step approximation of the density distribution. Changes in the properties of the target nucleus during the cascade development have been taken into account. The results of these calculations have been compared with experiment and with the data which had been obtained by means of a time-independent cascade model. The consideration of time improved agreement between experiment and theory particularly for high-energy shower particles; however, for low-energy cascade particles (with grey and black tracks in photoemulsion) a discrepancy remains at T >= 10 GeV. (orig.)

  19. Placement of Synchronized Measurements for Power System Observability during Cascaded Outages

    Science.gov (United States)

    Thirugnanasambandam, Venkatesh; Jain, Trapti

    2017-11-01

    Cascaded outages often result in power system islanding followed by a blackout and therefore considered as a severe disturbance. Maintaining the observability of each island may help in taking proper control actions to preserve the stability of individual islands thus, averting system collapse. With this intent, a strategy for placement of synchronized measurements, which can be obtained from phasor measurement units (PMU), has been proposed in this paper to keep the system observable during cascaded outages also. Since, all the cascaded failures may not lead to islanding situations, therefore, failures leading to islanding as well as non-islanding situations have been considered. A topology based algorithm has been developed to identify the islanding/non-islanding condition created by a particular cascaded event. Additional contingencies such as single line loss and single PMU failure have also been considered after the occurrence of cascaded events. The proposed method is further extended to incorporate the measurement redundancy, which is desirable for a reliable state estimation. The proposed scheme is tested on IEEE 14-bus, IEEE 30-bus and a practical Indian 246-bus networks. The numerical results ensure the observability of the power system under system intact as well as during cascaded islanding and non-islanding disturbances.

  20. Clinicopathological and prognostic significance of mitogen-activated protein kinases (MAPK) in breast cancers.

    Science.gov (United States)

    Ahmad, Dena A J; Negm, Ola H; Alabdullah, M Layth; Mirza, Sameer; Hamed, Mohamed R; Band, Vimla; Green, Andrew R; Ellis, Ian O; Rakha, Emad A

    2016-10-01

    Mitogen-activated protein kinases (MAPKs) are signalling transduction molecules that have different functions and diverse behaviour in cancer. In breast cancer, MAPK is related to oestrogen receptor (ER) and HER2. Protein expression of a large panel of MAPKs (JNK1/2, ERK, p38, C-JUN and ATF2 including phosphorylated forms) were assessed immunohistochemically in a large (n = 1400) and well-characterised breast cancer series prepared as tissue microarray. Moreover, reverse phase protein array was applied to quantify protein expression of MAPKs in six breast cancer cell lines with different phenotypes including HER2-transfected cells. MAPKs expression was associated with clinicopathological variables characteristic of good prognosis. These associations were most significant in the whole series and in the ER+ subgroup compared to other BC classes. Most of MAPKs showed a positive association with ER, BCL2 and better outcome and were negatively associated with the proliferation marker Ki67 and p53. Association of MAPK with HER2 was mainly seen in the ER- subgroup. Reverse phase protein array confirmed immunohistochemistry results and revealed differential expression of MAPK proteins in ER+ and ER- cell lines. MAPKs are associated with good prognosis and their expression is mainly related to ER. Studying a large panel rather than individual biomarkers may provide improved understanding of the pathway.

  1. 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.

  2. Real-Time Observation of Target Search by the CRISPR Surveillance Complex Cascade

    Directory of Open Access Journals (Sweden)

    Chaoyou Xue

    2017-12-01

    Full Text Available CRISPR-Cas systems defend bacteria and archaea against infection by bacteriophage and other threats. The central component of these systems are surveillance complexes that use guide RNAs to bind specific regions of foreign nucleic acids, marking them for destruction. Surveillance complexes must locate targets rapidly to ensure timely immune response, but the mechanism of this search process remains unclear. Here, we used single-molecule FRET to visualize how the type I-E surveillance complex Cascade searches DNA in real time. Cascade rapidly and randomly samples DNA through nonspecific electrostatic contacts, pausing at short PAM recognition sites that may be adjacent to the target. We identify Cascade motifs that are essential for either nonspecific sampling or positioning and readout of the PAM. Our findings provide a comprehensive structural and kinetic model for the Cascade target-search mechanism, revealing how CRISPR surveillance complexes can rapidly search large amounts of genetic material en route to target recognition.

  3. Uric acid stimulates proliferative pathways in vascular smooth muscle cells through the activation of p38 MAPK, p44/42 MAPK and PDGFRβ.

    Science.gov (United States)

    Kırça, M; Oğuz, N; Çetin, A; Uzuner, F; Yeşilkaya, A

    2017-04-01

    Hyperuricemia and angiotensin II (Ang II) may have a pathogenetic role in the development of hypertension and atherosclerosis as well as cardiovascular disease (CVD) and its prognosis. The purpose of this study was to investigate whether uric acid can induce proliferative pathways of vascular smooth muscle cell (VSMC) that are thought to be responsible for the development of CVD. The phosphorylation of p38 mitogen-activated protein kinase (p38 MAPK), p44/42 mitogen-activated protein kinase (p44/42 MAPK) and platelet-derived growth factor receptor β (PDGFRβ) was measured by Elisa and Western blot techniques to determine the activation of proliferative pathways in primary cultured VSMCs from rat aorta. Results demonstrated that uric acid can stimulate p38 MAPK, p44/42 MAPK and PDGFRβ phosphorylation in a time- and concentration-dependent manner. Furthermore, treatment of VSMCs with the angiotensin II type I receptor (AT1R) inhibitor losartan suppressed p38 MAPK and p44/42 MAPK induction by uric acid. The stimulatory effect of uric acid on p38 MAPK was higher compared to that of Ang II. The results of this study show for the first time that uric acid-induced PDGFRβ phosphorylation plays a crucial role in the development of CVDs and that elevated uric acid levels could be a potential therapeutical target in CVD patients.

  4. 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°.

  5. OK-432-stimulated chemokine secretion from human monocytes depends on MEK1/2, and involves p38 MAPK and NF-κB phosphorylation, in vitro.

    Science.gov (United States)

    Olsnes, Carla; Bredholt, Therese; Olofsson, Jan; Aarstad, Hans J

    2013-04-01

    Interaction between the immune system and cancer cells allows for the use of biological response modifiers, like OK-432, in cancer therapy. We have studied the involvement of monocytes (MOs) in the immune response to OK-432 by examining MCP-1, MIP-1α and MIP-1β secretion, in vitro. OK-432-induced IL-6/TNF-α secretion has previously been shown to depend on mitogen-activated protein kinases (MAPKs) ERK1/2 and p38, and we therefore investigated the role of these MAPKs in OK-432-induced chemokine secretion. Here we demonstrate that pharmacological MEK1/2 kinase inhibition generally impaired chemokine secretion from MOs, whereas p38 MAPK inhibition in particular reduced MIP-1α production. Furthermore, simultaneous inhibition of MEK1/2 and Syk kinase was seen to have an additive impact on reduced MCP-1, MIP-1α and MIP-1β secretion. Based on single cell flow cytometry analyses, OK-432, lipoteichoic acid (LTA) and lipopolysaccharide (LPS) were seen to induce p38 MAPK and NF-κB phosphorylation in MOs with different time kinetics. LTA and LPS have been shown to induce ERK1/2 phosphorylation, whereas the levels of phosphorylated ERK1/2 remained constant following OK-432 treatment at the time points tested. Toll-like receptors (TLRs) recognize pathogen-associated molecular patterns, and we demonstrate increased TLR2 cell surface levels on the MO population, most profoundly following stimulation with LTA and OK-432. Together these results indicate that modulation of MEK1/2 and p38 MAPK signalling could affect the response to OK-432 treatment, having the potential to improve its therapeutic potential within cancer and lymphangioma treatment. © 2012 The Authors APMIS © 2012 APMIS.

  6. Systems biology. Conditional density-based analysis of T cell signaling in single-cell data.

    Science.gov (United States)

    Krishnaswamy, Smita; Spitzer, Matthew H; Mingueneau, Michael; Bendall, Sean C; Litvin, Oren; Stone, Erica; Pe'er, Dana; Nolan, Garry P

    2014-11-28

    Cellular circuits sense the environment, process signals, and compute decisions using networks of interacting proteins. To model such a system, the abundance of each activated protein species can be described as a stochastic function of the abundance of other proteins. High-dimensional single-cell technologies, such as mass cytometry, offer an opportunity to characterize signaling circuit-wide. However, the challenge of developing and applying computational approaches to interpret such complex data remains. Here, we developed computational methods, based on established statistical concepts, to characterize signaling network relationships by quantifying the strengths of network edges and deriving signaling response functions. In comparing signaling between naïve and antigen-exposed CD4(+) T lymphocytes, we find that although these two cell subtypes had similarly wired networks, naïve cells transmitted more information along a key signaling cascade than did antigen-exposed cells. We validated our characterization on mice lacking the extracellular-regulated mitogen-activated protein kinase (MAPK) ERK2, which showed stronger influence of pERK on pS6 (phosphorylated-ribosomal protein S6), in naïve cells as compared with antigen-exposed cells, as predicted. We demonstrate that by using cell-to-cell variation inherent in single-cell data, we can derive response functions underlying molecular circuits and drive the understanding of how cells process signals. Copyright © 2014, American Association for the Advancement of Science.

  7. Photoexcitation cascade and quantum-relativistic jet formation in graphene

    Science.gov (United States)

    Lewandowski, Cyprian; Levitov, Leonid

    Interactions between ultra-relativistic particles can lead to striking behavior in which a high-energy particle creates showers of softer particles characterized by a collimated angular distribution aligned with the particle velocity. These showers, known as jets, are a generic phenomenon relevant for all quantum cascades of linearly dispersing particles. This talk will discuss jets formed upon photoexcitation in graphene, which due to its linear dispersion provides an appealing medium for exploring quantum-relativistic phenomena. We will study the cascade generated by carrier-carrier collisions in photon absorption, wherein a single photon creates an electron-hole (e-h) excitation that decays producing multiple near-collinear secondary e-h excitations. We will argue that the cascade can occur through an off-shell mechanism such that all the particles and holes involved reside outside the energy-momentum dispersion manifold, relieving the bottleneck arising in the on-shell process due to energy and momentum conservation. The characteristics of the jets such as the angular and energy distribution of the particles will be discussed. Photogenerated jets provide an interesting setting to investigate the carrier-carrier collision processes in graphene and other Dirac materials. We acknowledge support of the Center for Integrated Quantum Materials (CIQM) under NSF award DMR-1231319.

  8. Kinetic Simulation of the Dissipation of a Turbulent Cascade

    Science.gov (United States)

    Roberts, D. A.; Roytershteyn, V.; Wicks, R. T.

    2015-12-01

    The solar wind fluctuations undergo a turbulent cascade that presumably results, in some unknown fashion, in the deposition of energy into randomized motions, i.e. "heating." The observed evolution of spectra, cross-helicity, and non-adiabatic thermal properties of the plasma provide strong evidence for a nonlinear cascade, but the currently available temporal/spatial resolution of (mostly) single spacecraft measurments leaves many questions open. Large-scale particle-in-cell simulations allow us to explore the fate of cascading energy from "MHD" scales to the scales where wave-particle interactions become important. Simulations to date have shown a number of characteristics similar to that of solar wind plasma, including steeper magnetic spectra parallel to the mean magnetic field than perpendicular to it, a spectral break near the ion inertial length, and bounded anisotropic temperatures. Detailed analysis has revealed "magnetic holes" and nonthermal particle distributions. We are in the process of analyzing a variety of initial conditions as well as looking in more detail at issues such as nonlinear vs linear dynamics, and of how distribution functions vary with conditions in the plasma. This paper will report latest results on these and other issues.

  9. Cascade Baryon Spectrum from Lattice QCD

    International Nuclear Information System (INIS)

    Mathur, Nilmani; Bulava, John; Edwards, Robert; Engelson, Eric; Joo, Balint; Lichtl, Adam; Lin, Huey-Wen; Morningstar, Colin; Richards, David; Wallace, Stephen

    2008-01-01

    A comprehensive study of the cascade baryon spectrum using lattice QCD affords the prospect of predicting the masses of states not yet discovered experimentally, and determining the spin and parity of those states for which the quantum numbers are not yet known. The study of the cascades, containing two strange quarks, is particularly attractive for lattice QCD in that the chiral effects are reduced compared to states composed only of u/d quarks, and the states are typically narrow. We report preliminary results for the cascade spectrum obtained by using anisotropic Nf = 2 Wilson lattices with temporal lattice spacing 5.56 GeV?1.

  10. Calf Spleen Extractive Injection (CSEI, a small peptides enriched extraction, induces human hepatocellular carcinoma cell apoptosis via ROS/MAPKs dependent mitochondrial pathway

    Directory of Open Access Journals (Sweden)

    Dongxu Jia

    2016-10-01

    Full Text Available Calf Spleen Extractive Injection (CSEI, a small peptides enriched extraction, performs immunomodulatory activity on cancer patients suffering from radiotherapy or chemotherapy. The present study aims to investigate the anti-hepatocellular carcinoma effects of CSEI in cells and tumor-xenografted mouse models. In HepG2 and SMMC-7721 cells, CSEI reduced cell viability, enhanced apoptosis rate, caused reactive oxygen species (ROS accumulation, inhibited migration ability, and induced caspases cascade and mitochondrial membrane potential dissipation. CSEI significantly inhibited HepG2-xenografted tumor growth in nude mice. In cell and animal experiments, CSEI increased the activations of pro-apoptotic proteins including caspase 8, caspase 9 and caspase 3; meanwhile, it suppressed the expressions of anti-apoptotic protein B-cell lymphoma 2 (Bcl-2 and anti-oxidation proteins, such as nuclear factor-erythroid 2 related factor 2 (Nrf2 and catalase (CAT. The enhanced phosphorylation of P38 and c-JunN-terminalkinase (JNK, and decreased phosphorylation of extra cellular signal-regulated protein kinase (ERKs were observed in CSEI-treated cells and tumor tissues. CSEI-induced cell viability reduction was significantly attenuated by N-Acetyl-l-cysteine (a ROS inhibitor pretreatment. All data demonstrated that the upregulated oxidative stress status and the altered mitogen-activated protein kinases (MAPKs phosphorylation contributed to CSEI-driven mitochondrial dysfunction. Taken together, CSEI exactly induced apoptosis in human hepatocellular carcinoma cells via ROS/MAPKs dependent mitochondrial pathway.

  11. DAF-18/PTEN signals through AAK-1/AMPK to inhibit MPK-1/MAPK in feedback control of germline stem cell proliferation.

    Directory of Open Access Journals (Sweden)

    Patrick Narbonne

    2017-04-01

    Full Text Available Under replete growth conditions, abundant nutrient uptake leads to the systemic activation of insulin/IGF-1 signalling (IIS and the promotion of stem cell growth/proliferation. Activated IIS can stimulate the ERK/MAPK pathway, the activation of which also supports optimal stem cell proliferation in various systems. Stem cell proliferation rates can further be locally refined to meet the resident tissue's need for differentiated progeny. We have recently shown that the accumulation of mature oocytes in the C. elegans germ line, through DAF-18/PTEN, inhibits adult germline stem cell (GSC proliferation, despite high systemic IIS activation. We show here that this feedback occurs through a novel cryptic signalling pathway that requires PAR-4/LKB1, AAK-1/AMPK and PAR-5/14-3-3 to inhibit the activity of MPK-1/MAPK, antagonize IIS, and inhibit both GSC proliferation and the production of additional oocytes. Interestingly, our results imply that DAF-18/PTEN, through PAR-4/LKB1, can activate AAK-1/AMPK in the absence of apparent energy stress. As all components are conserved, similar signalling cascades may regulate stem cell activities in other organisms and be widely implicated in cancer.

  12. 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)

  13. Embedded Hardware-Efficient Real-Time Classification With Cascade Support Vector Machines.

    Science.gov (United States)

    Kyrkou, Christos; Bouganis, Christos-Savvas; Theocharides, Theocharis; Polycarpou, Marios M

    2016-01-01

    Cascade support vector machines (SVMs) are optimized to efficiently handle problems, where the majority of the data belong to one of the two classes, such as image object classification, and hence can provide speedups over monolithic (single) SVM classifiers. However, SVM classification is a computationally demanding task and existing hardware architectures for SVMs only consider monolithic classifiers. This paper proposes the acceleration of cascade SVMs through a hybrid processing hardware architecture optimized for the cascade SVM classification flow, accompanied by a method to reduce the required hardware resources for its implementation, and a method to improve the classification speed utilizing cascade information to further discard data samples. The proposed SVM cascade architecture is implemented on a Spartan-6 field-programmable gate array (FPGA) platform and evaluated for object detection on 800×600 (Super Video Graphics Array) resolution images. The proposed architecture, boosted by a neural network that processes cascade information, achieves a real-time processing rate of 40 frames/s for the benchmark face detection application. Furthermore, the hardware-reduction method results in the utilization of 25% less FPGA custom-logic resources and 20% peak power reduction compared with a baseline implementation.

  14. Cyclization cascade of allenyl azides: A dual mechanism

    Science.gov (United States)

    López, Carlos Silva; Faza, Olalla Nieto; Feldman, Ken S.; Iyer, Malliga R.; Hester, D. Keith

    2008-01-01

    A density functional theory based computational approach to describing the mechanistic course of the allene azide cycloaddition cascade sequence has been developed. The results of these calculations permit characterization of key reactive intermediates (diradicals and/or indolidenes), and explain the different behaviour observed in the experimental studies between conjugated and non-conjugated species. Furthermore, computational analysis of certain intermediates offer insight into issues of regioselectivity and stereoselectivity in cases where different reaction channels are in competition, suggesting suitable substitutions to achieve a single regioisomer in the indole synthesis via azide-allene cyclization. PMID:17530848

  15. Influence of interface roughness in quantum cascade lasers

    International Nuclear Information System (INIS)

    Krivas, K. A.; Winge, D. O.; Franckié, M.; Wacker, A.

    2015-01-01

    We use a numerical model based on non-equilibrium Green's functions to investigate the influence of interface roughness (IFR) scattering in terahertz quantum cascade lasers. We confirm that IFR is an important phenomenon that affects both current and gain. The simulations indicate that IFR causes a leakage current that transfers electrons from the upper to the lower laser state. In certain cases, this current can greatly reduce gain. In addition, individual interfaces and their impact on the renormalized single particle energies are studied and shown to give both blue- and red-shifts of the gain spectrum

  16. 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

  17. {tau} polarization in SUSY cascade decays

    Energy Technology Data Exchange (ETDEWEB)

    Choi, S.Y. [Chonbuk Univ., Jeonju (Korea), Dept. of Physics and RIPC]|[Deutsches Elektronen-Synchrotron (DESY), Hamburg (Germany); Hagiwara, K. [KEK National High Energy Physics, Tsukuba (Japan); Kim, Y.G. [Sejong Univ., Seoul (Korea). ARCSEC; Mawatari, K. [Korea Institute for Advanced Study, Seoul (Korea). School of Physics; Zerwas, P.M. [Deutsches Elektronen-Synchrotron (DESY), Hamburg (Germany)]|[KEK National High Energy Physics, Tsukuba (Japan)

    2006-12-15

    {tau} 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.)

  18. 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.

  19. 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.)

  20. 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.)

  1. Compression limits in cascaded quadratic soliton compression

    DEFF Research Database (Denmark)

    Bache, Morten; Bang, Ole; Krolikowski, Wieslaw

    2008-01-01

    Cascaded quadratic soliton compressors generate under optimal conditions few-cycle pulses. Using theory and numerical simulations in a nonlinear crystal suitable for high-energy pulse compression, we address the limits to the compression quality and efficiency.......Cascaded quadratic soliton compressors generate under optimal conditions few-cycle pulses. Using theory and numerical simulations in a nonlinear crystal suitable for high-energy pulse compression, we address the limits to the compression quality and efficiency....

  2. 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.

  3. 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.

  4. In Vitro Treatment of Melanoma Brain Metastasis by Simultaneously Targeting the MAPK and PI3K Signaling Pathways

    Directory of Open Access Journals (Sweden)

    Inderjit Daphu

    2014-05-01

    Full Text Available Malignant melanoma is the most lethal form of skin cancer, with a high propensity to metastasize to the brain. More than 60% of melanomas have the BRAFV600E mutation, which activates the mitogen-activated protein kinase (MAPK pathway [1]. In addition, increased PI3K (phosphoinositide 3-kinase pathway activity has been demonstrated, through the loss of activity of the tumor suppressor gene, PTEN [2]. Here, we treated two melanoma brain metastasis cell lines, H1_DL2, harboring a BRAFV600E mutation and PTEN loss, and H3, harboring WT (wild-type BRAF and PTEN loss, with the MAPK (BRAF inhibitor vemurafenib and the PI3K pathway associated mTOR inhibitor temsirolimus. Combined use of the drugs inhibited tumor cell growth and proliferation in vitro in H1_DL2 cells, compared to single drug treatment. Treatment was less effective in the H3 cells. Furthermore, a strong inhibitory effect on the viability of H1_DL2 cells, when grown as 3D multicellular spheroids, was seen. The treatment inhibited the expression of pERK1/2 and reduced the expression of pAKT and p-mTOR in H1_DL2 cells, confirming that the MAPK and PI3K pathways were inhibited after drug treatment. Microarray experiments followed by principal component analysis (PCA mapping showed distinct gene clustering after treatment, and cell cycle checkpoint regulators were affected. Global gene analysis indicated that functions related to cell survival and invasion were influenced by combined treatment. In conclusion, we demonstrate for the first time that combined therapy with vemurafenib and temsirolimus is effective on melanoma brain metastasis cells in vitro. The presented results highlight the potential of combined treatment to overcome treatment resistance that may develop after vemurafenib treatment of melanomas.

  5. Role of MAPK/AP-1 signaling pathway in the protection of CEES-induced lung injury by antioxidant liposome

    International Nuclear Information System (INIS)

    Mukhopadhyay, Sutapa; Mukherjee, Shyamali; Stone, William L.; Smith, Milton; Das, Salil K.

    2009-01-01

    We have recently reported that antioxidant liposomes can be used as antidotes for mustard gas induced lung injury in guinea pigs. The maximum protection was achieved with a liposome composed of tocopherols (α, γ, δ) and N-acetylcysteine (NAC) when administered after 5 min of exposure of 2-chloroethyl ethyl sulfide (CEES), a half sulfur mustard gas. We also reported an association of mustard gas-induced lung injury with an activation of MAPK/AP-1 signaling pathway and cell proliferation. The objective of the present study was to investigate whether CEES-induced MAPKs/AP-1 signaling pathway is influenced by antioxidant liposome therapy. A single dose (200 μl) of the antioxidant liposome was administered intratracheally after 5 min of exposure of CEES (0.5 mg/kg). The animals were sacrificed after 1 h and 30 days of CEES exposure. Although the liposome treatment did not have any significant effect on the activation of the MAPKs family (ERK1/2, p38 and JNK1/2), it significantly counteracted the CEES-induced activation of AP-1 transcription factors and corresponding increase in the protein levels of Fos, ATF and Jun family members. The liposome treatment significantly blocked the CEES-induced increase in the protein levels of cyclin D1, a cell cycle protein and PCNA, a cell differentiation marker. Furthermore, it protected lung against CEES-induced inflammation and infiltration of neutrophils, eosinophils and erythrocytes in the alveolar space. This suggests that the protective effect of antioxidant liposome against CEES-induced lung damage is mediated via control of AP-1 signaling.

  6. Discriminating cascading processes in nonlinear optics: A QED analysis based on their molecular and geometric origin

    Science.gov (United States)

    Bennett, Kochise; Chernyak, Vladimir Y.; Mukamel, Shaul

    2017-03-01

    The nonlinear optical response of a system of molecules often contains contributions whereby the products of lower-order processes in two separate molecules give signals that appear on top of a genuine direct higher-order process with a single molecule. These many-body contributions are known as cascading and complicate the interpretation of multidimensional stimulated Raman and other nonlinear signals. In a quantum electrodynamic treatment, these cascading processes arise from second-order expansion in the molecular coupling to vacuum modes of the radiation field, i.e., single-photon exchange between molecules, which also gives rise to other collective effects. We predict the relative phase of the direct and cascading nonlinear signals and its dependence on the microscopic dynamics as well as the sample geometry. This phase may be used to identify experimental conditions for distinguishing the direct and cascading signals by their phase. Higher-order cascading processes involving the exchange of several photons between more than two molecules are discussed.

  7. Lack of plasma kallikrein-kinin system cascade in teleosts.

    Directory of Open Access Journals (Sweden)

    Marty Kwok-Shing Wong

    Full Text Available The kallikrein-kinin system (KKS consists of two major cascades in mammals: "plasma KKS" consisting of high molecular-weight (HMW kininogen (KNG, plasma kallikrein (KLKB1, and bradykinin (BK; and "tissue KKS" consisting of low molecular-weight (LMW KNG, tissue kallikreins (KLKs, and [Lys(0]-BK. Some components of the KKS have been identified in the fishes, but systematic analyses have not been performed, thus this study aims to define the KKS components in teleosts and pave a way for future physiological and evolutionary studies. Through a combination of genomics, molecular, and biochemical methods, we showed that the entire plasma KKS cascade is absent in teleosts. Instead of two KNGs as found in mammals, a single molecular weight KNG was found in various teleosts, which is homologous to the mammalian LMW KNG. Results of molecular phylogenetic and synteny analyses indicated that the all current teleost genomes lack KLKB1, and its unique protein structure, four apple domains and one trypsin domain, could not be identified in any genome or nucleotide databases. We identified some KLK-like proteins in teleost genomes by synteny and conserved domain analyses, which could be the orthologs of tetrapod KLKs. A radioimmunoassay system was established to measure the teleost BK and we found that [Arg(0]-BK is the major circulating form instead of BK, which supports that the teleost KKS is similar to the mammalian tissue KKS. Coincidently, coelacanths are the earliest vertebrate that possess both HMW KNG and KLKB1, which implies that the plasma KKS could have evolved in the early lobe-finned fish and descended to the tetrapod lineage. The co-evolution of HMW KNG and KLKB1 in lobe-finned fish and early tetrapods may mark the emergence of the plasma KKS and a contact activation system in blood coagulation, while teleosts may have retained a single KKS cascade.

  8. Differential NF-κB and MAPK activation underlies fluoride- and TPA-mediated CXCL8 (IL-8 induction in lung epithelial cells

    Directory of Open Access Journals (Sweden)

    Refsnes M

    2014-12-01

    Full Text Available Magne Refsnes, Tonje Skuland, Marit Låg, Per E Schwarze, Johan Øvrevik Department of Air Pollution and Noise, Division of Environmental Medicine, Norwegian Institute of Public Health, Oslo, Norway Abstract: Different toxic agents have a varying potential to induce the production of the proinflammatory chemokine, CXCL8 (interleukin [IL]-8, in lung cells. A critical question is which mechanisms determine the magnitude and persistence of the CXCL8 responses to different stimuli. To approach this, we compared the potential of the phorbol ester, 12-O-tetradecanoylphorbol-13-acetate (TPA, and sodium fluoride (NaF to induce CXCL8 responses in A549 cells, with emphasis on the importance of nuclear factor kappa B (NF-κB- and mitogen-activated protein kinase (MAPK signaling. Notably, TPA induced a greater release of CXCL8 than did NaF. Furthermore, TPA induced a strong, rapid, but transient upregulation of CXCL8 messenger (mRNA, whereas NaF induced a weaker, more delayed, but persistent upregulation. With respect to signaling, TPA led to an early, strong, and relatively transient extracellular signal-regulated kinase (ERK1/2 phosphorylation, and a less marked and even more transient phosphorylation of c-jun-N-terminal kinases (JNK1/2 and p38. In contrast, NaF elicited a lower, but relatively sustained increase in phosphorylation of ERK1/2, and a marked phosphorylation of p38 and JNK1/2, with the JNK1/2 response as most transient. Only ERK1/2 inhibition affected the TPA response, whereas inhibition of all the three MAPK cascades reduced NaF-induced CXCL8 release. TPA also induced an early, marked phosphorylation/translocation of p65 (NF-κB, whereas NaF induced slower, less pronounced effects on p65. The CXCL8 responses by TPA and NaF were reduced by p65-siRNA. In conclusion, all MAPK cascades were involved in NaF-induced CXCL8 release, whereas only ERK1/2 activation was involved in response to TPA. Furthermore, NF-κB activation appeared to be

  9. 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

  10. Impact of MAPK Pathway Activation in BRAFV600 Melanoma on T Cell and Dendritic Cell Function

    Directory of Open Access Journals (Sweden)

    Patrick A. Ott

    2013-10-01

    Full Text Available Constitutive upregulation of the MAPK pathway by a BRAFV600 mutation occurs in about half of melanomas. This leads to increased oncogenic properties such as tumor cell invasion, metastatic potential, and resistance to apoptosis. Blockade of the MAPK pathway with highly specific kinase inhibitors induces unprecedented tumor response rates in patients with advanced BRAFV600 mutant melanoma. Immune checkpoint blockade with monoclonal antibodies targeting cytotoxic T-lymphocyte antigen 4 and programed death-1/PD-L1 has also demonstrated striking anti-tumor activity in patients with advanced melanoma. Tumor responses are likely limited by multiple additional layers of immune suppression in the tumor microenvironment. There is emerging preclinical and clinical evidence suggesting that MAPK inhibition has a beneficial effect on the immunosuppressive tumor microenvironment, providing a strong rationale for combined immunotherapy and MAPK pathway inhibition in melanoma. The T cell response has been the main focus in the studies reported to date. Since dendritic cells (DCs are important in the induction of tumor-specific T cell responses, the impact of MAPK pathway activation in melanoma on DC function is critical for the melanoma directed immune response. BRAFV600E melanoma cells modulate DCs through the MAPK pathway because its blockade in melanoma cells can reverse suppression of DC function. As both MEK/BRAF inhibition and immune checkpoint blockade have recently taken center stage in the treatment of melanoma, a deeper understanding of how MAPK pathway inhibition affects the tumor immune response is needed.

  11. Lung development requires an active ERK/MAPK pathway in the lung mesenchyme.

    Science.gov (United States)

    Boucherat, Olivier; Landry-Truchon, Kim; Aoidi, Rifdat; Houde, Nicolas; Nadeau, Valérie; Charron, Jean; Jeannotte, Lucie

    2017-01-01

    Reciprocal epithelial-mesenchymal communications are critical throughout lung development, dictating branching morphogenesis and cell specification. Numerous signaling molecules are involved in these interactions, but the way epithelial-mesenchymal crosstalk is coordinated remains unclear. The ERK/MAPK pathway transduces several important signals in lung formation. Epithelial inactivation of both Mek genes, encoding ERK/MAPK kinases, causes lung agenesis and death. Conversely, Mek mutation in mesenchyme results in lung hypoplasia, trachea cartilage malformations, kyphosis, omphalocele, and death. Considering the negative impact of kyphosis and omphalocele on intrathoracic space and, consequently, on lung growth, the exact role of ERK/MAPK pathway in lung mesenchyme remains unresolved. To address the role of the ERK/MAPK pathway in lung mesenchyme in absence of kyphosis and omphalocele, we used the Tbx4 Cre deleter mouse line, which acts specifically in lung mesenchyme. These Mek mutants did not develop kyphosis and omphalocele but they presented lung hypoplasia, tracheal defects, and neonatal death. Tracheal cartilage anomalies suggested a role for the ERK/MAPK pathway in the control of chondrocyte hypertrophy. Moreover, expression data indicated potential interactions between the ERK/MAPK and canonical Wnt pathways during lung formation. Lung development necessitates a functional ERK/MAPK pathway in the lung mesenchymal layer in order to coordinate efficient epithelial-mesenchymal interactions. Developmental Dynamics 246:72-82, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  12. Data on the phosphorylation of p38MAPK and JNK induced by chlorpyrifos in Drosophila melanogaster

    Directory of Open Access Journals (Sweden)

    J.E.S. Batista

    2016-12-01

    Full Text Available Exposure to organophosphate compounds, such as chlorpyrifos, has been linked to disturbances on cell signaling pathways. Mitogen activated protein kinases (MAPK are a family of protein kinases involved in a range of cellular processes, including stress response, apoptosis and survival. Therefore, changes in the activation state of these kinases may characterize key mechanisms of toxicity elicited by xenobiotics. Here we report data on the phosphorylation of p38MAPK and JNK, members of the MAPK family, in Drosophila melanogaster exposed to chlorpyrifos, as characterized by western blotting assays.

  13. Involvement of the OsMKK4-OsMPK1 Cascade and its Downstream Transcription Factor OsWRKY53 in the Wounding Response in Rice

    Directory of Open Access Journals (Sweden)

    Seung Jin Yoo

    2014-06-01

    Full Text Available Plant has possessed diverse stress signals from outside and maintained its fitness. Out of such plant responses, it is well known that mitogen-activated protein kinase (MAPK cascade plays important role in wounding and pathogen attack in most dicot plants. However, little is understood about its role in wounding response for the economically important monocot rice plant. In this study, therefore, the involvement of MAPK was investigated to understand the wounding signaling pathway in rice. The OsMPK1 was rapidly activated by wounding within 10 min, and OsMPK1 was also activated by challenge of rice blast fungus. Further analysis revealed that OsMKK4, the upstream kinase of OsMPK1, phosphorylated OsMPK1 by wounding in vivo. Furthermore, OsMPK1 directly interacted with a rice defense-related transcription factor OsWRKY53. To understand a functional link between MAPK and its target transcription factor, we showed that OsMPK1 activated by the constitutively active mutant OsMKK4DD phosphorylated OsWRKY53 in vitro. Taken together, components involving in the wounding signaling pathway, OsMKK4-OsMPK1-OsWRKY53, can be important players in regulating crosstalk between abiotic stress and biotic stress.

  14. Tunable Optical Filter Based on Mechanically Induced Cascaded Long Period Optical Fiber Grating

    Directory of Open Access Journals (Sweden)

    Sunita P. Ugale

    2013-01-01

    Full Text Available We have proposed and demonstrated experimentally a novel and simple tunable optical filter based on mechanically induced and cascaded long period optical fiber gratings. In this filter variable FWHM and center wavelength is provided by cascading long period and ultralong period optical fiber gratings with different periods in a novel fiber structure. We report here for the first time to our knowledge the characterization of mechanically induced long period fiber gratings with periods up to several millimeters in novel multimode-single-mode-multimode fiber structure. We have obtained maximum loss peak of around 20 dB.

  15. HOMFLYPT polynomial is the best quantifier for topological cascades of vortex knots

    Science.gov (United States)

    Ricca, Renzo L.; Liu, Xin

    2018-02-01

    In this paper we derive and compare numerical sequences obtained by adapted polynomials such as HOMFLYPT, Jones and Alexander-Conway for the topological cascade of vortex torus knots and links that progressively untie by a single reconnection event at a time. Two cases are considered: the alternate sequence of knots and co-oriented links (with positive crossings) and the sequence of two-component links with oppositely oriented components (negative crossings). New recurrence equations are derived and sequences of numerical values are computed. In all cases the adapted HOMFLYPT polynomial proves to be the best quantifier for the topological cascade of torus knots and links.

  16. New quantum cascade laser sources for sensing applications (Conference Presentation)

    Science.gov (United States)

    Troccoli, Mariano

    2017-05-01

    In this presentation we will review our most recent results on development of Quantum Cascade Lasers (QCLs) for analytical and industrial applications. QCLs have demonstrated the capability to cover the entire range of Mid-IR, Far-IR, and THz wavelengths by skillful tuning of the material design and composition and by use of intrinsic material properties via a set of techniques collectively called "bandgap engineering". The use of MOCVD, pioneered on industrial scale by AdTech Optics, has enabled the deployment of QCL devices into a diverse range of environments and applications. QCLs can be tailored to the specific application requirements due to their unprecedented flexibility in design and thanks to the leveraging of well-known III-V fabrication technologies inherited from the NIR domain. Nevertheless, several applications and new frontiers in R and D need the constant support of new developments in device features, capabilities, and performances. We have developed a wide range of devices, from high power, high efficiency multi-mode sources, to narrow-band, single mode devices with low-power consumption, and from non-linear, multi-wavelength generating devices to broadband sources and multi-emitter arrays. All our devices are grown and processed using MOCVD technology and allow us to attain competitive performances across the whole mid-IR spectral range. This talk will present an overview of our current achievements. References 1. M. Troccoli, "High power emission and single mode operation of quantum cascade lasers for industrial applications", J. Sel. Topics in Quantum Electron., 21 (6), 1-7 (2015). Invited Review. 2. Seungyong Jung, Aiting Jiang, Yifan Jiang, Karun Vijayraghavan, Xiaojun Wang, Mariano Troccoli, and Mikhail A. Belkin, "Broadly Tunable Monolithic Terahertz Quantum Cascade Laser Sources", Nature Comm. 5, 4267 (2014).. 3. Mariano Troccoli, Arkadiy Lyakh, Jenyu Fan, Xiaojun Wang, Richard Maulini, Alexei G Tsekoun, Rowel Go, C Kumar N Patel, "Long

  17. CDK and MAPK Synergistically Regulate Signaling Dynamics via a Shared Multi-site Phosphorylation Region on the Scaffold Protein Ste5.

    Science.gov (United States)

    Repetto, María Victoria; Winters, Matthew J; Bush, Alan; Reiter, Wolfgang; Hollenstein, David Maria; Ammerer, Gustav; Pryciak, Peter M; Colman-Lerner, Alejandro

    2018-03-15

    We report an unanticipated system of joint regulation by cyclin-dependent kinase (CDK) and mitogen-activated protein kinase (MAPK), involving collaborative multi-site phosphorylation of a single substrate. In budding yeast, the protein Ste5 controls signaling through a G1 arrest pathway. Upon cell-cycle entry, CDK inhibits Ste5 via multiple phosphorylation sites, disrupting its membrane association. Using quantitative time-lapse microscopy, we examined Ste5 membrane recruitment dynamics at different cell-cycle stages. Surprisingly, in S phase, where Ste5 recruitment should be blocked, we observed an initial recruitment followed by a steep drop-off. This delayed inhibition revealed a requirement for both CDK activity and negative feedback from the pathway MAPK Fus3. Mutagenesis, mass spectrometry, and electrophoretic analyses suggest that the CDK and MAPK modify shared sites, which are most extensively phosphorylated when both kinases are active and able to bind their docking sites on Ste5. Such collaborative phosphorylation can broaden regulatory inputs and diversify output dynamics of signaling pathways. Copyright © 2018 Elsevier Inc. All rights reserved.

  18. Epidemic and Cascading Survivability of Complex Networks

    DEFF Research Database (Denmark)

    Manzano, Marc; Calle, Eusebi; Ripoll, Jordi

    2014-01-01

    Our society nowadays is governed by complex networks, examples being the power grids, telecommunication networks, biological networks, and social networks. It has become of paramount importance to understand and characterize the dynamic events (e.g. failures) that might happen in these complex...... networks. For this reason, in this paper, we propose two measures to evaluate the vulnerability of complex networks in two different dynamic multiple failure scenarios: epidemic-like and cascading failures. Firstly, we present epidemic survivability ( ES ), a new network measure that describes...... the vulnerability of each node of a network under a specific epidemic intensity. Secondly, we propose cascading survivability ( CS ), which characterizes how potentially injurious a node is according to a cascading failure scenario. Then, we show that by using the distribution of values obtained from ES and CS...

