Energetic particles in spherical tokamak plasmas

DOE PAGES

McClements, K. G.; Fredrickson, E. D.

2017-03-21

Spherical tokamaks (STs) typically have lower magnetic fields than conventional tokamaks, but similar mass densities. Suprathermal ions with relatively modest energies, in particular beam-injected ions, consequently have speeds close to or exceeding the Alfvén velocity, and can therefore excite a range of Alfvénic instabilities which could be driven by (and affect the behaviour of) fusion α-particles in a burning plasma. STs heated with neutral beams, including the small tight aspect ratio tokamak (START), the mega amp spherical tokamak (MAST), the national spherical torus experiment (NSTX) and Globus-M, have thus provided an opportunity to study toroidal Alfvén eigenmodes (TAEs), together withmore » higher frequency global Alfvén eigenmodes (GAEs) and compressional Alfvén eigenmodes (CAEs), which could affect beam current drive and channel fast ion energy into bulk ions in future devices. In NSTX GAEs were correlated with a degradation of core electron energy confinement. In MAST pulses with reduced magnetic field, CAEs were excited across a wide range of frequencies, extending to the ion cyclotron range, but were suppressed when hydrogen was introduced to the deuterium plasma, apparently due to mode conversion at ion–ion hybrid resonances. At lower frequencies fishbone instabilities caused fast particle redistribution in some MAST and NSTX pulses, but this could be avoided by moving the neutral beam line away from the magnetic axis or by operating the plasma at either high density or elevated safety factor. Fast ion redistribution has been observed during GAE avalanches on NSTX, while in both NSTX and MAST fast ions were transported by saturated kink modes, sawtooth crashes, resonant magnetic perturbations and TAEs. The energy dependence of fast ion redistribution due to both sawteeth and TAEs has been studied in Globus-M. High energy charged fusion products are unconfined in present-day STs, but have been shown in MAST to provide a useful diagnostic of beam ion behaviour, supplementing the information provided by neutron detectors. In MAST electrons were accelerated to highly suprathermal energies as a result of edge localised modes, while in both MAST and NSTX ions were accelerated due to internal reconnection events. Lastly, ion acceleration has also been observed during merging-compression start-up in MAST.« less

Statistical spatio-temporal properties of the Laser MegaJoule speckle

DOE Office of Scientific and Technical Information (OSTI.GOV)

Le Cain, A.; Sajer, J. M.; Riazuelo, G.

2012-10-15

This paper investigates a statistical model to describe the spatial and temporal properties of hot spots generated by the superimposition of multiple laser beams. In the context of the Laser MegaJoule design, we introduce the formula for contrasts, trajectories and velocities of the speckle pattern. Single bundle of four beams, two-cones and three-cones configurations are considered. Statistical properties of the speckle in the zone where all the beams overlap are studied with different configurations of polarizations. These properties are shown to be very different from the case of one single bundle of four beams. The configuration of polarization has onlymore » a slight effect in the two-cones or three cones configuration. Indeed, the impact of the double polarization smoothing is reduced in the area in which all the beams overlap, while it is much more significant when they split. Moreover, the size of the hot-spots decreases as the number of laser beams increases, but we show that their velocity decreases. As a matter of fact, the maximal velocity of hot spots is found to be only about 10{sup -5} of the velocity of light and the integrated contrast is about 15% when the beams overlap.« less

Sensitivity of 30-cm mercury bombardment ion thruster characteristics to accelerator grid design

NASA Technical Reports Server (NTRS)

Rawlin, V. K.

1978-01-01

The design of ion optics for bombardment thrusters strongly influences overall performance and lifetime. The operation of a 30 cm thruster with accelerator grid open area fractions ranging from 43 to 24 percent, was evaluated and compared with experimental and theoretical results. Ion optics properties measured included the beam current extraction capability, the minimum accelerator grid voltage to prevent backstreaming, ion beamlet diameter as a function of radial position on the grid and accelerator grid hole diameter, and the high energy, high angle ion beam edge location. Discharge chamber properties evaluated were propellant utilization efficiency, minimum discharge power per beam amp, and minimum discharge voltage.

Relation between lineal energy distribution and relative biological effectiveness for photon beams according to the microdosimetric kinetic model.

PubMed

Okamoto, Hiroyuki; Kanai, Tatsuaki; Kase, Yuki; Matsumoto, Yoshitaka; Furusawa, Yoshiya; Fujita, Yukio; Saitoh, Hidetoshi; Itami, Jun; Kohno, Toshiyuki

2011-01-01

Our cell survival data showed the obvious dependence of RBE on photon energy: The RBE value for 200 kV X-rays was approximately 10% greater than those for mega-voltage photon beams. In radiation therapy using mega-voltage photon beams, the photon energy distribution outside the field is different with that in the radiation field because of a large number of low energy scattering photons. Hence, the RBE values outside the field become greater. To evaluate the increase in RBE, the method of deriving the RBE using the Microdosimetric Kinetic model (MK model) was proposed in this study. The MK model has two kinds of the parameters, tissue-specific parameters and the dose-mean lineal energy derived from the lineal energy distributions measured with a Tissue-Equivalent Proportional Counter (TEPC). The lineal energy distributions with the same geometries of the cell irradiations for 200 kV X-rays, (60)Co γ-rays, and 6 MV X-rays were obtained with the TEPC and Monte Carlo code GEANT4. The measured lineal energy distribution for 200 kV X-rays was quite different from those for mega-voltage photon beams. The dose-mean lineal energy of 200 kV X-rays showed the greatest value, 4.51 keV/µm, comparing with 2.34 and 2.36 keV/µm for (60)Co γ-rays and 6 MV X-rays, respectively. By using the results of the TEPC and cell irradiations, the tissue-specific parameters in the MK model were determined. As a result, the RBE of the photon beams (y(D): 2~5 keV/µm) in arbitrary conditions can be derived by the measurements only or the calculations only of the dose-mean lineal energy.

Latest developments on the Dutch 1MW free electron maser

NASA Astrophysics Data System (ADS)

Caplan, M.; Verhoeven, A. G. A.; Urbanus, W.

1999-05-01

The FOM Institute (Rijnhuizen, Netherlands), as part of their fusion technology program, has undertaken the development of a Free Electron Maser with the goal of producing 1MW long pulse to CW microwave output in the range 130 GHz-250GHz with wall plug efficiencies of 60%. This project has been carried out as a collaborative effort with Institute of Applied Physics, Nizhny Novgorod Russia, Kurchatov Institute, Moscow Russia, Lawrence Livermore Laboratory, U.S.A and CPI, U.S.A. The key design features of this FEM consists first of a conventional DC acceleration system at high voltage (2MV) which supplies only the unwanted beam interception current and a depressed collector system at 250kV which provides the main beam power. Low body current interception (<25mA) is ensured by using robust inline beam focussing, a low emittance electron gun with halo suppression and periodic magnet side array focussing in the wiggler. The second key feature is use of a low-loss step corrugated waveguide circuit for broad band CW power handling and beam/RF separation. Finally, the required interaction efficiency and mode control is provided by a two stage stepped wiggler. The FEM has been constructed and recently undergone initial short pulse (<10 usec) testing in an inverted mode with the depressed collector absent. Results to date have demonstrated 98.8% beam transmission (over 5 Meters) at currents as high as 8.4 Amps, with 200GHz microwave output at 700kW. There has been good agreement between theory and experiment at the beam current levels tested so far. Details of the most recent experimental results will be presented, in particular the output frequency characteristics with detailed comparisons to theory. The immediate future plans are to operate the system at the design value of 12 Amps with at least 1MW output. The system will then be reconfigured with a 3 stage depressed collector to demonstrate, in the next year, long pulse operation (100 msec) and high wall plug efficiency. Long term future plans call for upgrading the FEM to 2MW and extrapolations up to 5MW are shown to be theoretically possible.

Statistical properties of edge plasma turbulence in the Large Helical Device

NASA Astrophysics Data System (ADS)

Dewhurst, J. M.; Hnat, B.; Ohno, N.; Dendy, R. O.; Masuzaki, S.; Morisaki, T.; Komori, A.

2008-09-01

Ion saturation current (Isat) measurements made by three tips of a Langmuir probe array in the Large Helical Device are analysed for two plasma discharges. Absolute moment analysis is used to quantify properties on different temporal scales of the measured signals, which are bursty and intermittent. Strong coherent modes in some datasets are found to distort this analysis and are consequently removed from the time series by applying bandstop filters. Absolute moment analysis of the filtered data reveals two regions of power-law scaling, with the temporal scale τ ≈ 40 µs separating the two regimes. A comparison is made with similar results from the Mega-Amp Spherical Tokamak. The probability density function is studied and a monotonic relationship between connection length and skewness is found. Conditional averaging is used to characterize the average temporal shape of the largest intermittent bursts.

Synthetic Aperture Microwave Imaging (SAMI) of the plasma edge on NSTX-U

NASA Astrophysics Data System (ADS)

Vann, Roddy; Taylor, Gary; Brunner, Jakob; Ellis, Bob; Thomas, David

2016-10-01

The Synthetic Aperture Microwave Imaging (SAMI) system is a unique phased-array microwave camera with a +/-40° field of view in both directions. It can image cut-off surfaces corresponding to frequencies in the range 10-34.5GHz; these surfaces are typically in the plasma edge. SAMI operates in two modes: either imaging thermal emission from the plasma (often modified by its interaction with the plasma edge e.g. via BXO mode conversion) or ``active probing'' i.e. injecting a broad beam at the plasma surface and imaging the reflected/back-scattered signal. SAMI was successfully pioneered on the Mega-Amp Spherical Tokamak (MAST) at Culham Centre for Fusion Energy. SAMI has now been installed and commissioned on the National Spherical Torus Experiment Upgrade (NSTX-U) at Princeton Plasma Physics Laboratory. The firmware has been upgraded to include real-time digital filtering, which enables continuous acquisition of the Doppler back-scattered active probing data. In this poster we shall present SAMI's analysis of the plasma edge on NSTX-U including measurements of the edge pitch angle on NSTX-U using SAMI's unique 2-D Doppler-backscattering capability.

Preliminary measurements of the edge magnetic field pitch from 2-D Doppler backscattering in MAST and NSTX-U (invited)

DOE PAGES

Vann, R. G. L.; Brunner, K. J.; Ellis, R.; ...

2016-09-13

The Synthetic Aperture Microwave Imaging (SAMI) system is a novel diagnostic consisting of an array of 8 independently phased antennas. At any one time, SAMI operates at one of the 16 frequencies in the range 10-34.5 GHz. The imaging beam is steered in software post-shot to create a picture of the entire emission surface. In SAMI’s active probing mode of operation, the plasma edge is illuminated with a monochromatic source and SAMI reconstructs an image of the Doppler back-scattered (DBS) signal. By assuming that density fluctuations are extended along magnetic field lines, and knowing that the strongest back-scattered signals aremore » directed perpendicular to the density fluctuations, SAMI’s 2-D DBS imaging capability can be used to measure the pitch of the edge magnetic field. In this paper, we present preliminary pitch angle measurements obtained by SAMI on the Mega Amp Spherical Tokamak (MAST) at Culham Centre for Fusion Energy and on the National Spherical Torus Experiment Upgrade at Princeton Plasma Physics Laboratory. Lastly, the results demonstrate encouraging agreement between SAMI and other independent measurements.« less

Toroidal ripple transport of beam ions in the mega-ampere spherical tokamak

DOE Office of Scientific and Technical Information (OSTI.GOV)

McClements, K. G.; Hole, M. J.

The transport of injected beam ions due to toroidal magnetic field ripple in the mega-ampere spherical tokamak (MAST) is quantified using a full orbit particle tracking code, with collisional slowing-down and pitch-angle scattering by electrons and bulk ions taken into account. It is shown that the level of ripple losses is generally rather low, although it depends sensitively on the major radius of the outer midplane plasma edge; for typical values of this parameter in MAST plasmas, the reduction in beam heating power due specifically to ripple transport is less than 1%, and the ripple contribution to beam ion diffusivitymore » is of the order of 0.1 m{sup 2} s{sup -1} or less. It is concluded that ripple effects make only a small contribution to anomalous transport rates that have been invoked to account for measured neutron rates and plasma stored energies in some MAST discharges. Delayed (non-prompt) losses are shown to occur close to the outer midplane, suggesting that banana-drift diffusion is the most likely cause of the ripple-induced losses.« less

The 80 kV electrostatic wire septum for AmPS

NASA Astrophysics Data System (ADS)

Vanderlinden, A.; Bijleveld, J. H. M.; Rookhuizen, H. Boer; Bruinsma, P. J. T.; Heine, E.; Lassing, P.; Prins, E.

The characteristics of the wire septum for the Amsterdam Pulse Stretcher (AmPS) are summarized. In the extraction process of the AmPS the extracted beam is intercepted from the circulating beam by the 1 m long electrostatic wire septum. For a bending angle of 4.4 mrad, the maximum anode voltage is 80 kV. The system developed consists of a wire spacing of 0.65 mm between tungsten wires of 50 micrometers diameter. Stainless steel spring wires, bent in a half cylindrical carrier, stretch the septum wires two by two. Prototype tests were successful up to an anode voltage of 120 kV.

Mega-pixel PQR laser chips for interconnect, display ITS, and biocell-tweezers OEIC

NASA Astrophysics Data System (ADS)

Kwon, O'Dae; Yoon, J. H.; Kim, D. K.; Kim, Y. C.; Lee, S. E.; Kim, S. S.

2008-02-01

We describe a photonic quantum ring (PQR) laser device of three dimensional toroidal whispering gallery cavity. We have succeeded in fabricating the first genuine mega-pixel laser chips via regular semiconductor technology. This has been realized since the present injection laser emitting surface-normal dominant 3D whispering gallery modes (WGMs) can be operated CW with extremely low operating currents (μA-nA per pixel), together with the lasing temperature stabilities well above 140 deg C with minimal redshifts, which solves the well-known integration problems facing the conventional VCSEL. Such properties unusual for quantum well lasers become usual because the active region, involving vertically confining DBR structure in addition to the 2D concave WGM geometry, induces a 'photonic quantum ring (PQR)-like' carrier distribution through a photonic quantum corral effect. A few applications of such mega-pixel PQR chips are explained as follows: (A) Next-generation 3D semiconductor technologies demand a strategy on the inter-chip and intra-chip optical interconnect schemes with a key to the high-density emitter array. (B) Due to mounting traffic problems and fatalities ITS technology today is looking for a revolutionary change in the technology. We will thus outline how 'SLEEP-ITS' can emerge with the PQR's position-sensing capability. (C) We describe a recent PQR 'hole' laser of convex WGM: Mega-pixel PQR 'hole' laser chips are even easier to fabricate than PQR 'mesa' lasers. Genuine Laguerre-Gaussian (LG) beam patterns of PQR holes are very promising for biocell manipulations like sorting mouse myeloid leukemia (M1s) cells. (D) Energy saving and 3D speckle-free POR laser can outdo LEDs in view of red GaAs and blue GaN devices fabricated recently.

Mathematical model of the current density for the 30-cm engineering model thruster

NASA Technical Reports Server (NTRS)

Cuffel, R. F.

1975-01-01

Mathematical models are presented for both the singly and doubly charged ion current densities downstream of the 30-cm engineering model thruster with 0.5% compensated dished grids. These models are based on the experimental measurements of Vahrenkamp at a 2-amp ion beam operating condition. The cylindrically symmetric beam of constant velocity ions is modeled with continuous radial source and focusing functions across 'plane' grids with similar angular distribution functions. A computer program is used to evaluate the double integral for current densities in the near field and to obtain a far field approximation beyond 10 grid radii. The utility of the model is demonstrated for (1) calculating the directed thrust and (2) determining the impingement levels on various spacecraft surfaces from a two-axis gimballed, 2 x 3 thruster array.

Feasibility study for mega-electron-volt electron beam tomography.

PubMed

Hampel, U; Bärtling, Y; Hoppe, D; Kuksanov, N; Fadeev, S; Salimov, R

2012-09-01

Electron beam tomography is a promising imaging modality for the study of fast technical processes. But for many technical objects of interest x rays of several hundreds of keV energy are required to achieve sufficient material penetration. In this article we report on a feasibility study for fast electron beam computed tomography with a 1 MeV electron beam. The experimental setup comprises an electrostatic accelerator with beam optics, transmission target, and a single x-ray detector. We employed an inverse fan-beam tomography approach with radiographic projections being generated from the linearly moving x-ray source. Angular projections were obtained by rotating the object.

A stable partitioned FSI algorithm for incompressible flow and deforming beams

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, L., E-mail: lil19@rpi.edu; Henshaw, W.D., E-mail: henshw@rpi.edu; Banks, J.W., E-mail: banksj3@rpi.edu

2016-05-01

An added-mass partitioned (AMP) algorithm is described for solving fluid–structure interaction (FSI) problems coupling incompressible flows with thin elastic structures undergoing finite deformations. The new AMP scheme is fully second-order accurate and stable, without sub-time-step iterations, even for very light structures when added-mass effects are strong. The fluid, governed by the incompressible Navier–Stokes equations, is solved in velocity-pressure form using a fractional-step method; large deformations are treated with a mixed Eulerian-Lagrangian approach on deforming composite grids. The motion of the thin structure is governed by a generalized Euler–Bernoulli beam model, and these equations are solved in a Lagrangian frame usingmore » two approaches, one based on finite differences and the other on finite elements. The key AMP interface condition is a generalized Robin (mixed) condition on the fluid pressure. This condition, which is derived at a continuous level, has no adjustable parameters and is applied at the discrete level to couple the partitioned domain solvers. Special treatment of the AMP condition is required to couple the finite-element beam solver with the finite-difference-based fluid solver, and two coupling approaches are described. A normal-mode stability analysis is performed for a linearized model problem involving a beam separating two fluid domains, and it is shown that the AMP scheme is stable independent of the ratio of the mass of the fluid to that of the structure. A traditional partitioned (TP) scheme using a Dirichlet–Neumann coupling for the same model problem is shown to be unconditionally unstable if the added mass of the fluid is too large. A series of benchmark problems of increasing complexity are considered to illustrate the behavior of the AMP algorithm, and to compare the behavior with that of the TP scheme. The results of all these benchmark problems verify the stability and accuracy of the AMP scheme. Results for one benchmark problem modeling blood flow in a deforming artery are also compared with corresponding results available in the literature.« less

Particle acceleration during merging-compression plasma start-up in the Mega Amp Spherical Tokamak

NASA Astrophysics Data System (ADS)

McClements, K. G.; Allen, J. O.; Chapman, S. C.; Dendy, R. O.; Irvine, S. W. A.; Marshall, O.; Robb, D.; Turnyanskiy, M.; Vann, R. G. L.

2018-02-01

Magnetic reconnection occurred during merging-compression plasma start-up in the Mega Amp Spherical Tokamak (MAST), resulting in the prompt acceleration of substantial numbers of ions and electrons to highly suprathermal energies. Accelerated field-aligned ions (deuterons and protons) were detected using a neutral particle analyser at energies up to about 20 keV during merging in early MAST pulses, while nonthermal electrons have been detected indirectly in more recent pulses through microwave bursts. However no increase in soft x-ray emission was observed until later in the merging phase, by which time strong electron heating had been detected through Thomson scattering measurements. A test-particle code CUEBIT is used to model ion acceleration in the presence of an inductive toroidal electric field with a prescribed spatial profile and temporal evolution based on Hall-MHD simulations of the merging process. The simulations yield particle distributions with properties similar to those observed experimentally, including strong field alignment of the fast ions and the acceleration of protons to higher energies than deuterons. Particle-in-cell modelling of a plasma containing a dilute field-aligned suprathermal electron component suggests that at least some of the microwave bursts can be attributed to the anomalous Doppler instability driven by anisotropic fast electrons, which do not produce measurable enhancements in soft x-ray emission either because they are insufficiently energetic or because the nonthermal bremsstrahlung emissivity during this phase of the pulse is below the detection threshold. There is no evidence of runaway electron acceleration during merging, possibly due to the presence of three-dimensional field perturbations.

Mega-Analysis of School Psychology Blueprint for Training and Practice Domains

ERIC Educational Resources Information Center

Burns, Matthew K.; Kanive, Rebecca; Zaslofsky, Anne F.; Parker, David C.

2013-01-01

Meta-analytic research is an effective method for synthesizing existing research and for informing practice and policy. Hattie (2009) suggested that meta-analytic procedures could be employed to existing meta-analyses to create a mega-analysis. The current mega-analysis examined a sample of 47 meta-analyses according to the "School…

Measurements of the temporal onset of mega-Gauss magnetic fields in a laser-driven solenoid

NASA Astrophysics Data System (ADS)

Goyon, Clement; Polllock, B. B.; Turnbull, D. T.; Hazi, A.; Ross, J. S.; Mariscal, D. A.; Patankar, S.; Williams, G. J.; Farmer, W. A.; Moody, J. D.; Fujioka, S.; Law, K. F. F.

2016-10-01

We report on experimental results obtained at Omega EP showing a nearly linear increase of the B-field up to about 2 mega-Gauss in 0.75 ns in a 1 mm3 region. The field is generated using 1 TW of 351 nm laser power ( 8*1015 W/cm2) incident on a laser-driven solenoid target. The coil target converts about 1% of the laser energy into the B-field measured both inside and outside the coil using proton deflectometry with a grid and Faraday rotation of probe beam through SiO2 glass. Proton data indicates a current rise up to hundreds of kA with a spatial distribution in the Au solenoid conductor evolving in time. These results give insight into the generating mechanism of the current between the plates and the time behavior of the field. These experiments are motivated by recent efforts to understand and utilize High Energy Density (HED) plasmas in the presence of external magnetic fields in areas of research from Astrophysics to Inertial Confinement Fusion. We will describe the experimental results and scale them to a NIF hohlraum size. This work was performed under the auspices of the U.S. Department of Energy by LLNL under Contract DE-AC52-07NA27344.

Chip-Scale Controlled Storage All-Optical Memory

DTIC Science & Technology

2007-02-01

half width at half maximum KHZ kilo Hertz KK Kramers-Kronig LH light hole MBE molecular beam epitaxy MHz mega Hertz MZI Mach-Zehnder...waveguide geometry. The sample used in experiments 1 and 2 consists of 15 GaAs (135Å)/Al0.3Ga0.7As(150 Å) QWs grown by molecular beam epitaxy (MBE...We developed the capability to grow GaAs QWs on (110)-oriented substrates using molecular beam epitaxy in a very short amount of time. The very

Evaluating success levels of mega-projects

NASA Technical Reports Server (NTRS)

Kumaraswamy, Mohan M.

1994-01-01

Today's mega-projects transcend the traditional trajectories traced within national and technological limitations. Powers unleashed by internationalization of initiatives, in for example space exploration and environmental protection, are arguably only temporarily suppressed by narrower national, economic, and professional disagreements as to how best they should be harnessed. While the world gets its act together there is time to develop the technologies of such supra-mega-project management that will synergize truly diverse resources and smoothly mesh their interfaces. Such mega-projects and their management need to be realistically evaluated, when implementing such improvements. This paper examines current approaches to evaluating mega-projects and questions the validity of extrapolations to the supra-mega-projects of the future. Alternatives to improve such evaluations are proposed and described.

Advanced Shutter Control for a Molecular Beam Epitaxy Reactor

DTIC Science & Technology

An open-source hardware and software-based shutter controller solution was developed that communicates over Ethernet with our original equipment...manufacturer (OEM) molecular beam epitaxy (MBE) reactor control software. An Arduino Mega microcontroller is the used for the brain of the shutter... controller , while a custom-designed circuit board distributes 24-V power to each of the 16 shutter solenoids available on the MBE. Using Ethernet

New data acquisition system for beam loss monitor used in J-PARC main ring

NASA Astrophysics Data System (ADS)

Satou, K.; Toyama, T.; Kamikubota, N.; Yoshida, S.; Matsushita, J.; Wakita, T.; Sugiyama, M.; Morino, T.

2018-04-01

A new data acquisition system has been developed continually as a part of the development of a new beam loss monitor (BLM) system for the J-PARC main ring. This development includes a newly designed front-end isolation amp that uses photo-couplers and a VME-based new analog-to-digital converter (ADC) system. Compared to the old amp, the new amp has a 10 times higher conversion impedance for the input current to the output voltage; this value is 1 M Ω. Moreover, the bandwidth was improved to from DC to 50 kHz, which is about two orders of magnitude greater than the previously used bandwidth. The theoretical estimations made in this study roughly agree with the frequency response obtained for the new system. The new ADC system uses an on-board field-programmable gate array chip for signal processing. By replacing the firmware of this chip, changes pertaining to future accelerator upgrade plans may be introduced into the new ADC system; in addition, the ADC system can be used in other applications. The sampling speed of the system is 1 MS/s, and it exhibits a 95 dBc spurious-free dynamic range and 16.5 effective number of bits. The obtained waveform and integrated charge data are compared with two reference levels in the ADC system. If the data exceeds the reference level, the system generates an alarm to dump the beams. By using the new data acquisition system, it was proved that the new BLM system shows a wide dynamic range of 160 dB. In this study, the details of the new data acquisition system are described.

Pulse charging of lead-acid traction cells

NASA Technical Reports Server (NTRS)

Smithrick, J. J.

1980-01-01

Pulse charging, as a method of rapidly and efficiently charging 300 amp-hour lead-acid traction cells for an electric vehicle application was investigated. A wide range of charge pulse current square waveforms were investigated and the results were compared to constant current charging at the time averaged pulse current values. Representative pulse current waveforms were: (1) positive waveform-peak charge pulse current of 300 amperes (amps), discharge pulse-current of zero amps, and a duty cycle of about 50%; (2) Romanov waveform-peak charge pulse current of 300 amps, peak discharge pulse current of 15 amps, and a duty of 50%; and (3) McCulloch waveform peak charge pulse current of 193 amps, peak discharge pulse current of about 575 amps, and a duty cycle of 94%. Experimental results indicate that on the basis of amp-hour efficiency, pulse charging offered no significant advantage as a method of rapidly charging 300 amp-hour lead-acid traction cells when compared to constant current charging at the time average pulse current value. There were, however, some disadvantages of pulse charging in particular a decrease in charge amp-hour and energy efficiencies and an increase in cell electrolyte temperature. The constant current charge method resulted in the best energy efficiency with no significant sacrifice of charge time or amp-hour output. Whether or not pulse charging offers an advantage over constant current charging with regard to the cell charge/discharge cycle life is unknown at this time.

The Los ALamos Neutron Science Center Hydrogen Moderator System

NASA Astrophysics Data System (ADS)

Jarmer, J. J.; Knudson, J. N.

2006-04-01

At the Los Alamos Neutron Science Center (LANSCE), spallation neutrons are produced by an 800-MeV proton beam interacting with tungsten targets. Gun-barrel-type penetrations through the heavy concrete and steel shielding that surround the targets collimate neutrons to form neutron beams used for scattering experiments. Two liquid hydrogen moderators of one-liter volume each are positioned adjacent to the neutron-production targets. Some of the neutrons that pass through a moderator interact with or scatter from protons in the hydrogen. The neutron-proton interaction reduces the energy or moderates neutrons to lower energies. Lower energy "moderated" neutrons are the most useful for some neutron scattering experiments. We provide a description of the LANSCE hydrogen-moderator system and its cryogenic performance with proton beams of up to 125 micro-amp average current.

Increase in Ca2+ current by sustained cAMP levels enhances proliferation rate in GH3 cells.

PubMed

Rodrigues, Andréia Laura; Brescia, Marcella; Koschinski, Andreas; Moreira, Thaís Helena; Cameron, Ryan T; Baillie, George; Beirão, Paulo S L; Zaccolo, Manuela; Cruz, Jader S

2018-01-01

Ca 2+ and cAMP are important intracellular modulators. In order to generate intracellular signals with various amplitudes, as well as different temporal and spatial properties, a tightly and precise control of these modulators in intracellular compartments is necessary. The aim of this study was to evaluate the effects of elevated and sustained cAMP levels on voltage-dependent Ca 2+ currents and proliferation in pituitary tumor GH3 cells. Effect of long-term exposure to forskolin and dibutyryl-cyclic AMP (dbcAMP) on Ca 2+ current density and cell proliferation rate were determined by using the whole-cell patch-clamp technique and real time cell monitoring system. The cAMP levels were assayed, after exposing transfected GH3 cells with the EPAC-1 cAMP sensor to forskolin and dbcAMP, by FRET analysis. Sustained forskolin treatment (24 and 48h) induced a significant increase in total Ca 2+ current density in GH3 cells. Accordingly, dibutyryl-cAMP incubation (dbcAMP) also elicited increase in Ca 2+ current density. However, the maximum effect of dbcAMP occurred only after 72h incubation, whereas forskolin showed maximal effect at 48h. FRET-experiments confirmed that the time-course to elevate intracellular cAMP was distinct between forskolin and dbcAMP. Mibefradil inhibited the fast inactivating current component selectively, indicating the recruitment of T-type Ca 2+ channels. A significant increase on cell proliferation rate, which could be related to the elevated and sustained intracellular levels of cAMP was observed. We conclude that maintaining high levels of intracellular cAMP will cause an increase in Ca 2+ current density and this phenomenon impacts proliferation rate in GH3 cells. Copyright © 2017 Elsevier Inc. All rights reserved.

Evidence cross-validation and Bayesian inference of MAST plasma equilibria

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nessi, G. T. von; Hole, M. J.; Svensson, J.

2012-01-15

In this paper, current profiles for plasma discharges on the mega-ampere spherical tokamak are directly calculated from pickup coil, flux loop, and motional-Stark effect observations via methods based in the statistical theory of Bayesian analysis. By representing toroidal plasma current as a series of axisymmetric current beams with rectangular cross-section and inferring the current for each one of these beams, flux-surface geometry and q-profiles are subsequently calculated by elementary application of Biot-Savart's law. The use of this plasma model in the context of Bayesian analysis was pioneered by Svensson and Werner on the joint-European tokamak [Svensson and Werner,Plasma Phys. Controlledmore » Fusion 50(8), 085002 (2008)]. In this framework, linear forward models are used to generate diagnostic predictions, and the probability distribution for the currents in the collection of plasma beams was subsequently calculated directly via application of Bayes' formula. In this work, we introduce a new diagnostic technique to identify and remove outlier observations associated with diagnostics falling out of calibration or suffering from an unidentified malfunction. These modifications enable a good agreement between Bayesian inference of the last-closed flux-surface with other corroborating data, such as that from force balance considerations using EFIT++[Appel et al., ''A unified approach to equilibrium reconstruction'' Proceedings of the 33rd EPS Conference on Plasma Physics (Rome, Italy, 2006)]. In addition, this analysis also yields errors on the plasma current profile and flux-surface geometry as well as directly predicting the Shafranov shift of the plasma core.« less

Two-fluid and magnetohydrodynamic modelling of magnetic reconnection in the MAST spherical tokamak and the solar corona

NASA Astrophysics Data System (ADS)

Browning, P. K.; Cardnell, S.; Evans, M.; Arese Lucini, F.; Lukin, V. S.; McClements, K. G.; Stanier, A.

2016-01-01

Twisted magnetic flux ropes are ubiquitous in laboratory and astrophysical plasmas, and the merging of such flux ropes through magnetic reconnection is an important mechanism for restructuring magnetic fields and releasing free magnetic energy. The merging-compression scenario is one possible start-up scheme for spherical tokamaks, which has been used on the Mega Amp Spherical Tokamak (MAST). Two current-carrying plasma rings or flux ropes approach each due to mutual attraction, forming a current sheet and subsequently merge through magnetic reconnection into a single plasma torus, with substantial plasma heating. Two-dimensional resistive and Hall-magnetohydrodynamic simulations of this process are reported, including a strong guide field. A model of the merging based on helicity-conserving relaxation to a minimum energy state is also presented, extending previous work to tight-aspect-ratio toroidal geometry. This model leads to a prediction of the final state of the merging, in good agreement with simulations and experiment, as well as the average temperature rise. A relaxation model of reconnection between two or more flux ropes in the solar corona is also described, allowing for different senses of twist, and the implications for heating of the solar corona are discussed.

Decommissioning of the High Flux Beam Reactor at Brookhaven National Laboratory.

PubMed

Hu, Jih-Perng; Reciniello, Richard N; Holden, Norman E

2012-08-01

The High Flux Beam Reactor (HFBR) at the Brookhaven National Laboratory was a heavy-water cooled and moderated reactor that achieved criticality on 31 October 1965. It operated at a power level of 40 mega-watts. An equipment upgrade in 1982 allowed operations at 60 mega-watts. After a 1989 reactor shutdown to reanalyze safety impact of a hypothetical loss of coolant accident, the reactor was restarted in 1991 at 30 mega-watts. The HFBR was shut down in December 1996 for routine maintenance and refueling. At that time, a leak of tritiated water was identified by routine sampling of ground water from wells located adjacent to the reactor's spent fuel pool. The reactor remained shut down for almost 3 y for safety and environmental reviews. In November 1999, the United States Department of Energy decided to permanently shut down the HFBR. The decontamination and decommissioning of the HFBR complex, consisting of multiple structures and systems to operate and maintain the reactor, were complete in 2009 after removing and shipping off all the control rod blades. The emptied and cleaned HFBR dome, which still contains the irradiated reactor vessel is presently under 24/7 surveillance for safety. Details of the HFBR's cleanup performed during 1999-2009, to allow the BNL facilities to be re-accessed by the public, will be described in the paper.

Nuclotron Beam Momentum Estimation Using Multiwire Proportional Chambers and Drift Chambers in the BM@N Experiment

NASA Astrophysics Data System (ADS)

Kapishin, Mikhail; Lenivenko, Vasilisa; Palichik, Vladimir; Voytishin, Nikolay

2018-02-01

The BM@N experiment is considered as the first phase of NICA Mega science project. The energy of the beam will vary from 1 to 6 GeV/u. The beams delivered by Nuclotron will be of different types from protons to Au. The ability to reconstruct the beam momentum with high precision is one way for showing that the tracking detectors are tuned in the right way and the reconstruction procedure performs well. A quick overview of the experimental setup is given in the work along with the description of some of the main tracking detectors. The beam momentum reconstruction procedure is described and results are presented for different values of the beam energy.

Deep sea mega-geomorphology: Progress and problems

NASA Technical Reports Server (NTRS)

Bryan, W. B.

1985-01-01

Historically, marine geologists have always worked with mega-scale morphology. This is a consequence both of the scale of the ocean basins and of the low resolution of the observational remote sensing tools available until very recently. In fact, studies of deep sea morphology have suffered from a serious gap in observational scale. Traditional wide-beam echo sounding gave images on a scale of miles, while deep sea photography has been limited to scales of a few tens of meters. Recent development of modern narrow-beam echo sounding coupled with computer-controlled swath mapping systems, and development of high-resolution deep-towed side-scan sonar, are rapidly filling in the scale gap. These technologies also can resolve morphologic detail on a scale of a few meters or less. As has also been true in planetary imaging projects, the ability to observe phenomena over a range of scales has proved very effective in both defining processes and in placing them in proper context.

A statistical method for determining the dimensions, tolerances and specification of optics for the Laser Megajoule facility (LMJ)

NASA Astrophysics Data System (ADS)

Denis, Vincent

2008-09-01

This paper presents a statistical method for determining the dimensions, tolerance and specifications of components for the Laser MegaJoule (LMJ). Numerous constraints inherent to a large facility require specific tolerances: the huge number of optical components; the interdependence of these components between the beams of same bundle; angular multiplexing for the amplifier section; distinct operating modes between the alignment and firing phases; the definition and use of alignment software in the place of classic optimization. This method provides greater flexibility to determine the positioning and manufacturing specifications of the optical components. Given the enormous power of the Laser MegaJoule (over 18 kJ in the infrared and 9 kJ in the ultraviolet), one of the major risks is damage the optical mounts and pollution of the installation by mechanical ablation. This method enables estimation of the beam occultation probabilities and quantification of the risks for the facility. All the simulations were run using the ZEMAX-EE optical design software.

Rip currents, mega-cusps, and eroding dunes

USGS Publications Warehouse

Thornton, E.B.; MacMahan, J.; Sallenger, A.H.

2007-01-01

Dune erosion is shown to occur at the embayment of beach mega-cusps O(200 m alongshore) that are associated with rip currents. The beach is the narrowest at the embayment of the mega-cusps allowing the swash of large storm waves coincident with high tides to reach the toe of the dune, to undercut the dune and to cause dune erosion. Field measurements of dune, beach, and rip current morphology are acquired along an 18 km shoreline in southern Monterey Bay, California. This section of the bay consists of a sandy shoreline backed by extensive dunes, rising to heights exceeding 40 m. There is a large increase in wave height going from small wave heights in the shadow of a headland, to the center of the bay where convergence of waves owing to refraction over the Monterey Bay submarine canyon results in larger wave heights. The large alongshore gradient in wave height results in a concomitant alongshore gradient in morphodynamic scale. The strongly refracted waves and narrow bay aperture result in near normal wave incidence, resulting in well-developed, persistent rip currents along the entire shoreline. The alongshore variations of the cuspate shoreline are found significantly correlated with the alongshore variations in rip spacing at 95% confidence. The alongshore variations of the volume of dune erosion are found significantly correlated with alongshore variations of the cuspate shoreline at 95% confidence. Therefore, it is concluded the mega-cusps are associated with rip currents and that the location of dune erosion is associated with the embayment of the mega-cusp.

Fabricating specialised orthopaedic implants using additive manufacturing

NASA Astrophysics Data System (ADS)

Unwin, Paul

2014-03-01

It has been hypothesised that AM is ideal for patient specific orthopaedic implants such as those used in bone cancer treatment, that can rapidly build structures such as lattices for bone and tissues to in-grow, that would be impossible using current conventional subtractive manufacturing techniques. The aim of this study was to describe the adoption of AM (direct metal laser sintering and electron beam melting) into the design manufacturing and post-manufacturing processes and the early clinical use. Prior to the clinical use of AM implants, extensive metallurgical and mechanical testing of both laser and electron beam fabrications were undertaken. Concurrently, post-manufacturing processes evaluated included hipping, cleaning and coating treatments. The first clinical application of a titanium alloy mega-implant was undertaken in November 2010. A 3D model of the pelvic wing implant was designed from CT scans. Novel key features included extensive lattice structures at the bone interfaces and integral flanges to fix the implant to the bone. The pelvic device was implanted with the aid of navigation and to date the patient remains active. A further 18 patient specific mega-implants have now been implanted. The early use of this advanced manufacturing route for patient specific implants has been very encouraging enabling the engineer to produce more advanced and anatomical conforming implants. However, there are a new set of design, manufacturing and regulatory challenges that require addressing to permit this technique to be used more widely. This technology is changing the design and manufacturing paradigm for the fabrication of specialised orthopaedic implants.

Free electron lasers for transmission of energy in space

NASA Technical Reports Server (NTRS)

Segall, S. B.; Hiddleston, H. R.; Catella, G. C.

1981-01-01

A one-dimensional resonant-particle model of a free electron laser (FEL) is used to calculate laser gain and conversion efficiency of electron energy to photon energy. The optical beam profile for a resonant optical cavity is included in the model as an axial variation of laser intensity. The electron beam profile is matched to the optical beam profile and modeled as an axial variation of current density. Effective energy spread due to beam emittance is included. Accelerators appropriate for a space-based FEL oscillator are reviewed. Constraints on the concentric optical resonator and on systems required for space operation are described. An example is given of a space-based FEL that would produce 1.7 MW of average output power at 0.5 micrometer wavelength with over 50% conversion efficiency of electrical energy to laser energy. It would utilize a 10 m-long amplifier centered in a 200 m-long optical cavity. A 3-amp, 65 meV electrostatic accelerator would provide the electron beam and recover the beam after it passes through the amplifier. Three to five shuttle flights would be needed to place the laser in orbit.

Bolt beam propagation analysis

NASA Astrophysics Data System (ADS)

Shokair, I. R.

BOLT (Beam on Laser Technology) is a rocket experiment to demonstrate electron beam propagation on a laser ionized plasma channel across the geomagnetic field in the ion focused regime (IFR). The beam parameters for BOLT are: beam current I(sub b) = 100 Amps, beam energy of 1--1.5 MeV (gamma =3-4), and a Gaussian beam and channel of radii r(sub b) = r(sub c) = 1.5 cm. The N+1 ionization scheme is used to ionize atomic oxygen in the upper atmosphere. This scheme utilizes 130 nm light plus three IR lasers to excite and then ionize atomic oxygen. The limiting factor for the channel strength is the energy of the 130 nm laser, which is assumed to be 1.6 mJ for BOLT. At a fixed laser energy and altitude (fixing the density of atomic oxygen), the range can be varied by adjusting the laser tuning, resulting in a neutralization fraction axial profile of the form: f(z) = f(sub 0) e(exp minus z)/R, where R is the range. In this paper we consider the propagation of the BOLT beam and calculate the range of the electron beam taking into account the fact that the erosion rates (magnetic and inductive) vary with beam length as the beam and channel dynamically respond to sausage and hose instabilities.

cAMP modulates multiple K+ currents, increasing spike duration and excitability in Aplysia sensory neurons.

PubMed

Goldsmith, B A; Abrams, T W

1992-12-01

Enhancement of the defensive withdrawal reflex of Aplysia involves a prolongation of the action potentials of mechanosensory neurons, which contributes to facilitation of transmitter release from these cells. Recent reports have suggested that whereas cAMP-dependent modulation of K+ current increases sensory neuron excitability, a cAMP-independent decrease in K+ current may increase the action potential duration and, thus, facilitate transmitter release. We have tested this proposal using Walsh cAMP-dependent protein kinase inhibitor or activators of the cAMP cascade and found that cAMP plays a major role in the spike-broadening effects of facilitatory transmitter; however, broadening requires higher levels of activation of the cAMP-dependent kinase than does increasing excitability. A steeply voltage-dependent transient K+ current, termed IKV,early, and the slowly activating S-type K+ (S-K+) current are both reduced by activation of the cAMP cascade, although with different sensitivities to the second messenger, enabling excitability and spike duration to be regulated independently. Differences in cAMP sensitivity also suggested that the originally described S-K+ current actually consists of two independent components, a slowly activating component and a time-independent, "steady-state" current that is activated at rest.

A socio-ecological adaptive approach to contaminated mega-site management: from 'control and correct' to 'coping with change'.

PubMed

Schirmer, Mario; Lyon, Ken; Armstrong, James E; Farrell, Katharine N

2012-01-01

Mega-sites have a notable impact on surrounding ecological systems. At such sites there are substantial risks associated with complex socio-ecological interactions that are hard to characterize, let alone model and predict. While the urge to control and clean-up mega-sites (control and correct) is understandable, rather than setting a goal of cleaning up such sites, we suggest a more realistic response strategy is to address these massive and persistent sources of contamination by acknowledging their position as new features of the socio-ecological landscapes within which they are located. As it seems nearly impossible to clean up such sites, we argue for consideration of a 'coping with change' rather than a 'control and correct' approach. This strategy recognizes that the current management option for a mega-site, in light of its physical complexities and due to changing societal preferences, geochemical transformations, hydrogeology knowledge and remedial technology options may not remain optimal in future, and therefore needs to be continuously adapted, as community, ecology, technology and understanding change over time. This approach creates an opportunity to consider the relationship between a mega-site and its human and ecological environments in a different and more dynamic way. Our proposed approach relies on iterative adaptive management to incorporate mega-site management into the overall socio-ecological systems of the site's context. This approach effectively embeds mega-site management planning in a triple bottom line and environmental sustainability structure, rather than simply using single measures of success, such as contaminant-based guidelines. Recognizing that there is probably no best solution for managing a mega-site, we present a starting point for engaging constructively with this seemingly intractable issue. Therefore, we aim to initiate discussion about a new approach to mega-site management, in which the complexity of the problems posed by mega-sites is reflected upon in its entirety. These complexities are associated with uncertainties and unknowns that have to be addressed, as they have an impact on the strategies being developed and applied. We contend that the best that can be hoped for in mega-site management is an acceptable solution for the current state of affairs, with good flexibility to modify strategies as new site conditions, remediation possibilities, community preferences and management objectives develop over time. Copyright © 2011 Elsevier B.V. All rights reserved.

Mega-Containerships and Mega-Containerports in the Gulf of Mexico: A Literature Review and Annotated Bibliography

DOT National Transportation Integrated Search

2000-05-01

Original Report Date: May 1999/Revised October 1999. Container shipping plays a key role in international transshipments and is currently the system of choice for most global shippers handling non-bulk commodities. In the competitive maritime industr...

Two-dimensional studies of relativistic electron beam plasma instabilities in an inhomogeneous plasma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shukla, Chandrasekhar; Das, Amita, E-mail: amita@ipr.res.in; Patel, Kartik

Relativistic electron beam propagation in plasma is fraught with several micro instabilities like two stream, filamentation, etc., in plasma. This results in severe limitation of the electron transport through a plasma medium. Recently, however, there has been an experimental demonstration of improved transport of Mega Ampere of electron currents (generated by the interaction of intense laser with solid target) in a carbon nanotube structured solid target [G. Chatterjee et al., Phys. Rev. Lett. 108, 235005 (2012)]. This then suggests that the inhomogeneous plasma (created by the ionization of carbon nanotube structured target) helps in containing the growth of the beammore » plasma instabilities. This manuscript addresses this issue with the help of a detailed analytical study and 2-D Particle-In-Cell simulations. The study conclusively demonstrates that the growth rate of the dominant instability in the 2-D geometry decreases when the plasma density is chosen to be inhomogeneous, provided the scale length 1/k{sub s} of the inhomogeneous plasma is less than the typical plasma skin depth (c/ω{sub 0}) scale. At such small scale lengths channelization of currents is also observed in simulation.« less

OVERVIEW OF MONO-ENERGETIC GAMMA-RAY SOURCES & APPLICATIONS

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hartemann, F V; Albert, F; Anderson, G G

2010-05-18

Recent progress in accelerator physics and laser technology have enabled the development of a new class of tunable gamma-ray light sources based on Compton scattering between a high-brightness, relativistic electron beam and a high intensity laser pulse produced via chirped-pulse amplification (CPA). A precision, tunable Mono-Energetic Gamma-ray (MEGa-ray) source driven by a compact, high-gradient X-band linac is currently under development and construction at LLNL. High-brightness, relativistic electron bunches produced by an X-band linac designed in collaboration with SLAC NAL will interact with a Joule-class, 10 ps, diode-pumped CPA laser pulse to generate tunable {gamma}-rays in the 0.5-2.5 MeV photon energymore » range via Compton scattering. This MEGa-ray source will be used to excite nuclear resonance fluorescence in various isotopes. Applications include homeland security, stockpile science and surveillance, nuclear fuel assay, and waste imaging and assay. The source design, key parameters, and current status are presented, along with important applications, including nuclear resonance fluorescence. In conclusion, we have optimized the design of a high brightness Compton scattering gamma-ray source, specifically designed for NRF applications. Two different parameters sets have been considered: one where the number of photons scattered in a single shot reaches approximately 7.5 x 10{sup 8}, with a focal spot size around 8 {micro}m; in the second set, the spectral brightness is optimized by using a 20 {micro}m spot size, with 0.2% relative bandwidth.« less

Commissioning and Plans for the NSTX-U Facility

NASA Astrophysics Data System (ADS)

Ono, Masayuki; NSTX-U Team

2016-10-01

The National Spherical Torus Experiment - Upgrade (NSTX-U) has started its first year of plasma operations after the successful completion of the CD-4 milestones. The unique operating regimes of NSTX-U can contribute to several important issues in the physics of burning plasmas to optimize the performance of ITER. The major mission of NSTX-U is also to develop the physics and technology basis for an ST-based Fusion Nuclear Science Facility (FNSF). The new center stack will provide toroidal field of 1 Tesla at a major radius of 0.93 m which should enable a plasma current of up to 2 mega-Amp for 5 sec. A much more tangential 2nd NBI system, with 2-3 times higher current drive efficiency compared to the 1st NBI system, is installed. NSTX-U is designed to attain the 100% non-inductive operation needed for a compact FNSF design. With higher fields and heating powers of 14 MW, the NSTX-U plasma collisionality will be reduced by a factor of 3-6 to help explore the trend in transport towards the low collisionality FNSF regime. If the favorable trends observed on NSTX holds at low collisionality, high fusion neutron fluences could be achievable in very compact ST devices.

Relation of field-aligned currents measured by AMPERE project to solar wind and substorms

NASA Astrophysics Data System (ADS)

McPherron, R. L.; Anderson, B. J.; Chu, X.

2016-12-01

Magnetic perturbations measured in the Active Magnetosphere and Planetary Electrodynamics Response Experiment (AMPERE) by the Iridium constellation of spacecraft have been processed to obtain the time history of field-aligned currents (FAC) connecting the magnetosphere to the ionosphere. We find that the strength of these currents is closely related to the strength of the solar wind driver defined as a running average of the previous three hours of the optimum AL (auroral lower) coupling function. The relation is well represented by a saturation model I = A*S*Ss/(S+Ss) with I the current strength in mega Amps, S the driver strength in mV/m, Ss the saturation value of 7.78 mV/m, and A = 2.55 scales the relation to units of current. We also find that in general the upward current on the nightside increases with each substorm expansion onset defined by a combination of the SuperMag SML (SuperMag AL) and midlatitude positive bay (MPB) onset lists. A superposed epoch analysis using 700 onsets in 2010 shows the following: solar wind coupling peaks at expansion onset; dayside outward current starts to increase one hour before onset while nightside outward current starts suddenly at onset; nightside outward current reaches a peak at 28 minutes as do SML and MPB indices; FAC, SML, and MPB respectively take 1, 2, and 3 hours to decay to background. The data indicate that the substorm current wedge is superposed on a pre-existing field-aligned current system and that the location and properties of the current wedge can be studied with the AMPERE data.

Can Coulomb repulsion for charged particle beams be overcome?

NASA Astrophysics Data System (ADS)

Retsky, Michael W.