  19. 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.)

  20. 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.

  1. Nitric oxide mediates the indole acetic acid induction activation of a mitogen-activated protein kinase cascade involved in adventitious root development.

    Science.gov (United States)

    Pagnussat, Gabriela Carolina; Lanteri, María Luciana; Lombardo, María Cristina; Lamattina, Lorenzo

    2004-05-01

    Recently, it was demonstrated that nitric oxide (NO) and cGMP are involved in the auxin response during the adventitious rooting process in cucumber (Cucumis sativus; Pagnussat et al., 2002, 2003). However, not much is known about the complex molecular network operating during the cell proliferation and morphogenesis triggered by auxins and NO in that process. Anatomical studies showed that formation of adventitious root primordia was clearly detected in indole acetic acid (IAA)- and NO-treated cucumber explants, while neither cell proliferation nor differentiation into root primordia could be observed in control explants 3 d after primary root was removed. In order to go further with signal transduction mechanisms that operate during IAA- and NO-induced adventitious root formation, experiments were designed to test the involvement of a mitogen-activated protein kinase (MAPK) cascade in that process. Cucumber explants were treated with the NO-donor sodium nitroprusside (SNP) or with SNP plus the specific NO-scavenger cPTIO. Protein extracts from those explants were assayed for protein kinase (PK) activity by using myelin basic protein (MBP) as substrate in both in vitro and in-gel assays. The activation of a PK of approximately 48 kD could be detected 1 d after NO treatment with a maximal activation after 3 d of treatment. In control explants, a PK activity was detected only after 4 d of treatment. The MBP-kinase activity was also detected in extracts from IAA-treated explants, while no signal was observed in IAA + cPTIO treatments. The PK activity could be inhibited by the cell-permeable MAPK kinase inhibitor PD098059, suggesting that the NO-dependent MBP-kinase activity is a MAPK. Furthermore, when PD098059 was administered to explants treated with SNP or IAA, it produced a delay in root emergence and a dose-dependent reduction in root number. Altogether, our results suggest that a MAPK signaling cascade is activated during the adventitious rooting process

  2. Piscivores, Trophic Cascades, and Lake Management

    Directory of Open Access Journals (Sweden)

    Ray W. Drenner

    2002-01-01

    Full Text Available The concept of cascading trophic interactions predicts that an increase in piscivore biomass in lakes will result in decreased planktivorous fish biomass, increased herbivorous zooplankton biomass, and decreased phytoplankton biomass. Though often accepted as a paradigm in the ecological literature and adopted by lake managers as a basis for lake management strategies, the trophic cascading interactions hypothesis has not received the unequivocal support (in the form of rigorous experimental testing that might be expected of a paradigm. Here we review field experiments and surveys, testing the hypothesis that effects of increasing piscivore biomass will cascade down through the food web yielding a decline in phytoplankton biomass. We found 39 studies in the scientific literature examining piscivore effects on phytoplankton biomass. Of the studies, 22 were confounded by supplemental manipulations (e.g., simultaneous reduction of nutrients or removal of planktivores and could not be used to assess piscivore effects. Of the 17 nonconfounded studies, most did not find piscivore effects on phytoplankton biomass and therefore did not support the trophic cascading interactions hypothesis. However, the trophic cascading interactions hypothesis also predicts that lake systems containing piscivores will have lower phytoplankton biomass for any given phosphorus concentration. Based on regression analyses of chlorophyll�total phosphorus relationships in the 17 nonconfounded piscivore studies, this aspect of the trophic cascading interactions hypothesis was supported. The slope of the chlorophyll vs. total phosphorus regression was lower in lakes with planktivores and piscivores compared with lakes containing only planktivores but no piscivores. We hypothesize that this slope can be used as an indicator of “functional piscivory” and that communities with extremes of functional piscivory (zero and very high represent classical 3- and 4-trophic level

  3. 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

  4. Dynamics of soliton cascades in fiber amplifiers.

    Science.gov (United States)

    Arteaga-Sierra, F R; Antikainen, A; Agrawal, Govind P

    2016-11-15

    We study numerically the formation of cascading solitons when femtosecond optical pulses are launched into a fiber amplifier with less energy than required to form a soliton of equal duration. As the pulse is amplified, cascaded fundamental solitons are created at different distances, without soliton fission, as each fundamental soliton moves outside the gain bandwidth through the Raman-induced spectral shifts. As a result, each input pulse creates multiple, temporally separated, ultrashort pulses of different wavelengths at the amplifier output. The number of pulses depends not only on the total gain of the amplifier but also on the width of the input pulse.

  5. 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.

  6. Abnormal circadian oscillation of hippocampal MAPK activity and power spectrums in NF1 mutant mice.

    Science.gov (United States)

    Chen, Lei; Serdyuk, Tatiana; Yang, Beimeng; Wang, Shuai; Chen, Shiqing; Chu, Xixia; Zhang, Xu; Song, Jinjing; Bao, Hechen; Zhou, Chengbin; Wang, Xiang; Dong, Shuangle; Song, Lulu; Chen, Fujun; He, Guang; He, Lin; Zhou, Ying; Li, Weidong

    2017-07-03

    Studies have implied that the circadian oscillation of mitogen-activated protein kinase (MAPK) signal pathways is crucial for hippocampus-dependent memory. NF1 mouse models (Nf1 heterozygous null mutants; Nf1 +/- ) displayed enhanced MAPK activity in the hippocampus and resulted in memory deficits. We assumed a link between MAPK pathways and hippocampal rhythmic oscillations, which have never been explored in Nf1 +/- mice. We demonstrated that the level of extracellular signal-regulated kinases 1 and 2 (ERK1/2) phosphorylation in Nf1 +/- mice were significantly higher at nighttime than at daytime. Moreover, the in vivo recording revealed that for the Nf1 +/- group, the power spectral density of theta rhythm significantly decreased and the firing rates of pyramidal neurons increased. Our results indicated that the hippocampal MAPK oscillation and theta rhythmic oscillations in Nf1 +/- mice were disturbed and hinted about a possible mechanism for the brain dysfunction in Nf1 +/- mice.

  7. RasGRP3 Mediates MAPK Pathway Activation in GNAQ Mutant Uveal Melanoma.

    Science.gov (United States)

    Chen, Xu; Wu, Qiuxia; Depeille, Philippe; Chen, Peirong; Thornton, Sophie; Kalirai, Helen; Coupland, Sarah E; Roose, Jeroen P; Bastian, Boris C

    2017-05-08

    Constitutive activation of Gαq signaling by mutations in GNAQ or GNA11 occurs in over 80% of uveal melanomas (UMs) and activates MAPK. Protein kinase C (PKC) has been implicated as a link, but the mechanistic details remained unclear. We identified PKC δ and ɛ as required and sufficient to activate MAPK in GNAQ mutant melanomas. MAPK activation depends on Ras and is caused by RasGRP3, which is significantly and selectively overexpressed in response to GNAQ/11 mutation in UM. RasGRP3 activation occurs via PKC δ- and ɛ-dependent phosphorylation and PKC-independent, DAG-mediated membrane recruitment, possibly explaining the limited effect of PKC inhibitors to durably suppress MAPK in UM. The findings nominate RasGRP3 as a therapeutic target for cancers driven by oncogenic GNAQ/11. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Segregation of cascade induced interstitial loops at dislocations: possible effect on initiation of plastic deformation

    Energy Technology Data Exchange (ETDEWEB)

    Trinkaus, H. [Forschungszentrum Juelich GmbH (Germany). Inst. fuer Festkoerperforschung; Singh, B.N. [Materials Research Department, Risoe National Laboratory, DK-4000 Roskilde (Denmark); Foreman, A.J.E. [Materials Performance Department, Harwell Laboratory, Oxfordshire OX11 0RA (United Kingdom)

    1997-11-01

    In metals and alloys subjected to cascade damage dislocations are frequently found to be decorated with a high density of small clusters of self-interstitial atoms (SIAs) in the form of dislocation loops. In the present paper it is shown that this effect may be attributed to the glide and trapping of SIA loops, produced directly in cascades (rather than to the enhanced agglomeration of single SIAs), in the strain field of the dislocations. The conditions for the accumulation of glissile SIA loops near dislocations as well as the dose and temperature dependencies of this phenomenon are discussed. It is suggested that the decoration of dislocations with loops may play a key role in radiation hardening subjected to cascade damage. It is shown, for example, that the increase in the upper yield stress followed by a yield drop and plastic instability in metals andalloys subjected to cascade damage cannot be rationalized in terms of conventional dispersed barrier hardening (DBH) but may be understood in terms of cascade induced source hardening (CISH) in which the dislocations are considered to be locked by the loops decorating them. Estimates for the stress necessary to pull a dislocation away from its loop `cloud` are used to discuss the dose and temperature dependence of plastic flow initiation. (orig.). 55 refs.

  9. Segregation of cascade induced interstitial loops at dislocations: possible effect on initiation of plastic deformation

    International Nuclear Information System (INIS)

    Trinkaus, H.; Foreman, A.J.E.

    1997-01-01

    In metals and alloys subjected to cascade damage dislocations are frequently found to be decorated with a high density of small clusters of self-interstitial atoms (SIAs) in the form of dislocation loops. In the present paper it is shown that this effect may be attributed to the glide and trapping of SIA loops, produced directly in cascades (rather than to the enhanced agglomeration of single SIAs), in the strain field of the dislocations. The conditions for the accumulation of glissile SIA loops near dislocations as well as the dose and temperature dependencies of this phenomenon are discussed. It is suggested that the decoration of dislocations with loops may play a key role in radiation hardening subjected to cascade damage. It is shown, for example, that the increase in the upper yield stress followed by a yield drop and plastic instability in metals andalloys subjected to cascade damage cannot be rationalized in terms of conventional dispersed barrier hardening (DBH) but may be understood in terms of cascade induced source hardening (CISH) in which the dislocations are considered to be locked by the loops decorating them. Estimates for the stress necessary to pull a dislocation away from its loop 'cloud' are used to discuss the dose and temperature dependence of plastic flow initiation. (orig.)

  10. Essential roles of Cdc42 and MAPK in cadmium-induced apoptosis in Litopenaeus vannamei

    International Nuclear Information System (INIS)

    Peng, Ting; Wang, Wei-Na; Gu, Mei-Mei; Xie, Chen-Ying; Xiao, Yu-Chao; Liu, Yuan; Wang, Lei

    2015-01-01

    Highlights: • Cd 2+ induces Cdc42 and MAPKs pathway related gene of Litopenaeus vannamei up-regulation. • Reduction of THC, increase of ROS production and apoptotic cell rate were observed when the shrimps exposure to Cd 2+ . • DsRNA-suppression of LvCdc42 and MAPKs during Cd 2+ stress reduces the ROS production and apoptosis. • We conclude that LvCdc42 and MAPKs play key roles in Cd 2+ stress responses of shrimps. - Abstract: Cadmium, one of the most toxic heavy metals in aquatic environments, has severe effects on marine invertebrates and fishes. The MAPK signaling pathway plays a vital role in stress responses of animals. The mitogen-activated protein kinase (MAPK) signaling pathway plays a vital role in animals’ stress responses, including mediation of apoptosis induced by the Rho GTPase Cdc42. However, there is limited knowledge about its function in shrimps, although disorders exacerbated by environmental stresses (including heavy metal pollution) have caused serious mortality in commercially cultured shrimps. Thus, we probed roles of Cdc42 in Litopenaeus vannamei shrimps (LvCdc42) during cadmium exposure by inhibiting its expression using dsRNA-mediated RNA interference. The treatment successfully reduced expression levels of MAPKs (including p38, JNK, and ERK). Cadmium exposure induced significant increases in expression levels of LvCdc42 and MAPKs, accompanied by reductions in total hemocyte counts (THC) and increases in apoptotic hemocyte ratios and ROS production. However, all of these responses were much weaker in LvCdc42-suppressed shrimps, in which mortality rates were higher than in controls. Our results suggest that the MAPK pathway plays a vital role in shrimps’ responses to Cd 2+ . They also indicate that LvCdc42 in shrimps participates in its regulation, and thus plays key roles in ROS production, regulation of apoptosis and associated stress responses

  11. 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

  12. The relationship between p38MAPK and apoptosis during paclitaxel resistance of ovarian cancer cells.

    Science.gov (United States)

    Lu, Meisong; Xiao, Lan; Li, Zhimin

    2007-12-01

    To investigate the relationship between p38 mitogen-activated protein kinase (p38MAPK) and cell apoptosis during the paclitaxel resistance of ovarian carcinoma cell lines, flow cytometry (FCM) and PI staining were employed to determine the effect of p38MAPK inhibitor SB203580 on the apoptosis of A2780/Taxol cells, a drug-resistant human ovarian carcinoma cell line. p38MAPK protein expression in SB203580-treated cells was immunochemically measured. The 50% inhibition concentration (IC(50)) of paclitaxel on A2780/Taxol cells was determined by MTT assay. MDR-1 mRNA, and expression of p38MAPK and phospho-p53 protein were detected by RT-PCR and Western blotting, respectively. The apoptosis rate of A2780/Taxol cells was (19.7+/-1.04)% 24 h after SB203580 treatment. A significant difference in apoptosis rate was found among experiment group, control group and untreated group (Pp53 protein was significantly increased. It is concluded that p38MAPK pathway is related to paclitaxel resistance of ovarian carcinoma, and blockade of this pathway can promote the apoptosis of the drug-resistant cells and reverse the drug-resistance. Moreover, p38MAPK-mediated apoptosis in paclitaxel-resistant ovarian carcinoma cells depends on the activation of p53.

  13. EDITORIAL A CASCADE OF BIOCHEMICAL AND PHYSIOLOGICAL ...

    African Journals Online (AJOL)

    pharm-chem

    A CASCADE OF BIOCHEMICAL AND PHYSIOLOGICAL MARKERS IN PATHOLOGICAL. DISORDERS. A few years ago, a neurophysiology lecturer in the Department of Medical Physiology, University of. Nairobi, was doing ... from haemolysis of RBC is rapidly distributed into cells and excreted in kidney. It would have been.

  14. 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

  15. Dynamics of cascade processes of muonic atoms

    International Nuclear Information System (INIS)

    Kalantari, Z.; Pirahmadian, M. H.; Ebrahimi, A.

    2006-01-01

    Studies on exotic atoms are important in different ways. They are important for strong interaction with nucleus and the theory of QCD in low energies. They are also important in muon catalyzed fusion. Their properties can be revealed by studies on cascade of muonic atoms. In this paper, unlike the others, we do not consider the kinetic energy of muonic atoms, constant (the kinetic energy of muonic atoms can vary due to cascade processes). We have used multi group method. The energy dependence of the rates of collisional cascade processes can take into account by this method. In addition, the energy spectra of muonic atoms in the ground state are calculated. For this purpose we divided the energy spectrum to 10 groups, and then use the rate of external Auger effect, Coulomb de-excitation, muon transfer and elastic scattering to solve the dynamics of cascade processes in each group. These equations are coupled linear differential equations. To solve them we use the Runge-Kutta method in the fourth order. One of the conclusions of this paper is that, this energy spectrum is not Maxwellian distribution. Finally our results are compared with the results of the Monte-Carlo simulation.

  16. Geothermal research, Oregon Cascades: Final technical report

    Energy Technology Data Exchange (ETDEWEB)

    Priest, G.R.; Black, G.L.

    1988-10-27

    Previous USDOE-funded geothermal studies have produced an extensive temperature gradient and heat flow data base for the State of Oregon. One of the important features identified as a result of these studies is a rapid transition from heat flow values on the order of 40 mW/m/sup 2/ in the Willamette Valley and Western Cascades to values of greater than or equal to100 mW/m/sup 2/ in the High Cascades and the eastern portion of the Western Cascades. These data indicate that the Cascade Range in Oregon has potential as a major geothermal province and stimulated much of the later work completed by government agencies and private industry. Additional data generated as a result of this grant and published in DOGAMI Open-File Report 0-86-2 further define the location and magnitude of this transition zone. In addition, abundant data collected from the vicinity of Breitenbush and Austin Hot Springs have permitted the formulation of relatively detailed models of these hydrothermal systems. These models are published in DOGAMI Open-File Report 0-88-5. Task 1.2 of the Deliverables section of Amendment M001 is fulfilled by DOGAMI publication GMS-48, Geologic map of the McKenzie Bridge quadrangle, Lane County, Oregon. This map was printed in October, 1988, and is part of the final submission to USDOE. 8 refs.

  17. MID-INFRARED QUANTUM CASCADE LASERS

    African Journals Online (AJOL)

    2012-11-03

    Nov 3, 2012 ... Abstract. Quantum cascade lasers (QCL) based on intersubband transitions operating at room temperature in the mid-infrared or 'molecular fingerprint' spectral region (3.4–17 im) have been found useful for several applications including environmental sensing, pollution monitoring, and medical appli-.

  18. Population analysis for atomic cascade decay processes

    International Nuclear Information System (INIS)

    Suto, Keiko; Kagawa, Takashi; Futaba, Kaoru

    1998-01-01

    Down-stream cascade decay processes in atomic systems are analyzed by solving a coupled rate equation for which an analytical solution for a population in each excited state is obtained. Some typical numerical examples for populations to interpret the decay passes connecting to features of optical or electron spectra observed in various collision experiments are also given. (author)

  19. Robustness of interrelated traffic networks to cascading failures.

    Science.gov (United States)

    Su, Zhen; Li, Lixiang; Peng, Haipeng; Kurths, Jürgen; Xiao, Jinghua; Yang, Yixian

    2014-06-24

    The vulnerability to real-life networks against small initial attacks has been one of outstanding challenges in the study of interrelated networks. We study cascading failures in two interrelated networks S and B composed from dependency chains and connectivity links respectively. This work proposes a realistic model for cascading failures based on the redistribution of traffic flow. We study the Barabási-Albert networks (BA) and Erdős-Rényi graphs (ER) with such structure, and found that the efficiency sharply decreases with increasing percentages of the dependency nodes for removing a node randomly. Furthermore, we study the robustness of interrelated traffic networks, especially the subway and bus network in Beijing. By analyzing different attacking strategies, we uncover that the efficiency of the city traffic system has a non-equilibrium phase transition at low capacity of the networks. This explains why the pressure of the traffic overload is relaxed by singly increasing the number of small buses during rush hours. We also found that the increment of some buses may release traffic jam caused by removing a node of the bus network randomly if the damage is limited. However, the efficiencies to transfer people flow will sharper increase when the capacity of the subway network α(S) > α0.

  20. Temperature insensitive curvature sensor based on cascading photonic crystal fiber

    Science.gov (United States)

    Fu, Guangwei; Li, Yunpu; Fu, Xinghu; Jin, Wa; Bi, Weihong

    2018-03-01

    A temperature insensitive curvature sensor is proposed based on cascading photonic crystal fiber. Using the arc fusion splicing method, this sensor is fabricated by cascading together a single-mode fiber (SMF), a three layers air holes structure of photonic crystal fiber (3PCF), a five layers air holes structure of photonic crystal fiber (5PCF) and a SMF in turn. So the structure SMF-3PCF-5PCF-SMF can be obtained with a total length of 20 mm. During the process of fabrication, the splicing machine parameters and the length of each optical fiber are adjusted to obtain a high sensitivity curvature sensor. The experimental results show that the curvature sensitivity is -8.40 nm/m-1 in the curvature variation range of 0-1.09 m-1, which also show good linearity. In the range of 30-90 °C, the temperature sensitivity is only about 3.24 pm/°C, indicating that the sensor is not sensitive to temperature. The sensor not only has the advantages of easy fabricating, simple structure, high sensitivity but also can solve the problem of temperature measurement cross sensitivity, so it can be used for different areas including aerospace, large-scale bridge, architectural structure health monitoring and so on.

  1. Diabetic Zucker rat Tibialis anterior muscle high-frequency electrical stimulation (HFES data: Regulation of MAPKs associated proteins

    Directory of Open Access Journals (Sweden)

    Gautam K. Ginjupalli

    2018-02-01

    Full Text Available Anaerobic exercise has been advocated as a prescribed treatment for the management of diabetes: however, alterations in exercise-induced signaling remain largely unexplored in the diabetic muscle. Here, we compare the basal and the in situ contraction-induced phosphorylation of the mitogen-activated protein kinases (MAPKs ERK 1/2, p38, and JNK in the lean and obese (fa/fa Zucker rat tibialus anterior (TA muscle following a single bout of contractile stimuli. This article represents data associated with prior publications from our lab (Katta et al., 2009, Katta et al., 2009, Tullgren et al., 1991 [1–3] and concurrent Data in Brief articles (Ginjupalli et al., 2017, Rice et al., 2017, Rice et al., 2017, Rice et al., 2017 [4–7].

  2. 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.

  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. Hollow Anode Cascading Plasma Focus | Alabraba | Journal of the ...

    African Journals Online (AJOL)

    Using the 3-phase model for each focus event, the 9-phase, two solid disc auxiliary anode cascading plasma focus has been extended to include holes at the center of each cascade anode (hereafter referred to as hollow anode cascading focus) with a view of increasing the neutron yield with each focus event. Results ...

  5. Linear B-cell epitope mapping of MAPK3 and MAPK4 from Leishmania braziliensis: implications for the serodiagnosis of human and canine leishmaniasis.

    Science.gov (United States)

    Menezes-Souza, Daniel; de Oliveira Mendes, Tiago Antônio; de Araújo Leão, Ana Carolina; de Souza Gomes, Matheus; Fujiwara, Ricardo Toshio; Bartholomeu, Daniella Castanheira

    2015-02-01

    The correct and early identification of humans and dogs infected with Leishmania are key steps in the control of leishmaniasis. Additionally, a method with high sensitivity and specificity at low cost that allows the screening of a large number of samples would be extremely valuable. In this study, we analyzed the potential of mitogen-activated protein kinase 3 (MAPK3) and mitogen-activated protein kinase 4 (MAPK4) proteins from Leishmania braziliensis to serve as antigen candidates for the serodiagnosis of human visceral and tegumentary leishmaniasis, as well as canine visceral disease. Moreover, we mapped linear B-cell epitopes in these proteins and selected those epitopes with sequences that were divergent in the corresponding orthologs in Homo sapiens, in Canis familiaris, and in Trypanosoma cruzi. We compared the performance of these peptides with the recombinant protein using ELISA. Both MAPK3 and MAPK4 recombinant proteins showed better specificity in the immunodiagnosis of human and canine leishmaniasis than soluble parasite antigens and the EIE-leishmaniose-visceral-canina-bio-manguinhos (EIE-LVC) kit. Furthermore, the performance of this serodiagnosis assay was improved using synthetic peptides corresponding to B-cell epitopes derived from both proteins.

  6. Up-regulation of COX-2/PGE2 by endothelin-1 via MAPK-dependent NF-κB pathway in mouse brain microvascular endothelial cells

    Directory of Open Access Journals (Sweden)

    Lin Chih-Chung

    2013-01-01

    Full Text Available Abstract Background Endothelin-1 (ET-1 is a proinflammatory mediator and elevated in the regions of several brain injury and inflammatory diseases. The deleterious effects of ET-1 on endothelial cells may aggravate brain inflammation mediated through the regulation of cyclooxygenase-2 (COX-2/prostaglandin E2 (PGE2 system in various cell types. However, the signaling mechanisms underlying ET-1-induced COX-2 expression in brain microvascular endothelial cells remain unclear. Herein we investigated the effects of ET-1 in COX-2 regulation in mouse brain microvascular endothelial (bEnd.3 cells. Results The data obtained with Western blotting, RT-PCR, and immunofluorescent staining analyses showed that ET-1-induced COX-2 expression was mediated through an ETB-dependent transcriptional activation. Engagement of Gi- and Gq-protein-coupled ETB receptors by ET-1 led to phosphorylation of ERK1/2, p38 MAPK, and JNK1/2 and then activated transcription factor NF-κB. Moreover, the data of chromatin immunoprecipitation (ChIP and promoter reporter assay demonstrated that the activated NF-κB was translocated into nucleus and bound to its corresponding binding sites in COX-2 promoter, thereby turning on COX-2 gene transcription. Finally, up-regulation of COX-2 by ET-1 promoted PGE2 release in these cells. Conclusions These results suggested that in mouse bEnd.3 cells, activation of NF-κB by ETB-dependent MAPK cascades is essential for ET-1-induced up-regulation of COX-2/PGE2 system. Understanding the mechanisms of COX-2 expression and PGE2 release regulated by ET-1/ETB system on brain microvascular endothelial cells may provide rationally therapeutic interventions for brain injury or inflammatory diseases.

  7. Hepatoprotective Role of Hydrangea macrophylla against Sodium Arsenite-Induced Mitochondrial-Dependent Oxidative Stress via the Inhibition of MAPK/Caspase-3 Pathways

    Directory of Open Access Journals (Sweden)

    Md Rashedunnabi Akanda

    2017-07-01

    Full Text Available Sodium arsenite (NaAsO2 has been recognized as a worldwide health concern. Hydrangea macrophylla (HM is used as traditional Chinese medicine possessing antioxidant activities. The study was performed to investigate the therapeutic role and underlying molecular mechanism of HM on NaAsO2-induced toxicity in human liver cancer (HepG2 cells and liver in mice. The hepatoprotective role of HM in HepG2 cells was assessed by using 3-(4,5-dimethylthiazol-2-Yl-2,5-diphenyltetrazolium bromide (MTT, reactive oxygen species (ROS, and lactate dehydrogenase (LDH assays. Histopathology, lipid peroxidation, serum biochemistry, quantitative real-time polymerase chain reaction (qPCR and Western blot analyses were performed to determine the protective role of HM against NaAsO2 intoxication in liver tissue. In this study, we found that co-treatment with HM significantly attenuated the NaAsO2-induced cell viability loss, intracellular ROS, and LDH release in HepG2 cells in a dose-dependent manner. Hepatic histopathology, lipid peroxidation, and the serum biochemical parameters alanine aminotransferase (ALT and aspartate aminotransferase (AST were notably improved by HM. HM effectively downregulated the both gene and protein expression level of the mitogen-activated protein kinase (MAPK cascade. Moreover, HM well-regulated the Bcl-2-associated X protein (Bax/B-cell lymphoma-2 (Bcl-2 ratio, remarkably suppressed the release of cytochrome c, and blocked the expression of the post-apoptotic transcription factor caspase-3. Therefore, our study provides new insights into the hepatoprotective role of HM through its reduction in apoptosis, which likely involves in the modulation of MAPK/caspase-3 signaling pathways.

  8. MAPK signaling pathway regulates p27 phosphorylation at threonin 187 as part of the mechanism triggered by early-weaning to induce cell proliferation in rat gastric mucosa.

    Directory of Open Access Journals (Sweden)

    Luciana H Osaki

    Full Text Available During rat postnatal development, gastric cell proliferation and differentiation depend on many elements, which include dietary pattern, hormones, growth factors and their signaling pathways. Among them, EGFR activity is increased through MAPK and Src cascades in response to early weaning that represents the abrupt transition from milk to solid food. We herein investigated the direct involvement of ERK pathway in the control of cell cycle progression during early weaning, and studied the specific role of p27. At 15 days, Wistar rats were separated from dams, fed with powdered chow and daily injected with PD98059 (MEK inhibitor, 300 µg/kg or 0.5% DMSO (control. By using HE staining and immunohistochemistry for PCNA, we respectively detected mitotic (MI and proliferative (PI indices in 18-day-old pups, and observed that both were reduced by PD98059. As cell cycle-related proteins (cyclin E, CDK2, cyclin D1, CDK4, p21 and p27 are involved in proliferative regulation, we compared samples obtained at 17 days in the morning (17 d and evening (17.5 d. We found that they were not altered after ERK inhibition, but cyclin D1, p21 and p27 levels changed throughout the day in the control group. As p27 activity depends on its integrity, we studied p27 phosphorylation (threonin 187, and observed that ERK inhibition reduced this process. We suggest that MAPK pathway interferes in the regulation of p27 function in the gastric mucosa during early weaning, possibly by controlling its degradation, and altogether this mechanism might contribute to the increase of epithelial proliferation at this condition.

  9. Cystatin C is downregulated in prostate cancer and modulates invasion of prostate cancer cells via MAPK/Erk and androgen receptor pathways.

    Science.gov (United States)

    Wegiel, Barbara; Jiborn, Thomas; Abrahamson, Magnus; Helczynski, Leszek; Otterbein, Leo; Persson, Jenny Liao; Bjartell, Anders

    2009-11-23

    Cystatin C is believed to prevent tumor progression by inhibiting the activities of a family of lysosomal cysteine proteases. However, little is known about the precise mechanism of cystatin C function in prostate cancer. In the present study, we examined the expression of cystatin C and its association with matrix metalloproteinases 2 (MMP2) and androgen receptor (AR) in a tissue microarray comparing benign and malignant specimens from 448 patients who underwent radical prostatectomy for localized prostate cancer. Cystatin C expression was significantly lower in cancer specimens than in benign tissues (pcystatin C and MMP2 (r(s) (2) = -0.056, p = 0.05). There was a clear trend that patients with decreased level of cystatin C had lower overall survival. Targeted inhibition of cystatin C using specific siRNA resulted in an increased invasiveness of PC3 cells, whereas induction of cystatin C overexpression greatly reduced invasion rate of PC3 in vitro. The effect of cystatin C on modulating the PC3 cell invasion was provoked by Erk2 inhibitor that specifically inhibited MAPK/Erk2 activity. This suggests that cystatin C may mediate tumor cell invasion by modulating the activity of MAPK/Erk cascades. Consistent with our immunohistochemical findings that patients with low expression of cystatin C and high expression of androgen receptor (AR) tend to have worse overall survival than patients with high expression of cystatin C and high AR expression, induced overexpression of AR in PC3 cells expressing cystatin C siRNA greatly enhanced the invasiveness of PC3 cells. This suggests that there may be a crosstalk between cystatin C and AR-mediated pathways. Our study uncovers a novel role for cystatin C and its associated cellular pathways in prostate cancer invasion and metastasis.

  10. Cystatin C is downregulated in prostate cancer and modulates invasion of prostate cancer cells via MAPK/Erk and androgen receptor pathways.

    Directory of Open Access Journals (Sweden)

    Barbara Wegiel

    Full Text Available Cystatin C is believed to prevent tumor progression by inhibiting the activities of a family of lysosomal cysteine proteases. However, little is known about the precise mechanism of cystatin C function in prostate cancer. In the present study, we examined the expression of cystatin C and its association with matrix metalloproteinases 2 (MMP2 and androgen receptor (AR in a tissue microarray comparing benign and malignant specimens from 448 patients who underwent radical prostatectomy for localized prostate cancer. Cystatin C expression was significantly lower in cancer specimens than in benign tissues (p<0.001 and there was a statistically significant inverse correlation between expression of cystatin C and MMP2 (r(s (2 = -0.056, p = 0.05. There was a clear trend that patients with decreased level of cystatin C had lower overall survival. Targeted inhibition of cystatin C using specific siRNA resulted in an increased invasiveness of PC3 cells, whereas induction of cystatin C overexpression greatly reduced invasion rate of PC3 in vitro. The effect of cystatin C on modulating the PC3 cell invasion was provoked by Erk2 inhibitor that specifically inhibited MAPK/Erk2 activity. This suggests that cystatin C may mediate tumor cell invasion by modulating the activity of MAPK/Erk cascades. Consistent with our immunohistochemical findings that patients with low expression of cystatin C and high expression of androgen receptor (AR tend to have worse overall survival than patients with high expression of cystatin C and high AR expression, induced overexpression of AR in PC3 cells expressing cystatin C siRNA greatly enhanced the invasiveness of PC3 cells. This suggests that there may be a crosstalk between cystatin C and AR-mediated pathways. Our study uncovers a novel role for cystatin C and its associated cellular pathways in prostate cancer invasion and metastasis.

  11. Complement-induced activation of MAPKs and Akt during sepsis: role in cardiac dysfunction.

    Science.gov (United States)

    Fattahi, Fatemeh; Kalbitz, Miriam; Malan, Elizabeth A; Abe, Elizabeth; Jajou, Lawrence; Huber-Lang, Markus S; Bosmann, Markus; Russell, Mark W; Zetoune, Firas S; Ward, Peter A

    2017-09-01

    Polymicrobial sepsis in mice causes myocardial dysfunction after generation of the complement anaphylatoxin, complement component 5a (C5a). C5a interacts with its receptors on cardiomyocytes (CMs), resulting in redox imbalance and cardiac dysfunction that can be functionally measured and quantitated using Doppler echocardiography. In this report we have evaluated activation of MAPKs and Akt in CMs exposed to C5a in vitro and after cecal ligation and puncture (CLP) in vivo In both cases, C5a in vitro caused activation (phosphorylation) of MAPKs and Akt in CMs, which required availability of both C5a receptors. Using immunofluorescence technology, activation of MAPKs and Akt occurred in left ventricular (LV) CMs, requiring both C5a receptors, C5aR1 and -2. Use of a water-soluble p38 inhibitor curtailed activation in vivo of MAPKs and Akt in LV CMs as well as the appearance of cytokines and histones in plasma from CLP mice. When mouse macrophages were exposed in vitro to LPS, activation of MAPKs and Akt also occurred. The copresence of the p38 inhibitor blocked these activation responses. Finally, the presence of the p38 inhibitor in CLP mice reduced the development of cardiac dysfunction. These data suggest that polymicrobial sepsis causes cardiac dysfunction that appears to be linked to activation of MAPKs and Akt in heart.-Fattahi, F., Kalbitz, M., Malan, E. A., Abe, E., Jajou, L., Huber-Lang, M. S., Bosmann, M., Russell, M. W., Zetoune, F. S., Ward, P. A. Complement-induced activation of MAPKs and Akt during sepsis: role in cardiac dysfunction. © FASEB.

  12. Human prostate luminal cell differentiation requires NOTCH3 induction by p38-MAPK and MYC.

    Science.gov (United States)

    Frank, Sander B; Berger, Penny L; Ljungman, Mats; Miranti, Cindy K

    2017-06-01

    Many pathways dysregulated in prostate cancer are also involved in epithelial differentiation. To better understand prostate tumor initiation, we sought to investigate specific genes and mechanisms required for normal basal to luminal cell differentiation. Utilizing human prostate basal epithelial cells and an in vitro differentiation model, we tested the hypothesis that regulation of NOTCH3 by the p38 MAPK family (hereafter p38-MAPK), via MYC, is required for luminal differentiation. Inhibition (SB202190 and BIRB796) or knockdown of p38α (also known as MAPK14) and/or p38δ (also known as MAPK13) prevented proper differentiation. Additionally, treatment with a γ-secretase inhibitor (RO4929097) or knockdown of NOTCH1 and/or NOTCH3 greatly impaired differentiation and caused luminal cell death. Constitutive p38-MAPK activation through MKK6(CA) increased NOTCH3 (but not NOTCH1) mRNA and protein levels, which was diminished upon MYC inhibition (10058-F4 and JQ1) or knockdown. Furthermore, we validated two NOTCH3 enhancer elements through a combination of enhancer (e)RNA detection (BruUV-seq) and luciferase reporter assays. Finally, we found that the NOTCH3 mRNA half-life increased during differentiation or upon acute p38-MAPK activation. These results reveal a new connection between p38-MAPK, MYC and NOTCH signaling, demonstrate two mechanisms of NOTCH3 regulation and provide evidence for NOTCH3 involvement in prostate luminal cell differentiation. © 2017. Published by The Company of Biologists Ltd.

  13. Geothermal gradient drilling, north-central Cascades of Oregon, 1979

    Energy Technology Data Exchange (ETDEWEB)

    Youngquist, W.

    1980-01-01

    A geothermal gradient drilling program was conducted on the western flank of the north-central Cascade Mountains in Oregon. Six wells were drilled during this program, although in effect seven were drilled, as two wells were drilled at site 3, the second well, however, actually going to a lesser depth than the first. Three of the wells (3, 4, and 5) were drilled in areas which topographically are subject to strong throughflows of ground water. None of these wells reached the regional water table, and all showed essentially isothermal geothermal gradients. The single well which was started essentially at the water table (well 6) shows a linear temperature rise with depth essentially from the top of the well bore. Well No. 2 shows an isothermal gradient down to the level of the regional water table and then shows a linear gradient of about 70/sup 0/C/km from the regional water table to total depth.

  14. Regulation of heme oxygenase-1 expression and MAPK pathways in response to kaempferol and rhamnocitrin in PC12 cells

    International Nuclear Information System (INIS)

    Hong, J.-T.; Yen, J.-H.; Wang Lisu; Lo, Y.-H.; Chen, Z.-T.; Wu, M.-J.

    2009-01-01

    Oxidative stress has been considered as a major cause of cellular injuries in a variety of clinical abnormalities, especially neural diseases. Our aim of research is to investigate the protective effects and mechanisms of kaempferol and rhamnocitrin (kaempferol-7-methyl ether) on oxidative damage in rat pheochromocytoma PC12 cells induced by a limited supply of serum and hydrogen peroxide (H 2 O 2 ). The current result demonstrated that kaempferol protected PC12 cells from serum deprivation-induced apoptosis. Pretreatment of cells with kaempferol also diminished intracellular generation of reactive oxygen species (ROS) in response to H 2 O 2 and strongly elevated cell viability. RT-Q-PCR and Western blotting revealed that kaempferol and rhamnocitrin significantly induced heme oxygenase (HO)-1 gene expression. Addition of zinc protoporphyrin (Znpp), a HO-1 competitive inhibitor, significantly attenuated their protective effects in H 2 O 2 -treated cells, indicating the vital role of HO-1 in cell resistance to oxidative injury. While investigating the signaling pathways responsible for HO-1 induction, we observed that kaempferol induced sustained extracellular signal-regulated protein kinase 1/2 (ERK1/2) in PC12 cells grown in low serum medium; while rhamnocitrin only stimulated transient ERK cascade. Addition of U0126, a highly selective inhibitor of MEK1/2, which is upstream of ERK1/2, had no effect on kaempferol- or rhamnocitrin-induced HO-1 mRNA expression, indicating no direct cross-talk between these two pathways. Furthermore, both kaempferol and rhamnocitrin were able to persistently attenuate p38 phosphorylation. Taking together, the above findings suggest that kaempferol and rhamnocitrin can augment cellular antioxidant defense capacity, at least in part, through regulation of HO-1 expression and MAPK signal transduction.