2004-01-01

Mutual repulsion of discrete charged particles or Coulomb repulsion is widely considered to be an ultimate hard limit in charged particle optics. It prevents the ability to finely focus high current beams into a small spots at large distances from the defining apertures. A classic example is the 1970s era "Star Wars" study of an electron beam directed energy weapon as an orbiting antiballistic missile device. After much analysis, it was considered physically impossible to focus a 1000-amp 1-GeV beam into a 1-cm diameter spot 1000-km from the beam generator. The main reason was that a 1-cm diameter beam would spread to 5-m diameter at 1000-km due to Coulomb repulsion. Since this could not be overcome, the idea was abandoned. But is this true? What if the rays were reversed? That is, start with a 5-m beam converging slightly with the same nonuniform angular and energy distribution as the electrons from the original problem were spreading at 1000-km distance. Could Coulomb repulsion be overcome? Looking at the terms in computational studies, some are reversible while others are not. Since the nonreversible terms should be small, it might be possible to construct an electron beam directed energy weapon.

Current status of Kumgang laser system

NASA Astrophysics Data System (ADS)

Kong, Hong Jin; Park, Sangwoo; Ahn, HeeKyung; Lee, Hwihyeong; Oh, Jungsuk; Kim, Jom Sool

2015-02-01

In KAIST, Kumgang laser is being developed for demonstration of the kW level coherent beam combination using stimulated Brillouin scattering phase conjugation mirrors. It will combine 4 modules of DPSSL rod amplifier which produces 1 kW output power. It is composed of the single frequency front-end, pre-amplifier module, and main amplifier. The output powers of the pre-amp and main amplifier module are 200 W (20 mJ @ 10 kHz / 10 ns) and 1.07kW (107 mJ @ 10 kHz / 10 ns), respectively.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Barty, C J

A renaissance in nuclear physics is occurring around the world because of a new kind of incredibly bright, gamma-ray light source that can be created with short pulse lasers and energetic electron beams. These highly Mono-Energetic Gamma-ray (MEGa-ray) sources produce narrow, laser-like beams of incoherent, tunable gamma-rays and are enabling access and manipulation of the nucleus of the atom with photons or so called 'Nuclear Photonics'. Just as in the early days of the laser when photon manipulation of the valence electron structure of the atom became possible and enabling to new applications and science, nuclear photonics with laser-based gamma-raymore » sources promises both to open up wide areas of practical isotope-related, materials applications and to enable new discovery-class nuclear science. In the United States, the development of high brightness and high flux MEGa-ray sources is being actively pursued at the Lawrence Livermore National Laboratory in Livermore (LLNL), California near San Francisco. The LLNL work aims to create by 2013 a machine that will advance the state of the art with respect to source the peak brightness by 6 orders of magnitude. This machine will create beams of 1 to 2.3 MeV photons with color purity matching that of common lasers. In Europe a similar but higher photon energy gamma source has been included as part of the core capability that will be established at the Extreme Light Infrastructure Nuclear Physics (ELI-NP) facility in Magurele, Romania outside of Bucharest. This machine is expected to have an end point gamma energy in the range of 13 MeV. The machine will be co-located with two world-class, 10 Petawatt laser systems thus allowing combined intense-laser and gamma-ray interaction experiments. Such capability will be unique in the world. In this talk, Dr. Chris Barty from LLNL will review the state of the art with respect to MEGa-ray source design, construction and experiments and will describe both the ongoing projects around the world as well some of the exciting applications that these machines will enable. The optimized interaction of short-duration, pulsed lasers with relativistic electron beams (inverse laser-Compton scattering) is the key to unrivaled MeV-scale photon source monochromaticity, pulse brightness and flux. In the MeV spectral range, such Mono-Energetic Gamma-ray (MEGa-ray) sources can have many orders of magnitude higher peak brilliance than even the world's largest synchrotrons. They can efficiently perturb and excite the isotope-specific resonant structure of the nucleus in a manner similar to resonant laser excitation of the valence electron structure of the atom.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Thirolf, P. G.; Habs, D.; Filipescu, D.

Next-generation {gamma} beams from laser Compton-backscattering facilities like ELI-NP (Bucharest)] or MEGa-Ray (Livermore) will drastically exceed the photon flux presently available at existing facilities, reaching or even exceeding 10{sup 13}{gamma}/sec. The beam structure as presently foreseen for MEGa-Ray and ELI-NP builds upon a structure of macro-pulses ({approx}120 Hz) for the electron beam, accelerated with X-band technology at 11.5 GHz, resulting in a micro structure of 87 ps distance between the electron pulses acting as mirrors for a counterpropagating intense laser. In total each 8.3 ms a {gamma} pulse series with a duration of about 100 ns will impinge on themore » target, resulting in an instantaneous photon flux of about 10{sup 18}{gamma}/s, thus introducing major challenges in view of pile-up. Novel {gamma} optics will be applied to monochromatize the {gamma} beam to ultimately {Delta}E/E{approx}10{sup -6}. Thus level-selective spectroscopy of higher multipole excitations will become accessible with good contrast for the first time. Fast responding {gamma} detectors, e.g. based on advanced scintillator technology (e.g. LaBr{sub 3}(Ce)) allow for measurements with count rates as high as 10{sup 6}-10{sup 7}{gamma}/s without significant drop of performance. Data handling adapted to the beam conditions could be performed by fast digitizing electronics, able to sample data traces during the micro-pulse duration, while the subsequent macro-pulse gap of ca. 8 ms leaves ample time for data readout. A ball of LaBr{sub 3} detectors with digital readout appears to best suited for this novel type of nuclear photonics at ultra-high counting rates.« less

Statistical spatial properties of speckle patterns generated by multiple laser beams

DOE Office of Scientific and Technical Information (OSTI.GOV)

Le Cain, A.; Sajer, J. M.; Riazuelo, G.

2011-08-15

This paper investigates hot spot characteristics generated by the superposition of multiple laser beams. First, properties of speckle statistics are studied in the context of only one laser beam by computing the autocorrelation function. The case of multiple laser beams is then considered. In certain conditions, it is shown that speckles have an ellipsoidal shape. Analytical expressions of hot spot radii generated by multiple laser beams are derived and compared to numerical estimates made from the autocorrelation function. They are also compared to numerical simulations performed within the paraxial approximation. Excellent agreement is found for the speckle width as wellmore » as for the speckle length. Application to the speckle patterns generated in the Laser MegaJoule configuration in the zone where all the beams overlap is presented. Influence of polarization on the size of the speckles as well as on their abundance is studied.« less

An added-mass partition algorithm for fluid–structure interactions of compressible fluids and nonlinear solids

DOE Office of Scientific and Technical Information (OSTI.GOV)

Banks, J.W., E-mail: banksj3@rpi.edu; Henshaw, W.D., E-mail: henshw@rpi.edu; Kapila, A.K., E-mail: kapila@rpi.edu

We describe an added-mass partitioned (AMP) algorithm for solving fluid–structure interaction (FSI) problems involving inviscid compressible fluids interacting with nonlinear solids that undergo large rotations and displacements. The computational approach is a mixed Eulerian–Lagrangian scheme that makes use of deforming composite grids (DCG) to treat large changes in the geometry in an accurate, flexible, and robust manner. The current work extends the AMP algorithm developed in Banks et al. [1] for linearly elasticity to the case of nonlinear solids. To ensure stability for the case of light solids, the new AMP algorithm embeds an approximate solution of a nonlinear fluid–solidmore » Riemann (FSR) problem into the interface treatment. The solution to the FSR problem is derived and shown to be of a similar form to that derived for linear solids: the state on the interface being fundamentally an impedance-weighted average of the fluid and solid states. Numerical simulations demonstrate that the AMP algorithm is stable even for light solids when added-mass effects are large. The accuracy and stability of the AMP scheme is verified by comparison to an exact solution using the method of analytical solutions and to a semi-analytical solution that is obtained for a rotating solid disk immersed in a fluid. The scheme is applied to the simulation of a planar shock impacting a light elliptical-shaped solid, and comparisons are made between solutions of the FSI problem for a neo-Hookean solid, a linearly elastic solid, and a rigid solid. The ability of the approach to handle large deformations is demonstrated for a problem of a high-speed flow past a light, thin, and flexible solid beam.« less

Amps particle accelerator definition study

NASA Technical Reports Server (NTRS)

Sellen, J. M., Jr.

1975-01-01

The Particle Accelerator System of the AMPS (Atmospheric, Magnetospheric, and Plasmas in Space) payload is a series of charged particle accelerators to be flown with the Space Transportation System Shuttle on Spacelab missions. In the configuration presented, the total particle accelerator system consists of an energetic electron beam, an energetic ion accelerator, and both low voltage and high voltage plasma acceleration devices. The Orbiter is illustrated with such a particle accelerator system.

GTP-Binding Proteins Inhibit cAMP Activation of Chloride Channels in Cystic Fibrosis Airway Epithelial Cells

NASA Astrophysics Data System (ADS)

Schwiebert, Erik M.; Kizer, Neil; Gruenert, Dieter C.; Stanton, Bruce A.

1992-11-01

Cystic fibrosis (CF) is a genetic disease characterized, in part, by defective regulation of Cl^- secretion by airway epithelial cells. In CF, cAMP does not activate Cl^- channels in the apical membrane of airway epithelial cells. We report here whole-cell patch-clamp studies demonstrating that pertussis toxin, which uncouples heterotrimeric GTP-binding proteins (G proteins) from their receptors, and guanosine 5'-[β-thio]diphosphate, which prevents G proteins from interacting with their effectors, increase Cl^- currents and restore cAMP-activated Cl^- currents in airway epithelial cells isolated from CF patients. In contrast, the G protein activators guanosine 5'-[γ-thio]triphosphate and AlF^-_4 reduce Cl^- currents and inhibit cAMP from activating Cl^- currents in normal airway epithelial cells. In CF cells treated with pertussis toxin or guanosine 5'-[β-thio]diphosphate and in normal cells, cAMP activates a Cl^- conductance that has properties similar to CF transmembrane-conductance regulator Cl^- channels. We conclude that heterotrimeric G proteins inhibit cAMP-activated Cl^- currents in airway epithelial cells and that modulation of the inhibitory G protein signaling pathway may have the therapeutic potential for improving cAMP-activated Cl^- secretion in CF.

Initial Testing of the Mark-0 X-Band RF Gun at SLAC

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vlieks, Arnold; Adolphsen, C.; Dolgashev, V.

A new X-band RF gun (Mark-0) has been assembled, tuned and was tested in the ASTA facility at SLAC. This gun has been improved from an earlier gun used in Compton-scattering experiments at SLAC by the introduction of a racetrack dual-input coupler to reduce quadrupole fields. Waveguide-to-coupler irises were also redesigned to reduce surface magnetic fields and therefore peak pulse surface heating. Tests of this photocathode gun will allow us to gain early operational experience for beam tests of a new gun with further improvements (Mark-1) being prepared for SLAC's X-Band Test Area (XTA) program and the LLNL MEGa-ray program.more » Results of current testing up to {approx} 200 MV/m peak surface Electric fields are presented.« less

A Robust High Current Density Electron Gun

NASA Astrophysics Data System (ADS)

Mako, F.; Peter, W.; Shiloh, J.; Len, L. K.

1996-11-01

Proof-of-principle experiments are proposed to validate a new concept for a robust, high-current density Pierce electron gun (RPG) for use in klystrons and high brightness electron sources for accelerators. This rugged, long-life electron gun avoids the difficulties associated with plasma cathodes, thermionic emitters, and field emission cathodes. The RPG concept employs the emission of secondary electrons in a transmission mode as opposed to the conventional mode of reflection, i.e., electrons exit from the back face of a thin negative electron affinity (NEA) material, and in the same direction as the incident beam. Current amplification through one stage of a NEA material could be over 50 times. The amplification is accomplished in one or more stages consisting of one primary emitter and one or more secondary emitters. The primary emitter is a low current density robust emitter (e.g., thoriated tungsten). The secondary emitters are thin NEA electrodes which emit secondary electrons in the same direction as the incident beam. Specific application is targeted for a klystron gun to be used by SLAC with a cold cathode at 30-40 amps/cm^2 output from the secondary emission stage, a ~2 μs pulse length, and ~200 pulses/second.

Electromagnetic interference assessment of an ion drive electric propulsion system

NASA Technical Reports Server (NTRS)

Whittlesey, A. C.

1979-01-01

The electromagnetic interference (EMI) form elements of an ion drive electric propulsion system was analyzed, and the effects of EMI interaction with a typical interplanetary spacecraft engineering and scientific subsystems were predicted. SEMCAP, a computerized electromagnetic compatibility assessment code, was used to analyze the impact of EMI noise sources on 65 engineering/telemetry circuits and 48 plasma wave and planetary radio astronomy channels measuring over the range of 100 Hz to 40 MHz in a spacecraft of the Voyager type; manual methods were used to evaluate electrostatics, magnetics, and communications effects. Results indicate that some conducted and radiated spectra are in excess of electromagnetic compatibility specification limits; direct design changes may be required for filtering and shielding of thrust system elements. The worst source of broadband radiated noise appears to be the power processor. The magnetic field necessary to thruster operation is equivalent to about 18 amp-sq m per amp of beam current at right angles to the axis caused by the neutralizer/plume loop.

Separate Cl^- Conductances Activated by cAMP and Ca2+ in Cl^--Secreting Epithelial Cells

NASA Astrophysics Data System (ADS)

Cliff, William H.; Frizzell, Raymond A.

1990-07-01

We studied the cAMP- and Ca2+-activated secretory Cl^- conductances in the Cl^--secreting colonic epithelial cell line T84 using the whole-cell patch-clamp technique. Cl^- and K^+ currents were measured under voltage clamp. Forskolin or cAMP increased Cl^- current 2-15 times with no change in K^+ current. The current-voltage relation for cAMP-activated Cl^- current was linear from -100 to +100 mV and showed no time-dependent changes in current during voltage pulses. Ca2+ ionophores or increased pipette Ca2+ increased both Cl^- and K^+ currents 2-30 times. The Ca2+-activated Cl^- current was outwardly rectified, activated during depolarizing voltage pulses, and inactivated during hyperpolarizing voltage pulses. Addition of ionophore after forskolin further increased Cl^- conductance 1.5-5 times, and the current took on the time-dependent characteristics of that stimulated by Ca2+. Thus, cAMP and Ca2+ activate Cl^- conductances with different properties, implying that these second messengers activate different Cl^- channels or that they induce different conductive and kinetic states in the same Cl^- channel.

Coulomb repulsion and the electron beam directed energy weapon

NASA Astrophysics Data System (ADS)

Retsky, Michael W.

2004-09-01

Mutual repulsion of discrete charged particles or Coulomb repulsion is widely considered to be an ultimate hard limit in charged particle optics. It prevents the ability to finely focus high current beams into small spots at large distances from defining apertures. A classic example is the 1970s era "Star Wars" study of an electron beam directed energy weapon as an orbiting antiballistic missile device. After much analysis, it was considered physically impossible to focus a 1000-amp 1-GeV beam into a 1-cm diameter spot 1000-km from the beam generator. The main reason was that a 1-cm diameter beam would spread to 5-m diameter at 1000-km due to Coulomb repulsion. Since this could not be overcome, the idea was abandoned. But is this true? What if the rays were reversed? That is, start with a 5-m beam converging slightly with the same nonuniform angular and energy distribution as the electrons from the original problem were spreading at 1000-km distance. Could Coulomb repulsion be overcome? Looking at the terms in computational studies, some are reversible while others are not. Based on estimates, the nonreversible terms should be small - of the order of 0.1 mm. If this is true, it is possible to design a practical electron beam directed weapon not limited by Coulomb repulsion.

Characterisation of edge turbulence in relation to edge magnetic field configuration in L-mode plasmas in the Mega Amp Spherical Tokamak.

NASA Astrophysics Data System (ADS)

Dewhurst, J.; Hnat, B.; Dudson, B.; Dendy, R. O.; Counsell, G. F.; Kirk, A.

2007-12-01

Almost all astrophysical and magnetically confined fusion plasmas are turbulent. Here, we examine ion saturation current (Isat) measurements of edge plasma turbulence for three MAST L-mode plasmas that differ primarily in their edge magnetic field configurations. First, absolute moments of the coarse grained data are examined to obtain accurate values of scaling exponents. The dual scaling behaviour is identified in all samples, with the temporal scale τ ≍ 40-60 μs separating the two regimes. Strong universality is then identified in the functional form of the probability density function (PDF) for Isat fluctuations, which is well approximated by the Fréchet distribution on temporal scales τ ≤ 40μs. For temporal scales τ > 40μs, the PDFs appear to converge to the Gumbel distribution, which has been previously identified as a universal feature of many other complex phenomena. The optimal fitting parameters k=1.15 for Fréchet and a=1.35 for Gumbel provide a simple quantitative characterisation of the full spectrum of fluctuations. We conclude that, to good approximation, the properties of the edge turbulence are independent of the edge magnetic field configuration.

Characterization of edge turbulence in relation to edge magnetic field configuration in Ohmic L-mode plasmas in the Mega Amp Spherical Tokamak

NASA Astrophysics Data System (ADS)

Hnat, B.; Dudson, B. D.; Dendy, R. O.; Counsell, G. F.; Kirk, A.; MAST Team

2008-08-01

Ion saturation current (Isat) measurements of edge plasma turbulence are analysed for six MAST L-mode plasmas that differ primarily in their edge magnetic field configurations. The analysis techniques are designed to capture the strong nonlinearities of the datasets. First, absolute moments of the data are examined to obtain accurate values of scaling exponents. This confirms dual scaling behaviour in all samples, with the temporal scale τ ≈ 40-60 µs separating the two regimes. Strong universality is then identified in the functional form of the probability density function (PDF) for Isat fluctuations, which is well approximated by the Fréchet distribution on temporal scales τ <= 40 µs. For temporal scales τ > 40 µs, the PDFs appear to converge to the Gumbel distribution, which has been previously identified as a universal feature of many other complex phenomena. The optimal fitting parameters k = 1.15 for Fréchet and a = 1.35 for Gumbel provide a simple quantitative characterization of the full spectrum of fluctuations. It is concluded that, to good approximation, the properties of the edge turbulence are independent of the edge magnetic field configuration.

Rapid, efficient charging of lead-acid and nickel-zinc traction cells

NASA Technical Reports Server (NTRS)

Smithrick, J. J.

1978-01-01

Lead-acid and nickel-zinc traction cells were rapidly and efficiently charged using a high rate tapered direct current (HRTDC) charge method which could possibly be used for on-the-road service recharge of electric vehicles. The HRTDC method takes advantage of initial high cell charge acceptance and uses cell gassing rate and temperature as an indicator of charging efficiency. On the average, in these preliminary tests, 300 amp-hour nickel-zinc traction cells were given a HRTDC (initial current 500 amps, final current 100 amps) to 78 percent of rated amp-hour capacity within 53 minutes at an amp-hour efficiency of 92 percent and an energy efficiency of 52 percent. Three hundred amp-hour lead-acid traction cells were charged to 69 percent of rated amp-hour capacity within 46 minutes at an amp-hour efficiency of 91 percent with an energy efficiency of 64 percent. In order to find ways to further decrease the recharge times, the effect of periodically (0 to 400 Hz) pulse discharging cells during a constant current charging process (94% duty cycle) was investigated. Preliminary data indicate no significant effect of this type of pulse discharging during charge on charge acceptance of lead-acid or nickel-zinc cells.

Femtosecond MeV Electron Energy-Loss Spectroscopy

NASA Astrophysics Data System (ADS)

Li, R. K.; Wang, X. J.

2017-11-01

Pump-probe electron energy-loss spectroscopy (EELS) with femtosecond temporal resolution will be a transformative research tool for studying nonequilibrium chemistry and electronic dynamics of matter. In this paper, we propose a concept of femtosecond EELS utilizing mega-electron-volt electron beams from a radio-frequency (rf) photocathode source. The high acceleration gradient and high beam energy of the rf gun are critical to the generation of 10-fs electron beams, which enables an improvement of the temporal resolution by more than 1 order of magnitude beyond the state of the art. In our proposal, the "reference-beam technique" relaxes the energy stability requirement of the rf power source by roughly 2 orders of magnitude. The requirements for the electron-beam quality, photocathode, spectrometer, and detector are also discussed. Supported by particle-tracking simulations, we demonstrate the feasibility of achieving sub-electron-volt energy resolution and approximately 10-fs temporal resolution with existing or near-future hardware performance.

Plasma Radiation Source on the Basis of the Gas Puff with Outer Plasma Shell in the Circuit of a Mega-Ampere Load Current Doubler

NASA Astrophysics Data System (ADS)

Kokshenev, V. A.; Labetsky, A. Yu.; Shishlov, A. V.; Kurmaev, N. E.; Fursov, F. I.; Cherdizov, R. K.

2017-12-01

Characteristics of Z-pinch plasma radiation in the form of a double shell neon gas puff with outer plasma shell are investigated in the microsecond implosion mode. Experiments are performed using a GIT-12 mega-joule generator with load current doubler having a ferromagnetic core at implosion currents up to 5 MA. Conditions for matching of the nonlinear load with the mega-ampere current multiplier circuit are determined. The load parameters (plasma shell characteristics and mass and geometry of gas puff shells) are optimized on the energy supplied to the gas puff and n energy characteristics of radiation. It is established that the best modes of K-shell radiation in neon are realized for such radial distribution of the gas-puff material at which the compression velocity of the shell is close to a constant and amounts to 27-30 cm/μs. In these modes, up to 40% of energy supplied to the gas puff is converted into K-shell radiation. The reasons limiting the efficiency of the radiation source with increasing implosion current are analyzed. A modernized version of the energy supply from the current doubler to the Z-pinch is proposed.

Mega-electron-volt ultrafast electron diffraction at SLAC National Accelerator Laboratory

DOE Office of Scientific and Technical Information (OSTI.GOV)

Weathersby, S. P.; Brown, G.; Chase, T. F.

Ultrafast electron probes are powerful tools, complementary to x-ray free-electron lasers, used to study structural dynamics in material, chemical, and biological sciences. High brightness, relativistic electron beams with femtosecond pulse duration can resolve details of the dynamic processes on atomic time and length scales. SLAC National Accelerator Laboratory recently launched the Ultrafast Electron Diffraction (UED) and microscopy Initiative aiming at developing the next generation ultrafast electron scattering instruments. As the first stage of the Initiative, a mega-electron-volt (MeV) UED system has been constructed and commissioned to serve ultrafast science experiments and instrumentation development. The system operates at 120-Hz repetition ratemore » with outstanding performance. In this paper, we report on the SLAC MeV UED system and its performance, including the reciprocal space resolution, temporal resolution, and machine stability.« less

Mega-electron-volt ultrafast electron diffraction at SLAC National Accelerator Laboratory.

PubMed

Weathersby, S P; Brown, G; Centurion, M; Chase, T F; Coffee, R; Corbett, J; Eichner, J P; Frisch, J C; Fry, A R; Gühr, M; Hartmann, N; Hast, C; Hettel, R; Jobe, R K; Jongewaard, E N; Lewandowski, J R; Li, R K; Lindenberg, A M; Makasyuk, I; May, J E; McCormick, D; Nguyen, M N; Reid, A H; Shen, X; Sokolowski-Tinten, K; Vecchione, T; Vetter, S L; Wu, J; Yang, J; Dürr, H A; Wang, X J

2015-07-01

Ultrafast electron probes are powerful tools, complementary to x-ray free-electron lasers, used to study structural dynamics in material, chemical, and biological sciences. High brightness, relativistic electron beams with femtosecond pulse duration can resolve details of the dynamic processes on atomic time and length scales. SLAC National Accelerator Laboratory recently launched the Ultrafast Electron Diffraction (UED) and microscopy Initiative aiming at developing the next generation ultrafast electron scattering instruments. As the first stage of the Initiative, a mega-electron-volt (MeV) UED system has been constructed and commissioned to serve ultrafast science experiments and instrumentation development. The system operates at 120-Hz repetition rate with outstanding performance. In this paper, we report on the SLAC MeV UED system and its performance, including the reciprocal space resolution, temporal resolution, and machine stability.

TEBPP: Theoretical and Experimental study of Beam-Plasma-Physics

NASA Technical Reports Server (NTRS)

Anderson, H. R.; Bernstein, W.; Linson, L. M.; Papadopoulos, K.; Kellogg, P. J.; Szuszczewicz, E. P.; Hallinan, T. J.; Leinbach, H.

1980-01-01

The interaction of an electron beam (0 to 10 keV, 0 to 1.5 Amp) with the plasma and neutral atmospheres at 200 to 400 km altitude is studied with emphasis on applications to near Earth and cosmical plasmas. The interaction occurs in four space time regions: (1) near electron gun, beam coming into equilibrium with medium; (2) equilibrium propagation in ionosphere; (3) ahead of beam pulse, temporal and spatial precursors; (4) behind a beam pulse. While region 2 is of the greatest interest, it is essential to study Region 1 because it determines the characteristics of the beam as it enters 2 through 4.

Overview of Mono-Energetic Gamma-Ray Sources and Applications

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hartemann, Fred; /LLNL, Livermore; Albert, Felicie

2012-06-25

Recent progress in accelerator physics and laser technology have enabled the development of a new class of tunable gamma-ray light sources based on Compton scattering between a high-brightness, relativistic electron beam and a high intensity laser pulse produced via chirped-pulse amplification (CPA). A precision, tunable Mono-Energetic Gamma-ray (MEGa-ray) source driven by a compact, high-gradient X-band linac is currently under development and construction at LLNL. High-brightness, relativistic electron bunches produced by an X-band linac designed in collaboration with SLAC NAL will interact with a Joule-class, 10 ps, diode-pumped CPA laser pulse to generate tunable {gamma}-rays in the 0.5-2.5 MeV photon energymore » range via Compton scattering. This MEGaray source will be used to excite nuclear resonance fluorescence in various isotopes. Applications include homeland security, stockpile science and surveillance, nuclear fuel assay, and waste imaging and assay. The source design, key parameters, and current status are presented, along with important applications, including nuclear resonance fluorescence.« less

Description of a 2.3 kW power transformer for space applications

NASA Technical Reports Server (NTRS)

Hansen, I.

1979-01-01

The principle features and special testing of a high voltage high power transformer designed and developed for space application are described. The transformer is operated in a series resonant inverter supplying beam power to a 30 cm mercury ion thruster. Electrical requirements include operation of 2.3 kW continuous power output, primary currents to 35 amps rms, and frequencies up to 20 kHz. High efficiency was obtained through detailed considerations of the tradeoffs available in core materials, wire selection, coil configurations and thermal control. A number of novel heat removal techniques are discussed which control the winding temperature using only the available conductive cooling.

Effect of cAMP on short-circuit current in isolated human ciliary body.

PubMed

Wu, Ren-yi; Ma, Ning; Hu, Qian-qian

2013-07-01

Cyclic adenosine monophosphate (cAMP) could activate chloride channels in bovine ciliary body and trigger an increase in the ionic current (short-circuit current, Isc) across the ciliary processes in pigs. The purpose of this study was to investigate how cAMP modulates Isc in isolated human ciliary processes and the possible involvement of chloride transport across the tissue in cAMP-induced Isc change. In an Ussing-type chamber system, the Isc changes induced by the cAMP analogue 8-bromo-cAMP and an adenylyl cyclase activator forskolin in isolated human ciliary processes were assessed. The involvement of Cl(-) component in the bath solution was investigated. The effect of Cl(-) channel (10 µmol/L niflumic acid and 1 mmol/L 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS)), K(+) channel (10 mmol/L tetraethylammonium chloride (TEA)), or Na(+) channel blockers (1 mmol/L amiloride) on 8-bromo-cAMP-induced Isc change was also studied. Dose-dependently, 8-bromo-cAMP (10 nmol/L-30 µmol/L) or forskolin (10 nmol/L-3 µmol/L) increased Isc across the ciliary processes with an increase in negative potential difference on the non-pigmented epithelium (NPE) side of the tissue. Isc increase induced by 8-bromo-cAMP was more pronounced when the drug was applied on the NPE side than on the pigmented epithelium side. When the tissue was bathed in low Cl(-) solutions, the Isc increase was significantly inhibited. Finally, niflumic acid and DIDS, but not TEA or amiloride, significantly prevented the Isc increase induced by 8-bromo-cAMP. cAMP stimulates stroma-to-aqueous anionic transport in isolated human ciliary processes. Chloride is likely to be among the ions, the transportation of which across the tissue is triggered by cAMP, suggesting the potential role of cAMP in the process of aqueous humor formation in human eyes.

75 FR 22503 - Airworthiness Directives; Bombardier, Inc. Model DHC-8-400 Series Airplanes

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-29

... an inrush current less than or equal to 1.6 amps, before further flight, replace the vane with a new... AOA vane is found to have an inrush current greater than 1.6 amps, repeat the measurement of the vane... the serviceable AOA transducer is-- Then repeat the measurement-- More than 1.60 amps, but less than...

An overview of antimicrobial peptides and the latest advances in their development.

PubMed

Sierra, Josep M; Fusté, Ester; Rabanal, Francesc; Vinuesa, Teresa; Viñas, Miguel

2017-06-01

The recent dramatic increase in the incidence of antimicrobial resistance has been recognized by organizations such as the United Nations and World Health Organization as well as the governments of the USA and several European countries. A relatively new weapon in the fight against severe infections caused by multi-drug resistant bacteria is antimicrobial peptides (AMPs). These include colistin, currently regarded as the last line of antimicrobial therapy against multi-drug resistant microorganisms. Areas covered: Here, the authors provide an overview of the current research on AMPs. The focus is AMPs currently being developed for the treatment of recalcitrant bacterial infections, the synergies of AMPs and antibiotics, and the activity of AMPs against biofilm. This review also includes a brief introduction into the use of AMPs in infections caused by Mycobacterium, fungi, and parasites. Expert opinion: In research into new antimicrobials, AMPs are gaining increasing attention. While many are natural and are produced by a wide variety of organisms, others are being newly designed and chemically synthesized in the laboratory to achieve novel antimicrobial agents. The same strategy to fight infections in nature is thus being effectively exploited to safeguard human and animal health.

Solid core dipoles and switching power supplies: lower cost light sources?

NASA Astrophysics Data System (ADS)

Benesch, J.; Philip, S.

2015-05-01

As a result of improvements in power semiconductors, moderate frequency switching supplies can now provide the hundreds of amps typically required by accelerators with zero-to-peak noise in the kHz region ~ 0.06% in current or voltage mode. Modeling was undertaken using a finite electromagnetic program to determine if eddy currents induced in the solid steel of CEBAF magnets and small supplemental additions would bring the error fields down to the 5ppm level needed for beam quality. The expected maximum field of the magnet under consideration is 0.85 T and the DC current required to produce that field is used in the calculations. An additional 0.1% current ripple is added to the DC current at discrete frequencies 360 Hz, 720 Hz or 7200 Hz. Over the region of the pole within 0.5% of the central integrated BdL the resulting AC field changes can be reduced to less than 1% of the 0.1% input ripple for all frequencies, and a sixth of that at 7200 Hz. Doubling the current, providing 1.5 T central field, yielded the same fractional reduction in ripple at the beam for the cases checked. A small dipole was measured at 60, 120, 360 and 720 Hz in two conditions and the results compared to the larger model for the latter two frequencies with surprisingly good agreement. For light sources with aluminum vacuum vessels and full energy linac injection, the combination of solid core dipoles and switching power supplies may result in significant cost savings. The work may also be used to guide retrofit of existing machines to reduce the level of ripple in the particle beam path.

cAMP Stimulates Transepithelial Short-Circuit Current and Fluid Transport Across Porcine Ciliary Epithelium.

PubMed

Cheng, Angela King-Wah; Civan, Mortimer M; To, Chi-Ho; Do, Chi-Wai

2016-12-01

To investigate the effects of cAMP on transepithelial electrical parameters and fluid transport across porcine ciliary epithelium. Transepithelial electrical parameters were determined by mounting freshly isolated porcine ciliary epithelium in a modified Ussing chamber. Similarly, fluid movement across intact ciliary body was measured with a custom-made fluid flow chamber. Addition of 1, 10, and 100 μM 8-Br-cAMP (cAMP) to the aqueous side (nonpigmented ciliary epithelium, NPE) induced a sustained increase in short-circuit current (Isc). Addition of niflumic acid (NFA) to the aqueous surface effectively blocked the cAMP-induced Isc stimulation. The administration of cAMP to the stromal side (pigmented ciliary epithelium, PE) triggered a significant stimulation of Isc only at 100 μM. No additive effect was observed with bilateral application of cAMP. Likewise, forskolin caused a significant stimulation of Isc when applied to the aqueous side. Concomitantly, cAMP and forskolin increased fluid transport across porcine ciliary epithelium, and this stimulation was effectively inhibited by aqueous NFA. Depleting Cl- in the bathing solution abolished the baseline Isc and inhibited the subsequent stimulation by cAMP. Pretreatment with protein kinase A (PKA) blockers (H89/KT5720) significantly inhibited the cAMP- and forskolin-induced Isc responses. Our results suggest that cAMP triggers a sustained stimulation of Cl- and fluid transport across porcine ciliary epithelium; Cl- channels in the NPE cells are potentially a cellular site for this PKA-sensitive cAMP-mediated response.

Overview of MAST results

NASA Astrophysics Data System (ADS)

Chapman, I. T.; Adamek, J.; Akers, R. J.; Allan, S.; Appel, L.; Asunta, O.; Barnes, M.; Ben Ayed, N.; Bigelow, T.; Boeglin, W.; Bradley, J.; Brünner, J.; Cahyna, P.; Carr, M.; Caughman, J.; Cecconello, M.; Challis, C.; Chapman, S.; Chorley, J.; Colyer, G.; Conway, N.; Cooper, W. A.; Cox, M.; Crocker, N.; Crowley, B.; Cunningham, G.; Danilov, A.; Darrow, D.; Dendy, R.; Diallo, A.; Dickinson, D.; Diem, S.; Dorland, W.; Dudson, B.; Dunai, D.; Easy, L.; Elmore, S.; Field, A.; Fishpool, G.; Fox, M.; Fredrickson, E.; Freethy, S.; Garzotti, L.; Ghim, Y. C.; Gibson, K.; Graves, J.; Gurl, C.; Guttenfelder, W.; Ham, C.; Harrison, J.; Harting, D.; Havlickova, E.; Hawke, J.; Hawkes, N.; Hender, T.; Henderson, S.; Highcock, E.; Hillesheim, J.; Hnat, B.; Holgate, J.; Horacek, J.; Howard, J.; Huang, B.; Imada, K.; Jones, O.; Kaye, S.; Keeling, D.; Kirk, A.; Klimek, I.; Kocan, M.; Leggate, H.; Lilley, M.; Lipschultz, B.; Lisgo, S.; Liu, Y. Q.; Lloyd, B.; Lomanowski, B.; Lupelli, I.; Maddison, G.; Mailloux, J.; Martin, R.; McArdle, G.; McClements, K.; McMillan, B.; Meakins, A.; Meyer, H.; Michael, C.; Militello, F.; Milnes, J.; Morris, A. W.; Motojima, G.; Muir, D.; Nardon, E.; Naulin, V.; Naylor, G.; Nielsen, A.; O'Brien, M.; O'Gorman, T.; Ono, Y.; Oliver, H.; Pamela, S.; Pangione, L.; Parra, F.; Patel, A.; Peebles, W.; Peng, M.; Perez, R.; Pinches, S.; Piron, L.; Podesta, M.; Price, M.; Reinke, M.; Ren, Y.; Roach, C.; Robinson, J.; Romanelli, M.; Rozhansky, V.; Saarelma, S.; Sangaroon, S.; Saveliev, A.; Scannell, R.; Schekochihin, A.; Sharapov, S.; Sharples, R.; Shevchenko, V.; Silburn, S.; Simpson, J.; Storrs, J.; Takase, Y.; Tanabe, H.; Tanaka, H.; Taylor, D.; Taylor, G.; Thomas, D.; Thomas-Davies, N.; Thornton, A.; Turnyanskiy, M.; Valovic, M.; Vann, R.; Walkden, N.; Wilson, H.; van Wyk, F.; Yamada, T.; Zoletnik, S.; MAST; MAST Upgrade Teams

2015-10-01

The Mega Ampère Spherical Tokamak (MAST) programme is strongly focused on addressing key physics issues in preparation for operation of ITER as well as providing solutions for DEMO design choices. In this regard, MAST has provided key results in understanding and optimizing H-mode confinement, operating with smaller edge localized modes (ELMs), predicting and handling plasma exhaust and tailoring auxiliary current drive. In all cases, the high-resolution diagnostic capability on MAST is complemented by sophisticated numerical modelling to facilitate a deeper understanding. Mitigation of ELMs with resonant magnetic perturbations (RMPs) with toroidal mode number nRMP = 2, 3, 4, 6 has been demonstrated: at high and low collisionality; for the first ELM following the transition to high confinement operation; during the current ramp-up; and with rotating nRMP = 3 RMPs. nRMP = 4, 6 fields cause less rotation braking whilst the power to access H-mode is less with nRMP = 4 than nRMP = 3, 6. Refuelling with gas or pellets gives plasmas with mitigated ELMs and reduced peak heat flux at the same time as achieving good confinement. A synergy exists between pellet fuelling and RMPs, since mitigated ELMs remove fewer particles. Inter-ELM instabilities observed with Doppler backscattering are consistent with gyrokinetic simulations of micro-tearing modes in the pedestal. Meanwhile, ELM precursors have been strikingly observed with beam emission spectroscopy (BES) measurements. A scan in beta at the L-H transition shows that pedestal height scales strongly with core pressure. Gyro-Bohm normalized turbulent ion heat flux (as estimated from the BES data) is observed to decrease with increasing tilt of the turbulent eddies. Fast ion redistribution by energetic particle modes depends on density, and access to a quiescent domain with ‘classical’ fast ion transport is found above a critical density. Highly efficient electron Bernstein wave current drive (1 A W-1) has been achieved in solenoid-free start-up. A new proton detector has characterized escaping fusion products. Langmuir probes and a high-speed camera suggest filaments play a role in particle transport in the private flux region whilst coherence imaging has measured scrape-off layer (SOL) flows. BOUT++ simulations show that fluxes due to filaments are strongly dependent on resistivity and magnetic geometry of the SOL, with higher radial fluxes at higher resistivity. Finally, MAST Upgrade is due to begin operation in 2016 to support ITER preparation and importantly to operate with a Super-X divertor to test extended leg concepts for particle and power exhaust.

Kolmogorov-Kraichnan Scaling in the Inverse Energy Cascade of Two-Dimensional Plasma Turbulence

NASA Astrophysics Data System (ADS)

Antar, G. Y.

2003-08-01

Turbulence in plasmas that are magnetically confined, such as tokamaks or linear devices, is two dimensional or at least quasi two dimensional due to the strong magnetic field, which leads to extreme elongation of the fluctuations, if any, in the direction parallel to the magnetic field. These plasmas are also compressible fluid flows obeying the compressible Navier-Stokes equations. This Letter presents the first comprehensive scaling of the structure functions of the density and velocity fields up to 10th order in the PISCES linear plasma device and up to 6th order in the Mega-Ampère Spherical Tokamak (MAST). In the two devices, it is found that the scaling of the turbulent fields is in good agreement with the prediction of the Kolmogorov-Kraichnan theory for two-dimensional turbulence in the energy cascade subrange.

Global two-fluid simulations of geodesic acoustic modes in strongly shaped tight aspect ratio tokamak plasmas

DOE Office of Scientific and Technical Information (OSTI.GOV)

Robinson, J. R.; Hnat, B.; Thyagaraja, A.

2013-05-15

Following recent observations suggesting the presence of the geodesic acoustic mode (GAM) in ohmically heated discharges in the Mega Amp Spherical Tokamak (MAST) [J. R. Robinson et al., Plasma Phys. Controlled Fusion 54, 105007 (2012)], the behaviour of the GAM is studied numerically using the two fluid, global code CENTORI [P. J. Knight et al. Comput. Phys. Commun. 183, 2346 (2012)]. We examine mode localisation and effects of magnetic geometry, given by aspect ratio, elongation, and safety factor, on the observed frequency of the mode. An excellent agreement between simulations and experimental data is found for simulation plasma parameters matchedmore » to those of MAST. Increasing aspect ratio yields good agreement between the GAM frequency found in the simulations and an analytical result obtained for elongated large aspect ratio plasmas.« less

Palmatine, a protoberberine alkaloid, inhibits both Ca2+- and cAMP-activated Cl− secretion in isolated rat distal colon

PubMed Central

Wu, D Z; Yuan, J Y; Shi, H L; Hu, Z B

2008-01-01

Background and purpose: The protoberberine alkaloid berberine has been reported to inhibit colonic Cl− secretion. However, it is not known if other protoberberine alkaloids share these effects. We have therefore selected another protoberberine alkaloid, palmatine, to assess its effects on active ion transport across rat colonic epithelium. Experimental approach: Rat colonic mucosa was mounted in Ussing chambers and short circuit current (I SC), apical Cl− current and basolateral K+ current were recorded. Intracellular cAMP content was determined by an enzyme immunoassay. Intracellular Ca2+ concentration was measured with Fura-2 AM. Key results: Palmatine inhibited carbachol-induced Ca2+-activated Cl− secretion and the carbachol-induced increase of intracellular Ca2+ concentration. Palmatine also inhibited cAMP-activated Cl− secretion induced by prostaglandin E2 (PGE2) or forskolin. Palmatine prevented the elevation of intracellular cAMP by forskolin. Determination of apical Cl− currents showed that palmatine suppressed the forskolin-stimulated, apical cAMP-activated Cl− current but not the carbachol-stimulated apical Ca2+-activated Cl− current. Following permeabilization of apical membranes with nystatin, we found that palmatine inhibited a carbachol-stimulated basolateral K+ current that was sensitive to charybdotoxin and resistant to chromanol 293B. However, the forskolin-stimulated basolateral K+ current inhibited by palmatine was specifically blocked by chromanol 293B and not by charybdotoxin. Conclusions and implications: Palmatine attenuated Ca2+-activated Cl− secretion through inhibiting basolateral charybdotoxin-sensitive, SK4 K+ channels, whereas it inhibited cAMP-activated Cl− secretion by inhibiting apical CFTR Cl− channels and basolateral chromanol 293B-sensitive, KvLQT1 K+ channels. PMID:18204477

Recent Advances in the Development of Antimicrobial Peptides (AMPs): Attempts for Sustainable Medicine?

PubMed

Kokel, Anne; Torok, Marianna

2018-01-17

Since the first isolation of antimicrobial peptides (AMPs) they have attracted extensive interest in medicinal chemistry. However, only a few AMP-based drugs are currently available on the market. Despite their effectiveness, biodegradability, and versatile mode of action that is less likely to induce resistance compared to conventional antibiotics, AMPs suffer from major issues that need to be addressed to broaden their use. Notably, AMPs can lack selectivity leading to side effects and cytotoxicity, and also exhibit in vivo instability. Several strategies are being actively considered to overcome the limitations that restrain the success of AMPs. In the current work, recent strategies reported for improving AMPs in the context of drug design and delivery were surveyed, and also their possible impact on patients and the environment was assessed. As a major advantage AMPs possess an easily tunable skeleton offering opportunities to improve their properties. Strategic structural modifications and the beneficial properties of cyclic or branched AMPs in term of stability have been reported. The conjugation of AMPs with nanoparticles has also been explored to increase their in vivo stability. Other techniques such as the coupling of AMPs with specific antibodies aim to increase the selectivity of the potential drug towards the target. These strategies were evaluated for their effect on the environment highlighting green technologies. Although further research is needed taking into account both environmental and human health consequences of novel AMPs several of these compounds are promising drug candidates for use in sustainable medicine. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Ion Dynamic Capture Experiments With The High Performance Antiproton Trap (HiPAT)

NASA Technical Reports Server (NTRS)

Martin, James; Lewis, Raymond; Chakrabarti, Suman; Sims, William H.; Pearson, J. Boise; Fant, Wallace E.

2002-01-01

To take the first step towards using the energy produced from the matter-antimatter annihilation for propulsion applications, the NASA Marshall Space Flight Center (MSFC) Propulsion Research Center (PRC) has initiated a research activity examining the storage of low energy antiprotons. The High Performance Antiproton Trap (HiPAT) is an electromagnetic system (Penning-Malmberg design) consisting of a 4 Tesla superconductor, a high voltage electrode confinement system, and an ultra high vacuum test section. It has been designed with an ultimate goal of maintaining 10(exp 12) charged particles with a half-life of 18 days. Currently, this system is being evaluated experimentally using normal matter ions that are cheap to produce, relatively easy to handle, and provide a good indication of overall trap behavior (with the exception of assessing annihilation losses). The ions are produced via a positive hydrogen ion source and transported to HiPAT in a beam line equipped with electrostatic optics. The optics serve to both focus and gate the incoming ions, providing microsecond-timed beam pulses that are dynamically captured by cycling the HiPAT forward containment field like a "trap door". Initial dynamic capture experiments have been successfully performed with beam energy and currents set to 1.9 kV and 23 micro-amps, respectively. At these settings up to 2x10(exp 9) ions have been trapped during a single dynamic cycle.

Assessment of Proton Deflectometry for Exploding Wire Experiments

DOE Office of Scientific and Technical Information (OSTI.GOV)

Beg, Farhat Nadeem

2013-09-25

This project provides the first demonstration of the application of proton deflectometry for the diagnosis of electromagnetic field topology and current-carrying regions in Z-pinch plasma experiments. Over the course of this project several milestones were achieved. High-energy proton beam generation was demonstrated on the short-pulse high-intensity Leopard laser, (10 Joules in ~350 femtoseconds, and the proton beam generation was shown to be reproducible. Next, protons were used to probe the electromagnetic field structure of short circuit loads in order to benchmark the two numerical codes, the resistive-magnetohydrodynamics (MHD) code, Gorgon, and the hybrid particle-in-cell code, LSP for the interpretation ofmore » results. Lastly, the proton deflectometry technique was used to map the magnetic field structure of pulsed-power-driven plasma loads including wires and supersonic jets formed with metallic foils. Good agreement between the modeling and experiments has been obtained. The demonstrated technique holds great promise to significantly improve the understanding of current flow and electromagnetic field topology in pulsed power driven high energy density plasmas. Proton probing with a high intensity laser was for the first time implemented in the presence of the harsh debris and x-ray producing z-pinch environment driven by a mega-ampere-scale pulsed-power machine. The intellectual merit of the program was that it investigated strongly driven MHD systems and the influence of magnetic field topology on plasma evolution in pulsed power driven plasmas. The experimental program involved intense field-matter interaction in the generation of the proton probe, as well as the generation of plasma subjected to 1 MegaGauss scale magnetic fields. The computational aspect included two well-documented codes, in combination for the first time to provide accurate interpretation of the experimental results. The broader impact included the support of 2 graduate students, one at UCSD and one at NTF, who were exposed to both the experimental physics work, the MHD and PIC modeling of the system. A first generation college undergraduate student was employed to assist in experiments and data analysis throughout the project. Data resulting from the research program were broadly disseminated by publication in scientific journals, and presentation at international and national conferences and workshops.« less

Retrospective study of urinalysis for dl-amphetamine and dl-methamphetamine analysis under current Department of Defense guidelines.

PubMed

Shippee, R L; Kippenberger, D J

2000-09-01

Under current Department of Defense (DOD) directive, the laboratories certified to conduct urinalyis testing in support of the DOD Drug Deterrence Program are required to conduct dl-isomer analysis on all specimens that confirm at a concentration greater than 500 ng/mL methamphetamine (METH). Although the same cutoff concentration is required for amphetamine (AMP) reporting, there is no requirement for dl-isomer analysis of AMP-positive specimens. Of the 894,823 specimens screened by the Army Drug Testing Laboratory at Ft. Meade, MD during a 19-month period, 339 confirmed positive for METH. From this positive population, seven specimens failed to confirm at or above the DOD cutoff of > 20% d-isomer. One of the seven specimens contained 534 ng/mL l-AMP and was reported positive for AMP. Although 100% of the AMP was the l-isomer, under current DOD directive, this information was not passed along to the Medical Review Officers (MRO) to assist them during the interview process. Although this situation appears to be a rare event, consideration should be given to requiring dl-isomer analysis of AMP-positive specimens and forwarding this information to the MRO.

Hohlraum design for the LMJ ignition target

NASA Astrophysics Data System (ADS)

Malinie, G.; Cherfils, C.; Gauthier, P.; Lambert, F.; Monteil, M. C.

2011-10-01

First experiments with the Laser MegaJoule (LMJ) are scheduled to be performed in 2014. The current nominal point design for ignition with 160 beams on the LMJ has been described in. It consists of an indirectly driven A943 capsule, with a plastic ablator doped with Germanium. This capsule is mounted in the center of a Rugby-shaped hohlraum, which is filled with a low density H/He gas, and has a gold-uranium cocktail wall lined with pure gold. We investigate the influence of two key parameters of the hohlraum design: the radius of the laser entrance holes (LEHs), and the thickness of the cocktail layer. Since the Rugby shape of the nominal point design is that of a half-ellipse going from the hohlraum waist to the LEH, any change in the LEH radius has a global effect on the hohlraum shape. Taking into account the current laser spot profiles of the LMJ and using 2D integrated calculations with our FCI2 radiation hydrodynamics code, we assess the flexiblility we have to reduce the LEH radius and/or the cocktail layer thickness.

Energy-Sensitive Ion- and Cathode-Luminescent Radiation-Beam Monitors Based on Multilayer Thin-Film Designs.

PubMed

Gil-Rostra, Jorge; Ferrer, Francisco J; Espinós, Juan Pedro; González-Elipe, Agustín R; Yubero, Francisco

2017-05-17

A multilayer luminescent design concept is presented to develop energy-sensitive radiation-beam monitors on the basis of colorimetric analysis. Each luminescent layer within the stack consists of rare-earth-doped transparent oxides of optical quality and a characteristic luminescent emission under excitation with electron or ion beams. For a given type of particle beam (electron, protons, α particles, etc.), its penetration depth and therefore its energy loss at a particular buried layer within the multilayer stack depend on the energy of the initial beam. The intensity of the luminescent response of each layer is proportional to the energy deposited by the radiation beam within the layer, so characteristic color emission will be achieved if different phosphors are considered in the layers of the luminescent stack. Phosphor doping, emission efficiency, layer thickness, and multilayer structure design are key parameters relevant to achieving a broad colorimetric response. Two case examples are designed and fabricated to illustrate the capabilities of these new types of detector to evaluate the kinetic energy of either electron beams of a few kilo-electron volts or α particles of a few mega-electron volts.

P2Y6 receptor mediates colonic NaCl secretion via differential activation of cAMP-mediated transport

PubMed Central

Köttgen, Michael; Löffler, Thomas; Jacobi, Christoph; Nitschke, Roland; Pavenstädt, Hermann; Schreiber, Rainer; Frische, Sebastian; Nielsen, Søren; Leipziger, Jens

2003-01-01

Extracellular nucleotides are important regulators of epithelial ion transport. Here we investigated nucleotide-mediated effects on colonic NaCl secretion and the signal transduction mechanisms involved. Basolateral UDP induced a sustained activation of Cl– secretion, which was completely inhibited by 293B, a specific inhibitor of cAMP-stimulated basolateral KCNQ1/KCNE3 K+ channels. We therefore speculated that a basolateral P2Y6 receptor could increase cAMP. Indeed UDP elevated cAMP in isolated crypts. We identified an epithelial P2Y6 receptor using crypt [Ca2+]i measurements, RT-PCR, and immunohistochemistry. To investigate whether the rat P2Y6elevates cAMP, we coexpressed the P2Y1 or P2Y6 receptor together with the cAMP-regulated cystic fibrosis transmembrane conductance regulator (CFTR) Cl– channel in Xenopus oocytes. A two-electrode voltage clamp was used to monitor nucleotide-induced Cl– currents. In oocytes expressing the P2Y1 receptor, ATP transiently activated the endogenous Ca2+-activated Cl– current, but not CFTR. In contrast, in oocytes expressing the P2Y6receptor, UDP transiently activated the Ca2+-activated Cl– current and subsequently CFTR. CFTR Cl– currents were identified by their halide conductance sequence. In summary we find a basolateral P2Y6 receptor in colonic epithelial cells stimulating sustained NaCl secretion by way of a synergistic increase of [Ca2+]i and cAMP. In support of these data P2Y6 receptor stimulation differentially activates CFTR in Xenopus oocytes. PMID:12569163

Blocking adenylyl cyclase inhibits olfactory generator currents induced by "IP(3)-odors".

PubMed

Chen, S; Lane, A P; Bock, R; Leinders-Zufall, T; Zufall, F

2000-07-01

Vertebrate olfactory receptor neurons (ORNs) transduce odor stimuli into electrical signals by means of an adenylyl cyclase/cAMP second messenger cascade, but it remains widely debated whether this cAMP cascade mediates transduction for all odorants or only certain odor classes. To address this problem, we have analyzed the generator currents induced by odors that failed to produce cAMP in previous biochemical assays but instead produced IP(3) ("IP(3)-odors"). We show that in single salamander ORNs, sensory responses to "cAMP-odors" and IP(3)-odors are not mutually exclusive but coexist in the same cells. The currents induced by IP(3)-odors exhibit identical biophysical properties as those induced by cAMP odors or direct activation of the cAMP cascade. By disrupting adenylyl cyclase to block cAMP formation using two potent antagonists of adenylyl cyclase, SQ22536 and MDL12330A, we show that this molecular step is necessary for the transduction of both odor classes. To assess whether these results are also applicable to mammals, we examine the electrophysiological responses to IP(3)-odors in intact mouse main olfactory epithelium (MOE) by recording field potentials. The results show that inhibition of adenylyl cyclase prevents EOG responses to both odor classes in mouse MOE, even when "hot spots" with heightened sensitivity to IP(3)-odors are examined.

Femtosecond MeV Electron Energy-Loss Spectroscopy

DOE PAGES

Li, R. K.; Wang, X. J.

2017-11-09

Pump-probe electron energy-loss spectroscopy (EELS) with femtosecond temporal resolution will be a transformative research tool for studying nonequilibrium chemistry and electronic dynamics of matter. Here in this article, we propose a concept of femtosecond EELS utilizing mega-electron-volt electron beams from a radio-frequency (rf) photocathode source. The high acceleration gradient and high beam energy of the rf gun are critical to the generation of 10-fs electron beams, which enables an improvement of the temporal resolution by more than 1 order of magnitude beyond the state of the art. In our proposal, the “referencebeam technique” relaxes the energy stability requirement of themore » rf power source by roughly 2 orders of magnitude. The requirements for the electron-beam quality, photocathode, spectrometer, and detector are also discussed. Supported by particle-tracking simulations, we demonstrate the feasibility of achieving subelectron- volt energy resolution and approximately 10-fs temporal resolution with existing or near-future hardware performance.« less

Femtosecond MeV Electron Energy-Loss Spectroscopy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, R. K.; Wang, X. J.

Pump-probe electron energy-loss spectroscopy (EELS) with femtosecond temporal resolution will be a transformative research tool for studying nonequilibrium chemistry and electronic dynamics of matter. Here in this article, we propose a concept of femtosecond EELS utilizing mega-electron-volt electron beams from a radio-frequency (rf) photocathode source. The high acceleration gradient and high beam energy of the rf gun are critical to the generation of 10-fs electron beams, which enables an improvement of the temporal resolution by more than 1 order of magnitude beyond the state of the art. In our proposal, the “referencebeam technique” relaxes the energy stability requirement of themore » rf power source by roughly 2 orders of magnitude. The requirements for the electron-beam quality, photocathode, spectrometer, and detector are also discussed. Supported by particle-tracking simulations, we demonstrate the feasibility of achieving subelectron- volt energy resolution and approximately 10-fs temporal resolution with existing or near-future hardware performance.« less

A large contribution of a cyclic AMP-independent pathway to turtle olfactory transduction

PubMed Central

1994-01-01

Although multiple pathways are involved in the olfactory transduction mechanism, cAMP-dependent pathway has been considered to contribute mainly to the transduction. We examined the degree of contribution of cAMP-independent pathway to the turtle olfactory response by recording inward currents from isolated cells, nerve impulses from cilia and olfactory bulbar responses. The results obtained by the three recordings were essentially consistent with each other, but detail studies were carried out by recording the bulbar response to obtain quantitative data. Application of an odorant cocktail to the isolated olfactory neuron after injection of 1 mM cAMP from the patch pipette elicited a large inward current. Mean amplitude of inward currents evoked by the cocktail with 1 mM cAMP in the patch pipette was similar to that without cAMP in the pipette. Application of the cocktail after the response to 50 microM forskolin was adapted also induced a large inward current. Application of the odorant cocktail to the olfactory epithelium, after the response to 50 microM forskolin was adapted, brought about an appreciable increase in the impulse frequency. The bulbar response to forskolin alone reached a saturation level around 10 microM. After the response to 50 microM forskolin was adapted, 11 species of odorants were applied to the olfactory epithelium. The magnitudes of responses to the odorants after forskolin were 45-80% of those of the control responses. There was no essential difference in the degree of the suppression by forskolin between cAMP- and IP3- producing odorants classified in the rat, suggesting that certain part of the forskolin-suppressive component was brought about by nonspecific action of forskolin. Application of a membrane permeant cAMP analogue, cpt-cAMP elicited a large response, and 0.1 mM citralva after 3 mM cpt- cAMP elicited 51% of the control response which was close to the response to citralva after 50 microM forskolin. A membrane permeant cGMP analogue, db-cGMP elicited a small response and the response to 0.1 mM citralva was unaffected by db-cGMP. It was concluded that cAMP- independent (probably IP3-independent) pathway greatly contributes to the turtle olfactory transduction. PMID:7523576

Narrow linewidth picosecond UV pulsed laser with mega-watt peak power.

PubMed

Huang, Chunning; Deibele, Craig; Liu, Yun

2013-04-08

We demonstrate a master oscillator power amplifier (MOPA) burst mode laser system that generates 66 ps/402.5 MHz pulses with mega-watt peak power at 355 nm. The seed laser consists of a single frequency fiber laser (linewidth < 5 KHz), a high bandwidth electro-optic modulator (EOM), a picosecond pulse generator, and a fiber based preamplifier. A very high extinction ratio (45 dB) has been achieved by using an adaptive bias control of the EOM. The multi-stage Nd:YAG amplifier system allows a uniformly temporal shaping of the macropulse with a tunable pulse duration. The light output from the amplifier is converted to 355 nm, and over 1 MW peak power is obtained when the laser is operating in a 5-μs/10-Hz macropulse mode. The laser output has a transform-limited spectrum with a very narrow linewidth of individual longitudinal modes. The immediate application of the laser system is the laser-assisted hydrogen ion beam stripping for the Spallation Neutron Source (SNS).

Strength and fracture energy of foamed concrete incorporating rice husk ash and polypropylene mega-mesh 55

NASA Astrophysics Data System (ADS)

Jaini, Z. M.; Rum, R. H. M.; Boon, K. H.

2017-10-01

This paper presents the utilization of rice husk ash (RHA) as sand replacement and polypropylene mega-mesh 55 (PMM) as fiber reinforcement in foamed concrete. High pozzolanic reaction and the ability to become filler make RHA as a strategic material to enhance the strength and durability of foamed concrete. Furthermore, the presence of PMM optimizes the toughness of foamed concrete in resisting shrinkage and cracking. In this experimental study, cube and cylinder specimens were prepared for the compression and splitting-tensile tests. Meanwhile, notched beam specimens were cast for the three-point bending test. It was found that 40% RHA and 9kg/m3 PMM contribute to the highest strength and fracture energy. The compressive, tensile and flexural strengths are 32MPa, 2.88MPa and 6.68MPa respectively, while the fracture energy achieves 42.19N/m. The results indicate high potential of RHA and PMM in enhancing the mechanical properties of foamed concrete.

Exchange protein activated by cAMP (Epac) mediates cAMP-dependent but protein kinase A-insensitive modulation of vascular ATP-sensitive potassium channels

PubMed Central

Purves, Gregor I; Kamishima, Tomoko; Davies, Lowri M; Quayle, John M; Dart, Caroline

2009-01-01

Exchange proteins directly activated by cyclic AMP (Epacs or cAMP-GEF) represent a family of novel cAMP-binding effector proteins. The identification of Epacs and the recent development of pharmacological tools that discriminate between cAMP-mediated pathways have revealed previously unrecognized roles for cAMP that are independent of its traditional target cAMP-dependent protein kinase (PKA). Here we show that Epac exists in a complex with vascular ATP-sensitive potassium (KATP) channel subunits and that cAMP-mediated activation of Epac modulates KATP channel activity via a Ca2+-dependent mechanism involving the activation of Ca2+-sensitive protein phosphatase 2B (PP-2B, calcineurin). Application of the Epac-specific cAMP analogue 8-pCPT-2′-O-Me-cAMP, at concentrations that activate Epac but not PKA, caused a 41.6 ± 4.7% inhibition (mean ±s.e.m.; n= 7) of pinacidil-evoked whole-cell KATP currents recorded in isolated rat aortic smooth muscle cells. Importantly, similar results were obtained when cAMP was elevated by addition of the adenylyl cyclase activator forskolin in the presence of the structurally distinct PKA inhibitors, Rp-cAMPS or KT5720. Activation of Epac by 8-pCPT-2′-O-Me-cAMP caused a transient 171.0 ± 18.0 nm (n= 5) increase in intracellular Ca2+ in Fura-2-loaded aortic myocytes, which persisted in the absence of extracellular Ca2+. Inclusion of the Ca2+-specific chelator BAPTA in the pipette-filling solution or preincubation with the calcineurin inhibitors, cyclosporin A or ascomycin, significantly reduced the ability of 8-pCPT-2′-O-Me-cAMP to inhibit whole-cell KATP currents. These results highlight a previously undescribed cAMP-dependent regulatory mechanism that may be essential for understanding the physiological and pathophysiological roles ascribed to arterial KATP channels in the control of vascular tone and blood flow. PMID:19491242

Investigation of merging/reconnection heating during solenoid-free startup of plasmas in the MAST Spherical Tokamak

NASA Astrophysics Data System (ADS)

Tanabe, H.; Yamada, T.; Watanabe, T.; Gi, K.; Inomoto, M.; Imazawa, R.; Gryaznevich, M.; Scannell, R.; Conway, N. J.; Michael, C.; Crowley, B.; Fitzgerald, I.; Meakins, A.; Hawkes, N.; McClements, K. G.; Harrison, J.; O'Gorman, T.; Cheng, C. Z.; Ono, Y.; The MAST Team

2017-05-01

We present results of recent studies of merging/reconnection heating during central solenoid (CS)-free plasma startup in the Mega Amp Spherical Tokamak (MAST). During this process, ions are heated globally in the downstream region of an outflow jet, and electrons locally around the X-point produced by the magnetic field of two internal P3 coils and of two plasma rings formed around these coils, the final temperature being proportional to the reconnecting field energy. There is an effective confinement of the downstream thermal energy, due to a thick layer of reconnected flux. The characteristic structure is sustained for longer than an ion-electron energy relaxation time, and the energy exchange between ions and electrons contributes to the bulk electron heating in the downstream region. The peak electron temperature around the X-point increases with toroidal field, but the downstream electron and ion temperatures do not change.

Electron energy boosting in laser-wake-field acceleration with external magnetic field Bapprox1 T and laser prepulses

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hosokai, Tomonao; Zhidkov, Alexei; Yamazaki, Atsushi

2010-03-22

Hundred-mega-electron-volt electron beams with quasi-monoenergetic distribution, and a transverse geometrical emittance as small as approx0.02 pi mm mrad are generated by low power (7 TW, 45 fs) laser pulses tightly focused in helium gas jets in an external static magnetic field, Bapprox1 T. Generation of monoenergetic beams strongly correlates with appearance of a straight, at least 2 mm length plasma channel in a short time before the main laser pulse and with the energy of copropagating picosecond pedestal pulses (PPP). For a moderate energy PPP, the multiple or staged electron self-injection in the channel gives several narrow peaks in themore » electron energy distribution.« less

Construction and performance of the sTGC and MicroMegas chambers for ATLAS NSW upgrade

NASA Astrophysics Data System (ADS)

Sekhniaidze, G.

2017-03-01

The innermost stations of the current ATLAS muon end-cap system, the Small Wheels, must be upgraded in 2019 to retain their good precision tracking and trigger capabilities in the high background environment expected with the upcoming luminosity increase of the LHC. The New Small Wheels (NSW) will employ two chamber technologies: eight layers of MicroMegas (MM) arranged in two quadruplets, sandwiched between two quadruplets of small-strip Thin Gap Chambers (sTGC) for a total of about 2400 m2 of detection planes. All quadruplets have trapezoidal shapes with surface areas between 1 and 3 m2. Both MM and sTGC systems will independently provide trigger and tracking capabilities. The readout boards are industrially produced for both technologies and an accurate quality control is needed. In order to achieve a 15% transverse momentum resolution for 1 TeV muons, in addition to an excellent intrinsic resolution (010 μm), the mechanical precision of each plane of the assembled modules must be as good as 30 μm along the precision coordinate and 80 μm perpendicular to the chamber. In 2016 the milestone to build the first module-0 prototypes for both technologies has been reached. The construction procedure of the module-0 detectors will be reviewed, along with the results of the quality control checks performed during construction. The module-0 have been measured and subjected to a thorough validation. Results obtained with high-energy particle beams, with cosmic rays and with X-rays will be presented.

Negative feedback exerted by cAMP-dependent protein kinase and cAMP phosphodiesterase on subsarcolemmal cAMP signals in intact cardiac myocytes: an in vivo study using adenovirus-mediated expression of CNG channels.

PubMed

Rochais, Francesca; Vandecasteele, Grégoire; Lefebvre, Florence; Lugnier, Claire; Lum, Hazel; Mazet, Jean-Luc; Cooper, Dermot M F; Fischmeister, Rodolphe

2004-12-10

Intracardiac cAMP levels are modulated by hormones and neuromediators with specific effects on contractility and metabolism. To understand how the same second messenger conveys different information, mutants of the rat olfactory cyclic nucleotide-gated (CNG) channel alpha-subunit CNGA2, encoded into adenoviruses, were used to monitor cAMP in adult rat ventricular myocytes. CNGA2 was not found in native myocytes but was strongly expressed in infected cells. In whole cell patch-clamp experiments, the forskolin analogue L-858051 (L-85) elicited a non-selective, Mg2+ -sensitive current observed only in infected cells, which was thus identified as the CNG current (ICNG). The beta-adrenergic agonist isoprenaline (ISO) also activated ICNG, although the maximal efficiency was approximately 5 times lower than with L-85. However, ISO and L-85 exerted a similar maximal increase of the L-type Ca2+ current. The use of a CNGA2 mutant with a higher sensitivity for cAMP indicated that this difference is caused by the activation of a localized fraction of CNG channels by ISO. cAMP-dependent protein kinase (PKA) blockade with H89 or PKI, or phosphodiesterase (PDE) inhibition with IBMX, dramatically potentiated ISO- and L-85-stimulated ICNG. A similar potentiation of beta-adrenergic stimulation occurred when PDE4 was blocked, whereas PDE3 inhibition had a smaller effect (by 2-fold). ISO and L-85 increased total PDE3 and PDE4 activities in cardiomyocytes, although this effect was insensitive to H89. However, in the presence of IBMX, H89 had no effect on ISO stimulation of ICNG. This study demonstrates that subsarcolemmal cAMP levels are dynamically regulated by a negative feedback involving PKA stimulation of subsarcolemmal cAMP-PDE.

Solid core dipoles and switching power supplies: Lower cost light sources?

DOE Office of Scientific and Technical Information (OSTI.GOV)

Benesch, Jay; Philip, Sarin

As a result of improvements in power semiconductors, moderate frequency switching supplies can now provide the hundreds of amps typically required by accelerators with zero-to-peak noise in the kHz region ~ 0.06% in current or voltage mode. Modeling was undertaken using a finite electromagnetic program to determine if eddy currents induced in the solid steel of CEBAF magnets and small supplemental additions would bring the error fields down to the 5ppm level needed for beam quality. The expected maximum field of the magnet under consideration is 0.85 T and the DC current required to produce that field is used inmore » the calculations. An additional 0.1% current ripple is added to the DC current at discrete frequencies 360 Hz, 720 Hz or 7200 Hz. Over the region of the pole within 0.5% of the central integrated BdL the resulting AC field changes can be reduced to less than 1% of the 0.1% input ripple for all frequencies, and a sixth of that at 7200 Hz. Doubling the current, providing 1.5 T central field, yielded the same fractional reduction in ripple at the beam for the cases checked. A small dipole was measured at 60, 120, 360 and 720 Hz in two conditions and the results compared to the larger model for the latter two frequencies with surprisingly good agreement. Thus, for light sources with aluminum vacuum vessels and full energy linac injection, the combination of solid core dipoles and switching power supplies may result in significant cost savings.« less

Identification and functional characterization of an uncharacterized antimicrobial peptide from a ciliate Paramecium caudatum.

PubMed

Cui, Pengfei; Dong, Yuan; Li, Zhijian; Zhang, Yubo; Zhang, Shicui

2016-07-01

The global ever-growing concerns about multi-drug resistant (MDR) microbes leads to urgent demands for exploration of new antibiotics including antimicrobial peptides (AMPs). Here we demonstrated that a cDNA from Ciliata Paramecium caudatum, designated Pcamp1, coded for a protein with features characteristic of AMPs, which is not homologous to any AMPs currently known. Both the C-terminal 91 amino acid residues of PcAMP1, cPcAMP1, expressed in Escherichia coli and the C-terminal 26 amino acid residues (predicted mature AMP), cPcAMP1/26, synthesized, underwent a coil-to-helix transition in the presence of TFE, SDS or DPC. Functional assays revealed that cPcAMP1 and cPcAMP1/26 were both able to kill Aeromonas hydrophila and Staphylococcus aureus. ELISA showed that cPcAMP1 and cPcAMP1/26 were able to bind to microbe-associated molecular pattern molecules LPS and LTA, which was further corroborated by the observations that cPcAMP1 could deposit onto the bacterial membranes. Importantly, both cPcAMP1 and cPcAMP1/26 were able to induce bacterial membrane permeabilization and depolarization, and to increase intracellular ROS levels. Additionally, cPcAMP1 and cPcAMP1/26 were not cytotoxic to mammalian cells. Taken together, our results show that PcAMP1 is a potential AMP with a membrane selectivity towards bacterial cells, which renders it a promising template for the design of novel peptide antibiotics against MDR microbes. It also shows that use of signal conserved sequence of AMPs can be an effective tool to identify potential AMPs across different animal classes. Copyright © 2016 Elsevier Ltd. All rights reserved.

Investigation of the LMJ ignition target sensitivity to the laser pulse shape with 2D integrated calculations

NASA Astrophysics Data System (ADS)

Cherfils, Catherine; Malinie, Guy; Boniface, Claude; Gauthier, Pascal; Laffite, Stephane; Loiseau, Pascal

2010-11-01

The A943 cryogenic target in a Rugby hohlraum is our current nominal design for ignition with 160 beams on the Laser MegaJoule (Laffite et al 2007, 49th Annual Meeting of the Division of Plasma Physics, Loiseau et al 2010, 40th Annual Anomalous Absorption Conference). In this study we redesign the laser pulse of the target under the form of a sum of six supergaussians, which is more amenable to a sensitivity study : four supergaussians are used to launch the four main shocks in the capsule, and two additional supergaussians are used first to remove the LEH windows and then to control the acceleration of the first shock, respectively. We use our 2D FCI2 code to compare the radiation hydro of the capsule, obtained with this new pulse, to what was previously obtained. We investigate the sensitivity of the yield on some parameters, which are the maximum powers and respective timings of the different components of the laser pulse.

MEGA-CC: computing core of molecular evolutionary genetics analysis program for automated and iterative data analysis.

PubMed

Kumar, Sudhir; Stecher, Glen; Peterson, Daniel; Tamura, Koichiro

2012-10-15

There is a growing need in the research community to apply the molecular evolutionary genetics analysis (MEGA) software tool for batch processing a large number of datasets and to integrate it into analysis workflows. Therefore, we now make available the computing core of the MEGA software as a stand-alone executable (MEGA-CC), along with an analysis prototyper (MEGA-Proto). MEGA-CC provides users with access to all the computational analyses available through MEGA's graphical user interface version. This includes methods for multiple sequence alignment, substitution model selection, evolutionary distance estimation, phylogeny inference, substitution rate and pattern estimation, tests of natural selection and ancestral sequence inference. Additionally, we have upgraded the source code for phylogenetic analysis using the maximum likelihood methods for parallel execution on multiple processors and cores. Here, we describe MEGA-CC and outline the steps for using MEGA-CC in tandem with MEGA-Proto for iterative and automated data analysis. http://www.megasoftware.net/.

Overview of Advanced Space Propulsion Activities in the Space Environmental Effects Team at MSFC

NASA Technical Reports Server (NTRS)

Edwards, David; Carruth, Ralph; Vaughn, Jason; Schneider, Todd; Kamenetzky, Rachel; Gray, Perry

2000-01-01

Exploration of our solar system, and beyond, requires spacecraft velocities beyond our current technological level. Technologies addressing this limitation are numerous. The Space Environmental Effects (SEE) Team at the Marshall Space Flight Center (MSFC) is focused on three discipline areas of advanced propulsion; Tethers, Beamed Energy, and Plasma. This presentation will give an overview of advanced propulsion related activities in the Space Environmental Effects Team at MSFC. Advancements in the application of tethers for spacecraft propulsion were made while developing the Propulsive Small Expendable Deployer System (ProSEDS). New tether materials were developed to meet the specifications of the ProSEDS mission and new techniques had to be developed to test and characterize these tethers. Plasma contactors were developed, tested and modified to meet new requirements. Follow-on activities in tether propulsion include the Air-SEDS activity. Beamed energy activities initiated with an experimental investigation to quantify the momentum transfer subsequent to high power, 5J, ablative laser interaction with materials. The next step with this experimental investigation is to quantify non-ablative photon momentum transfer. This step was started last year and will be used to characterize the efficiency of solar sail materials before and after exposure to Space Environmental Effects (SEE). Our focus with plasma, for propulsion, concentrates on optimizing energy deposition into a magnetically confined plasma and integration of measurement techniques for determining plasma parameters. Plasma confinement is accomplished with the Marshall Magnetic Mirror (M3) device. Initial energy coupling experiments will consist of injecting a 50 amp electron beam into a target plasma. Measurements of plasma temperature and density will be used to determine the effect of changes in magnetic field structure, beam current, and gas species. Experimental observations will be compared to predictions from computer modeling.

The Design of Operational Amplifier for Low Voltage and Low Current Sound Energy Harvesting System

NASA Astrophysics Data System (ADS)

Fang, Liew Hui; Rahim, Rosemizi Bin Abd; Isa, Muzamir; Idris Syed Hassan, Syed; Ismail, Baharuddin Bin

2018-03-01

The objective of this paper is to design a combination of an operational amplifier (op-amp) with a rectifier used in an alternate current (ac) to direct current (dc) power conversion. The op-amp was designed to specifically work at low voltage and low current for a sound energy harvesting system. The goal of the op-amp design with adjustable gain was to control output voltage based on the objectives of the experiment conducted. The op-amp was designed for minimum power dissipation performance, with the means of increasing the output current when receiving a large amount of load. The harvesting circuits which designed further improved the power output efficiency by shortening the fully charged time needed by a supercapacitor bank. It can fulfil the long-time power demands for low power device. Typically, a small amount of energy sources were converted to electricity and stored in the supercapacitor bank, which was built by 10 pieces of capacitors with 0.22 F each, arranged in parallel connection. The highest capacitance was chosen based on the characteristic that have the longest discharging time to support the applications of a supercapacitor bank. Testing results show that the op-amp can boost the low input ac voltage (∼3.89 V) to high output dc voltage (5.0 V) with output current of 30 mA and stored the electrical energy in a big supercapacitor bank having a total of 2.2 F, effectively. The measured results agree well with the calculated results.

Extragalactic circuits, transmission lines, and CR particle acceleration

NASA Astrophysics Data System (ADS)

Kronberg, Philipp P.; Lovelace, Richard V. E.

2015-08-01

A non-negligible fraction of a Supermassive Black Hole's (SMBH) rest mass energy gets transported into extragalactic space by a remarkable process in jets which are incompletely understood. What are the physical processes which transport this energy? It is likely that the energy flows electromagnetically, rather than via a particle beam flux. The deduced electromagnetic fields may produce particles of energy as high as ˜ 1020 eV. The energetics of SMBH accretion disk models and the electromagnetic energy transfer imply that a SMBH should generate a 1018 - 1019 Ampères current close to the black hole and its accretion disk. We describe the so far best observation-based estimate of the magnitude of the current flow along the axis of the jet extending from the nucleus of the active galaxy in 3C303. The current is measured to be I ˜ 1018 Ampères at ˜ 40 kpc away from the AGN. This indicates that organised current flow remains intact over multi-kpc distances. The electric current I transports electromagnetic power into free space, P = I2Z, where Z ˜ 30 Ohms is related to the impedance of free space, and this points to the existence of cosmic electric circuit. The associated electric potential drop, V = IZ, is of the order of that required to generate Ultra High Energy Cosmic Rays (UHECR). We also explore further implications, including disruption/deflection of the power flow and also why such measurements, exemplified by those on 3C303, are currently very difficult to make and to unambiguously interpret. This naturally leads to the topic of how such measurements can be extended and improved in the future. We describe the analogy of electromagnetically dominated jets with transmission lines. High powered jets in vacuo can be understood by approximate analogy with a waveguide. The importance of inductance, impedance, and other laboratory electrical concepts are discussed in this context.

Temperate and boreal forest mega-fires: characteristics and challenges

Treesearch

Scott L. Stephens; Neil Burrows; Alexander Buyantuyev; Robert W. Gray; Robert E. Keane; Rick Kubian; Shirong Liu; Francisco Seijo; Lifu Shu; Kevin G. Tolhurst; Jan W. van Wagtendonk

2014-01-01

Mega-fires are often defined according to their size and intensity but are more accurately described by their socioeconomic impacts. Three factors - climate change, fire exclusion, and antecedent disturbance, collectively referred to as the "mega-fire triangle" - likely contribute to today's mega-fires. Some characteristics of mega-fires may emulate...

Cyclic AMP efflux inhibitors as potential therapeutic agents for leukemia.

PubMed

Perez, Dominique R; Smagley, Yelena; Garcia, Matthew; Carter, Mark B; Evangelisti, Annette; Matlawska-Wasowska, Ksenia; Winter, Stuart S; Sklar, Larry A; Chigaev, Alexandre

2016-06-07

Apoptotic evasion is a hallmark of cancer. We propose that some cancers may evade cell death by regulating 3'-5'-cyclic adenosine monophosphate (cAMP), which is associated with pro-apoptotic signaling. We hypothesize that leukemic cells possess mechanisms that efflux cAMP from the cytoplasm, thus protecting them from apoptosis. Accordingly, cAMP efflux inhibition should result in: cAMP accumulation, activation of cAMP-dependent downstream signaling, viability loss, and apoptosis. We developed a novel assay to assess cAMP efflux and performed screens to identify inhibitors. In an acute myeloid leukemia (AML) model, several identified compounds reduced cAMP efflux, appropriately modulated pathways that are responsive to cAMP elevation (cAMP-responsive element-binding protein phosphorylation, and deactivation of Very Late Antigen-4 integrin), and induced mitochondrial depolarization and caspase activation. Blocking adenylyl cyclase activity was sufficient to reduce effects of the most potent compounds. These compounds also decreased cAMP efflux and viability of B-lineage acute lymphoblastic leukemia (B-ALL) cell lines and primary patient samples, but not of normal primary peripheral blood mononuclear cells. Our data suggest that cAMP efflux is a functional feature that could be therapeutically targeted in leukemia. Furthermore, because some of the identified drugs are currently used for treating other illnesses, this work creates an opportunity for repurposing.

Coexpression of alpha and beta subunits of the rod cyclic GMP-gated channel restores native sensitivity to cyclic AMP: role of D604/N1201.

PubMed Central

Pagès, F; Ildefonse, M; Ragno, M; Crouzy, S; Bennett, N

2000-01-01

Coexpression of the betawt and alphawt subunits of the bovine rod channel restores two characteristics of the native channels: higher sensitivity to cAMP and potentiation of cGMP-induced currents by low cAMP concentrations. To test whether the increased sensitivity to cAMP is due to the uncharged nature of the asparagine residue (N1201) situated in place of aspartate D604 in the beta subunit as previously suggested (, Neuron. 15:619-625), we compared currents from wild-type (alphawt and alphawt/betawt) and from mutated channels (alphaD604N, alphaD604N/betawt, and alphawt/betaN1201D). The results show that the sensitivity to cAMP and cAMP potentiation is partly but not entirely determined by the charge of residue 1201 in the beta subunit. The D604N mutation in the alpha subunit and, to a lesser extent, coexpression of the betawt subunit with the alphawt subunit reduce the open probability for cGMP compared to that of the alphawt channel. Interpretation of the data with the MWC allosteric model (model of Monod, Wyman, Changeux;, J. Mol. Biol. 12:88-118) suggests that the D604N mutation in the alpha subunits and coassembly of alpha and beta subunits alter the free energy of gating by cAMP more than that of cAMP binding. PMID:10692312

Increase in the neutron yield from a dense plasma-focus experiment performed with a conical tip placed in the centre of the anode end

NASA Astrophysics Data System (ADS)

Kubes, P.; Paduch, M.; Cikhardt, J.; Cikhardtova, B.; Klir, D.; Kravarik, J.; Rezac, K.; Zielinska, E.; Sadowski, M. J.; Szymaszek, A.; Tomaszewski, K.; Zaloga, D.

2017-09-01

The paper describes the evolution of self-organized structures inside a pinched plasma column during the phase of the effective production of fusion neutrons, as observed in the mega-ampere plasma focus experiment performed with a conical tip placed in the centre of the anode face. In a comparison with the plane anode face configuration, the described anode shape facilitated transformations in the pinch column during the neutron production and increased the neutron yield several times. Simultaneously, it decreased the minimal diameter and the length of the pinched column, and it depressed the first neutron pulse. It also induced shorter pulses of X-rays and neutrons, which enabled the determination of a temporal difference between the emission of electron and deuteron beams. The fast electrons were produced mainly during a disruption of the pinch constriction, while the fast deuterons - during the formation and explosion of plasmoids. The paper also presents the temporal evolution of a current distribution in the plasmoid during the neutron production, as well as the appearance and stable positions of current filaments traces upon the surface of the conical anode tip.

DOE Office of Scientific and Technical Information (OSTI.GOV)

H.Zhang, P. Titus, P. Rogoff, A.Zolfaghari, D. Mangra, M. Smith

The National Spherical Torus Experiment (NSTX) is a low aspect ratio, spherical torus (ST) configuration device which is located at Princeton Plasma Physics Laboratory (PPPL) This device is presently being updated to enhance its physics by doubling the TF field to 1 Tesla and increasing the plasma current to 2 Mega-amperes. The upgrades include a replacement of the centerstack and addition of a second neutral beam. The upgrade analyses have two missions. The first is to support design of new components, principally the centerstack, the second is to qualify existing NSTX components for higher loads, which will increase by amore » factor of four. Cost efficiency was a design goal for new equipment qualification, and reanalysis of the existing components. Showing that older components can sustain the increased loads has been a challenging effort in which designs had to be developed that would limit loading on weaker components, and would minimize the extent of modifications needed. Two areas representing this effort have been chosen to describe in more details: analysis of the current distribution in the new TF inner legs, and, second, analysis of the out-of-plane support of the existing TF outer legs.« less

Measuring Polycentricity of Mega-City Regions in China Based on the Intercity Migration Flows

NASA Astrophysics Data System (ADS)

Mu, Xiaoyan; Yeh, Anthony G. O.

2016-06-01

This paper uses the intercity migration flows to examine relations between Chinese cities, identify the important mega-city regions and measure each region's polycentricity from an interaction perspective. Data set contains the long-term residential migration trajectories of three million Sina weibo users across 345 cities. Cities with close connectivity deployed around one or several mega cities are identified as mega-city regions. Features of the mega-city regions are characterized by the strength of migration flows, density of connections, and regional migration patterns. The results show that the disparities exist in different mega-city regions; most mega-city regions are lack of polycentricity.

DOE Office of Scientific and Technical Information (OSTI.GOV)

McNally, J.J.

The effects on the properties of Ta/sub 2/O/sub 5/, Al/sub 2/O/sub 3/, SiO/sub 2/ and HfO/sub 2/ single- and multi-layer optical coatings deposited using ion-assisted deposition (IAD) were investigated. IAD is a novel deposition technique which utilizes a separate ion source to direct a beam of ions at the growing film. A Kaufman ion source was used to provide a monoenergetic, neutralized beam of oxygen ions independent of the material evaporation process. The optical and physical properties, as well as laser induced damage threshold (LIDT) values, were studied for coatings bombarded with 200, 300, 500 and 1000 eV oxygen ionsmore » at values of current density from 0 to 200 microAmp/sq cm. IAD was successfully applied to deposit coatings at low temperature on heavy metal fluoride (HMF) glass substrates. The coatings deposited using IAD were hard and dense. The IAD coatings improved the durability and abrasion resistance of the HMF glass substrates. The results of this investigation show that IAD can be used to improve the optical and physical properties of optical coatings.« less

Antimicrobial Peptides: A Promising Therapeutic Strategy in Tackling Antimicrobial Resistance.

PubMed

Nuti, Ramya; Goud, Nerella S; Saraswati, A Prasanth; Alvala, Ravi; Alvala, Mallika

2017-01-01

Antimicrobial resistance (AMR) has posed a serious threat to global public health and it requires immediate action, preferably long term. Current drug therapies have failed to curb this menace due to the ability of microbes to circumvent the mechanisms through which the drugs act. From the drug discovery point of view, the majority of drugs currently employed for antimicrobial therapy are small molecules. Recent trends reveal a surge in the use of peptides as drug candidates as they offer remarkable advantages over small molecules. Newer synthetic strategies like organometalic complexes, Peptide-polymer conjugates, solid phase, liquid phase and recombinant DNA technology encouraging the use of peptides as therapeutic agents with a host of chemical functions, and tailored for specific applications. In the last decade, many peptide based drugs have been successfully approved by the Food and Drug Administration (FDA). This success can be attributed to their high specificity, selectivity and efficacy, high penetrability into the tissues, less immunogenicity and less tissue accumulation. Considering the enormity of AMR, the use of Antimicrobial Peptides (AMPs) can be a viable alternative to current therapeutics strategies. AMPs are naturally abundant allowing synthetic chemists to develop semi-synthetics peptide molecules. AMPs have a broad spectrum of activity towards microbes and they possess the ability to bypass the resistance induction mechanisms of microbes. The present review focuses on the potential applications of AMPs against various microbial disorders and their future prospects. Several resistance mechanisms and their strategies have also been discussed to highlight the importance in the current scenario. Breakthroughs in AMP designing, peptide synthesis and biotechnology have shown promise in tackling this challenge and has revived the interest of using AMPs as an important weapon in fighting AMR. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Enrichment of cardiac pacemaker-like cells: neuregulin-1 and cyclic AMP increase I(f)-current density and connexin 40 mRNA levels in fetal cardiomyocytes.

PubMed

Ruhparwar, Arjang; Er, Fikret; Martin, Ulrich; Radke, Kristin; Gruh, Ina; Niehaus, Michael; Karck, Matthias; Haverich, Axel; Hoppe, Uta C

2007-02-01

Generation of a large number of cells belonging to the cardiac pacemaker system would constitute an important step towards their utilization as a biological cardiac pacemaker system. The aim of the present study was to identify factors, which might induce transformation of a heterogenous population of fetal cardiomyocytes into cells with a pacemaker-like phenotype. Neuregulin-1 (alpha- and beta-isoform) or the cAMP was added to fresh cell cultures of murine embryonic cardiomyocytes. Quantitative northern blot analysis and flowcytometry were performed to detect the expression of connexins 40, 43 and 45. Patch clamp recordings in the whole cell configuration were performed to determine current density of I (f), a characteristic ion current of pacemaker cells. Fetal cardiomyocytes without supplement of neuregulin or cAMP served as control group. Neuregulin and cAMP significantly increased mRNA levels of connexin 40 (Cx-40), a marker of the early differentiating conduction system in mice. On the protein level, flowcytometry revealed no significant differences between treated and untreated groups with regard to the expression of connexins 40, 43 and 45. Treatment with cAMP (11.2 +/- 2.24 pA/pF; P < 0.001) and neuregulin-1-beta (6.23 +/- 1.07 pA/pF; P < 0.001) significantly increased the pacemaker current density compared to control cardiomyocytes (1.76 +/- 0.49 pA/pF). Our results indicate that neuregulin-1 and cAMP possess the capacity to cause significant transformation of a mixed population of fetal cardiomyocytes into cardiac pacemaker-like cells as shown by electrophysiology and increase of Cx-40 mRNA. This method may allow the development of a biological cardiac pacemaker system when applied to adult or embryonic stem cells.

(Sn)DICE: A Calibration System Designed for Wide Field Imagers

NASA Astrophysics Data System (ADS)

Regnault, N.; Barrelet, E.; Guyonnet, A.; Juramy, C.; Rocci, P.-F.; Le Guillou, L.; Schahmanèche, K.; Villa, F.

2016-05-01

Dark Energy studies with type Ia supernovae set very tight constraints on the photometric calibration of the imagers used to detect the supernovae and follow up their flux variations. Among the key challenges is the measurement of the shape and normalization of the instrumental throughput. The DICE system was developed by members of the Supernova Legacy Survey (SNLS) , building upon the lessons learnt working with the MegaCam imager. It consists in a very stable light source, placed in the telescope enclosure, and generating compact, conical beams, yielding an almost flat illumination of the imager focal plane. The calibration light is generated by narrow spectrum LEDs selected to cover the entire wavelength range of the imager. It is monitored in real time using control photodiodes. A first DICE demonstrator, SnDICE has been installed at CFHT. A second generation instrument (SkyDICE) has been installed in the enclosure of the SkyMapper telescope. We present the main goals of the project. We discuss the main difficulties encoutered when trying to calibrate a wide field imager, such as MegaCam (or SkyMapper) using such a calibrated light source.

The Laser Mega-Joule : LMJ & PETAL status and Program Overview

NASA Astrophysics Data System (ADS)

Miquel, J.-L.; Lion, C.; Vivini, P.

2016-03-01

The laser Megajoule (LMJ), developed by the French Commissariat à l'Energie Atomique et aux Energies Alternatives (CEA), will be a cornerstone of the French Simulation Program, which combines improvement of physics models, high performance numerical simulation, and experimental validation. The LMJ facility is under construction at CEA CESTA near Bordeaux and will provide the experimental capabilities to study High-Energy Density Physics (HEDP). One of its goals is to obtain ignition and burn of DT-filled capsules imploded, through indirect drive scheme, inside rugby-shape hohlraum. The PETAL project consists in the addition of one short-pulse (ps) ultra-high-power, high-energy beam (kJ) to the LMJ facility. PETAL will offer a combination of a very high intensity multi-petawatt beam, synchronized with the nanosecond beams of the LMJ. This combination will expand the LMJ experimental field on HEDP. This paper presents an update of LMJ & PETAL status, together with the development of the overall program including targets, plasma diagnostics and simulation tools.

On the frequency-magnitude distribution of converging boundaries

NASA Astrophysics Data System (ADS)

Marzocchi, W.; Laura, S.; Heuret, A.; Funiciello, F.

2011-12-01

The occurrence of the last mega-thrust earthquake in Japan has clearly remarked the high risk posed to society by such events in terms of social and economic losses even at large spatial scale. The primary component for a balanced and objective mitigation of the impact of these earthquakes is the correct forecast of where such kind of events may occur in the future. To date, there is a wide range of opinions about where mega-thrust earthquakes can occur. Here, we aim at presenting some detailed statistical analysis of a database of worldwide interplate earthquakes occurring at current subduction zones. The database has been recently published in the framework of the EURYI Project 'Convergent margins and seismogenesis: defining the risk of great earthquakes by using statistical data and modelling', and it provides a unique opportunity to explore in detail the seismogenic process in subducting lithosphere. In particular, the statistical analysis of this database allows us to explore many interesting scientific issues such as the existence of different frequency-magnitude distributions across the trenches, the quantitative characterization of subduction zones that are able to produce more likely mega-thrust earthquakes, the prominent features that characterize converging boundaries with different seismic activity and so on. Besides the scientific importance, such issues may lead to improve our mega-thrust earthquake forecasting capability.

The Church Mountain Sturzstrom (Mega-Landslide), Glacier, Washington

DOE Office of Scientific and Technical Information (OSTI.GOV)

Carpenter, M.R.; Easterbrook, D.J.

1993-04-01

Detailed investigation of an ancient sturzstrom or mega-landslide near Glacier, Washington has revealed it areal extent, approximate volume, age, geomorphology, source area, and possible causes. Stratigraphic and lithologic investigations indicate Church Mountain as the source area; therefore, this mega-landslide has been named the Church Mountain Sturzstrom (CMS). The CMS deposit is approximately 9 km in length, averages about 1 km in width, and has an estimated volume of 3 [times] 10[sup 8] m[sup 3]. Characteristics of the morphology and stratigraphy of the CMS deposit are suggestive of a sturzstrom origin, and may be indicative of sturzstrom elsewhere in the world.more » The overall stratigraphy of the deposit mimics the stratigraphy of the source area. The deposit is very compact, poorly sorted, matrix supported, and composed of highly angular clasts. Over steepening of the mountain due to glacial erosion may have contributed to the cause of failure, although the age of the CMS is at least 7,000 years younger than deglaciation. Four trees were C[sup 14] dated, yielding ages of about 2,700 B.P. for the CMS. Several other mega-landslides have been identified within 5--30 km of the CMS. The close proximity of these mega-landslides to the CMS suggests the possibility that they may have been triggered by an earthquake, although the ages of the other slides are currently unknown. The age of the CMS correlates approximately with age ranges of co-seismic events occurring along the west coast of Washington, further suggesting the possibility of an earthquake triggering mechanism.« less

West African monsoon dynamics inferred from abrupt fluctuations of Lake Mega-Chad

PubMed Central

Armitage, Simon J.; Bristow, Charlie S.; Drake, Nick A.

2015-01-01

From the deglacial period to the mid-Holocene, North Africa was characterized by much wetter conditions than today. The broad timing of this period, termed the African Humid Period, is well known. However, the rapidity of the onset and termination of the African Humid Period are contested, with strong evidence for both abrupt and gradual change. We use optically stimulated luminescence dating of dunes, shorelines, and fluviolacustrine deposits to reconstruct the fluctuations of Lake Mega-Chad, which was the largest pluvial lake in Africa. Humid conditions first occur at ∼15 ka, and by 11.5 ka, Lake Mega-Chad had reached a highstand, which persisted until 5.0 ka. Lake levels fell rapidly at ∼5 ka, indicating abrupt aridification across the entire Lake Mega-Chad Basin. This record provides strong terrestrial evidence that the African Humid Period ended abruptly, supporting the hypothesis that the African monsoon responds to insolation forcing in a markedly nonlinear manner. In addition, Lake Mega-Chad exerts strong control on global biogeochemical cycles because the northern (Bodélé) basin is currently the world’s greatest single dust source and possibly an important source of limiting nutrients for both the Amazon Basin and equatorial Atlantic. However, we demonstrate that the final desiccation of the Bodélé Basin occurred around 1 ka. Consequently, the present-day mode and scale of dust production from the Bodélé Basin cannot have occurred before 1 ka, suggesting that its role in fertilizing marine and terrestrial ecosystems is either overstated or geologically recent. PMID:26124133

Expression profiles of antimicrobial peptides (AMPs) and their regulation by Relish

NASA Astrophysics Data System (ADS)

Wang, Dongdong; Li, Fuhua; Li, Shihao; Wen, Rong; Xiang, Jianhai

2012-07-01

Antimicrobial peptides (AMPs), as key immune effectors, play important roles in the innate immune system of invertebrates. Different types of AMPs, including Penaeidin, Crustin, ALF (antilipopolysaccharide factor) have been identified in different penaeid shrimp; however, systematic analyses on the function of different AMPs in shrimp responsive to different types of bacteria are very limited. In this study, we analyzed the expression profiles of AMPs in the Chinese shrimps, Fenneropenaeus chinensis, simultaneously by real-time RT-PCR (reverse transcription-polymerase chain reaction) when shrimp were challenged with Micrococcus lysodeikticus (Gram-positive, G+) or Vibrio anguillarium (Gram-negative, G-). Different AMPs showed different expression profiles when shrimp were injected with one type of bacterium, and one AMP also showed different expression profiles when shrimp were challenged with different bacteria. Furthermore, the expression of these AMPs showed temporal expression profiles, suggesting that different AMPs function coordinately in bacteria-infected shrimp. An RNA interference approach was used to study the function of the Relish transcription factor in regulating the transcription of different AMPs. The current study showed that Relish could regulate the transcription of different AMPs in shrimp. Differential expression profiles of AMPs in shrimp injected with different types of bacteria indicated that a complicated antimicrobial response network existed in shrimp. These data contribute to our understanding of immunity in shrimp and may provide a strategy for the control of disease in shrimp.

Beam dynamics studies of a 30 MeV RF linac for neutron production

NASA Astrophysics Data System (ADS)

Nayak, B.; Krishnagopal, S.; Acharya, S.

2018-02-01

Design of a 30 MeV, 10 Amp RF linac as neutron source has been carried out by means of ASTRA simulation code. Here we discuss details of design simulations for three different cases i.e Thermionic , DC and RF photocathode guns and compare them as injectors to a 30 MeV RF linac for n-ToF production. A detailed study on choice of input parameters of the beam from point of view of transmission efficiency and beam quality at the output have been described. We found that thermionic gun isn't suitable for this application. Both DC and RF photocathode gun can be used. RF photocathode gun would be of better performance.

MEGA X: Molecular Evolutionary Genetics Analysis across Computing Platforms.

PubMed

Kumar, Sudhir; Stecher, Glen; Li, Michael; Knyaz, Christina; Tamura, Koichiro

2018-06-01

The Molecular Evolutionary Genetics Analysis (Mega) software implements many analytical methods and tools for phylogenomics and phylomedicine. Here, we report a transformation of Mega to enable cross-platform use on Microsoft Windows and Linux operating systems. Mega X does not require virtualization or emulation software and provides a uniform user experience across platforms. Mega X has additionally been upgraded to use multiple computing cores for many molecular evolutionary analyses. Mega X is available in two interfaces (graphical and command line) and can be downloaded from www.megasoftware.net free of charge.

Large scale ab initio modeling of structurally uncharacterized antimicrobial peptides reveals known and novel folds.

PubMed

Kozic, Mara; Fox, Stephen J; Thomas, Jens M; Verma, Chandra S; Rigden, Daniel J

2018-05-01

Antimicrobial resistance within a wide range of infectious agents is a severe and growing public health threat. Antimicrobial peptides (AMPs) are among the leading alternatives to current antibiotics, exhibiting broad spectrum activity. Their activity is determined by numerous properties such as cationic charge, amphipathicity, size, and amino acid composition. Currently, only around 10% of known AMP sequences have experimentally solved structures. To improve our understanding of the AMP structural universe we have carried out large scale ab initio 3D modeling of structurally uncharacterized AMPs that revealed similarities between predicted folds of the modeled sequences and structures of characterized AMPs. Two of the peptides whose models matched known folds are Lebocin Peptide 1A (LP1A) and Odorranain M, predicted to form β-hairpins but, interestingly, to lack the intramolecular disulfide bonds, cation-π or aromatic interactions that generally stabilize such AMP structures. Other examples include Ponericin Q42, Latarcin 4a, Kassinatuerin 1, Ceratotoxin D, and CPF-B1 peptide, which have α-helical folds, as well as mixed αβ folds of human Histatin 2 peptide and Garvicin A which are, to the best of our knowledge, the first linear αββ fold AMPs lacking intramolecular disulfide bonds. In addition to fold matches to experimentally derived structures, unique folds were also obtained, namely for Microcin M and Ipomicin. These results help in understanding the range of protein scaffolds that naturally bear antimicrobial activity and may facilitate protein design efforts towards better AMPs. © 2018 The Authors Proteins: Structure, Function, and Bioinformatics Published by Wiley Periodicals, Inc.