  15. PARAMETRIC STUDY OF ENERGY, EXERGY AND THERMOECONOMIC ANALYSES ON VAPOR-COMPRESSION SYSTEM CASCADED WITH LIBR/WATER AND NH3/WATER ABSORBTION CASCADE REFRIGERATION CYCLE

    Directory of Open Access Journals (Sweden)

    ahmet selim dalkilic

    2017-03-01

    Full Text Available Energy savings on cooling systems can be performed by using novel refrigeration cycles. For this aim, vapour compression-vapour absorption cascade refrigeration systems can be considered as substitute to single-stage vapour compression refrigeration systems. Renewable energy sources of geothermal and solar heat, waste heat of processes have been used by these cycles to provide cooling and they also require less electrical energy than vapour compression cycles having alternative refrigerants. In this study, a vapour compression (VC and vapour absorption (VA cascade systems are analysed with the second law analysis for varied cooling capacities. While lithium bromide-water and NH3/H2O are the working fluids in VA part, various refrigerants are used in VC section. The refrigerants of R134a and R600a, R410A and R407C are tested as drop in alternatives for R12 and R22, respectively. The effects of alteration in cooling capacity, superheating and sub cooling in VC part, temperature in the generator and absorber, and degree of overlap in cascade condenser in VA part on the coefficient of system performance are studied. Validation of the results have been performed by the values given in the literature. Improvement in COP of VC, VA and cascade system are obtained separately. According to the analyses, cascade systems’ COP values increase with increasing the temperatures of generator and evaporator and they also increase with decreasing the condenser and absorber temperatures. Moreover, the generator has the highest exergy destruction rates, second and third one were the condenser and absorber, respectively. Electricity consumption and payback period are also determined considering the various parameters of the study.

  16. Biexciton cascade emission in multilayered organic nanofibers

    Science.gov (United States)

    Evaristo de Sousa, Leonardo; Ferreira da Cunha, Wiliam; Antônio da Silva Filho, Demétrio; de Oliveira Neto, Pedro Henrique

    2018-04-01

    The optical performance of multilayered organic nanofibers results from the dynamics of excited states in the system. Here, we show that the presence of biexcitons is crucial to correctly describe such dynamics. This may be the case even if the intensity of the light source is not high. The cascade emission mediated by biexcitons is mainly responsible for the behavior of the photoluminescence profile in the initial steps after light absorption. By using a combination of Kinetic Monte Carlo model and Genetic Algorithm, we simulate Time-Resolved Photoluminescence measurements of multilayered nanofibers. These simulations are compared with experimental results, thus revealing that the usual singlet exciton recombination is insufficient to reproduce the complete physical picture. Our results also include predictions for the behavior of the biexciton signal. These findings are observed to be valid for a wide temperature range, showing the importance of the biexciton cascade emission in several regimes for organic nanofibers in general.

  17. Cascade Apartments: Deep Energy Multifamily Retrofit

    Energy Technology Data Exchange (ETDEWEB)

    Gordon, A. [Washington State Univ. Energy Program, Olympia, WA (United States); Mattheis, L. [Washington State Univ. Energy Program, Olympia, WA (United States); Kunkle, R. [Washington State Univ. Energy Program, Olympia, WA (United States); Howard, L. [Washington State Univ. Energy Program, Olympia, WA (United States); Lubliner, M. [Washington State Univ. Energy Program, Olympia, WA (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.

  18. 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.

  19. Cascadable spatial-soliton logic gates.

    Science.gov (United States)

    Blair, S; Wagner, K

    2000-11-10

    The three-terminal spatial-soliton angular-deflection geometry provides the characteristics of an inverting logic gate with gain, and phase-insensitive implementations can be realized by a number of specific nonlinear interactions between orthogonally polarized waves. In particular, numerical simulations of spatial-soliton dragging and collision are used to calculate the transfer functions of inverter and multiple configurations of two-input nor gates and to address their cascadability. These transfer functions converge in cascaded operation and suggest that fan-out greater than 2 with a large noise margin is attainable in a system with standardized signal levels. These results are obtained with the material properties of fused silica and are representative of low-loss Kerr media.

  20. Gastrodin inhibits expression of inducible NO synthase, cyclooxygenase-2 and proinflammatory cytokines in cultured LPS-stimulated microglia via MAPK pathways.

    Directory of Open Access Journals (Sweden)

    Ji-Nan Dai

    Full Text Available Microglial activation plays an important role in neurodegenerative diseases by producing several proinflammatory enzymes and proinflammatory cytokines. The phenolic glucoside gastrodin, a main constituent of a Chinese herbal medicine, has been known to display anti-inflammatory properties. The current study investigates the potential mechanisms whereby gastrodin affects the expression of potentially pro-inflammatory proteins by cultured murine microglial BV-2 cells stimulated with lipopolysaccharide (LPS.BV-2 cells were pretreated with gastrodin (30, 40, and 60 µM for 1 h and then stimulated with LPS (1 µg/ml for another 4 h. The effects on proinflammatory enzymes, inducible nitric oxide synthase (iNOS and cyclooxygenase-2 (COX-2, and proinflammatory cytokines, tumor necrosis factor-α (TNF-α, and interleukin-1β (IL-1β, are analysed by double-immunofluorescence labeling and RT-PCR assay. To reveal the mechanisms of action of gastrodin we investigated the involvement of mitogen-activated protein kinases (MAPKs cascades and their downstream transcription factors, nuclear factor-κB (NF-κB and cyclic AMP-responsive element (CRE-binding protein (CREB. Gastrodin significantly reduced the LPS-induced protein and mRNA expression levels of iNOS, COX-2, TNF-α, IL-1β and NF-κB. LPS (1 µg/ml, 30 min-induced phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2, c-Jun N-terminal protein kinase (JNK and p38 mitogen-activated protein kinase (p38 MAPK and this was inhibited by pretreatment of BV-2 cells with different concentrations of gastrodin (30, 40, and 60 µM. In addition, gastrodin blocked LPS-induced phosphorylation of inhibitor κB-α (IκB-α (and hence the activation of NF-κB and of CREB, respectively.This study indicates that gastrodin significantly attenuate levels of neurotoxic proinflammatory mediators and proinflammatory cytokines by inhibition of the NF-κB signaling pathway and phosphorylation of MAPKs in LPS

  1. Cigarette smoke extract induces placental growth factor release from human bronchial epithelial cells via ROS/MAPK(ERK-1/2/Egr-1 axis

    Directory of Open Access Journals (Sweden)

    Wu D

    2016-12-01

    Full Text Available Dong Wu,1,* Yalian Yuan,1,* Zhixiu Lin,2,* Tianwen Lai,1 Min Chen,1 Wen Li,1 Quanchao Lv,1 Binfan Yuan,1 Dongmin Li,1 Bin Wu1 1Department of Respiratory, Institute of Respiratory Diseases, 2Department of Pharmacy, The Affiliated Hospital of Guangdong Medical University, Zhanjiang, People’s Republic of China *These authors contributed equally to this work Abstract: Etiological evidence demonstrates that there is a significant association between cigarette smoking and chronic airway inflammatory disease. Abnormal expression of placental growth factor (PlGF has been reported in COPD, and its downstream signaling molecules have been reported to contribute to the pathogenesis of airway epithelial cell apoptosis and emphysema. However, the signaling mechanisms underlying cigarette smoke extract (CSE-induced PlGF expression in airway microenvironment remain unclear. Herein, we investigated the effects of reactive oxygen species (ROS-dependent activation of the mitogen-activated protein kinase (MAPK (extracellular signal-regulated kinase1/2 [ERK-1/2]/early growth response-1 (Egr-1 pathway on CSE-induced PlGF upregulation in human bronchial epithelium (HBE. The data obtained with quantitative reverse transcription polymerase chain reaction, Western blot, enzyme-linked immunosorbent assay (ELISA and immunofluorescence staining analyses showed that CSE-induced Egr-1 activation was mainly mediated through production of ROS and activation of the MAPK (ERK-1/2 cascade. The binding of Egr-1 to the PlGF promoter was corroborated by an ELISA-based DNA binding activity assay. These results demonstrate that ROS activation of the MAPK (ERK-1/2/Egr-1 pathway is a main player in the regulatory mechanism for CSE-induced PlGF production and that the use of an antioxidant could partly abolish these effects. Understanding the mechanisms of PlGF upregulation by CSE in the airway microenvironment may provide rational therapeutic interventions for cigarette smoking

  2. Involvement of the MAPK and PI3K pathways in chitinase 3-like 1-regulated hyperoxia-induced airway epithelial cell death

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Mi Na; Lee, Kyung Eun; Hong, Jung Yeon; Heo, Won Il; Kim, Kyung Won; Kim, Kyu Earn [Department of Pediatrics and Institute of Allergy, Severance Medical Research Institute, Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, Seoul (Korea, Republic of); Sohn, Myung Hyun, E-mail: mhsohn@yuhs.ac [Department of Pediatrics and Institute of Allergy, Severance Medical Research Institute, Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, Seoul (Korea, Republic of)

    2012-05-18

    Highlights: Black-Right-Pointing-Pointer Hyperoxia induces apoptosis and chitinase 3-like 1 expression in human airway epithelial cells. Black-Right-Pointing-Pointer Presence of chitinase 3-like 1 affects airway epithelial cell death after hyperoxic exposure. Black-Right-Pointing-Pointer Silencing chitinase 3-like 1 manipulate the phosphorylation of ERK, p38 and Akt. -- Abstract: Background: Exposure to 100% oxygen causes hyperoxic acute lung injury characterized by cell death and injury of alveolar epithelial cells. Recently, the role of chitinase 3-like 1 (CHI3L1), a member of the glycosyl hydrolase 18 family that lacks chitinase activity, in oxidative stress was demonstrated in murine models. High levels of serum CHI3L1 have been associated with various diseases of the lung, such as asthma, chronic obstructive pulmonary disease, and cancer. However, the role of CHI3L1 in human airway epithelial cells undergoing oxidative stress remains unknown. In addition, the signaling pathways associated with CHI3L1 in this process are poorly understood. Purpose: In this study, we demonstrate the role of CHI3L1, along with the MAPK and PI3K signaling pathways, in hyperoxia-exposed airway epithelial cells. Method: The human airway epithelial cell line, BEAS-2B, was exposed to >95% oxygen (hyperoxia) for up to 72 h. Hyperoxia-induced cell death was determined by assessing cell viability, Annexin-V FITC staining, caspase-3 and -7 expression, and electron microscopy. CHI3L1 knockdown and overexpression studies were conducted in BEAS-2B cells to examine the role of CHI3L1 in hyperoxia-induced apoptosis. Activation of the MAPK and PI3K pathways was also investigated to determine the role of these signaling cascades in this process. Results: Hyperoxia exposure increased CHI3L1 expression and apoptosis in a time-dependent manner. CHI3L1 knockdown protected cells from hyperoxia-induced apoptosis. In contrast, CHI3L1 overexpression promoted cell death after hyperoxia exposure. Finally

  3. Design Mining Microbial Fuel Cell Cascades

    OpenAIRE

    Preen, Richard J.; You, Jiseon; Bull, Larry; Ieropoulos, Ioannis A.

    2016-01-01

    Microbial fuel cells (MFCs) perform wastewater treatment and electricity production through the conversion of organic matter using microorganisms. For practical applications, it has been suggested that greater efficiency can be achieved by arranging multiple MFC units into physical stacks in a cascade with feedstock flowing sequentially between units. In this paper, we investigate the use of computational intelligence to physically explore and optimise (potentially) heterogeneous MFC designs ...

  4. Hadron cascades in iron and uranium

    CERN Document Server

    Fabjan, Christian Wolfgang; Lankford, A J; Rehak, P; Struczinski, W; Willis, W J

    1975-01-01

    Cascade developments of hadrons and electrons are studied in iron and uranium-238 through the measurement of the total ionization produced in a fine grained multiplate ion chamber array. In iron the distribution of total ionization is dominated by nuclear binding energy fluctuations. In uranium-238, however, this fluctuation is compensated by correlated fission energy deposit resulting in a considerable reduction in the measured ionization fluctuation. (7 refs).

  5. 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.

  6. PAF-mediated MAPK signaling hyperactivation via LAMTOR3 induces pancreatic tumorigenesis.

    Science.gov (United States)

    Jun, Sohee; Lee, Sunhye; Kim, Han-Cheon; Ng, Christopher; Schneider, Andrea M; Ji, Hong; Ying, Haoqiang; Wang, Huamin; DePinho, Ronald A; Park, Jae-Il

    2013-10-31

    Deregulation of mitogen-activated protein kinase (MAPK) signaling leads to development of pancreatic cancer. Although Ras-mutation-driven pancreatic tumorigenesis is well understood, the underlying mechanism of Ras-independent MAPK hyperactivation remains elusive. Here, we have identified a distinct function of PCNA-associated factor (PAF) in modulating MAPK signaling. PAF is overexpressed in pancreatic cancer and required for pancreatic cancer cell proliferation. In mouse models, PAF expression induced pancreatic intraepithelial neoplasia with expression of pancreatic cancer stem cell markers. PAF-induced ductal epithelial cell hyperproliferation was accompanied by extracellular signal-regulated kinase (ERK) phosphorylation independently of Ras or Raf mutations. Intriguingly, PAF transcriptionally activated the expression of late endosomal/lysosomal adaptor, MAPK and mTOR activator 3 (LAMTOR3), which hyperphosphorylates MEK and ERK and is necessary for pancreatic cancer cell proliferation. Our results reveal an unsuspected mechanism of mitogenic signaling activation via LAMTOR3 and suggest that PAF-induced MAPK hyperactivation contributes to pancreatic tumorigenesis.

  7. PAF-Mediated MAPK Signaling Hyperactivation via LAMTOR3 Induces Pancreatic Tumorigenesis

    Directory of Open Access Journals (Sweden)

    Sohee Jun

    2013-10-01

    Full Text Available Deregulation of mitogen-activated protein kinase (MAPK signaling leads to development of pancreatic cancer. Although Ras-mutation-driven pancreatic tumorigenesis is well understood, the underlying mechanism of Ras-independent MAPK hyperactivation remains elusive. Here, we have identified a distinct function of PCNA-associated factor (PAF in modulating MAPK signaling. PAF is overexpressed in pancreatic cancer and required for pancreatic cancer cell proliferation. In mouse models, PAF expression induced pancreatic intraepithelial neoplasia with expression of pancreatic cancer stem cell markers. PAF-induced ductal epithelial cell hyperproliferation was accompanied by extracellular signal-regulated kinase (ERK phosphorylation independently of Ras or Raf mutations. Intriguingly, PAF transcriptionally activated the expression of late endosomal/lysosomal adaptor, MAPK and mTOR activator 3 (LAMTOR3, which hyperphosphorylates MEK and ERK and is necessary for pancreatic cancer cell proliferation. Our results reveal an unsuspected mechanism of mitogenic signaling activation via LAMTOR3 and suggest that PAF-induced MAPK hyperactivation contributes to pancreatic tumorigenesis.

  8. Parainfluenza Virus Type 1 Induces Epithelial IL-8 Production via p38-MAPK Signalling

    Directory of Open Access Journals (Sweden)

    Miguel Ángel Galván Morales

    2014-01-01

    Full Text Available Human parainfluenza virus type 1 (HPIV-1 is the most common cause of croup in infants. The aim of this study was to describe molecular mechanisms associated with IL-8 production during HPIV-1 infection and the role of viral replication in MAPK synthesis and activation. An in vitro model of HPIV-1 infection in the HEp-2 and A549 cell lines was used; a kinetic-based ELISA for IL-8 detection was also used, phosphorylation of the mitogen-activated protein kinases (MAPKs was identified by Western blot analysis, and specific inhibitors for each kinase were used to identify which MAPK was involved. Inactivated viruses were used to assess whether viral replication is required for IL-8 production. Results revealed a gradual increase in IL-8 production at different selected times, when phosphorylation of MAPK was detected. The secretion of IL-8 in the two cell lines infected with the HPIV-1 is related to the phosphorylation of the MAPK as well as viral replication. Inhibition of p38 suppressed the secretion of IL-8 in the HEp-2 cells. No kinase activation was observed when viruses were inactivated.

  9. High-power resistance exercise induces MAPK phosphorylation in weightlifting trained men.

    Science.gov (United States)

    Galpin, Andrew J; Fry, Andrew C; Chiu, Loren Z F; Thomason, Donald B; Schilling, Brian K

    2012-02-01

    Power is critical to muscle performance, specifically in athletic populations. Mitogen-activated protein kinase (MAPK) pathways (extracellular signal-regulated protein kinase (ERK 1/2), p38, and c-Jun NH(2)-terminal kinase (JNK)) are intracellular signal transduction mechanisms that partially regulate exercise-induced skeletal muscle alterations. These pathways are highly responsive to exercise, but their reaction to high power, multi-joint resistance exercise is yet to be examined. Nine weightlifting-trained men performed 15 sets of three repetitions of a dynamic clean pull exercise at 85% of their one repetition maximum. Vastus lateralis biopsies were obtained prior to (pre) and after the 8th (mid) and 15th set (post) of exercise. Three subjects returned to serve as non-exercising controls for a similar sequence of biopsies (CON). The ratio of phosphorylated MAPK to total MAPK increased significantly for p38 (3.0 fold, p  0.05), and thus the biopsy procedure itself did not account for the entire increase in MAPK phosphorylation during EX. These data indicate MAPK pathways are activated early and remain elevated throughout the duration of high power resistance exercise. These findings help describe the mechanisms partially responsible for chronic adaptations in response to high intensity, high power resistance training in humans.

  10. p38 MAPK downregulates phosphorylation of Bad in doxorubicin-induced endothelial apoptosis

    International Nuclear Information System (INIS)

    Grethe, Simone; Coltella, Nadia; Di Renzo, Maria Flavia; Poern-Ares, M. Isabella

    2006-01-01

    Doxorubicin is the anthracycline with the widest spectrum of antitumor activity, and it has been shown that the antitumor activity is mediated in vivo by selective triggering of apoptosis in proliferating endothelial cells. We studied cultured human endothelial cells and observed that doxorubicin-induced apoptosis was mediated by p38 mitogen-activated protein kinase (MAPK). Doxorubicin-provoked apoptosis was significantly inhibited by expression of dominant negative p38 MAPK or pharmacological inhibition with SB203580. Furthermore, blocking phosphatidylinositol-3-kinase/Akt signaling significantly increased doxorubicin-induced caspase-3 activity and cell death, indicating that Akt is a survival factor in this system. Notably, we also found that doxorubicin-provoked apoptosis included p38 MAPK-mediated inhibition of Akt and Bad phosphorylation. Furthermore, doxorubicin-stimulated phosphorylation of Bad in cells expressing dominant negative p38 MAPK was impeded by the inhibition of PI3-K. In addition to the impact on Bad phosphorylation, doxorubicin-treatment caused p38 MAPK-dependent downregulation of Bcl-xL protein

  11. Tetraspanin CD9 regulates osteoclastogenesis via regulation of p44/42 MAPK activity

    International Nuclear Information System (INIS)

    Yi, TacGhee; Kim, Hye-Jin; Cho, Je-Yoel; Woo, Kyung Mi; Ryoo, Hyun-Mo; Kim, Gwan-Shik; Baek, Jeong-Hwa

    2006-01-01

    Tetraspanin CD9 has been shown to regulate cell-cell fusion in sperm-egg fusion and myotube formation. However, the role of CD9 in osteoclast, another multinucleated cell type, is not still clear. Therefore, we investigated the role of CD9 in osteoclast differentiation. CD9 was expressed in osteoclast lineage cells and its expression level increased during the progression of RANKL-induced osteoclastogenesis. KMC8, a neutralizing antibody specific to CD9, significantly suppressed RANKL-induced multinucleated osteoclast formation and the mRNA expression of osteoclast differentiation marker genes. To define CD9-regulated osteoclastogenic signaling pathway, MAPK pathways were examined. KMC8 induced long-term phosphorylation of p44/42 MAPK, but not of p38 MAPK. Constitutive activation of p44/42 MAPK by overexpressing constitutive-active mutant of MEK1 almost completely blocked osteoclast differentiation. Taken together, these results suggest that CD9 expressed on osteoclast lineage cells might positively regulate osteoclastogenesis via the regulation of p44/42 MAPK activity

  12. [Effect of sleep deprivation on p38MAPK phosphorylation in the rat hippocampus].

    Science.gov (United States)

    Guo, Xia; Chen, Chang-xiang; Chen, Gui-zhi; Li, Shu-xing; Li, Jian-min; Zhao, Ya-ning

    2011-03-01

    To investigate the effect of sleep deprivation (SD) on the expression of p38Mitogen-activated protein kinase (p38MAPK) phosphorylation in the rat hippocampus. Male Sprague-Dawley rats (n=60) were divided randomly into control and sleep deprivation groups. The sleep deprivation models were established with the modified multiple platform methods. At 1 d, 3 d, 5 d, and 7 d after sleep deprivations, changes of neuron morphous in the hippocampal region of the rats were observed by HE staining. The expression of p38MAPK phosphorylation was detected by immunohistochemistry and Western blot. The learning-memory function was tested with Morris water maze and 4-PTT dry path maze. More obvious neuronal morphous damages, increased p38MAPK phosphorylation cells and p38MAPK phosphorylation expression, and decreased learning-memory function were found in the rats subject to sleep deprivation than those in the control. The changes were enhanced with the length of sleep deprivation. p38MAPK can be activated by sleep deprivation, which mediates the process of neuronal injury.

  13. TAB3 involves in hepatic insulin resistance through activation of MAPK pathway.

    Science.gov (United States)

    Zhao, Yun; Tang, Zhuqi; Zhu, Xiaohui; Wang, Xueqin; Wang, Cuifang; Zhang, Wanlu; Xia, Nana; Wang, Suxin; Huang, Jieru; Cui, Shiwei

    2015-12-01

    Insulin resistance is often accompanied by chronic inflammatory responses. The mitogen-activated protein kinase (MAPK) pathway is rapidly activated in response to many inflammatory cytokines. But the functional role of MAPKs in palmitate-induced insulin resistance has yet to be clarified. In this study, we found that transforming growth factor β-activated kinase binding protein-3 (TAB3) was up-regulated in insulin resistance. Considering the relationship between transforming growth factor β-activated kinase (TAK1) and MAPK pathway, we assumed TAB3 involved in insulin resistance through activation of MAPK pathway. To certify this hypothesis, we knocked down TAB3 in palmitate treated HepG2 cells and detected subsequent biological responses. Importantly, TAB3 siRNA directly reversed insulin sensitivity by improving insulin signal transduction. Moreover, silencing of TAB3 could facilitate hepatic glucose uptake, reverse gluconeogenesis and improve ectopic fat accumulation. Meanwhile, we found that the positive effect of knocking down TAB3 was more significant when insulin resistance occurred. All these results indicate that TAB3 acts as a negative regulator in insulin resistance through activation of MAPK pathway. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. MKK3 Was Involved in Larval Settlement of the Barnacle Amphibalanus amphitrite through Activating the Kinase Activity of p38MAPK

    KAUST Repository

    Zhang, Gen

    2013-07-29

    The p38 mitogen-activated protein kinase (p38MAPK) plays a key role in larval settlement of the barnacle Amphibalanus amphitrite. To study the signaling pathway associated with p38MAPK during larval settlement, we sought to identify the upstream kinase of p38MAPK. Three MKKs (MKK3, MKK4 and MKK7) and three MAPKs (p38MAPK, ERK and JNK) in A. amphitrite were cloned and recombinantly expressed in E. coli. Through kinase assays, we found that MKK3, but not MKK4 or MKK7, phosphorylated p38MAPK. Furthermore, MKK3 activity was specific to p38MAPK, as it did not phosphorylate ERK or JNK. To further investigate the functional relationship between MKK3 and p38MAPK in vivo, we studied the localization of phospho-MKK3 (pMKK3) and MKK3 by immunostaining. Consistent with the patterns of p38MAPK and phospho-p38MAPK (pp38MAPK), pMKK3 and MKK3 mainly localized to the antennules of the cyprids. Western blot analysis revealed that pMKK3 levels, like pp38MAPK levels, were elevated at cyprid stage, compared to nauplii and juvenile stages. Moreover, pMKK3 levels increased after treatment with adult barnacle crude extracts, suggesting that MKK3 might mediate the stimulatory effects of adult barnacle extracts on the p38MAPK pathway. © 2013 Zhang et al.

  15. 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

  16. Hadronic event generation for hadron cascade calculations and detector simulation. 2

    International Nuclear Information System (INIS)

    Haenssgen, K.; Moehring, H.J.; Ranft, J.

    1983-01-01

    A model for inelastic hadron-nucleus interactions at energies between 0.1 and 5 GeV is described. It includes particle production, cascade proton and neutron emission, described via empirical formulae and nuclear excitation energy. All stable hadrons can be used as primary or secondary particles. The model is constructed via the Monte Carlo generation of complete events. Good agreement is found in comparing average multiplicities and single and double differential cross sections with experimental data. (author)

  17. Thromboxane A2 Receptor Inhibition Suppresses Multiple Myeloma Cell Proliferation by Inducing p38/c-Jun N-terminal Kinase (JNK) Mitogen-activated Protein Kinase (MAPK)-mediated G2/M Progression Delay and Cell Apoptosis*

    Science.gov (United States)

    Liu, Qian; Tao, Bo; Liu, Guizhu; Chen, Guilin; Zhu, Qian; Yu, Ying; Yu, Yu; Xiong, Hong

    2016-01-01

    Multiple myeloma (MM) is a plasma cell malignancy without effective therapeutics. Thromboxane A2 (TxA2)/TxA2 receptor (T prostanoid receptor (TP)) modulates the progression of some carcinomas; however, its effects on MM cell proliferation remain unclear. In this study, we evaluated cyclooxygenase (COX) enzymes and downstream prostaglandin profiles in human myeloma cell lines RPMI-8226 and U-266 and analyzed the effects of COX-1/-2 inhibitors SC-560 and NS-398 on MM cell proliferation. Our observations implicate COX-2 as being involved in modulating cell proliferation. We further incubated MM cells with prostaglandin receptor antagonists or agonists and found that only the TP antagonist, SQ29548, suppressed MM cell proliferation. TP silencing and the TP agonist, U46619, further confirmed this finding. Moreover, SQ29548 and TP silencing promoted MM cell G2/M phase delay accompanied by reducing cyclin B1/cyclin-dependent kinase-1 (CDK1) mRNA and protein expression. Notably, cyclin B1 overexpression rescued MM cells from G2/M arrest. We also found that the TP agonist activated JNK and p38 MAPK phosphorylation, and inhibitors of JNK and p38 MAPK depressed U46619-induced proliferation and cyclin B1/CDK1 protein expression. In addition, SQ29548 and TP silencing led to the MM cell apoptotic rate increasing with improving caspase 3 activity. The knockdown of caspase 3 reversed the apoptotic rate. Taken together, our results suggest that TxA2/TP promotes MM cell proliferation by reducing cell delay at G2/M phase via elevating p38 MAPK/JNK-mediated cyclin B1/CDK1 expression and hindering cell apoptosis. The TP inhibitor has potential as a novel agent to target kinase cascades for MM therapy. PMID:26724804

  18. PsMPK7, a stress-associated mitogen-activated protein kinase (MAPK) in Phytophthora sojae, is required for stress tolerance, reactive oxygenated species detoxification, cyst germination, sexual reproduction and infection of soybean.

    Science.gov (United States)

    Gao, Jian; Cao, Mingna; Ye, Wenwu; Li, Haiyang; Kong, Liang; Zheng, Xiaobo; Wang, Yuanchao

    2015-01-01

    The sensing of stress signals and their transduction into appropriate responses are crucial for the adaptation, survival and infection of phytopathogenic fungi and oomycetes. Amongst evolutionarily conserved pathways, mitogen-activated protein kinase (MAPK) cascades function as key signal transducers that use phosphorylation to convey information. In this study, we identified a gene, designated PsMPK7, one of 14 predicted genes encoding MAPKs in Phytophthora sojae. PsMPK7 was highly transcribed in each tested stage, but was up-regulated in the zoospore, cyst and cyst germination stages. Silencing of PsMPK7 affected the growth of germinated cysts, oospore production and the pathogenicity of soybean. PsMPK7 transcription was induced by stresses from sorbitol, NaCl and hydrogen peroxide. Transformants in which PsMPK7 expression was silenced (PsMPK7-silenced) were significantly more sensitive to osmotic and oxidative stress. Aniline blue and diaminobenzidine staining revealed that the silenced lines did not suppress the host reactive oxygen species (ROS) burst, indicating that either the inoculated plants activated stronger defence responses to the transformants and/or the PsMPK7-silenced transformants failed to overcome plant defences. In addition, extracellular secretion of laccase decreased in the silenced lines. Overall, our results indicate that the PsMPK7 gene encodes a stress-associated MAPK in P. sojae that is important not only for responses to various stresses, but also for ROS detoxification, cyst germination, sexual oospore production and infection of soybean. © 2014 BSPP AND JOHN WILEY & SONS LTD.

  19. Magnetic field sensor based on cascaded microfiber coupler with magnetic fluid

    Energy Technology Data Exchange (ETDEWEB)

    Mao, Lianmin; Su, Delong; Wang, Zhaofang [College of Science, University of Shanghai for Science and Technology, Shanghai 200093 (China); Pu, Shengli, E-mail: shlpu@usst.edu.cn [College of Science, University of Shanghai for Science and Technology, Shanghai 200093 (China); Shanghai Key Laboratory of Modern Optical System, University of Shanghai for Science and Technology, Shanghai 200093 (China); Zeng, Xianglong [The Key Lab of Specialty Fiber Optics and Optical Access Network, Shanghai University, Shanghai 200072 (China); Lahoubi, Mahieddine [Laboratory L.P.S., Department of Physics, Faculty of Sciences, Badji-Mokhtar Annaba University, Annaba 23000 (Algeria)

    2016-09-07

    A kind of magnetic field sensor based on cascaded microfiber coupler with magnetic fluid is proposed and experimentally demonstrated. The magnetic fluid is utilized as the cladding of the fused regions of the cascaded microfiber coupler. As the interference valley wavelength of the sensing structure is sensitive to the ambient variation, considering the magnetic-field-dependent refractive index of magnetic fluid, the proposed structure is employed for magnetic field sensing. The effective coupling length for each coupling region of the as-fabricated cascaded microfiber coupler is 6031 μm. The achieved sensitivity is 125 pm/Oe, which is about three times larger than that of the previously similar structure based on the single microfiber coupler. Experimental results indicate that the sensing sensitivity can be easily improved by increasing the effective coupling length or cascading more microfiber couplers. The proposed magnetic field sensor is attractive due to its low cost, immunity to electromagnetic interference, as well as high sensitivity, which also has the potentials in other tunable all-fiber photonic devices, such as filter.

  20. Characteristics of multi-stage AGMD-DCMD cascade system for oxygen isotope production

    International Nuclear Information System (INIS)

    Kim, Jae Woo; Choi, Hwa Rim; Chang, Dae Sik; Kim, Taek Soo; Lim, Gwon; Jeong, Do Young

    2005-01-01

    Membrane distillation (MD) appears to be useful for the separation of the light isotopes such as oxygen and hydrogen isotopes contained in water, because membrane permeation units are compact and simple, and more importantly its energy consumption is low compared to conventional water fractional distillation.1-4 Permeation fluxes and the degree of oxygen isotope separation of AGMD (Air Gap Membrane Distillation) and VEMD (Vacuum Enhanced Membrane Distillation) processes were measured by using the hot water feed. Even though VEMD shows slightly higher isotopic separation degree with higher permeation flux, it is very difficult to apply VEMD to multi-stage cascade system. Since local oxygen isotope separation coefficient for a single membrane unit is low, multi-stage membrane cascade system is required to increase isotopic concentration further in product. Although AGMD is suitable for constructing the membrane cascading system, permeation flux for AGMD is still too low to apply to the isotope production system. In this investigation, we increased permeation flux of AGMD using AGMD-DCMD (Direct Contact Membrane Distillation) combined process. Permeation flux and degree of isotope separation of AGMD-DCMD combined process were measured by using 10 stages cascade system

  1. Deuterium values from volcanic glass: A paleoelevation proxy for Oregon's Cascade Range

    Science.gov (United States)

    Carlson, T. B.; Bershaw, J. T.

    2016-12-01

    Hydrated volcanic glass has been used as a proxy to constrain Cenozoic paleoclimate across many of the world's mountain ranges. However, there are concerns that volcanic glass may not preserve the isotopic composition of syndepositional meteoric water. The Cascades are an excellent location to study the validity of hydrated volcanic glass as a paleoenvironmental proxy for several reasons. Moisture is derived from a single oceanic source and falls as orographic precipitation in the Cascades, leading to a characteristic altitude effect, or inverse relationship between elevation and the isotopic composition of meteoric water (δD). In addition, past studies have inferred uplift of the Cascades and an increase in the rain shadow effect since the Eocene through independent methods such as changing fossil assemblages, and other isotopic proxies including carbonates and fossil teeth. In this study, δD values of two hydrated tuff samples are compared: one prior to ( 29 Ma) and one following ( 5 Ma) the onset of High Cascade volcanism. The isotopic composition of these samples are interpreted in the context of modern water across the range to understand the potential of volcanic glass as a proxy for paleoelevation in the Pacific Northwest.

  2. Study of optical confinement of quantum cascade lasers and applications to detection

    International Nuclear Information System (INIS)

    Moreau, Virginie

    2008-01-01

    Quantum cascade lasers have been invented in 1994 and they have already established themselves as the semiconductor laser source of choice in the mid- and far-infrared ranges of the electromagnetic spectrum. As most molecules of chemical interest exhibit roto-vibrational transitions in these spectral ranges, quantum cascade lasers are especially suited for applications such as spectroscopy, trace gas detection or medical imaging. One of the current leading research axis targets the device optimization and miniaturization, with possible applications in detection microsystems. This PhD thesis work focused on the study and optimization of the vertical optical confinement in quantum cascade lasers featuring optical waveguides without top cladding layers. These structures are interesting because they are compatible with two different guiding mechanisms at the same time, i.e. surface-plasmons and air confinement. The study of the characteristics of the optical mode and of the electrical current dispersion allowed us to conceive original structures which open new perspectives, for instance in the domain of analytic detection in a fluidic environment. Furthermore, we have shown that the observation by near field microscopy is a powerful tool to characterize and understand quantum cascade lasers. Finally, we have laid the foundations for the optimization of miniaturized arrays of single-mode lasers based on photonic crystal technology. (author) [fr

  3. MAPK/ERK signaling pathway-induced hyper-O-GlcNAcylation enhances cancer malignancy.

    Science.gov (United States)

    Zhang, Xinling; Ma, Leina; Qi, Jieqiong; Shan, Hui; Yu, Wengong; Gu, Yuchao

    2015-12-01

    Dysregulated MAPK/ERK signaling is implicated in one-third of human tumors and represents an attractive target for the development of anticancer drugs. Similarly, elevated protein O-GlcNAcylation and O-GlcNAc transferase (OGT) are detected in various cancers and serve as attractive novel cancer-specific therapeutic targets. However, the potential connection between them remains unexplored. Here, a positive correlation was found between the activated MAPK/ERK signaling and hyper-O-GlcNAcylation in various cancer types and inhibition of the MAPK/ERK signaling by 10 µM U0126 significantly decreased the expression of OGT and O-GlcNAcylation in H1299, BPH-1 and DU145 cells; then, the pathway analysis of the potential regulators of OGT obtained from the UCSC Genome Browser was done, and ten downstream targets of ERK pathway were uncovered; the following results showed that ELK1, one of the ten targets of ERK pathway, mediated ERK signaling-induced OGT upregulation; finally, the MTT assay and the soft agar assay showed that the inhibition of MAPK/ERK signaling reduced the promotion effect of hyper-O-GlcNAcylation on cancer cell proliferation and anchorage-independent growth. Taken together, our data originally provided evidence for the regulatory mechanism of hyper-O-GlcNAcylation in tumors, which will be helpful for the development of anticancer drugs targeting to hyper-O-GlcNAcylation. This study also provided a new mechanism by which MAPK/ERK signaling-enhanced cancer malignancy. Altogether, the recently discovered oncogenic factor O-GlcNAc was linked to the classical MAPK/ERK signaling which is essential for the maintenance of malignant phenotype of cancers.

  4. p38 MAPK and MMP-9 cooperatively regulate mucus overproduction in mice exposed to acrolein fog.

    Science.gov (United States)

    Liu, Dai-Shun; Wang, Tao; Han, Su-Xia; Dong, Jia-Jia; Liao, Zeng-Lin; He, Guang-Ming; Chen, Lei; Chen, Ya-Juan; Xu, Dan; Hou, Yan; Li, Yan-Ping; Wen, Fu-Qiang

    2009-09-01

    To evaluate the role of p38 mitogen-activated protein kinase (MAPK) on mice airway inflammation, mucus production and the possible cross-talk between p38 MAPK and matrix metalloproteinase-9 (MMP-9) in mucin protein synthesis. Mice were exposed to 4.0 ppm of acrolein for 21 days with daily intraperitoneal injection of SB203580, a specific inhibitor of p38 MAPK. In control mice, sterile saline was administered instead. On days 7 and 21, mice were sacrificed to examine airway inflammation and mucus production by BALF cell counts, cytokine ELISA, and H&E and AB-PAS staining. The mRNA and protein levels of Muc5ac, p38 MAPK and MMP-9 in the lung were determined by RT-PCR, immunohistochemistry and Western blotting analysis. MMP-9 activity was measured by gelatin zymography. Both the numbers of inflammatory cells and mucus-secreting goblet cells were significantly increased in the airways of mice exposed to acrolein as compared to the control mice. Acrolein-increased phosphorylation of p38 MAPK was significantly reduced by SB203580. The airway inflammation and goblet cell hyperplasia after acrolein challenge were also attenuated by SB203580 administration. Moreover, SB203580 treatment decreased the acrolein-induced increase of Muc5ac and MMP-9 expression and MMP-9 activity in airway epithelium. The results indicate an important role of p38 MAPK in acrolein-induced airway inflammation and mucus hypersecretion in mice. The cooperation of p38 and MMP-9 may contribute to the mucin overproduction after inflammatory challenge.

  5. Differential Roles of Grb2 and AP-2 in p38 MAPK- and EGF-Induced EGFR Internalization

    DEFF Research Database (Denmark)

    Grandal, Michael V; Grøvdal, Lene M; Henriksen, Lasse

    2012-01-01

    epidermal growth factor (EGF)-induced EGFR internalization also required Grb2, p38 MAPK-induced internalization did not. Interestingly, AP-2 knock down blocked p38 MAPK-induced EGFR internalization, but only mildly affected EGF-induced internalization. In line with this, simultaneously mutating two AP-2...

  6. The Vibrio parahaemolyticus Type III Secretion Systems manipulate host cell MAPK for critical steps in pathogenesis.

    LENUS (Irish Health Repository)

    Matlawska-Wasowska, Ksenia

    2010-12-01

    Vibrio parahaemolyticus is a food-borne pathogen causing inflammation of the gastrointestinal epithelium. Pathogenic strains of this bacterium possess two Type III Secretion Systems (TTSS) that deliver effector proteins into host cells. In order to better understand human host cell responses to V. parahaemolyticus, the modulation of Mitogen Activated Protein Kinase (MAPK) activation in epithelial cells by an O3:K6 clinical isolate, RIMD2210633, was investigated. The importance of MAPK activation for the ability of the bacterium to be cytotoxic and to induce secretion of Interleukin-8 (IL-8) was determined.

  7. The Fourth International Symposium on Genetic Disorders of the Ras/MAPK pathway.

    Science.gov (United States)

    Stevenson, David A; Schill, Lisa; Schoyer, Lisa; Andresen, Brage S; Bakker, Annette; Bayrak-Toydemir, Pinar; Burkitt-Wright, Emma; Chatfield, Kathryn; Elefteriou, Florent; Elgersma, Ype; Fisher, Michael J; Franz, David; Gelb, Bruce D; Goriely, Anne; Gripp, Karen W; Hardan, Antonio Y; Keppler-Noreuil, Kim M; Kerr, Bronwyn; Korf, Bruce; Leoni, Chiara; McCormick, Frank; Plotkin, Scott R; Rauen, Katherine A; Reilly, Karlyne; Roberts, Amy; Sandler, Abby; Siegel, Dawn; Walsh, Karin; Widemann, Brigitte C

    2016-08-01

    The RASopathies are a group of disorders due to variations of genes associated with the Ras/MAPK pathway. Some of the RASopathies include neurofibromatosis type 1 (NF1), Noonan syndrome, Noonan syndrome with multiple lentigines, cardiofaciocutaneous (CFC) syndrome, Costello syndrome, Legius syndrome, and capillary malformation-arteriovenous malformation (CM-AVM) syndrome. In combination, the RASopathies are a frequent group of genetic disorders. This report summarizes the proceedings of the 4th International Symposium on Genetic Disorders of the Ras/MAPK pathway and highlights gaps in the field. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  8. Comprehensive integration of homogeneous bioassays via centrifugo-pneumatic cascading.

    Science.gov (United States)

    Godino, Neus; Gorkin, Robert; Linares, Ana V; Burger, Robert; Ducrée, Jens

    2013-02-21

    This work for the first time presents the full integration and automation concept for a range of bioassays leveraged by cascading a centrifugo-pneumatic valving scheme to sequentially move several liquids through shared channel segments for multi-step sample preparation into the detection zone. This novel centrifugo-pneumatic liquid handling significantly simplifies system manufacture by obviating the need for complex surface functionalization procedures or hybrid material integration, as it is common in conventional valving methods such as capillary burst valves or sacrificial valves. Based on the centrifugo-pneumatic valving scheme, this work presents a toolkit of operational elements implementing liquid loading/transfer, metering, mixing and sedimentation in a microstructured polymer disc. As a proof of concept for the broad class of homogeneous bioassays, the full integration and automation of a colorimetric nitrate/nitrite test for the detection of clinically relevant nitric oxide (NO) in whole blood is implemented. First, 40 μL of plasma is extracted from a 100 μL sample of human blood, incubated for one hour with the enzymatic mixture (60 μL), and finally reacted with 100 μL of colorimetric (Greiss) reagents. Following just a single loading phase at the beginning of the process, all of these steps are automated through the centrifugo-pneumatic cascade with a high level of flow control and synchronization. Our system shows good correlation with controls up to 50 μM of nitrate, which adequately covers the healthy human range (4 to 45.3 μM).

  9. Accumulated effects on landscape pattern by hydroelectric cascade exploitation in the Yellow River basin from 1977 to 2006

    NARCIS (Netherlands)

    Ouyang, W.; Skidmore, A.K.; Hao, F.H.; Toxopeus, A.G.; Abkar, A.

    2009-01-01

    The accumulated impacts of hydroelectric cascade exploitation (HCE) on the landscape are greater than the simple sum of the impacts from a single dam. The spatial–temporal landscape characteristics resulting from the accumulated impacts of HCE from 1977 to 2006 in Longliu Watershed, a part of the

  10. Recent Advances in the Inhibition of p38 MAPK as a Potential Strategy for the Treatment of Alzheimer's Disease.

    Science.gov (United States)

    Lee, Jong Kil; Kim, Nam-Jung

    2017-08-02

    P38 mitogen-activated protein kinase (MAPK) is a crucial target for chronic inflammatory diseases. Alzheimer's disease (AD) is characterized by the presence of amyloid plaques and neurofibrillary tangles in the brain, as well as neurodegeneration, and there is no known cure. Recent studies on the underlying biology of AD in cellular and animal models have indicated that p38 MAPK is capable of orchestrating diverse events related to AD, such as tau phosphorylation, neurotoxicity, neuroinflammation and synaptic dysfunction. Thus, the inhibition of p38 MAPK is considered a promising strategy for the treatment of AD. In this review, we summarize recent advances in the targeting of p38 MAPK as a potential strategy for the treatment of AD and envision possibilities of p38 MAPK inhibitors as a fundamental therapeutics for AD.

  11. 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.)

  12. Split energy cascade in turbulent thin fluid layers

    Science.gov (United States)

    Musacchio, Stefano; Boffetta, Guido

    2017-11-01

    We discuss the phenomenology of the split energy cascade in a three-dimensional thin fluid layer by means of high resolution numerical simulations of the Navier-Stokes equations. We observe the presence of both an inverse energy cascade at large scales, as predicted for two-dimensional turbulence, and a direct energy cascade at small scales, as in three-dimensional turbulence. The inverse energy cascade is associated with a direct cascade of enstrophy in the intermediate range of scales. Notably, we find that the inverse cascade of energy in this system is not a purely 2D phenomenon, as the coupling with the 3D velocity field is necessary to guarantee the constancy of fluxes.

  13. Atom localization with double-cascade configuration

    Science.gov (United States)

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

    2016-03-01

    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.

  14. 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.

  15. 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).

  16. The Cascade of Non-Stationarity

    Science.gov (United States)

    Belmont, P.; Kumarasamy, K.; Kelly, S. A.; Schaffrath, K. R.; Beach, T. J.

    2014-12-01

    Landscapes and channel networks are dynamic systems, often characterized by immense variability in time and space. Systematic shifts in hydrologic, geomorphic, or ecologic drivers can cause a cascade of changes within the system, which may fundamentally alter the way the system itself functions. Due to variability in resilience and resisting forces throughout the landscape, this cascade of changes may manifest in different ways within any given system. Humans may also exert considerable influence, often amplifying or damping system response. We illustrate the cascading effects of non-stationary hydrology and geomorphology in the Minnesota River Basin (MRB), a 44,000 km2 natural laboratory in which pervasive landscape disturbance has been triggered by several well-documented events. Rapid base-level lowering 13,400 YBP along the mainstem Minnesota River created a wave of incision, which continues to propagate up tributary channel networks. Temperature and precipitation have changed significantly in the MRB over the past century with rising temperatures, shifting precipitation patterns and an increase in heavy rainfall events. Streamflow has changed drastically and variably throughout the basin with 5% exceedance flows increasing 60-100% in recent decades, as increases in precipitation have been amplified by land management and artificial drainage. Increases in channel width and depth have occurred variably in the mainstem Minnesota River, the actively incising lower (knick zone) reaches of tributaries, and the low gradient, passively meandering reaches above the knick zones. Altered hydrologic regimes and channel morphologies, combined with increased sedimentation and nutrient loading have adversely affected aquatic biota via disruption of life cycles and habitat degradation. Existing landscape, water quality, and flood risk models are poorly equipped to deal with the cascading effects of non-stationarity and therefore may grossly over- or under

  17. Long-Haul TCP vs. Cascaded TCP

    OpenAIRE

    Feng, Wu-chun

    2006-01-01

    In this work, we investigate the bandwidth and transfer time of long-haul TCP versus cascaded TCP [5]. First, we discuss the models for TCP throughput. For TCP flows in support of bulk data transfer (i.e., long-lived TCP flows), the TCP throughput models have been derived [2, 3]. These models rely on the congestion-avoidance algorithm of TCP. Though these models cannot be applied with short-lived TCP connections, our interest relative to logistical networking is in longer-li...

  18. Multiheterodyne spectroscopy using interband cascade lasers

    Science.gov (United States)

    Sterczewski, Lukasz A.; Westberg, Jonas; Patrick, Charles Link; Kim, Chul Soo; Kim, Mijin; Canedy, Chadwick L.; Bewley, William W.; Merritt, Charles D.; Vurgaftman, Igor; Meyer, Jerry R.; Wysocki, Gerard

    2018-01-01

    While midinfrared radiation can be used to identify and quantify numerous chemical species, contemporary broadband midinfrared spectroscopic systems are often hindered by large footprints, moving parts, and high power consumption. In this work, we demonstrate multiheterodyne spectroscopy (MHS) using interband cascade lasers, which combines broadband spectral coverage with high spectral resolution and energy-efficient operation. The lasers generate up to 30 mW of continuous-wave optical power while consuming portable and high-resolution solid-state spectroscopic chemical sensors operating in the midinfrared.

  19. 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)

  20. 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.

  1. 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

  2. In Silico Screening and In Vitro Activity Measurement of Javamide Analogues as Potential p38 MAPK Inhibitors.

    Science.gov (United States)

    Park, Jae B

    2017-12-13

    p38 Mitogen-activated protein kinase (p38 MAPK) is a protein kinase critically involved in the progress of inflammation/stress-associated diseases. Our data suggested that javamide analogues may contain strong anti-inflammation activities, but there is little information about their effects on p38 MAPK. Therefore, in this paper, the effects of thirty javamide analogues on p38 MAPK were investigated using in silico screening and in vitro p38 MAPK assay methods. The javamide analogues were synthesized and their chemical structures were confirmed using nuclear magnetic resonance (NMR) spectroscopic methods. Then, the javamide analogues were screened using an in silico modeling program. The screened analogues demonstrated a wide range of binding energy (ΔE; -20 to -39) and several analogues with ΔE; -34 to -39 showed strong binding affinity to p38 MAPK. In vitro p38 MAPK assay, the kinase was significantly inhibited by the analogues with great binding energy (ΔE; -34 to -39) and in silico scores (Avg. score; -27.5 to -29.3). Furthermore, the comparative analysis of both assays showed a positive correlation between the in silico scores and p38 MAPK inhibition. In fact, the javamide analogues with top five in silico scores (Avg. score; -27.5 to -29.3) were found to inhibit p38 MAPK by 27-31% ( p silico score (Avg. score; -29.2) inhibited p38 MAPK (IC 50 = 9.9 μM) a little better than its methyl ester with best in silico score (Avg. score; -29.3). To support the ability to inhibit p38 MAPK, the treatment of javamide-II-ethyl and -methyl esters could suppress the production of IL-8 and MCP-1 protein significantly by 22-73% ( p silico and in vitro assay approach may be a useful and efficient solution as a functional screening approach in searching new lead compounds for targeted molecules.

  3. 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.

  4. 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%.

  5. 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.)

  6. Interleukin-1β-induced iNOS expression in human lung carcinoma A549 cells: involvement of STAT and MAPK pathways

    International Nuclear Information System (INIS)

    Ravichandran, Kameswaran; Tyagi, Alpna; Deep, Gagan; Agarwal, Chapla; Agarwal, Rajesh

    2011-01-01

    For understanding of signaling molecules important in lung cancer growth and progression, IL-1β effect was analyzed on iNOS expression and key signaling molecules in human lung carcinoma A549 cells and established the role of specific signaling molecules by using specific chemical inhibitors. IL-1β exposure (10 ng/ml) induced strong iNOS expression in serum starved A549 cells. Detailed molecular analyses showed that IL-1β increased expression of phosphorylated STAT1 (Tyr701 and Ser727) and STAT3 (Tyr705 and Ser727) both in total cell lysates and nuclear lysates. Further, IL-1β exposure strongly activated MAPKs (ERK1/2, JNK1/2 and p38) and Akt as well as increased nuclear levels of NF-κB and HIF-1α in A549 cells. Use of specific chemical inhibitors for JAK1 kinase (piceatannol), JAK2 kinase (AG-490), MEK1/2 (PD98059) and JNK1/2 (SP600125) revealed that IL-1β-induced iNOS expression involved signaling pathways in addition to JAKSTAT and ERK1/2-JNK1/2 activation. Overall, these results suggested that instead of specific pharmacological inhibitors, use of chemopreventive agents with broad spectrum efficacy to inhibit IL-1β-induced signaling cascades and iNOS expression would be a better strategy towards lung cancer prevention and/or treatment. (author)

  7. ZNF322, a novel human C2H2 Krueppel-like zinc-finger protein, regulates transcriptional activation in MAPK signaling pathways

    International Nuclear Information System (INIS)

    Li Yongqing; Wang Yuequn; Zhang Caibo; Yuan Wuzhou; Wang Jun; Zhu Chuanbing; Chen Lei; Huang Wen; Zeng Weiqi; Wu Xiushan; Liu Mingyao

    2004-01-01

    Cardiac differentiation involves a cascade of coordinated gene expression that regulates cell proliferation and matrix protein formation in a defined temporal-spatial manner. The C 2 H 2 zinc finger-containing transcription factors have been implicated as critical regulators of multiple cardiac-expressed genes and are important for human heart development and diseases. Here we have identified and characterized a novel zinc-finger gene named ZNF322 using degenerated primers from a human embryo heart cDNA library. The gene contains four exons and spans 23.2 kb in chromosome 6p22.1 region, and transcribes a 2.7 kb mRNA that encodes a protein with 402 amino acid residues. The predicted protein contains 9 tandem C 2 H 2 -type zinc-finger motifs. Northern blot analysis shows that ZNF322 is expressed in every human tissue examined at adult stage and during embryonic developmental stages from 80 days to 24 weeks. When overexpressed in COS-7 cells, ZNF322-EGFP fusion protein is detected in the nucleus and cytoplasm. Reporter gene assays show that ZNF322 is a transcriptional activator. Furthermore, overexpression of ZNF322 in COS-7 cells activates the transcriptional activity of SRE and AP-1. Together, these results suggest that ZNF322 is a member of the zinc-finger transcription factor family and may act as a positive regulator in gene transcription mediated by the MAPK signaling pathways

  8. Systems theory and cascades in developmental psychopathology.

    Science.gov (United States)

    Cox, Martha J; Mills-Koonce, Roger; Propper, Cathi; Gariépy, Jean-Louis

    2010-08-01

    In the wake of prominent theoreticians in developmental science, whose contributions we review in this article, many developmental psychologists came to endorse a systems approach to understanding how the individual, as it develops, establishes functional relationships to social ecological contexts that from birth to school entry rapidly increase in complexity. The concept of developmental cascade has been introduced in this context to describe lawful processes by which antecedent conditions may be related with varying probabilities to specified outcomes. These are understood as processes by which function at one level or in one domain of behavior affect the organization of competency in later developing domains of general adaptation. Here we propose a developmental sequence by which the developing child acquires regulative capacities that are key to adjustment to a society that demands considerable control of emotional and cognitive functions early in life. We report empirical evidence showing that the acquisition of regulative capacities may be understood as a cascade of shifts in control parameters induced by the progressive integration of biological, transactional, and socioaffective systems over development. We conclude by suggesting how the developmental process may be accessed for effective intervention in populations deemed "at risk" for later problems of psychosocial adjustment.

  9. Cascade biocatalysis by multienzyme-nanoparticle assemblies.

    Science.gov (United States)

    Kang, Wei; Liu, Jiahui; Wang, Jianpeng; Nie, Yunyu; Guo, Zhihong; Xia, Jiang

    2014-08-20

    Multienzyme complexes are of paramount importance in biosynthesis in cells. Yet, how sequential enzymes of cascade catalytic reactions synergize their activities through spatial organization remains elusive. Recent development of site-specific protein-nanoparticle conjugation techniques enables us to construct multienzyme assemblies using nanoparticles as the template. Sequential enzymes in menaquinone biosynthetic pathway were conjugated to CdSe-ZnS quantum dots (QDs, a nanosized particulate material) through metal-affinity driven self-assembly. The assemblies were characterized by electrophoretic methods, the catalytic activities were monitored by reverse-phase chromatography, and the composition of the multienzyme-QD assemblies was optimized through a progressive approach to achieve highly efficient catalytic conversion. Shorter enzyme-enzyme distance was discovered to facilitate intermediate transfer, and a fine control on the stoichiometric ratio of the assembly was found to be critical for the maximal synergy between the enzymes. Multienzyme-QD assemblies thereby provide an effective model to scrutinize the synergy of cascade enzymes in multienzyme complexes.

  10. 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.

  11. Cascaded clocks measurement and simulation findings

    Science.gov (United States)

    Chislow, Don; Zampetti, George

    1994-05-01

    This paper will examine aspects related to network synchronization distribution and the cascading of timing elements. Methods of timing distribution have become a much debated topic in standards forums and among network service providers (both domestically and internationally). Essentially these concerns focus on the need to migrate their existing network synchronization plans (and capabilities) to those required for the next generation of transport technologies (namely, the Synchronous Digital Hierarchy (SDH), Synchronous Optical Networks (SONET), and Asynchronous Transfer Mode (ATM). The particular choices for synchronization distribution network architectures are now being evaluated and are demonstrating that they can indeed have a profound effect on the overall service performance levels that will be delivered to the customer. The salient aspects of these concerns reduce to the following: (1) identifying that the devil is in the details of the timing element specifications and the distribution of timing information (i.e., small design choices can have a large performance impact); (2) developing a standardized method of performance verification that will yield unambiguous results; and (3) presentation of those results. Specifically, this will be done for two general cases: an ideal input, and a noisy input to a cascaded chain of slave clocks.

  12. 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

  13. Effect of a p38 MAPK inhibitor on FFA-induced hepatic insulin resistance in vivo.

    Science.gov (United States)

    Pereira, S; Yu, W Q; Moore, J; Mori, Y; Tsiani, E; Giacca, A

    2016-05-02

    The mechanisms whereby prolonged plasma free fatty acids elevation, as found in obesity, causes hepatic insulin resistance are not fully clarified. We herein investigated whether inhibition of p38 mitogen-activated protein kinase (MAPK) prevented hepatic insulin resistance following prolonged lipid infusion. Chronically cannulated rats were subdivided into one of four intravenous (i.v.) treatments that lasted 48 h: Saline (5.5 μl min(-1)), Intralipid plus heparin (IH, 20% Intralipid+20 U ml(-1) heparin; 5.5 μl min(-1)), IH+p38 MAPK inhibitor (SB239063) and SB239063 alone. During the last 2 h of treatment, a hyperinsulinemic (5 mU kg(-1) min(-1)) euglycemic clamp together with [3-(3)H] glucose methodology was carried out to distinguish hepatic from peripheral insulin sensitivity. We found that SB239063 prevented IH-induced hepatic insulin resistance, but not peripheral insulin resistance. SB239063 also prevented IH-induced phosphorylation of activating transcription factor 2 (ATF2), a marker of p38 MAPK activity, in the liver. Moreover, in another lipid infusion model in mice, SB239063 prevented hepatic but not peripheral insulin resistance caused by 48 h combined ethyloleate plus ethylpalmitate infusion. Our results suggest that inhibition of p38 MAPK may be a useful strategy in alleviating hepatic insulin resistance in obesity-associated disorders.

  14. Involvement of p38MAPK in Impaired Neutrophil Bactericidal Activity of Hemodialysis Patients.

    Science.gov (United States)

    Kamikawa, Yasutaka; Sakai, Norihiko; Miyake, Taito; Sagara, Akihiro; Shinozaki, Yasuyuki; Kitajima, Shinji; Toyama, Tadashi; Hara, Akinori; Iwata, Yasunori; Shimizu, Miho; Furuichi, Kengo; Imamura, Ryu; Suda, Takashi; Kaneko, Shuichi; Wada, Takashi

    2018-01-10

    Mortality from infections has been reported to be higher in hemodialysis (HD) patients. Although dysfunction of neutrophils against bacterial infection was reported in HD patients, the precise mechanism remains to be clarified. We therefore examined the impacts of neutrophil inflammatory signaling on bactericidal activity in HD patients. Comprehensive analyses of intracellular signalings were performed in whole blood of HD patients and control using a microarray system. To confirm the contribution of the signaling to bactericidal activity in neutrophils, we examined the phosphorylation, bacterial killing function, reactive oxygen species (ROS) production, and myeloperoxidase (MPO) release in neutrophils against Staphylococcus aureus. RNA microarray analysis showed the suppression of p38 mitogen activated protein kinase (MAPK) signaling in HD patients. Neutrophils in HD patients showed the impairment of bactericidal activity against S. aureus compared to healthy subjects. Phosphorylation rate of p38MAPK of neutrophils in response to S. aureus was lower in HD patients than healthy subjects. The levels of ROS produced by neutrophils after co-culture with S. aureus were lower in HD patients, on the other hand, there was no difference of MPO release between HD patients and healthy subjects. A selective pharmacological inhibitor of p38MAPK suppressed bacterial killing function as well as ROS production in neutrophils of healthy subjects. Impairment of p38MAPK signaling pathway might contribute to the suppression of neutrophil bactericidal activity in HD patients through less production of ROS. © 2018 International Society for Apheresis, Japanese Society for Apheresis, and Japanese Society for Dialysis Therapy.

  15. Estimating Network Kinetics of the MAPK/ERK Pathway Using Biochemical Data

    NARCIS (Netherlands)

    Purutcuoglu, Vilda; Wit, Ernst

    2012-01-01

    The MAPK/ERK pathway is a major signal transduction system which regulates many fundamental cellular processes including the growth control and the cell death. As a result of these roles, it has a crucial importance in cancer as well as normal developmental processes. Therefore, it has been

  16. MAPK/FoxA2-mediated cigarette smoke-induced squamous metaplasia of bronchial epithelial cells.

    Science.gov (United States)

    Du, Chunling; Lu, Jinchang; Zhou, Lei; Wu, Bo; Zhou, Feng; Gu, Liang; Xu, Donghui; Sun, Yingxin

    2017-01-01

    To explore the effect of cigarette smoke (CS) on the development of squamous metaplasia in human airway epithelial cells and the role of MAPK- and FoxA2-signaling pathways in the process. In an in vitro study, we treated the bronchial epithelial cell line BEAS2B with CS extract, followed by treatment with the ERK inhibitor U0126, the JNK inhibitor SP600125, or the p38 inhibitor SB203580. In vivo, we used a CS-induced rat model. After treatment with CS with or without MAPK inhibitors for 90 days, lung tissues were harvested. p-ERK, p-p38 and p-JNK protein levels in cells and lung tissue were measured using enzyme-linked immunosorbent assays, mRNA- and protein-expression profiles of FoxA2, E-cadherin, CD44, and ZO1 were measured using quantitative real-time polymerase chain reaction and Western blotting, respectively, and morphological changes in bronchial epithelial cells were observed using lung-tissue staining. In both the in vitro and in vivo studies, phosphorylation of the ERK1/2, JNK, and p38 proteins was significantly increased ( P FoxA2 significantly decreased ( P FoxA2 expression. MAPK and FoxA2 mediate CS-induced squamous metaplasia. MAPK inhibitors upregulate FoxA2, resulting in a reduction in the degree of squamous metaplasia.

  17. Dusuqing granules (DSQ) suppress inflammation in Klebsiella pneumonia rat via NF-κB/MAPK signaling.

    Science.gov (United States)

    Mei, Xue; Wang, Hao-Xun; Li, Jian-Sheng; Liu, Xiao-Hui; Lu, Xiao-Fan; Li, Ya; Zhang, Wei-Yu; Tian, Yan-Ge

    2017-04-17

    Dusuqing granules (DSQ) have been used in the treatment of bacterial pneumonia clinically, with remarkable benefits. This study was initiated to explore the effects of DSQ on pulmonary inflammation by regulating nuclear factor (NF)-κB/mitogen-activated protein kinase (MAPK) signaling in bacterial pneumonia rats. Rat model was duplicated with Klebsiella pneumonia by a one-time intratracheal injection. Rats were randomized into control, model, DSQ and levofloxacin (LVX) groups. After administrated with appropriate medicines for 7 days, lung tissues were harvested and prepared for pathological analysis, and interleukin (IL)-1, IL-6, monocyte chemotactic protein (MCP)-1and macrophage inflammatory protein (MIP)-2 detections. NF-κB mRNA was measured by real-time qPCR, and the phosphorylation and total proteins of P38MAPK, JNK46/54, ERK42/44 were determined by Western blotting. Marked pathological impairments were observed in model rats, whereas were improved in DSQ group. The cytokines levels, NF-κB mRNA expression and the phosphorylation of P38MAPK, JNK46/54 and ERK42/44 proteins were significantly higher in model group, and were significantly depressed in DSQ group. The protective effects of DSQ on Klebsiella pneumonia might be attributed to its inactivative effects of NF-κB/ MAPK pathway.

  18. Phosphofructokinase-P Modulates P44/42 MAPK Levels in HeLa Cells.

    Science.gov (United States)

    Cardim Pires, Thyago Rubens; Albanese, Jamille Mansur; Schwab, Michael; Marette, André; Carvalho, Renato Sampaio; Sola-Penna, Mauro; Zancan, Patricia

    2017-05-01

    It is known that interfering with glycolysis leads to profound modification of cancer cell proliferation. However, energy production is not the major reason for this correlation. Here, using HeLa cells as a model for cancer, we demonstrate that phosphofructokinase-P (PFK-P), which is overexpressed in diverse types of cancer including HeLa cells, modulates expression of P44/42 mitogen-activated protein kinase (MAPK). Silencing of PFK-P did not alter HeLa cell viability or energy production, including the glycolytic rate. On the other hand, silencing of PFK-P induced the downregulation of p44/42 MAPK, augmenting the sensitivity of HeLa cells to different drugs. Conversely, overexpression of PFK-P promotes the upregulation of p44/42 MAPK, making the cells more resistant to the drugs. These results indicate that overexpression of PFK-P by cancer cells is related to activation of survival pathways via upregulation of MAPK and suggest PFK-P as a promising target for cancer therapy. J. Cell. Biochem. 118: 1216-1226, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  19. PKG-Mediated MAPK Signaling Is Necessary for Long-Term Operant Memory in "Aplysia"

    Science.gov (United States)

    Michel, Maximilian; Green, Charity L.; Eskin, Arnold; Lyons, Lisa C.

    2011-01-01

    Signaling pathways necessary for memory formation, such as the mitogen-activated protein kinase (MAPK) pathway, appear highly conserved across species and paradigms. Learning that food is inedible (LFI) represents a robust form of associative, operant learning that induces short- (STM) and long-term memory (LTM) in "Aplysia." We investigated the…

  20. LcMKK, a MAPK kinase from Lycium chinense, confers cadmium ...

    Indian Academy of Sciences (India)

    Ethylene is an important phytohormone in the regulation of plant growth, development and stress response. Mitogen-activated protein kinase (MAPK) activation has been observed in plants exposed to Cd stress and was suggested to be involved in ethylene biosynthesis. We hypothesized that there may be a link between ...

  1. In Vitro Manganese Exposure Disrupts MAPK Signaling Pathways in Striatal and Hippocampal Slices from Immature Rats

    Directory of Open Access Journals (Sweden)

    Tanara Vieira Peres

    2013-01-01

    Full Text Available The molecular mechanisms mediating manganese (Mn-induced neurotoxicity, particularly in the immature central nervous system, have yet to be completely understood. In this study, we investigated whether mitogen-activated protein kinases (MAPKs and tyrosine hydroxylase (TH could represent potential targets of Mn in striatal and hippocampal slices obtained from immature rats (14 days old. The aim of this study was to evaluate if the MAPK pathways are modulated after subtoxic Mn exposure, which do not significantly affect cell viability. The concentrations of manganese chloride (MnCl2; 10–1,000 μM caused no change in cell viability in slices exposed for 3 or 6 hours. However, Mn exposure significantly increased extracellular signal-regulated kinase (ERK 1/2, as well as c-Jun N-terminal kinase (JNK 1/2/3 phosphorylation at both 3 and 6 hours incubations, in both brain structures. Furthermore, Mn exposure did not change the total content or phosphorylation of TH at the serine 40 site in striatal slices. Thus, Mn at concentrations that do not disrupt cell viability causes activation of MAPKs (ERK1/2 and JNK1/2/3 in immature hippocampal and striatal slices. These findings suggest that altered intracellular MAPKs signaling pathways may represent an early event concerning the effects of Mn in the immature brain.

  2. Rotationally invariant pattern recognition by use of linear and nonlinear cascaded filters

    Science.gov (United States)

    Wu, Ning; Alcock, Robin D.; Halliwell, Neil A.; Coupland, Jeremy M.

    2005-07-01

    We discuss the merits of using single-layer (linear and nonlinear) and multiple-layer (nonlinear) filters for rotationally invariant and noise-tolerant pattern recognition. The capability of each approach is considered with reference to a two-class, rotation-invariant, character recognition problem. The minimum average correlation energy (MACE) filter is a linear filter that is generally accepted to be optimal for detecting signals that are free from noise. Here it is found that an optimized MACE filter cannot differentiate between the characters E and F in a rotation-invariant manner. We have found, however, that this task is possible when a single optimized linear filter is used to achieve the required response when a nonlinear threshold function is included after the filter. We show that this structure can be cascaded to form a multiple-layer, cascaded filter and that the capability of such a system is enhanced by its increased noise tolerance in the character recognition problem. Finally, we show the capability of a two-layer cascade as a means to detect different species of bacteria in images obtained from a phase-contrast microscope.

  3. Chrysin protects against cisplatin-induced colon. toxicity via amelioration of oxidative stress and apoptosis: Probable role of p38MAPK and p53

    Energy Technology Data Exchange (ETDEWEB)

    Khan, Rehan; Khan, Abdul Quaiyoom; Qamar, Wajhul; Lateef, Abdul; Tahir, Mir; Rehman, Muneeb U; Ali, Farrah; Sultana, Sarwat, E-mail: sarwat786@rediffmail.com

    2012-02-01

    Cisplatin, an antineoplastic drug, is widely used as a foremost therapy against numerous forms of cancer but it has pronounced adverse effects viz., nephrotoxicity, ototoxicity etc. CDDP-induced emesis and diarrhea are also marked toxicities that may be due to intestinal injury. Chrysin (5,7-dihydroxyflavone), a natural flavone commonly found in many plants possesses multiple biological activities, such as antioxidant, anti-inflammatory and anti-cancer effects. In the present study, we investigated the protective effect of chrysin against CDDP-induced colon toxicity. The plausible mechanism of CDDP-induced colon toxicity and damage includes oxidative stress, activation of p38MAPK and p53, and colonic epithelial cell apoptosis via upregulating the expression of Bak and cleaved caspase-3. Chrysin was administered to Wistar rats once daily for 14 consecutive days at the doses of 25 and 50 mg/kg body weight orally in corn oil. On day 14, a single intraperitoneal injection of cisplatin was given at the dose of 7.5 mg/kg body weight and animals were euthanized after 24 h of cisplatin injection. Chrysin ameliorated CDDP-induced lipid peroxidation, xanthine oxidase activity, glutathione depletion, decrease in antioxidant (catalase, glutathione reductase, glutathione peroxidase and glucose-6 phosphate dehydrogenase) and phase-II detoxifying (glutathione-S-transferase and quinone reductase) enzyme activities. Chrysin also attenuated goblet cell disintegration, expression of phospho-p38MAPK and p53, and apoptotic tissue damage which were induced by CDDP. Histological findings further supported the protective effects of chrysin against CDDP-induced colonic damage. The results of the present study suggest that the protective effect of chrysin against CDDP-induced colon toxicity was related with attenuation of oxidative stress, activation of p38MAPK and p53, and apoptotic tissue damage. Highlights: ► Cisplatin-induced colon toxicity is associated with oxidative stress and

  4. TGF-β1-induced cell migration in pancreatic carcinoma cells is RAC1 and NOX4-dependent and requires RAC1 and NOX4-dependent activation of p38 MAPK.

    Science.gov (United States)

    Witte, David; Bartscht, Tobias; Kaufmann, Roland; Pries, Ralph; Settmacher, Utz; Lehnert, Hendrik; Ungefroren, Hendrik

    2017-12-01

    Transforming growth factor (TGF)-β promotes epithelial-mesenchymal transition and cell invasion of cancer cells in part through the small GTPase RAC1. Since RAC1 can signal through reactive oxygen species (ROS), we probed the role of the ROS-producing NADPH oxidase (NOX) and p38 mitogen-activated protein kinase (MAPK) in mediating TGF-β1/RAC1-driven random cell migration (chemokinesis). Although the NOX isoforms NOX2, 4, 5, 6, and RAC1 were readily detectable by RT-PCR in pancreatic ductal adenocarcinoma (PDAC)-derived Panc1 and Colo357 cells, only NOX4 and RAC1 were expressed at higher levels comparable to those in peripheral blood monocytes. TGF-β1 treatment resulted in upregulation of NOX4 (and NOX2) and rapid intracellular production of ROS. To analyze whether RAC1 functions through NOX and ROS to promote cell motility, we performed real-time cell migration assays with xCELLigence® technology in the presence of the ROS scavenger N-acetyl-L-cysteine (NAC) and various NOX inhibitors. NAC, the NOX4 inhibitor diphenylene iodonium or small interfering RNA (siRNA) to NOX4, and the NOX2 inhibitor apocynin all suppressed TGF-β1-induced chemokinesis of Panc1 and Colo357 cells as did various inhibitors of RAC1 used as control. In addition, we showed that blocking NOX4 or RAC1 function abrogated phosphorylation of p38 MAPK signaling by TGF-β1 and that inhibition of p38 MAPK reduced TGF-β1-induced random cell migration, while ectopic expression of a kinase-active version of the p38 activating kinase MKK6 was able to partially rescue the decline in migration after RAC1 inhibition. Our data suggest that TGF-β1-induced chemokinesis in PDAC cells is mediated through a RAC1/NOX4/ROS/p38 MAPK cascade.

  5. Cadmium stimulates MAPKs and Hsp27 phosphorylation in bovine adrenal chromaffin cells

    International Nuclear Information System (INIS)

    Leal, Rodrigo B.; Posser, Thais; Rigon, Ana Paula; Oliveira, Camila S.; Goncalves, Carlos Alberto; Gelain, Daniel P.; Dunkley, Peter R.

    2007-01-01

    Cadmium (Cd 2+ ) is a common environmental pollutant, which is widely used in industry and is a constituent of tobacco smoke. Exposure to this heavy metal has been linked to a wide range of detrimental effects on mammalian cells. In this study, the action of Cd 2+ on protein phosphorylation in bovine adrenal chromaffin cells (BACCs) was examined. Cells were incubated with 32 Pi in the presence of Cd 2+ (1-50 μM) and proteins were separated by one- or two-dimensional electrophoresis. An increase in the phosphorylation of BACCs proteins, without changing cell viability, was observed in response to Cd 2+ (5-50 μM). Particularly at three spots, with molecular weight of 25 kDa and isoeletric point range 4.0-4.5, which were identified as phosphorylated isoforms of the heat shock protein of 27 kDa (Hsp27). Phosphorylation of the p38 MAPK , a member of mitogen-activated protein kinase (MAPK) family, was stimulated by Cd 2+ over the same concentration range and it was the major upstream protein kinase involved in the phosphorylation of all three spots of Hsp27. Cd 2+ also stimulated the phosphorylation of other MAPK family member, the extracellular signal-regulated kinase (ERK)-1/2. Therefore, primary adrenal chromaffin cells are a target for Cd 2+ and both the ERK1/2 and the p38 MAPK are activated. Additionally, Hsp27 is highly phosphorylated in response to the metal exposure, due to p38 MAPK activation. These biochemical effects of Cd 2+ might disrupt the normal secretory function of these cells

  6. The Role of MAPK Modules and ABA during Abiotic Stress Signaling

    KAUST Repository

    Zélicourt, Axel de

    2016-05-01

    To respond to abiotic stresses, plants have developed specific mechanisms that allow them to rapidly perceive and respond to environmental changes. The phytohormone abscisic acid (ABA) was shown to be a pivotal regulator of abiotic stress responses in plants, triggering major changes in plant physiology. The ABA core signaling pathway largely relies on the activation of SnRK2 kinases to mediate several rapid responses, including gene regulation, stomatal closure, and plant growth modulation. Mitogen-activated protein kinases (MAPKs) have also been implicated in ABA signaling, but an entire ABA-activated MAPK module was uncovered only recently. In this review, we discuss the evidence for a role of MAPK modules in the context of different plant ABA signaling pathways. Abiotic stresses impact average yield in agriculture by more than 50% globally.Since ABA is a key regulator of abiotic stress responses, an understanding of its functioning at the molecular level is essential for plant breeding. Although the ABA core signaling pathway has been unraveled, several downstream events are still unclear.MAPKs are involved in most plant developmental stages and in response to stresses. Several members of the MAPK family were shown to be directly or indirectly activated by the ABA core signaling pathway.Recent evidence shows that the complete MAP3K17/18-MKK3-MPK1/2/7/14 module is under the control of ABA, whose members are under the transcriptional and post-translational control of the ABA core signaling pathway. © 2016 Elsevier Ltd.

  7. Oxidative bioelectrocatalysis: From natural metabolic pathways to synthetic metabolons and minimal enzyme cascades.

    Science.gov (United States)

    Minteer, Shelley D

    2016-05-01

    Anodic bioelectrodes for biofuel cells are more complex than cathodic bioelectrodes for biofuel cells, because laccase and bilirubin oxidase can individually catalyze four electron reduction of oxygen to water, whereas most anodic enzymes only do a single two electron oxidation of a complex fuel (i.e. glucose oxidase oxidizing glucose to gluconolactone while generating 2 electrons of the total 24 electrons), so enzyme cascades are typically needed for complete oxidation of the fuel. This review article will discuss the lessons learned from natural metabolic pathways about multi-step oxidation and how those lessons have been applied to minimal or artificial enzyme cascades. This article is part of a Special Issue entitled Biodesign for Bioenergetics--the design and engineering of electronic transfer cofactors, proteins and protein networks, edited by Ronald L. Koder and J.L. Ross Anderson. Copyright © 2015. Published by Elsevier B.V.

  8. Analysis of Multicarrier PWM techniques for Photovoltaic fed Cascaded H-Bridge Multilevel Inverter

    Directory of Open Access Journals (Sweden)

    VENKATRAMAN Thiyagarajan

    2017-05-01

    Full Text Available Recently multilevel inverter technology emerging as an important alternative in the field of high power, medium voltage energy control. The various topologies for multilevel inverters such as diode-clamped, flying capacitor and cascaded H-bridge have been proposed over the years. This paper analysis the performance of a single phase seven level cascaded H-bridge inverter for photovoltaic applications. The Phase Disposition PWM (PDPWM technique is used to generate gate signals. The performance is compared for both sinusoidal reference waveform and trapezoidal reference waveform. The analysis is carried out for different modulation index and different shading pattern of photovoltaic (PV array. The simulation is carried out using MATLAB/SIMULINK software.

  9. Distributed torsion sensor based on cascaded coaxial cable Fabry–Perot interferometers

    International Nuclear Information System (INIS)

    Cheng, Baokai; Zhu, Wenge; Hua, Liwei; Liu, Jie; Xiao, Hai; Li, Yurong; Nygaard, Runar

    2016-01-01

    Cascaded coaxial cable Fabry–Perot interferometers (FPI) are studied and demonstrated for distributed torsion measurement. Multiple weak reflectors are implemented on a coaxial cable so that any two consecutive reflectors can form a Fabry–Perot cavity. By fixing the cable sensor in a helical form on a shaft, the distributed torsion of the shaft can be measured by the cascaded Fabry–Perot cavities. A test on a single section shows that the sensor has a linear response with a sensitivity of 1.834 MHz (rad/m) −1 in the range of twisted rate from 0 to 8.726 rad m −1 . The distributed torsion sensing capability is useful in drilling process monitoring, structure health monitoring and machine failure detection. (paper)

  10. Simulation and optimization of stable isotope 18O separation by cascade distillation

    International Nuclear Information System (INIS)

    Jiang Yongyue; Chen Yuyan; Qin Chuanjiang; Liu Yan; Gu Hongsen

    2011-01-01

    The research about started from the plan of four cascade towers design was carried. Firstly, the method of experiment design was using uniform design. Then the incidence formula with the method of binomial stepwise regression was gotten. Last, the optimal operation conditions were gotten by using the method of genetic algorithm. Considering comprehensive factors of drawn from feed rate and from flow rates between cascade column, conclusions were reached on the study of the impact on the abundance of the isotope 18 O. Finally, the incidence formula between the abundance of the isotope 18 O and four operating variables were gotten. Also the incidence formula between heat consumption of the isotope 18 O and four operating variables were gotten. Besides, single factor response diagram of four factors were shown at last. The results showed that the method of simulation and optimization could be applied to 18 O industrial design and would be popular in traditional distillation process to realize optimization design. (authors)

  11. An automated Monte-Carlo based method for the calculation of cascade summing factors

    Science.gov (United States)

    Jackson, M. J.; Britton, R.; Davies, A. V.; McLarty, J. L.; Goodwin, M.