Glutamate quantification by PRESS or MEGA-PRESS: Validation, repeatability, and concordance.

PubMed

van Veenendaal, Tamar M; Backes, Walter H; van Bussel, Frank C G; Edden, Richard A E; Puts, Nicolaas A J; Aldenkamp, Albert P; Jansen, Jacobus F A

2018-05-01

While PRESS is often employed to measure glutamate concentrations, MEGA-PRESS enables simultaneous Glx (glutamate and glutamine) and GABA measurements. This study aimed to compare validation, repeatability, and concordance of different approaches for glutamate quantification at 3T to aid future studies in their selection of the appropriate sequence and quantification method. Nine phantoms with different glutamate and glutamine concentrations and five healthy participants were scanned twice to assess respectively the validation and repeatability of measurements with PRESS and MEGA-PRESS. To assess concordance between the different methods, results from 95 human participants were compared. PRESS, MEGA-PRESS (i.e. difference), and the MEGA-PRESS OFF spectra were analyzed with both LCModel and Gannet. In vitro, excellent agreement was shown between actual and measured glutamate concentrations for all measurements (r>0.98). In vivo CVs were better for PRESS (2.9%) than MEGA-PRESS (4.9%) and MEGA-PRESS OFF (4.2%). However, the concordance between the sequences was low (PRESS and MEGA-PRESS OFF, r=0.3) to modest (MEGA-PRESS versus MEGA-PRESS OFF, r=0.8). Both PRESS and MEGA-PRESS can be employed to measure in vivo glutamate concentrations, although PRESS shows a better repeatability. Comparisons between in vivo glutamate measures of different sequences however need to be interpreted cautiously. Copyright © 2018 Elsevier Inc. All rights reserved.

AMP Is an Adenosine A1 Receptor Agonist*

PubMed Central

Rittiner, Joseph E.; Korboukh, Ilia; Hull-Ryde, Emily A.; Jin, Jian; Janzen, William P.; Frye, Stephen V.; Zylka, Mark J.

2012-01-01

Numerous receptors for ATP, ADP, and adenosine exist; however, it is currently unknown whether a receptor for the related nucleotide adenosine 5′-monophosphate (AMP) exists. Using a novel cell-based assay to visualize adenosine receptor activation in real time, we found that AMP and a non-hydrolyzable AMP analog (deoxyadenosine 5′-monophosphonate, ACP) directly activated the adenosine A1 receptor (A1R). In contrast, AMP only activated the adenosine A2B receptor (A2BR) after hydrolysis to adenosine by ecto-5′-nucleotidase (NT5E, CD73) or prostatic acid phosphatase (PAP, ACPP). Adenosine and AMP were equipotent human A1R agonists in our real-time assay and in a cAMP accumulation assay. ACP also depressed cAMP levels in mouse cortical neurons through activation of endogenous A1R. Non-selective purinergic receptor antagonists (pyridoxalphosphate-6-azophenyl-2′,4′-disulfonic acid and suramin) did not block adenosine- or AMP-evoked activation. Moreover, mutation of His-251 in the human A1R ligand binding pocket reduced AMP potency without affecting adenosine potency. In contrast, mutation of a different binding pocket residue (His-278) eliminated responses to AMP and to adenosine. Taken together, our study indicates that the physiologically relevant nucleotide AMP is a full agonist of A1R. In addition, our study suggests that some of the physiological effects of AMP may be direct, and not indirect through ectonucleotidases that hydrolyze this nucleotide to adenosine. PMID:22215671

AMP is an adenosine A1 receptor agonist.

PubMed

Rittiner, Joseph E; Korboukh, Ilia; Hull-Ryde, Emily A; Jin, Jian; Janzen, William P; Frye, Stephen V; Zylka, Mark J

2012-02-17

Numerous receptors for ATP, ADP, and adenosine exist; however, it is currently unknown whether a receptor for the related nucleotide adenosine 5'-monophosphate (AMP) exists. Using a novel cell-based assay to visualize adenosine receptor activation in real time, we found that AMP and a non-hydrolyzable AMP analog (deoxyadenosine 5'-monophosphonate, ACP) directly activated the adenosine A(1) receptor (A(1)R). In contrast, AMP only activated the adenosine A(2B) receptor (A(2B)R) after hydrolysis to adenosine by ecto-5'-nucleotidase (NT5E, CD73) or prostatic acid phosphatase (PAP, ACPP). Adenosine and AMP were equipotent human A(1)R agonists in our real-time assay and in a cAMP accumulation assay. ACP also depressed cAMP levels in mouse cortical neurons through activation of endogenous A(1)R. Non-selective purinergic receptor antagonists (pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid and suramin) did not block adenosine- or AMP-evoked activation. Moreover, mutation of His-251 in the human A(1)R ligand binding pocket reduced AMP potency without affecting adenosine potency. In contrast, mutation of a different binding pocket residue (His-278) eliminated responses to AMP and to adenosine. Taken together, our study indicates that the physiologically relevant nucleotide AMP is a full agonist of A(1)R. In addition, our study suggests that some of the physiological effects of AMP may be direct, and not indirect through ectonucleotidases that hydrolyze this nucleotide to adenosine.

Net field-aligned currents observed by Triad

NASA Technical Reports Server (NTRS)

Sugiura, M.; Potemra, T. A.

1975-01-01

From the Triad magnetometer observation of a step-like level shift in the east-west component of the magnetic field at 800 km altitude, the existence of a net current flowing into or away from the ionosphere in a current layer was inferred. The current direction is toward the ionosphere on the morning side and away from it on the afternoon side. The field aligned currents observed by Triad are considered as being an important element in the electro-dynamical coupling between the distant magnetosphere and the ionosphere. The current density integrated over the thickness of the layer increases with increasing magnetic activity, but the relation between the current density and Kp in individual cases is not a simple linear relation. An extrapolation of the statistical relation to Kp = 0 indicates existence of a sheet current of order 0.1 amp/m even at extremely quiet times. During periods of higher magnetic activity an integrated current of approximately 1 amp/m and average current density of order 0.000001 amp/sq m are observed. The location and the latitudinal width of the field aligned current layer carrying the net current very roughly agree with those of the region of high electron intensities in the trapping boundary.

Temperate and boreal forest mega-fires: characteristics and challenges

USGS Publications Warehouse

Stephens, Scott L.; Burrows, Neil; Buyantuyev, Alexander; Gray, Robert W.; Keane, Robert E.; Kubian, Rick; Liu, Shirong; Seijo, Francisco; Shu, Lifu; Tolhurst, Kevin G.; Van Wagtendonk, Jan W.

2014-01-01

Mega-fires are often defined according to their size and intensity but are more accurately described by their socioeconomic impacts. Three factors – climate change, fire exclusion, and antecedent disturbance, collectively referred to as the “mega-fire triangle” – likely contribute to today's mega-fires. Some characteristics of mega-fires may emulate historical fire regimes and can therefore sustain healthy fire-prone ecosystems, but other attributes decrease ecosystem resiliency. A good example of a program that seeks to mitigate mega-fires is located in Western Australia, where prescribed burning reduces wildfire intensity while conserving ecosystems. Crown-fire-adapted ecosystems are likely at higher risk of frequent mega-fires as a result of climate change, as compared with other ecosystems once subject to frequent less severe fires. Fire and forest managers should recognize that mega-fires will be a part of future wildland fire regimes and should develop strategies to reduce their undesired impacts.

Antimicrobial peptides: Possible anti-infective agents.

PubMed

Lakshmaiah Narayana, Jayaram; Chen, Jyh-Yih

2015-10-01

Multidrug-resistant bacterial, fungal, viral, and parasitic infections are major health threats. The Infectious Diseases Society of America has expressed concern on the decrease of pharmaceutical companies working on antibiotic research and development. However, small companies, along with academic research institutes, are stepping forward to develop novel therapeutic methods to overcome the present healthcare situation. Among the leading alternatives to current drugs are antimicrobial peptides (AMPs), which are abundantly distributed in nature. AMPs exhibit broad-spectrum activity against a wide variety of bacteria, fungi, viruses, and parasites, and even cancerous cells. They also show potential immunomodulatory properties, and are highly responsive to infectious agents and innate immuno-stimulatory molecules. In recent years, many AMPs have undergone or are undergoing clinical development, and a few are commercially available for topical and other applications. In this review, we outline selected anion and cationic AMPs which are at various stages of development, from preliminary analysis to clinical drug development. Moreover, we also consider current production methods and delivery tools for AMPs, which must be improved for the effective use of these agents. Copyright © 2015 Elsevier Inc. All rights reserved.

Particle damage sources for fused silica optics and their mitigation on high energy laser systems.

PubMed

Bude, J; Carr, C W; Miller, P E; Parham, T; Whitman, P; Monticelli, M; Raman, R; Cross, D; Welday, B; Ravizza, F; Suratwala, T; Davis, J; Fischer, M; Hawley, R; Lee, H; Matthews, M; Norton, M; Nostrand, M; VanBlarcom, D; Sommer, S

2017-05-15

High energy laser systems are ultimately limited by laser-induced damage to their critical components. This is especially true of damage to critical fused silica optics, which grows rapidly upon exposure to additional laser pulses. Much progress has been made in eliminating damage precursors in as-processed fused silica optics (the advanced mitigation process, AMP3), and very high damage resistance has been demonstrated in laboratory studies. However, the full potential of these improvements has not yet been realized in actual laser systems. In this work, we explore the importance of additional damage sources-in particular, particle contamination-for fused silica optics fielded in a high-performance laser environment, the National Ignition Facility (NIF) laser system. We demonstrate that the most dangerous sources of particle contamination in a system-level environment are laser-driven particle sources. In the specific case of the NIF laser, we have identified the two important particle sources which account for nearly all the damage observed on AMP3 optics during full laser operation and present mitigations for these particle sources. Finally, with the elimination of these laser-driven particle sources, we demonstrate essentially damage free operation of AMP3 fused silica for ten large optics (a total of 12,000 cm 2 of beam area) for shots from 8.6 J/cm 2 to 9.5 J/cm 2 of 351 nm light (3 ns Gaussian pulse shapes). Potentially many other pulsed high energy laser systems have similar particle sources, and given the insight provided by this study, their identification and elimination should be possible. The mitigations demonstrated here are currently being employed for all large UV silica optics on the National Ignition Facility.

Cystic Fibrosis Gene Encodes a cAMP-Dependent Chloride Channel in Heart

NASA Astrophysics Data System (ADS)

Hart, Padraig; Warth, John D.; Levesque, Paul C.; Collier, Mei Lin; Geary, Yvonne; Horowitz, Burton; Hume, Joseph R.

1996-06-01

cAMP-dependent chloride channels in heart contribute to autonomic regulation of action potential duration and membrane potential and have been inferred to be due to cardiac expression of the epithelial cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel. In this report, a cDNA from rabbit ventricle was isolated and sequenced, which encodes an exon 5 splice variant (exon 5-) of CFTR, with >90% identity to human CFTR cDNA present in epithelial cells. Expression of this cDNA in Xenopus oocytes gave rise to robust cAMP-activated chloride currents that were absent in control water-injected oocytes. Antisense oligodeoxynucleotides directed against CFTR significnatly reduced the density of cAMP-dependent chloride currents in acutely cultured myocytes, thereby establishing a direct functional link between cardiac expression of CFTR protein and an endogenous chloride channel in native cardiac myocytes.

The National Ignition Facility Project: An Update

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hogan, W.J.; Moses, E.; Warner, B.

2000-12-07

The National Ignition Facility (NIT) consists of 192 forty-centimeter-square laser beams and a 10-m-diameter target chamber. Physical construction began in 1997. The Laser and Target Area Building and the Optics Assembly Building were the first major construction activities, and despite several unforeseen obstacles, the buildings are now 92% complete and have been done on time and within cost. Prototype component development and testing has proceeded in parallel. Optics vendors have installed full-scale production lines and have done prototype production runs. The assembly and integration of the beam path infrastructure has been reconsidered and a new approach has been developed. Thismore » paper will discuss the status of the NIF project and the plans for completion. It will also include summary information on Laser MegaJoule (LMJ) provided by M. Andre, LMJ Project Director.« less

cAMP signalling in the vasculature: the role of Epac (exchange protein directly activated by cAMP).

PubMed

Roberts, Owain Llŷr; Dart, Caroline

2014-02-01

The second messenger cAMP plays a central role in mediating vascular smooth muscle relaxation in response to vasoactive transmitters and in strengthening endothelial cell-cell junctions that regulate the movement of solutes, cells and macromolecules between the blood and the surrounding tissue. The vasculature expresses three cAMP effector proteins: PKA (protein kinase A), CNG (cyclic-nucleotide-gated) ion channels, and the most recently discovered Epacs (exchange proteins directly activated by cAMP). Epacs are a family of GEFs (guanine-nucleotide-exchange factors) for the small Ras-related GTPases Rap1 and Rap2, and are being increasingly implicated as important mediators of cAMP signalling, both in their own right and in parallel with the prototypical cAMP target PKA. In the present paper, we review what is currently known about the role of Epac within blood vessels, particularly with regard to the regulation of vascular tone, endothelial barrier function and inflammation.

MEGA: the next generation Medium Energy Gamma-ray Telescope

NASA Astrophysics Data System (ADS)

Ryan, James M.; Andritschke, Robert; Bloser, Peter F.; Cravens, James P.; Cherry, Michael L.; Di Cocco, Guido; Guzik, T. G.; Hartmann, Dieter H.; Hunter, Stanley H.; Kanbach, Gottfried; Kippen, R. M.; Kurfess, James; Macri, John R.; McConnell, Mark L.; Miller, Richard S.; Paciesas, William S.; Phlips, Bernard; Reglero, Victor; Stacy, J. G.; Strickman, Mark; Vestrand, W. Thomas; Wefel, John P.; Wulf, Eric; Zoglauer, Andreas; Zych, Allen D.

2004-10-01

The MEGA mission would enable a sensitive all-sky survey of the medium-energy ?-ray sky (0.3-50 MeV). This mission will bridge the huge sensitivity gap between the COMPTEL and OSSE experiments on the Compton Gamma Ray Observatory, the SPI and IBIS instruments on INTEGRAL and the visionary ACT mission. It will, among other things, serve to compile a much larger catalog of sources in this energy range, perform far deeper searches for supernovae, better measure the galactic continuum emission as well as identify the components of the cosmic diffuse emission. The large field of view will allow MEGA to continuously monitor the sky for transient and variable sources. It will accomplish these goals with a stack of Si-strip detector (SSD) planes surrounded by a dense high-Z calorimeter. At lower photon energies (below ~30 MeV), the design is sensitive to Compton interactions, with the SSD system serving as a scattering medium that also detects and measures the Compton recoil energy deposit. If the energy of the recoil electron is sufficiently high (> 2 MeV), the track of the recoil electron can also be defined. At higher photon energies (above ~10 MeV), the design is sensitive to pair production events, with the SSD system measuring the tracks of the electron and positron. We will discuss the various types of event signatures in detail and describe the advantages of this design over previous Compton telescope designs. Effective area, sensitivity and resolving power estimates are also presented along with simulations of expected scientific results and beam calibration results from the prototype instrument.

Bifurcated helical core equilibrium states in tokamaks

NASA Astrophysics Data System (ADS)

Cooper, W. A.; Chapman, I. T.; Schmitz, O.; Turnbull, A. D.; Tobias, B. J.; Lazarus, E. A.; Turco, F.; Lanctot, M. J.; Evans, T. E.; Graves, J. P.; Brunetti, D.; Pfefferlé, D.; Reimerdes, H.; Sauter, O.; Halpern, F. D.; Tran, T. M.; Coda, S.; Duval, B. P.; Labit, B.; Pochelon, A.; Turnyanskiy, M. R.; Lao, L.; Luce, T. C.; Buttery, R.; Ferron, J. R.; Hollmann, E. M.; Petty, C. C.; van Zeeland, M.; Fenstermacher, M. E.; Hanson, J. M.; Lütjens, H.

2013-07-01

Tokamaks with weak to moderate reversed central shear in which the minimum inverse rotational transform (safety factor) qmin is in the neighbourhood of unity can trigger bifurcated magnetohydrodynamic equilibrium states, one of which is similar to a saturated ideal internal kink mode. Peaked prescribed pressure profiles reproduce the ‘snake’ structures observed in many tokamaks which has led to a novel explanation of the snake as a bifurcated equilibrium state. Snake equilibrium structures are computed in simulations of the tokamak à configuration variable (TCV), DIII-D and mega amp spherical torus (MAST) tokamaks. The internal helical deformations only weakly modulate the plasma-vacuum interface which is more sensitive to ripple and resonant magnetic perturbations. On the other hand, the external perturbations do not alter the helical core deformation in a significant manner. The confinement of fast particles in MAST simulations deteriorate with the amplitude of the helical core distortion. These three-dimensional bifurcated solutions constitute a paradigm shift that motivates the applications of tools developed for stellarator research in tokamak physics investigations.

Distinct profiling of antimicrobial peptide families

PubMed Central

Khamis, Abdullah M.; Essack, Magbubah; Gao, Xin; Bajic, Vladimir B.

2015-01-01

Motivation: The increased prevalence of multi-drug resistant (MDR) pathogens heightens the need to design new antimicrobial agents. Antimicrobial peptides (AMPs) exhibit broad-spectrum potent activity against MDR pathogens and kills rapidly, thus giving rise to AMPs being recognized as a potential substitute for conventional antibiotics. Designing new AMPs using current in-silico approaches is, however, challenging due to the absence of suitable models, large number of design parameters, testing cycles, production time and cost. To date, AMPs have merely been categorized into families according to their primary sequences, structures and functions. The ability to computationally determine the properties that discriminate AMP families from each other could help in exploring the key characteristics of these families and facilitate the in-silico design of synthetic AMPs. Results: Here we studied 14 AMP families and sub-families. We selected a specific description of AMP amino acid sequence and identified compositional and physicochemical properties of amino acids that accurately distinguish each AMP family from all other AMPs with an average sensitivity, specificity and precision of 92.88%, 99.86% and 95.96%, respectively. Many of our identified discriminative properties have been shown to be compositional or functional characteristics of the corresponding AMP family in literature. We suggest that these properties could serve as guides for in-silico methods in design of novel synthetic AMPs. The methodology we developed is generic and has a potential to be applied for characterization of any protein family. Contact: vladimir.bajic@kaust.edu.sa Supplementary information: Supplementary data are available at Bioinformatics online. PMID:25388148

Design of a 100 MW X-band klystron

NASA Astrophysics Data System (ADS)

Eppley, Kenneth

1989-02-01

Future linear colliders will require klystrons with higher peak power at higher frequency than are currently in use. SLAC is currently designing a 100 MW klystron at 11.4 GHz as a prototype for such a tube. The gun has been designed for 440 kV and 510 amps. Transporting this beam through a 5 mm radius X-band drift tube presents the major design problem. The area convergence ratio of 190 to one is over ten times higher than is found in conventional klystrons. Even with high magnetic fields of 6 to 7 kilogauss careful matching is required to prevent excessive scalloping. Extensive EGUN and CONDOR simulations have been made to optimize the transmission and RF efficiency. The EGUN simulations indicate that better matching is possible by using resonant magnetic focusing. CONDOR calculations indicate efficiencies of 45 percent are possible with a double output cavity. We will discuss the results of the simulations and the status of the experimental program.

Antimicrobial Peptides: An Emerging Category of Therapeutic Agents.

PubMed

Mahlapuu, Margit; Håkansson, Joakim; Ringstad, Lovisa; Björn, Camilla

2016-01-01

Antimicrobial peptides (AMPs), also known as host defense peptides, are short and generally positively charged peptides found in a wide variety of life forms from microorganisms to humans. Most AMPs have the ability to kill microbial pathogens directly, whereas others act indirectly by modulating the host defense systems. Against a background of rapidly increasing resistance development to conventional antibiotics all over the world, efforts to bring AMPs into clinical use are accelerating. Several AMPs are currently being evaluated in clinical trials as novel anti-infectives, but also as new pharmacological agents to modulate the immune response, promote wound healing, and prevent post-surgical adhesions. In this review, we provide an overview of the biological role, classification, and mode of action of AMPs, discuss the opportunities and challenges to develop these peptides for clinical applications, and review the innovative formulation strategies for application of AMPs.

Modafinil inhibits K(Ca)3.1 currents and muscle contraction via a cAMP-dependent mechanism.

PubMed

Choi, Shinkyu; Kim, Moon Young; Joo, Ka Young; Park, Seonghee; Kim, Ji Aee; Jung, Jae-Chul; Oh, Seikwan; Suh, Suk Hyo

2012-07-01

Modafinil has been used as a psychostimulant for the treatment of narcolepsy. However, its primary mechanism of action remains elusive. Therefore, we examined the effects of modafinil on K(Ca)3.1 channels and vascular smooth muscle contraction. K(Ca)3.1 currents and channel activity were measured using a voltage-clamp technique and inside-out patches in mouse embryonic fibroblast cell line, NIH-3T3 fibroblasts. Intracellular adenosine 3',5'-cyclic monophosphate (cAMP) concentration was measured, and the phosphorylation of K(Ca)3.1 channel protein was examined using western blotting in NIH-3T3 fibroblasts and/or primary cultured mouse aortic smooth muscle cells (SMCs). Muscle contractions were recorded from mouse aorta and rat pulmonary artery by using a myograph developed in-house. Modafinil was found to inhibit K(Ca)3.1 currents in a concentration-dependent manner, and the half-maximal inhibition (IC(50)) of modafinil for the current inhibition was 6.8 ± 0.7 nM. The protein kinase A (PKA) activator forskolin also inhibited K(Ca)3.1 currents. The inhibitory effects of modafinil and forskolin on K(Ca)3.1 currents were blocked by the PKA inhibitors PKI(14-22) or H-89. In addition, modafinil relaxed blood vessels (mouse aorta and rat pulmonary artery) in a concentration-dependent manner. Modafinil increased cAMP concentrations in NIH-3T3 fibroblasts or primary cultured mouse aortic SMCs and phosphorylated K(Ca)3.1 channel protein in NIH-3T3 fibroblasts. However, open probability and single-channel current amplitudes of K(Ca)3.1 channels were not changed by modafinil. From these results, we conclude that modafinil inhibits K(Ca)3.1 channels and vascular smooth muscle contraction by cAMP-dependent phosphorylation, suggesting that modafinil can be used as a cAMP-dependent K(Ca)3.1 channel blocker and vasodilator. Copyright © 2012 Elsevier Ltd. All rights reserved.

Defensins: antifungal lessons from eukaryotes

PubMed Central

Silva, Patrícia M.; Gonçalves, Sónia; Santos, Nuno C.

2014-01-01

Over the last years, antimicrobial peptides (AMPs) have been the focus of intense research toward the finding of a viable alternative to current antifungal drugs. Defensins are one of the major families of AMPs and the most represented among all eukaryotic groups, providing an important first line of host defense against pathogenic microorganisms. Several of these cysteine-stabilized peptides present a relevant effect against fungi. Defensins are the AMPs with the broader distribution across all eukaryotic kingdoms, namely, Fungi, Plantae, and Animalia, and were recently shown to have an ancestor in a bacterial organism. As a part of the host defense, defensins act as an important vehicle of information between innate and adaptive immune system and have a role in immunomodulation. This multidimensionality represents a powerful host shield, hard for microorganisms to overcome using single approach resistance strategies. Pathogenic fungi resistance to conventional antimycotic drugs is becoming a major problem. Defensins, as other AMPs, have shown to be an effective alternative to the current antimycotic therapies, demonstrating potential as novel therapeutic agents or drug leads. In this review, we summarize the current knowledge on some eukaryotic defensins with antifungal action. An overview of the main targets in the fungal cell and the mechanism of action of these AMPs (namely, the selectivity for some fungal membrane components) are presented. Additionally, recent works on antifungal defensins structure, activity, and cytotoxicity are also reviewed. PMID:24688483

Bypass Diode Temperature Tests of a Solar Array Coupon Under Space Thermal Environment Conditions

NASA Technical Reports Server (NTRS)

Wright, Kenneth H., Jr.; Schneider, Todd A.; Vaughn, Jason A.; Hoang, Bao; Wong, Frankie; Wu, Gordon

2016-01-01

Tests were performed on a 56-cell Advanced Triple Junction solar array coupon whose purpose was to determine margin available for bypass diodes integrated with new, large multi-junction solar cells that are manufactured from a 4-inch wafer. The tests were performed under high vacuum with coupon back side thermal conditions of both cold and ambient. The bypass diodes were subjected to a sequence of increasing discrete current steps from 0 Amp to 2.0 Amp in steps of 0.25 Amp. At each current step, a temperature measurement was obtained via remote viewing by an infrared camera. This paper discusses the experimental methodology, experiment results, and the thermal model.

By-Pass Diode Temperature Tests of a Solar Array Coupon Under Space Thermal Environment Conditions

NASA Technical Reports Server (NTRS)

Wright, Kenneth H., Jr.; Schneider, Todd A.; Vaughn, Jason A.; Hoang, Bao; Wong, Frankie

2016-01-01

Tests were performed on a 56-cell Advanced Triple Junction solar array coupon whose purpose was to determine margin available for bypass diodes integrated with new, large multi-junction solar cells that are manufactured from a 4-inch wafer. The tests were performed under high vacuum with cold and ambient coupon back-side. The bypass diodes were subjected to a sequence of increasing discrete current steps from 0 Amp to 2.0 Amp in steps of 0.25 Amp. At each current step, a temperature measurement was obtained via remote viewing by an infrared camera. This paper discusses the experimental methodology, including the calibration of the thermal imaging system, and the results.

Determination of neutral beam injection accelerator grid deformation using beam emission measurements

NASA Astrophysics Data System (ADS)

Nightingale, M. P. S.; Kugel, H.; Gee, S. J.; Price, M. N.

1999-01-01

Theoretical modeling of 1-2 MW positive hydrogen ion neutral injectors developed at Oak Ridge National Laboratory (ORNL) has suggested that the plasma grid temperature could rise by up to 180 °C at pulse lengths above 0.5 s, leading to a grid deformation on the order of 5 mm, with a consequent change in focal length (from 4 to 2 m) and beamlet focusing. One of these injectors (on loan from ORNL) was used to achieve record β values on the Small Tight Aspect Ratio Tokamak at Culham, and two more are to be used on the Mega-Ampere Spherical Tokamak (MAST) at pulse lengths of up to 5 s. Since the grid modeling has never been tested experimentally, a method for diagnosing changes in beam transport as a function of pulse length using light emitted by the beam is now under development at Culham to see if grid modifications are required for MAST. Initial experimental results, carried out using a 50 A 30 keV hydrogen beam, are presented (including comparison with thermocouple data using an EK98 graphite beam stop). These confirm that emission measurement should allow the accelerator focal length and beamlet divergence to be determined to accuracies of better than ±0.45 m and ±0.2°, respectively (compared to nominal values of 4 m and 1.2°).

It may be possible to use Microscopic Black Holes as a Propulsion Beam

NASA Astrophysics Data System (ADS)

Kriske, Richard

2017-04-01

Several years ago during the commissioning of the LHC, the question as to whether a miniature Black Hole would be formed, and what to do with it if it was, came up as a legitimate topic of discussion. It was calculated at that time that although it was possible, the possibility was extremely small, and it would evaporate quickly, and would be safely ejected into space, as its mass would be so great as to simply continue along its inertial path, out the end of the circular LHC accelerator. New improvements to the LHC are the increase in energy to about 15 TEV. Linear accelerators, such as the ILC, claim to be able to produce much higher TEV, as they collide electrons and positrons, as opposed to Protons, as does the LHC. This author has heard incredible numbers, such as 250 TEV, with a beam current of 1 Amp. With this incredible increase in Energy and Current, one could turn the Black Hole investigation around, and try to determine how one could produce a steady stream of Microscopic Black Holes. A Black Hole machine. When the Black Holes evaporate do they expand, space in space time. Would the old theory of expanding space behind a craft warp space, and enable the craft to exceed the speed of light. The warp theory was proposed before Star Trek, is it now feasible to prove?

A Rapid Phenotypic Whole Cell Screening Approach for the Identification of Small Molecule Inhibitors that Counter Beta-lactamase Resistance in Pseudomonas aeruginosa

PubMed Central

Collia, Deanna; Bannister, Thomas D.; Tan, Hao; Jin, Shouguang; Langaee, Taimour; Shumate, Justin; Scampavia, Louis; Spicer, Timothy P.

2017-01-01

Pseudomonas aeruginosa is an opportunistic human pathogen which is prevalent in hospitals and continues to develop resistance to multiple classes of antibiotics. Historically, β-lactam antibiotics have been the first line of therapeutic defense. However, the emergence of multidrug-resistant (MDR) strains of P. aeruginosa, such as AmpC β-lactamase overproducing mutants, limits the effectiveness of current antibiotics. Among AmpC hyper producing clinical isolates, inactivation of AmpG, which is essential for the expression of AmpC, increases bacterial sensitivity to β-lactam antibiotics. We hypothesize that inhibition of AmpG activity will enhance the efficacy of β-lactams against P. aeruginosa. Here, using a highly drug resistant AmpC inducible laboratory strain PAO1, we describe an ultra-high throughput whole cell turbidity assay designed to identify small molecule inhibitors of the AmpG. We screened 645K compounds to identify compounds with the ability to inhibit bacterial growth in the presence of Cefoxitin; an AmpC inducer, and identified 2,663 inhibitors which were also tested in the absence of Cefoxitin to determine AmpG specificity. The Z′ and S:B were robust at 0.87 ± 0.05 and 2.2 ± 0.2, respectively. Through a series of secondary and tertiary studies, including a novel luciferase based counterscreen, we ultimately identified 8 potential AmpG specific inhibitors. PMID:28850797

A Rapid Phenotypic Whole-Cell Screening Approach for the Identification of Small-Molecule Inhibitors That Counter β-Lactamase Resistance in Pseudomonas aeruginosa.

PubMed

Collia, Deanna; Bannister, Thomas D; Tan, Hao; Jin, Shouguang; Langaee, Taimour; Shumate, Justin; Scampavia, Louis; Spicer, Timothy P

2018-01-01

Pseudomonas aeruginosa is an opportunistic human pathogen that is prevalent in hospitals and continues to develop resistance to multiple classes of antibiotics. Historically, β-lactam antibiotics have been the first line of therapeutic defense. However, the emergence of multidrug-resistant (MDR) strains of P. aeruginosa, such as AmpC β-lactamase overproducing mutants, limits the effectiveness of current antibiotics. Among AmpC hyperproducing clinical isolates, inactivation of AmpG, which is essential for the expression of AmpC, increases bacterial sensitivity to β-lactam antibiotics. We hypothesize that inhibition of AmpG activity will enhance the efficacy of β-lactams against P. aeruginosa. Here, using a highly drug-resistant AmpC-inducible laboratory strain PAO1, we describe an ultra-high-throughput whole-cell turbidity assay designed to identify small-molecule inhibitors of the AmpG. We screened 645,000 compounds to identify compounds with the ability to inhibit bacterial growth in the presence of cefoxitin, an AmpC inducer, and identified 2663 inhibitors that were also tested in the absence of cefoxitin to determine AmpG specificity. The Z' and signal-to-background ratio were robust at 0.87 ± 0.05 and 2.2 ± 0.2, respectively. Through a series of secondary and tertiary studies, including a novel luciferase-based counterscreen, we ultimately identified eight potential AmpG-specific inhibitors.

A hollow cathode neutralizer for a 30-cm diameter bombardment thruster

NASA Technical Reports Server (NTRS)

Bechtel, R. T.

1973-01-01

Recent improvements in overall thrustor performance have imposed new constraints on neutralizer performance. The use of compensated grid extraction system requires a re-evaluation of neutralizer position. In addition a suitable control logic for the neutralizer has proven difficult. A series of tests were conducted to determine what effect neutralizer cathode geometry has on performance. The parameters investigated included orifice diameter and length, and cathode diameter. Similar tests investigated open and enclosed keeper geometries. Neutralizer position tests with compensated grids suggest positions approximately 10 cm from the accelerator and radially out of the beam envelope should result in satisfactory performance and long life. Finally operation at keeper currents of 1.5 amp has resulted in lower total neutralizer power, the elimination of tip heater power, and suitable closed loop control of the neutralizer vaporizer.

Membrane Active Antimicrobial Peptides: Translating Mechanistic Insights to Design

PubMed Central

Li, Jianguo; Koh, Jun-Jie; Liu, Shouping; Lakshminarayanan, Rajamani; Verma, Chandra S.; Beuerman, Roger W.

2017-01-01

Antimicrobial peptides (AMPs) are promising next generation antibiotics that hold great potential for combating bacterial resistance. AMPs can be both bacteriostatic and bactericidal, induce rapid killing and display a lower propensity to develop resistance than do conventional antibiotics. Despite significant progress in the past 30 years, no peptide antibiotic has reached the clinic yet. Poor understanding of the action mechanisms and lack of rational design principles have been the two major obstacles that have slowed progress. Technological developments are now enabling multidisciplinary approaches including molecular dynamics simulations combined with biophysics and microbiology toward providing valuable insights into the interactions of AMPs with membranes at atomic level. This has led to increasingly robust models of the mechanisms of action of AMPs and has begun to contribute meaningfully toward the discovery of new AMPs. This review discusses the detailed action mechanisms that have been put forward, with detailed atomistic insights into how the AMPs interact with bacterial membranes. The review further discusses how this knowledge is exploited toward developing design principles for novel AMPs. Finally, the current status, associated challenges, and future directions for the development of AMP therapeutics are discussed. PMID:28261050

Diversity, evolution and medical applications of insect antimicrobial peptides

PubMed Central

Mylonakis, Eleftherios; Podsiadlowski, Lars; Muhammed, Maged

2016-01-01

Antimicrobial peptides (AMPs) are short proteins with antimicrobial activity. A large portion of known AMPs originate from insects, and the number and diversity of these molecules in different species varies considerably. Insect AMPs represent a potential source of alternative antibiotics to address the limitation of current antibiotics, which has been caused by the emergence and spread of multidrug-resistant pathogens. To get more insight into AMPs, we investigated the diversity and evolution of insect AMPs by mapping their phylogenetic distribution, allowing us to predict the evolutionary origins of selected AMP families and to identify evolutionarily conserved and taxon-specific families. Furthermore, we highlight the use of the nematode Caenorhabditis elegans as a whole-animal model in high-throughput screening methods to identify AMPs with efficacy against human pathogens, including Acinetobacter baumanii and methicillin-resistant Staphylococcus aureus. We also discuss the potential medical applications of AMPs, including their use as alternatives for conventional antibiotics in ectopic therapies, their combined use with antibiotics to restore the susceptibility of multidrug-resistant pathogens, and their use as templates for the rational design of peptidomimetic drugs that overcome the disadvantages of therapeutic peptides. The article is part of the themed issue ‘Evolutionary ecology of arthropod antimicrobial peptides’. PMID:27160593

Antimicrobial Activity of Cationic Antimicrobial Peptides against Gram-Positives: Current Progress Made in Understanding the Mode of Action and the Response of Bacteria.

PubMed

Omardien, Soraya; Brul, Stanley; Zaat, Sebastian A J

2016-01-01

Antimicrobial peptides (AMPs) have been proposed as a novel class of antimicrobials that could aid the fight against antibiotic resistant bacteria. The mode of action of AMPs as acting on the bacterial cytoplasmic membrane has often been presented as an enigma and there are doubts whether the membrane is the sole target of AMPs. Progress has been made in clarifying the possible targets of these peptides, which is reported in this review with as focus gram-positive vegetative cells and spores. Numerical estimates are discussed to evaluate the possibility that targets, other than the membrane, could play a role in susceptibility to AMPs. Concerns about possible resistance that bacteria might develop to AMPs are addressed. Proteomics, transcriptomics, and other molecular techniques are reviewed in the context of explaining the response of bacteria to the presence of AMPs and to predict what resistance strategies might be. Emergent mechanisms are cell envelope stress responses as well as enzymes able to degrade and/or specifically bind (and thus inactivate) AMPs. Further studies are needed to address the broadness of the AMP resistance and stress responses observed.

Antimicrobial Activity of Cationic Antimicrobial Peptides against Gram-Positives: Current Progress Made in Understanding the Mode of Action and the Response of Bacteria

PubMed Central

Omardien, Soraya; Brul, Stanley; Zaat, Sebastian A. J.

2016-01-01

Antimicrobial peptides (AMPs) have been proposed as a novel class of antimicrobials that could aid the fight against antibiotic resistant bacteria. The mode of action of AMPs as acting on the bacterial cytoplasmic membrane has often been presented as an enigma and there are doubts whether the membrane is the sole target of AMPs. Progress has been made in clarifying the possible targets of these peptides, which is reported in this review with as focus gram-positive vegetative cells and spores. Numerical estimates are discussed to evaluate the possibility that targets, other than the membrane, could play a role in susceptibility to AMPs. Concerns about possible resistance that bacteria might develop to AMPs are addressed. Proteomics, transcriptomics, and other molecular techniques are reviewed in the context of explaining the response of bacteria to the presence of AMPs and to predict what resistance strategies might be. Emergent mechanisms are cell envelope stress responses as well as enzymes able to degrade and/or specifically bind (and thus inactivate) AMPs. Further studies are needed to address the broadness of the AMP resistance and stress responses observed. PMID:27790614

SiO and CH3OH mega-masers in NGC 1068

PubMed Central

Wang, Junzhi; Zhang, Jiangshui; Gao, Yu; Zhang, Zhi-Yu; Li, Di; Fang, Min; Shi, Yong

2014-01-01

Maser is an acronym for microwave amplification by stimulated emission of radiation; in astronomy mega-masers are masers in galaxies that are ≥106 times more luminous than typical galactic maser sources. Observational studies of mega-masers can help us to understand their origins and characteristics. More importantly, mega-masers can be used as diagnostic tracers to probe the physical properties of their parent galaxies. Since the late 1970s, only three types of molecules have been found to form mega-masers: H2O, OH and H2CO. Here we report the detection of both SiO and CH3OH mega-masers near the centre of Seyfert 2 galaxy NGC 1068 at millimetre wavelengths, obtained using the IRAM 30-m telescope. We argue that the SiO mega-maser originated from the nuclear disk and the CH3OH mega-maser originated from shock fronts. High-resolution observations in the future will enable us to investigate AGN feedback and determine the masses of central supermassive black holes in such galaxies. PMID:25386834

UDCM Operating Procedure (Limited Functionality prototype)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Newell, Matthew R.

2016-06-14

The UDCM is a two channel low current measurement device designed to record sub-nano-amp to micro-amp currents from radiation detectors. The UDCM incorporates a Commercial-Off-The- Shelf (COTS) processor enabling both serial over USB as well as Ethernet communications. The instrument includes microSD and USB flash memory for data storage as well as a programmable High Voltage (HV) power supply for detector bias. The UDCM incorporates a unique TTL output feature first used in the LANL Current to Pulse Converter (CPC). Two SMA connectors on the UDCM provide TTL pulses at a frequency proportional to the input currents.

Image storage in radiation oncology: What did we learn from diagnostic radiology?

NASA Astrophysics Data System (ADS)

Blodgett, Kurt; Luick, Marc; Colonias, Athanasios; Gayou, Olivier; Karlovits, Stephen; Werts, E. Day

2009-02-01

The Digital Imaging and Communications in Medicine (DICOM) standard was developed by the National Electrical Manufacturers Association (NEMA) and the American College of Radiology (ACR) for medical image archiving and retrieval. An extension to this implemented a standard named DICOM-RT for use in Radiation Oncology. There are currently seven radiotherapy-specific DICOM objects which include: RT Structure Set, RT Plan, RT Dose, RT Image, RT Beams Treatment Record, RT Brachy Treatment Record, and RT Treatment Summary Record. The type of data associated with DICOM-RT includes (1) Radiation treatment planning datasets (CT, MRI, PET) with radiation treatment plans showing beam arrangements, isodose distributions, and dose volume histograms of targets/normal tissues and (2) Image-guided radiation modalities such as Siemens MVision mega-voltage cone beam CT (MV-CBCT). With the advent of such advancing technologies, there has been an exponential increase in image data collected for each patient, and the need for reliable and accessible image storage has become critical. A potential solution is a Radiation Oncology specific picture archiving and communication systems (PACS) that would allow data storage from multiple vendor devices and support the storage and retrieval needs not only of a single site but of a large, multi-facility network of radiation oncology clinics. This PACS system must be reliable, expandable, and cost-effective to operate while protecting sensitive patient image information in a Health Insurance Portability and Accountability Act (HIPAA) compliant environment. This paper emphasizes the expanding DICOM-RT storage requirements across our network of 8 radiation oncology clinics and the initiatives we undertook to address the increased volume of data by using the ImageGrid (CANDELiS Inc, Irvine CA) server and the IGViewer license (CANDELiS Inc, Irvine CA) to create a DICOM-RT compatible PACS system.

Spatiotemporal regulation of cAMP signaling controls the human trophoblast fusion

PubMed Central

Gerbaud, Pascale; Taskén, Kjetil; Pidoux, Guillaume

2015-01-01

During human placentation, mononuclear cytotrophoblasts fuse to form multinucleated syncytia ensuring hormonal production and nutrient exchanges between the maternal and fetal circulation. Syncytial formation is essential for the maintenance of pregnancy and for fetal growth. The cAMP signaling pathway is the major route to trigger trophoblast fusion and its activation results in phosphorylation of specific intracellular target proteins, in transcription of fusogenic genes and assembly of macromolecular protein complexes constituting the fusogenic machinery at the plasma membrane. Specificity in cAMP signaling is ensured by generation of localized pools of cAMP controlled by cAMP phosphodiesterases (PDEs) and by discrete spatial and temporal activation of protein kinase A (PKA) in supramolecular signaling clusters inside the cell organized by A-kinase-anchoring proteins (AKAPs) and by organization of signal termination by protein phosphatases (PPs). Here we present original observations on the available components of the cAMP signaling pathway in the human placenta including PKA, PDE, and PP isoforms as well as AKAPs. We continue to discuss the current knowledge of the spatiotemporal regulation of cAMP signaling triggering trophoblast fusion. PMID:26441659

Femtosecond mega-electron-volt electron microdiffraction

DOE PAGES

Shen, X.; Li, R. K.; Lundstrom, U.; ...

2017-09-01

To understand and control the basic functions of physical, chemical and biological processes from micron to nano-meter scale, an instrument capable of visualizing transient structural changes of inhomogeneous materials with atomic spatial and temporal resolutions, is required. One such technique is femtosecond electron microdiffraction, in which a short electron pulse with femtosecond-scale duration is focused into a micron-scale spot and used to obtain diffraction images to resolve ultrafast structural dynamics over a localized crystalline domain. In this letter, we report the experimental demonstration of time-resolved mega-electron-volt electron microdiffraction which achieves a 5 μm root-mean-square (rms) beam size on the samplemore » and a 110 fs rms temporal resolution. Using pulses of 10k electrons at 4.2 MeV energy with a normalized emittance 3 nm-rad, we obtained high quality diffraction from a single 10 μm paraffin ( C 44 H 90) crystal. The phonon softening mode in optical-pumped polycrystalline Bi was also time-resolved, demonstrating the temporal resolution limits of the instrument. In conclusion, this new characterization capability will open many research opportunities in material and biological sciences.« less

Femtosecond mega-electron-volt electron microdiffraction

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shen, X.; Li, R. K.; Lundstrom, U.

To understand and control the basic functions of physical, chemical and biological processes from micron to nano-meter scale, an instrument capable of visualizing transient structural changes of inhomogeneous materials with atomic spatial and temporal resolutions, is required. One such technique is femtosecond electron microdiffraction, in which a short electron pulse with femtosecond-scale duration is focused into a micron-scale spot and used to obtain diffraction images to resolve ultrafast structural dynamics over a localized crystalline domain. In this letter, we report the experimental demonstration of time-resolved mega-electron-volt electron microdiffraction which achieves a 5 μm root-mean-square (rms) beam size on the samplemore » and a 110 fs rms temporal resolution. Using pulses of 10k electrons at 4.2 MeV energy with a normalized emittance 3 nm-rad, we obtained high quality diffraction from a single 10 μm paraffin ( C 44 H 90) crystal. The phonon softening mode in optical-pumped polycrystalline Bi was also time-resolved, demonstrating the temporal resolution limits of the instrument. In conclusion, this new characterization capability will open many research opportunities in material and biological sciences.« less

Characterisation of mega-voltage electron pencil beam dose distributions: viability of a measurement-based approach.

PubMed

Barnes, M P; Ebert, M A

2008-03-01

The concept of electron pencil-beam dose distributions is central to pencil-beam algorithms used in electron beam radiotherapy treatment planning. The Hogstrom algorithm, which is a common algorithm for electron treatment planning, models large electron field dose distributions by the superposition of a series of pencil beam dose distributions. This means that the accurate characterisation of an electron pencil beam is essential for the accuracy of the dose algorithm. The aim of this study was to evaluate a measurement based approach for obtaining electron pencil-beam dose distributions. The primary incentive for the study was the accurate calculation of dose distributions for narrow fields as traditional electron algorithms are generally inaccurate for such geometries. Kodak X-Omat radiographic film was used in a solid water phantom to measure the dose distribution of circular 12 MeV beams from a Varian 21EX linear accelerator. Measurements were made for beams of diameter, 1.5, 2, 4, 8, 16 and 32 mm. A blocked-field technique was used to subtract photon contamination in the beam. The "error function" derived from Fermi-Eyges Multiple Coulomb Scattering (MCS) theory for corresponding square fields was used to fit resulting dose distributions so that extrapolation down to a pencil beam distribution could be made. The Monte Carlo codes, BEAM and EGSnrc were used to simulate the experimental arrangement. The 8 mm beam dose distribution was also measured with TLD-100 microcubes. Agreement between film, TLD and Monte Carlo simulation results were found to be consistent with the spatial resolution used. The study has shown that it is possible to extrapolate narrow electron beam dose distributions down to a pencil beam dose distribution using the error function. However, due to experimental uncertainties and measurement difficulties, Monte Carlo is recommended as the method of choice for characterising electron pencil-beam dose distributions.

Atmosphere, Magnetosphere and Plasmas in Space (AMPS). Spacelab payload definition study. Volume 7, book 3: Supporting Research and Technology (SR and T) report

NASA Technical Reports Server (NTRS)

1976-01-01

The items identified as required to support the AMPS mission and requiring SR and T support and further work are: (1) a general purpose Experiment Pointing Mount; (2) a technique for measuring the attitude of the pallet-mounted or deployed experiments; (3) the development of a common optics cryogenically cooled interferometer spectrometer; (4) the development of a differential absorption lidar system for the measurement of ozone densitites in the earth's atmosphere; (5) the development of dc to dc power processors which are capable of converting energy stored in a capacitor system at 500 V to energy supplied to equipment operating at 40 kV and at 20 kW (eventually up to 100 kW); and (6) the development of a magnetic or possibly electrostatic deflection system capable of bending the beam of an electron accelerator. A data sheet is included for each item, briefly describing the background and need for each item, and the general objectives of the required development, and identifying the schedule requirements in support of the AMPS program.

GABA editing with macromolecule suppression using an improved MEGA-SPECIAL sequence.

PubMed

Gu, Meng; Hurd, Ralph; Noeske, Ralph; Baltusis, Laima; Hancock, Roeland; Sacchet, Matthew D; Gotlib, Ian H; Chin, Frederick T; Spielman, Daniel M

2018-01-01

The most common γ-aminobutyric-acid (GABA) editing approach, MEGA-PRESS, uses J-editing to measure GABA distinct from larger overlapping metabolites, but suffers contamination from coedited macromolecules (MMs) comprising 40 to 60% of the observed signal. MEGA-SPECIAL is an alternative method with better MM suppression, but is not widely used primarily because of its relatively poor spatial localization. Our goal was to develop an improved MM-suppressed GABA editing sequence at 3 Tesla. We modified a single-voxel MEGA-SPECIAL sequence with an oscillating readout gradient for improved spatial localization, and used very selective 30-ms editing pulses for improved suppression of coedited MMs. Simulation and in vivo experiments confirmed excellent MM suppression, insensitive to the range of B 0 frequency drifts typically encountered in vivo. Both intersubject and intrasubject studies showed that MMs, when suppressed by the improved MEGA-SPECIAL method, contributed approximately 40% to the corresponding MEGA-PRESS measurements. From the intersubject study, the coefficient of variation for GABA+/Cre (MEGA-PRESS) was 11.2% versus 7% for GABA/Cre (improved MEGA-SPECIAL), demonstrating significantly reduced variance (P = 0.005), likely coming from coedited MMs. This improved MEGA-SPECIAL sequence provides unbiased GABA measurements with reduced variance as compared with conventional MEGA-PRESS. This approach is also relatively insensitive to the range of B 0 drifts typically observed in in vivo human studies. Magn Reson Med 79:41-47, 2018. © 2017 International Society for Magnetic Resonance in Medicine. © 2017 International Society for Magnetic Resonance in Medicine.

Different impacts of mega-ENSO and conventional ENSO on the Indian summer rainfall: developing phase

NASA Astrophysics Data System (ADS)

Zhang, Lei; Wu, Zhiwei; Zhou, Yefan

2016-04-01

Mega-El Niño-Southern Oscillation (ENSO), a boarder version of conventional ENSO, is found to be a main driving force of Northern Hemisphere summer monsoon rainfall including the Indian summer rainfall (ISR). The simultaneous impacts of "pure" mega-ENSO and "pure" conventional ENSO events on the ISR in its developing summer remains unclear. This study examines the different linkages between mega-ENSO-ISR and conventional ENSO-ISR. During the developing summer of mega-El Niño, negative rainfall anomalies are seen over the northeastern Indian subcontinent, while the anomalous rainfall pattern is almost the opposite for mega-La Niña; as for the conventional ENSO, the approximate "linear opposite" phenomenon vanishes. Furthermore, the global zonal wave trains anomalous are found at mid-latitude zones, with a local triple circulation pattern over the central-east Eurasia during mega-ENSO events, which might be an explanation of corresponding rainfall response over the Indian Peninsula. Among 106-year historical run (1900-2005) of 9 state-of-the-art models from the Coupled Model Inter-comparison Project Phase 5 (CMIP5), HadGEM2-ES performs a promising skill in simulating the anomalous circulation pattern over mid-latitude and central-east Eurasia while CanESM2 cannot. Probably, it is the models' ability of capturing the mega-ENSO-ISR linkage and the characteristic of mega-ENSO that make the difference.