    2016-10-01

    A versatile method has been developed to calculate cascade summing factors for use in quantitative gamma-spectrometry analysis procedures. The proposed method is based solely on Evaluated Nuclear Structure Data File (ENSDF) nuclear data, an X-ray energy library, and accurate efficiency characterisations for single detector counting geometries. The algorithm, which accounts for γ-γ, γ-X, γ-511 and γ-e- coincidences, can be applied to any design of gamma spectrometer and can be expanded to incorporate any number of nuclides. Efficiency characterisations can be derived from measured or mathematically modelled functions, and can accommodate both point and volumetric source types. The calculated results are shown to be consistent with an industry standard gamma-spectrometry software package. Additional benefits including calculation of cascade summing factors for all gamma and X-ray emissions, not just the major emission lines, are also highlighted.

  12. Mouse preimplantation embryo responses to culture medium osmolarity include increased expression of CCM2 and p38 MAPK activation

    Directory of Open Access Journals (Sweden)

    Watson Andrew J

    2007-01-01

    Full Text Available Abstract Background Mechanisms that confer an ability to respond positively to environmental osmolarity are fundamental to ensuring embryo survival during the preimplantation period. Activation of p38 mitogen-activated protein kinase (MAPK occurs following exposure to hyperosmotic treatment. Recently, a novel scaffolding protein called Osmosensing Scaffold for MEKK3 (OSM was linked to p38 MAPK activation in response to sorbitol-induced hypertonicity. The human ortholog of OSM is cerebral cavernous malformation 2 (CCM2. The present study was conducted to investigate whether CCM2 is expressed during mouse preimplantation development and to determine whether this scaffolding protein is associated with p38 MAPK activation following exposure of preimplantation embryos to hyperosmotic environments. Results Our results indicate that Ccm2 along with upstream p38 MAPK pathway constituents (Map3k3, Map2k3, Map2k6, and Map2k4 are expressed throughout mouse preimplantation development. CCM2, MAP3K3 and the phosphorylated forms of MAP2K3/MAP2K6 and MAP2K4 were also detected throughout preimplantation development. Embryo culture in hyperosmotic media increased p38 MAPK activity in conjunction with elevated CCM2 levels. Conclusion These results define the expression of upstream activators of p38 MAPK during preimplantation development and indicate that embryo responses to hyperosmotic environments include elevation of CCM2 and activation of p38 MAPK.

  13. Oncogenic Effects of High MAPK Activity in Colorectal Cancer Mark Progenitor Cells and Persist Irrespective of RAS Mutations.

    Science.gov (United States)

    Blaj, Cristina; Schmidt, Eva Marina; Lamprecht, Sebastian; Hermeking, Heiko; Jung, Andreas; Kirchner, Thomas; Horst, David

    2017-04-01

    About 40% of colorectal cancers have mutations in KRAS accompanied by downstream activation of MAPK signaling, which promotes tumor invasion and progression. Here, we report that MAPK signaling shows strong intratumoral heterogeneity and unexpectedly remains regulated in colorectal cancer irrespective of KRAS mutation status. Using primary colorectal cancer tissues, xenograft models, and MAPK reporter constructs, we showed that tumor cells with high MAPK activity resided specifically at the leading tumor edge, ceased to proliferate, underwent epithelial-mesenchymal transition (EMT), and expressed markers related to colon cancer stem cells. In KRAS-mutant colon cancer, regulation of MAPK signaling was preserved through remaining wild-type RAS isoforms. Moreover, using a lineage tracing strategy, we provide evidence that high MAPK activity marked a progenitor cell compartment of growth-fueling colon cancer cells in vivo Our results imply that differential MAPK signaling balances EMT, cancer stem cell potential, and tumor growth in colorectal cancer. Cancer Res; 77(7); 1763-74. ©2017 AACR . ©2017 American Association for Cancer Research.

  14. A cell-death-defying factor, anamorsin mediates cell growth through inactivation of PKC and p38MAPK

    International Nuclear Information System (INIS)

    Saito, Yuri; Shibayama, Hirohiko; Tanaka, Hirokazu; Tanimura, Akira; Kanakura, Yuzuru

    2011-01-01

    Research highlights: → Anamorsin (AM) (also called CIAPIN-1) is a cell-death-defying factor. → Biological mechanisms of AM functions have not been elucidated yet. → PKCθ , PKCδ and p38MAPK were more phosphorylated in AM deficient MEF cells. → AM may negatively regulates PKCs and p38MAPK in MEF cells. -- Abstract: Anamorsin (AM) plays crucial roles in hematopoiesis and embryogenesis. AM deficient (AM KO) mice die during late gestation; AM KO embryos are anemic and very small compared to wild type (WT) embryos. To determine which signaling pathways AM utilizes for these functions, we used murine embryonic fibroblast (MEF) cells generated from E-14.5 AM KO or WT embryos. Proliferation of AM KO MEF cells was markedly retarded, and PKCθ, PKCδ, and p38MAPK were more highly phosphorylated in AM KO MEF cells. Expression of cyclinD1, the target molecule of p38MAPK, was down-regulated in AM KO MEF cells. p38MAPK inhibitor as well as PKC inhibitor restored expression of cyclinD1 and cell growth in AM KO MEF cells. These data suggest that PKCθ, PKCδ, and p38MAPK activation lead to cell cycle retardation in AM KO MEF cells, and that AM may negatively regulate novel PKCs and p38MAPK in MEF cells.

  15. 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

  16. 36 CFR 7.66 - North Cascades National Park.

    Science.gov (United States)

    2010-07-01

    ... 36 Parks, Forests, and Public Property 1 2010-07-01 2010-07-01 false North Cascades National Park. 7.66 Section 7.66 Parks, Forests, and Public Property NATIONAL PARK SERVICE, DEPARTMENT OF THE INTERIOR SPECIAL REGULATIONS, AREAS OF THE NATIONAL PARK SYSTEM § 7.66 North Cascades National Park. (a...

  17. 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...

  18. 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.

  19. 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.)

  20. 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

  1. A nine-level hybrid symmetric cascaded multilevel converter for ...

    Indian Academy of Sciences (India)

    Indrajit Sarkar

    Abstract. A nine-level hybrid symmetric cascaded multilevel converter (MLC) fed induction motor drive is proposed in this paper. The proposed converter is capable of producing nine output voltage levels by using the same number of power cells as that of conventional five-level symmetric cascaded H-bridge converter.

  2. Cascade vulnerability for risk analysis of water infrastructure.

    Science.gov (United States)

    Sitzenfrei, R; Mair, M; Möderl, M; Rauch, W

    2011-01-01

    One of the major tasks in urban water management is failure-free operation for at least most of the time. Accordingly, the reliability of the network systems in urban water management has a crucial role. The failure of a component in these systems impacts potable water distribution and urban drainage. Therefore, water distribution and urban drainage systems are categorized as critical infrastructure. Vulnerability is the degree to which a system is likely to experience harm induced by perturbation or stress. However, for risk assessment, we usually assume that events and failures are singular and independent, i.e. several simultaneous events and cascading events are unconsidered. Although failures can be causally linked, a simultaneous consideration in risk analysis is hardly considered. To close this gap, this work introduces the term cascade vulnerability for water infrastructure. Cascade vulnerability accounts for cascading and simultaneous events. Following this definition, cascade risk maps are a merger of hazard and cascade vulnerability maps. In this work cascade vulnerability maps for water distribution systems and urban drainage systems based on the 'Achilles-Approach' are introduced and discussed. It is shown, that neglecting cascading effects results in significant underestimation of risk scenarios.

  3. Influence of blood flow on the coagulation cascade

    DEFF Research Database (Denmark)

    The influence of diffusion and convetive flows on the blood coagulation cascade is investigated for a controlled perfusion experiment. We present a cartoon model and reaction schemes for parts of the coagulation cascade with sunsequent set up of a mathematical model in two space dimensions plus one...

  4. A nine-level hybrid symmetric cascaded multilevel converter for ...

    Indian Academy of Sciences (India)

    A nine-level hybrid symmetric cascaded multilevel converter (MLC) fed induction motor drive is proposed in this paper. The proposed converter is capable of producing nine output voltage levels by using the same number of power cells as that of conventional five-level symmetric cascaded H-bridge converter. Eachphase in ...

  5. Intrinsic JNK-MAPK pathway involvement requires daf-16-mediated immune response during Shigella flexneri infection in C. elegans.

    Science.gov (United States)

    Marudhupandiyan, Shanmugam; Balamurugan, Krishnaswamy

    2017-06-01

    The c-Jun N-terminal kinase-mitogen-activated protein kinase (JNK-MAPK) pathway assists in modulating signals for growth, survival, and metabolism, thereby coordinating many cellular events during normal and stress conditions. To understand the role of the JNK-MAPK pathway during bacterial infection, an in vivo model organism Caenorhabditis elegans was used. In order to check the involvement of the JNK-MAPK pathway, the survival rate of C. elegans wild type (WT), and JNK-MAPK pathway mutant worms' upon exposure to selective Gram-positive and Gram-negative pathogenic bacteria, was studied. Among the pathogens, Shigella flexneri M9OT was found to efficiently colonize inside the WT and JNK-MAPK pathway mutant worms. qPCR studies had suggested that the above pathway-specific genes kgb-2 and jnk-1 were prominently responsible for the immune response elicited by the host during the M9OT infection. In addition, daf-16, which is a major transcription factor of the insulin/insulin growth factor-1 signaling (IIS) pathway, was also found to be involved during the host response. Crosstalk between IIS and JNK-MAPK pathways has probably been involved in the activation of the host immune system, which consequently leads to lifespan extension. Furthermore, it is also observed that daf-16 activation by JNK-MAPK pathway leads to antimicrobial response, by activating lys-7 expression. These findings suggest that JNK-MAPK is not the sole pathway that enhances the immunity of the host. Nonetheless, the IIS pathway bridges the JNK-MAPK pathway that influences in protecting the host in counter to the M9OT infection.

  6. Genomic and transcriptome analyses reveal that MAPK- and phosphatidylinositol-signaling pathways mediate tolerance to 5-hydroxymethyl-2-furaldehyde for industrial yeast Saccharomyces cerevisiae.

    Science.gov (United States)

    Zhou, Qian; Liu, Z Lewis; Ning, Kang; Wang, Anhui; Zeng, Xiaowei; Xu, Jian

    2014-10-09

    The industrial yeast Saccharomyces cerevisiae is a traditional ethanologenic agent and a promising biocatalyst for advanced biofuels production using lignocellulose materials. Here we present the genomic background of type strain NRRL Y-12632 and its transcriptomic response to 5-hydroxymethyl-2-furaldehyde (HMF), a commonly encountered toxic compound liberated from lignocellulosic-biomass pretreatment, in dissecting the genomic mechanisms of yeast tolerance. Compared with the genome of laboratory model strain S288C, we identified more than 32,000 SNPs in Y-12632 with 23,000 missense and nonsense SNPs. Enriched sequence mutations occurred for genes involved in MAPK- and phosphatidylinositol (PI)- signaling pathways in strain Y-12632, with 41 and 13 genes containing non-synonymous SNPs, respectively. Many of these mutated genes displayed consistent up-regulated signature expressions in response to challenges of 30 mM HMF. Analogous single-gene deletion mutations of these genes showed significantly sensitive growth response on a synthetic medium containing 20 mM HMF. Our results suggest at least three MAPK-signaling pathways, especially for the cell-wall integrity pathway, and PI-signaling pathways to be involved in mediation of yeast tolerance against HMF in industrial yeast Saccharomyces cerevisiae. Higher levels of sequence variations were also observed for genes involved in purine and pyrimidine metabolism pathways.

  7. Arabidopsis LIP5, a positive regulator of multivesicular body biogenesis, is a critical target of pathogen-responsive MAPK cascade in plant basal defense.

    Directory of Open Access Journals (Sweden)

    Fei Wang

    2014-07-01

    Full Text Available Multivesicular bodies (MVBs play essential roles in many cellular processes. The MVB pathway requires reversible membrane association of the endosomal sorting complexes required for transports (ESCRTs for sustained protein trafficking. Membrane dissociation of ESCRTs is catalyzed by the AAA ATPase SKD1, which is stimulated by LYST-interacting protein 5 (LIP5. We report here that LIP5 is a target of pathogen-responsive mitogen-activated protein kinases (MPKs and plays a critical role in plant basal resistance. Arabidopsis LIP5 interacts with MPK6 and MPK3 and is phosphorylated in vitro by activated MPK3 and MPK6 and in vivo upon expression of MPK3/6-activating NtMEK2DD and pathogen infection. Disruption of LIP5 has little effects on flg22-, salicylic acid-induced defense responses but compromises basal resistance to Pseudomonas syringae. The critical role of LIP5 in plant basal resistance is dependent on its ability to interact with SKD1. Mutation of MPK phosphorylation sites in LIP5 does not affect interaction with SKD1 but reduces the stability and compromises the ability to complement the lip5 mutant phenotypes. Using the membrane-selective FM1-43 dye and transmission electron microscopy, we demonstrated that pathogen infection increases formation of both intracellular MVBs and exosome-like paramural vesicles situated between the plasma membrane and the cell wall in a largely LIP5-dependent manner. These results indicate that the MVB pathway is positively regulated by pathogen-responsive MPK3/6 through LIP5 phosphorylation and plays a critical role in plant immune system likely through relocalization of defense-related molecules.

  8. Nox Complex signal and MAPK cascade pathway are cross-linked and essential for pathogenicity and conidiation of mycoparasite Coniothyrium minitans

    Science.gov (United States)

    The NADPH oxidase complex of a sclerotial mycoparasite Coniothyrium minitans, an important biocontrol agent against crop diseases caused by Sclerotinia sclerotiorum, was identified and its functions involved in conidiation and mycoparasitism were studied. Gene knock-out and complementation experimen...

  9. Andrographolide induces vascular smooth muscle cell apoptosis through a SHP-1-PP2A-p38MAPK-p53 cascade

    OpenAIRE

    Chen, Yu-Ying; Hsieh, Cheng-Ying; Jayakumar, Thanasekaran; Lin, Kuan-Hung; Chou, Duen-Suey; Lu, Wan-Jung; Hsu, Ming-Jen; Sheu, Joen-Rong

    2014-01-01

    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 ...

  10. Decoherence in high barrier quantum cascade structures

    Science.gov (United States)

    Freeman, Will

    2017-07-01

    High barrier AlxGa1-xAs terahertz quantum cascade structures with AlAs compositions up to 30% are studied. The influence of thermally excited leakage scattering to higher bound energy states and decoherence effects are investigated using a density matrix method where the pure dephasing time is self-consistently solved. The lattice temperature dependence of the light output in diagonal optical transition structures is calculated and shown to be consistent with experiment. Scattering from the upper lasing state to higher bound energy states is found to have minimal effects, and rather the decoherence from the calculated reduction of the pure dephasing time due to the impurity interaction is primarily responsible for the temperature dependence of a recently reported structure. This shows that the effects from an increased impurity interaction due to thinner barriers and different well dimensions can dominate over that from the increased interface roughness interaction due to higher potentials.

  11. 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

  12. 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.

  13. 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

  14. 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.

  15. 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.

  16. Availability Cascades and the Sharing Economy

    DEFF Research Database (Denmark)

    Netter, Sarah

    2016-01-01

    As scholars search for a new concept that will provide answers on how modern societies should make sense of and resolve the social and environmental problems linked to our modes of production and consumption, the sharing economy is attracting increased attention. To better understand this emergent...... focus on a sharing economy and associated business and consumption models, this conceptual chapter applies cascade theory to some of the most pronounced narratives , suggesting a win-win scenario, especially as they relate to the claim of sustainability. Given academics, practitioners, and civil society......’s shared history of (too) rapidly embracing new concepts that enable both business opportunities and a clear conscience, this chapter proposes that the implications of the sharing economy should be critically explored before it is actively promoted as the latest best fix....

  17. 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

  18. DMPD: DUSP meet immunology: dual specificity MAPK phosphatases in control of theinflammatory response. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 17114416 DUSP meet immunology: dual specificity MAPK phosphatases in control of the...inflammatory response. Lang R, Hammer M, Mages J. J Immunol. 2006 Dec 1;177(11):7497-504. (.png) (.svg) (.ht...ml) (.csml) Show DUSP meet immunology: dual specificity MAPK phosphatases in control of theinflammatory resp...onse. PubmedID 17114416 Title DUSP meet immunology: dual specificity MAPK phospha...tases in control of theinflammatory response. Authors Lang R, Hammer M, Mages J. Publication J Immunol. 2006

  19. Role of AMPA receptors in homocysteine-NMDA receptor-induced crosstalk between ERK and p38 MAPK.

    Science.gov (United States)

    Poddar, Ranjana; Chen, Alexandria; Winter, Lucas; Rajagopal, Sathyanarayanan; Paul, Surojit

    2017-08-01

    Homocysteine, a metabolite of the methionine cycle has been reported to play a role in neurotoxicity through activation of N-methyl-d-aspartate receptors (NMDAR)-mediated signaling pathway. The proposed mechanisms associated with homocysteine-NMDAR-induced neurotoxicity involve a unique signaling pathway that triggers a crosstalk between extracellular signal-regulated kinase (ERK) and p38 MAPKs, where activation of p38 MAPK is downstream of and dependent on ERK MAPK. However, the molecular basis of the ERK MAPK-mediated p38 MAPK activation is not understood. This study investigates whether α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) play a role in facilitating the ERK MAPK-mediated p38 MAPK activation. Using surface biotinylation and immunoblotting approaches we show that treatment with homocysteine leads to a decrease in surface expression of GluA2-AMPAR subunit in neurons, but have no effect on the surface expression of GluA1-AMPAR subunit. Inhibition of NMDAR activation with D-AP5 or ERK MAPK phosphorylation with PD98059 attenuates homocysteine-induced decrease in surface expression of GluA2-AMPAR subunit. The decrease in surface expression of GluA2-AMPAR subunit is associated with p38 MAPK phosphorylation, which is inhibited by 1-napthyl acetyl spermine trihydrochloride (NASPM), a selective antagonist of GluA2-lacking Ca 2+ -permeable AMPARs. These results suggest that homocysteine-NMDAR-mediated ERK MAPK phosphorylation leads to a decrease in surface expression of GluA2-AMPAR subunit resulting in Ca 2+ influx through the GluA2-lacking Ca 2+ -permeable AMPARs and p38 MAPK phosphorylation. Cell death assays further show that inhibition of AMPAR activity with 2,3-dioxo-6-nitro-1,2,3,4,tetrahydrobenzoquinoxaline-7-sulfonamide (NBQX)/6-cyano-7-nitroquinoxaline-2,3, -dione (CNQX) or GluA2-lacking Ca 2+ -permeable AMPAR activity with NASPM attenuates homocysteine-induced neurotoxicity. We have identified an important mechanism involved in

  20. Tumor cell phenotype is sustained by selective MAPK oxidation in mitochondria.

    Directory of Open Access Journals (Sweden)

    Soledad Galli

    2008-06-01

    Full Text Available Mitochondria are major cellular sources of hydrogen peroxide (H(2O(2, the production of which is modulated by oxygen availability and the mitochondrial energy state. An increase of steady-state cell H(2O(2 concentration is able to control the transition from proliferating to quiescent phenotypes and to signal the end of proliferation; in tumor cells thereby, low H(2O(2 due to defective mitochondrial metabolism can contribute to sustain proliferation. Mitogen-activated protein kinases (MAPKs orchestrate signal transduction and recent data indicate that are present in mitochondria and regulated by the redox state. On these bases, we investigated the mechanistic connection of tumor mitochondrial dysfunction, H(2O(2 yield, and activation of MAPKs in LP07 murine tumor cells with confocal microscopy, in vivo imaging and directed mutagenesis. Two redox conditions were examined: low 1 microM H(2O(2 increased cell proliferation in ERK1/2-dependent manner whereas high 50 microM H(2O(2 arrested cell cycle by p38 and JNK1/2 activation. Regarding the experimental conditions as a three-compartment model (mitochondria, cytosol, and nuclei, the different responses depended on MAPKs preferential traffic to mitochondria, where a selective activation of either ERK1/2 or p38-JNK1/2 by co-localized upstream kinases (MAPKKs facilitated their further passage to nuclei. As assessed by mass spectra, MAPKs activation and efficient binding to cognate MAPKKs resulted from oxidation of conserved ERK1/2 or p38-JNK1/2 cysteine domains to sulfinic and sulfonic acids at a definite H(2O(2 level. Like this, high H(2O(2 or directed mutation of redox-sensitive ERK2 Cys(214 impeded binding to MEK1/2, caused ERK2 retention in mitochondria and restricted shuttle to nuclei. It is surmised that selective cysteine oxidations adjust the electrostatic forces that participate in a particular MAPK-MAPKK interaction. Considering that tumor mitochondria are dysfunctional, their inability to

  1. Complex interdependent supply chain networks: Cascading failure and robustness

    Science.gov (United States)

    Tang, Liang; Jing, Ke; He, Jie; Stanley, H. Eugene

    2016-02-01

    A supply chain network is a typical interdependent network composed of an undirected cyber-layer network and a directed physical-layer network. To analyze the robustness of this complex interdependent supply chain network when it suffers from disruption events that can cause nodes to fail, we use a cascading failure process that focuses on load propagation. We consider load propagation via connectivity links as node failure spreads through one layer of an interdependent network, and we develop a priority redistribution strategy for failed loads subject to flow constraint. Using a giant component function and a one-to-one directed interdependence relation between nodes in a cyber-layer network and physical-layer network, we construct time-varied functional equations to quantify the dynamic process of failed loads propagation in an interdependent network. Finally, we conduct a numerical simulation for two cases, i.e., single node removal and multiple node removal at the initial disruption. The simulation results show that when we increase the number of removed nodes in an interdependent supply chain network its robustness undergoes a first-order discontinuous phase transition, and that even removing a small number of nodes will cause it to crash.

  2. Coevolving MAPK and PID phosphosites indicate an ancient environmental control of PIN auxin transporters in land plants.

    Science.gov (United States)

    Dory, Magdalena; Hatzimasoura, Elizabeth; Kállai, Brigitta M; Nagy, Szilvia K; Jäger, Katalin; Darula, Zsuzsanna; Nádai, Tímea V; Mészáros, Tamás; López-Juez, Enrique; Barnabás, Beáta; Palme, Klaus; Bögre, László; Ditengou, Franck A; Dóczi, Róbert

    2018-01-01

    Plant growth flexibly adapts to environmental conditions, implying cross-talk between environmental signalling and developmental regulation. Here, we show that the PIN auxin efflux carrier family possesses three highly conserved putative mitogen-activated protein kinase (MAPK) sites adjacent to the phosphorylation sites of the well-characterised AGC kinase PINOID, which regulates the polar localisation of PINs and directional auxin transport, thereby underpinning organ growth. The conserved sites of PIN1 are phosphorylated in vitro by two environmentally activated MAPKs, MPK4 and MPK6. In contrast to AGC kinases, MAPK-mediated phosphorylation of PIN1 at adjacent sites leads to a partial loss of the plasma membrane localisation of PIN1. MAPK-mediated modulation of PIN trafficking may participate in environmental adjustment of plant growth. © 2017 The Authors. FEBS Letters published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.

  3. Convergence of Multiple MAP3Ks on MKK3 Identifies a Set of Novel Stress MAPK Modules

    KAUST Repository

    Colcombet, Jean

    2016-12-22

    Since its first description in 1995 and functional characterization 12 years later, plant MKK3-type MAP2Ks have emerged as important integrators in plant signaling. Although they have received less attention than the canonical stress-activated mitogen-activated protein kinases (MAPKs), several recent publications shed light on their important roles in plant adaptation to environmental conditions. Nevertheless, the MKK3-related literature is complicated. This review summarizes the current knowledge and discrepancies on MKK3 MAPK modules in plants and highlights the singular role of MKK3 in green plants. In the light of the latest data, we hypothesize a general model that all clade-III MAP3Ks converge on MKK3 and C-group MAPKs, thereby defining a set of novel MAPK modules which are activated by stresses and internal signals through the transcriptional regulation of MAP3K genes.

  4. Risk Assessment of Cascading Outages: Methodologies and Challenges

    Energy Technology Data Exchange (ETDEWEB)

    Vaiman, Marianna; Bell, Keith; Chen, Yousu; Chowdhury, Badrul; Dobson, Ian; Hines, Paul; Papic, Milorad; Miller, Stephen; Zhang, Pei

    2012-05-31

    Abstract- This paper is a result of ongoing activity carried out by Understanding, Prediction, Mitigation and Restoration of Cascading Failures Task Force under IEEE Computer Analytical Methods Subcommittee (CAMS). The task force's previous papers are focused on general aspects of cascading outages such as understanding, prediction, prevention and restoration from cascading failures. This is the first of two new papers, which extend this previous work to summarize the state of the art in cascading failure risk analysis methodologies and modeling tools. This paper is intended to be a reference document to summarize the state of the art in the methodologies for performing risk assessment of cascading outages caused by some initiating event(s). A risk assessment should cover the entire potential chain of cascades starting with the initiating event(s) and ending with some final condition(s). However, this is a difficult task and heuristic approaches and approximations have been suggested. This paper discusses different approaches to this and suggests directions for future development of methodologies. The second paper summarizes the state of the art in modeling tools for risk assessment of cascading outages.

  5. Cascading Failures as Continuous Phase-Space Transitions

    Science.gov (United States)

    Yang, Yang; Motter, Adilson E.

    2017-12-01

    In network systems, a local perturbation can amplify as it propagates, potentially leading to a large-scale cascading failure. Here we derive a continuous model to advance our understanding of cascading failures in power-grid networks. The model accounts for both the failure of transmission lines and the desynchronization of power generators and incorporates the transient dynamics between successive steps of the cascade. In this framework, we show that a cascade event is a phase-space transition from an equilibrium state with high energy to an equilibrium state with lower energy, which can be suitably described in a closed form using a global Hamiltonian-like function. From this function, we show that a perturbed system cannot always reach the equilibrium state predicted by quasi-steady-state cascade models, which would correspond to a reduced number of failures, and may instead undergo a larger cascade. We also show that, in the presence of two or more perturbations, the outcome depends strongly on the order and timing of the individual perturbations. These results offer new insights into the current understanding of cascading dynamics, with potential implications for control interventions.

  6. A thermal modelling of displacement cascades in uranium dioxide

    Science.gov (United States)

    Martin, G.; Garcia, P.; Sabathier, C.; Devynck, F.; Krack, M.; Maillard, S.

    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 UO2. 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 UO2. This definition of the cascade volume could also make sense in other materials, like iron.

  7. In Silico Screening and In Vitro Activity Measurement of Javamide Analogues as Potential p38 MAPK Inhibitors

    Directory of Open Access Journals (Sweden)

    Jae B. Park

    2017-12-01

    Full Text Available p38 Mitogen-activated protein kinase (p38 MAPK is a protein kinase critically involved in the progress of inflammation/stress-associated diseases. Our data suggested that javamide analogues may contain strong anti-inflammation activities, but there is little information about their effects on p38 MAPK. Therefore, in this paper, the effects of thirty javamide analogues on p38 MAPK were investigated using in silico screening and in vitro p38 MAPK assay methods. The javamide analogues were synthesized and their chemical structures were confirmed using nuclear magnetic resonance (NMR spectroscopic methods. Then, the javamide analogues were screened using an in silico modeling program. The screened analogues demonstrated a wide range of binding energy (ΔE; −20 to −39 and several analogues with ΔE; −34 to −39 showed strong binding affinity to p38 MAPK. In vitro p38 MAPK assay, the kinase was significantly inhibited by the analogues with great binding energy (ΔE; −34 to −39 and in silico scores (Avg. score; −27.5 to −29.3. Furthermore, the comparative analysis of both assays showed a positive correlation between the in silico scores and p38 MAPK inhibition. In fact, the javamide analogues with top five in silico scores (Avg. score; −27.5 to −29.3 were found to inhibit p38 MAPK by 27–31% (p < 0.05 better than those with less scores (ΔE < −27.0. Especially, javamide-II-O-ethyl ester with relatively high in silico score (Avg. score; −29.2 inhibited p38 MAPK (IC50 = 9.9 μM a little better than its methyl ester with best in silico score (Avg. score; −29.3. To support the ability to inhibit p38 MAPK, the treatment of javamide-II-ethyl and -methyl esters could suppress the production of IL-8 and MCP-1 protein significantly by 22–73% (p < 0.05 in the differentiated THP-1 cells, and the inhibition was slightly stronger by the ethyl ester than the methyl ester. Altogether, this study suggests that javamide-II-O-ethyl ester may

  8. Balance between MKK6 and MKK3 mediates p38 MAPK associated resistance to cisplatin in NSCLC.

    Directory of Open Access Journals (Sweden)

    Eva M Galan-Moya

    Full Text Available The p38 MAPK signaling pathway has been proposed as a critical mediator of the therapeutic effect of several antitumor agents, including cisplatin. Here, we found that sensitivity to cisplatin, in a system of 7 non-small cell lung carcinoma derived cell lines, correlated with high levels of MKK6 and marked activation of p38 MAPK. However, knockdown of MKK6 modified neither the response to cisplatin nor the activation of p38 MAPK. Deeper studies showed that resistant cell lines also displayed higher basal levels of MKK3. Interestingly, MKK3 knockdown significantly decreased p38 phosphorylation upon cisplatin exposure and consequently reduced the response to the drug. Indeed, cisplatin poorly activated MKK3 in resistant cells, while in sensitive cell lines MKK3 showed the opposite pattern in response to the drug. Our data also demonstrate that the low levels of MKK6 expressed in resistant cell lines are the consequence of high basal activity of p38 MAPK mediated by the elevated levels of MKK3. This finding supports the existence of a regulatory mechanism between both MAPK kinases through their MAPK. Furthermore, our results were also mirrored in head and neck carcinoma derived cell lines, suggesting our observations boast a potential universal characteristic in cancer resistance of cisplatin. Altogether, our work provides evidence that MKK3 is the major determinant of p38 MAPK activation in response to cisplatin and, hence, the resistance associated with this MAPK. Therefore, these data suggest that the balance between both MKK3 and MKK6 could be a novel mechanism which explains the cellular response to cisplatin.

  9. Balance between MKK6 and MKK3 Mediates p38 MAPK Associated Resistance to Cisplatin in NSCLC

    Science.gov (United States)

    Galan-Moya, Eva M.; Callejas-Valera, Juan L.; Melgar-Rojas, Pedro; Losa, Javier Hernadez; Salcedo, Mayte; Fernández-Aramburo, Antonio; Cajal, Santiago Ramon y.; Sánchez-Prieto, Ricardo

    2011-01-01

    The p38 MAPK signaling pathway has been proposed as a critical mediator of the therapeutic effect of several antitumor agents, including cisplatin. Here, we found that sensitivity to cisplatin, in a system of 7 non-small cell lung carcinoma derived cell lines, correlated with high levels of MKK6 and marked activation of p38 MAPK. However, knockdown of MKK6 modified neither the response to cisplatin nor the activation of p38 MAPK. Deeper studies showed that resistant cell lines also displayed higher basal levels of MKK3. Interestingly, MKK3 knockdown significantly decreased p38 phosphorylation upon cisplatin exposure and consequently reduced the response to the drug. Indeed, cisplatin poorly activated MKK3 in resistant cells, while in sensitive cell lines MKK3 showed the opposite pattern in response to the drug. Our data also demonstrate that the low levels of MKK6 expressed in resistant cell lines are the consequence of high basal activity of p38 MAPK mediated by the elevated levels of MKK3. This finding supports the existence of a regulatory mechanism between both MAPK kinases through their MAPK. Furthermore, our results were also mirrored in head and neck carcinoma derived cell lines, suggesting our observations boast a potential universal characteristic in cancer resistance of cisplatin. Altogether, our work provides evidence that MKK3 is the major determinant of p38 MAPK activation in response to cisplatin and, hence, the resistance associated with this MAPK. Therefore, these data suggest that the balance between both MKK3 and MKK6 could be a novel mechanism which explains the cellular response to cisplatin. PMID:22164285

  10. Functional analysis of Arabidopsis immune-related MAPKs uncovers a role for MPK3 as negative regulator of inducible defences

    KAUST Repository

    Frei dit Frey, Nicolas

    2014-06-30

    Background Mitogen-activated protein kinases (MAPKs) are key regulators of immune responses in animals and plants. In Arabidopsis, perception of microbe-associated molecular patterns (MAMPs) activates the MAPKs MPK3, MPK4 and MPK6. Increasing information depicts the molecular events activated by MAMPs in plants, but the specific and cooperative contributions of the MAPKs in these signalling events are largely unclear. Results In this work, we analyse the behaviour of MPK3, MPK4 and MPK6 mutants in early and late immune responses triggered by the MAMP flg22 from bacterial flagellin. A genome-wide transcriptome analysis reveals that 36% of the flg22-upregulated genes and 68% of the flg22-downregulated genes are affected in at least one MAPK mutant. So far MPK4 was considered as a negative regulator of immunity, whereas MPK3 and MPK6 were believed to play partially redundant positive functions in defence. Our work reveals that MPK4 is required for the regulation of approximately 50% of flg22-induced genes and we identify a negative role for MPK3 in regulating defence gene expression, flg22-induced salicylic acid accumulation and disease resistance to Pseudomonas syringae. Among the MAPK-dependent genes, 27% of flg22-upregulated genes and 76% of flg22-downregulated genes require two or three MAPKs for their regulation. The flg22-induced MAPK activities are differentially regulated in MPK3 and MPK6 mutants, both in amplitude and duration, revealing a highly interdependent network. Conclusions These data reveal a new set of distinct functions for MPK3, MPK4 and MPK6 and indicate that the plant immune signalling network is choreographed through the interplay of these three interwoven MAPK pathways.

  11. The p38 MAPK inhibitor, SB203580, inhibits cell invasion by Neospora caninum.

    Science.gov (United States)

    Jin, Xiaoxia; Gong, Pengtao; Li, Guojiang; Zhang, Xichen; Li, Jianhua

    2017-02-01

    The Apicomplexan parasite Neospora caninum is an obligate intracellular parasitic protozoan. It can cause severe diseases in a number of animals throughout the world. Infection with N. caninum leads to abortions in pregnant animals and neuromuscular disorders of newborns which cause great economic losses to animal husbandry. However, the mechanism of cell invasion by N. caninum is still unclear. This paper aims to investigate the impact of SB203580, a p38 MAPK inhibitor, on host cell invasion by N. caninum. The results suggested the presence of putative p38 MAPK homologues in N. caninum, and incubation of N. caninum with SB203580 markedly reduced the tachyzoite motility and microneme exocytosis (NcMIC2, 3, and 6). Furthermore, treatment or pretreatment of MDBK cells with SB203580 effectively reduced cell invasion by N. caninum. Therefore, SB203580 affected both, parasites and host cells, resulting in inhibition of cell invasion by N. caninum.

  12. Thermodynamic analysis of a thermally operated cascade sorption heat pump for continuous cold generation

    Energy Technology Data Exchange (ETDEWEB)

    Muthukumar, P.; Lakshmi, D.V.N. [Department of Mechanical Engineering, Indian Institute of Technology, Guwahati – 781039 (India)

    2013-07-01

    In this paper, the thermodynamic analysis of a cascade sorption system consists of a two-stage metal hydride heat pump as topping cycle and a single-stage lithium bromide water system as bottom cycle is presented. The effects of various operating temperatures such as driving heat, heat release and refrigeration temperatures, and design parameters such as ratio of metal hydride mass to reactor mass and sensible heat exchange factor on the combined coefficient of performance (COP) of the cascade cycle, and specific cooling power (SCP) and total cold output of the metal hydride heat pump cycle are presented. It is observed that the combined COP is found to increase with heat release and refrigeration temperatures and however, decreases with driving heat temperature. Increase of sensible heat exchange factor improves the system performances significantly. Reduction in mass ratio from 0.5 to 0.1 improves the combined COP of the cascade system by about 10 %. The maximum predicted combined COP of the system is about 1.66 at the driving heat, heat release and refrigeration temperatures of 270 deg C, 125 deg C and 12deg C, respectively.

  13. [A method of recognizing biology surface spectrum using cascade-connection artificial neural nets].

    Science.gov (United States)

    Shi, Wei-Jie; Yao, Yong; Zhang, Tie-Qiang; Meng, Xian-Jiang

    2008-05-01

    A method of recognizing the visible spectrum of micro-areas on the biological surface with cascade-connection artificial neural nets is presented in the present paper. The visible spectra of spots on apples' pericarp, ranging from 500 to 730 nm, were obtained with a fiber-probe spectrometer, and a new spectrum recognition system consisting of three-level cascade-connection neural nets was set up. The experiments show that the spectra of rotten, scar and bumped spot on an apple's pericarp can be recognized by the spectrum recognition system, and the recognition accuracy is higher than 85% even when noise level is 15%. The new recognition system overcomes the disadvantages of poor accuracy and poor anti-noise with the traditional system based on single cascade neural nets. Finally, a new method of expression of recognition results was proved. The method is based on the conception of degree of membership in fuzzing mathematics, and through it the recognition results can be expressed exactly and objectively.

  14. Thermoeconomic Optimization of Cascade Refrigeration System Using Mixed Carbon Dioxide and Hydrocarbons at Low Temperature Circuit

    Directory of Open Access Journals (Sweden)

    Nasruddin Nasruddin

    2016-12-01

    Full Text Available Many applications and industrial processes require very low cooling temperature, such as cold storage in the biomedical field, requiring temperature below -80 °C. However,single-cycle refrigeration systems can only achieve the effective cooling temperature of -40 °C and, also, the performance of the cycle will decrease drastically for cooling temperatures lower than -35°C. Currently, most of cascade refrigeration systems use refrigerants that have ozone depletion potential (ODP and global warming potential (GWP, therefore, in this study, a cascade system is simulated using a mixture of environmentally friendly refrigerants, namely, carbon dioxide and a hydrocarbon (propane, ethane or ethylene as the refrigerant of the low temperature circuit. A thermodynamic analysis is performed to determine the optimal composition of the mixture of carbon dioxide and hydrocarbons in the scope of certain operating parameters. In addition, an economic analysis was also performed to determine the annual cost to be incurred from the cascade refrigeration system. The multi-objective/thermoeconomic optimization points out optimal operating parameter values of the system, to addressing both exergy efficiency and its relation to the costs to be incurred.

  15. Experimental calibration of the mathematical model of Air Torque Position dampers with non-cascading blades

    Directory of Open Access Journals (Sweden)

    Bikić Siniša M.

    2016-01-01

    Full Text Available This paper is focused on the mathematical model of the Air Torque Position dampers. The mathematical model establishes a link between the velocity of air in front of the damper, position of the damper blade and the moment acting on the blade caused by the air flow. This research aims to experimentally verify the mathematical model for the damper type with non-cascading blades. Four different types of dampers with non-cascading blades were considered: single blade dampers, dampers with two cross-blades, dampers with two parallel blades and dampers with two blades of which one is a fixed blade in the horizontal position. The case of a damper with a straight pipeline positioned in front of and behind the damper was taken in consideration. Calibration and verification of the mathematical model was conducted experimentally. The experiment was conducted on the laboratory facility for testing dampers used for regulation of the air flow rate in heating, ventilation and air conditioning systems. The design and setup of the laboratory facility, as well as construction, adjustment and calibration of the laboratory damper are presented in this paper. The mathematical model was calibrated by using one set of data, while the verification of the mathematical model was conducted by using the second set of data. The mathematical model was successfully validated and it can be used for accurate measurement of the air velocity on dampers with non-cascading blades under different operating conditions. [Projekat Ministarstva nauke Republike Srbije, br. TR31058

  16. FERMI @ Elettra A Seeded Harmonic Cascade FEL for EUV and Soft X-Rays

    CERN Document Server

    Bocchetta, C J; Craievich, P; D'Auria, G; Danailov, M B; De Ninno, G; Di Mitri, S; Diviacco, B; Ferianis, M; Gomezel, A; Iazzourene, F; Karantzoulis, E; Penco, G; Trovò, M

    2005-01-01

    We describe the machine layout and major performance parameters for the FERMI FEL project funded for construction at Sincrotrone Trieste, Italy. The project will be the first user facility based on seeded harmonic cascade FELs, providing controlled, high peak-power pulses. With a high-brightness rf photocathode gun, and using the existing 1.2 GeV S-band linac, the facility will provide tunable output over a range from ~100 nm to ~10 nm, with pulse duration from 40 fs to ~ 1ps, and with fully variable output polarization. Initially, two FEL cascades are planned; a single-stage harmonic generation to operate > 40 nm, and a two-stage cascade operating from ~40 nm to ~10 nm or shorter wavelength. The output is spatially and temporally coherent, with peak power in the GW range. Lasers provide modulation to the electron beam, as well as driving the photocathode and other systems, and the facility will integrate laser systems with the accelerator infrastructure, including a state-of-the-art optical timing sys...

  17. 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)

  18. Increased p38-MAPK is responsible for chemotherapy resistance in human gastric cancer cells

    International Nuclear Information System (INIS)

    Guo, Xianling; Zhang, Baihe; Wu, Mengchao; Wei, Lixin; Ma, Nannan; Wang, Jin; Song, Jianrui; Bu, Xinxin; Cheng, Yue; Sun, Kai; Xiong, Haiyan; Jiang, Guocheng

    2008-01-01

    Chemoresistance is one of the main obstacles to successful cancer therapy and is frequently associated with Multidrug resistance (MDR). Many different mechanisms have been suggested to explain the development of an MDR phenotype in cancer cells. One of the most studied mechanisms is the overexpression of P-glycoprotein (P-gp), which is a product of the MDR1 gene. Tumor cells often acquire the drug-resistance phenotype due to upregulation of the MDR1 gene. Overexpression of MDR1 gene has often been reported in primary gastric adenocarcinoma. This study investigated the role of p38-MAPK signal pathway in vincristine-resistant SGC7901/VCR cells. P-gp and MDR1 RNA were detected by Western blot analysis and RT-PCR amplification. Mitgen-activated protein kinases and function of P-gp were demonstrated by Western blot and FACS Aria cytometer analysis. Ap-1 activity and cell apoptosis were detected by Dual-Luciferase Reporter Assay and annexin V-PI dual staining. The vincristine-resistant SGC7901/VCR cells with increased expression of the multidrug-resistance 1 (MDR1) gene were resistant to P-gp-related drug and P-gp-unrelated drugs. Constitutive increases of phosphorylated p38-MAPK and AP-1 activities were also found in the drug-resistant cells. Inhibition of p38-MAPK by SB202190 reduced activator protein-1 (AP-1) activity and MDR1 expression levels and increased the sensitivity of SGC7901/VCR cells to chemotherapy. Activation of the p38-MAPK pathway might be responsible for the modulation of P-glycoprotein-mediated and P-glycoprotein-unmediated multidrug resistance in the SGC7901/VCR cell line

  19. Resveratrol, an antioxidant, protects spinal cord injury in rats by suppressing MAPK pathway

    Directory of Open Access Journals (Sweden)

    Song Fu

    2018-02-01

    Full Text Available Resveratrol, a polyphenol found in various plants, including grapes, plums and peanuts has shown various medIRInal properties, including antioxidant, protection of cardiovascular disease and cancer risk. However, the effects of resveratrol on spinal cord reperfusion injury have not been investigated. Hence, the present study was designed to evaluate the effect of resveratrol on nitric oxide synthase (iNOS/p38MAPK signaling pathway and to elucidate its regulating effect on the protection of spinal cord injury. Spinal cord ischemia–reperfusion injury (IRI was performed by the infrarenal abdominal aorta with mini aneurysm clip model. The expressions of iNOS and p38MAPK and the levels of biochemical parameters, including nitrite/nitrate, malondialdehyde (MDA, advanced oxidation products (AOPP, reduced glutathione (GSH, superoxide dismutase (SOD and catalase (CAT were measured in control and experimental groups. IRI-induced rats treated with 10 mg/kg resveratrol protected spinal cord from ischemia injury as supported by improved biological parameters measured in spinal cord tissue homogenates. The resveratrol treatment significantly decreased the levels of plasma nitrite/nitrate, iNOS mRNA and protein expressions and phosphorylation of p38MAPK in IRI-induced rats. Further, IRI-produced free radicals were reduced by resveratrol treatment by increasing enzymatic and non-enzymatic antioxidant levels such as GSH, SOD and CAT. Taken together, administration of resveratrol protects the damage caused by spinal cord ischemia with potential mechanism of suppressing the activation of iNOS/p38MAPK pathway and subsequent reduction of oxidative stress due to IRI.

  20. Central sensitization and MAPKs are involved in occlusal interference-induced facial pain in rats.

    Science.gov (United States)

    Cao, Ye; Li, Kai; Fu, Kai-Yuan; Xie, Qiu-Fei; Chiang, Chen-Yu; Sessle, Barry J

    2013-08-01

    We previously developed a rat dental occlusal interference model of facial pain that was produced by bonding a crown onto the right maxillary first molar and was reflected in sustained facial hypersensitivity that was suggestive of the involvement of central sensitization mechanisms. The aim of the present study was to investigate potential central mechanisms involved in the occlusal interference-induced facial hypersensitivity. A combination of behavioral, immunohistochemical, Western blot, and electrophysiological recording procedures was used in 98 male adult Sprague Dawley rats that either received the occlusal interference or were sham-operated or naive rats. Immunohistochemically labeled astrocytes and microglia in trigeminal subnucleus caudalis (Vc) showed morphological changes indicative of astrocyte and microglial activation after the occlusal interference. Prolonged upregulation of p38 mitogen-activated protein kinase (MAPK) and extracellular signal-regulated kinase (ERK) was also documented in Vc after placement of the occlusal interference and was expressed in both neurons and glial cells at time points when rats showed peak mechanical facial hypersensitivity. The intrathecal administration of the p38 MAPK inhibitor SB203580 to the medulla significantly inhibited the occlusal interference-induced hypersensitivity, and the ERK inhibitor PD98059 produced an even stronger effect. Central sensitization of functionally identified Vc nociceptive neurons following placement of the occlusal interference was also documented by extracellular electrophysiological recordings, and intrathecal administration of PD98059 could reverse the neuronal central sensitization. These novel findings suggest that central mechanisms including central sensitization of trigeminal nociceptive neurons and non-neuronal processes involving MAPKs play significant roles in the production of occlusal interference-induced facial pain. Central mechanisms including trigeminal nociceptive

  1. Isocryptotanshinone Induced Apoptosis and Activated MAPK Signaling in Human Breast Cancer MCF-7 Cells.

    Science.gov (United States)

    Zhang, Xuenong; Luo, Weiwei; Zhao, Wenwen; Lu, Jinjian; Chen, Xiuping

    2015-06-01

    Isocryptotanshinone (ICTS) is a natural bioactive product that is isolated from the roots of the widely used medical herb Salvia miltiorrhiza. However, few reports exist on the mechanisms underlying the therapeutic effects of ICTS. Here, we report that ICTS has anticancer activity and describe the mechanism underlying this effect. The antiproliferative effect of ICTS was determined using 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) and clonogenic assays. The effect of ICTS on the cell cycle was measured using flow cytometry. Apoptosis was determined by Hoechst 33342 staining, DNA fragmentation assays, and Western blotting for apoptotic proteins. Finally, the effect of ICTS on mitogen-activated protein kinases (MAPKs) was determined by Western blotting. ICTS significantly inhibited proliferation of MCF-7 and MDA-MB-231 human breast cancer cells, HepG2 human liver cancer cells, and A549 human lung cancer cells in vitro. Among the tested cell lines, MCF-7 cells showed the highest sensitivity to ICTS. ICTS significantly inhibited colony formation by MCF-7 cells. Furthermore, exposure of MCF-7 cells to ICTS induced cell cycle arrest at the G1 phase and decreased mitochondrial membrane potential. Hoechst 33342 staining and Western blot analysis for apoptotic proteins suggested that ICTS induced apoptosis in MCF-7 cells. In addition, ICTS activated MAPK signaling in MCF-7 cells by inducing time- and concentration-dependent phosphorylation of JNK, ERK, and p38 MAPK. Our results suggest that ICTS inhibited MCF-7 cell proliferation by inducing apoptosis and activating MAPK signaling pathways.

  2. The MAPK pathway is a predominant regulator of HLA-A expression in esophageal and gastric cancer.

    Science.gov (United States)

    Mimura, Kousaku; Shiraishi, Kensuke; Mueller, Anja; Izawa, Shinichiro; Kua, Ley-Fang; So, Jimmy; Yong, Wei-Peng; Fujii, Hideki; Seliger, Barbara; Kiessling, Rolf; Kono, Koji

    2013-12-15

    Downregulation of HLA class I expression may contribute to a poor prognosis in cancer patients. There is limited information about epigenetic and oncogenic regulation of HLA class I, and multiple mechanisms may be involved. In the current study, we examined the relationship between the HER2-signaling pathway (MAPK and PI3K-Akt) and the expression of HLA class I and Ag-processing machinery (APM) components. A panel of gastric and esophageal cancer cell lines was treated with wortmannin as an Akt-signal inhibitor; the MAPK signal inhibitor PD98059; lapatinib, which inhibits both the epidermal growth factor receptor and HER2 tyrosine kinase; or siRNA for MAPK. The levels of HER2-signaling molecules, APM components, and HLA class I were evaluated by Western blot, quantitative PCR, and flow cytometry. Resected gastric tumor tissues (n = 102) were analyzed for p-Erk and HLA class I expression by immunohistochemistry. As a result, inhibition of the MAPK pathway induced upregulation of HLA-A02 and HLA-A24 expression in parallel with an increase in APM components and enhanced target sensitivity to tumor Ag-specific CTL lysis. HLA-A expression was predominantly regulated by the MAPK pathway, but it was also influenced, in part, by the Akt pathway. There was a strong inverse correlation between p-Erk expression and HLA class I expression in clinical tumor samples. In conclusion, HLA-A expression is predominantly regulated by the MAPK pathway in gastric and esophageal cancer.

  3. P38 mitogen-activated protein kinase (p38 MAPK) overexpression in clinical staging of nasopharyngeal carcinoma

    Science.gov (United States)

    Farhat; Asnir, R. A.; Yudhistira, A.; Daulay, E. R.; Muzakkir, M. M.; Yulius, S.

    2018-03-01

    Molecular biological research on nasopharyngeal carcinoma has been widely practiced, such as VEGF, EGFR, COX-2 expression and so on. MAPK plays a role in cell growth such as proliferation, differentiation, and apoptosis, primarily contributing to gene expression, where p38 MAPK pathway mostly associate with anti-apoptosis and cause cell transformation. The aim of this study is to determine the expression of p38 MAPK in clinical stage of nasopharyngeal carcinoma so that the result can be helpful in prognosis and adjunctive therapy in nasopharyngeal carcinoma. The research design is descriptive. It was done in THT- KL Department of FK USU/RSUP Haji Adam Malik, Medan and Pathology Anatomical Department of FK USU. The study was conducted from December 2011 to May 2012. The Samples are all patients who diagnosed with nasopharyngeal carcinoma in oncology division of Otorhinolaryngology Department. p38 MAPK overexpression was found in 21 samples (70%) from 30 nasopharyngeal carcinoma samples. The elevated of p38 MAPK expression most found on T4 by eight samples (38.1%), N3 lymph node group by nine samples (42.9%), stage IV of clinical staging is as many as 15 samples (71.4%). p38 MAPK most expressed in stage IV clinical staging of patients with nasopharyngeal carcinoma.

  4. p38MAPK Signaling Enhances Glycolysis Through the Up-Regulation of the Glucose Transporter GLUT-4 in Gastric Cancer Cells.

    Science.gov (United States)

    Liu, Jingjing; Wen, Dacheng; Fang, Xuedong; Wang, Xudong; Liu, Tianzhou; Zhu, Jiaming

    2015-01-01

    Previous studies have shown that p38MAPK is involved in gastric cancer, yet the underlying mechanism remains unclear. q-PCR, Western blot and immunohistochemistry were used to explore the expression of PP2A and the phosphorylation of p38MAPK in gastric cancer tissues and normal gastric tissues. Activated p38MAPK in the gastric cancer cell line MKN45 using activator, then q-PCR, glucose uptake assay and colony formation assay were performed to determine whether p38MAPK promotes gastric cancer through the enhancement of glycolysis. After transfection of p38MAPK dominant negative mutation (p38DN) into MKN45 cells or MKN45 cells treated with an inhibitor of p38MAPK, Western blot was performed to detect the expression of GLUT-4. The knock down of MEF2α in MKN45 cells by siRNA was followed by Western blot and luciferase reporter assay to investigate the underlying mechanism of the role of p38MAPK in the promotion of gastric cancer. Finally, q-PCR, Western blot and immunohistochemistry were performed to examine GLUT-4 expression in gastric cancer tissues and normal gastric tissues. We found that p38MAPK activation significantly increases GLUT-4 expression and promotes glucose uptake and cell growth in gastric cancer cells. Inhibition of p38MAPK abrogates the up-regulation of GLUT-4. MEF2α knockdown abolishes p38MAPK-mediated GLUT-4 up-regulation. PP2A, an inhibitor of p38MAPK, is down-regulated in gastric cancer tissues, which might contribute to the activation of p38MAPK. Our data indicate that the abnormal activation of p38MAPK promotes glycolysis within gastric cancer cells through the upregulation of GLUT-4 in a MEF2a-dependent manner.

  5. BMP7 retards peripheral myelination by activating p38 MAPK in Schwann cells

    Science.gov (United States)

    Liu, Xiaoyu; Zhao, Yahong; Peng, Su; Zhang, Shuqiang; Wang, Meihong; Chen, Yeyue; Zhang, Shan; Yang, Yumin; Sun, Cheng

    2016-01-01

    Schwann cell (SC) myelination is pivotal for the proper physiological functioning of the nervous system, but the underlying molecular mechanism remains less well understood. Here, we showed that the expression of bone morphogenetic protein 7 (BMP7) inversely correlates with myelin gene expression during peripheral myelination, which suggests that BMP7 is likely a negative regulator for myelin gene expression. Our experiments further showed that the application of BMP7 attenuates the cAMP induced myelin gene expression in SCs. Downstream pathway analysis suggested that both p38 MAPK and SMAD are activated by exogenous BMP7 in SCs. The pharmacological intervention and gene silence studies revealed that p38 MAPK, not SMAD, is responsible for BMP7-mediated suppression of myelin gene expression. In addition, c-Jun, a potential negative regulator for peripheral myelination, was up-regulated by BMP7. In vivo experiments showed that BMP7 treatment greatly impaired peripheral myelination in newborn rats. Together, our results established that BMP7 is a negative regulator for peripheral myelin gene expression and that p38 MAPK/c-Jun axis might be the main downstream target of BMP7 in this process. PMID:27491681

  6. Human Th17 Migration in Three-Dimensional Collagen Involves p38 MAPK.

    Science.gov (United States)

    Kadiri, Maleck; El Azreq, Mohammed-Amine; Berrazouane, Sofiane; Boisvert, Marc; Aoudjit, Fawzi

    2017-09-01

    T cell migration across extracellular matrix (ECM) is an important step of the adaptive immune response but is also involved in the development of inflammatory autoimmune diseases. Currently, the molecular mechanisms regulating the motility of effector T cells in ECM are not fully understood. Activation of p38 MAPK has been implicated in T cell activation and is critical to the development of immune and inflammatory responses. In this study, we examined the implication of p38 MAPK in regulating the migration of human Th17 cells through collagen. Using specific inhibitor and siRNA, we found that p38 is necessary for human Th17 migration in three-dimensional (3D) collagen and that 3D collagen increases p38 phosphorylation. We also provide evidence that the collagen receptor, discoidin domain receptor 1 (DDR1), which promotes Th17 migration in 3D collagen, is involved in p38 activation. Together, our findings suggest that targeting DDR1/p38 MAPK pathway could be beneficial for the treatment of Th17-mediated inflammatory diseases. J. Cell. Biochem. 118: 2819-2827, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  7. Conservation of protein abundance patterns reveals the regulatory architecture of the EGFR-MAPK pathway

    Energy Technology Data Exchange (ETDEWEB)

    Shi, T.; Niepel, M.; McDermott, J. E.; Gao, Y.; Nicora, C. D.; Chrisler, W. B.; Markillie, L. M.; Petyuk, V. A.; Smith, R. D.; Rodland, K. D.; Sorger, P. K.; Qian, W. -J.; Wiley, H. S.

    2016-07-12

    It is not known whether cancer cells generally show quantitative differences in the expression of signaling pathway proteins that could dysregulate signal transduction. To explore this issue, we first defined the primary components of the EGF-MAPK pathway in normal human mammary epithelial cells, identifying 16 core proteins and 10 feedback regulators. We then quantified their absolute abundance across a panel of normal and cancer cell lines. We found that core pathway proteins were expressed at very similar levels across all cell types. In contrast, the EGFR and transcriptionally controlled feedback regulators were expressed at highly variable levels. The absolute abundance of most core pathway proteins was between 50,000- 70,000 copies per cell, but the adaptors SOS1, SOS2, and GAB1 were found at far lower levels (2,000-5,000 per cell). MAPK signaling showed saturation in all cells between 3,000-10,000 occupied EGFR, consistent with the idea that low adaptor levels limit signaling. Our results suggest that the core MAPK pathway is essentially invariant across different cell types, with cell- specific differences in signaling likely due to variable levels of feedback regulators. The low abundance of adaptors relative to the EGFR could be responsible for previous observation of saturable signaling, endocytosis, and high affinity EGFR.

  8. Arctigenin induces apoptosis in colon cancer cells through ROS/p38MAPK pathway.

    Science.gov (United States)

    Li, Qing-chun; Liang, Yun; Tian, Yuan; Hu, Guang-rui

    2016-01-01

    In the current study the antiproliferative effect of arctigenin, plant lignin, was evaluated on human colon cancer cell line HT-29. Furthermore, attempts were made to explore the signaling mechanism which may be responsible for its effect. Cell growth inhibition was assessed by MTT and LDH assays. Flow cytometric analysis was performed to determine cell arrest in the cell cycle phase and apoptosis. Furthermore, to confirm the apoptotic activity of arctigenin, caspase-9 and -3 activities analysis was performed. The levels of reactive oxygen species (ROS) and p38 mitogen activated protein kinase (MAPK) were investigated to determine their role in inducing apoptosis in arctigenin-treated HT-29 colon cancer cell line. MTT and LDH results demonstrated significant cell growth inhibitory effect of arctigenin on HT-29 cells in a dose-dependent manner. Furthermore, increase in cell number arrested at G2/M phase was observed in flow cytometric analysis upon arctigenin treatment. In addition, arctigenin increased the apoptotic ratio in a dose-dependent manner. The involvement of intrinsic apoptotic pathway was indicated by the activation of caspase-9 and -3. Moreover, increased ROS production, activation of p38 MAPK and changes in mitochondrial membrane potential (ΔΨm) also revealed the role of intrinsic apoptotic signaling pathway in cell growth inhibition after arctigenin exposure. Arctigenin induces apoptosis in HT-29 colon cancer cells by regulating ROS and p38 MAPK pathways.

  9. Manganese overload affects p38 MAPK phosphorylation and metalloproteinase activity during sea urchin embryonic development.

    Science.gov (United States)

    Pinsino, A; Roccheri, M C; Matranga, V

    2014-02-01

    In the marine environment, manganese represents a potential emerging contaminant, resulting from an increased production of manganese-containing compounds. In earlier reports we found that the exposure of Paracentrotus lividus sea urchin embryos to manganese produced phenotypes with no skeleton. In addition, manganese interfered with calcium uptake, perturbed extracellular signal-regulated kinase (ERK) signaling, affected the expression of skeletogenic genes, and caused an increase of the hsc70 and hsc60 protein levels. Here, we extended our studies focusing on the temporal activation of the p38 mitogen-activated protein kinase (p38 MAPK) and the proteolytic activity of metalloproteinases (MMPs). We found that manganese affects the stage-dependent dynamics of p38 MAPK activation and inhibits the total gelatin-auto-cleaving activity of MMPs, with the exclusion of the 90-85 kDa and 68-58 kDa MMPs, whose levels remain high all throughout development. Our findings correlate, for the first time to our knowledge, an altered activation pattern of the p38 MAPK with an aberrant MMP proteolytic activity in the sea urchin embryo. Copyright © 2013 Elsevier Ltd. All rights reserved.

  10. Trihydrophobin 1 Phosphorylation by c-Src Regulates MAPK/ERK Signaling and Cell Migration

    Science.gov (United States)

    Wu, Weibin; Sun, Zhichao; Wu, Jingwen; Peng, Xiaomin; Gan, Huacheng; Zhang, Chunyi; Ji, Lingling; Xie, Jianhui; Zhu, Haiyan; Ren, Shifang

    2012-01-01

    c-Src activates Ras-MAPK/ERK signaling pathway and regulates cell migration, while trihydrophobin 1 (TH1) inhibits MAPK/ERK activation and cell migration through interaction with A-Raf and PAK1 and inhibiting their kinase activities. Here we show that c-Src interacts with TH1 by GST-pull down assay, coimmunoprecipitation and confocal microscopy assay. The interaction leads to phosphorylation of TH1 at Tyr-6 in vivo and in vitro. Phosphorylation of TH1 decreases its association with A-Raf and PAK1. Further study reveals that Tyr-6 phosphorylation of TH1 reduces its inhibition on MAPK/ERK signaling, enhances c-Src mediated cell migration. Moreover, induced tyrosine phosphorylation of TH1 has been found by EGF and estrogen treatments. Taken together, our findings demonstrate a novel mechanism for the comprehensive regulation of Ras/Raf/MEK/ERK signaling and cell migration involving tyrosine phosphorylation of TH1 by c-Src. PMID:22238675

  11. Use of p38 MAPK Inhibitors for the Treatment of Werner Syndrome

    Directory of Open Access Journals (Sweden)

    Mark C. Bagley

    2010-06-01

    Full Text Available Werner syndrome provides a convincing model for aspects of the normal ageing phenotype and may provide a suitable model for therapeutic interventions designed to combat the ageing process. Cultured primary fibroblast cells from Werner syndrome patients provide a powerful model system to study the link between replicative senescence in vitro and in vivo pathophysiology. Genome instability, together with an increased pro-oxidant state, and frequent replication fork stalling, all provide plausible triggers for intracellular stress in Werner syndrome cells, and implicates p38 MAPK signaling in their shortened replicative lifespan. A number of different p38 MAPK inhibitor chemotypes have been prepared rapidly and efficiently using microwave heating techniques for biological study in Werner syndrome cells, including SB203580, VX-745, RO3201195, UR-13756 and BIRB 796, and their selectivity and potency evaluated in this cellular context. Werner syndrome fibroblasts treated with a p38 MAPK inhibitor reveal an unexpected reversal of the accelerated ageing phenotype. Thus the study of p38 inhibition and its effect upon Werner pathophysiology is likely to provide new revelations into the biological mechanisms operating in cellular senescence and human ageing in the future.

  12. Atractylodin Inhibits Interleukin-6 by Blocking NPM-ALK Activation and MAPKs in HMC-1.

    Science.gov (United States)

    Chae, Hee-Sung; Kim, Young-Mi; Chin, Young-Won

    2016-09-02

    Atractylodin is one of the major constituents of the rhizome of Atractylodes lancea, which is widely used in Korean traditional medicine as a remedy for the treatment of gastritis and gastric ulcers. Despite of a major constituent of widely used botanical to treat inflammatory responses little is known about anti-inflammatory effect of atractylodin in the human mast cell (HMC-1). Hence, we evaluated the effect of atractylodin on the release of IL-6, the involvement of nucleophosmin-anaplastic lymphoma kinase (NPM-ALK) and mitogen-activated protein kinases (MAPKs) in phorbol-12-myristate-13-acetate and A23187-induced HMC-1. In addition, Janus kinase 2 (JAK2), signal transducer and activator of transcription 3 (STAT3), phospholipase C (PLC) gamma 1, and AKT phosphorylation relevant to NPM-ALK signal pathway were assessed. IL-6 levels in the HMC-1 stimulated by phorbol-12-myristate-13-acetate and A23187 were apparently decreased by the treatment of atractylodin. Concurrently, atractylodin not only inhibited the phosphorylation of NPM-ALK, but also suppressed the phosphorylation of JAK2, STAT3, PLC gamma 1, and AKT. Furthermore, the activated mitogen-activated protein kinases (MAPKs) by phorbol-12-myristate-13-acetate and A23187 were inhibited by atractylodin. These results suggested that atractylodin might have a potential regulatory effect on inflammatory mediator expression through blockade of both the phosphorylation of MAPKs and the NPM-ALK signaling pathway.

  13. Modulation of inflammation and pathology during dengue virus infection by p38 MAPK inhibitor SB203580.

    Science.gov (United States)

    Fu, Yilong; Yip, Andy; Seah, Peck Gee; Blasco, Francesca; Shi, Pei-Yong; Hervé, Maxime

    2014-10-01

    Dengue virus (DENV) infection could lead to dengue fever (DF), dengue hemorrhagic fever (DHF) or dengue shock syndrome (DSS). The disease outcome is controlled by both viral and host factors. Inflammation mediators from DENV-infected cells could contribute to increased vascular permeability, leading to severe DHF/DSS. Therefore, suppression of inflammation could be a potential therapeutic approach for treatment of dengue patients. In this context, p38 MAPK (mitogen-activated protein kinase) is a key enzyme that modulates the initiation of stress and inflammatory responses. Here we show that SB203580, a p38 MAPK inhibitor, suppressed the over production of DENV-induced pro-inflammatory mediators such as TNF-α, IL-8, and RANTES from human PBMCs, monocytic THP-1, and granulocyte KU812 cell lines. Oral administration of SB203580 in DENV-infected AG129 mice prevented hematocrit rise and lymphopenia, limited the development of inflammation and pathology (including intestine leakage), and significantly improved survival. These results, for the first time, have provided experimental evidence to imply that a short term inhibition of p38 MAPK may be beneficial to reduce disease symptoms in dengue patients. Copyright © 2014 Elsevier B.V. All rights reserved.

  14. Deuterium Values from Hydrated Volcanic Glass: A Paleoelevation Proxy for Oregon's Cascade Range

    Science.gov (United States)

    Carlson, T. B.; Bershaw, J. T.; Cassel, E. J.

    2017-12-01

    Deuterium ratios (δD) of hydrated volcanic glass have been used to reconstruct Cenozoic paleoenvironments. However, the reliability and proper sample preparation protocol have been debated. The Cascades are an excellent location to study the validity of hydrated volcanic glass as a paleoelevation proxy for several reasons. Moisture is largely derived from a single oceanic source and falls as orographic precipitation in the Cascades, leading to a characteristic altitude effect, or inverse relationship between elevation and the isotopic composition of meteoric water (δD). Additionally, past studies have inferred uplift of the Cascades since the Miocene based on changing fossil assemblages, tectonic models, and other isotopic proxies including soil carbonates and fossil teeth. In this study, hydrated volcanic ash samples from the lee of the Cascades were rinsed with hydrochloric acid and sonicated before glass shards were hand-selected and analyzed for δD and wt. % water. These preliminary results exhibited δD values becoming enriched with time, a trend opposite of other paleowater proxy studies in the area. A possible explanation for this trend is contamination due to inadequate removal of materials adhered to shard surfaces that can readily exchange with environmental water. Recent research asserts that hydrofluoric acid (HF) etching during sample preparation is necessary to accurately measure δD values of syndepositional water. Volcanic ash samples were reanalyzed after preparation using HF abrasion and heavy liquid separation. The data from these two subsets are interpreted in the context of modern water across the range, as well as other paleowater proxy and geologic studies to determine the implications of volcanic glass as a paleoelevation proxy in the Pacific Northwest.

  15. Structural basis for promiscuous PAM recognition in type I-E Cascade from E. coli.

    Science.gov (United States)

    Hayes, Robert P; Xiao, Yibei; Ding, Fran; van Erp, Paul B G; Rajashankar, Kanagalaghatta; Bailey, Scott; Wiedenheft, Blake; Ke, Ailong

    2016-02-25

    Clustered regularly interspaced short palindromic repeats (CRISPRs) and the cas (CRISPR-associated) operon form an RNA-based adaptive immune system against foreign genetic elements in prokaryotes. Type I accounts for 95% of CRISPR systems, and has been used to control gene expression and cell fate. During CRISPR RNA (crRNA)-guided interference, Cascade (CRISPR-associated complex for antiviral defence) facilitates the crRNA-guided invasion of double-stranded DNA for complementary base-pairing with the target DNA strand while displacing the non-target strand, forming an R-loop. Cas3, which has nuclease and helicase activities, is subsequently recruited to degrade two DNA strands. A protospacer adjacent motif (PAM) sequence flanking target DNA is crucial for self versus foreign discrimination. Here we present the 2.45 Å crystal structure of Escherichia coli Cascade bound to a foreign double-stranded DNA target. The 5'-ATG PAM is recognized in duplex form, from the minor groove side, by three structural features in the Cascade Cse1 subunit. The promiscuity inherent to minor groove DNA recognition rationalizes the observation that a single Cascade complex can respond to several distinct PAM sequences. Optimal PAM recognition coincides with wedge insertion, initiating directional target DNA strand unwinding to allow segmented base-pairing with crRNA. The non-target strand is guided along a parallel path 25 Å apart, and the R-loop structure is further stabilized by locking this strand behind the Cse2 dimer. These observations provide the structural basis for understanding the PAM-dependent directional R-loop formation process.

  16. Cascade Optimization Strategy for Aircraft and Air-Breathing Propulsion System Concepts

    Science.gov (United States)

    Patnaik, Surya N.; Lavelle, Thomas M.; Hopkins, Dale A.; Coroneos, Rula M.

    1996-01-01

    Design optimization for subsonic and supersonic aircraft and for air-breathing propulsion engine concepts has been accomplished by soft-coupling the Flight Optimization System (FLOPS) and the NASA Engine Performance Program analyzer (NEPP), to the NASA Lewis multidisciplinary optimization tool COMETBOARDS. Aircraft and engine design problems, with their associated constraints and design variables, were cast as nonlinear optimization problems with aircraft weight and engine thrust as the respective merit functions. Because of the diversity of constraint types and the overall distortion of the design space, the most reliable single optimization algorithm available in COMETBOARDS could not produce a satisfactory feasible optimum solution. Some of COMETBOARDS' unique features, which include a cascade strategy, variable and constraint formulations, and scaling devised especially for difficult multidisciplinary applications, successfully optimized the performance of both aircraft and engines. The cascade method has two principal steps: In the first, the solution initiates from a user-specified design and optimizer, in the second, the optimum design obtained in the first step with some random perturbation is used to begin the next specified optimizer. The second step is repeated for a specified sequence of optimizers or until a successful solution of the problem is achieved. A successful solution should satisfy the specified convergence criteria and have several active constraints but no violated constraints. The cascade strategy available in the combined COMETBOARDS, FLOPS, and NEPP design tool converges to the same global optimum solution even when it starts from different design points. This reliable and robust design tool eliminates manual intervention in the design of aircraft and of air-breathing propulsion engines where it eases the cycle analysis procedures. The combined code is also much easier to use, which is an added benefit. This paper describes COMETBOARDS

  17. 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.

  18. Optimization Issues in a Harmonic Cascade FEL

    CERN Document Server

    De Ninno, G

    2005-01-01

    Presently there is significant interest by multiple groups (e.g. BNL, ELETTRA, LBNL, BESSY, MIT) to reach short output wavelengths via a harmonic cascade FEL using an external seed laser. In a multistage device, there are a number of "free" parameters such as the nominal power of the input seed, the lengths of the individual modulator and radiator undulators, the strengths (i.e. the R56's) of the dispersive sections, the choice of the actual harmonic numbers to reach a given wavelength, etc., whose optimization is a non-trivial exercise. In particular, one can choose whether to operate predominantly in the "high gain" regime such as was proposed by Yu [1] in which case each radiator undulator is many gain lengths long or, alternatively, in the "low gain" regime in which case all undulators (except possibly the last radiator) are a couple gain lengths or less long and the output from each radiator essentially corresponds to coherent spontaneous emission from a pre-bunched beam. With particular emphasis upon th...

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. Lean and Obese Zucker Rat Extensor Digitorum Longus Muscle high-frequency electrical stimulation (HFES) Data: Regulation of MAPKs Associated Proteins.

    Science.gov (United States)

    Rice, Kevin M; Katta, Anjaiah; Manne, Nandini D P K; Arvapalli, Ravikumar; Ginjupalli, Gautam K; Wu, Miaozong; Asano, Shinichi; Blough, Eric R

    2018-02-01

    Anaerobic exercise has been advocated as a prescribed treatment for the management of diabetes: however, alterations in exercise-induced signaling remain largely unexplored in the diabetic muscle. Here, we compare the basal and the in situ contraction-induced phosphorylation of the mitogen-activated protein kinases (MAPKs) ERK 1/2, p38, and JNK in the lean and obese (fa/fa) Zucker rat extensor digitorum longus (EDL) muscle following a single bout of contractile stimuli. This article represents data associated with prior publications from our (Katta et al., 2009a, 2009b, 2008) [1-3] and concurrent Data in Brief articles (Ginjupalli et al., 2017a, 2017b; Rice et al., 2017a, 2017b) [4-7].

  4. Coherent frequency combs produced by self frequency modulation in quantum cascade lasers

    Science.gov (United States)

    Khurgin, J. B.; Dikmelik, Y.; Hugi, A.; Faist, J.

    2014-02-01

    One salient characteristic of Quantum Cascade Laser (QCL) is its very short τ ˜ 1 ps gain recovery time that so far thwarted the attempts to achieve self-mode locking of the device into a train of single pulses. We show theoretically that four wave mixing, combined with the short gain recovery time causes QCL to operate in the self-frequency-modulated regime characterized by a constant power in time domain and stable coherent comb in the frequency domain. Coherent frequency comb may enable many potential applications of QCL's in sensing and measurement.

  5. Cascaded switched-inductor and taped-inductor Z-source inverters

    DEFF Research Database (Denmark)

    Li, Ding; Loh, Poh Chiang; Zhu, Miao

    2011-01-01

    applications like the grid connection of low-voltage renewable sources that might not favor multiple series connection. To enhance its gain, while yet preserving its voltage-buck flexibility, modifications to the traditional Z-source inverter are now proposed to develop a new family of cascaded switched-inductor...... and tapped-inductor Z-source inverters. Unlike existing techniques, voltage stresses within the proposed inverters are better distributed among the passive components, hence avoiding likely single points of failure. For verifying these performance findings, experimental testing on a number of implemented...

  6. Coherent frequency combs produced by self frequency modulation in quantum cascade lasers

    International Nuclear Information System (INIS)

    Khurgin, J. B.; Dikmelik, Y.; Hugi, A.; Faist, J.

    2014-01-01

    One salient characteristic of Quantum Cascade Laser (QCL) is its very short τ ∼ 1 ps gain recovery time that so far thwarted the attempts to achieve self-mode locking of the device into a train of single pulses. We show theoretically that four wave mixing, combined with the short gain recovery time causes QCL to operate in the self-frequency-modulated regime characterized by a constant power in time domain and stable coherent comb in the frequency domain. Coherent frequency comb may enable many potential applications of QCL's in sensing and measurement

  7. Mechanisms for decoration of dislocations by small dislocation loops under cascade damage conditions

    DEFF Research Database (Denmark)

    Trinkaus, H.; Singh, B.N.; Foreman, A.J.E.

    1997-01-01

    . This effect may arise as a result of either (a) migration and enhanced agglomeration of single SIAs in the form of loops in the strain field of the dislocation or (b) glide and trapping of SIA loops (produced directly in the cascades) in the strain field of the dislocation, In the present paper, both...... of these possibilities are examined. It is shown that the strain field of the dislocation causes a SIA depletion in the compressive as well as in the dilatational region resulting in a reduced rather than enhanced agglomeration of SIAs. (SIA depletion may, however, induce enhanced vacancy agglomeration near dislocations...

  8. Lactone radical cyclizations and cyclization cascades mediated by SmI2-H2O.

    Science.gov (United States)

    Parmar, Dixit; Matsubara, Hiroshi; Price, Kieran; Spain, Malcolm; Procter, David J

    2012-08-01

    Unsaturated lactones undergo reductive radical cyclizations upon treatment with SmI(2)-H(2)O to give decorated cycloheptanes in a single highly selective operation during which up to three contiguous stereocenters are generated. Furthermore, cascade processes involving lactones bearing two alkenes, an alkene and an alkyne, or an allene and an alkene allow "one-pot" access to biologically significant molecular scaffolds with the construction of up to four contiguous stereocenters. The cyclizations proceed by the trapping of radical anions formed by electron transfer reduction of the lactone carbonyl.

  9. Integration of a terahertz quantum cascade laser with a hollow waveguide

    Science.gov (United States)

    Wanke, Michael C [Albuquerque, NM; Nordquist, Christopher D [Albuquerque, NM

    2012-07-03

    The present invention is directed to the integration of a quantum cascade laser with a hollow waveguide on a chip to improve both the beam pattern and manufacturability. By coupling the QCL output into a single-mode rectangular waveguide the radiation mode structure can be known and the propagation, manipulation, and broadcast of the QCL radiation can then be entirely controlled by well-established rectangular waveguide techniques. By controlling the impedance of the interface, enhanced functions, such as creating amplifiers, efficient coupling to external cavities, and increasing power output from metal-metal THz QCLs, are also enabled.