Multiple Facets of cAMP Signalling and Physiological Impact: cAMP Compartmentalization in the Lung

PubMed Central

Oldenburger, Anouk; Maarsingh, Harm; Schmidt, Martina

2012-01-01

Therapies involving elevation of the endogenous suppressor cyclic AMP (cAMP) are currently used in the treatment of several chronic inflammatory disorders, including chronic obstructive pulmonary disease (COPD). Characteristics of COPD are airway obstruction, airway inflammation and airway remodelling, processes encompassed by increased airway smooth muscle mass, epithelial changes, goblet cell and submucosal gland hyperplasia. In addition to inflammatory cells, airway smooth muscle cells and (myo)fibroblasts, epithelial cells underpin a variety of key responses in the airways such as inflammatory cytokine release, airway remodelling, mucus hypersecretion and airway barrier function. Cigarette smoke, being next to environmental pollution the main cause of COPD, is believed to cause epithelial hyperpermeability by disrupting the barrier function. Here we will focus on the most recent progress on compartmentalized signalling by cAMP. In addition to G protein-coupled receptors, adenylyl cyclases, cAMP-specific phospho-diesterases (PDEs) maintain compartmentalized cAMP signalling. Intriguingly, spatially discrete cAMP-sensing signalling complexes seem also to involve distinct members of the A-kinase anchoring (AKAP) superfamily and IQ motif containing GTPase activating protein (IQGAPs). In this review, we will highlight the interaction between cAMP and the epithelial barrier to retain proper lung function and to alleviate COPD symptoms and focus on the possible molecular mechanisms involved in this process. Future studies should include the development of cAMP-sensing multiprotein complex specific disruptors and/or stabilizers to orchestrate cellular functions. Compartmentalized cAMP signalling regulates important cellular processes in the lung and may serve as a therapeutic target. PMID:24281338

Exchange protein directly activated by cAMP (epac): a multidomain cAMP mediator in the regulation of diverse biological functions.

PubMed

Schmidt, Martina; Dekker, Frank J; Maarsingh, Harm

2013-04-01

Since the discovery nearly 60 years ago, cAMP is envisioned as one of the most universal and versatile second messengers. The tremendous feature of cAMP to tightly control highly diverse physiologic processes, including calcium homeostasis, metabolism, secretion, muscle contraction, cell fate, and gene transcription, is reflected by the award of five Nobel prizes. The discovery of Epac (exchange protein directly activated by cAMP) has ignited a new surge of cAMP-related research and has depicted novel cAMP properties independent of protein kinase A and cyclic nucleotide-gated channels. The multidomain architecture of Epac determines its activity state and allows cell-type specific protein-protein and protein-lipid interactions that control fine-tuning of pivotal biologic responses through the "old" second messenger cAMP. Compartmentalization of cAMP in space and time, maintained by A-kinase anchoring proteins, phosphodiesterases, and β-arrestins, contributes to the Epac signalosome of small GTPases, phospholipases, mitogen- and lipid-activated kinases, and transcription factors. These novel cAMP sensors seem to implement certain unexpected signaling properties of cAMP and thereby to permit delicate adaptations of biologic responses. Agonists and antagonists selective for Epac are developed and will support further studies on the biologic net outcome of the activation of Epac. This will increase our current knowledge on the pathophysiology of devastating diseases, such as diabetes, cognitive impairment, renal and heart failure, (pulmonary) hypertension, asthma, and chronic obstructive pulmonary disease. Further insights into the cAMP dynamics executed by the Epac signalosome will help to optimize the pharmacological treatment of these diseases.

The cyclic AMP cascade is altered in the fragile X nervous system.

PubMed

Kelley, Daniel J; Davidson, Richard J; Elliott, Jamie L; Lahvis, Garet P; Yin, Jerry C P; Bhattacharyya, Anita

2007-09-26

Fragile X syndrome (FX), the most common heritable cause of mental retardation and autism, is a developmental disorder characterized by physical, cognitive, and behavioral deficits. FX results from a trinucleotide expansion mutation in the fmr1 gene that reduces levels of fragile X mental retardation protein (FMRP). Although research efforts have focused on FMRP's impact on mGluR signaling, how the loss of FMRP leads to the individual symptoms of FX is not known. Previous studies on human FX blood cells revealed alterations in the cyclic adenosine 3', 5'-monophosphate (cAMP) cascade. We tested the hypothesis that cAMP signaling is altered in the FX nervous system using three different model systems. Induced levels of cAMP in platelets and in brains of fmr1 knockout mice are substantially reduced. Cyclic AMP induction is also significantly reduced in human FX neural cells. Furthermore, cAMP production is decreased in the heads of FX Drosophila and this defect can be rescued by reintroduction of the dfmr gene. Our results indicate that a robust defect in cAMP production in FX is conserved across species and suggest that cAMP metabolism may serve as a useful biomarker in the human disease population. Reduced cAMP induction has implications for the underlying causes of FX and autism spectrum disorders. Pharmacological agents known to modulate the cAMP cascade may be therapeutic in FX patients and can be tested in these models, thus supplementing current efforts centered on mGluR signaling.

Measurement of small lesions near metallic implants with mega-voltage cone beam CT

NASA Astrophysics Data System (ADS)

Grigorescu, Violeta; Prevrhal, Sven; Pouliot, Jean

2008-03-01

Metallic objects severely limit diagnostic CT imaging because of their high X-ray attenuation in the diagnostic energy range. In contrast, radiation therapy linear accelerators now offer CT imaging with X-ray energies in the megavolt range, where the attenuation coefficients of metals are significantly lower. We hypothesized that Mega electron-Voltage Cone-Beam CT (MVCT) implemented on a radiation therapy linear accelerator can detect and quantify small features in the vicinity of metallic implants with accuracy comparable to clinical Kilo electron-Voltage CT (KVCT) for imaging. Our test application was detection of osteolytic lesions formed near the metallic stem of a hip prosthesis, a condition of severe concern in hip replacement surgery. Both MVCT and KVCT were used to image a phantom containing simulated osteolytic bone lesions centered around a Chrome-Cobalt hip prosthesis stem with hemispherical lesions with sizes and densities ranging from 0.5 to 4 mm radius and 0 to 500 mg•cm -3, respectively. Images for both modalities were visually graded to establish lower limits of lesion visibility as a function of their size. Lesion volumes and mean density were determined and compared to reference values. Volume determination errors were reduced from 34%, on KVCT, to 20% for all lesions on MVCT, and density determination errors were reduced from 71% on KVCT to 10% on MVCT. Localization and quantification of lesions was improved with MVCT imaging. MVCT offers a viable alternative to clinical CT in cases where accurate 3D imaging of small features near metallic hardware is critical. These results need to be extended to other metallic objects of different composition and geometry.

The pro-apoptotic protein Bim is a convergence point for cAMP/protein kinase A- and glucocorticoid-promoted apoptosis of lymphoid cells.

PubMed

Zhang, Lingzhi; Insel, Paul A

2004-05-14

The mechanisms by which cAMP mediates apoptosis are not well understood. In the current studies, we used wild-type (WT) S49 T-lymphoma cells and the kin(-) variant (which lacks protein kinase A (PKA)) to examine cAMP/PKA-mediated apoptosis. The cAMP analog, 8-CPT-cAMP, increased phosphorylation of the cAMP response element-binding protein (CREB), activated caspase-3, and induced apoptosis in WT but not in kin(-) S49 cells. Using an array of 96 apoptosis-related genes, we found that treatment of WT cells with 8-CPT-cAMP for 24 h induced expression of mRNA for the pro-apoptotic gene, Bim. Real-time PCR analysis indicated that 8-CPT-cAMP increased Bim RNA in WT cells in <2 h and maintained this increase for >24 h. Bim protein expression increased in WT but not kin(-) cells treated with 8-CPT-cAMP or with the beta-adrenergic receptor agonist isoproterenol. Both apoptosis and Bim expression were reversible with removal of 8-CPT-cAMP after <6 h. The glucocorticoid dexamethasone also promoted apoptosis and Bim expression in S49 cells. In contrast, both UV light and anti-mouse Fas monoclonal antibody promoted apoptosis in S49 cells but did not induce Bim expression. 8-CPT-cAMP also induced Bim expression and enhanced dexamethasone-promoted apoptosis in human T-cell leukemia CEM-C7-14 (glucocorticoid-sensitive) and CEM-C1-15 (glucocorticoid-resistant) cells; increased Bim expression in 8-CPT-cAMP-treated CEM-C1-15 cells correlated with conversion of the cells from resistance to sensitivity to glucocorticoid-promoted apoptosis. Induction of Bim appears to be a key event in cAMP-promoted apoptosis in both murine and human T-cell lymphoma and leukemia cells and thus appears to be a convergence point for the killing of such cells by glucocorticoids and agents that elevate cAMP.

A Computational approach in optimizing process parameters of GTAW for SA 106 Grade B steel pipes using Response surface methodology

NASA Astrophysics Data System (ADS)

Sumesh, A.; Sai Ramnadh, L. V.; Manish, P.; Harnath, V.; Lakshman, V.

2016-09-01

Welding is one of the most common metal joining techniques used in industry for decades. As in the global manufacturing scenario the products should be more cost effective. Therefore the selection of right process with optimal parameters will help the industry in minimizing their cost of production. SA 106 Grade B steel has a wide application in Automobile chassis structure, Boiler tubes and pressure vessels industries. Employing central composite design the process parameters for Gas Tungsten Arc Welding was optimized. The input parameters chosen were weld current, peak current and frequency. The joint tensile strength was the response considered in this study. Analysis of variance was performed to determine the statistical significance of the parameters and a Regression analysis was performed to determine the effect of input parameters over the response. From the experiment the maximum tensile strength obtained was 95 KN reported for a weld current of 95 Amp, frequency of 50 Hz and peak current of 100 Amp. With an aim of maximizing the joint strength using Response optimizer a target value of 100 KN is selected and regression models were optimized. The output results are achievable with a Weld current of 62.6148 Amp, Frequency of 23.1821 Hz, and Peak current of 65.9104 Amp. Using Die penetration test the weld joints were also classified in to 2 categories as good weld and weld with defect. This will also help in getting a defect free joint when welding is performed using GTAW process.

Electron Beam Diagnostics Of The JLAB UV FEL

DOE Office of Scientific and Technical Information (OSTI.GOV)

Evtushenko, Pavel; Benson, Stephen; Biallas, George

2011-03-01

In this contribution we describe various systems and aspects of the electron beam diagnostics of the JLab UV FEL. The FEL is installed on a new bypass beam line at the existing 10 kW IR Upgrade FEL. Here, we describe a set of the following systems. A combination of OTR and phosphor viewers is used for measurements of the transverse beam profile, transverse emittance, and Twiss parameters. This system is also used for alignment of the optical cavity of the UV oscillator and to ensure the overlap between the electron beam and optical mode in the FEL wiggler. A systemmore » of beam position monitors equipped with log-amp based BPM electronics. Bunch length on the order of 120 fs RMS is measured with the help of a modified Martin-Puplett interferometer. The longitudinal transfer function measurement system is used to set up bunch compression in an optimal way, such that the LINAC RF curvature is compensated using only higher order magnetic elements of the beam transport. This set of diagnostic systems made a significant contribution in achieving first lasing of the FEL after only about 60 hours of beam operation.« less

Urnaloricus gadi nov. gen. et nov. sp. (Loricifera, Urnaloricidae nov. fam.), an aberrant Loricifera with a viviparous pedogenetic life cycle.

PubMed

Heiner, Iben; Kristensen, Reinhardt Møbjerg

2009-02-01

A new species of Loricifera, Urnaloricus gadi nov. gen. et nov. sp., is described from the Faroe Bank, located Southwest of the Faroe Islands, North Atlantic. The new species does not fit into any known families of Loricifera and therefore it is grouped into a new family Urnaloricidae nov. fam. The new species is characterized by having a very complicated life cycle that involves a large cyst-like mega-larva, two reduced larval instars and the Higgins-larvae eating their maternal stage from within. An adult stage is missing. This form of reproduction is called viviparous pedogenesis and normally is found only in nematodes and insects. In the life cycle of Urnaloricidae nov. fam., there are two types of free-living larval stages: a Higgins-larva and a mega-larva. The latter is found in two different forms, a pre- and a cyst-forming mega-larva. Additionally, there are two reduced life history stages, the reduced larval stage (probably a postlarva) and the ghost-larval stage inside the cyst-forming mega-larva. The external morphology of the two forms of mega-larvae is much reduced, e.g., the introvert has only a few rows of scalids when compared with the Higgins-larva. The pre mega-larva is free-living and can sometimes be covered with coccoliths. Internally, a large ovary with a few oocytes, a digestive system, and an internal armature with retracted scalids are present. The pre mega-larva presumably molts into a cyst-forming mega-larva and thereby the ovary is now seen inside the cyst-forming mega-larva. The cyst-forming mega-larva has the same structures as in the pre mega-larva though here the scalids are protruded and there is a gonopore. Inside the cyst-forming mega-larva the ovary produces more oocytes and begins to fill out the entire lumen. At this stage the cyst-forming mega-larva molts first to the presumed postlarval stage, and then this stage molts to a ghost-larva. Hence, the ovary now matures inside the ghost-larva, which is surrounded by both the cuticle of the reduced postlarval stage and the cuticle of the cyst-forming mega-larva. The oocytes mature into eggs, and then into embryos and finally into Higgins-larvae while reabsorbing all the tissue of their maternal stage, the ghost-larva. During this maturation the cuticle of the cyst-forming mega-larva starts to harden and become cyst-like. The fully developed Higgins-larvae emerge through the gonopore of the cyst-forming mega-larva by penetrating the thin cuticles of the ghost-larva and the postlarva. The embryos have holoblastic radial cleavage and later a fluid-filled blastocoel is formed. The eggshells are extremely elastic; hence, they can become very elongated as the embryos mature into Higgins-larvae. (c) 2008 Wiley-Liss, Inc.

Sodium and calcium currents in neuroblastoma x glioma hybrid cells before and after morphological differentiation by dibutyryl cyclic AMP.

PubMed

Bodewei, R; Hering, S; Schubert, B; Wollenberger, A

1985-04-01

Sodium and calcium inward currents (INa and ICa) were measured in neuroblastoma X glioma hybrid cells of clones 108CC5 and 108CC15 by a single suction pipette method for internal perfusion and voltage clamp. Morphologically undifferentiated, exponentially growing cells were compared with cells differentiated by cultivation with 1 mmol/l dibutyryl cyclic AMP. Outward currents were eliminated by perfusing the cells with a K+-free solution. Voltage dependence and ion selectivity as well as steady state inactivation characteristics of INa and ICa resembled those of differentiated mouse neuroblastoma cells, clone N1E-115 (Moolenaar and Spector 1978, 1979). These parameters were identical in undifferentiated and differentiated cells of both clones. After differentiation the average density of the peak sodium and calcium currents was increased two and four-fold, respectively, in both cell lines. Our data indicate that exponentially growing, morphologically undifferentiated 108CC5 and 108CC15 neuroblastoma X glioma hybrid cells possess functional Na+ and Ca2+ channels undistinguishable from those of non-proliferating cells of these clones differentiated morphologically by treatment with dibutyryl cyclic AMP. That Na+ and Ca2+ spikes were not detected by other authors in these cells prior to morphological differentiation by dibutyryl cyclic AMP may be attributed to the fact that at the low resting membrane potential measured the Na+ and Ca2+ channels are inactivated.

ImaSim, a software tool for basic education of medical x-ray imaging in radiotherapy and radiology

NASA Astrophysics Data System (ADS)

Landry, Guillaume; deBlois, François; Verhaegen, Frank

2013-11-01

Introduction: X-ray imaging is an important part of medicine and plays a crucial role in radiotherapy. Education in this field is mostly limited to textbook teaching due to equipment restrictions. A novel simulation tool, ImaSim, for teaching the fundamentals of the x-ray imaging process based on ray-tracing is presented in this work. ImaSim is used interactively via a graphical user interface (GUI). Materials and methods: The software package covers the main x-ray based medical modalities: planar kilo voltage (kV), planar (portal) mega voltage (MV), fan beam computed tomography (CT) and cone beam CT (CBCT) imaging. The user can modify the photon source, object to be imaged and imaging setup with three-dimensional editors. Objects are currently obtained by combining blocks with variable shapes. The imaging of three-dimensional voxelized geometries is currently not implemented, but can be added in a later release. The program follows a ray-tracing approach, ignoring photon scatter in its current implementation. Simulations of a phantom CT scan were generated in ImaSim and were compared to measured data in terms of CT number accuracy. Spatial variations in the photon fluence and mean energy from an x-ray tube caused by the heel effect were estimated from ImaSim and Monte Carlo simulations and compared. Results: In this paper we describe ImaSim and provide two examples of its capabilities. CT numbers were found to agree within 36 Hounsfield Units (HU) for bone, which corresponds to a 2% attenuation coefficient difference. ImaSim reproduced the heel effect reasonably well when compared to Monte Carlo simulations. Discussion: An x-ray imaging simulation tool is made available for teaching and research purposes. ImaSim provides a means to facilitate the teaching of medical x-ray imaging.

Functional desensitization to isoproterenol without reducing cAMP production in canine failing cardiocytes.

PubMed

Laurent, C E; Cardinal, R; Rousseau, G; Vermeulen, M; Bouchard, C; Wilkinson, M; Armour, J A; Bouvier, M

2001-02-01

To corroborate alterations in the functional responses to beta-adrenergic receptor (beta-AR) stimulation with changes in beta-AR signaling in failing cardiomyocytes, contractile and L-type Ca(2+) current responses to isoproterenol along with stimulated cAMP generation were compared among cardiomyocytes isolated from canines with tachycardia-induced heart failure or healthy hearts. The magnitude of shortening of failing cardiomyocytes was significantly depressed (by 22 +/- 4.4%) under basal conditions, and the maximal response to isoproterenol was significantly reduced (by 45 +/- 18%). Similar results were obtained when the responses in the rate of contraction and rate of relaxation to isoproterenol were considered. The L-type Ca(2+) current amplitude measured in failing cardiomyocytes under basal conditions was unchanged, but the responses to isoproterenol were significantly reduced compared with healthy cells. Isoproterenol-stimulated cAMP generation was similar in sarcolemmal membranes derived from the homogenates of failing (45 +/- 6.8) and healthy cardiomyocytes (52 +/- 8.5 pmol cAMP. mg protein(-1). min(-1)). However, stimulated cAMP generation was found to be significantly reduced when the membranes were derived from the homogenates of whole tissue (failing: 67 +/- 8.1 vs. healthy: 140 +/- 27.8 pmol cAMP. mg protein(-1). min(-1)). Total beta-AR density was not reduced in membranes derived from either whole tissue or isolated cardiomyocyte homogenates, but the beta(1)/beta(2) ratio was significantly reduced in the former (failing: 45/55 vs. healthy: 72/28) without being altered in the latter (failing: 72/28, healthy: 77/23). We thus conclude that, in tachycardia-induced heart failure, reduction in the functional responses of isolated cardiomyocytes to beta-AR stimulation may be attributed to alterations in the excitation-contraction machinery rather than to limitation of cAMP generation.

Suppression of Adenosine-Activated Chloride Transport by Ethanol in Airway Epithelia

PubMed Central

Raju, Sammeta V.; Wang, Guoshun

2012-01-01

Alcohol abuse is associated with increased lung infections. Molecular understanding of the underlying mechanisms is not complete. Airway epithelial ion transport regulates the homeostasis of airway surface liquid, essential for airway mucosal immunity and lung host defense. Here, air-liquid interface cultures of Calu-3 epithelial cells were basolaterally exposed to physiologically relevant concentrations of ethanol (0, 25, 50 and 100 mM) for 24 hours and adenosine-stimulated ion transport was measured by Ussing chamber. The ethanol exposure reduced the epithelial short-circuit currents (ISC) in a dose-dependent manner. The ion currents activated by adenosine were chloride conductance mediated by cystic fibrosis transmembrane conductance regulator (CFTR), a cAMP-activated chloride channel. Alloxazine, a specific inhibitor for A2B adenosine receptor (A2BAR), largely abolished the adenosine-stimulated chloride transport, suggesting that A2BAR is a major receptor responsible for regulating the chloride transport of the cells. Ethanol significantly reduced intracellular cAMP production upon adenosine stimulation. Moreover, ethanol-suppression of the chloride secretion was able to be restored by cAMP analogs or by inhibitors to block cAMP degradation. These results imply that ethanol exposure dysregulates CFTR-mediated chloride transport in airways by suppression of adenosine-A2BAR-cAMP signaling pathway, which might contribute to alcohol-associated lung infections. PMID:22442662

A mega-nourishment creates novel habitat for intertidal macroinvertebrates by enhancing habitat relief of the sandy beach

NASA Astrophysics Data System (ADS)

van Egmond, E. M.; van Bodegom, P. M.; Berg, M. P.; Wijsman, J. W. M.; Leewis, L.; Janssen, G. M.; Aerts, R.

2018-07-01

Globally, sandy beaches are subject to coastal squeeze due to erosion. Soft-sediment strategies, such as sand nourishment, are increasingly applied to mitigate effects of erosion, but have long-term negative impacts on beach flora and fauna. As a more ecologically and sustainable alternative to regular beach nourishments, a mega-nourishment has been constructed along the Dutch coast by depositing 21.5 Mm3 of sand, from which sand is gradually redistributed along the coast by natural physical processes. The 'Sand Motor' mega-nourishment was constructed as a long-term management alternative for coastal protection and is the first large-scale experiment of its kind. We evaluated the development of intertidal macroinvertebrate communities in relation to this mega-nourishment, and compared it to species composition of beaches subject to regular beach or no nourishment. We found that a mega-nourishment resulted initially in a higher macroinvertebrate richness, but a lower macroinvertebrate abundance, compared to regular beach nourishment. As there was no effect of year after nourishment, this finding suggests that colonization and/or local extinction were not limiting macroinvertebrate richness at the mega-nourishment. In addition, a mega-nourishment does not converge to an intertidal macroinvertebrate community similar to those on unnourished beaches within a time scale of four years. Beach areas at the mega-nourishment sheltered from waves harbored a distinct macroinvertebrate community compared to typical wave-exposed sandy beach communities. Thus, a mega-nourishment temporally creates new habitat for intertidal macroinvertebrates by enhancing habitat relief of the sandy beach. We conclude that a mega-nourishment may be a promising coastal defense strategy for sandy shores in terms of the macroinvertebrate community of the intertidal beach.

Unattended Dual Current Monitor (UDCM) FY17 Summary Report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Newell, Matthew R.

The UDCM is a low current measurement device designed to record pico-amp to micro-amp currents from radiation detectors. The UDCM is the planned replacement for the IAEA’s obsolete MiniGRAND data acquisition module. Preliminary testing of the UDCM at the IAEA facilities lead to the following recommendations from the IAEA: Increase the measurement range. Lower range by a factor of 5 and upper range by 2 orders of magnitude; Modifications to the web interface; Increase programmable acquisition time to 3600s; Develop a method to handle current offsets and negative current; Error checking when writing data to the uSD card; and Writingmore » BID files along with the currently stored BI0 files.« less

[Physiopathology of cAMP/PKA signaling in neurons].

PubMed

Castro, Liliana; Yapo, Cedric; Vincent, Pierre

2016-01-01

Cyclic adenosine monophosphate (cAMP) and the cyclic-AMP dependent protein kinase (PKA) regulate a plethora of cellular functions in virtually all eukaryotic cells. In neurons, the cAMP/PKA signaling cascade controls a number of biological properties such as axonal growth, synaptic transmission, regulation of excitability or long term changes in the nucleus. Genetically-encoded optical biosensors for cAMP or PKA considerably improved our understanding of these processes by providing a real-time measurement in living neurons. In this review, we describe the recent progresses made in the creation of biosensors for cAMP or PKA activity. These biosensors revealed profound differences in the amplitude of the cAMP signal evoked by neuromodulators between various neuronal preparations. These responses can be resolved at the level of individual neurons, also revealing differences related to the neuronal type. At the subcellular level, biosensors reported different signal dynamics in domains like dendrites, cell body, nucleus and axon. Combining this imaging approach with pharmacology or genetical models points at phosphodiesterases and phosphatases as critical regulatory proteins. Biosensor imaging will certainly help understand the mechanism of action of current drugs as well as help in devising novel therapeutic strategies for neuropsychiatric diseases. © Société de Biologie, 2017.

Running-specific prostheses permit energy cost similar to nonamputees.

PubMed

Brown, Mary Beth; Millard-Stafford, Mindy L; Allison, Andrew R

2009-05-01

Improvements in prosthesis design have facilitated participation in competitive running for persons with lower limb loss (AMP). The purpose of this study was to examine the physiological responses of AMP using a run-specific prosthesis (RP) versus a traditional prosthesis (P) and cross-referenced with nonamputee controls (C) matched by training status, age, gender, and body composition during level treadmill running (TM). Twelve trained runners completed a multistage submaximal TM exercise during which HR and oxygen uptake (VO(2)) were obtained. Steady state measures at 134 m x min(-1) were compared between RP and P in AMP. AMP using RP (AMP-RP) and C also performed a continuous speed-incremented maximal TM test until volitional fatigue. RP elicited lower HR and VO(2) compared with P in AMP. Using RP, AMP achieved similar VO(2max) and peak TM speed compared with C but with higher HR(max). Relative HR (%HR(max)) and oxygen uptake (%VO(2max)), the regression intercept, slope, SEE, and Pearson's r correlation were not different between AMP-RP and C. %HR(max) calculated with the published equation, %HR(max) = 0.73(%VO(2max)) + 30, was not significantly different from actual %HR(max) for AMP-RP or C in any stage. RP permits AMP to attain peak TM speed and aerobic capacity similar to trained nonamputees and significantly attenuates HR and energy cost of submaximal running compared with a P. Use of RP confers no physiological advantage compared with nonamputee runners because energy cost at the set speed was not significantly different for AMP-RP. Current equations on the basis of the relative HR-VO(2) relationship seem appropriate to prescribe exercise intensity for persons with transtibial amputations using RP.

Video-based beam position monitoring at CHESS

NASA Astrophysics Data System (ADS)

Revesz, Peter; Pauling, Alan; Krawczyk, Thomas; Kelly, Kevin J.

2012-10-01

CHESS has pioneered the development of X-ray Video Beam Position Monitors (VBPMs). Unlike traditional photoelectron beam position monitors that rely on photoelectrons generated by the fringe edges of the X-ray beam, with VBPMs we collect information from the whole cross-section of the X-ray beam. VBPMs can also give real-time shape/size information. We have developed three types of VBPMs: (1) VBPMs based on helium luminescence from the intense white X-ray beam. In this case the CCD camera is viewing the luminescence from the side. (2) VBPMs based on luminescence of a thin (~50 micron) CVD diamond sheet as the white beam passes through it. The CCD camera is placed outside the beam line vacuum and views the diamond fluorescence through a viewport. (3) Scatter-based VBPMs. In this case the white X-ray beam passes through a thin graphite filter or Be window. The scattered X-rays create an image of the beam's footprint on an X-ray sensitive fluorescent screen using a slit placed outside the beam line vacuum. For all VBPMs we use relatively inexpensive 1.3 Mega-pixel CCD cameras connected via USB to a Windows host for image acquisition and analysis. The VBPM host computers are networked and provide live images of the beam and streams of data about the beam position, profile and intensity to CHESS's signal logging system and to the CHESS operator. The operational use of VBPMs showed great advantage over the traditional BPMs by providing direct visual input for the CHESS operator. The VBPM precision in most cases is on the order of ~0.1 micron. On the down side, the data acquisition frequency (50-1000ms) is inferior to the photoelectron based BPMs. In the future with the use of more expensive fast cameras we will be able create VBPMs working in the few hundreds Hz scale.

Calibration of the low-energy channel Thomson parabola of the LMJ-PETAL diagnostic SEPAGE with protons and carbon ions.

PubMed

Ducret, J-E; Batani, D; Boutoux, G; Chancé, A; Gastineau, B; Guillard, J-C; Harrault, F; Jakubowska, K; Lantuejoul-Thfoin, I; Leboeuf, D; Loiseau, D; Lotode, A; Pès, C; Rabhi, N; Saïd, A; Semsoum, A; Serani, L; Thomas, B; Toussaint, J-C; Vauzour, B

2018-02-01

The SEPAGE diagnostic will detect charged particles (electrons, protons, and ions) accelerated in the interaction of the PETAL (PETawatt Aquitaine Laser) laser with its targets on the LMJ (Laser MegaJoule)-PETAL laser facility. SEPAGE will be equipped with a proton-radiography front detector and two Thomson parabolas (TP), corresponding to different ranges of the particle energy spectra: Above 0.1 MeV for electrons and protons in the low-energy channel, with a separation capability between protons and 12 C 6+ up to 20 MeV proton energy and above 8 MeV for the high-energy channel, with a separation capability between protons and 12 C 6+ up to 200 MeV proton kinetic energy. This paper presents the calibration of the SEPAGE's low-energy channel TP at the Tandem facility of Orsay (France) with proton beams between 3 and 22 MeV and carbon-ion beams from 5.8 to 84 MeV. The magnetic and electric fields' integrals were determined with an accuracy of 10 -3 by combining the deflections measured at different energies with different target thicknesses and materials, providing different in-target energy losses of the beam particles and hence different detected energies for given beam energies.

Calibration of the low-energy channel Thomson parabola of the LMJ-PETAL diagnostic SEPAGE with protons and carbon ions

NASA Astrophysics Data System (ADS)

Ducret, J.-E.; Batani, D.; Boutoux, G.; Chancé, A.; Gastineau, B.; Guillard, J.-C.; Harrault, F.; Jakubowska, K.; Lantuejoul-Thfoin, I.; Leboeuf, D.; Loiseau, D.; Lotode, A.; Pès, C.; Rabhi, N.; Saïd, A.; Semsoum, A.; Serani, L.; Thomas, B.; Toussaint, J.-C.; Vauzour, B.

2018-02-01

The SEPAGE diagnostic will detect charged particles (electrons, protons, and ions) accelerated in the interaction of the PETAL (PETawatt Aquitaine Laser) laser with its targets on the LMJ (Laser MegaJoule)-PETAL laser facility. SEPAGE will be equipped with a proton-radiography front detector and two Thomson parabolas (TP), corresponding to different ranges of the particle energy spectra: Above 0.1 MeV for electrons and protons in the low-energy channel, with a separation capability between protons and 12C6+ up to 20 MeV proton energy and above 8 MeV for the high-energy channel, with a separation capability between protons and 12C6+ up to 200 MeV proton kinetic energy. This paper presents the calibration of the SEPAGE's low-energy channel TP at the Tandem facility of Orsay (France) with proton beams between 3 and 22 MeV and carbon-ion beams from 5.8 to 84 MeV. The magnetic and electric fields' integrals were determined with an accuracy of 10-3 by combining the deflections measured at different energies with different target thicknesses and materials, providing different in-target energy losses of the beam particles and hence different detected energies for given beam energies.

Open-Access Mega-Journals: A Bibliometric Profile.

PubMed

Wakeling, Simon; Willett, Peter; Creaser, Claire; Fry, Jenny; Pinfield, Stephen; Spezi, Valérie

2016-01-01

In this paper we present the first comprehensive bibliometric analysis of eleven open-access mega-journals (OAMJs). OAMJs are a relatively recent phenomenon, and have been characterised as having four key characteristics: large size; broad disciplinary scope; a Gold-OA business model; and a peer-review policy that seeks to determine only the scientific soundness of the research rather than evaluate the novelty or significance of the work. Our investigation focuses on four key modes of analysis: journal outputs (the number of articles published and changes in output over time); OAMJ author characteristics (nationalities and institutional affiliations); subject areas (the disciplinary scope of OAMJs, and variations in sub-disciplinary output); and citation profiles (the citation distributions of each OAMJ, and the impact of citing journals). We found that while the total output of the eleven mega-journals grew by 14.9% between 2014 and 2015, this growth is largely attributable to the increased output of Scientific Reports and Medicine. We also found substantial variation in the geographical distribution of authors. Several journals have a relatively high proportion of Chinese authors, and we suggest this may be linked to these journals' high Journal Impact Factors (JIFs). The mega-journals were also found to vary in subject scope, with several journals publishing disproportionately high numbers of articles in certain sub-disciplines. Our citation analsysis offers support for Björk & Catani's suggestion that OAMJs's citation distributions can be similar to those of traditional journals, while noting considerable variation in citation rates across the eleven titles. We conclude that while the OAMJ term is useful as a means of grouping journals which share a set of key characteristics, there is no such thing as a "typical" mega-journal, and we suggest several areas for additional research that might help us better understand the current and future role of OAMJs in scholarly communication.

Open-Access Mega-Journals: A Bibliometric Profile

PubMed Central

Willett, Peter; Creaser, Claire; Fry, Jenny; Pinfield, Stephen; Spezi, Valérie

2016-01-01

In this paper we present the first comprehensive bibliometric analysis of eleven open-access mega-journals (OAMJs). OAMJs are a relatively recent phenomenon, and have been characterised as having four key characteristics: large size; broad disciplinary scope; a Gold-OA business model; and a peer-review policy that seeks to determine only the scientific soundness of the research rather than evaluate the novelty or significance of the work. Our investigation focuses on four key modes of analysis: journal outputs (the number of articles published and changes in output over time); OAMJ author characteristics (nationalities and institutional affiliations); subject areas (the disciplinary scope of OAMJs, and variations in sub-disciplinary output); and citation profiles (the citation distributions of each OAMJ, and the impact of citing journals). We found that while the total output of the eleven mega-journals grew by 14.9% between 2014 and 2015, this growth is largely attributable to the increased output of Scientific Reports and Medicine. We also found substantial variation in the geographical distribution of authors. Several journals have a relatively high proportion of Chinese authors, and we suggest this may be linked to these journals’ high Journal Impact Factors (JIFs). The mega-journals were also found to vary in subject scope, with several journals publishing disproportionately high numbers of articles in certain sub-disciplines. Our citation analsysis offers support for Björk & Catani’s suggestion that OAMJs’s citation distributions can be similar to those of traditional journals, while noting considerable variation in citation rates across the eleven titles. We conclude that while the OAMJ term is useful as a means of grouping journals which share a set of key characteristics, there is no such thing as a “typical” mega-journal, and we suggest several areas for additional research that might help us better understand the current and future role of OAMJs in scholarly communication. PMID:27861511

Analysis of ESBL- and AmpC-positive Enterobacteriaceae at the Department of Neonatology, University Hospital Olomouc.

PubMed

Husičková, Vendula; Chromá, Magdaléna; Kolář, Milan; Hricová, Kristýna; Stosová, Taťána; Kantor, Lumír; Dubrava, Lubomír

2011-06-01

Bacterial infections are an important issue in current clinical medicine. The severity of infectious diseases has increased dramatically in recent years, which is also due to increasing numbers of resistant bacteria, including strains producing broad-spectrum beta-lactamases. The study aimed at determining the prevalence of ESBL- and AmpC-positive Enterobacteriaceae at the Department of Neonatology, University Hospital Olomouc. Enterobacteriaceae were isolated from clinical samples from infants hospitalized at the Department of Neonatology, University Hospital Olomouc over a period of 2 years. ESBL- and AmpC-positive isolates were subjected to basic genetic analysis. In the study period, a total of 1,526 isolates of the Enterobacteriaceae family were identified, including 55 (3.6%) cases of the ESBL phenotype and 17 (1.1%) AmpC-positive isolates. Genetic analysis of ESBL-positive isolates revealed a majority of CTX-M enzymes. Among AmpC beta-lactamases, the EBC, CIT, DHA, and MOX types were detected. An Escherichia coli strain was isolated with mutations in the promoter region of the ampC chromosomal gene that are associated with overproduction of the relevant enzyme.

D0 Solenoid Upgrade Project: D0 Solenoid Current Leads

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rucinski, R.; /Fermilab

This engineering note documents information gathered and design decisions made regarding the vapor cooled current leads for the D-Zero Solenoid. The decision was made during design group meetings that the D-Zero Solenoid, rated at 4825 amps, should use vapor cooled current leads rated at 6000 amps. CDF uses 6000 amp leads from American Magnetics Inc. (AMI) and has two spares in their storage lockers. Because of the spares situation and AMI's reputation, AMI would be the natural choice of vendor. The manufacturer's listed helium consumption is 19.2 liters/hr. From experience with these types of leads, more stable operation is acheivedmore » at an increased gas flow. See attached E-Mail message from RLS. We have decided to list the design flow rate at 28.8 liquid liters/hr in the design report. This corresponds to COFs operating point. A question was raised regarding how long the current leads could last at full current should the vapor cooling flow was stopped. This issue was discussed with Scott Smith from AMI. We do not feel that there is a problem for this failure scenario.« less

Phloretin differentially inhibits volume-sensitive and cyclic AMP-activated, but not Ca-activated, Cl− channels

PubMed Central

Fan, Hai-Tian; Morishima, Shigeru; Kida, Hajime; Okada, Yasunobu

2001-01-01

Some phenol derivatives are known to block volume-sensitive Cl− channels. However, effects on the channel of the bisphenol phloretin, which is a known blocker of glucose uniport and anion antiport, have not been examined. In the present study, we investigated the effects of phloretin on volume-sensitive Cl− channels in comparison with cyclic AMP-activated CFTR Cl− channels and Ca2+-activated Cl− channels using the whole-cell patch-clamp technique.Extracellular application of phloretin (over 10 μM) voltage-independently, and in a concentration-dependent manner (IC50 ∼30 μM), inhibited the Cl− current activated by a hypotonic challenge in human epithelial T84, Intestine 407 cells and mouse mammary C127/CFTR cells.In contrast, at 30 μM phloretin failed to inhibit cyclic AMP-activated Cl− currents in T84 and C127/CFTR cells. Higher concentrations (over 100 μM) of phloretin, however, partially inhibited the CFTR Cl− currents in a voltage-dependent manner.At 30 and 300 μM, phloretin showed no inhibitory effect on Ca2+-dependent Cl− currents induced by ionomycin in T84 cells.It is concluded that phloretin preferentially blocks volume-sensitive Cl− channels at low concentrations (below 100 μM) and also inhibits cyclic AMP-activated Cl− channels at higher concentrations, whereas phloretin does not inhibit Ca2+-activated Cl− channels in epithelial cells. PMID:11487521

Ion and Electron Heating Characteristics of Magnetic Re- Connection in Mast Tokamak Merging Experiment

NASA Astrophysics Data System (ADS)

Tanabe, Hiroshi; Inomoto, Michiaki; Ono, Yasushi; Yamada, Takuma; Imazawa, Ryota; Cheng, Chio-Zong

2016-07-01

We present results of recent studies of high power heating of magnetic reconnection, the fundamental process of several astrophysical events such as solar flare, in the Mega Amp Spherical Tokamak (MAST) - the world largest merging experiment. In addition to the previously reported significant reconnection heating up to ˜1keV [1], detailed local profiles of electron and ion temperature have been measured using a ultra-fine 300 channel Ruby- and a 130 channel YAG-Thomson scattering and a new 32 channel ion Doppler tomography diagnostics [2]. 2D profile measurement of electron temperature revealed highly localized heating structure at the X point with the characteristic scale length of 0.02-0.05m0.3T), a thick layer of closed flux surface surrounding the current sheet sustains the temperature profile for longer time than the electron and ion energy relaxation time ˜4-10ms, finally forming triple peak structures of ion and electron temperatures at the X point and in the downstream. While the peak electron temperature at the X point increases with toroidal field, the bulk electron temperature and the ion temperature in the downstream are unaffected. [1] Y. Ono et.al., Plasma Phys. Control. Fusion 54, 124039 (2012) [2] H. Tanabe et. al., Nucl. Fusion 53, 093027 (2013). [3] H. Tanabe et.al., Phys. Rev. Lett. 115, 215004 (2015)

The Canadian Teaching Commons: The Scholarship of Teaching and Learning in Canadian Higher Education

ERIC Educational Resources Information Center

Wuetherick, Brad; Yu, Stan

2016-01-01

This chapter reports on a national study exploring the current state of the Scholarship of Teaching and Learning (SoTL) and assessing the perceptions of Canadian SoTL scholars at the micro (individual), meso (departmental), macro (institutional), and mega (disciplinary) contexts.

Map of Pseudo-F-statistics of seismic noise parameters as an indicator of current seismic danger in Japan

NASA Astrophysics Data System (ADS)

Lyubushin, Alexey

2016-04-01

The problem of estimate of current seismic danger based on monitoring of seismic noise properties from broadband seismic network F-net in Japan (84 stations) is considered. Variations of the following seismic noise parameters are analyzed: multifractal singularity spectrum support width, generalized Hurst exponent, minimum Hölder-Lipschitz exponent and minimum normalized entropy of squared orthogonal wavelet coefficients. These parameters are estimated within adjacent time windows of the length 1 day for seismic noise waveforms from each station. Calculating daily median values of these parameters by all stations provides 4-dimensional time series which describes integral properties of the seismic noise in the region covered by the network. Cluster analysis is applied to the sequence of clouds of 4-dimensional vectors within moving time window of the length 365 days with mutual shift 3 days starting from the beginning of 1997 up to the current time. The purpose of the cluster analysis is to find the best number of clusters (BNC) from probe numbers which are varying from 1 up to the maximum value 40. The BNC is found from the maximum of pseudo-F-statistics (PFS). A 2D map could be created which presents dependence of PFS on the tested probe number of clusters and the right-hand end of moving time window which is rather similar to usual spectral time-frequency diagrams. In the paper [1] it was shown that the BNC before Tohoku mega-earthquake on March 11, 2011, has strongly chaotic regime with jumps from minimum up to maximum values in the time interval 1 year before the event and this time intervals was characterized by high PFS values. The PFS-map is proposed as the method for extracting time intervals with high current seismic danger. The next danger time interval after Tohoku mega-EQ began at the end of 2012 and was finished at the middle of 2013. Starting from middle of 2015 the high PFS values and chaotic regime of BNC variations were returned. This could be interpreted as the increasing of the danger of the next mega-EQ in Japan in the region of Nankai Trough [1] at the first half of 2016. References 1. Lyubushin, A., 2013. How soon would the next mega-earthquake occur in Japan? // Natural Science, 5 (8A1), 1-7. http://dx.doi.org/10.4236/ns.2013.58A1001

Perfectionism and Depressive Symptoms in Early Adolescence

ERIC Educational Resources Information Center

Rice, Kenneth G.; Leever, Brooke A.; Noggle, Chad A.; Lapsley, Daniel K.

2007-01-01

The "Adaptive/Maladaptive Perfectionism Scale" (AMPS; K.G. Rice & K.J. Preusser, 2002) was developed on samples of 9- to 11-year-old children. A primary purpose of the current research was to examine whether the AMPS could be useful in studies of adolescents, and in particular, studies of adolescent depression. This study of 145 early adolescents…

Accessing the mega-region : evaluating the role of livable community patterns in Gulf Coast mega-region planning.

DOT National Transportation Integrated Search

2015-03-01

This research analyzes both the need and mechanisms for integrating livability components such as : transit and active transportation into a broader mega-regions transportation framework. The research : builds a conceptual framework for understanding...

New kids on the block: The Popeye domain containing (POPDC) protein family acting as a novel class of cAMP effector proteins in striated muscle.

PubMed

Brand, Thomas; Schindler, Roland

2017-12-01

The cyclic 3',5'-adenosine monophosphate (cAMP) signalling pathway constitutes an ancient signal transduction pathway present in prokaryotes and eukaryotes. Previously, it was thought that in eukaryotes three effector proteins mediate cAMP signalling, namely protein kinase A (PKA), exchange factor directly activated by cAMP (EPAC) and the cyclic-nucleotide gated channels. However, recently a novel family of cAMP effector proteins emerged and was termed the Popeye domain containing (POPDC) family, which consists of three members POPDC1, POPDC2 and POPDC3. POPDC proteins are transmembrane proteins, which are abundantly present in striated and smooth muscle cells. POPDC proteins bind cAMP with high affinity comparable to PKA. Presently, their biochemical activity is poorly understood. However, mutational analysis in animal models as well as the disease phenotype observed in patients carrying missense mutations suggests that POPDC proteins are acting by modulating membrane trafficking of interacting proteins. In this review, we will describe the current knowledge about this gene family and also outline the apparent gaps in our understanding of their role in cAMP signalling and beyond. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

cAMP Regulation of Airway Smooth Muscle Function

PubMed Central

Billington, Charlotte K.; Ojo, Oluwaseun O.; Penn, Raymond B.; Ito, Satoru

2013-01-01

Agonists activating β2-adrenoceptors (β2ARs) on airway smooth muscle (ASM) are the drug of choice for rescue from acute bronchoconstriction in patients with both asthma and chronic obstructive pulmonary disease (COPD). Moreover, the use of long-acting β-agonists combined with inhaled corticosteroids constitutes an important maintenance therapy for these diseases. β-Agonists are effective bronchodilators due primarily to their ability to antagonize ASM contraction. The presumed cellular mechanism of action involves the generation of intracellular cAMP, which in turn can activate the effector molecules cAMP-dependent protein kinase (PKA) and Epac. Other agents such as prostaglandin E2 and phosphodiesterase inhibitors that also increase intracellular cAMP levels in ASM, can also antagonize ASM contraction, and inhibit other ASM functions including proliferation and migration. Therefore, β2ARs and cAMP are key players in combating the pathophysiology of airway narrowing and remodeling. However, limitations of β-agonist therapy due to drug tachyphylaxis related to β2AR desensitization, and recent findings regarding the manner in which β2ARs and cAMP signal, have raised new and interesting questions about these well-studied molecules. In this review we discuss current concepts regarding β2ARs and cAMP in the regulation of ASM cell functions and their therapeutic roles in asthma and COPD. PMID:22634112

The effects of Chinese medicines on cAMP/PKA signaling in central nervous system dysfunction.

PubMed

Li, Lin; Fan, Xiang; Zhang, Xi-Ting; Yue, Shao-Qian; Sun, Zuo-Yan; Zhu, Jin-Qiang; Zhang, Jun-Hua; Gao, Xiu-Mei; Zhang, Han

2017-06-01

Neuropathological injury in the mammalian adult central nervous system (CNS) may cause axon disruption, neuronal death and lasting neurological deficits. Failure of axon regeneration is one of the major challenges for CNS functional recovery. Recently, the cAMP/PKA signaling pathway has been proven to be a critical regulator for neuronal regeneration, neuroplasticity, learning and memory. Also, previous studies have shown the effects of Chinese medicines on the prevention and treatment of CNS dysfunction mediated in part by cAMP/PKA signaling. In this review, the authors discuss current knowledge of the role of cAMP/PKA signaling pathway in neuronal regeneration and provide an overview of the Chinese medicines that may enable CNS functional recovery via this signaling pathway. Copyright © 2017 Elsevier Inc. All rights reserved.

Test Report - Fault Current Through Graphite Filament Reinforced Plastic

NASA Technical Reports Server (NTRS)

Evans, R. W.

1997-01-01

Tests were performed to determine the damage to samples of composite material when a current carrying wire is shorted to the surface of the composite material, and to determine whether enough current can flow through the material to blow a fuse before damage can occur. Fault current tests were performed on samples of graphite epoxy materials. Samples consisted of six layers of IM7 graphite fiber mat in Hercules 8552 epoxy resin. A variable power supply provided up to 35 amps of current. The high voltage side of the power supply was attached to a wire at the end of a hinged arm, and the low side was attached to the edge of the sample. To test joints, the return was connected to the edge of one sample, and the high side was shorted to the top of the other sample. Tests show that when current exceeds approximately 5 amps, the graphite glows, and the epoxy melts out at the shorted contact. At higher current levels the epoxy burns. At voltages above 15 volts the epoxy outer coat is easily broken, and fire, flame, and a rise in current occur suddenly. When joints are introduced, resistance is increased, and the maximum current resulting from a short circuit to the graphite epoxy is reduced. This condition can easily result in fault current lower than the circuit breaker limit and higher than the 5 amp ignition level. The shorting contact and the joint become hot spots with melting epoxy, smoke, and fire.

Enhancer Activation Requires Trans-Recruitment of a Mega Transcription Factor Complex

PubMed Central

Liu, Zhijie; Merkurjev, Daria; Yang, Feng; Li, Wenbo; Oh, Soohwan; Friedman, Meyer J.; Song, Xiaoyuan; Zhang, Feng; Ma, Qi; Ohgi, Kenneth; Krones, Anna; Rosenfeld, Michael G.

2014-01-01

Summary Enhancers provide critical information directing cell-type specific transcriptional programs, regulated by binding of signal-dependent transcription factors and their associated cofactors. Here we report that the most strongly activated estrogen (E2)-responsive enhancers are characterized by trans-recruitment and in situ assembly of a large 1-2 MDa complex of diverse DNA-binding transcription factors by ERα at ERE-containing enhancers. We refer to enhancers recruiting these factors as mega transcription factor-bound in trans (MegaTrans) enhancers. The MegaTrans complex is a signature of the most potent functional enhancers and is required for activation of enhancer RNA transcription and recruitment of coactivators, including p300 and Med1. The MegaTrans complex functions, in part, by recruiting specific enzymatic machinery, exemplified by DNA-dependent protein kinase. Thus, MegaTrans-containing enhancers represent a cohort of functional enhancers that mediate a broad and important transcriptional program and provide a molecular explanation for transcription factor clustering and hotspots noted in the genome. PMID:25303530

Research on Trypanosoma cruzi and Analysis of Inflammatory Infiltrate in Esophagus and Colon from Chronic Chagasic Patients with and without Mega

PubMed Central

Côbo, Eliângela de Castro; Silveira, Thales Parenti; Micheletti, Adilha Misson; Crema, Eduardo; Adad, Sheila Jorge

2012-01-01

To compare parasitism and inflammatory process in esophagus and colon from chronic chagasic patients, immunohistochemistry was carried out to research for T. cruzi and to evaluate the inflammatory infiltrate in the muscular and myenteric plexus in 39 esophagi (20 with and 19 without megaesophagus) and 50 colons (25 with and 25 without megacolon). The frequency of T. cruzi in megaesophagus was 20%, and in megacolon it was 4%. No amastigotes were found in organs without mega; considering the total of esophagi (with and without mega), the frequency of T. cruzi would be 10% and 2% in the colon. Myositis and ganglionitis were more frequent and intense in organs with mega compared to those without mega, and in esophagus compared to colon. Qualitatively, inflammatory infiltration in esophagus and colon, with or without mega, was similar, consisting predominantly of T lymphocytes (CD3+), scarce macrophages (CD68+), and rare B lymphocytes (CD20+). PMID:22131997

Development of high temperature gallium phosphide rectifiers

NASA Technical Reports Server (NTRS)

Craford, M. G.; Keune, D. L.

1972-01-01

Large area high performance, GaP rectifiers were fabricated by means of Zn diffusion into vapor phase epitaxial GaP. Devices with an active area of 0.01 sq cm typically exhibit forward voltages of 3 volts for a bias current of 1 ampere and have reverse breakdown voltages of 300 volts for temperatures from 27 C to 400 C. Typical device reverse saturation current at a reverse bias of 150 volts is less than 10 to the minus 9th power amp at 27 C and less than 0.000050 amp at 400 C.

[The fiscal position of medical specialists].

PubMed

Stevens, S; Moors, M

2013-01-01

Independent medical specialists in the Netherlands are treated as entrepreneurs for tax purposes and therefore enjoy tax benefits. A change in the legal relationship between medical specialists and hospitals is foreseen in 2015. Independent medical specialists will then no longer be considered to be entrepreneurs. This could negatively affect their tax position. The Dutch government has adopted a policy aimed at controlling expenses arising from medical specialists' fees. According to this policy, the formation of regional practices or mega-practices of specialists will be discouraged. In contrast, the current fiscal legislation encourages medical specialists to incorporate their practice into regional practices or mega-practices or to become shareholders of their hospitals. It has been proposed that fiscal benefits be linked to certain aspects of entrepreneurship, such as investing in medical equipment or employing medical personnel.

Antimicrobial peptides as a possible interlink between periodontal diseases and its risk factors: A systematic review.

PubMed

Li, S; Schmalz, G; Schmidt, J; Krause, F; Haak, R; Ziebolz, D

2018-04-01

Antimicrobial peptides (AMPs) play a critical role in controlling innate and acquired immune responses. Local dysregulation of AMP is implicated in the pathogenesis of periodontal diseases as a response to periodontal pathogen challenge. Changes in AMP expression also characterize tobacco smoking, diabetes mellitus, obesity and rheumatoid arthritis, which are established risk factors of periodontal diseases, suggesting AMP may act as putative mechanistic links between these. The aim was to evaluate and summarize critically the current evidence pertaining to interrelationships between AMPs, periodontal diseases and selected periodontal disease risk factors. General and theme specific keywords were used to search the PUBMED database for studies relevant to AMP, periodontal diseases, smoking, diabetes mellitus, obesity and rheumatoid arthritis and critically reviewed. A total of 131 abstracts and 119 full text articles were screened for relevance; 13 studies were selected for inclusion after critical review. Local AMP dysregulation characteristic to periodontal diseases appears to occur within a broader landscape of complex systemic immune perturbations independently induced by smoking, metabolic and rheumatoid disease. The nature of these interactions and mechanistic pathways involved are inadequately understood. AMPs could be possible mechanistic interlinks between periodontal diseases and its risk factors. However, such evidence is very limited and more in vivo and in vitro studies are necessary to clarify the nature of such relationships. A greater understanding of AMPs as shared mediators is essential for unraveling their value as therapeutic or biomarker candidates. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Simulations of toroidal Alfvén eigenmode excited by fast ions on the Experimental Advanced Superconducting Tokamak

NASA Astrophysics Data System (ADS)

Pei, Youbin; Xiang, Nong; Shen, Wei; Hu, Youjun; Todo, Y.; Zhou, Deng; Huang, Juan

2018-05-01

Kinetic-MagnetoHydroDynamic (MHD) hybrid simulations are carried out to study fast ion driven toroidal Alfvén eigenmodes (TAEs) on the Experimental Advanced Superconducting Tokamak (EAST). The first part of this article presents the linear benchmark between two kinetic-MHD codes, namely MEGA and M3D-K, based on a realistic EAST equilibrium. Parameter scans show that the frequency and the growth rate of the TAE given by the two codes agree with each other. The second part of this article discusses the resonance interaction between the TAE and fast ions simulated by the MEGA code. The results show that the TAE exchanges energy with the co-current passing particles with the parallel velocity |v∥ | ≈VA 0/3 or |v∥ | ≈VA 0/5 , where VA 0 is the Alfvén speed on the magnetic axis. The TAE destabilized by the counter-current passing ions is also analyzed and found to have a much smaller growth rate than the co-current ions driven TAE. One of the reasons for this is found to be that the overlapping region of the TAE spatial location and the counter-current ion orbits is narrow, and thus the wave-particle energy exchange is not efficient.

Caffeine accelerates recovery from general anesthesia via multiple pathways.

PubMed

Fong, Robert; Khokhar, Suhail; Chowdhury, Atif N; Xie, Kelvin G; Wong, Josiah Hiu-Yuen; Fox, Aaron P; Xie, Zheng

2017-09-01

Various studies have explored different ways to speed emergence from anesthesia. Previously, we have shown that three drugs that elevate intracellular cAMP (forskolin, theophylline, and caffeine) accelerate emergence from anesthesia in rats. However, our earlier studies left two main questions unanswered. First, were cAMP-elevating drugs effective at all anesthetic concentrations? Second, given that caffeine was the most effective of the drugs tested, why was caffeine more effective than forskolin since both drugs elevate cAMP? In our current study, emergence time from anesthesia was measured in adult rats exposed to 3% isoflurane for 60 min. Caffeine dramatically accelerated emergence from anesthesia, even at the high level of anesthetic employed. Caffeine has multiple actions including blockade of adenosine receptors. We show that the selective A 2a adenosine receptor antagonist preladenant or the intracellular cAMP ([cAMP] i )-elevating drug forskolin, accelerated recovery from anesthesia. When preladenant and forskolin were tested together, the effect on anesthesia recovery time was additive indicating that these drugs operate via different pathways. Furthermore, the combination of preladenant and forskolin was about as effective as caffeine suggesting that both A 2A receptor blockade and [cAMP] i elevation play a role in caffeine's ability to accelerate emergence from anesthesia. Because anesthesia in rodents is thought to be similar to that in humans, these results suggest that caffeine might allow for rapid and uniform emergence from general anesthesia in humans at all anesthetic concentrations and that both the elevation of [cAMP] i and adenosine receptor blockade play a role in this response. NEW & NOTEWORTHY Currently, there is no method to accelerate emergence from anesthesia. Patients "wake" when they clear the anesthetic from their systems. Previously, we have shown that caffeine can accelerate emergence from anesthesia. In this study, we show that caffeine is effective even at high levels of anesthetic. We also show that caffeine operates by both elevating intracellular cAMP levels and by blocking adenosine receptors. This complicated pharmacology makes caffeine especially effective in accelerating emergence from anesthesia. Copyright © 2017 the American Physiological Society.

Hepatic gene expression profiling of 5'-AMP-induced hypometabolism in mice.

PubMed

Zhao, Zhaoyang; Miki, Takao; Van Oort-Jansen, Anita; Matsumoto, Tomoko; Loose, David S; Lee, Cheng Chi

2011-04-12

There is currently much interest in clinical applications of therapeutic hypothermia. Hypothermia can be a consequence of hypometabolism. We have recently established a procedure for the induction of a reversible deep hypometabolic state in mice using 5'-adenosine monophosphate (5'-AMP) in conjunction with moderate ambient temperature. The current study aims at investigating the impact of this technology at the gene expression level in a major metabolic organ, the liver. Our findings reveal that expression levels of the majority of genes in liver are not significantly altered by deep hypometabolism. However, among those affected by hypometabolism, more genes are differentially upregulated than downregulated both in a deep hypometabolic state and in the early arousal state. These altered gene expression levels during 5'-AMP induced hypometabolism are largely restored to normal levels within 2 days of the treatment. Our data also suggest that temporal control of circadian genes is largely stalled during deep hypometabolism.

Role of exchange protein directly activated by cAMP (EPAC1) in breast cancer cell migration and apoptosis.

PubMed

Kumar, Naveen; Gupta, Sonal; Dabral, Surbhi; Singh, Shailja; Sehrawat, Seema

2017-06-01

Despite the current progress in cancer research and therapy, breast cancer remains the leading cause of mortality among half a million women worldwide. Migration and invasion of cancer cells are associated with prevalent tumor metastasis as well as high mortality. Extensive studies have powerfully established the role of prototypic second messenger cAMP and its two ubiquitously expressed intracellular cAMP receptors namely the classic protein kinaseA/cAMP-dependent protein kinase (PKA) and the more recently discovered exchange protein directly activated by cAMP/cAMP-regulated guanine nucleotide exchange factor (EPAC/cAMP-GEF) in cell migration, cell cycle regulation, and cell death. Herein, we performed the analysis of the Cancer Genome Atlas (TCGA) dataset to evaluate the essential role of cAMP molecular network in breast cancer. We report that EPAC1, PKA, and AKAP9 along with other molecular partners are amplified in breast cancer patients, indicating the importance of this signaling network. To evaluate the functional role of few of these proteins, we used pharmacological modulators and analyzed their effect on cell migration and cell death in breast cancer cells. Hence, we report that inhibition of EPAC1 activity using pharmacological modulators leads to inhibition of cell migration and induces cell death. Additionally, we also observed that the inhibition of EPAC1 resulted in disruption of its association with the microtubule cytoskeleton and delocalization of AKAP9 from the centrosome as analyzed by in vitro imaging. Finally, this study suggests for the first time the mechanistic insights of mode of action of a primary cAMP-dependent sensor, Exchange protein activated by cAMP 1 (EPAC1), via its interaction with A-kinase anchoring protein 9 (AKAP9). This study provides a new cell signaling cAMP-EPAC1-AKAP9 direction to the development of additional biotherapeutics for breast cancer.

High frequency characteristic of a monolithic 500 °C OpAmp-RC integrator in SiC bipolar IC technology

NASA Astrophysics Data System (ADS)

Tian, Ye; Zetterling, Carl-Mikael

2017-09-01

This paper presents a comprehensive investigation of the frequency response of a monolithic OpAmp-RC integrator implemented in a 4H-SiC bipolar IC technology. The circuits and devices have been measured and characterized from 27 to 500 °C. The devices have been modelled to identify that the substrate capacitance is a dominant factor affecting the OpAmp's high-frequency response. Large Miller compensation capacitors of more than 540 pF are required to ensure stability of the internal OpAmp. The measured unit-gain-bandwidth product of the OpAmp is ∼1.1 MHz at 27 °C, and decreases to ∼0.5 MHz at 500 °C mainly due to the reduction of the transistor's current gain. On the other hand, it is not necessary to compensate the integrator in a relatively wide bandwidth ∼0.7 MHz over the investigated temperature range. At higher frequencies, the integrator's frequency response has been identified to be significantly affected by that of the OpAmp and load impedance. This work demonstrates the potential of this technology for high temperature applications requiring bandwidths of several megahertz.

Flavonoid Regulation of HCN2 Channels*

PubMed Central

Carlson, Anne E.; Rosenbaum, Joel C.; Brelidze, Tinatin I.; Klevit, Rachel E.; Zagotta, William N.

2013-01-01

The hyperpolarization-activated cyclic nucleotide-modulated (HCN) channels are pacemaker channels whose currents contribute to rhythmic activity in the heart and brain. HCN channels open in response to hyperpolarizing voltages, and the binding of cAMP to their cyclic nucleotide-binding domain (CNBD) facilitates channel opening. Here, we report that, like cAMP, the flavonoid fisetin potentiates HCN2 channel gating. Fisetin sped HCN2 activation and shifted the conductance-voltage relationship to more depolarizing potentials with a half-maximal effective concentration (EC50) of 1.8 μm. When applied together, fisetin and cAMP regulated HCN2 gating in a nonadditive fashion. Fisetin did not potentiate HCN2 channels lacking their CNBD, and two independent fluorescence-based binding assays reported that fisetin bound to the purified CNBD. These data suggest that the CNBD mediates the fisetin potentiation of HCN2 channels. Moreover, binding assays suggest that fisetin and cAMP partially compete for binding to the CNBD. NMR experiments demonstrated that fisetin binds within the cAMP-binding pocket, interacting with some of the same residues as cAMP. Together, these data indicate that fisetin is a partial agonist for HCN2 channels. PMID:24085296

[Occurrence of AmpC-positive Klebsiella pneumoniae strains in patients with haematological malignancies].

PubMed

Chromá, Magdaléna; Kolár, Milan; Sauer, Pavel; Faber, Edgar; Stosová, Tatána; Koukalová, Dagmar; Indrák, Karel

2008-10-01

Currently, important bacterial beta-lactamases of increasing clinical significance include AmpC enzymes. The aim was to assess their occurrence in Klebsiella pneumoniae strains isolated from patients with haematological malignancies in a prospective study. Over a 2-month period, strains of the species were isolated from clinical material obtained from patients hospitalized at the Department of Haemato-Oncology of the University Hospital Olomouc. The strains were identified using standard microbiological techniques and the Vitek 2 automated system. Production of AmpC beta-lactamases was roughly determined by phenotypic tests and subsequently confirmed by PCR detection of genes encoding these enzymes. During the above-mentioned period, a total of 35 K. pneumoniae isolates were collected. In 7 of them, production of AmpC beta-lactamases was preliminarily detected by phenotypic test. The multiplex PCR method confirmed phenotyping and determined DHA types in all the isolates. All AmpC-positive isolates were false-susceptible to at least one of the tested third-generation cephalosporins. In one patient, clinically apparent infection caused by this strain was documented. The reported results suggest the possibility of occurrence of AmpC-beta-lactamases in K. pneumoniae strains with clinical significance.

Mega trends in business create mega changes for training and education

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shealy, R.E.; Moore, N.E.

1996-12-31

Four mega-trends for business organizations are clearly emerging: globalization, computerization, information economy, and management. These mega-trends will have a profound impact on the human resources of business organizations, particularly related to new skill requirements that will be more complex, more in-depth, and broader in scope. New skill requirements, coupled with new technological advances in the delivery of employee development programs, will have significant ramifications for internal training departments and educational institutions. This paper explores the ramifications for those involved in the training and education of employees in business organizations.

Kv7.5 Potassium Channel Subunits Are the Primary Targets for PKA-Dependent Enhancement of Vascular Smooth Muscle Kv7 Currents.

PubMed

Mani, Bharath K; Robakowski, Christina; Brueggemann, Lyubov I; Cribbs, Leanne L; Tripathi, Abhishek; Majetschak, Matthias; Byron, Kenneth L

2016-03-01

Kv7 (KCNQ) channels, formed as homo- or heterotetramers of Kv7.4 and Kv7.5 α-subunits, are important regulators of vascular smooth muscle cell (VSMC) membrane voltage. Recent studies demonstrate that direct pharmacological modulation of VSMC Kv7 channel activity can influence blood vessel contractility and diameter. However, the physiologic regulation of Kv7 channel activity is still poorly understood. Here, we study the effect of cAMP/protein kinase A (PKA) activation on whole cell K(+) currents through endogenous Kv7.5 channels in A7r5 rat aortic smooth muscle cells or through Kv7.4/Kv7.5 heteromeric channels natively expressed in rat mesenteric artery smooth muscle cells. The contributions of specific α-subunits are further dissected using exogenously expressed human Kv7.4 and Kv7.5 homo- or heterotetrameric channels in A7r5 cells. Stimulation of Gαs-coupled β-adrenergic receptors with isoproterenol induced PKA-dependent activation of endogenous Kv7.5 currents in A7r5 cells. The receptor-mediated enhancement of Kv7.5 currents was mimicked by pharmacological agents that increase [cAMP] (forskolin, rolipram, 3-isobutyl-1-methylxanthine, and papaverine) or mimic cAMP (8-bromo-cAMP); the 2- to 4-fold PKA-dependent enhancement of currents was also observed with exogenously expressed Kv7.5 channels. In contrast, exogenously-expressed heterotetrameric Kv7.4/7.5 channels in A7r5 cells or native mesenteric artery smooth muscle Kv7.4/7.5 channels were only modestly enhanced, and homo-tetrameric Kv7.4 channels were insensitive to this regulatory pathway. Correspondingly, proximity ligation assays indicated that isoproterenol induced PKA-dependent phosphorylation of exogenously expressed Kv7.5 channel subunits, but not of Kv7.4 subunits. These results suggest that signal transduction-mediated responsiveness of vascular smooth muscle Kv7 channel subunits to cAMP/PKA activation follows the order of Kv7.5 > Kv7.4/Kv7.5 > Kv7.4. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

Kv7.5 Potassium Channel Subunits Are the Primary Targets for PKA-Dependent Enhancement of Vascular Smooth Muscle Kv7 Currents

PubMed Central

Mani, Bharath K.; Robakowski, Christina; Brueggemann, Lyubov I.; Cribbs, Leanne L.; Tripathi, Abhishek; Majetschak, Matthias

2016-01-01

Kv7 (KCNQ) channels, formed as homo- or heterotetramers of Kv7.4 and Kv7.5 α-subunits, are important regulators of vascular smooth muscle cell (VSMC) membrane voltage. Recent studies demonstrate that direct pharmacological modulation of VSMC Kv7 channel activity can influence blood vessel contractility and diameter. However, the physiologic regulation of Kv7 channel activity is still poorly understood. Here, we study the effect of cAMP/protein kinase A (PKA) activation on whole cell K+ currents through endogenous Kv7.5 channels in A7r5 rat aortic smooth muscle cells or through Kv7.4/Kv7.5 heteromeric channels natively expressed in rat mesenteric artery smooth muscle cells. The contributions of specific α-subunits are further dissected using exogenously expressed human Kv7.4 and Kv7.5 homo- or heterotetrameric channels in A7r5 cells. Stimulation of Gαs-coupled β-adrenergic receptors with isoproterenol induced PKA-dependent activation of endogenous Kv7.5 currents in A7r5 cells. The receptor-mediated enhancement of Kv7.5 currents was mimicked by pharmacological agents that increase [cAMP] (forskolin, rolipram, 3-isobutyl-1-methylxanthine, and papaverine) or mimic cAMP (8-bromo-cAMP); the 2- to 4-fold PKA-dependent enhancement of currents was also observed with exogenously expressed Kv7.5 channels. In contrast, exogenously-expressed heterotetrameric Kv7.4/7.5 channels in A7r5 cells or native mesenteric artery smooth muscle Kv7.4/7.5 channels were only modestly enhanced, and homo-tetrameric Kv7.4 channels were insensitive to this regulatory pathway. Correspondingly, proximity ligation assays indicated that isoproterenol induced PKA-dependent phosphorylation of exogenously expressed Kv7.5 channel subunits, but not of Kv7.4 subunits. These results suggest that signal transduction-mediated responsiveness of vascular smooth muscle Kv7 channel subunits to cAMP/PKA activation follows the order of Kv7.5 >> Kv7.4/Kv7.5 > Kv7.4. PMID:26700561

Bright perspectives for nuclear photonics

NASA Astrophysics Data System (ADS)

Thirolf, P. G.; Habs, D.

2014-05-01

With the advent of new high-power, short-pulse laser facilities in combination with novel technologies for the production of highly brilliant, intense γ beams (like, e.g., Extreme Light Infrastructure - Nuclear Physics (ELI-NP) in Bucharest, MEGaRay in Livermore or a planned upgrade of the HIγS facility at Duke University), unprecedented perspectives will open up in the coming years for photonuclear physics both in basic sciences as in various fields of applications. Ultra-high sensitivity will be enabled by an envisaged increase of the γ-beam spectral density from the presently typical 102γ/eVs to about 104γ/eVs, thus enabling a new quality of nuclear photonics [1], assisted by new γ-optical elements [2]. Photonuclear reactions with highly brilliant γ beams will allow to produce radioisotopes for nuclear medicine with much higher specific activity and/or more economically than with conventional methods. This will open the door for completely new clinical applications of radioisotopes [3]. The isotopic, state-selective sensitivity of the well-established technique of nuclear resonance fluorescence (NRF) will be boosted by the drastically reduced energy bandwidth (<0.1%) of the novel γ beams. Together with a much higher intensity of these beams, this will pave the road towards a γ-beam based non-invasive tomography and microscopy, assisting the management of nuclear materials, such as radioactive waste management, the detection of nuclear fissile material in the recycling process or the detection of clandestine fissile materials. Moreover, also secondary sources like low-energy, pulsed, polarized neutron beams of high intensity and high brilliance [4] or a new type of positron source with significantly increased brilliance, for the first time fully polarized [5], can be realized and lead to new applications in solid state physics or material sciences.

Analysis of copper mixed kerosene servotherm in EDM of Monel 400™

NASA Astrophysics Data System (ADS)

Anandakumar, P. A.; Molla, Baya; Biruke, Fisha; Aravind, S.

2017-05-01

Powder mixed electro discharge machine process (PMEDM) is a hybrid machine process where a conductive powders is mixed to the dielectric fluid to facilitate effective machining of advanced material. This present study focused on performance of copper mixed kerosene servotherm as dielectric medium in EDM of Monel 400TM. The ratio of kerosene sevothermis 75 : 25. The copper powder was mixed with dielectric medium of kerosene servothem of 6g, 8g and 10 g respectively. This mixture was analyzed using different current rate of 8 amps, 10 amps and 12 amps to know the performance characteristics by using material removal rate, tool wear rate, diameter overcut, surface finish and dimensional accuracy. Based on the experimental investigation it is concluded that copper powder of 10g with 10 amps performed well than that of all other parameters.

Polarized deuterium internal target at AmPS (NIKHEF)

NASA Astrophysics Data System (ADS)

Ferro-Luzzi, M.; Zhou, Z.-L.; van den Brand, J. F. J.; Bulten, H. J.; Alarcon, R.; van Bakel, N.; Botto, T.; Bouwhuis, M.; van Buuren, L.; Comfort, J.; Doets, M.; Dolfini, S.; Ent, R.; Geurts, D.; Heimberg, P.; Higinbotham, D. W.; de Jager, C. W.; Lang, J.; de Lange, D. J.; Norum, B.; Passchier, I.; Poolman, H. R.; Six, E.; Steijger, J.; Szczerba, D.; Unal, O.; de Vries, H.

1998-01-01

We describe the polarized deuterium target internal to the NIKHEF medium-energy electron storage ring. Tensor polarized deuterium was produced in an atomic beam source and injected into a storage cell target. A Breit-Rabi polarimeter was used to monitor the injected atomic beam intensity and polarization. An electrostatic ion-extraction system and a Wien filter were utilized to measure on-line the atomic fraction of the target gas in the storage cell. This device was supplemented with a tensor polarization analyzer using the neutron anisotropy of the 3H(d,n)α reaction at 60 keV. This method allows determining the density-averaged nuclear polarization of the target gas, independent of spatial and temporal variations. We address issues important for polarized hydrogen/deuterium internal targets, such as the effects of spin-exchange collisions and resonant transitions induced by the RF fields of the charged particle beam.

Polarized deuterium internal target at AmPS (NIKHEF)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Norum, Blaine; De Jager, Cornelis; Geurts, D.

1997-08-01

We describe the polarized deuterium target internal to the NIKHEF medium-energy electron storage ring. Tensor polarized deuterium was produced in an atomic beam source and injected into a storage cell target. A Breit-Rabi polarimeter was used to monitor the injected atomic beam intensity and polarization. An electrostatic ion-extraction system and a Wien filter were utilized to measure on-line the atomic fraction of the target gas in the storage cell. This device was supplemented with a tensor polarization analyzer using the neutron anisotropy of the 3H(d,n)sigma reaction at 60 keV. This method allows determining the density-averaged nuclear polarization of the targetmore » gas, independent of spatial and temporal variations. We address issues important for polarized hydrogen/deuterium internal targets, such as the effects of spin-exchange collisions and resonant transitions induced by the RF fields of the charged particle beam.« less

Polarized deuterium internal target at AmPS (NIKHEF)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ferro-Luzzi, M.; NIKHEF, P.O. Box 41882, 1009 DB Amsterdam; Zhou, Z.-L.

1998-01-20

We describe the polarized deuterium target internal to the NIKHEF medium-energy electron storage ring. Tensor polarized deuterium was produced in an atomic beam source and injected into a storage cell target. A Breit-Rabi polarimeter was used to monitor the injected atomic beam intensity and polarization. An electrostatic ion-extraction system and a Wien filter were utilized to measure on-line the atomic fraction of the target gas in the storage cell. This device was supplemented with a tensor polarization analyzer using the neutron anisotropy of the {sup 3}H(d,n){alpha} reaction at 60 keV. This method allows determining the density-averaged nuclear polarization of themore » target gas, independent of spatial and temporal variations. We address issues important for polarized hydrogen/deuterium internal targets, such as the effects of spin-exchange collisions and resonant transitions induced by the RF fields of the charged particle beam.« less

Trapped buckyball turns up the amp

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hellemans, A.

1997-02-21

Since their discovery in 1985, the soccer-ball shaped molecules of 60 or more carbon atoms known as fullerenes have displayed a dazzling variety of tricks, coaxed by researchers to become superconductors at low temperature, light and carbon ion beam emittors. Two European researchers have added something to this list: they have created an electronic-mechanical amplifier from a single buckyball. This article describes the circumstances of the discovery and future directions of the research.

Simultaneous detection of valine and lactate using MEGA-PRESS editing in pyogenic brain abscess.

PubMed

Lange, Thomas; Ko, Cheng-Wen; Lai, Ping-Hong; Dacko, Michael; Tsai, Shang-Yueh; Buechert, Martin

2016-12-01

Valine and lactate have been recognized as important metabolic markers to diagnose brain abscess by means of MRS. However, in vivo unambiguous detection and quantification is hampered by macromolecular contamination. In this work, MEGA-PRESS difference editing of valine and lactate is proposed. The method is validated in vitro and applied for quantitative in vivo experiments in one healthy subject and two brain abscess patients. It is demonstrated that with this technique the overlapping lipid signal can be reduced by more than an order of magnitude and thus the robustness of valine and lactate detection in vivo can be enhanced. Quantification of the two abscess MEGA-PRESS spectra yielded valine/lactate concentration ratios of 0.10 and 0.27. These ratios agreed with the concentration ratios determined from concomitantly acquired short-T E PRESS data and were in line with literature values. The quantification accuracy of lactate (as measured with Cramér-Rao lower bounds in LCModel processing) was better for MEGA-PRESS than for short-T E PRESS in all acquired in vivo datasets. The Cramér-Rao lower bounds of valine were only better for MEGA-PRESS in one of the two abscess cases, while in the other case coediting of isoleucine confounded the quantification in the MEGA-PRESS analysis. MEGA-PRESS and short-T E PRESS should be combined for unambiguous quantification of amino acids in abscess measurements. Simultaneous valine/lactate MEGA-PRESS editing might benefit the distinction of brain abscesses from tumors, and further categorization of bacteria with reasonable sensitivity and specificity. Copyright © 2016 John Wiley & Sons, Ltd.

cAMP regulation of airway smooth muscle function.

PubMed

Billington, Charlotte K; Ojo, Oluwaseun O; Penn, Raymond B; Ito, Satoru

2013-02-01

Agonists activating β(2)-adrenoceptors (β(2)ARs) on airway smooth muscle (ASM) are the drug of choice for rescue from acute bronchoconstriction in patients with both asthma and chronic obstructive pulmonary disease (COPD). Moreover, the use of long-acting β-agonists combined with inhaled corticosteroids constitutes an important maintenance therapy for these diseases. β-Agonists are effective bronchodilators due primarily to their ability to antagonize ASM contraction. The presumed cellular mechanism of action involves the generation of intracellular cAMP, which in turn can activate the effector molecules cAMP-dependent protein kinase (PKA) and Epac. Other agents such as prostaglandin E(2) and phosphodiesterase inhibitors that also increase intracellular cAMP levels in ASM, can also antagonize ASM contraction, and inhibit other ASM functions including proliferation and migration. Therefore, β(2)ARs and cAMP are key players in combating the pathophysiology of airway narrowing and remodeling. However, limitations of β-agonist therapy due to drug tachyphylaxis related to β(2)AR desensitization, and recent findings regarding the manner in which β(2)ARs and cAMP signal, have raised new and interesting questions about these well-studied molecules. In this review we discuss current concepts regarding β(2)ARs and cAMP in the regulation of ASM cell functions and their therapeutic roles in asthma and COPD. Copyright © 2012 Elsevier Ltd. All rights reserved.

Decoding spatial and temporal features of neuronal cAMP/PKA signaling with FRET biosensors.

PubMed

Castro, Liliana R V; Guiot, Elvire; Polito, Marina; Paupardin-Tritsch, Daniéle; Vincent, Pierre

2014-02-01

Cyclic adenosine monophosphate (cAMP) and the cyclic-AMP-dependent protein kinase (PKA) regulate a plethora of cellular functions in virtually all eukaryotic cells. In neurons, the cAMP/PKA signaling cascade controls a number of biological properties such as axonal growth, pathfinding, efficacy of synaptic transmission, regulation of excitability, or long term changes. Genetically encoded optical biosensors for cAMP or PKA are considerably improving our understanding of these processes by providing a real-time measurement in living neurons. In this review, we describe the recent progress made in the creation of biosensors for cAMP or PKA activity. These biosensors revealed profound differences in the amplitude of the cAMP signal evoked by neuromodulators between various neuronal preparations. These responses can be resolved at the level of individual neurons, also revealing differences related to the neuronal type. At the sub-cellular level, biosensors reported different signal dynamics in domains like dendrites, cell body, nucleus, and axon. Combining this imaging approach with pharmacology or genetic models points at phosphodiesterases and phosphatases as critical regulatory proteins. Biosensor imaging will certainly emerge as a forefront tool to decipher the subtle mechanics of intracellular signaling. This will certainly help us to understand the mechanism of action of current drugs and foster the development of novel molecules for neuropsychiatric diseases. Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Applicability of "MEGA"[Eighth Note] to Sexually Abusive Youth with Low Intellectual Functioning

ERIC Educational Resources Information Center

Miccio-Fonseca, L. C.; Rasmussen, Lucinda A.

2013-01-01

The study explored the predictive validity of "Multiplex Empirically Guided Inventory of Ecological Aggregates for Assessing Sexually Abusive Children and Adolescents (Ages 4 to 19)" ("MEGA"[eighth note]; Miccio-Fonseca, 2006b), a comprehensive developmentally sensitive risk assessment outcome tool. "MEGA"[eighth note] assesses risk for coarse…

MEGA7: Molecular Evolutionary Genetics Analysis Version 7.0 for Bigger Datasets.

PubMed

Kumar, Sudhir; Stecher, Glen; Tamura, Koichiro

2016-07-01

We present the latest version of the Molecular Evolutionary Genetics Analysis (Mega) software, which contains many sophisticated methods and tools for phylogenomics and phylomedicine. In this major upgrade, Mega has been optimized for use on 64-bit computing systems for analyzing larger datasets. Researchers can now explore and analyze tens of thousands of sequences in Mega The new version also provides an advanced wizard for building timetrees and includes a new functionality to automatically predict gene duplication events in gene family trees. The 64-bit Mega is made available in two interfaces: graphical and command line. The graphical user interface (GUI) is a native Microsoft Windows application that can also be used on Mac OS X. The command line Mega is available as native applications for Windows, Linux, and Mac OS X. They are intended for use in high-throughput and scripted analysis. Both versions are available from www.megasoftware.net free of charge. © The Author 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

More Intense Mega Heat Waves in the Warmer World

NASA Astrophysics Data System (ADS)

Choi, G.; Robinson, D. A.

2017-12-01

In this study, changes in the occurrences of heat waves on the globe since the mid- 20th century and the synoptic characteristics of mega heat waves at regional scales in the warmer climate are examined. The NCEP-NCAR reanalysis surface data show that there have been no obvious linear changes in the heat wave frequencies at the continental scales since the mid-20th century, but amplified interdecadal variations led to unprecedented intense heat waves in the recent decades at the regional scales. Such mega heat waves have been more frequently observed in the poleward subtropical climate belts as well as in the interior region of continents. According to the analyses of upper tropospheric data, the occurrences of more intense mega heat waves since the late 20th century may be associated with the expansion of subtropical high pressures. These results suggest that populous cities near the subtropical climate zones should provide proactive mega heat wave warning systems for residents due to their vulnerability to the sudden attack of human lives harvest by mega heat waves in the warmer 21st century.

Role of Dynamics in the Autoinhibition and Activation of the Hyperpolarization-activated Cyclic Nucleotide-modulated (HCN) Ion Channels*♦

PubMed Central

VanSchouwen, Bryan; Akimoto, Madoka; Sayadi, Maryam; Fogolari, Federico; Melacini, Giuseppe

2015-01-01

The hyperpolarization-activated cyclic nucleotide-modulated (HCN) ion channels control rhythmicity in neurons and cardiomyocytes. Cyclic AMP allosterically modulates HCN through the cAMP-dependent formation of a tetrameric gating ring spanning the intracellular region (IR) of HCN, to which cAMP binds. Although the apo versus holo conformational changes of the cAMP-binding domain (CBD) have been previously mapped, only limited information is currently available on the HCN IR dynamics, which have been hypothesized to play a critical role in the cAMP-dependent gating of HCN. Here, using molecular dynamics simulations validated and complemented by experimental NMR and CD data, we comparatively analyze HCN IR dynamics in the four states of the thermodynamic cycle arising from the coupling between cAMP binding and tetramerization equilibria. This extensive set of molecular dynamics trajectories captures the active-to-inactive transition that had remained elusive for other CBDs, and it provides unprecedented insight on the role of IR dynamics in HCN autoinhibition and its release by cAMP. Specifically, the IR tetramerization domain becomes more flexible in the monomeric states, removing steric clashes that the apo-CDB structure would otherwise impose. Furthermore, the simulations reveal that the active/inactive structural transition for the apo-monomeric CBD occurs through a manifold of pathways that are more divergent than previously anticipated. Upon cAMP binding, these pathways become disallowed, pre-confining the CBD conformational ensemble to a tetramer-compatible state. This conformational confinement primes the IR for tetramerization and thus provides a model of how cAMP controls HCN channel gating. PMID:25944904

An odor-specific threshold deficit implicates abnormal cAMP signaling in youths at clinical risk for psychosis.

PubMed

Kamath, Vidyulata; Moberg, Paul J; Calkins, Monica E; Borgmann-Winter, Karin; Conroy, Catherine G; Gur, Raquel E; Kohler, Christian G; Turetsky, Bruce I

2012-07-01

While olfactory deficits have been reported in schizophrenia and youths at-risk for psychosis, few studies have linked these deficits to current pathophysiological models of the illness. There is evidence that disrupted cyclic adenosine 3',5'-monophosphate (cAMP) signaling may contribute to schizophrenia pathology. As cAMP mediates olfactory signal transduction, the degree to which this disruption could manifest in olfactory impairment was ascertained. Odor-detection thresholds to two odorants that differ in the degree to which they activate intracellular cAMP were assessed in clinical risk and low-risk participants. Birhinal assessments of odor-detection threshold sensitivity to lyral and citralva were acquired in youths experiencing prodromal symptoms (n=17) and controls at low risk for developing psychosis (n=15). Citralva and lyral are odorants that differ in cAMP activation; citralva is a strong cAMP activator and lyral is a weak cAMP activator. The overall group-by-odor interaction was statistically significant. At-risk youths showed significantly reduced odor detection thresholds for lyral, but showed intact detection thresholds for citralva. This odor-specific threshold deficit was uncorrelated with deficits in odor identification or discrimination, which were also present. ROC curve analysis revealed that olfactory performance correctly classified at-risk and low-risk youths with greater than 97% accuracy. This study extends prior findings of an odor-specific hyposmia implicating cAMP-mediated signal transduction in schizophrenia and unaffected first-degree relatives to include youths at clinical risk for developing the disorder. These results suggest that dysregulation of cAMP signaling may be present during the psychosis prodrome. Copyright © 2012 Elsevier B.V. All rights reserved.

An odor-specific threshold deficit implicates abnormal cAMP signaling in youths at clinical risk for psychosis

PubMed Central

Kamath, Vidyulata; Moberg, Paul J.; Calkins, Monica E.; Borgmann-Winter, Karin; Conroy, Catherine G.; Gur, Raquel E.; Kohler, Christian G.; Turetsky, Bruce I.

2012-01-01

Background While olfactory deficits have been reported in schizophrenia and youths at-risk for psychosis, few studies have linked these deficits to current pathophysiological models of the illness. There is evidence that disrupted cyclic adenosine 3’,5’-monophosphate (cAMP) signaling may contribute to schizophrenia pathology. As cAMP mediates olfactory signal transduction, the degree to which this disruption could manifest in olfactory impairment was ascertained. Odor-detection thresholds to two odorants that differ in the degree to which they activate intracellular cAMP were assessed in clinical risk and low-risk participants. Method Birhinal assessments of odor-detection threshold sensitivity to lyral and citralva were acquired in youths experiencing prodromal symptoms (n = 17) and controls at low risk for developing psychosis (n = 15). Citralva and lyral are odorants that differ in cAMP activation; citralva is a strong cAMP activator and lyral is a weak cAMP activator. Results The overall group-by-odor interaction was statistically significant. At-risk youths showed significantly reduced odor detection thresholds for lyral, but showed intact detection thresholds for citralva. This odor-specific threshold deficit was uncorrelated with deficits in odor identification or discrimination, which were also present. ROC curve analysis revealed that olfactory performance correctly classified at-risk and low-risk youths with greater than 97% accuracy. Conclusions This study extends prior findings of an odor-specific hyposmia implicating cAMP-mediated signal transduction in schizophrenia and unaffected first-degree relatives to include youths at clinical risk for developing the disorder. These results suggest that dysregulation of cAMP signaling may be present during the psychosis prodrome. PMID:22537567

Twenty-First Century Literacy: A Matter of Scale from Micro to Mega

ERIC Educational Resources Information Center

Brown, Abbie; Slagter van Tryon, Patricia J.

2010-01-01

Twenty-first century technologies require educators to look for new ways to teach literacy skills. Current communication methods are combinations of traditional and newer, network-driven forms. This article describes the changes twenty-first century technologies cause in the perception of time, size, distance, audience, and available data, and…

An Inexpensive Toroidal Solenoid for an Investigative Student Lab

NASA Astrophysics Data System (ADS)

Ferstl, Andrew; Broberg, John

2008-09-01

Magnetism and Ampère's law is a common subject in most calculus-based introductory physics courses. Many textbooks offer examples to calculate the magnetic field produced by a symmetric current by using Ampère's law. These examples include the solenoid and the toroidal solenoid (sometimes called a torus; see Fig. 1), which are used in many applications, including the study of plasmas.

Observation of fast expansion velocity with insulating tungsten wires on ∼80 kA facility

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, M.; Li, Y.; State Key Laboratory of Intense Pulsed Radiation Simulation and Effect, Northwest Institute of Nuclear Technology, Xi'an 710024

2016-07-15

This paper presents experimental results on the effects of insulating coatings on tungsten planar wire array Z-pinches on an 80 kA, 100 ns current facility. Expansion velocity is obviously increased from ∼0.25 km/s to ∼3.5 km/s by using the insulating coatings. It can be inferred that the wire cores are in gaseous state with this fast expansion velocity. An optical framing camera and laser probing images show that the standard wire arrays have typical ablation process which is similar to their behaviors on mega-ampere facilities. The ablation process and precursor plasma are suppressed for dielectric tungsten wires. The wire array implosion might be improvedmore » if these phenomena can be reproduced on Mega-ampere facilities.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Habs, D.; Guenther, M. M.; Jentschel, M.

With the planned new {gamma}-beam facilities like MEGa-ray at LLNL (USA) or ELI-NP at Bucharest (Romania) with 10{sup 13}{gamma}/s and a band width of {Delta}E{gamma}/E{gamma} Almost-Equal-To 10{sup -3}, a new era of {gamma} beams with energies up to 20MeV comes into operation, compared to the present world-leading HI{gamma}S facility at Duke University (USA) with 10{sup 8}{gamma}/s and {Delta}E{gamma}/E{gamma} Almost-Equal-To 3 Dot-Operator 10{sup -2}. In the long run even a seeded quantum FEL for {gamma} beams may become possible, with much higher brilliance and spectral flux. At the same time new exciting possibilities open up for focused {gamma} beams. Here wemore » describe a new experiment at the {gamma} beam of the ILL reactor (Grenoble, France), where we observed for the first time that the index of refraction for {gamma} beams is determined by virtual pair creation. Using a combination of refractive and reflective optics, efficient monochromators for {gamma} beams are being developed. Thus, we have to optimize the total system: the {gamma}-beam facility, the {gamma}-beam optics and {gamma} detectors. We can trade {gamma} intensity for band width, going down to {Delta}E{gamma}/E{gamma} Almost-Equal-To 10{sup -6} and address individual nuclear levels. The term 'nuclear photonics' stresses the importance of nuclear applications. We can address with {gamma}-beams individual nuclear isotopes and not just elements like with X-ray beams. Compared to X rays, {gamma} beams can penetrate much deeper into big samples like radioactive waste barrels, motors or batteries. We can perform tomography and microscopy studies by focusing down to {mu}m resolution using Nuclear Resonance Fluorescence (NRF) for detection with eV resolution and high spatial resolution at the same time. We discuss the dominating M1 and E1 excitations like the scissors mode, two-phonon quadrupole octupole excitations, pygmy dipole excitations or giant dipole excitations under the new facet of applications. We find many new applications in biomedicine, green energy, radioactive waste management or homeland security. Also more brilliant secondary beams of neutrons and positrons can be produced.« less

A Concept for the Use and Integration of Super-Conducting Magnets in Structural Systems in General and Maglev Guideway Mega-Structures in Particular

NASA Technical Reports Server (NTRS)

Ussery, Wilfred T.; MacCalla, Eric; MacCalla, Johnetta; Elnimeiri, Mahjoub; Goldsmith, Myron; Polk, Sharon Madison; Jenkins, Mozella; Bragg, Robert H.

1996-01-01

Recent breakthroughs in several different fields now make it possible to incorporate the use of superconducting magnets in structures in ways which enhance the performance of structural members or components of structural systems in general and Maglev guideway mega-structures in particular. The building of structural systems which connect appropriately scaled superconducting magnets with the post-tensioned tensile components of beams, girders, or columns would, if coupled with 'state of the art' structure monitoring, feedback and control systems, and advanced computer software, constitute a distinct new generation of structures that would possess the unique characteristic of being heuristic and demand or live-load responsive. The holistic integration of powerful superconducting magnets in structures so that they do actual structural work, creates a class of 'technologically endowed' structures that, in part - literally substitute superconductive electric power and magnetism for concrete and steel. The research and development engineering, and architectural design issues associated with such 'technologically endowed' structural system can now be conceptualized, designed, computer simulates built and tested. The Maglev guideway mega-structure delineated herein incorporates these concepts, and is designed for operation in the median strip of U.S. Interstate Highway 5 from San Diego to Seattle an Vancouver, and possibly on to Fairbanks, Alaska. This system also fits in the median strip of U.S. Interstate Highway 55 and 95 North-South, and 80 and 10, East-West. As a Western Region 'Peace Dividend' project, it could become a National or Bi-National research, design and build, super turnkey project that would create thousands of jobs by applying superconducting, material science, electronic aerospace and other defense industry technologies to a multi-vehicle, multi-use Maglev guideway megastructure that integrates urban mass transit Lower Speed (0-100 mph), High Speed (100-200 mph), Super Speed (200-400 mph), and Hypersonic evacuated tube (400-10,000 mph) Maglev systems.

Validation of a Detailed Scoring Checklist for Use During Advanced Cardiac Life Support Certification

PubMed Central

McEvoy, Matthew D.; Smalley, Jeremy C.; Nietert, Paul J.; Field, Larry C.; Furse, Cory M.; Blenko, John W.; Cobb, Benjamin G.; Walters, Jenna L.; Pendarvis, Allen; Dalal, Nishita S.; Schaefer, John J.

2012-01-01

Introduction Defining valid, reliable, defensible, and generalizable standards for the evaluation of learner performance is a key issue in assessing both baseline competence and mastery in medical education. However, prior to setting these standards of performance, the reliability of the scores yielding from a grading tool must be assessed. Accordingly, the purpose of this study was to assess the reliability of scores generated from a set of grading checklists used by non-expert raters during simulations of American Heart Association (AHA) MegaCodes. Methods The reliability of scores generated from a detailed set of checklists, when used by four non-expert raters, was tested by grading team leader performance in eight MegaCode scenarios. Videos of the scenarios were reviewed and rated by trained faculty facilitators and by a group of non-expert raters. The videos were reviewed “continuously” and “with pauses.” Two content experts served as the reference standard for grading, and four non-expert raters were used to test the reliability of the checklists. Results Our results demonstrate that non-expert raters are able to produce reliable grades when using the checklists under consideration, demonstrating excellent intra-rater reliability and agreement with a reference standard. The results also demonstrate that non-expert raters can be trained in the proper use of the checklist in a short amount of time, with no discernible learning curve thereafter. Finally, our results show that a single trained rater can achieve reliable scores of team leader performance during AHA MegaCodes when using our checklist in continuous mode, as measures of agreement in total scoring were very strong (Lin’s Concordance Correlation Coefficient = 0.96; Intraclass Correlation Coefficient = 0.97). Discussion We have shown that our checklists can yield reliable scores, are appropriate for use by non-expert raters, and are able to be employed during continuous assessment of team leader performance during the review of a simulated MegaCode. This checklist may be more appropriate for use by Advanced Cardiac Life Support (ACLS) instructors during MegaCode assessments than current tools provided by the AHA. PMID:22863996

Global mega forces: Implications for the future of natural resources

Treesearch

George H. Kubik

2012-01-01

The purpose of this paper is to provide an overview of leading global mega forces and their importance to the future of natural resource decisionmaking, policy development, and operation. Global mega forces are defined as a combination of major trends, preferences, and probabilities that come together to produce the potential for future high-impact outcomes. These...

Population Growth and Policies in Mega-Cities. Sao Paulo.

ERIC Educational Resources Information Center

United Nations New York, NY. Dept. of Economic and Social Information and Policy Analysis.

This document is one in a series of studies that focus on the population policies and plans of a number of mega-cities in developing countries. The object of the series is to examine the formulation, implementation, and evaluation of the population policies of mega-cities from a broad perspective, emphasizing the reciprocal links between…

Teacher Counter Stories to a Citizenship Education Mega Policy Narrative. Preparing for Citizenship in Chile

ERIC Educational Resources Information Center

Cavieres-Fernández, Eduardo

2017-01-01

The present article focuses on the counter stories of two Chilean social studies high school teachers. Counter stories describe how teachers use their professional experience to confront those mega narratives composed of dominant educational policies that impinge upon their pedagogical practices. The mega narrative described in this study as a…

Electrophysiological Evidence for the Presence of Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) in Mouse Sperm

PubMed Central

Dulce, Figueiras Fierro; José, Acevedo Juan; Pablo, Martínez; Escoffier, Jessica; Sepúlveda, Francisco V.; Enrique, Balderas; Gerardo, Orta; Pablo, Visconti; Alberto, Darszon

2014-01-01

Mammalian sperm must undergo a maturational process, named capacitation, in the female reproductive tract to fertilize the egg. Sperm capacitation is regulated by a cAMP/PKA pathway and involves increases in intracellular Ca2+, pH, Cl−, protein tyrosine phosphorylation, and in mouse and some other mammals a membrane potential hyperpolarization. The cystic fibrosis transmembrane conductance regulator (CFTR), a Cl− channel modulated by cAMP/PKA and ATP, was detected in mammalian sperm and proposed to modulate capacitation. Our whole-cell patch-clamp recordings from testicular mouse sperm now reveal a Cl− selective component to membrane current that is ATP-dependent, stimulated by cAMP, cGMP and genistein (a CFTR agonist, at low concentrations), and inhibited by DPC and CFTRinh-172, two well-known CFTR antagonists. Furthermore, the Cl− current component activated by cAMP and inhibited by CFTRinh-172 is absent in recordings on testicular sperm from mice possessing the CFTR ΔF508 loss-of-function mutation, indicating that CFTR is responsible for this component. A Cl− selective like current component displaying CFTR characteristics was also found in wild type epididymal sperm bearing the cytoplasmatic droplet. Capacitated sperm treated with CFTRinh-172 undergo a shape change, suggesting that CFTR is involved in cell volume regulation. These findings indicate that functional CFTR channels are present in mouse sperm and their biophysical properties are consistent with their proposed participation in capacitation. PMID:22833409

cAMP controls rod photoreceptor sensitivity via multiple targets in the phototransduction cascade

PubMed Central

Astakhova, Luba A.; Samoiliuk, Evgeniia V.; Govardovskii, Victor I.