  10. A simple method for potential flow simulation of cascades

    Indian Academy of Sciences (India)

    machinery; aerodynamics; conformal mapping. 1. Introduction. Potential flow in cascades is a well-studied problem. Gostelow (1984) gives reference to several sources in the literature where such studies have been undertaken. Broadly, the problem ...

  11. Packaged, cascadable wideband monolithic feedback amplifiers for radar systems applications

    OpenAIRE

    Alleva, V.; Calori, M.; Cetronio, A.; Lanzieri, C.; Proietti, C.; Rapisarda, S.

    1990-01-01

    Design criteria and fabrication of a packaged, monolithic, cascadable, feedback amplifier are presented. The good performances in term of bandwidth, gain, flatness, reproducibility and reliability makes this component highly suitable for many radar applications.

  12. Enantiomer separation in a cascaded micellar-enhanced ultrafiltration system

    NARCIS (Netherlands)

    Overdevest, P.E.M.; Hoenders, M.H.J.; Riet, van 't K.; Padt, van der A.; Keurentjes, J.T.F.

    2002-01-01

    The increasing demand for optically pure compounds (enantiomers) stimulates the development of new enantiomer separation processes on an industrial scale. The separation of enantiomers by ultrafiltration of enantioselective micelles was studied in a cascaded system. The feasibility of this

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

    Indian Academy of Sciences (India)

    - rofluorocarbons have been criticized for their adverse impact on the Earth's protective ozone layer and for their significant global warming potential (GWP). CO2 has been receiving great concern as an alternative refrigerant. Cascade ...

  14. 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.

  15. 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.

  16. 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.

  17. 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...

  18. Production of defects in metals by collision cascades: TEM experiments

    International Nuclear Information System (INIS)

    Kirk, M.A.

    1995-01-01

    The author reviews his experimental TEM data on the production of dislocation loops by low energy ion bombardment to low doses, as simulations of similar collision cascades produced by fast neutron irradiation, in various metal and alloys. The dependence of vacancy dislocation loop formation on recoil energy, sample temperature, and specific metal or alloy will be examined. Special emphasis will be placed on the effects of dilute alloy additions. A model for cascade melting will be employed to understand these effects, and will require an examination of the role of electron-phonon coupling in cascade cooling and recrystallization. The formation of interstitial dislocation loops as cascade defects, and the influence of the nearby surfaces in these experiments will be briefly discussed

  19. 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.

  20. Vulnerability and Cosusceptibility Determine the Size of Network Cascades

    Science.gov (United States)

    Yang, Yang; Nishikawa, Takashi; Motter, Adilson E.

    2017-01-01

    In a network, a local disturbance can propagate and eventually cause a substantial part of the system to fail in cascade events that are easy to conceptualize but extraordinarily difficult to predict. Here, we develop a statistical framework that can predict cascade size distributions by incorporating two ingredients only: the vulnerability of individual components and the cosusceptibility of groups of components (i.e., their tendency to fail together). Using cascades in power grids as a representative example, we show that correlations between component failures define structured and often surprisingly large groups of cosusceptible components. Aside from their implications for blackout studies, these results provide insights and a new modeling framework for understanding cascades in financial systems, food webs, and complex networks in general.

  1. Targeting the MAPK Signaling Pathway in Cancer: Promising Preclinical Activity with the Novel Selective ERK1/2 Inhibitor BVD-523 (Ulixertinib).

    Science.gov (United States)

    Germann, Ursula A; Furey, Brinley F; Markland, William; Hoover, Russell R; Aronov, Alex M; Roix, Jeffrey J; Hale, Michael; Boucher, Diane M; Sorrell, David A; Martinez-Botella, Gabriel; Fitzgibbon, Matthew; Shapiro, Paul; Wick, Michael J; Samadani, Ramin; Meshaw, Kathryn; Groover, Anna; DeCrescenzo, Gary; Namchuk, Mark; Emery, Caroline M; Saha, Saurabh; Welsch, Dean J

    2017-11-01

    Aberrant activation of signaling through the RAS-RAF-MEK-ERK (MAPK) pathway is implicated in numerous cancers, making it an attractive therapeutic target. Although BRAF and MEK-targeted combination therapy has demonstrated significant benefit beyond single-agent options, the majority of patients develop resistance and disease progression after approximately 12 months. Reactivation of ERK signaling is a common driver of resistance in this setting. Here we report the discovery of BVD-523 (ulixertinib), a novel, reversible, ATP-competitive ERK1/2 inhibitor with high potency and ERK1/2 selectivity. In vitro BVD-523 treatment resulted in reduced proliferation and enhanced caspase activity in sensitive cells. Interestingly, BVD-523 inhibited phosphorylation of target substrates despite increased phosphorylation of ERK1/2. In in vivo xenograft studies, BVD-523 showed dose-dependent growth inhibition and tumor regression. BVD-523 yielded synergistic antiproliferative effects in a BRAF V600E -mutant melanoma cell line xenograft model when used in combination with BRAF inhibition. Antitumor activity was also demonstrated in in vitro and in vivo models of acquired resistance to single-agent and combination BRAF/MEK-targeted therapy. On the basis of these promising results, these studies demonstrate BVD-523 holds promise as a treatment for ERK-dependent cancers, including those whose tumors have acquired resistance to other treatments targeting upstream nodes of the MAPK pathway. Assessment of BVD-523 in clinical trials is underway (NCT01781429, NCT02296242, and NCT02608229). Mol Cancer Ther; 16(11); 2351-63. ©2017 AACR . ©2017 American Association for Cancer Research.

  2. Keratins Regulate p38MAPK-Dependent Desmoglein Binding Properties in Pemphigus

    Science.gov (United States)

    Vielmuth, Franziska; Walter, Elias; Fuchs, Michael; Radeva, Mariya Y.; Buechau, Fanny; Magin, Thomas M.; Spindler, Volker; Waschke, Jens

    2018-01-01

    Keratins are crucial for the anchorage of desmosomes. Severe alterations of keratin organization and detachment of filaments from the desmosomal plaque occur in the autoimmune dermatoses pemphigus vulgaris and pemphigus foliaceus (PF), which are mainly caused by autoantibodies against desmoglein (Dsg) 1 and 3. Keratin alterations are a structural hallmark in pemphigus pathogenesis and correlate with loss of intercellular adhesion. However, the significance for autoantibody-induced loss of intercellular adhesion is largely unknown. In wild-type (wt) murine keratinocytes, pemphigus autoantibodies induced keratin filament retraction. Under the same conditions, we used murine keratinocytes lacking all keratin filaments (KtyII k.o.) as a model system to dissect the role of keratins in pemphigus. KtyII k.o. cells show compromised intercellular adhesion without antibody (Ab) treatment, which was not impaired further by pathogenic pemphigus autoantibodies. Nevertheless, direct activation of p38MAPK via anisomycin further decreased intercellular adhesion indicating that cell cohesion was not completely abrogated in the absence of keratins. Direct inhibition of Dsg3, but not of Dsg1, interaction via pathogenic autoantibodies as revealed by atomic force microscopy was detectable in both cell lines demonstrating that keratins are not required for this phenomenon. However, PF-IgG shifted Dsg1-binding events from cell borders toward the free cell surface in wt cells. This led to a distribution pattern of Dsg1-binding events similar to KtyII k.o. cells under resting conditions. In keratin-deficient keratinocytes, PF-IgG impaired Dsg1-binding strength, which was not different from wt cells under resting conditions. In addition, pathogenic autoantibodies were capable of activating p38MAPK in both KtyII wt and k.o. cells, the latter of which already displayed robust p38MAPK activation under resting conditions. Since inhibition of p38MAPK blocked autoantibody-induced loss of

  3. Silica nanoparticles induce endoplasmic reticulum stress response and activate mitogen activated kinase (MAPK signalling

    Directory of Open Access Journals (Sweden)

    Verena Christen

    Full Text Available Humans may be exposed to engineered silica nanoparticles (SiO2-NPs but potential adverse effects are poorly understood, in particular in relation to cellular effects and modes of action. Here we studied effects of SiO2-NPs on cellular function in human hepatoma cells (Huh7. Exposure for 24 h to 10 and 50 μg/ml SiO2-NPs led to induction of endoplasmic reticulum (ER stress as demonstrated by transcriptional induction of DNAJB9, GADD34, CHOP, as well as CHOP target genes BIM, CHAC-1, NOXA and PUMA. In addition, CHOP protein was induced. In addition, SiO2-NPs induced an inflammatory response as demonstrated by induction of TNF-α and IL-8. Activation of MAPK signalling was investigated employing a PCR array upon exposure of Huh7 cells to SiO2-NPs. Five of 84 analysed genes, including P21, P19, CFOS, CJUN and KSR1 exhibited significant transcriptional up-regulation, and 18 genes a significant down-regulation. Strongest down-regulation occurred for the proto-oncogene BRAF, MAPK11, one of the four p38 MAPK genes, and for NFATC4. Strong induction of CFOS, CJUN, FRA1 and CMYC was found after exposure to 50 μg/ml SiO2-NPs for 24 h. To analyse for effects derived from up-regulation of TNF-α, Huh7 cells were exposed to SiO2-NPs in the presence of the TNF-α inhibitor sauchinone, which reduced the induction of the TNF-α transcript by about 50%. These data demonstrate that SiO2-NPs induce ER stress, MAPK pathway and lead to inflammatory reaction in human hepatoma cells. Health implications of SiO2-NPs exposure should further be investigated for a risk assessment of these frequently used nanoparticles. Keywords: Silica nanoparticles, Endoplasmic reticulum stress, MAPK, TNF-α, Huh7 cells

  4. MAPK/FoxA2-mediated cigarette smoke-induced squamous metaplasia of bronchial epithelial cells

    Directory of Open Access Journals (Sweden)

    Du C

    2017-11-01

    Full Text Available Chunling Du,* Jinchang Lu,* Lei Zhou, Bo Wu, Feng Zhou, Liang Gu, Donghui Xu, Yingxin Sun Department of Respiratory Medicine, Qingpu Branch of Zhongshan Hospital, Fudan University, Shanghai, China *These authors contributed equally to this work Objective: To explore the effect of cigarette smoke (CS on the development of squamous metaplasia in human airway epithelial cells and the role of MAPK- and FoxA2-signaling pathways in the process.Materials and methods: In an in vitro study, we treated the bronchial epithelial cell line BEAS2B with CS extract, followed by treatment with the ERK inhibitor U0126, the JNK inhibitor SP600125, or the p38 inhibitor SB203580. In vivo, we used a CS-induced rat model. After treatment with CS with or without MAPK inhibitors for 90 days, lung tissues were harvested. p-ERK, p-p38 and p-JNK protein levels in cells and lung tissue were measured using enzyme-linked immunosorbent assays, mRNA- and protein-expression profiles of FoxA2, E-cadherin, CD44, and ZO1 were measured using quantitative real-time polymerase chain reaction and Western blotting, respectively, and morphological changes in bronchial epithelial cells were observed using lung-tissue staining.Results: In both the in vitro and in vivo studies, phosphorylation of the ERK1/2, JNK, and p38 proteins was significantly increased (P<0.05 and mRNA and protein expression of E-cadherin and FoxA2 significantly decreased (P<0.05 compared with the control group. ERK, JNK, and p38 inhibitors reversed the CS-extract-induced changes in E-cadherin, CD44, and ZO1 mRNA and protein expression (P<0.05, decreased p-ERK, p-p38, and p-JNK protein levels in cells and lung tissue, suppressed bronchial epithelial hyperplasia and local squamous metaplasia, and decreased FoxA2 expression.Conclusion: MAPK and FoxA2 mediate CS-induced squamous metaplasia. MAPK inhibitors upregulate FoxA2, resulting in a reduction in the degree of squamous metaplasia. Keywords: MAPK, FoxA2, cigarette

  5. Differential gene expressions of the MAPK signaling pathway in enterovirus 71-infected rhabdomyosarcoma cells

    Directory of Open Access Journals (Sweden)

    Weifeng Shi

    Full Text Available BACKGROUND: Mitogen-activated protein kinase (MAPK signaling pathway plays an important role in response to viral infection. The aim of this study was to explore the function and mechanism of MAPK signaling pathway in enterovirus 71 (EV71 infection of human rhabdomyosarcoma (RD cells. METHODS: Apoptosis of RD cells was observed using annexin V-FITC/PI binding assay under a fluorescence microscope. Cellular RNA was extracted and transcribed to cDNA. The expressions of 56 genes of MAPK signaling pathway in EV71-infected RD cells at 8 h and 20 h after infection were analyzed by PCR array. The levels of IL-2, IL-4, IL-10, and TNF-α in the supernatant of RD cells infected with EV71 at different time points were measured by ELISA. RESULTS: The viability of RD cells decreased obviously within 48 h after EV71 infection. Compared with the control group, EV71 infection resulted in the significantly enhanced releases of IL-2, IL-4, IL-10 and TNF-α from infected RD cells (p < 0.05. At 8 h after infection, the expressions of c-Jun, c-Fos, IFN-i, MEKK1, MLK3 and NIK genes in EV71-infected RD cells were up-regulated by 2.08-6.12-fold, whereas other 19 genes (e.g. AKT1, AKT2, E2F1, IKK and NF-κB1 exhibited down-regulation. However, at 20 h after infection, those MAPK signaling molecules including MEKK1, ASK1, MLK2, MLK3, NIK, MEK1, MEK2, MEK4, MEK7, ERK1, JNK1 and JNK2 were up-regulated. In addition, the expressions of AKT2, ELK1, c-Jun, c-Fos, NF-κB p65, PI3K and STAT1 were also increased. CONCLUSION: EV71 infection induces the differential gene expressions of MAPK signaling pathway such as ERK, JNK and PI3K/AKT in RD cells, which may be associated with the secretions of inflammatory cytokines and host cell apoptosis.

  6. 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)

  7. Cascaded Soliton Compression of Energetic Femtosecond Pulses at 1030 nm

    DEFF Research Database (Denmark)

    Bache, Morten; Zhou, Binbin

    2012-01-01

    We discuss soliton compression with cascaded second-harmonic generation of energetic femtosecond pulses at 1030 nm. We discuss problems encountered with soliton compression of long pulses and show that sub-10 fs compressed pulses can be achieved.......We discuss soliton compression with cascaded second-harmonic generation of energetic femtosecond pulses at 1030 nm. We discuss problems encountered with soliton compression of long pulses and show that sub-10 fs compressed pulses can be achieved....

  8. Critical Boundary of Cascaded Quadratic Soliton Compression in PPLN

    DEFF Research Database (Denmark)

    Guo, Hairun; Zeng, Xianglong; Zhou, Binbin

    2012-01-01

    Cascaded quadratic soliton compression in PPLN is investigated and a general critical soliton number is found as the compression boundary. An optimal-parameter diagram for compression at 1550 nm is presented.......Cascaded quadratic soliton compression in PPLN is investigated and a general critical soliton number is found as the compression boundary. An optimal-parameter diagram for compression at 1550 nm is presented....

  9. Synthesis of Pyridoacridines through Anionic Cascade Ring Closure

    DEFF Research Database (Denmark)

    Petersen, I.N.; Kristensen, Jesper Langgaard

    2014-01-01

    A new synthesis of 13-deazaascididemin (AK-37) based on a recently developed anionic cascade ring closure is presented. Although the isolated yields are modest, the approach provides ready access to new substituted derivatives of 13-deazaascididemin.......A new synthesis of 13-deazaascididemin (AK-37) based on a recently developed anionic cascade ring closure is presented. Although the isolated yields are modest, the approach provides ready access to new substituted derivatives of 13-deazaascididemin....

  10. 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....

  11. Vortex merging and spectral cascade in two-dimensional flows

    DEFF Research Database (Denmark)

    Nielsen, A.H.; He, X.; Juul Rasmussen, J.

    1996-01-01

    The merging of two identical vortices is studied numerically using a spectral code. It is noted that the enstrophy cascade is most active on the distorted vortex boundaries, with a Kolmogorov-like spectrum E(k) approximate to k(-alpha), alpha less than or equal to 4, developed at high wave numbers....... The inverse energy cascade is completed when the vortices merge into one of larger size. (C) 1996 American Institute of Physics....

  12. Modulation of ERK1/2 and p38MAPK by lead in the cerebellum of Brazilian catfish Rhamdia quelen

    International Nuclear Information System (INIS)

    Leal, Rodrigo B.; Ribeiro, Sandro Jose; Posser, Thais; Cordova, Fabiano M.; Rigon, Ana Paula; Filho, Evoy Zaniboni; Bainy, Afonso C.D.

    2006-01-01

    Lead (Pb 2+ ) is a neurotoxic trace metal, widespread in aquatic environment that can change physiologic, biochemical and behavioral parameters in diverse fish species. Chemical exposure may drive modulation of mitogen-activated protein kinases (MAPKs) that are a family of highly conserved enzymes which comprise ubiquitous groups of signaling proteins playing critical regulatory roles in cell physiology. Extracellular signal-regulated kinases (ERK1/2) and p38 MAPK control complex programs such as gene expression, embryogenesis, cell differentiation, cell proliferation, cell death and synaptic plasticity. Little information is available about MAPKs in aquatic organisms and their modulation by trace metals. The aim of this work was to determine the modulation of ERK1/2 and p38 MAPK phosphorylation by Pb 2+ in vivo and in vitro, in cerebellar slices of the catfish, Rhamdia quelen. In the in vitro model, slices were incubated for 3 h with lead acetate (1-10 μM). In the in vivo studies, the animals were exposed for 2 days to lead acetate (1 mg L -1 ). ERK1/2 and p38 MAPK (total and phosphorylated forms) were immunodetected in cerebellar slices by Western blotting. Pb 2+ added in vitro at 5 and 10 μM increased significantly the phosphorylation of both MAPKs. The in vivo exposed animals also showed a significant increase of ERK1/2 and p38 MAPK phosphorylation without changes in the total content of the enzymes. In conclusion, the present work indicates that it is possible to evaluate the ERK1/2 and p38 MAPK activation in the central nervous system (CNS) of a freshwater fish largely distributed in South America. Moreover, Pb 2+ , an important environmental pollutant may activate in vitro and in vivo ERK1/2 and p38 MAPK enzymes. These findings are important considering the functional and ecologic implications associated to Pb 2+ exposure of a freshwater fish species, such as R. quelen, and the roles of ERK1/2 and p38 MAPK in the control of brain development

  13. Blind I/Q imbalance and nonlinear ISI mitigation in Nyquist-SCM direct detection system with cascaded widely linear and Volterra equalizer

    Science.gov (United States)

    Liu, Na; Ju, Cheng

    2018-02-01

    Nyquist-SCM signal after fiber transmission, direct detection (DD), and analog down-conversion suffers from linear ISI, nonlinear ISI, and I/Q imbalance, simultaneously. Theoretical analysis based on widely linear (WL) and Volterra series is given to explain the relationship and interaction of these three interferences. A blind equalization algorithm, cascaded WL and Volterra equalizer, is designed to mitigate these three interferences. Furthermore, the feasibility of the proposed cascaded algorithm is experimentally demonstrated based on a 40-Gbps data rate 16-quadrature amplitude modulation (QAM) virtual single sideband (VSSB) Nyquist-SCM DD system over 100-km standard single mode fiber (SSMF) transmission. In addition, the performances of conventional strictly linear equalizer, WL equalizer, Volterra equalizer, and cascaded WL and Volterra equalizer are experimentally evaluated, respectively.

  14. Three component laser anemometer measurements in an annular cascade of core turbine vanes with contoured end wall

    Science.gov (United States)

    Goldman, Louis J.; Seasholtz, Richard G.

    1988-01-01

    The three mean velocity components were measured in a full-scale annular turbine stator cascade with contoured hub end wall using a newly developed laser anemometer system. The anemometer consists of a standard fringe configuration using fluorescent seed particles to measure the axial and tangential components. The radial component is measured with a scanning confocal Fabry-Perot interferometer. These two configurations are combined in a single optical system that can operate simultaneously in a backscatter mode through a single optical access port. Experimental measurements were obtained both within and downstream of the stator vane row and compared with calculations from a three-dimensional inviscid computer program. In addition, detailed calibration procedures are described that were used, prior to the experiment, to accurately determine the laser beam probe volume location relative to the cascade hardware.

  15. Signal transduction in a covalent post-assembly modification cascade

    Science.gov (United States)

    Pilgrim, Ben S.; Roberts, Derrick A.; Lohr, Thorsten G.; Ronson, Tanya K.; Nitschke, Jonathan R.

    2017-12-01

    Natural reaction cascades control the movement of biomolecules between cellular compartments. Inspired by these systems, we report a synthetic reaction cascade employing post-assembly modification reactions to direct the partitioning of supramolecular complexes between phases. The system is composed of a self-assembled tetrazine-edged FeII8L12 cube and a maleimide-functionalized FeII4L6 tetrahedron. Norbornadiene (NBD) functions as the stimulus that triggers the cascade, beginning with the inverse-electron-demand Diels-Alder reaction of NBD with the tetrazine moieties of the cube. This reaction generates cyclopentadiene as a transient by-product, acting as a relay signal that subsequently undergoes a Diels-Alder reaction with the maleimide-functionalized tetrahedron. Cyclooctyne can selectively inhibit the cascade by outcompeting NBD as the initial trigger. Initiating the cascade with 2-octadecyl NBD leads to selective alkylation of the tetrahedron upon cascade completion. The increased lipophilicity of the C18-tagged tetrahedron drives this complex into a non-polar phase, allowing its isolation from the initially inseparable mixture of complexes.

  16. 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

  17. 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.

  18. 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.

  19. Cascade screening program for familial hypercholesterolemia.

    Science.gov (United States)

    Rubio-Marín, Patricia; Michán-Doña, Alfredo; Maraver-Delgado, Juan; Arroyo-Olivares, Raquel; Barrado Varea, Rosalía; Pérez de Isla, Leopoldo; Mata, Pedro

    2018-03-06

    Early detection of heterozygous familial hypercholesterolemia (HFH) is needed to prevent premature cardiovascular events. Our aim isto describe the course of an HFH screening detection day in the Northern Cadiz Health Area in Spain and to analyze the data recorded. Descriptive study of an FH cascade screening program. Index cases (ICs) and their 1st and 2nd grade relatives were appointed during a weekend by the FH Foundation. Venous blood samples were taken from the subjects for genetic, blood, and chemistry tests; specialized medical consultation and physical examination were performed. The study sample consisted of 132 subjects: 21 ICs and 111 relatives (16 under 18years old), with a mean age of 11.4years (SD4.57). Mean age of subjects over 18years was 45.2years. A gene mutation was found in 90 relatives. Mean age at diagnosis was 25years (SD17.7) for relatives and for 36.4years (SD17.2; P=.01) for ICs. Smoking rate was higher in relatives than in ICs (26.3% vs 4.8%; P=.02) and corneal arcus was more common in ICs as compared to relatives (47.6% vs 12.6%; P<.001). Prior myocardial infarction was recorded in 14.3% of ICs and 4.2% of relatives respectively (P=.07). Maximum lipid lowering treatment was being administered to 43.1%. The screening detection approach identified the estimated 4% population with HFH in the area, and allows for diagnosing HFH 11.4years earlier. Copyright © 2018 SEEN y SED. Publicado por Elsevier España, S.L.U. All rights reserved.

  20. 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.

  1. Electroacupuncture Inhibits the Activation of p38MAPK in the Central Descending Facilitatory Pathway in Rats with Inflammatory Pain

    Directory of Open Access Journals (Sweden)

    Man-Li Hu

    2017-01-01

    Full Text Available The mitogen-activated protein kinases (MAPKs, especially p38MAPK, play a pivotal role in chronic pain. Electroacupuncture (EA relieves inflammatory pain underlying the descending pathway, that is, the periaqueductal gray (PAG, the rostral ventromedial medulla (RVM, and the spinal cord dorsal horn (SCDH. However, whether EA antagonizes inflammatory pain through regulation of p38MAPK in this descending facilitatory pathway is unclear. Complete Freund’s adjuvant (CFA was injected into the hind paw of rats to establish inflammatory pain model. EA was administrated for 30 min at Zusanli and Kunlun acupoints at 0.5, 24.5, 48.5, and 72.5 h, respectively. The paw withdrawal threshold (PWT, paw edema, and Phosphor-p38MAPK-Immunoreactivity (p-p38MAPK-IR cells were measured before (0 h and at 1, 3, 5, 7, 25, and 73 h after CFA or saline injection. EA increased PWT at 1, 3, 25, and 73 h and inhibited paw edema at 25 and 73 h after CFA injection. Moreover, the increasing number of p-p38MAPK-IR cells which was induced by CFA was suppressed by EA stimulation in PAG and RVM at 3 and 5 h and in SCDH at 5, 7, 25, and 73 h. These results suggest that EA suppresses inflammation-induced hyperalgesia probably through inhibiting p38MAPK activation in the descending facilitatory pathway.

  2. Glucocorticoids induce apoptosis and matrix metalloproteinase-13 expression in chondrocytes through the NOX4/ROS/p38 MAPK pathway.

    Science.gov (United States)

    Huang, Ying; Cai, Gui-Quan; Peng, Jian-Ping; Shen, Chao

    2018-03-08

    Based on the results from our previous study, dexamethasone (Dex) increases reactive oxygen species (ROS) levels and subsequently induces cell death and matrix catabolism in chondrocytes. Nevertheless, the mechanism underlying this phenomenon remains unclear. Nicotinamide adenine dinucleotide (phosphate) (NADPH) oxidase 4 (NOX4) is one of the major enzymes responsible for intracellular ROS production during the inflammatory process. The objective of the current study was to investigate the role of NOX4 in Dex-induced ROS over-production. Healthy chondrocytes were harvested from the cartilage debris from 6 female patients. NOX4 and p38 mitogen-activated protein kinase (MAPK) expression levels in these cells were evaluated in the presence of Dex. Changes in the number of apoptotic and viable Dex-treated chondrocytes were recorded after the cells were treated with NOX and p38 MAPK inhibitors. Changes in matrix metalloproteinase 13 (MMP-13) expression levels in Dex-treated chondrocytes were also investigated. The Dex treatment increased NOX4 expression via the glucocorticoid receptor (GR). Treatment of cells with apocynin, a NOX inhibitor, decreased intracellular ROS levels and inhibited p38 MAPK activation. Treatment of cells with a ROS scavenger also reduced p38 MAPK expression. Treatment of cells with a NOX inhibitor, ROS scavenger and p38 MAPK inhibitor rescued chondrocytes from Dex-induced apoptosis. Moreover, treatment of cells with these agents blocked MMP-13 expression in Dex-treated chondrocytes. NOX4 silencing also suppressed p38 MAPK and MMP-13 expression. Dex triggered apoptosis and MMP-13 expression through the NOX4/ROS/p38 MAPK signaling pathway. NOX4 may be a therapeutic target in the management of Dex-induced complications. Copyright © 2018 Elsevier Ltd. All rights reserved.

  3. Phosphoproteomics Reveals MAPK Inhibitors Enhance MET- and EGFR-Driven AKT Signaling in KRAS-Mutant Lung Cancer.

    Science.gov (United States)

    Kim, Jae-Young; Welsh, Eric A; Fang, Bin; Bai, Yun; Kinose, Fumi; Eschrich, Steven A; Koomen, John M; Haura, Eric B

    2016-10-01

    Pathway inhibition of the RAS-driven MAPK pathway using small-molecule kinase inhibitors has been a key focus for treating cancers driven by oncogenic RAS, yet significant clinical responses are lacking. Feedback reactivation of ERK driven by drug-induced RAF activity has been suggested as one of the major drug resistance mechanisms, especially in the context of oncogenic RAS. To determine whether additional adaptive resistance mechanisms may coexist, we characterized global phosphoproteomic changes after MEK inhibitor selumetinib (AZD6244) treatment in KRAS-mutant A427 and A549 lung adenocarcinoma cell lines employing mass spectrometry-based phosphoproteomics. We identified 9,075 quantifiable unique phosphosites (corresponding to 3,346 unique phosphoproteins), of which 567 phosphosites were more abundant and 512 phosphosites were less abundant after MEK inhibition. Selumetinib increased phosphorylation of KSR-1, a scaffolding protein required for assembly of MAPK signaling complex, as well as altered phosphorylation of GEF-H1, a novel regulator of KSR-1 and implicated in RAS-driven MAPK activation. Moreover, selumetinib reduced inhibitory serine phosphorylation of MET at Ser985 and potentiated HGF- and EGF-induced AKT phosphorylation. These results were recapitulated by pan-RAF (LY3009120), MEK (GDC0623), and ERK (SCH772984) inhibitors, which are currently under early-phase clinical development against RAS-mutant cancers. Our results highlight the unique adaptive changes in MAPK scaffolding proteins (KSR-1, GEF-H1) and in RTK signaling, leading to enhanced PI3K-AKT signaling when the MAPK pathway is inhibited. This study highlights the unique adaptive changes in MAPK scaffolding proteins (KSR-1, GEF-H1) and in RTK signaling, leading to enhanced PI3K/AKT signaling when the MAPK pathway is inhibited. Mol Cancer Res; 14(10); 1019-29. ©2016 AACR. ©2016 American Association for Cancer Research.

  4. Heat stress prevents lipopolysaccharide-induced apoptosis in pulmonary microvascular endothelial cells by blocking calpain/p38 MAPK signalling.

    Science.gov (United States)

    Liu, Zhi-Feng; Zheng, Dong; Fan, Guo-Chang; Peng, Tianqing; Su, Lei

    2016-08-01

    Pulmonary microvascular endothelial cells (PMECs) injury including apoptosis plays an important role in the pathogenesis of acute lung injury during sepsis. Our recent study has demonstrated that calpain activation contributes to apoptosis in PMECs under septic conditions. This study investigated how calpain activation mediated apoptosis and whether heat stress regulated calpain activation in lipopolysaccharides (LPS)-stimulated PMECs. In cultured mouse primary PMECs, incubation with LPS (1 μg/ml, 24 h) increased active caspase-3 fragments and DNA fragmentation, indicative of apoptosis. These effects of LPS were abrogated by pre-treatment with heat stress (43 °C for 2 h). LPS also induced calpain activation and increased phosphorylation of p38 MAPK. Inhibition of calpain and p38 MAPK prevented apoptosis induced by LPS. Furthermore, inhibition of calpain blocked p38 MAPK phosphorylation in LPS-stimulated PMECs. Notably, heat stress decreased the protein levels of calpain-1/2 and calpain activities, and blocked p38 MAPK phosphorylation in response to LPS. Additionally, forced up-regulation of calpain-1 or calpain-2 sufficiently induced p38 MAPK phosphorylation and apoptosis in PMECs, both of which were inhibited by heat stress. In conclusion, heat stress prevents LPS-induced apoptosis in PMECs. This effect of heat stress is associated with down-regulation of calpain expression and activation, and subsequent blockage of p38 MAPK activation in response to LPS. Thus, blocking calpain/p38 MAPK pathway may be a novel mechanism underlying heat stress-mediated inhibition of apoptosis in LPS-stimulated endothelial cells.

  5. Simvastatin and a plant galactolipid protect animals from septic shock by regulating oxylipin mediator dynamics through the MAPK-cPLA2 signaling pathway.

    Science.gov (United States)

    Apaya, Maria Karmella; Lin, Chih-Yu; Chiou, Ching-Yi; Yang, Chung-Chih; Ting, Chen-Yun; Shyur, Lie-Fen

    2015-12-14

    Sepsis remains a major medical issue despite decades of research. Identification of important inflammatory cascades and key molecular mediators are crucial for developing intervention and prevention strategies. In this study, we conducted a comparative oxylipin metabolomics study to gain a comprehensive picture of lipid mediator dynamics during the initial hyper-inflammatory phase of sepsis, and demonstrated, in parallel, the efficacy of simvastatin and plant galactolipid, 1,2-di-O-α-linolenoyl-3-O-β-galactopyranosyl-sn-glycerol (dLGG) in the homeostatic regulation of the oxylipin metabolome using a lipopolysaccharide (LPS)-induced sepsis C57BL/6J mouse model. LPS increased the systemic and organ levels of pro-inflammatory metabolites of linoleic acid including leukotoxin diols, i.e., 9,10-DHOME, 12,13-DHOME, and octadecadienoic acids, i.e., 9-HODE and 13-HODE; and arachidonic acid-derived prostanoid, PGE 2 , and hydroxyeicosatetraenoic acids, i.e., 8, 12- and 15-HETE. Treatment with either compound decreased the levels of pro-inflammatory metabolites and elevated pro-resolution lipoxin A 4 , 5(6)-EET, 11(12)-EET and 15-deoxy-PGJ 2 . dLGG and simvastatin ameliorated the effects of LPS-induced MAPK-dependent activation of cPLA 2 , cyclooxygenase-2, lipoxygenase, cytochrome P450, and/or epoxide hydrolase, lowered systemic TNF-α and IL-6 levels and aminotransferase activities and decreased organ-specific infiltration of inflammatory leukocytes and macrophages, and septic shock-induced multiple organ damage. Furthermore, both dLGG and simvastatin increased the survival rates in the cecal ligation and puncture (CLP) sepsis model. This study provides new insights into the role of oxylipins in sepsis pathogenesis and highlights the potential of simvastatin and dLGG in sepsis therapy and prevention.

  6. Netrin-1 induces the migration of Schwann cells via p38 MAPK and PI3K-Akt signaling pathway mediated by the UNC5B receptor

    Energy Technology Data Exchange (ETDEWEB)

    Lv, Jianwei [General Hospital of Tianjin Medical University, No. 154, Anshan Road, Heping District, Tianjin 300052 (China); Tianjin Institute of Orthopedics in Traditional Chinese and Western Medicine, No. 155, Munan Road, Tianjin 300050 (China); Sun, Xiaolei; Ma, Jianxiong [Tianjin Institute of Orthopedics in Traditional Chinese and Western Medicine, No. 155, Munan Road, Tianjin 300050 (China); Ma, Xinlong, E-mail: gengxiao502@163.com [General Hospital of Tianjin Medical University, No. 154, Anshan Road, Heping District, Tianjin 300052 (China); Tianjin Institute of Orthopedics in Traditional Chinese and Western Medicine, No. 155, Munan Road, Tianjin 300050 (China); Zhang, Yang; Li, Fengbo; Li, Yanjun; Zhao, Zhihu [Tianjin Institute of Orthopedics in Traditional Chinese and Western Medicine, No. 155, Munan Road, Tianjin 300050 (China)

    2015-08-14

    Schwann cells (SCs) play an essentially supportive role in the regeneration of injured peripheral nerve system (PNS). As Netrin-1 is crucial for the normal development of nervous system (NS) and can direct the process of damaged PNS regeneration, our study was designed to determine the role of Netrin-1 in RSC96 Schwann cells (an immortalized rat Schwann cell line) proliferation and migration. Our studies demonstrated that Netrin-1 had no effect on RSC96 cells proliferation, while significantly promoted RSC96 cells migration. The Netrin-1-induced RSC96 cells migration was significantly attenuated by inhibition of p38 and PI3K through pretreatment with SB203580 and LY294002 respectively, but not inhibition of MEK1/2 and JNK by U0126-EtOH and SP600125 individually. Treatment with Netrin-1 enhanced the phosphorylation of p38 and Akt. QRT-PCR indicated that Netrin-1 and only its receptors Unc5a, Unc5b and Neogenin were expressed in RSC96 cells, among which Unc5b expressed the most. And UNC5B protein was significantly increased after stimulated by Netrin-1. In conclusion, we show here that Netrin-1-enhanced SCs migration is mediated by activating p38 MAPK and PI3K-Akt signal cascades via receptor UNC5B, which suggests that Netrin-1 could serve as a new therapeutic strategy and has potential application value for PNS regeneration. - Highlights: • Netrin-1 attracts RSC96 Schwann cells migration in a dose dependent manner. • Netrin-1 induced Schwann cells migration is p38 and PI3K-Akt signaling dependent. • UNC5B may be dominant receptor mediating Netrin-1′ effect on RSC96 cells motility. • Netrin-1 may promote peripheral nerve repair by enhancing Schwann cells motility.

  7. SHP2 regulates IL-2 induced MAPK activation, but not Stat3 or Stat5 tyrosine phosphorylation, in cutaneous T cell lymphoma cells

    DEFF Research Database (Denmark)

    Lundin Brockdorff, Johannes; Woetmann, Anders; Mustelin, Tomas

    2002-01-01

    The phosphotyrosine phosphatase SHP2 has been suggested to regulate activation of MAPK, Stat3, and Stat5 in several experimental models. In this study we investigated the role of SHP2 in IL-2 induced activation of MAPK and the Stat proteins using the human CTCL cell line MyLa2059 derived from...... a cutaneous T cell lymphoma (CTCL). For this purpose, MyLa2059 cells were stably transfected with wild-type SHP2 or inactive SHP2. The cells transfected with inactive SHP2 showed reduced MAPK activation upon IL-2 stimulation, suggesting that SHP2 upregulates IL-2 induced MAPK activation in T cells. However...

  8. Experimental study on cascaded attitude angle control of a multi-rotor unmanned aerial vehicle with the simple internal model control method

    Energy Technology Data Exchange (ETDEWEB)

    Song, Jun Beom [Dept. of Aviation Maintenance, Dongwon Institute of Science and Technology, Yangsan (Korea, Republic of); Byun, Young Seop; Jeong, Jin Seok; Kim, Jeong; Kang, Beom Soo [Dept. of Aerospace Engineering, Pusan National University, Busan (Korea, Republic of)

    2016-11-15

    This paper proposes a cascaded control structure and a method of practical application for attitude control of a multi-rotor Unmanned aerial vehicle (UAV). The cascade control, which has tighter control capability than a single-loop control, is rarely used in attitude control of a multi-rotor UAV due to the input-output relation, which is no longer simply a set-point to Euler angle response transfer function of a single-loop PID control, but there are multiply measured signals and interactive control loops that increase the complexity of evaluation in conventional way of design. However, it is proposed in this research a method that can optimize a cascade control with a primary and secondary loops and a PID controller for each loop. An investigation of currently available PID-tuning methods lead to selection of the Simple internal model control (SIMC) method, which is based on the Internal model control (IMC) and direct-synthesis method. Through the analysis and experiments, this research proposes a systematic procedure to implement a cascaded attitude controller, which includes the flight test, system identification and SIMC-based PID-tuning. The proposed method was validated successfully from multiple applications where the application to roll axis lead to a PID-PID cascade control, but the application to yaw axis lead to that of PID-PI.