2012-01-01

In early studies, both cyclic AMP (cAMP) and cGMP were considered as potential secondary messengers regulating the conductivity of the vertebrate photoreceptor plasma membrane. Later discovery of the cGMP specificity of cyclic nucleotide–gated channels has shifted attention to cGMP as the only secondary messenger in the phototransduction cascade, and cAMP is not considered in modern schemes of phototransduction. Here, we report evidence that cAMP may also be involved in regulation of the phototransduction cascade. Using a suction pipette technique, we recorded light responses of isolated solitary rods from the frog retina in normal solution and in the medium containing 2 µM of adenylate cyclase activator forskolin. Under forskolin action, flash sensitivity rose more than twofold because of a retarded photoresponse turn-off. The same concentration of forskolin lead to a 2.5-fold increase in the rod outer segment cAMP, which is close to earlier reported natural day/night cAMP variations. Detailed analysis of cAMP action on the phototransduction cascade suggests that several targets are affected by cAMP increase: (a) basal dark phosphodiesterase (PDE) activity decreases; (b) at the same intensity of light background, steady background-induced PDE activity increases; (c) at light backgrounds, guanylate cyclase activity at a given fraction of open channels is reduced; and (d) the magnitude of the Ca2+ exchanger current rises 1.6-fold, which would correspond to a 1.6-fold elevation of [Ca2+]in. Analysis by a complete model of rod phototransduction suggests that an increase of [Ca2+]in might also explain effects (b) and (c). The mechanism(s) by which cAMP could regulate [Ca2+]in and PDE basal activity is unclear. We suggest that these regulations may have adaptive significance and improve the performance of the visual system when it switches between day and night light conditions. PMID:23008435

Animal Venom Peptides: Potential for New Antimicrobial Agents.

PubMed

Primon-Barros, Muriel; José Macedo, Alexandre

2017-01-01

Microbial infections affect people worldwide, causing diseases with significant impact on public health, indicating the need for research and development of new antimicrobial agents. Animal venoms represent a vast and largely unexploited source of biologically active molecules with attractive candidates for the development of novel therapeutics. Venoms consist of complex mixtures of molecules, including antimicrobial peptides (AMPs). Since the discovery of AMPs, they have been studied as promising new antimicrobial drugs. Amongst the remarkable sources of AMPs with known antimicrobial activities are ants, bees, centipedes, cone snails, scorpions, snakes, spiders, and wasps. The antimicrobial tests against bacteria, protozoans, fungi and viruses using 170 different peptides isolated directly from crude venoms or cDNA libraries of venom glands are listed and discussed in this review, as well as hemolytic ativity. The potential of venoms as source of new compounds, including AMPs, is extensively discussed. Currently, there are six FDA-approved drugs and many others are undergoing preclinical and clinical trials. The search for antimicrobial "weapons" makes the AMPs from venoms promising candidates. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

The Potential Use of Natural and Structural Analogues of Antimicrobial Peptides in the Fight against Neglected Tropical Diseases.

PubMed

Lewies, Angélique; Wentzel, Johannes F; Jacobs, Garmi; Du Plessis, Lissinda H; Angélique, Lewies; Frederik, Wentzel Johannes; Garmi, Jacobs; Hester, Du Plessis Lissinda

2015-08-24

Recently, research into the development of new antimicrobial agents has been driven by the increase in resistance to traditional antibiotics and Emerging Infectious Diseases. Antimicrobial peptides (AMPs) are promising candidates as alternatives to current antibiotics in the treatment and prevention of microbial infections. AMPs are produced by all known living species, displaying direct antimicrobial killing activity and playing an important role in innate immunity. To date, more than 2000 AMPs have been discovered and many of these exhibit broad-spectrum antibacterial, antiviral and anti-parasitic activity. Neglected tropical diseases (NTDs) are caused by a variety of pathogens and are particularly wide-spread in low-income and developing regions of the world. Alternative, cost effective treatments are desperately needed to effectively battle these medically diverse diseases. AMPs have been shown to be effective against a variety of NTDs, including African trypanosomes, leishmaniosis and Chagas disease, trachoma and leprosy. In this review, the potential of selected AMPs to successfully treat a variety of NTD infections will be critically evaluated.

Archetypal tryptophan-rich antimicrobial peptides: properties and applications.

PubMed

Shagaghi, Nadin; Palombo, Enzo A; Clayton, Andrew H A; Bhave, Mrinal

2016-02-01

Drug-resistant microorganisms ('superbugs') present a serious challenge to the success of antimicrobial treatments. Subsequently, there is a crucial need for novel bio-control agents. Many antimicrobial peptides (AMPs) show a broad-spectrum activity against bacteria, fungi or viruses and are strong candidates to complement or substitute current antimicrobial agents. Some AMPs are also effective against protozoa or cancer cells. The tryptophan (Trp)-rich peptides (TRPs) are a subset of AMPs that display potent antimicrobial activity, credited to the unique biochemical properties of tryptophan that allow it to insert into biological membranes. Further, many Trp-rich AMPs cross bacterial membranes without compromising their integrity and act intracellularly, suggesting interactions with nucleic acids and enzymes. In this work, we overview some archetypal TRPs derived from natural sources, i.e., indolicidin, tritrpticin and lactoferricin, summarising their biochemical properties, structures, antimicrobial activities, mechanistic studies and potential applications.

Continuous Monitoring of Mobility, Burial and Re exposure of Underwater Munitions in Energetic Near Shore Environments

DTIC Science & Technology

2017-01-01

parameters on Wasque Shoals ..................................................... 22 Figure 19. Rotary sonar imagery showing migrating mega- ripples and the...shown by the green and yellow lines reveals the convergence and divergence of the migrating mega- ripples ...26 Figure 24. Succesive rotary sonar images showing transient burial and reexposure of a surrogate UXO by migrating mega- ripples

Mega-earthquakes rupture flat megathrusts.

PubMed

Bletery, Quentin; Thomas, Amanda M; Rempel, Alan W; Karlstrom, Leif; Sladen, Anthony; De Barros, Louis

2016-11-25

The 2004 Sumatra-Andaman and 2011 Tohoku-Oki earthquakes highlighted gaps in our understanding of mega-earthquake rupture processes and the factors controlling their global distribution: A fast convergence rate and young buoyant lithosphere are not required to produce mega-earthquakes. We calculated the curvature along the major subduction zones of the world, showing that mega-earthquakes preferentially rupture flat (low-curvature) interfaces. A simplified analytic model demonstrates that heterogeneity in shear strength increases with curvature. Shear strength on flat megathrusts is more homogeneous, and hence more likely to be exceeded simultaneously over large areas, than on highly curved faults. Copyright © 2016, American Association for the Advancement of Science.

Giant Landslides, Mega-Tsunamis, and Paleo-Sea Level in the Hawaiian Islands

NASA Astrophysics Data System (ADS)

Watts, P.; McMurtry, G. M.; Fryer, G. J.; Smith, J. R.; Imamura, F.

2001-12-01

We show considerable agreement between the ages of the two giant Alika landslides and dating of debris found tens to hundreds of meters above sea level in Hawaii. Despite the size of the landslides, controversy persists as to the ability to generate landslide tsunamis big enough to deposit the debris. We affirm that tsunami deposits are a sufficient explanation of the observed pattern of debris height. We also show that our tsunami simulations can be used to reduce the considerable uncertainty in subsidence history of the different Hawaiian islands, a current obstacle to interpreting the supposed deposits. Finally, we show that the onset of interglacials provides a probable explanation for the timing of these giant landslides over the last five million years. We predict that the greatest tsunami hazard facing the Hawaiian islands are giant landslides and that the current interglacial promotes the generation of mega-tsunamis from catastrophic volcano collapse. Hawaiian giant submarine landslide events have been recognized from detached submarine landslide blocks and fields of smaller debris by offshore surveys. Mega-tsunamis produced by giant landslides were first proposed for Hawaii and have since been implicated globally at other oceanic islands and along the continental margins. While not discounting the possibility of locally-generated tsunamis, some researchers have cast doubt upon the original hypothesis of giant waves impacting Lanai and other Hawaiian islands from flank failures of the nearby Mauna Loa Volcano on Hawaii island. Landslide tsunami simulations have advanced to the point where the tsunamigenic potential of the giant submarine landslides can be affirmed, while the subsidence history of different Hawaiian islands is still subject to debate.

The appearance and propagation of filaments in the private flux region in Mega Amp Spherical Tokamak

DOE Office of Scientific and Technical Information (OSTI.GOV)

Harrison, J. R.; Fishpool, G. M.; Thornton, A. J.

2015-09-15

The transport of particles via intermittent filamentary structures in the private flux region (PFR) of plasmas in the MAST tokamak has been investigated using a fast framing camera recording visible light emission from the volume of the lower divertor, as well as Langmuir probes and IR thermography monitoring particle and power fluxes to plasma-facing surfaces in the divertor. The visible camera data suggest that, in the divertor volume, fluctuations in light emission above the X-point are strongest in the scrape-off layer (SOL). Conversely, in the region below the X-point, it is found that these fluctuations are strongest in the PFRmore » of the inner divertor leg. Detailed analysis of the appearance of these filaments in the camera data suggests that they are approximately circular, around 1–2 cm in diameter, but appear more elongated near the divertor target. The most probable toroidal quasi-mode number is between 2 and 3. These filaments eject plasma deeper into the private flux region, sometimes by the production of secondary filaments, moving at a speed of 0.5–1.0 km/s. Probe measurements at the inner divertor target suggest that the fluctuations in the particle flux to the inner target are strongest in the private flux region, and that the amplitude and distribution of these fluctuations are insensitive to the electron density of the core plasma, auxiliary heating and whether the plasma is single-null or double-null. It is found that the e-folding width of the time-average particle flux in the PFR decreases with increasing plasma current, but the fluctuations appear to be unaffected. At the outer divertor target, the fluctuations in particle and power fluxes are strongest in the SOL.« less

On meta- and mega-analyses for gene-environment interactions.

PubMed

Huang, Jing; Liu, Yulun; Vitale, Steve; Penning, Trevor M; Whitehead, Alexander S; Blair, Ian A; Vachani, Anil; Clapper, Margie L; Muscat, Joshua E; Lazarus, Philip; Scheet, Paul; Moore, Jason H; Chen, Yong

2017-12-01

Gene-by-environment (G × E) interactions are important in explaining the missing heritability and understanding the causation of complex diseases, but a single, moderately sized study often has limited statistical power to detect such interactions. With the increasing need for integrating data and reporting results from multiple collaborative studies or sites, debate over choice between mega- versus meta-analysis continues. In principle, data from different sites can be integrated at the individual level into a "mega" data set, which can be fit by a joint "mega-analysis." Alternatively, analyses can be done at each site, and results across sites can be combined through a "meta-analysis" procedure without integrating individual level data across sites. Although mega-analysis has been advocated in several recent initiatives, meta-analysis has the advantages of simplicity and feasibility, and has recently led to several important findings in identifying main genetic effects. In this paper, we conducted empirical and simulation studies, using data from a G × E study of lung cancer, to compare the mega- and meta-analyses in four commonly used G × E analyses under the scenario that the number of studies is small and sample sizes of individual studies are relatively large. We compared the two data integration approaches in the context of fixed effect models and random effects models separately. Our investigations provide valuable insights in understanding the differences between mega- and meta-analyses in practice of combining small number of studies in identifying G × E interactions. © 2017 WILEY PERIODICALS, INC.

Integrated Circuit Design of 3 Electrode Sensing System Using Two-Stage Operational Amplifier

NASA Astrophysics Data System (ADS)

Rani, S.; Abdullah, W. F. H.; Zain, Z. M.; N, Aqmar N. Z.

2018-03-01

This paper presents the design of a two-stage operational amplifier(op amp) for 3-electrode sensing system readout circuits. The designs have been simulated using 0.13μm CMOS technology from Silterra (Malaysia) with Mentor graphics tools. The purpose of this projects is mainly to design a miniature interfacing circuit to detect the redox reaction in the form of current using standard analog modules. The potentiostat consists of several op amps combined together in order to analyse the signal coming from the 3-electrode sensing system. This op amp design will be used in potentiostat circuit device and to analyse the functionality for each module of the system.

Mega-rings Surrounding Timber Mountain Nested Calderas, Geophysical Anomalies: Rethinking Structure and Volcanism Near Yucca Mountain (YM), Nevada

NASA Astrophysics Data System (ADS)

Tynan, M. C.; Smith, K. D.; Savino, J. M.; Vogt, T. J.

2004-12-01

Observed regional mega-rings define a zone ˜80-100 km in diameter centered on Timber Mountain (TM). The mega-rings encompass known smaller rhyolitic nested Miocene calderas ( ˜11-15 my, < 10 km circular to elliptical small "rings") and later stage basaltic features (< 11 my, small flows, cones, dikes) in the Southwest Nevada Volcanic Field. Miocene rhyolitic calderas cluster within the central area and on the outer margin of the interpreted larger mega-ring complex. The mega-ring interpretation is consistent with observations of regional physiography, tomographic images, seismicity patterns, and structural relationships. Mega-rings consist of arcuate faulted blocks with deformation (some remain active structures) patterns showing a genetic relationship to the TM volcanic system; they appear to be spatially associated and temporally correlated with Miocene volcanism and two geophysically identified crustal/upper mantle features. A 50+ km diameter pipe-like high velocity anomaly extends from crustal depth to over 200 km beneath TM (evidence for 400km depth to NE). The pipe is located between two ˜100 km sub-parallel N/S linear trends of small-magnitude earthquake activity, one extending through the central NV Test Site, and a second located near Beatty, NV. Neither the kinematics nor relational mechanism of 100km seismically active N/S linear zones, pipe, and mega-rings are understood. Interpreted mega-rings are: 1) Similar in size to larger terrestrial volcanic complexes (e.g., Yellowstone, Indonesia's Toba system); 2) Located in the region of structural transition from the Mohave block to the south, N/S Basin and Range features to the north, Walker Lane to the NW, and the Las Vegas Valley shear zone to the SE; 3) Associated with the two seismically active zones (similar to other caldera fault-bounded sags), the mantle high velocity feature, and possibly a regional bouguer gravity anomaly; 4) Nearly coincident with area hydrologic basins and sub-basins; 5) Similar to features described from terrestrial and planetary caldera-collapse studies, and as modeled in laboratory scaled investigations (ice melt, balloon/sand). Post Mid-Miocene basalts commonly occur within or adjacent to the older rhyolitic caldera moats; other basaltic material occurs marginal to both the outer rings of the interpreted mega-ring system and high velocity pipe. The YM repository may be situated in an isolated structural setting within the mega-ring system; basaltic materials are absent in the block for over 11my for geologic reasons. The mega-ring model may better explain YM area structures (Highway 95 fault), tectonism, and volcanism. Coincident physiographic, geologic, and geophysical features associated with the mega-rings feature, and temporal characteristics of regional seismicity and volcanism suggest the need to critically re-assess regional scale and YM tectonic, seismotectonic, and volcanic models.

Identification of the fatty acid activation site on human ClC-2.

PubMed

Cuppoletti, John; Tewari, Kirti P; Chakrabarti, Jayati; Malinowska, Danuta H

2017-06-01

Fatty acids (including lubiprostone and cobiprostone) are human ClC-2 (hClC-2) Cl - channel activators. Molecular and cellular mechanisms underlying this activation were examined. Role of a four-amino acid PKA activation site, RGET 691 , of hClC-2 was investigated using wild-type (WT) and mutant (AGET, RGEA, and AGAA) hClC-2 expressed in 293EBNA cells as well as involvement of PKA, intracellular cAMP concentration ([cAMP] i ), EP 2 , or EP 4 receptor agonist activity. All fatty acids [lubiprostone, cobiprostone, eicosatetraynoic acid (ETYA), oleic acid, and elaidic acid] caused significant rightward shifts in concentration-dependent Cl - current activation (increasing EC 50 s) with mutant compared with WT hClC-2 channels, without changing time and voltage dependence, current-voltage rectification, or methadone inhibition of the channel. As with lubiprostone, cobiprostone activation of hClC-2 occurred with PKA inhibitor (myristoylated protein kinase inhibitor) present or when using double PKA activation site (RRAA 655 /RGEA 691 ) mutant. Cobiprostone did not activate human CFTR. Fatty acids did not increase [cAMP] i in hClC-2/293EBNA or T84 cells. Using T84 CFTR knockdown cells, cobiprostone increased hClC-2 Cl - currents without increasing [cAMP] i, while PGE 2 and forskolin-IBMX increased both. Fatty acids were not agonists of EP 2 or EP 4 receptors. L-161,982, a supposed EP 4 -selective inhibitor, had no effect on lubiprostone-activated hClC-2 Cl - currents but significantly decreased T84 cell barrier function measured by transepithelial resistance and fluorescent dextran transepithelial movement. The present findings show that RGET 691 of hClC-2 (possible binding site) plays an important functional role in fatty acid activation of hClC-2. PKA, [cAMP] i , and EP 2 or EP 4 receptors are not involved. These studies provide the molecular basis for fatty acid regulation of hClC-2. Copyright © 2017 the American Physiological Society.

Aging management program of the reactor building concrete at Point Lepreau Generating Station

NASA Astrophysics Data System (ADS)

Aldea, C.-M.; Shenton, B.; Demerchant, M. M.; Gendron, T.

2011-04-01

In order for New Brunswick Power Nuclear (NBPN) to control the risks of degradation of the concrete reactor building at the Point Lepreau Generating Station (PLGS) the development of an aging management plan (AMP) was initiated. The intention of this plan was to determine the requirements for specific structural components of concrete of the reactor building that require regular inspection and maintenance to ensure the safe and reliable operation of the plant. The document is currently in draft form and presents an integrated methodology for the application of an AMP for the concrete of the reactor building. The current AMP addresses the reactor building structure and various components, such as joint sealant and liners that are integral to the structure. It does not include internal components housed within the structure. This paper provides background information regarding the document developed and the strategy developed to manage potential degradation of the concrete of the reactor building, as well as specific programs and preventive and corrective maintenance activities initiated.

Hepatic gene expression profiling of 5′-AMP-induced hypometabolism in mice

PubMed Central

Miki, Takao; Van Oort-Jansen, Anita; Matsumoto, Tomoko; Loose, David S.; Lee, Cheng Chi

2011-01-01

There is currently much interest in clinical applications of therapeutic hypothermia. Hypothermia can be a consequence of hypometabolism. We have recently established a procedure for the induction of a reversible deep hypometabolic state in mice using 5′-adenosine monophosphate (5′-AMP) in conjunction with moderate ambient temperature. The current study aims at investigating the impact of this technology at the gene expression level in a major metabolic organ, the liver. Our findings reveal that expression levels of the majority of genes in liver are not significantly altered by deep hypometabolism. However, among those affected by hypometabolism, more genes are differentially upregulated than downregulated both in a deep hypometabolic state and in the early arousal state. These altered gene expression levels during 5′-AMP induced hypometabolism are largely restored to normal levels within 2 days of the treatment. Our data also suggest that temporal control of circadian genes is largely stalled during deep hypometabolism. PMID:21224422

Sustained Release d-Amphetamine Reduces Cocaine but not ‘Speedball'-Seeking in Buprenorphine-Maintained Volunteers: A Test of Dual-Agonist Pharmacotherapy for Cocaine/Heroin Polydrug Abusers

PubMed Central

Greenwald, Mark K; Lundahl, Leslie H; Steinmiller, Caren L

2010-01-01

The aim of this study was to determine whether oral sustained release d-amphetamine (SR-AMP) reduces cocaine and opioid/cocaine combination (‘speedball'-like) seeking in volunteers with current opioid dependence and cocaine dependence. Following outpatient buprenorphine (BUP) 8 mg/day stabilization without SR-AMP, eight participants completed a 3-week in-patient study with continued BUP 8 mg/day maintenance and double-blind ascending SR-AMP weekly doses of 0, 30, and 60 mg/day, respectively. After 3 days (Saturday–Monday) stabilization at each SR-AMP weekly dose (0, 15, or 30 mg administered at 0700 and 1225 each day), on Tuesday–Friday mornings (0900–1200 hours), participants sampled four drug combinations in randomized, counterbalanced order under double-blind, double-dummy (intranasal cocaine and intramuscular hydromorphone) conditions: cocaine (COC 100 mg+saline); hydromorphone (COC 4 mg+HYD 24 mg); ‘speedball' (COC 100 mg+HYD 24 mg); and placebo (COC 4 mg+saline). Subjective and physiological effects of these drug combinations were measured. From 1230 to 1530 hours, participants could respond on a choice, 12-trial progressive ratio schedule to earn drug units (1/12th of total morning dose) or money units (US$2). SR-AMP significantly reduced COC, but not HYD or speedball, choices and breakpoints. SR-AMP also significantly reduced COC subjective (eg, abuse-related) effects and did not potentiate COC-induced cardiovascular responses. This study shows the ability of SR-AMP to attenuate COC self-administration, as well as its selectivity, in cocaine/heroin polydrug abusers. Further research is warranted to ascertain whether SR-AMP combined with BUP could be a useful dual-agonist pharmacotherapy. PMID:20881947

Role of Dynamics in the Autoinhibition and Activation of the Exchange Protein Directly Activated by Cyclic AMP (EPAC)*

PubMed Central

VanSchouwen, Bryan; Selvaratnam, Rajeevan; Fogolari, Federico; Melacini, Giuseppe

2011-01-01

The exchange protein directly activated by cAMP (EPAC) is a key receptor of cAMP in eukaryotes and controls critical signaling pathways. Currently, no residue resolution information is available on the full-length EPAC dynamics, which are known to be pivotal determinants of allostery. In addition, no information is presently available on the intermediates for the classical induced fit and conformational selection activation pathways. Here these questions are addressed through molecular dynamics simulations on five key states along the thermodynamic cycle for the cAMP-dependent activation of a fully functional construct of EPAC2, which includes the cAMP-binding domain and the integral catalytic region. The simulations are not only validated by the agreement with the experimental trends in cAMP-binding domain dynamics determined by NMR, but they also reveal unanticipated dynamic attributes, rationalizing previously unexplained aspects of EPAC activation and autoinhibition. Specifically, the simulations show that cAMP binding causes an extensive perturbation of dynamics in the distal catalytic region, assisting the recognition of the Rap1b substrate. In addition, analysis of the activation intermediates points to a possible hybrid mechanism of EPAC allostery incorporating elements of both the induced fit and conformational selection models. In this mechanism an entropy compensation strategy results in a low free-energy pathway of activation. Furthermore, the simulations indicate that the autoinhibitory interactions of EPAC are more dynamic than previously anticipated, leading to a revised model of autoinhibition in which dynamics fine tune the stability of the autoinhibited state, optimally sensitizing it to cAMP while avoiding constitutive activation. PMID:21873431

Research on Space Environmental Effect of Organic Composite Materials for Thermal Management of Satellites Using MC-50 Cyclotron

NASA Astrophysics Data System (ADS)

Kim, Dae-Weon; Kim, Dong-Iel; Huh, Yong-Hak; Yang, Tae-Keun; Lee, Ho-Young; Kim, Yong-Hyup

2005-12-01

The organic material is one of the most popular material for the satellites and the spacecrafts in order to perform the thermal management, and to protect direct exposure from the space environment. The present paper observes material property changes of organic material under the space environment by using ground facilities. One of the representative organic thermal management material of satellites, 2 mil ITO(Indium Tin Oxide) coated aluminized KAPTON was selected for experiments. In order to investigate the single parametric effect of protons in space environment, MC-50 cyclotron system in KIRAMS(Korea Institute of Radiological and Medical Science) was utilized for the ion beam irradiation of protons and ion beam dose was set to the Very Large August 1972 EVENT model, the highest protons occurrence near the earth orbit in history. The energy of ion beam is fixed to 30MeV(mega electron volt), observed average energy, and the equivalent irradiance time conditions were set to 1-year, 3-year, 5-year and 10-year exposure in space. The procedure of analyses includes the measurement of the ultimate tensile strength for the assessment of quantitative degradation in material properties, and the imaging analyses of crystalline transformation and damages on the exposed surface by FE-SEM(Field Emission Scanning Electron Spectroscopy) etc.

Reduction of extended-spectrum-β-lactamase- and AmpC-β-lactamase-producing Escherichia coli through processing in two broiler chicken slaughterhouses.

PubMed

Pacholewicz, Ewa; Liakopoulos, Apostolos; Swart, Arno; Gortemaker, Betty; Dierikx, Cindy; Havelaar, Arie; Schmitt, Heike

2015-12-23

Whilst broilers are recognised as a reservoir of extended-spectrum-β-lactamase (ESBL)- and AmpC-β-lactamase (AmpC)-producing Escherichia coli, there is currently limited knowledge on the effect of slaughtering on its concentrations on poultry meat. The aim of this study was to establish the concentration of ESBL/AmpC producing E. coli on broiler chicken carcasses through processing. In addition the changes in ESBL/AmpC producing E. coli concentrations were compared with generic E. coli and Campylobacter. In two slaughterhouses, the surface of the whole carcasses was sampled after 5 processing steps: bleeding, scalding, defeathering, evisceration and chilling. In total, 17 batches were sampled in two different slaughterhouses during the summers of 2012 and 2013. ESBL/AmpC producing E. coli was enumerated on MacConkey agar with 1mg/l cefotaxime, and the ESBL/AmpC phenotypes and genotypes were characterised. The ESBL/AmpC producing E. coli concentrations varied significantly between the incoming batches in both slaughterhouses. The concentrations on broiler chicken carcasses were significantly reduced during processing. In Slaughterhouse 1, all subsequent processing steps reduced the concentrations except evisceration which led to a slight increase that was statistically not significant. The changes in concentration between processing steps were relatively similar for all sampled batches in this slaughterhouse. In contrast, changes varied between batches in Slaughterhouse 2, and the overall reduction through processing was higher in Slaughterhouse 2. Changes in ESBL/AmpC producing E. coli along the processing line were similar to changes in generic E. coli in both slaughterhouses. The effect of defeathering differed between ESBL/AmpC producing E. coli and Campylobacter. ESBL/AmpC producing E. coli decreased after defeathering, whereas Campylobacter concentrations increased. The genotypes of ESBL/AmpC producing E. coli (blaCTX-M-1, blaSHV-12, blaCMY-2, blaTEM-52c, blaTEM-52cvar) from both slaughterhouses match typical poultry genotypes. Their distribution differed between batches and changed throughout processing for some batches. The concentration levels found after chilling were between 10(2) and 10(5)CFU/carcass. To conclude, changes in ESBL/AmpC producing E. coli concentrations on broiler chicken carcasses during processing are influenced by batch and slaughterhouse, pointing to the role of both primary production and process control for reducing ESBL/AmpC producing E. coli levels in final products. Due to similar changes upon processing, E. coli can be used as a process indicator of ESBL/AmpC producing E. coli, because the processing steps had similar impact on both organisms. Cross contamination may potentially explain shifts in genotypes within some batches through the processing. Copyright © 2015 Elsevier B.V. All rights reserved.

megaTALs: a rare-cleaving nuclease architecture for therapeutic genome engineering.

PubMed

Boissel, Sandrine; Jarjour, Jordan; Astrakhan, Alexander; Adey, Andrew; Gouble, Agnès; Duchateau, Philippe; Shendure, Jay; Stoddard, Barry L; Certo, Michael T; Baker, David; Scharenberg, Andrew M

2014-02-01

Rare-cleaving endonucleases have emerged as important tools for making targeted genome modifications. While multiple platforms are now available to generate reagents for research applications, each existing platform has significant limitations in one or more of three key properties necessary for therapeutic application: efficiency of cleavage at the desired target site, specificity of cleavage (i.e. rate of cleavage at 'off-target' sites), and efficient/facile means for delivery to desired target cells. Here, we describe the development of a single-chain rare-cleaving nuclease architecture, which we designate 'megaTAL', in which the DNA binding region of a transcription activator-like (TAL) effector is used to 'address' a site-specific meganuclease adjacent to a single desired genomic target site. This architecture allows the generation of extremely active and hyper-specific compact nucleases that are compatible with all current viral and nonviral cell delivery methods.

Urban Agglomeration and Extension in Northern Coast of West Java: A Transformation into Mega Region

NASA Astrophysics Data System (ADS)

Octifanny, Y.; Hudalah, D.

2017-07-01

In the past decade, at least three neighbouring metropolitan areas in the northwestern part of the island have been merging with each other: Jakarta Metropolitan Area (Jabodetabek), Bandung Metropolitan Area (Bandung Raya), and Cirebon Metropolitan Area (Ciayumajakuning). It is expected to be the first island-based mega-conurbation. This paper explores the potential emergence of mega region as a ground study, where mega region can be used for economic, logistic, transportation development. Authors use scoring analysis from economic and demographic indicators. The outcomes found a new and larger formation of city-region in the northern coast road networks (Pantura) - specifically western part of Java Island.

Progress on LMJ targets for ignition

NASA Astrophysics Data System (ADS)

Cherfils-Clérouin, C.; Boniface, C.; Bonnefille, M.; Fremerye, P.; Galmiche, D.; Gauthier, P.; Giorla, J.; Lambert, F.; Laffite, S.; Liberatore, S.; Loiseau, P.; Malinie, G.; Masse, L.; Masson-Laborde, P. E.; Monteil, M. C.; Poggi, F.; Seytor, P.; Wagon, F.; Willien, J. L.

2010-08-01

Targets designed to produce ignition on the Laser MegaJoule are presented. The LMJ experimental plans include the attempt of ignition and burn of an ICF capsule with 160 laser beams, delivering up to 1.4MJ and 380TW. New targets needing reduced laser energy with only a small decrease in robustness have then been designed for this purpose. Working specifically on the coupling efficiency parameter, i.e. the ratio of the energy absorbed by the capsule to the laser energy, has led to the design of a rugby-shaped cocktail hohlraum. 1D and 2D robustness evaluations of these different targets shed light on critical points for ignition, that can be traded off by tightening some specifications or by preliminary experimental and numerical tuning experiments.

Optimization and validation of a fast amplification protocol for AmpFlSTR® Profiler Plus® for rapid forensic human identification.

PubMed

Laurin, Nancy; Frégeau, Chantal

2012-01-01

The goal of this work was to optimize and validate a fast amplification protocol for the multiplex amplification of the STR loci included in AmpFlSTR(®) Profiler Plus(®) to expedite human DNA identification. By modifying the cycling conditions and by combining the use of a DNA polymerase optimized for high speed PCR (SpeedSTAR™ HS) and a more efficient thermal cycler instrument (Bio-RAD C1000™), we were able to reduce the amplification process from 4h to 26 min. No modification to the commercial AmpFlSTR(®) Profiler Plus(®) primer mix was required. When compared to the current Royal Canadian Mounted Police (RCMP) amplification protocol, no differences with regards to specificity, sensitivity, heterozygote peak height ratios and overall profile balance were noted. Moreover, complete concordance was obtained with profiles previously generated with the standard amplification protocol and minor alleles in mixture samples were reliably typed. An increase in n-4 stutter ratios (2.2% on average for all loci) was observed for profiles amplified with the fast protocol compared to the current procedure. Our results document the robustness of this rapid amplification protocol for STR profiling using the AmpFlSTR(®) Profiler Plus(®) primer set and demonstrate that comparable data can be obtained in substantially less time. This new approach could provide an alternative option to current multiplex STR typing amplification protocols in order to increase throughput or expedite time-sensitive cases. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Advanced Energy Conversion Concept for Beamed-Energy Propulsion.

DTIC Science & Technology

1987-08-21

pulsed simultaneously at 40 HL. the thruster will operate almost iMen&1 within the infra - sonIc regime. c) Asymmetric thrust considerations During low...LSD WAVES) - / TIME I-*- INFRA - SONIC I LEVITATIUN FREQUENCY Firm U-27 .?AmpUtude-laimpd macro-pulam .5 " I A. SIDE VIEW CUNICAL TIP ,?I , i...s equal local sta ic), and the sonic velocity. Since cool air can rush in only at the speed of sound, one would want to minimize the expanded plasma

MEGA5: Molecular Evolutionary Genetics Analysis Using Maximum Likelihood, Evolutionary Distance, and Maximum Parsimony Methods

PubMed Central

Tamura, Koichiro; Peterson, Daniel; Peterson, Nicholas; Stecher, Glen; Nei, Masatoshi; Kumar, Sudhir

2011-01-01

Comparative analysis of molecular sequence data is essential for reconstructing the evolutionary histories of species and inferring the nature and extent of selective forces shaping the evolution of genes and species. Here, we announce the release of Molecular Evolutionary Genetics Analysis version 5 (MEGA5), which is a user-friendly software for mining online databases, building sequence alignments and phylogenetic trees, and using methods of evolutionary bioinformatics in basic biology, biomedicine, and evolution. The newest addition in MEGA5 is a collection of maximum likelihood (ML) analyses for inferring evolutionary trees, selecting best-fit substitution models (nucleotide or amino acid), inferring ancestral states and sequences (along with probabilities), and estimating evolutionary rates site-by-site. In computer simulation analyses, ML tree inference algorithms in MEGA5 compared favorably with other software packages in terms of computational efficiency and the accuracy of the estimates of phylogenetic trees, substitution parameters, and rate variation among sites. The MEGA user interface has now been enhanced to be activity driven to make it easier for the use of both beginners and experienced scientists. This version of MEGA is intended for the Windows platform, and it has been configured for effective use on Mac OS X and Linux desktops. It is available free of charge from http://www.megasoftware.net. PMID:21546353

Mega-supramolecules for safer, cleaner fuel

NASA Astrophysics Data System (ADS)

Kornfield, Julie

Guided by the statistical mechanics of ring-chain equilibrium, we designed and synthesized polymers that self-assemble into ``mega-supramolecules'' (>=5,000 kg/mol) at low concentration (<=0.3%wt) in hydrocarbon liquids. Experimental results accord with model predictions that end-functional polymers, which distribute among cyclic and linear supramolecules, can form a significant population of mega-supramolecules at low total polymer concentration--if, and only if , the backbones are long (>400 kg/mol) and end-association strength is optimal (16-18kT). Hydrocarbon liquid fuels are the world's dominant power source (34% of global energy consumption). Transportation relies heavily on such liquids, presenting the risk of explosive post-impact fires. The collapse of the World Trade Center on September 11, 2001 inspired us to revisit polymers for mist control to mitigate post-impact fuel explosions. Rheological and both light and neutron scattering measurements of long end-functional polymers having polycyclooctadiene backbones and acid or amine end groups verify formation of mega-supramolecules. Post-impact flame propagations experiments show that mega-supramolecules control misting. Turbulent flow measurements show that mega-supramolecules reduce drag like ultra-long covalent polymers. With individual building blocks short enough to avoid hydrodynamic chain scission (400

Mega Tsunamis of the World Ocean and Their Implication for the Tsunami Hazard Assessment

NASA Astrophysics Data System (ADS)

Gusiakov, V. K.

2014-12-01

Mega tsunamis are the strongest tsunamigenic events of tectonic origin that are characterized by run-up heights up to 40-50 m measured along a considerable part of the coastline (up to 1000 km). One of the most important features of mega-tsunamis is their ability to cross the entire oceanic basin and to cause an essential damage to its opposite coast. Another important feature is their ability to penetrate into the marginal seas (like the Sea of Okhotsk, the Bering Sea) and cause dangerous water level oscillations along the parts of the coast, which are largely protected by island arcs against the impact of the strongest regional tsunamis. Among all known historical tsunamis (nearly 2250 events during the last 4000 years) they represent only a small fraction (less than 1%) however they are responsible for more than half the total tsunami fatalities and a considerable part of the overall tsunami damage. The source of all known mega tsunamis is subduction submarine earthquakes with magnitude 9.0 or higher having a return period from 200-300 years to 1000-1200 years. The paper presents a list of 15 mega tsunami events identified so far in historical catalogs with their basic source parameters, near-field and far-field impact effects and their generation and propagation features. The far-field impact of mega tsunamis is largely controlled by location and orientation of their earthquake source as well as by deep ocean bathymetry features. We also discuss the problem of the long-term tsunami hazard assessment when the occurrence of mega tsunamis is taken into account.

Involvement of plasma membrane-located calmodulin in the response decay of cyclic nucleotide-gated cation channel of cultured carrot cells.

PubMed

Kurosaki, F; Kaburaki, H; Nishi, A

1994-03-07

Increase in cytoplasmic cyclic AMP concentration stimulates Ca2+ influx through the cyclic AMP-gated cation channel in the plasma membrane of cultured carrot cells. However, the Ca2+ current terminated after a few minutes even in the presence of high concentrations of cyclic AMP indicating that hydrolysis of the nucleotide is not responsible for stop of the Ca2+ influx. Cyclic AMP evoked discharge of Ca2+ from inside-out sealed vesicles of carrot plasma membrane, and it was strongly inhibited when the suspension of the vesicles was supplemented with 1 microM of free Ca2+, while Ca2+ lower than 0.1 microM did not affect the Ca(2+)-release. The Ca2+ flux across plasma membrane was restored from this Ca(2+)-induced inhibition by the addition of calmodulin inhibitors or anti-calmodulin. These results suggest that Ca2+ influx initiated by the increase in intracellular cAMP in cultured carrot cells is terminated when the cytosolic Ca2+ concentration reaches the excitatory level in the cells, and calmodulin located in the plasma membrane plays an important role in the response decay of the cyclic nucleotide-gated Ca2+ channel.

Atrial corrected Fourier amplitude ratios for the scintigraphic quantitation of valvar regurgitation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dae, M.W.; Botvinick, E.H.; O'Connell, J.W.

1984-01-01

Current scintigraphic methods commonly overestimate the degree of valvar regurgitation (VR), and displace normal ratios from unity, owing largely to RA contamination of the RV region of interest in the ''best septal'' LAO projection. The authors developed a method to correct for this overlap, using the Fourier amplitude (AMP) ratio. Amplitude is first ''weighted'' for phase angle using a vectorial sum, to improve assessment in patients (PTS) with contraction abnormalities. RV AMP is then corrected for underestimation by adding the product of mean LAO RA AMP times the difference between RA areas in anterior and LAO projections to the calculatedmore » RV AMP. In 15 PTS with aortic or mitral VR, corrected AMP ratios (CAR) were compared to ratios assessed angiographically and in 12 PTS without VR were compared to uncorrected AMP ratios (UAR), and to stroke volume ratios (SVR) from SV images (SVI), and ED and ES counts data (CT). CAR interobserver agreement was high (R=.97). When VR PTS ranked by CAR as mild (1.3-1.8), moderate (1.9-2.5), or severe (>2.5) were compared to similar chatheterization based ranks, there were no significant differences using the Mann Whitney test for ordinal data. CAR is a simple, objective and reproducible method of quantitating VR. It reduces the error in those without VR, allows sensitive identification of mild VR, and maintains accurate assessment of severe VR.« less

Safeguards Technology Factsheet - Unattended Dual Current Monitor (UDCM)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Newell, Matthew R.

2016-04-13

The UDCM is a low-current measurement device designed to record sub-nano-amp to micro-amp currents from radiation detectors. The UDCM is a two-channel device that incorporates a Commercial-Off-The-Shelf (COTS) processor enabling both serial over USB as well as Ethernet communications. The instrument includes microSD and USB flash memory for data storage as well as a programmable High Voltage (HV) power supply for detector bias. The UDCM is packaged in the same enclosure, employs the same processor and has a similar user interface as the UMSR. A serial over USB communication line to the UDCM allows the use of existing versions ofmore » MIC software, while the Ethernet port is compatible with the new IAEA RAINSTORM communication protocol.« less

CTX-M-15 and OXA-10 beta lactamases in multi drug resistant Pseudomonas aeruginosa: First report from Pakistan.

PubMed

Ullah, Waheed; Qasim, Muhammad; Rahman, Hazir; Khan, Saadullah; Rehman, Zia Ur; Ali, Nawab; Muhammad, Noor

2017-04-01

Pseudomonas aeruginosa is an emerging threat to public health worldwide due to their rapid development of drug resistance including beta-lactamases. The present study was designed to investigate the incidence of β-lactamases and genotypic pattern of CTX and OXA in the clinical isolate of multidrug resistant P. aeruginosa. In this study a total of 102 MDR P. aeruginosa isolates obtained from Lady Reading Hospital, Peshawar, Pakistan were subjected to extended spectrum beta lactamase (ESBL), metallo beta lactamase (MBL) and plasmid mediated β-lactamase (AmpC) detection using phenotypic and molecular methods. Furthermore, sequencing of CTX and OXA gene was performed. Out of 102 MDR P. aeruginosa isolates, 71 (69.6%) were beta lactamase producers. The incidence of ESBL, MBL and AmpC in clinical isolates of P. aeruginosa was found to be 23.94%, 40.84% and 35.21% respectively. Co-production of ESBL and AmpC were also observed in some isolates. There were 14 (19.71%) CTX-M-15 harboring isolates which were ESBL (64.28%), MBL (21.42%) and AmpC (14.28%) producer. Co-production of ESBL/MBL (14.28%), ESBL/AmpC (14.28%) and MBL/AmpC (14.28%) were also observed in the CTX M-15 harboring isolates while 12.28% isolates were not ESBL, MBL or AmpC producer. OXA-10 was detected in 8 (11.26%) isolates which were ESBL (12.5%), MBL (37.5%) and AmpC (12.5%) producer. OXA 10 isolates also exhibit co-production of ESBL/AmpC (12.5%) and MBL/AmpC (12.5%). All CTX-M-15 carried the class A β-lactamase conserved domain while OXA-10 harbored conserved domain of class D β-lactamase. The current study for the first time reported and characterized the CTX-M-15 and OXA-10 among MDR P. aeruginosa isolates from Pakistan. Further efforts are needed to understand the molecular mechanism of drug resistance with CTX and OXA harboring P. aeruginosa isolates. Copyright © 2017 Elsevier Ltd. All rights reserved.

An adaptable multiple power source for mass spectrometry and other scientific instruments.

PubMed

Lin, T-Y; Anderson, G A; Norheim, R V; Prost, S A; LaMarche, B L; Leach, F E; Auberry, K J; Smith, R D; Koppenaal, D W; Robinson, E W; Paša-Tolić, L

2015-09-01

An Adaptable Multiple Power Source (AMPS) system has been designed and constructed. The AMPS system can provide up to 16 direct current (DC) (±400 V; 5 mA), 4 radio frequency (RF) (two 500 VPP sinusoidal signals each, 0.5-5 MHz) channels, 2 high voltage sources (±6 kV), and one ∼40 W, 250 °C temperature-regulated heater. The system is controlled by a microcontroller, capable of communicating with its front panel or a computer. It can assign not only pre-saved fixed DC and RF signals but also profiled DC voltages. The AMPS system is capable of driving many mass spectrometry components and ancillary devices and can be adapted to other instrumentation/engineering projects.

Antimicrobial Peptides as Potential Alternatives to Antibiotics in Food Animal Industry.

PubMed

Wang, Shuai; Zeng, Xiangfang; Yang, Qing; Qiao, Shiyan

2016-05-03

Over the last decade, the rapid emergence of multidrug-resistant pathogens has become a global concern, which has prompted the search for alternative antibacterial agents for use in food animals. Antimicrobial peptides (AMPs), produced by bacteria, insects, amphibians and mammals, as well as by chemical synthesis, are possible candidates for the design of new antimicrobial agents because of their natural antimicrobial properties and a low propensity for development of resistance by microorganisms. This manuscript reviews the current knowledge of the basic biology of AMPs and their applications in non-ruminant nutrition. Antimicrobial peptides not only have broad-spectrum activity against bacteria, fungi, and viruses but also have the ability to bypass the common resistance mechanisms that are placing standard antibiotics in jeopardy. In addition, AMPs have beneficial effects on growth performance, nutrient digestibility, intestinal morphology and gut microbiota in pigs and broilers. Therefore, AMPs have good potential as suitable alternatives to conventional antibiotics used in swine and poultry industries.

Adenosine 5'-monophosphate blocks acetaminophen toxicity by increasing ubiquitination-mediated ASK1 degradation.

PubMed

Yang, Xiao; Zhan, Yibei; Sun, Qi; Xu, Xi; Kong, Yi; Zhang, Jianfa

2017-01-24

Acetaminophen (APAP) overdose is the most frequent cause of drug-induced liver failure in the world. Hepatic c-jun NH2-terminal protein kinase (JNK) activation is thought to be a consequence of oxidative stress produced during APAP metabolism. Activation of JNK signals causes hepatocellular damage with necrotic and apoptotic cell death. Here we found that APAP caused a feedback increase in plasma adenosine 5'-monophsphate (5'-AMP). We demonstrated that co-administration of APAP and 5'-AMP significantly ameliorated APAP-induced hepatotoxicity in mice, without influences on APAP metabolism and its analgesic function. The mechanism of protection by 5'-AMP was through inhibiting APAP-induced activation of JNK, and attenuating downstream c-jun and c-fos gene expression. This was triggered by attenuating apoptosis signal-regulated kinase 1(ASK1) methylation and increasing ubiquitination-mediated ASK1 protein degradation. Our findings indicate that replacing the current APAP with a safe and functional APAP/5'-AMP formulation could prevent APAP-induced hepatotoxicity.

Adenosine 5′-monophosphate blocks acetaminophen toxicity by increasing ubiquitination-mediated ASK1 degradation

PubMed Central

Sun, Qi; Xu, Xi; Kong, Yi; Zhang, Jianfa

2017-01-01

Acetaminophen (APAP) overdose is the most frequent cause of drug-induced liver failure in the world. Hepatic c-jun NH2-terminal protein kinase (JNK) activation is thought to be a consequence of oxidative stress produced during APAP metabolism. Activation of JNK signals causes hepatocellular damage with necrotic and apoptotic cell death. Here we found that APAP caused a feedback increase in plasma adenosine 5′-monophsphate (5′-AMP). We demonstrated that co-administration of APAP and 5′-AMP significantly ameliorated APAP-induced hepatotoxicity in mice, without influences on APAP metabolism and its analgesic function. The mechanism of protection by 5′-AMP was through inhibiting APAP-induced activation of JNK, and attenuating downstream c-jun and c-fos gene expression. This was triggered by attenuating apoptosis signal-regulated kinase 1(ASK1) methylation and increasing ubiquitination-mediated ASK1 protein degradation. Our findings indicate that replacing the current APAP with a safe and functional APAP/5′-AMP formulation could prevent APAP-induced hepatotoxicity. PMID:28031524

Mega wildfire in the World Biosphere Reserve (UNESCO), Torres del Paine National Park, Patagonia - Chile 2012: Work experience in extreme behavior conditions in the context of global warming

Treesearch

René Cifuentes Medina

2013-01-01

Mega wildfires are critical, high-impact events that cause severe environmental, economic and social damage, resulting, in turn, in high-cost suppression operations and the need for mutual support, phased use of resources and the coordinated efforts of civilian government agencies, the armed forces, private companies and the international community. The mega forest...

A Pair Production Telescope for Medium-Energy Gamma-Ray Polarimetry

NASA Technical Reports Server (NTRS)

Hunter, Stanley D.; Bloser, Peter F.; Depaola, Gerardo; Dion, Michael P.; DeNolfo, Georgia A.; Hanu, Andrei; Iparraguirre, Marcos; Legere, Jason; Longo, Francesco; McConnell, Mark L.;

Membrane electrode gasket assembly (MEGA) technology for polymer electrolyte fuel cells

NASA Astrophysics Data System (ADS)

Pozio, A.; Giorgi, L.; De Francesco, M.; Silva, R. F.; Lo Presti, R.; Danzi, A.

A new technology for the production of a membrane electrode gasket assembly (MEGA) for polymer electrolyte fuel cells (PEFCs) is defined. The MEGA system was prepared by sealing a previously prepared membrane electrode assembly (MEA) in a moulded gasket. For this aim, a proprietary silicone based liquid mixture was injected directly into the MEA borders. Gaskets obtained in different shapes and hardness grades are stable in a wide temperature range. The MEGA technology shows several advantages with respect to traditional PEFCs stack assembling systems: effective membrane saving, reduced fabrication time, possibility of quality control and failed elements substitution. This technology was successfully tested at the ENEA laboratories and the results were acquired in laboratory scale, but industrial production appears to be simple and cheap.

Can Boards of Directors Think Strategically? Some Issues in Developing Direction-Givers' Thinking to a Mega Level

ERIC Educational Resources Information Center

Garratt, Bob

2005-01-01

The author argues that current corporate government legislation and practice is weighted too much in the direction of "board compliance." It is, therefore, in danger of reducing the risks taken by boards of directors. In the long term this could slow significantly the growth of capitalism. He proposes a rebalancing of the fundamental board…

Cross-shore stratified tidal flow seaward of a mega-nourishment

NASA Astrophysics Data System (ADS)

Meirelles, Saulo; Henriquez, Martijn; Reniers, Ad; Luijendijk, Arjen P.; Pietrzak, Julie; Horner-Devine, Alexander R.; Souza, Alejandro J.; Stive, Marcel J. F.

2018-01-01

The Sand Engine is a 21.5 million m3 experimental mega-nourishment project that was built in 2011 along the Dutch coast. This intervention created a discontinuity in the previous straight sandy coastline, altering the local hydrodynamics in a region that is influenced by the buoyant plume generated by the Rhine River. This work investigates the response of the cross-shore stratified tidal flow to the coastal protrusion created by the Sand Engine emplacement by using a 13 h velocity and density survey. Observations document the development of strong baroclinic-induced cross-shore exchange currents dictated by the intrusion of the river plume fronts as well as the classic tidal straining which are found to extend further into the nearshore (from 12 to 6 m depth), otherwise believed to be a mixed zone. Estimates of the centrifugal acceleration directly after construction of the Sand Engine showed that the curvature effects were approximately 2 times stronger, suggesting that the Sand Engine might have played a role in controlling the cross-shore exchange currents during the first three years after the completion of the nourishment. Presently, the curvature effects are minute.

cGMP and cyclic nucleotide-gated channels participate in mouse sperm capacitation.

PubMed

Cisneros-Mejorado, Abraham; Sánchez Herrera, Daniel P

2012-01-20

During capacitation of mammalian sperm intracellular [Ca(2+)] and cyclic nucleotides increase, suggesting that CNG channels play a role in the physiology of sperm. Here we study the effect of capacitation, 8Br-cAMP (8-bromoadenosine 3',5'-cyclic monophosphate) and 8Br-cGMP (8-bromoguanosine 3',5'-cyclic monophosphate) on the macroscopic ionic currents of mouse sperm, finding the existence of different populations of sperm, in terms of the recorded current and its response to cyclic nucleotides. Our results show that capacitation and cyclic nucleotides increase the ionic current, having a differential sensitivity to cGMP (cyclic guanosine monophosphate) and cAMP (cyclic adenosine monophosphate). Using a specific inhibitor we determine the contribution of CNG channels to macroscopic current and capacitation. Copyright © 2011 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

Cross talk between cyclic AMP and the polyphosphoinositide signaling cascade in iris sphincter and other nonvascular smooth muscle.