  9. Experimental study on cascaded attitude angle control of a multi-rotor unmanned aerial vehicle with the simple internal model control method

    International Nuclear Information System (INIS)

    Song, Jun Beom; Byun, Young Seop; Jeong, Jin Seok; Kim, Jeong; Kang, Beom Soo

    2016-01-01

    This paper proposes a cascaded control structure and a method of practical application for attitude control of a multi-rotor Unmanned aerial vehicle (UAV). The cascade control, which has tighter control capability than a single-loop control, is rarely used in attitude control of a multi-rotor UAV due to the input-output relation, which is no longer simply a set-point to Euler angle response transfer function of a single-loop PID control, but there are multiply measured signals and interactive control loops that increase the complexity of evaluation in conventional way of design. However, it is proposed in this research a method that can optimize a cascade control with a primary and secondary loops and a PID controller for each loop. An investigation of currently available PID-tuning methods lead to selection of the Simple internal model control (SIMC) method, which is based on the Internal model control (IMC) and direct-synthesis method. Through the analysis and experiments, this research proposes a systematic procedure to implement a cascaded attitude controller, which includes the flight test, system identification and SIMC-based PID-tuning. The proposed method was validated successfully from multiple applications where the application to roll axis lead to a PID-PID cascade control, but the application to yaw axis lead to that of PID-PI

  10. Incorporating forcing terms in cascaded lattice Boltzmann approach by method of central moments.

    Science.gov (United States)

    Premnath, Kannan N; Banerjee, Sanjoy

    2009-09-01

    Cascaded lattice Boltzmann method (cascaded-LBM) employs a class of collision operators aiming to stabilize computations and remove certain modeling artifacts for simulation of fluid flow on lattice grids with sizes arbitrarily larger than the smallest physical dissipation length scale [Geier, Phys. Rev. E 63, 066705 (2006)]. It achieves this and distinguishes from other collision operators, such as in the standard single or multiple relaxation-time approaches, by performing relaxation process due to collisions in terms of moments shifted by the local hydrodynamic fluid velocity, i.e., central moments, in an ascending order by order at different relaxation rates. In this paper, we propose and derive source terms in the cascaded-LBM to represent the effect of external or internal forces on the dynamics of fluid motion. This is essentially achieved by matching the continuous form of the central moments of the source or forcing terms with its discrete version. Different forms of continuous central moments of sources, including one that is obtained from a local Maxwellian, are considered in this regard. As a result, the forcing terms obtained in this formulation are Galilean invariant by construction. To alleviate lattice artifacts due to forcing terms in the emergent macroscopic fluid equations, they are proposed as temporally semi-implicit and second order, and the implicitness is subsequently effectively removed by means of a transformation to facilitate computation. It is shown that the impressed force field influences the cascaded collision process in the evolution of the transformed distribution function. The method of central moments along with the associated orthogonal properties of the moment basis completely determines the analytical expressions for the source terms as a function of the force and macroscopic velocity fields. In contrast to the existing forcing schemes, it is found that they involve higher-order terms in velocity space. It is shown that the

  11. REX-1 expression and p38 MAPK activation status can determine proliferation/differentiation fates in human mesenchymal stem cells.

    Directory of Open Access Journals (Sweden)

    Dilli Ram Bhandari

    Full Text Available BACKGROUND: REX1/ZFP42 is a well-known embryonic stem cell (ESC marker. However, the role of REX1, itself, is relatively unknown because the function of REX1 has only been reported in the differentiation of ESCs via STAT signaling pathways. Human mesenchymal stem cells (hMSCs isolated from young tissues and cancer cells express REX1. METHODOLOGY/PRINCIPAL FINDING: Human umbilical cord blood-derived MSCs (hUCB-MSCs and adipose tissue-derived MSCs (hAD-MSCs strongly express REX1 and have a lower activation status of p38 MAPK, but bone marrow-derived MSCs (hBM-MSCs have weak REX1 expression and higher activation of p38 MAPK. These results indicated that REX1 expression in hMSCs was positively correlated with proliferation rates but inversely correlated with the phosphorylation of p38 MAPK. In hUCB-MSCs, the roles of REX1 and p38 MAPK were investigated, and a knockdown study was performed using a lentiviral vector-based small hairpin RNA (shRNA. After REX1 knockdown, decreased cell proliferation was observed. In REX1 knocked-down hUCB-MSCs, the osteogenic differentiation ability deteriorated, but the adipogenic potential increased or was similar to that observed in the controls. The phosphorylation of p38 MAPK in hUCB-MSCs significantly increased after REX1 knockdown. After p38 MAPK inhibitor treatment, the cell growth in REX1 knocked-down hUCB-MSCs almost recovered, and the suppressed expression levels of CDK2 and CCND1 were also restored. The expression of MKK3, an upstream regulator of p38 MAPK, significantly increased in REX1 knocked-down hUCB-MSCs. The direct binding of REX1 to the MKK3 gene was confirmed by a chromatin immunoprecipitation (ChIP assay. CONCLUSIONS/SIGNIFICANCE: These findings showed that REX1 regulates the proliferation/differentiation of hMSCs through the suppression of p38 MAPK signaling via the direct suppression of MKK3. Therefore, p38 MAPK and REX-1 status can determine the cell fate of adult stem cells (ASCs. These

  12. Effect of Repeated Electroacupuncture Intervention on Hippocampal ERK and p38MAPK Signaling in Neuropathic Pain Rats

    Directory of Open Access Journals (Sweden)

    Jun-ying Wang

    2015-01-01

    Full Text Available Results of our past studies showed that hippocampal muscarinic acetylcholine receptor (mAChR-1 mRNA and differentially expressed proteins participating in MAPK signaling were involved in electroacupuncture (EA induced cumulative analgesia in neuropathic pain rats, but the underlying intracellular mechanism remains unknown. The present study was designed to observe the effect of EA stimulation (EAS on hippocampal extracellular signal-regulated kinases (ERK and p38 MAPK signaling in rats with chronic constrictive injury (CCI of the sciatic nerve, so as to reveal its related intracellular targets in pain relief. After CCI, the thermal pain thresholds of the affected hind were significantly decreased compared with the control group (P<0.05. Following one and two weeks’ EAS of ST 36-GB34, the pain thresholds were significantly upregulated (P<0.05, and the effect of EA2W was remarkably superior to that of EA2D and EA1W (P<0.05. Correspondingly, CCI-induced decreased expression levels of Ras, c-Raf, ERK1 and p-ERK1/2 proteins, and p38 MAPK mRNA and p-p38MAPK protein in the hippocampus tissues were reversed by EA2W (P<0.05. The above mentioned results indicated that EA2W induced cumulative analgesic effect may be closely associated with its function in removing neuropathic pain induced suppression of intracellular ERK and p38MAPK signaling in the hippocampus.

  13. Astaxanthin Pretreatment Attenuates Hepatic Ischemia Reperfusion-Induced Apoptosis and Autophagy via the ROS/MAPK Pathway in Mice

    Directory of Open Access Journals (Sweden)

    Jingjing Li

    2015-05-01

    Full Text Available Background: Hepatic ischemia reperfusion (IR is an important issue in complex liver resection and liver transplantation. The aim of the present study was to determine the protective effect of astaxanthin (ASX, an antioxidant, on hepatic IR injury via the reactive oxygen species/mitogen-activated protein kinase (ROS/MAPK pathway. Methods: Mice were randomized into a sham, IR, ASX or IR + ASX group. The mice received ASX at different doses (30 mg/kg or 60 mg/kg for 14 days. Serum and tissue samples at 2 h, 8 h and 24 h after abdominal surgery were collected to assess alanine aminotransferase (ALT, aspartate aminotransferase (AST, inflammation factors, ROS, and key proteins in the MAPK family. Results: ASX reduced the release of ROS and cytokines leading to inhibition of apoptosis and autophagy via down-regulation of the activated phosphorylation of related proteins in the MAPK family, such as P38 MAPK, JNK and ERK in this model of hepatic IR injury. Conclusion: Apoptosis and autophagy caused by hepatic IR injury were inhibited by ASX following a reduction in the release of ROS and inflammatory cytokines, and the relationship between the two may be associated with the inactivation of the MAPK family.

  14. Astaxanthin Pretreatment Attenuates Hepatic Ischemia Reperfusion-Induced Apoptosis and Autophagy via the ROS/MAPK Pathway in Mice.

    Science.gov (United States)

    Li, Jingjing; Wang, Fan; Xia, Yujing; Dai, Weiqi; Chen, Kan; Li, Sainan; Liu, Tong; Zheng, Yuanyuan; Wang, Jianrong; Lu, Wenxia; Zhou, Yuqing; Yin, Qin; Lu, Jie; Zhou, Yingqun; Guo, Chuanyong

    2015-05-27

    Hepatic ischemia reperfusion (IR) is an important issue in complex liver resection and liver transplantation. The aim of the present study was to determine the protective effect of astaxanthin (ASX), an antioxidant, on hepatic IR injury via the reactive oxygen species/mitogen-activated protein kinase (ROS/MAPK) pathway. Mice were randomized into a sham, IR, ASX or IR + ASX group. The mice received ASX at different doses (30 mg/kg or 60 mg/kg) for 14 days. Serum and tissue samples at 2 h, 8 h and 24 h after abdominal surgery were collected to assess alanine aminotransferase (ALT), aspartate aminotransferase (AST), inflammation factors, ROS, and key proteins in the MAPK family. ASX reduced the release of ROS and cytokines leading to inhibition of apoptosis and autophagy via down-regulation of the activated phosphorylation of related proteins in the MAPK family, such as P38 MAPK, JNK and ERK in this model of hepatic IR injury. Apoptosis and autophagy caused by hepatic IR injury were inhibited by ASX following a reduction in the release of ROS and inflammatory cytokines, and the relationship between the two may be associated with the inactivation of the MAPK family.

  15. MAPK13 is preferentially expressed in gynecological cancer stem cells and has a role in the tumor-initiation

    Energy Technology Data Exchange (ETDEWEB)

    Yasuda, Kazuyo [Department of Pathology, Sapporo Medical University School of Medicine, South-1 West-17, Chuo-Ku, Sapporo, 060-8556 (Japan); Hirohashi, Yoshihiko, E-mail: hirohash@sapmed.ac.jp [Department of Pathology, Sapporo Medical University School of Medicine, South-1 West-17, Chuo-Ku, Sapporo, 060-8556 (Japan); Kuroda, Takafumi [Department of Obstetrics and Gynecology, Sapporo Medical University School of Medicine, South-1 West-17, Chuo-Ku, Sapporo, 060-8556 (Japan); Takaya, Akari; Kubo, Terufumi; Kanaseki, Takayuki; Tsukahara, Tomohide [Department of Pathology, Sapporo Medical University School of Medicine, South-1 West-17, Chuo-Ku, Sapporo, 060-8556 (Japan); Hasegawa, Tadashi [Department of Surgical Pathology, Sapporo Medical University School of Medicine, South-1 West-17, Chuo-Ku, Sapporo, 060-8556 (Japan); Saito, Tsuyoshi [Department of Obstetrics and Gynecology, Sapporo Medical University School of Medicine, South-1 West-17, Chuo-Ku, Sapporo, 060-8556 (Japan); Sato, Noriyuki [Department of Pathology, Sapporo Medical University School of Medicine, South-1 West-17, Chuo-Ku, Sapporo, 060-8556 (Japan); Torigoe, Toshihiko, E-mail: torigoe@sapmed.ac.jp [Department of Pathology, Sapporo Medical University School of Medicine, South-1 West-17, Chuo-Ku, Sapporo, 060-8556 (Japan)

    2016-04-15

    Cancer stem-like cells (CSCs)/cancer-initiating cells (CICs) are defined as small subpopulation of cancer cells that are endowed with higher tumor-initiating ability. CSCs/CICs are resistant to standard cancer therapies including chemotherapy and radiotherapy, and they are thus thought to be responsible for cancer recurrence and metastasis. Therefore, elucidation of molecular mechanisms of CSCs/CICs is essential to cure cancer. In this study, we analyzed the gene expression profiles of gynecological CSCs/CICs isolated as aldehyde dehydrogenase high (ALDH{sup high}) cells, and found that MAPK13, PTTG1IP, CAPN1 and UBQLN2 were preferentially expressed in CSCs/CICs. MAPK13 is expressed in uterine, ovary, stomach, colon, liver and kidney cancer tissues at higher levels compared with adjacent normal tissues. MAPK13 gene knockdown using siRNA reduced the ALDH{sup high} population and abrogated the tumor-initiating ability. These results indicate that MAPK13 is expressed in gynecological CSCs/CICs and has roles in the maintenance of CSCs/CICs and tumor-initiating ability, and MAPK13 might be a novel molecular target for treatment-resistant CSCs/CICs.

  16. Inhibition of spinal MAPKs by scorpion venom peptide BmK AGAP produces a sensory-specific analgesic effect.

    Science.gov (United States)

    Ruan, Jia-Ping; Mao, Qing-Hong; Lu, Wu-Guang; Cai, Xue-Ting; Chen, Jiao; Li, Qing-; Fu, Qun-; Yan, Huai-Jiang; Cao, Jun-Li; Cao, Peng

    2018-01-01

    Background Several studies have shown that scorpion venom peptide BmK AGAP has an analgesic activity. Our previous study also demonstrated that intraplantar injection of BmK AGAP ameliorates formalin-induced spontaneous nociceptive behavior. However, the effect of intrathecal injection of BmK AGAP on nociceptive processing is poorly understood. Methods We investigated the effects of intrathecal injection of BmK AGAP on spinal nociceptive processing induced by chronic constrictive injury or formalin. Thermal hyperalgesia and mechanical allodynia were measured using radiant heat and the von Frey filaments test. Formalin-induced spontaneous nociceptive behavior was also investigated. C-Fos expression was assessed by immunohistochemistry. Phosphorylated mitogen-activated protein kinase (p-MAPK) expression was monitored by Western blot assay. Results Intrathecal injection of BmK AGAP reduced chronic constrictive injury-induced neuropathic pain behavior and pain from formalin-induced inflammation, accompanied by decreased expression of spinal p-MAPKs and c-Fos protein. The results of combining low doses of different MAPK inhibitor (U0126, SP600125, or SB203580; 0.1 µg for each inhibitor) with a low dose of BmK AGAP (0.2 µg) suggested that BmK AGAP could potentiate the effects of MAPK inhibitors on inflammation-associated pain. Conclusion Our results demonstrate that intrathecal injection of BmK AGAP produces a sensory-specific analgesic effect via a p-MAPK-dependent mechanism.

  17. MAPK genes interact with diet and lifestyle factors to alter risk of breast cancer: The Breast Cancer Health Disparities Study

    Science.gov (United States)

    Slattery, Martha L.; Lundgreen, Abbie; John, Esther M.; Torres-Mejia, Gabriela; Hines, Lisa; Giuliano, Anna R.; Baumgartner, Kathy B.; Stern, Mariana C.; Wolff, Roger K.

    2015-01-01

    Mitogen-activated protein kinases (MAPK) are integration points for multiple biochemical signals. We evaluated 13 MAPK genes with breast cancer risk and determined if diet and lifestyle factors mediated risk. Data from three population-based case-control studies conducted in Southwestern United States, California, and Mexico included 4183 controls and 3592 cases. Percent Indigenous American (IA) ancestry was determined from 104 Ancestry Informative Markers. The adaptive rank truncated product (ARTP) was used to determine the significance of each gene and the pathway with breast cancer risk, by menopausal status, genetic ancestry level, and ER/PR strata. MAP3K9 was associated with breast cancer overall (PARTP=0.02) with strongest association among women with the highest IA ancestry (PARTP=0.04). Several SNPs in MAP3K9 were associated with ER+/PR+ tumors and interacted with dietary oxidative balance score (DOBS), dietary folate, body mass index (BMI), alcohol consumption, cigarette smoking, and a history of diabetes. DUSP4 and MAPK8 interacted with calories to alter breast cancer risk; MAPK1 interacted with DOBS, dietary fiber, folate and BMI; MAP3K2 interacted with dietary fat; and MAPK14 interacted with dietary folate and BMI. The patterns of association across diet and lifestyle factors with similar biological properties for the same SNPs within genes provide support for associations. PMID:25629224

  18. p38 Mitogen Activated Protein Kinase (MAPK): A New Therapeutic Target for Reducing the Risk of Adverse Pregnancy Outcomes

    Science.gov (United States)

    Menon, Ramkumar; Papaconstantinou, John

    2016-01-01

    Introduction Spontaneous preterm birth (PTB) and preterm premature rupture of the membranes (pPROM) remain as a major clinical and therapeutic problem for intervention and management. Current strategies, based on our knowledge of pathways of preterm labor, have only been effective, in part, due to major gaps in our existing knowledge of risks and risk specific pathways. Areas covered Recent literature has identified physiologic aging of fetal tissues as a potential mechanistic feature of normal parturition. This process is affected by telomere dependent and p38 mitogen activated protein kinase (MAPK) induced senescence activation. Pregnancy associated risk factors can cause pathologic activation of this pathway that can cause oxidative stress induced p38 MAPK activation leading to senescence and premature aging of fetal tissues. Premature aging is associated with sterile inflammation capable of triggering preterm labor or preterm premature rupture of membranes. Preterm activation of p38MAPK can be considered as a key contributor to adverse pregnancies. Expert Opinion This review considers p38MAPK activation as a potential target for therapeutic interventions to prevent adverse pregnancy outcomes mediated by stress factors. In this review, we propose multiple strategies to prevent p38MAPK activation and its functional effects. PMID:27459026

  19. Cyclic Compressive Stress Regulates Apoptosis in Rat Osteoblasts: Involvement of PI3K/Akt and JNK MAPK Signaling Pathways.

    Directory of Open Access Journals (Sweden)

    Fanglong Song

    Full Text Available It is widely accepted that physiological mechanical stimulation suppresses apoptosis and induces synthesis of extracellular matrix by osteoblasts; however, the effect of stress overloading on osteoblasts has not been fully illustrated. In the present study, we investigated the effect of cyclic compressive stress on rat osteoblasts apoptosis, using a novel liquid drop method to generate mechanical stress on osteoblast monolayers. After treatment with different levels of mechanical stress, apoptosis of osteoblasts and activations of mitogen-activated protein kinases (MAPKs and PI3-kinase (PI3K/Akt signaling pathways were investigated. Osteoblasts apoptosis was observed after treated with specific inhibitors prior to mechanical stimulation. Protein levels of Bax/Bcl-2/caspase-3 signaling were determined using western blot with or without inhibitors of PI3K/Akt and phosphorylation of c-jun N-terminal kinase (JNK MAPK. Results showed that mechanical stimulation led to osteoblasts apoptosis in a dose-dependent manner and a remarkable activation of MAPKs and PI3K/Akt signaling pathways. Activation of PI3K/Akt protected against apoptosis, whereas JNK MAPK increased apoptosis via regulation of Bax/Bcl-2/caspase-3 activation. In summary, the PI3K/Akt and JNK MAPK signaling pathways played opposing roles in osteoblasts apoptosis, resulting in inhibition of apoptosis upon small-magnitude stress and increased apoptosis upon large-magnitude stress.

  20. Design and optimization of cascaded DCG based holographic elements for spectrum-splitting PV systems

    Science.gov (United States)

    Wu, Yuechen; Chrysler, Benjamin; Pelaez, Silvana Ayala; Kostuk, Raymond K.

    2017-09-01

    In this work, the technique of designing and optimizing broadband volume transmission holograms using dichromate gelatin (DCG) is summarized for solar spectrum-splitting application. Spectrum splitting photovoltaic system uses a series of single bandgap PV cells that have different spectral conversion efficiency properties to more fully utilize the solar spectrum. In such a system, one or more high performance optical filters are usually required to split the solar spectrum and efficiently send them to the corresponding PV cells. An ideal spectral filter should have a rectangular shape with sharp transition wavelengths. DCG is a near ideal holographic material for solar applications as it can achieve high refractive index modulation, low absorption and scattering properties and long-term stability to solar exposure after sealing. In this research, a methodology of designing and modeling a transmission DCG hologram using coupled wave analysis for different PV bandgap combinations is described. To achieve a broad diffraction bandwidth and sharp cut-off wavelength, a cascaded structure of multiple thick holograms is described. A search algorithm is also developed to optimize both single and two-layer cascaded holographic spectrum splitters for the best bandgap combinations of two- and three-junction SSPV systems illuminated under the AM1.5 solar spectrum. The power conversion efficiencies of the optimized systems under the AM1.5 solar spectrum are then calculated using the detailed balance method, and shows an improvement compared with tandem structure.

  1. Insulin protects against Aβ-induced spatial memory impairment, hippocampal apoptosis and MAPKs signaling disruption.

    Science.gov (United States)

    Ghasemi, Rasoul; Zarifkar, Asadollah; Rastegar, Karim; maghsoudi, Nader; Moosavi, Maryam

    2014-10-01

    Alzheimer disease (AD) is a progressive neurodegenerative disease characterized by extracellular deposits of beta amyloid (Aβ) and neuronal loss particularly in the hippocampus. Accumulating evidences have implied that insulin signaling impairment plays a key role in the pathology of AD; as much as it is considered as type 3 Diabetes. MAPKs are a group of signaling molecules which are involved in pathobiology of AD. Therefore this study was designed to investigate if intrahippocampal insulin hinders Aβ-related memory deterioration, hippocampal apoptosis and MAPKs signaling alteration induced by Aβ. Adult male Sprague-Dawely rats weighing 250-300 g were used in this study. The canules were implanted bilaterally into CA1 region. Aβ25-35 was administered during first 4 days after surgery (5 μg/2.5 μL/daily). Insulin treatment (0.5 or 6 mU) was done during days 4-9. The animal's learning and memory capability was assessed on days 10-13 using Morris water maze. After finishing of behavioral studies the hippocampi was isolated and the amount of hippocampal cleaved caspase 3 (the landmark of apoptosis) and the phosphorylated (activated) forms of P38, JNK and ERK was analyzed by western blot. The results showed that insulin in 6 but not 0.5 mU reversed the memory loss induced by Aβ25-35. Western blot analysis revealed that Aβ25-35 induced elevation of caspase-3 and all 3 MAPks subfamily activity, while insulin in 6 mu restored ERK and P38 activation but has no effect on JNK. This study disclosed that intrahippocampal insulin treatment averts not only Aβ-induced memory deterioration but also hippocampal caspase-3, ERK and P38 activation. Copyright © 2014 Elsevier Ltd. All rights reserved.

  2. Acidic environment leads to ROS-induced MAPK signaling in cancer cells.

    Directory of Open Access Journals (Sweden)

    Anne Riemann

    Full Text Available Tumor micromilieu often shows pronounced acidosis forcing cells to adapt their phenotype towards enhanced tumorigenesis induced by altered cellular signalling and transcriptional regulation. In the presents study mechanisms and potential consequences of the crosstalk between extra- and intracellular pH (pH(e, pH(i and mitogen-activated-protein-kinases (ERK1/2, p38 was analyzed. Data were obtained mainly in AT1 R-3327 prostate carcinoma cells, but the principle importance was confirmed in 5 other cell types. Extracellular acidosis leads to a rapid and sustained decrease of pH(i in parallel to p38 phosphorylation in all cell types and to ERK1/2 phosphorylation in 3 of 6 cell types. Furthermore, p38 phosphorylation was elicited by sole intracellular lactacidosis at normal pH(e. Inhibition of ERK1/2 phosphorylation during acidosis led to necrotic cell death. No evidence for the involvement of the kinases c-SRC, PKC, PKA, PI3K or EGFR nor changes in cell volume in acidosis-induced MAPK activation was obtained. However, our data reveal that acidosis enhances the formation of reactive oxygen species (ROS, probably originating from mitochondria, which subsequently trigger MAPK phosphorylation. Scavenging of ROS prevented acidosis-induced MAPK phosphorylation whereas addition of H(2O(2 enhanced it. Finally, acidosis increased phosphorylation of the transcription factor CREB via p38, leading to increased transcriptional activity of a CRE-reporter even 24 h after switching the cells back to a normal environmental milieu. Thus, an acidic tumor microenvironment can induce a longer lasting p38-CREB-medited change in the transcriptional program, which may maintain the altered phenotype even when the cells leave the tumor environment.

  3. Advanced oxidative protein products induced human keratinocyte apoptosis through the NOX-MAPK pathway.

    Science.gov (United States)

    Sun, Baihui; Ding, Ruoting; Yu, Wenlin; Wu, Yanhong; Wang, Bulin; Li, Qin

    2016-07-01

    Impaired wound healing is a major diabetes-related complication. Keratinocytes play an important role in wound healing. Multiple factors have been proposed that can induce dysfunction in keratinocytes. The focus of present research is at a more specific molecular level. We investigated the role of advanced oxidative protein products (AOPPs) in inducing human immortalized keratinocyte (HaCaT) cell apoptosis and the cellular mechanism underlying the proapoptotic effect of AOPPs. HaCaT cells were treated with increasing concentrations of AOPP-human serum albumin or for increasing time durations. The cell viability was measured using the thiazolyl blue tetrazolium bromide method, and flow cytometry was used to assess the rate of cell apoptosis. A loss of mitochondrial membrane potential (MMP) and an increase in intracellular reactive oxygen species (ROS) were observed through a confocal laser scanning microscope system, and the level of ROS generation was determined using a microplate reader. Nicotinamide adenine dinucleotide phosphate oxidase (NOX)4, extracellular signal-regulated kinase (ERK)1/2, p38 mitogen-activated protein kinase (MAPK), and apoptosis-related downstream protein interactions were investigated using the Western blot analysis. We found that AOPPs triggered HaCaT cell apoptosis and MMP loss. After AOPP treatment, intracellular ROS generation increased in a time- and dose-dependent manner. Proapoptotic proteins, such as Bax, caspase 9/caspase 3, and poly(ADP-ribose) polymerase (PARP)-1 were activated, whereas anti-apoptotic Bcl-2 protein was downregulated. AOPPs also increased NOX4, ERK1/2, and p38 MAPK expression. Taken together, these findings suggest that extracellular AOPP accumulation triggered NOX-dependent ROS production, which activated ERK1/2 and p38 MAPK, and induced HaCaT cell apoptosis by activating caspase 3 and PARP-1.

  4. [Arnold-Chiari malformation in Noonan syndrome and other syndromes of the RAS/MAPK pathway].

    Science.gov (United States)

    Ejarque, Ismael; Millán-Salvador, José M; Oltra, Silvestre; Pesudo-Martínez, José V; Beneyto, Magdalena; Pérez-Aytés, Antonio

    2015-05-01

    Noonan syndrome (NS) and other syndromes with a similar phenotype, such as LEOPARD, cardiofaciocutaneous, Costello and Legius, are associated to mutations in genes included in the RAS/MAPK pathway (RASopathies), which is an important signalling pathway related to cell proliferation. Tonsillar descent into the upper cervical spinal canal, known as Arnold-Chiari malformation (ACM), has been reported in patients with NS and this has led some researchers to suggest that ACM could be part of the phenotypic spectrum of NS. We report two cases of NS and ACM. Case 1: 29-year-old female with Noonan phenotype who underwent surgery at the age of nine years due to pulmonary valve stenosis. At the age of 27, she presented symptomatic ACM that required surgical decompression. She presented the c.922A>G (N308D) mutation in the gene PTPN that belongs to the RAS/MAPK pathway. Case 2: a 10-year-old female with Noonan phenotype and asymptomatic ACM detected in magnetic resonance imaging of the brain. She was a carrier of the c.923A>G (N308S) mutation in gene PTPN11. Six patients with this association have been found in the literature, four with the Noonan phenotype and two with LEOPARD. Our two patients provide supplementary evidence that backs up the hypothesis by which ACM would be part of the phenotypic spectrum of NS. The small number of reported cases of patients with this association does not allow us to draw up recommendations about when and how often neuroimaging studies should be performed; a careful neurological examination, however, should be included in the anticipatory health guidelines in syndromes involving the RAS/MAPK pathway.

  5. A mechanism of male germ cell apoptosis induced by bisphenol-A and nonylphenol involving ADAM17 and p38 MAPK activation.

    Directory of Open Access Journals (Sweden)

    Paulina Urriola-Muñoz

    Full Text Available Germ cell apoptosis regulation is pivotal in order to maintain proper daily sperm production. Several reports have shown that endocrine disruptors such as Bisphenol-A (BPA and Nonylphenol (NP induce germ cell apoptosis along with a decrease in sperm production. Given their ubiquitous distribution in plastic products used by humans it is important to clarify their mechanism of action. TACE/ADAM17 is a widely distributed extracellular metalloprotease and participates in the physiological apoptosis of germ cells during spermatogenesis. The aims of this work were: 1 to determine whether BPA and NP induce ADAM17 activation; and 2 to study whether ADAM17 and/or ADAM10 are involved in germ cell apoptosis induced by BPA and NP in the pubertal rat testis. A single dose of BPA or NP (50 mg/kg induces germ cell apoptosis in 21-day-old male rats, which was prevented by a pharmacological inhibitor of ADAM17, but not by an inhibitor of ADAM10. In vitro, we showed that BPA and NP, at similar concentrations to those found in human samples, induce the shedding of exogenous and endogenous (TNF-α ADAM17 substrates in primary rat Sertoli cell cultures and TM4 cell line. In addition, pharmacological inhibitors of metalloproteases and genetic silencing of ADAM17 prevent the shedding induced in vitro by BPA and NP. Finally, we showed that in vivo BPA and NP induced early activation (phosphorylation of p38 MAPK and translocation of ADAM17 to the cell surface. Interestingly, the inhibition of p38 MAPK prevents germ cell apoptosis and translocation of ADAM17 to the cell surface. These results show for the first time that xenoestrogens can induce activation of ADAM17 at concentrations similar to those found in human samples, suggesting a mechanism by which they could imbalance para/juxtacrine cell-to-cell-communication and induce germ cell apoptosis.

  6. Socs36E Controls Niche Competition by Repressing MAPK Signaling in the Drosophila Testis.

    Directory of Open Access Journals (Sweden)

    Marc Amoyel

    2016-01-01

    Full Text Available The Drosophila testis is a well-established system for studying stem cell self-renewal and competition. In this tissue, the niche supports two stem cell populations, germ line stem cells (GSCs, which give rise to sperm, and somatic stem cells called cyst stem cells (CySCs, which support GSCs and their descendants. It has been established that CySCs compete with each other and with GSCs for niche access, and mutations have been identified that confer increased competitiveness to CySCs, resulting in the mutant stem cell and its descendants outcompeting wild type resident stem cells. Socs36E, which encodes a negative feedback inhibitor of the JAK/STAT pathway, was the first identified regulator of niche competition. The competitive behavior of Socs36E mutant CySCs was attributed to increased JAK/STAT signaling. Here we show that competitive behavior of Socs36E mutant CySCs is due in large part to unbridled Mitogen-Activated Protein Kinase (MAPK signaling. In Socs36E mutant clones, MAPK activity is elevated. Furthermore, we find that clonal upregulation of MAPK in CySCs leads to their outcompetition of wild type CySCs and of GSCs, recapitulating the Socs36E mutant phenotype. Indeed, when MAPK activity is removed from Socs36E mutant clones, they lose their competitiveness but maintain self-renewal, presumably due to increased JAK/STAT signaling in these cells. Consistently, loss of JAK/STAT activity in Socs36E mutant clones severely impairs their self-renewal. Thus, our results enable the genetic separation of two essential processes that occur in stem cells. While some niche signals specify the intrinsic property of self-renewal, which is absolutely required in all stem cells for niche residence, additional signals control the ability of stem cells to compete with their neighbors. Socs36E is node through which these processes are linked, demonstrating that negative feedback inhibition integrates multiple aspects of stem cell behavior.

  7. Morin Attenuates Ovalbumin-Induced Airway Inflammation by Modulating Oxidative Stress-Responsive MAPK Signaling

    Directory of Open Access Journals (Sweden)

    Yuan Ma

    2016-01-01

    Full Text Available Asthma is one of the most common inflammatory diseases characterized by airway hyperresponsiveness, inflammation, and remodeling. Morin, an active ingredient obtained from Moraceae plants, has been demonstrated to have promising anti-inflammatory activities in a range of disorders. However, its impacts on pulmonary diseases, particularly on asthma, have not been clarified. This study was designed to investigate whether morin alleviates airway inflammation in chronic asthma with an emphasis on oxidative stress modulation. In vivo, ovalbumin- (OVA- sensitized mice were administered with morin or dexamethasone before challenge. Bronchoalveolar lavage fluid (BALF and lung tissues were obtained to perform cell counts, histological analysis, and enzyme-linked immunosorbent assay. In vitro, human bronchial epithelial cells (BECs were challenged by tumor necrosis factor alpha (TNF-α. The supernatant was collected for the detection of the proinflammatory proteins, and the cells were collected for reactive oxygen species (ROS/mitogen-activated protein kinase (MAPK evaluations. Severe inflammatory responses and remodeling were observed in the airways of the OVA-sensitized mice. Treatment with morin dramatically attenuated the extensive trafficking of inflammatory cells into the BALF and inhibited their infiltration around the respiratory tracts and vessels. Morin administration also significantly suppressed goblet cell hyperplasia and collagen deposition/fibrosis and dose-dependently inhibited the OVA-induced increases in IgE, TNF-α, interleukin- (IL- 4, IL-13, matrix metalloproteinase-9, and malondialdehyde. In human BECs challenged by TNF-α, the levels of proteins such as eotaxin-1, monocyte chemoattractant protein-1, IL-8 and intercellular adhesion molecule-1, were consistently significantly decreased by morin. Western blotting and the 2′,7′-dichlorofluorescein assay revealed that the increases in intracellular ROS and MAPK phosphorylation were

  8. Nitric oxide and hypoxia stimulate erythropoietin receptor via MAPK kinase in endothelial cells.

    Science.gov (United States)

    Cokic, Bojana B Beleslin; Cokic, Vladan P; Suresh, Sukanya; Wirt, Stacey; Noguchi, Constance Tom

    2014-03-01

    Erythropoietin receptor (EPOR) expression level determines the extent of erythropoietin (EPO) response. Previously we showed that EPOR expression in endothelial cells is increased at low oxygen tension and that EPO stimulation of endothelial cells during hypoxia can increase endothelial nitric oxide (NO) synthase (eNOS) expression and activation as well as NO production. We now observe that while EPO can stimulate NO production, NO in turn can regulate EPOR expression. Human umbilical vein endothelial cells (HUVEC) treated with 10-50 μM of NO donor diethylenetriamine NONOate (DETANO) for 24h showed significant induction of EPOR gene expression at 5% and 2% of oxygen. Also human bone marrow microvascular endothelial cell line (TrHBMEC) cultured at 21 and 2% oxygen with 50 μM DETANO demonstrated a time and oxygen dependent induction of EPOR mRNA expression after 24 and 48 h, particularly at low oxygen tension. EPOR protein was also induced by DETANO at 2% oxygen in TrHBMEC and HUVEC. The activation of signaling pathways by NO donor stimulation appeared to be distinct from EPO stimulation. In reporter gene assays, DETANO treatment of HeLa cells at 2% oxygen increased EPOR promoter activity indicated by a 48% increase in luciferase activity with a 2 kb EPOR promoter fragment and a 71% increase in activity with a minimal EPOR promoter fragment containing 0.2 kb 5'. We found that DETANO activated MAPK kinase in TrHBMEC both in normoxia and hypoxia, while MAPK kinase inhibition showed significant reduction of EPOR mRNA gene expression at low oxygen tension, suggesting MAPK involvement in NO mediated induction of EPOR. Furthermore, DETANO stimulated Akt anti-apoptotic activity after 30 min in normoxia, whereas it inhibited Akt phosphorylation in hypoxia. In contrast, EPO did not significantly increase MAPK activity while EPO stimulated Akt phosphorylation in TrHBMEC in normoxia and hypoxia. These observations provide a new effect of NO on EPOR expression to enhance EPO

  9. MAPK signaling pathway regulates cerebrovascular receptor expression in human cerebral arteries

    DEFF Research Database (Denmark)

    Ansar, Saema; Eftekhari, Sajedeh; Waldsee, Roya

    2013-01-01

    if the upregulation of contractile cerebrovascular receptors after 48 h of organ culture of human cerebral arteries involves MAPK pathways and if it can be prevented by a MEK1/2 inhibitor. Human cerebral arteries were obtained from patients undergoing intracranial tumor surgery. The vessels were divided into ring...... segments and incubated for 48 h in the presence or absence of the specific MEK1/2 inhibitor U0126. The vessels were then examined by using in vitro pharmacological methods and protein immunohistochemistry....

  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. 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.

  12. 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

  13. 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.

  14. 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.

  15. Computational hydraulics of a cascade of experimental-scale landside dam failures

    Science.gov (United States)

    Wright, N.; Guan, M.

    2015-12-01

    Abstract: Landslide dams typically comprise unconsolidated and poorly sorted material, and are vulnerable to rapid failure and breaching, particularly in mountainous areas during high intense rainfalls. A large flash flood with high-concentrated sediment can be formed in a short period, and the magnitude is likely to be amplified along the flow direction due to the inclusion of a large amount of sediment. This can result in significant and sudden flood risk downstream for human life and property. Numerous field evidence has indicated the various risks of landslide dam failures. In general, cascading landslide dams can be formed along the sloping channel due to the randomness and unpredictability of landslides, which complexes the hydraulics of landslide dam failures. The failure process of a single dam and subsequent floods has attracted attention in multidisciplinary studies. However, the dynamic failure process of cascading landslide dams has been poorly understood. From a viewpoint of simulation, this study evaluates the formation and development of rapid sediment-charged floods due to cascading failure of landslide dams through detailed hydro-morphodynamic modelling. The model used is based on shallow water theory and it has been successful in predicting the flow and morphological process during sudden dam-break, as well as full and partial dyke-breach. Various experimental-scale scenarios are modelled, including: (1) failure of a single full dam in a sloping channel, (2) failure of two dams in a sloping channel, (3) failure of multiple landslide dams (four) in a sloping channel. For each scenario, different failure modes (sudden/gradual) and bed boundary (fixed /mobile) are assumed and simulated. The study systematically explores the tempo-spatial evolution of landslide-induced floods (discharge, flow velocity, and flow concentration) and geomorphic properties along the sloping channel. The effects of in-channel erosion and flow-driven sediment from dams on

  16. Inhibition of MAPK and PKC pathways by 60Co γ-radiation in cultured vascular smooth muscle cells

    International Nuclear Information System (INIS)

    Jia Guanghong; Ma Yexin; Xiao Jianming

    2002-01-01

    Objective: To investigate the signal transduction pathways inhibited by 60 Co γ-radiation in cultured vascular smooth muscle cells (VSMC). Methods: The cultured VSMC were irradiated with 60 Co γ-radiation of 3.5, 7.0 and 14 Gy respectively. VSMC proliferation was measured by 3 H-TdR incorporation, while PKC, MAPK activities were determined by radioactivity assay. Results: Proliferation of VSMC was inhibited by 7.0, 14 Gy 60 Co γ-irradiation and the activities of PKC, MAPK were decreased significantly. Conclusion: Inhibitory effect of 7.0, 14 Gy 60 Co γ-irradiation on proliferation of VSMC might be resulted from decrease of the activity of PKC, MAPK

  17. 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

  18. 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.

  19. The performance of pip-cascade controler in HVAC system

    Directory of Open Access Journals (Sweden)

    Legweel Khaled M.B.

    2014-01-01

    Full Text Available Primitive controllers used in the early version for HVAC systems, like the on-off (Bang-Bang controller, are inefficient, inaccurate, unstable, and suffer from high-level mechanical wear. On the other hand, other controllers like PI and cascade controllers, overcome these disadvantages but when an offset response (inaccurate response occurs, power consumption will increase. In order to acquire better performance in the central air-conditioning system, PIP-cascade control is investigated in this paper and compared to the traditional PI and PID, in simulation of experimental data. The output of the system is predicted through disturbances. Based on the mathematical model of air-conditioning space, the simulations in this paper have found that the PIP-cascade controller has the capability of self-adapting to system changes and results in faster response and better performance.

  20. 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...