PubMed

Abdel-Latif, A A

1996-02-01

Nonvascular smooth muscle, such as the iris sphincter, receives double reciprocal innervation: stimulation of the parasympathetic nervous system (cholinergic muscarinic), which functions through the polyphosphoinositide (PPI) signaling pathway, contracts it, while activation of the sympathetic nervous system (beta-adrenergic), which functions through the cAMP system, relaxes it. Interactions between the two second messenger systems are important in regulation of smooth muscle tone and represent an important focal point for pharmacological manipulation. Here, I have summarized the experimental evidence in support of the hypothesis that the cross talk between cAMP and the PPI cascade could constitute a biochemical correlate for this functional antagonism. Recent studies suggest that cAMP inhibition is on Ca2+ mobilization rather than myosin light chain phosphorylation. Thus, cAMP-elevating agents, which inhibit agonist-induced PPI hydrolysis, are effective relaxants. Furthermore, inositol 1,4,5-trisphosphate (IP3) appears to be involved in both Ca2+ release from the sarcoplasmic reticulum and in Ca2+ influx through the plasma membrane, and since a reduction in intracellular Ca2+ ([Ca2+]i) is the underlying mechanism for cAMP-mediated relaxation, an important target for cAMP inhibition would be either to inhibit IP3 production or to stimulate IP3 inactivation. In the iris sphincter and other nonvascular smooth muscle there is reasonable experimental evidence that shows that cAMP inhibits phospholipase C activation and stimulates IP3 3-kinase activity, both of which can result in: [i) reduction in IP3 concentrations and (ii) reduction in IP3-dependent Ca2+ mobilization, which may lead to muscle relaxation. In addition to IP3-induced Ca2+ mobilization, changes in [Ca2+]i are the result of the interplay of many processes which may also serve as potential sites for cAMP inhibition. A great deal of progress has been made on the cross talk between cAMP and the PPI signaling cascade in the past decade, and there will be more on the regulation of the second messenger systems and their involvement in smooth muscle tone in the coming years. Clearly, an understanding of the physiological and pathophysiological regulation of smooth muscle tone is central to the development of novel therapeutic agents for the treatment of diseases such as asthma and glaucoma, where cAMP-elevating drugs are currently employed.

Rupture process of the 2013 Okhotsk deep mega earthquake from iterative backprojection and compress sensing methods

NASA Astrophysics Data System (ADS)

Qin, W.; Yin, J.; Yao, H.

2013-12-01

On May 24th 2013 a Mw 8.3 normal faulting earthquake occurred at a depth of approximately 600 km beneath the sea of Okhotsk, Russia. It is a rare mega earthquake that ever occurred at such a great depth. We use the time-domain iterative backprojection (IBP) method [1] and also the frequency-domain compressive sensing (CS) technique[2] to investigate the rupture process and energy radiation of this mega earthquake. We currently use the teleseismic P-wave data from about 350 stations of USArray. IBP is an improved method of the traditional backprojection method, which more accurately locates subevents (energy burst) during earthquake rupture and determines the rupture speeds. The total rupture duration of this earthquake is about 35 s with a nearly N-S rupture direction. We find that the rupture is bilateral in the beginning 15 seconds with slow rupture speeds: about 2.5km/s for the northward rupture and about 2 km/s for the southward rupture. After that, the northward rupture stopped while the rupture towards south continued. The average southward rupture speed between 20-35 s is approximately 5 km/s, lower than the shear wave speed (about 5.5 km/s) at the hypocenter depth. The total rupture length is about 140km, in a nearly N-S direction, with a southward rupture length about 100 km and a northward rupture length about 40 km. We also use the CS method, a sparse source inversion technique, to study the frequency-dependent seismic radiation of this mega earthquake. We observe clear along-strike frequency dependence of the spatial and temporal distribution of seismic radiation and rupture process. The results from both methods are generally similar. In the next step, we'll use data from dense arrays in southwest China and also global stations for further analysis in order to more comprehensively study the rupture process of this deep mega earthquake. Reference [1] Yao H, Shearer P M, Gerstoft P. Subevent location and rupture imaging using iterative backprojection for the 2011 Tohoku Mw 9.0 earthquake. Geophysical Journal International, 2012, 190(2): 1152-1168. [2]Yao H, Gerstoft P, Shearer P M, et al. Compressive sensing of the Tohoku-Oki Mw 9.0 earthquake: Frequency-dependent rupture modes. Geophysical Research Letters, 2011, 38(20).

Spectra of electrons emitted as a result of the sticking and annihilation of low energy positrons to the surfaces of graphene and highly oriented pyrolytic graphite (HOPG)

NASA Astrophysics Data System (ADS)

Chrysler, M.; Chirayath, V.; McDonald, A.; Lim, Z.; Shastry, K.; Gladen, R.; Fairchild, A.; Koymen, A.; Weiss, A.

Positron annihilation induced Auger electron spectroscopy (PAES) was used to study the positron induced low energy electron spectra from HOPG and a sample composed of 6-8 layers of graphene grown on polycrystalline copper. A low energy (~2eV) beam of positrons was used to implant positrons into a surface localized state on the graphene and HOPG samples. Measurements of the energy spectra of the positron induced electrons obtained using a TOF spectrometer indicate the presence of an annihilation induced KLL C Auger peak (at ~263 eV) along with a narrow low energy secondary peak due to an Auger mediated positron sticking (AMPS) process. A broad spectral feature was also observed below ~15 eV which we believe may be due to a VVV C Auger transition not previously observed. The energy dependence of the integrated intensity of the AMPS peak was measured for a series of incident positron kinetic energies ranging from ~1.5 eV up to 11 eV from which the binding energy of the surface localized positron state on graphene and HOPG was estimated. The implication of our results regarding the applicability of AMPS and PAES to the study of graphene surfaces and interfaces will be discussed. This work was supported by NSF Grant No. DMR 1508719 and DMR 1338130.

NRSF causes cAMP-sensitive suppression of sodium current in cultured hippocampal neurons

NASA Technical Reports Server (NTRS)

Nadeau, H.; Lester, H. A.

2002-01-01

The neuron restrictive silencer factor (NRSF/REST) has been shown to bind to the promoters of many neuron-specific genes and is able to suppress transcription of Na(+) channels in PC12 cells, although its functional effect in terminally differentiated neurons is unknown. We constructed lentiviral vectors to express NRSF as a bicistronic message with green fluorescent protein (GFP) and followed infected hippocampal neurons in culture over a period of 1-2 wk. NRSF-expressing neurons showed a time-dependent suppression of Na(+) channel function as measured by whole cell electrophysiology. Suppression was reversed or prevented by the addition of membrane-permeable cAMP analogues and enhanced by cAMP antagonists but not affected by increasing protein expression with a viral enhancer. Secondary effects, including altered sensitivity to glutamate and GABA and reduced outward K(+) currents, were duplicated by culturing GFP-infected control neurons in TTX. The striking similarity of the phenotypes makes NRSF potentially useful as a genetic "silencer" and also suggests avenues of further exploration that may elucidate the transcription factor's in vivo role in neuronal plasticity.

Deep-sea seabed habitats: Do they support distinct mega-epifaunal communities that have different vulnerabilities to anthropogenic disturbance?

NASA Astrophysics Data System (ADS)

Bowden, David A.; Rowden, Ashley A.; Leduc, Daniel; Beaumont, Jennifer; Clark, Malcolm R.

2016-01-01

Growing economic interest in seabed resources in the deep-sea highlights the need for information about the spatial distribution and vulnerability to disturbance of benthic habitats and fauna. Categorisation of seabed habitats for management is often based on topographic features such as canyons and seamounts that can be distinguished using regional bathymetry ('mega-habitats'). This is practical but because such habitats are contiguous with others, there is potential for overlap in the communities associated with them. Because concepts of habitat and community vulnerability are based on the traits of individual taxa, the nature and extent of differences between communities have implications for strategies to manage the environmental effects of resource use. Using towed video camera transects, we surveyed mega-epifaunal communities of three topographically-defined habitats (canyon, seamount or knoll, and continental slope) and two physico-chemically defined meso-scale habitats (cold seep and hydrothermal vent) in two regions off New Zealand to assess whether each supports a distinct type of community. Cold seep and hydrothermal vent communities were strongly distinct from those in other habitats. Across the other habitats, however, distinctions between communities were often weak and were not consistent between regions. Dissimilarities among communities across all habitats were stronger and the density of filter-feeding taxa was higher in the Bay of Plenty than on the Hikurangi Margin, whereas densities of predatory and scavenging taxa were higher on the Hikurangi Margin. Substratum diversity at small spatial scales (<1 km) and trawl history were significantly correlated with community composition in both regions. We conclude that, (1) a lack of consistent distinction between communities raises questions about the general utility of topographically-defined mega-habitats in environmental management, (2) fine-scale survey of individual features is necessary to identify the locations, characteristics, and extents of ecologically important or vulnerable seabed communities, and (3) evaluation of habitat vulnerability to future events should be in the context of previous and current disturbances.

The styryl dye FM1-43 suppresses odorant responses in a subset of olfactory neurons by blocking cyclic nucleotide-gated (CNG) channels.

PubMed

Breunig, Esther; Kludt, Eugen; Czesnik, Dirk; Schild, Detlev

2011-08-12

Many olfactory receptor neurons use a cAMP-dependent transduction mechanism to transduce odorants into depolarizations. This signaling cascade is characterized by a sequence of two currents: a cation current through cyclic nucleotide-gated channels followed by a chloride current through calcium-activated chloride channels. To date, it is not possible to interfere with these generator channels under physiological conditions with potent and specific blockers. In this study we identified the styryl dye FM1-43 as a potent blocker of native olfactory cyclic nucleotide-gated channels. Furthermore, we characterized this substance to stain olfactory receptor neurons that are endowed with cAMP-dependent transduction. This allows optical differentiation and pharmacological interference with olfactory receptor neurons at the level of the signal transduction.

Space station power semiconductor package

NASA Technical Reports Server (NTRS)

Balodis, Vilnis; Berman, Albert; Devance, Darrell; Ludlow, Gerry; Wagner, Lee

1987-01-01

A package of high-power switching semiconductors for the space station have been designed and fabricated. The package includes a high-voltage (600 volts) high current (50 amps) NPN Fast Switching Power Transistor and a high-voltage (1200 volts), high-current (50 amps) Fast Recovery Diode. The package features an isolated collector for the transistors and an isolated anode for the diode. Beryllia is used as the isolation material resulting in a thermal resistance for both devices of .2 degrees per watt. Additional features include a hermetical seal for long life -- greater than 10 years in a space environment. Also, the package design resulted in a low electrical energy loss with the reduction of eddy currents, stray inductances, circuit inductance, and capacitance. The required package design and device parameters have been achieved. Test results for the transistor and diode utilizing the space station package is given.

Antimicrobial peptides expressed in medicinal maggots of the blow fly Lucilia sericata show combinatorial activity against bacteria.

PubMed

Pöppel, Anne-Kathrin; Vogel, Heiko; Wiesner, Jochen; Vilcinskas, Andreas

2015-05-01

The larvae of the common green bottle fly (Lucilia sericata) produce antibacterial secretions that have a therapeutic effect on chronic and nonhealing wounds. Recent developments in insect biotechnology have made it possible to use these larvae as a source of novel anti-infectives. Here, we report the application of next-generation RNA sequencing (RNA-Seq) to characterize the transcriptomes of the larval glands, crop, and gut, which contribute to the synthesis of antimicrobial peptides (AMPs) and proteins secreted into wounds. Our data confirm that L. sericata larvae have adapted in order to colonize microbially contaminated habitats, such as carrion and necrotic wounds, and are protected against infection by a diverse spectrum of AMPs. L. sericata AMPs include not only lucifensin and lucimycin but also novel attacins, cecropins, diptericins, proline-rich peptides, and sarcotoxins. We identified 47 genes encoding putative AMPs and produced 23 as synthetic analogs, among which some displayed activities against a broad spectrum of microbial pathogens, including Pseudomonas aeruginosa, Proteus vulgaris, and Enterococcus faecalis. Against Escherichia coli (Gram negative) and Micrococcus luteus (Gram positive), we found mostly additive effects but also synergistic activity when selected AMPs were tested in combination. The AMPs that are easy to synthesize are currently being produced in bulk to allow their evaluation as novel anti-infectives that can be formulated in hydrogels to produce therapeutic wound dressings and adhesive bandages. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Drug repurposing identifies a synergistic combination therapy with imatinib mesylate for gastrointestinal stromal tumor.

PubMed

Pessetto, Ziyan Y; Ma, Yan; Hirst, Jeff J; von Mehren, Margaret; Weir, Scott J; Godwin, Andrew K

2014-10-01

Gastrointestinal stromal tumor (GIST) is a rare and therefore often neglected disease. Introduction of the kinase inhibitor imatinib mesylate radically improved the clinical response of patients with GIST; however, its effects are often short-lived, with GISTs demonstrating a median time-to-progression of approximately two years. Although many investigational drugs, approved first for other cancers, have been subsequently evaluated for the management of GIST, few have greatly affected the overall survival of patients with advanced disease. We employed a novel, focused, drug-repurposing effort for GIST, including imatinib mesylate-resistant GIST, evaluating a large library of FDA-approved drugs regardless of current indication. As a result of the drug-repurposing screen, we identified eight FDA-approved drugs, including fludarabine phosphate (F-AMP), that showed synergy with and/or overcame resistance to imatinib mesylate. F-AMP induces DNA damage, Annexin V, and caspase-3/7 activities as the cytotoxic effects on GIST cells, including imatinib mesylate-resistant GIST cells. F-AMP and imatinib mesylate combination treatment showed greater inhibition of GIST cell proliferation when compared with imatinib mesylate and F-AMP alone. Successful in vivo experiments confirmed the combination of imatinib mesylate with F-AMP enhanced the antitumor effects compared with imatinib mesylate alone. Our results identified F-AMP as a promising, repurposed drug therapy for the treatment of GISTs, with potential to be administered in combination with imatinib mesylate or for treatment of imatinib mesylate-refractory tumors. ©2014 American Association for Cancer Research.

Improving Behavioral Support for Smoking Cessation in Pregnancy: What Are the Barriers to Stopping and Which Behavior Change Techniques Can Influence These? Application of Theoretical Domains Framework.

PubMed

Campbell, Katarzyna A; Fergie, Libby; Coleman-Haynes, Tom; Cooper, Sue; Lorencatto, Fabiana; Ussher, Michael; Dyas, Jane; Coleman, Tim

2018-02-17

Behavioral support interventions are used to help pregnant smokers stop; however, of those tested, few are proven effective. Systematic research developing effective pregnancy-specific behavior change techniques (BCTs) is ongoing. This paper reports contributory work identifying potentially-effective BCTs relative to known important barriers and facilitators (B&Fs) to smoking cessation in pregnancy; to detect priority areas for BCTs development. A Nominal Group Technique with cessation experts ( n = 12) elicited an expert consensus on B&Fs most influencing women's smoking cessation and those most modifiable through behavioral support. Effective cessation interventions in randomized trials from a recent Cochrane review were coded into component BCTs using existing taxonomies. B&Fs were categorized using Theoretical Domains Framework (TDF) domains. Matrices, mapping BCT taxonomies against TDF domains, were consulted to investigate the extent to which BCTs in existing interventions target key B&Fs. Experts ranked "smoking a social norm" and "quitting not a priority" as most important barriers and "desire to protect baby" an important facilitator to quitting. From 14 trials, 23 potentially-effective BCTs were identified (e.g., information about consequences). Most B&Fs fell into "Social Influences", "Knowledge", "Emotions" and "Intentions" TDF domains; few potentially-effective BCTs mapped onto every TDF domain. B&Fs identified by experts as important to cessation, are not sufficiently targeted by BCT's currently within interventions for smoking cessation in pregnancy.

Multifunctional Mitochondrial Epac1 Controls Myocardial Cell Death.

PubMed

Fazal, Loubina; Laudette, Marion; Paula-Gomes, Sílvia; Pons, Sandrine; Conte, Caroline; Tortosa, Florence; Sicard, Pierre; Sainte-Marie, Yannis; Bisserier, Malik; Lairez, Olivier; Lucas, Alexandre; Roy, Jérôme; Ghaleh, Bijan; Fauconnier, Jérémy; Mialet-Perez, Jeanne; Lezoualc'h, Frank

2017-02-17

Although the second messenger cyclic AMP (cAMP) is physiologically beneficial in the heart, it largely contributes to cardiac disease progression when dysregulated. Current evidence suggests that cAMP is produced within mitochondria. However, mitochondrial cAMP signaling and its involvement in cardiac pathophysiology are far from being understood. To investigate the role of MitEpac1 (mitochondrial exchange protein directly activated by cAMP 1) in ischemia/reperfusion injury. We show that Epac1 (exchange protein directly activated by cAMP 1) genetic ablation ( Epac1 -/- ) protects against experimental myocardial ischemia/reperfusion injury with reduced infarct size and cardiomyocyte apoptosis. As observed in vivo, Epac1 inhibition prevents hypoxia/reoxygenation-induced adult cardiomyocyte apoptosis. Interestingly, a deleted form of Epac1 in its mitochondrial-targeting sequence protects against hypoxia/reoxygenation-induced cell death. Mechanistically, Epac1 favors Ca 2+ exchange between the endoplasmic reticulum and the mitochondrion, by increasing interaction with a macromolecular complex composed of the VDAC1 (voltage-dependent anion channel 1), the GRP75 (chaperone glucose-regulated protein 75), and the IP3R1 (inositol-1,4,5-triphosphate receptor 1), leading to mitochondrial Ca 2+ overload and opening of the mitochondrial permeability transition pore. In addition, our findings demonstrate that MitEpac1 inhibits isocitrate dehydrogenase 2 via the mitochondrial recruitment of CaMKII (Ca 2+ /calmodulin-dependent protein kinase II), which decreases nicotinamide adenine dinucleotide phosphate hydrogen synthesis, thereby, reducing the antioxidant capabilities of the cardiomyocyte. Our results reveal the existence, within mitochondria, of different cAMP-Epac1 microdomains that control myocardial cell death. In addition, our findings suggest Epac1 as a promising target for the treatment of ischemia-induced myocardial damage. © 2017 American Heart Association, Inc.

Advanced Compton scattering light source R&D at LLNL

DOE Office of Scientific and Technical Information (OSTI.GOV)

Albert, F; Anderson, S G; Anderson, G

2010-02-16

We report the design and current status of a monoenergetic laser-based Compton scattering 0.5-2.5 MeV {gamma}-ray source. Previous nuclear resonance fluorescence results and future linac and laser developments for the source are presented. At MeV photon energies relevant for nuclear processes, Compton scattering light sources are attractive because of their relative compactness and improved brightness above 100 keV, compared to typical 4th generation synchrotrons. Recent progress in accelerator physics and laser technology have enabled the development of a new class of tunable Mono-Energetic Gamma-Ray (MEGa-Ray) light sources based on Compton scattering between a high-brightness, relativistic electron beam and a highmore » intensity laser pulse produced via chirped-pulse amplification (CPA). A new precision, tunable gamma-ray source driven by a compact, high-gradient X-band linac is currently under development and construction at LLNL. High-brightness, relativistic electron bunches produced by an X-band linac designed in collaboration with SLAC will interact with a Joule-class, 10 ps, diode-pumped CPA laser pulse to generate tunable {gamma}-rays in the 0.5-2.5 MeV photon energy range via Compton scattering. Based on the success of the previous Thomson-Radiated Extreme X-rays (T-REX) Compton scattering source at LLNL, the source will be used to excite nuclear resonance fluorescence lines in various isotopes; applications include homeland security, stockpile science and surveillance, nuclear fuel assay, and waste imaging and assay. After a brief presentation of successful nuclear resonance fluorescence (NRF) experiments done with T-REX, the new source design, key parameters, and current status are presented.« less

Adolescent and adult rat cortical protein kinase A display divergent responses to acute ethanol exposure

PubMed Central

Gigante, Eduardo D.; Santerre, Jessica L.; Carter, Jenna M.; Werner, David F.

2014-01-01

Adolescent rats display reduced sensitivity to many dysphoria-related effects of alcohol (ethanol) including motor ataxia and sedative hypnosis, but the underlying neurobiological factors that contribute to these differences remain unknown. The cyclic adenosine monophosphate (cAMP)-dependent protein kinase A (PKA) pathway, particularly the type II regulatory subunit (RII), has been implicated in ethanol-induced molecular and behavioral responses in adults. Therefore, the current study examined cerebral cortical PKA in adolescent and adult ethanol responses. With the exception of early adolescence, PKA RIIα and RIIβ subunit levels largely did not differ from adult levels in either whole cell lysate or P2 synaptosomal expression. However, following acute ethanol exposure, PKA RIIβ P2 synaptosomal expression and activity were increased in adults, but not in adolescents. Behaviorally, intracerebroventricular administration of the PKA activator Sp-cAMP and inhibitor Rp-cAMP prior to ethanol administration increased adolescent sensitivity to the sedative-hypnotic effects of ethanol compared to controls. Sp-cAMP was ineffective in adults whereas Rp-cAMP suggestively reduced loss of righting reflex (LORR) with paralleled increases in blood ethanol concentrations. Overall, these data suggest that PKA activity modulates the sedative/hypnotic effects of ethanol and may potentially play a wider role in the differential ethanol responses observed between adolescents and adults. PMID:24874150

Current state of a dual behaviour of antimicrobial peptides-Therapeutic agents and promising delivery vectors.

PubMed

Piotrowska, Urszula; Sobczak, Marcin; Oledzka, Ewa

2017-12-01

Micro-organism resistance is an important challenge in modern medicine due to the global uncontrolled use of antibiotics. Natural and synthetic antimicrobial peptides (AMPs) symbolize a new family of antibiotics, which have stimulated research and clinical interest as new therapeutic options for infections. They represent one of the most promising antimicrobial substances, due to their broad spectrum of biological activity, against bacteria, fungi, protozoa, viruses, yeast and even tumour cells. Besides, being antimicrobial, AMPs have been shown to bind and neutralize bacterial endotoxins, as well as possess immunomodulatory, anti-inflammatory, wound-healing, angiogenic and antitumour properties. In contrast to conventional antibiotics, which have very defined and specific molecular targets, host cationic peptides show varying, complex and very rapid mechanisms of actions that make it difficult to form an effective antimicrobial defence. Importantly, AMPs display their antimicrobial activity at micromolar concentrations or less. To do this, many peptide-based drugs are commercially available for the treatment of numerous diseases, such as hepatitis C, myeloma, skin infections and diabetes. Herein, we present an overview of the general mechanism of AMPs action, along with recent developments regarding carriers of AMPs and their potential applications in medical fields. © 2017 John Wiley & Sons A/S.

A Balanced Risk-Benefit Analysis to Determine Human Risks Associated with Pyrrolizidine Alkaloids (PA)-The Case of Tea and Herbal Infusions.

PubMed

Habs, Michael; Binder, Karin; Krauss, Stefan; Müller, Karolina; Ernst, Brigitte; Valentini, Luzia; Koller, Michael

2017-07-07

Humans are exposed to pyrrolizidine alkaloids (PA) through different sources, mainly from contaminated foodstuff. Teas and herbal infusions (T&HI) can be contaminated by PA producing weed. PA can possess toxic, mutagenic, genotoxic, and carcinogenic properties. Thus, possible health risks for the general population are under debate. There is a strong safety record for T&HI and additionally epidemiological evidence for the preventive effects of regular tea consumption on cardiovascular events and certain types of cancer. There is no epidemiological evidence, however, for human risks of regular low dose PA exposure. Recommended regulatory PA-threshold values are based on experimental data only, accepting big uncertainties. If a general risk exists through PA contaminated T&HI, it must be small compared to other frequently accepted risks of daily living and the proven health effects of T&HI. Decision making should be based on a balanced riskbenefit analysis. Based on analyses of the scientific data currently available, it is concluded that the benefits of drinking T&HI clearly outweigh the negligible health risk of possible PA contamination. At the same time, manufacturers must continue their efforts to secure good product quality and to be transparent on their measures of quality control and risk communication.

MEGA: the next generation Medium Energy Gamma-ray Telescope

NASA Astrophysics Data System (ADS)

Paciesas, W.; Miller, R. S.; Andritschke, R.; Kanbach, G.; Zoglauer, A.; Bloser, P.; Hunter, S.; Cravens, J.; Cherry, M.; Guzik, T. G.; Stacy, J. G.; Wefel, J. P.; Di Cocco, G.; Hartmann, D.; Kippen, R. M.; Vestrand, W. T.; Kurfess, J.; Phlips, B.; Strickman, M.; Wulf, E.; Macri, J. R.; McConnell, M. L.; Ryan, J. M.; Reglero, V.; Zych, A. D.

2004-08-01

The MEGA mission would enable a sensitive all-sky survey of the medium-energy gamma-ray sky (0.3-50 MeV). This mission will bridge the huge sensitivity gap between the COMPTEL and OSSE experiments on the Compton Gamma Ray Observatory, the SPI and IBIS instruments on INTEGRAL and the visionary ACT mission. It will, among other things, serve to compile a much larger catalog of sources in this energy range, perform far deeper searches for supernovae, better measure the galactic continuum emission as well as identify the components of the cosmic diffuse emission. It will accomplish these goals with a stack of Si-strip detector (SSD) planes surrounded by a dense high-Z calorimeter. At lower photon energies (below ˜ 30 MeV), the design is sensitive to Compton interactions, with the SSD system serving as a scattering medium that also detects and measures the Compton recoil energy deposit. If the energy of the recoil electron is sufficiently high (> 2 MeV), the track of the recoil electron can also be defined. At higher photon energies (above ˜ 10 MeV), the design is sensitive to pair production events, with the SSD system measuring the tracks of the electron and positron. We will discuss the various types of event signatures in detail and describe the advantages of this design over previous Compton telescope designs. Effective area, sensitivity and resolving power estimates are also presented along with simulations of expected scientific results and beam calibration results from the prototype instrument.

Finding ultracool brown dwarfs with MegaCam on CFHT: method and first results

NASA Astrophysics Data System (ADS)

Delorme, P.; Willott, C. J.; Forveille, T.; Delfosse, X.; Reylé, C.; Bertin, E.; Albert, L.; Artigau, E.; Robin, A. C.; Allard, F.; Doyon, R.; Hill, G. J.

2008-06-01

Aims: We present the first results of a wide field survey for cool brown dwarfs with the MegaCam camera on the CFHT telescope, the Canada-France Brown Dwarf Survey, hereafter CFBDS. Our objectives are to find ultracool brown dwarfs and to constrain the field-brown dwarf mass function thanks to a larger sample of L and T dwarfs. Methods: We identify candidates in CFHT/MegaCam i' and z' images using optimised psf-fitting within Source Extractor, and follow them up with pointed near-infrared imaging on several telescopes. Results: We have so far analysed over 350 square degrees and found 770 brown dwarf candidates brighter than z'_AB=22.5. We currently have J-band photometry for 220 of these candidates, which confirms 37% as potential L or T dwarfs. Some are among the reddest and farthest brown dwarfs currently known, including an independent identification of the recently published ULAS J003402.77-005206.7 and the discovery of a second brown dwarf later than T8, CFBDS J005910.83-011401.3. Infrared spectra of three T dwarf candidates confirm their nature, and validate the selection process. Conclusions: The completed survey will discover ~100 T dwarfs and ~500 L dwarfs or M dwarfs later than M8, approximately doubling the number of currently known brown dwarfs. The resulting sample will have a very well-defined selection function, and will therefore produce a very clean luminosity function. Based on observations obtained with MegaPrime/MegaCam, a joint project of CFHT and CEA/DAPNIA, at the Canada-France-Hawaii Telescope (CFHT) which is operated by the National Research Council (NRC) of Canada, the Institut National des Sciences de l'Univers of the Centre National de la Recherche Scientifique (CNRS) of France, and the University of Hawaii. This work is based in part on data products produced at TERAPIX and the Canadian Astronomy Data Centre as part of the Canada-France-Hawaii Telescope Legacy Survey, a collaborative project of NRC and CNRS. Based on observations made with the ESO New Technology Telescope at the La Silla Observatory under programme ID 76.C-0540(A), 77.C-0594, 77.A-0707, 78.A-0651, 78.C-0629 and 79.A-0663. Based on observations obtained at the Gemini Observatory, which is operated by the Association of Universities for Research in Astronomy, Inc., under a cooperative agreement with the NSF on behalf of the Gemini partnership: the National Science Foundation (United States), the Science and Technology Facilities Council (United Kingdom), the National Research Council (Canada), CONICYT (Chile), the Australian Research Council (Australia), CNPq (Brazil) and CONICET (Argentina). Based on observations with the Kitt Peak National Observatory, National Optical Astronomy Observatory, which is operated by the Association of Universities for Research in Astronomy, Inc. (AURA) under cooperative agreement with the National Science Foundation. Based on observations made with the Nordic Optical Telescope, operated on the island of La Palma jointly by Denmark, Finland, Iceland, Norway, and Sweden, in the Spanish Observatorio del Roque de los Muchachos of the Instituto de Astrofisica de Canarias. This paper includes data taken at The McDonald Observatory of The University of Texas at Austin.

Induction of a Torpor-Like State by 5’-AMP Does Not Depend on H2S Production

PubMed Central

Dugbartey, George J.; Bouma, Hjalmar R.; Strijkstra, Arjen M.; Boerema, Ate S.; Henning, Robert H.

2015-01-01

Background Therapeutic hypothermia is used to reduce ischemia/reperfusion injury (IRI) during organ transplantation and major surgery, but does not fully prevent organ injury. Interestingly, hibernating animals undergo repetitive periods of low body temperature called ‘torpor’ without signs of organ injury. Recently, we identified an essential role of hydrogen sulfide (H2S) in entrance into torpor and preservation of kidney integrity during hibernation. A torpor-like state can be induced pharmacologically by injecting 5’-Adenosine monophosphate (5’-AMP). The mechanism by which 5’-AMP leads to the induction of a torpor-like state, and the role of H2S herein, remains to be unraveled. Therefore, we investigated whether induction of a torpor-like state by 5-AMP depends on H2S production. Methods To study the role of H2S on the induction of torpor, amino-oxyacetic acid (AOAA), a non-specific inhibitor of H2S, was administered before injection with 5'-AMP to block endogenous H2S production in Syrian hamster. To assess the role of H2S on maintenance of torpor induced by 5’-AMP, additional animals were injected with AOAA during torpor. Key Results During the torpor-like state induced by 5’-AMP, the expression of H2S- synthesizing enzymes in the kidneys and plasma levels of H2S were increased. Blockade of these enzymes inhibited the rise in the plasma level of H2S, but neither precluded torpor nor induced arousal. Remarkably, blockade of endogenous H2S production was associated with increased renal injury. Conclusions Induction of a torpor-like state by 5’-AMP does not depend on H2S, although production of H2S seems to attenuate renal injury. Unraveling the mechanisms by which 5’-AMP reduces the metabolism without organ injury may allow optimization of current strategies to limit (hypothermic) IRI and improve outcome following organ transplantation, major cardiac and brain surgery. PMID:26295351

Transport variability of the Brazil Current from observations and a data assimilation model

NASA Astrophysics Data System (ADS)

Schmid, Claudia; Majumder, Sudip

2018-06-01

The Brazil Current transports from observations and the Hybrid Coordinate Model (HYCOM) model are analyzed to improve our understanding of the current's structure and variability. A time series of the observed transport is derived from a three-dimensional field of the velocity in the South Atlantic covering the years 1993 to 2015 (hereinafter called Argo & SSH). The mean transports of the Brazil Current increases from 3.8 ± 2.2 Sv (1 Sv is 106 m3 s-1) at 25° S to 13.9 ± 2.6 Sv at 32° S, which corresponds to a mean slope of 1.4 ± 0.4 Sv per degree. Transport estimates derived from HYCOM fields are somewhat higher (5.2 ± 2.7 and 18.7 ± 7.1 Sv at 25 and 32° S, respectively) than those from Argo & SSH, but these differences are small when compared with the standard deviations. Overall, the observed latitude dependence of the transport of the Brazil Current is in agreement with the wind-driven circulation in the super gyre of the subtropical South Atlantic. A mean annual cycle with highest (lowest) transports in austral summer (winter) is found to exist at selected latitudes (24, 35, and 38° S). The significance of this signal shrinks with increasing latitude (both in Argo & SSH and HYCOM), mainly due to mesoscale and interannual variability. Both Argo & SSH, as well as HYCOM, reveal interannual variability at 24 and 35° S that results in relatively large power at periods of 2 years or more in wavelet spectra. It is found that the interannual variability at 24° S is correlated with the South Atlantic Subtropical Dipole Mode (SASD), the Southern Annular Mode (SAM), and the Niño 3.4 index. Similarly, correlations between SAM and the Brazil Current transport are also found at 35° S. Further investigation of the variability reveals that the first and second mode of a coupled empirical orthogonal function of the meridional transport and the sea level pressure explain 36 and 15 % of the covariance, respectively. Overall, the results indicate that SAM, SASD, and El Niño-Southern Oscillation have an influence on the transport of the Brazil Current.

On meta- and mega-analyses for gene–environment interactions

PubMed Central

Huang, Jing; Liu, Yulun; Vitale, Steve; Penning, Trevor M.; Whitehead, Alexander S.; Blair, Ian A.; Vachani, Anil; Clapper, Margie L.; Muscat, Joshua E.; Lazarus, Philip; Scheet, Paul; Moore, Jason H.; Chen, Yong

2017-01-01

Gene-by-environment (G × E) interactions are important in explaining the missing heritability and understanding the causation of complex diseases, but a single, moderately sized study often has limited statistical power to detect such interactions. With the increasing need for integrating data and reporting results from multiple collaborative studies or sites, debate over choice between mega- versus meta-analysis continues. In principle, data from different sites can be integrated at the individual level into a “mega” data set, which can be fit by a joint “mega-analysis.” Alternatively, analyses can be done at each site, and results across sites can be combined through a “meta-analysis” procedure without integrating individual level data across sites. Although mega-analysis has been advocated in several recent initiatives, meta-analysis has the advantages of simplicity and feasibility, and has recently led to several important findings in identifying main genetic effects. In this paper, we conducted empirical and simulation studies, using data from a G × E study of lung cancer, to compare the mega- and meta-analyses in four commonly used G × E analyses under the scenario that the number of studies is small and sample sizes of individual studies are relatively large. We compared the two data integration approaches in the context of fixed effect models and random effects models separately. Our investigations provide valuable insights in understanding the differences between mega- and meta-analyses in practice of combining small number of studies in identifying G × E interactions. PMID:29110346

Accuracy and stability of measuring GABA, glutamate, and glutamine by proton magnetic resonance spectroscopy: A phantom study at 4 Tesla

NASA Astrophysics Data System (ADS)

Henry, Michael E.; Lauriat, Tara L.; Shanahan, Meghan; Renshaw, Perry F.; Jensen, J. Eric

2011-02-01

Proton magnetic resonance spectroscopy has the potential to provide valuable information about alterations in gamma-aminobutyric acid (GABA), glutamate (Glu), and glutamine (Gln) in psychiatric and neurological disorders. In order to use this technique effectively, it is important to establish the accuracy and reproducibility of the methodology. In this study, phantoms with known metabolite concentrations were used to compare the accuracy of 2D J-resolved MRS, single-echo 30 ms PRESS, and GABA-edited MEGA-PRESS for measuring all three aforementioned neurochemicals simultaneously. The phantoms included metabolite concentrations above and below the physiological range and scans were performed at baseline, 1 week, and 1 month time-points. For GABA measurement, MEGA-PRESS proved optimal with a measured-to-target correlation of R2 = 0.999, with J-resolved providing R2 = 0.973 for GABA. All three methods proved effective in measuring Glu with R2 = 0.987 (30 ms PRESS), R2 = 0.996 (J-resolved) and R2 = 0.910 (MEGA-PRESS). J-resolved and MEGA-PRESS yielded good results for Gln measures with respective R2 = 0.855 (J-resolved) and R2 = 0.815 (MEGA-PRESS). The 30 ms PRESS method proved ineffective in measuring GABA and Gln. When measurement stability at in vivo concentration was assessed as a function of varying spectral quality, J-resolved proved the most stable and immune to signal-to-noise and linewidth fluctuation compared to MEGA-PRESS and 30 ms PRESS.

VizieR Online Data Catalog: Photometric Calibration of SNLS (Regnault+, 2009)

NASA Astrophysics Data System (ADS)

Regnault, N.; Conley, A.; Guy, J.; Sullivan, M.; Cuillandre, J.-C.; Astier, P.; Balland, C.; Basa, S.; Carlberg, R. G.; Fouchez, D.; Hardin, D.; Hook, I. M.; Howell, D. A.; Pain, R.; Perrett, K.; Pritchet, C. J.

2009-08-01

This is the photometric calibration of the SuperNova Legacy Survey (SNLS) three year dataset. The SNLS corresponds to the DEEP component of the larger Canada-France-Hawaii Telescope Legacy Survey (CFHTLS). The SNLS repeatedly monitors four one square degree fields (labeled D[1-4]) with the MegaCam wide-field imager, in the g, r, i and z bands. u-band observations of the same fields are also available, although not formally part of the SNLS dataset. The non-uniformities of the MegaCam imager photometric response have been mapped as a function of the position on the focal plane. The fluxes, measured on the survey images processed with the CFHT Elixir pipeline, have been corrected for these non-uniformities in order to obtain measurements that are uniform at the ~1% level. The MegaCam passband transmissions were found to be non-uniform, the filters being 3 to 6 nanometers bluer on the edges of the camera than on the center. This result agrees with the filter scans provided by the filter manufacturer (Sagem/REOSC). This has important consequences on the definition of the MegaCam magnitudes: the natural magnitude system depends on the focal plane location where the observations were made. In order not to break the connection between calibrated magnitudes and their physical flux counterparts, we chose to report the *natural magnitudes* of each object, measured in the MegaCam passbands, at the focal plane location where the object was observed. We call this system, "Local Natural Magnitudes". The non-uniformities of the MegaCam effective passbands are small and, for main sequence stellar objects, they may be accounted for using linear color corrections. The relation between the Local Natural Magnitudes of a given star, observed at two locations x_0 and x of the focal plane are: g|x = g|x0 + dkggr(x) * ( (g-r)|x0 - (g-r)BD+17|x_0 ) ... z|x = z|x0 + dkziz(x) * ( (i-z)|x0 - (i-z)BD+17|x_0 ) where the dk(x) are (position dependant) color terms. We provide dk(x) maps for each MegaCam band (see below). The SNLS 3 year calibration relies on the (Landolt, 1992AJ....104..340) standard star catalog. Landolt fields are observed during each photometric night along with the SNLS fields. Zero-points are derived from these observations. Stable and isolated stars are detected on the SNLS fields and selected as "tertiary standards". The calibrated magnitudes of each tertiary standard obtained under photometric conditions are combined to produce a calibration catalog for each SNLS field. To interpret the tertiary standard magnitudes as physical fluxes, we need a primary standard, i.e. a star with known MegaCam magnitudes and whose spectral energy distribution has been measured absolutely. The SNLS uses BD+17 4708 whose SED has been measured in Bohlin & Gilliland, 2004, Cat. using the HST STIS and NICMOS spectrographs. BD+17 4708 has not been directly observed by SNLS, however, its MegaCam magnitudes were inferred from its known Landolt magnitudes (this paper, table 7). The tertiary star Local Natural Magnitudes are defined so that the associated physical broadband flux f|x is given by: f|x = 10{-0.4*(m|x-mref)}*{int}[Sref(l)*T(l;x)]dl where m|x is the tertiary star magnitudes at location x on the focal plane, mref is the MegaCam magnitude of BD+17 4708 (at the center of the focal plane, see table 7 of this paper), Sref(l) is the SED of BD+17 4708 measured in 2004AJ....128.3053B, and T(l;x) is the effective passband of MegaCam at location x. Attached is all the necessary information to tie MegaCam observations to this system. We provide (a) the griz magnitudes of the SNLS tertiary standards for all four SNLS fields (b) the MegaCam open transmission and the ugriz MegaCam filter scans at various position along a diagonal (c) the final uncertainty budget in the form of 3 covariance matrices. The u-band observations of the SNLS DEEP fields are not formally part of the SNLS. Nevetheless we give u-band magnitudes for a subset of the SNLS tertiary stars. (22 data files).

AMPS data management requirements study. [user manuals (computer programs)/display devices - computerized simulation/experimentation/ionosphere

NASA Technical Reports Server (NTRS)

1975-01-01

A data simulation is presented for instruments and associated control and display functions required to perform controlled active experiments of the atmosphere. A comprehensive user's guide is given for the data requirements and software developed for the following experiments: (1) electromagnetic wave transmission; (2) passive observation of ambient plasmas; (3) ionospheric measurements with a subsatellite; (4) electron accelerator beam measurements; and (5) measurement of acoustic gravity waves in the sodium layer using lasers. A complete description of each experiment is given.

The Inhomogeneous Light Shift in Alkali Atoms.

DTIC Science & Technology

1985-06-24

N AMP’. LAS R 1GEEAOCON R ’", DONTROLLERR MA LNETSHEL Fig. 1. Exp mn ta Ar a g m n . S i c o i i n A and B corr spon to the arSran e tsO used/ PtoS...Calculation Parameters laser linewidth A~V La 100 MHz laser beam diameter a - 0.45 cm absorption linewidth DV 50 ~ longitudinal relaxation rate y 100...Verlag, Berlin-Heidelberg-New York, 1975), pp. 176- 185. 12. S. Pancharatnam, J. Opt. Soc. Am. 56, 1636 (1966). 13. C. Cohen-Tannoudji, Metrologia 13

Measuring electrically charged particle fluxes in space using a fiber optic loop sensor

NASA Technical Reports Server (NTRS)

1992-01-01

The purpose of this program was to demonstrate the potential of a fiber optic loop sensor for the measurement of electrically charged particle fluxes in space. The key elements of the sensor are a multiple turn loop of low birefringence, single mode fiber, with a laser diode light source, and a low noise optical receiver. The optical receiver is designed to be shot noise limited, with this being the limiting sensitivity factor for the sensor. The sensing element is the fiber optic loop. Under a magnetic field from an electric current flowing along the axis of the loop, there is a non-vanishing line integral along the fiber optic loop. This causes a net birefringence producing two states of polarization whose phase difference is correlated to magnetic field strength and thus, current in the optical receiver electronic processing. The objectives in this program were to develop a prototype laser diode powered fiber optic sensor. The performance specification of a minimum detectable current density of 1 (mu)amp/sq m-(radical)Hz, should be at the shot noise limit of the detection electronics. OPTRA has successfully built and tested a 3.2 m diameter loop with 137 turns of low birefringence optical fiber and achieved a minimum detectable current density of 5.4 x 10(exp-5) amps/(radical)Hz. If laboratory space considerations were not an issue, with the length of optical fiber available to us, we would have achieved a minimum detectable current density of 4 x 10(exp -7) amps/(radical)Hz.

Second-messenger regulation of sodium transport in mammalian airway epithelia.

PubMed Central

Graham, A; Steel, D M; Alton, E W; Geddes, D M

1992-01-01

1. Sodium absorption is the dominant ion transport process in conducting airways and is a major factor regulating the composition of airway surface liquid. However, little is known about the control of airway sodium transport by intracellular regulatory pathways. 2. In sheep tracheae and human bronchi mounted in Ussing chambers under short circuit conditions, the sodium current can be isolated by pretreating tissues with acetazolamide (100 microM) to inhibit bicarbonate secretion, bumetanide (100 microM) to inhibit chloride secretion and phloridzin (200 microM) to inhibit sodium-glucose cotransport. This sodium current consists of amiloride-sensitive (57%) and amiloride-insensitive (43%) components. 3. The regulation of the isolated sodium current by three second messenger pathways was studied using the calcium ionophore A23187 to elevate intracellular calcium, a combination of forskolin and the phosphodiesterase inhibitor zardaverine to elevate intracellular cyclic AMP, and the phorbol ester 12,13-phorbol dibutyrate (PDB) to stimulate protein kinase C. 4. In sheep trachea, A23187 produces a dose-related inhibition of the sodium current with maximal effect (38% of ISC) at 10 microM and IC50 1 microM. This response affects both the amiloride-sensitive and insensitive components of the sodium current and is not altered by prior stimulation of protein kinase C or elevation of intracellular cyclic AMP. In human bronchi, A23187 (10 microM) produced a significantly greater inhibition of ISC (68%), a response which was unaffected by prior treatment with PDB or forskolin-zardaverine. 5. In sheep trachea, stimulation of protein kinase C with PDB produced a dose-related inhibition of ISC maximal (56% of ISC) at 50 nM (IC50 7 nM). This response was abolished by amiloride (100 microM) pretreatment suggesting a selective effect on the amiloride-sensitive component of the sodium current. The response was not altered by prior elevation of intracellular calcium or cyclic AMP. PDB (10 nM) caused a similar inhibition of ISC in human bronchi (43%). The effect of PKC stimulation following pretreatment with A23187 was diminished in human bronchi. Elevating intracellular cyclic AMP did not alter this response. 6. Addition of forskolin (1 microM) together with the phosphodiesterase inhibitor zardaverine (100 microM) produced a mean 35-fold increase in intracellular cyclic AMP in sheep trachea. This was associated with a small, but significant, 6% transient increase in ISC followed by a significant 4% fall. Neither effect could be abolished by amiloride pretreatment. In human bronchi, a small decrease in ISC which could not be distinguished from that occurring in controls was observed.(ABSTRACT TRUNCATED AT 400 WORDS) PMID:1464841

Minocycline inhibits D-amphetamine-elicited action potential bursts in a central snail neuron.

PubMed

Chen, Y-H; Lin, P-L; Wong, R-W; Wu, Y-T; Hsu, H-Y; Tsai, M-C; Lin, M-J; Hsu, Y-C; Lin, C-H

2012-10-25

Minocycline is a second-generation tetracycline that has been reported to have powerful neuroprotective properties. In our previous studies, we found that d-amphetamine (AMPH) elicited action potential bursts in an identifiable RP4 neuron of the African snail, Achatina fulica Ferussac. This study sought to determine the effects of minocycline on the AMPH-elicited action potential pattern changes in the central snail neuron, using the two-electrode voltage clamping method. Extracellular application of AMPH at 300 μM elicited action potential bursts in the RP4 neuron. Minocycline dose-dependently (300-900 μM) inhibited the action potential bursts elicited by AMPH. The inhibitory effects of minocycline on AMPH-elicited action potential bursts were restored by forskolin (50 μM), an adenylate cyclase activator, and by dibutyryl cAMP (N(6),2'-O-Dibutyryladenosine 3',5'-cyclic monophosphate; 1mM), a membrane-permeable cAMP analog. Co-administration of forskolin (50 μM) plus tetraethylammonium chloride (TEA; 5mM) or co-administration of TEA (5mM) plus dibutyryl cAMP (1mM) also elicited action potential bursts, which were prevented and inhibited by minocycline. In addition, minocycline prevented and inhibited forskolin (100 μM)-elicited action potential bursts. Notably, TEA (50mM)-elicited action potential bursts in the RP4 neuron were not affected by minocycline. Minocycline did not affect steady-state outward currents of the RP4 neuron. However, minocycline did decrease the AMPH-elicited steady-state current changes. Similarly, minocycline decreased the effects of forskolin-elicited steady-state current changes. Pretreatment with H89 (N-[2-(p-Bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide dihydrochloride; 10 μM), a protein kinase A inhibitor, inhibited AMPH-elicited action potential bursts and decreased AMPH-elicited steady-state current changes. These results suggest that the cAMP-protein kinase A signaling pathway and the steady-state current are involved in the inhibitory effects of minocycline upon AMPH-elicited action potential bursts. Copyright © 2012 IBRO. Published by Elsevier Ltd. All rights reserved.

A Preliminary Investigation of the E-Beam Induced Polymerization of Maleimide and Norbornene End-capped Polyimides

NASA Technical Reports Server (NTRS)

Palmese, Giuseppe R.; Meador, Michael A. (Technical Monitor)

2005-01-01

A research area of high activity in connection with aerospace engineering has been the development of polymer thermosetting resins that can resist temperature as high as 300 C while maintaining adequate toughness, and providing ease of processing to enable low temperature and low cost composite fabrication methods. In order to meet such requirements, sequential interpenetrating polymer networks (IPNs) based on bismaleimide (BMI) and cyanate ester (CE) monomers were investigated. In these systems, a polycyanurate network is first formed in the presence of BMI and appropriate reactive diluent monomers and in a second step, a network based on the BMI is created in the presence of a fully formed polycyanurate network. The materials developed can be processed at relatively low temperature (less than 150 C) and with the aid of electron beam (EB) curing. Of major importance to the success of this work was the identification of a reactive diluent that improves ease of processing and has tailored reactivity to allow for the controlled synthesis of CE-BMI sequential IPNs. Based on solubility and reactivity of a number of reactive diluents, N-acryloylmorpholine (AMP) was selected as a comonomer for BMI copolymerization. A donor-acceptoreaction mechanism was suggested to explain the relative reactivity of a variety of reactive diluents towards maleimide functionality. The optimum processing parameters for the formation of the first network were determined through the study of metal catalyzed cure and hydrolysis of cyanate esters, whereas the reaction behavior for second network formation in terms of the influence of EB dose rate and temperature was elucidated through an in-situ kinetics study of maleimide and AMP copolymerization. Structure-property relationships were developed which allowed for the design of improved resin systems. In particular, appropriate network coupler possessing cyanate ester and maleimide functionality was synthesized to link the polycyanurate first network to the BMI/AMP second network and thus form linked sequential IPNs (LIPNs). Consequently, Tg as high as 370 C was achieved and a fracture toughness of 120 Joules per square meters was obtained for resin systems that possess adequately low viscosity for processing using liquid molding techniques at low temperature.

The Magellan Evolution of Galaxies Spectroscopic and Ultraviolet Reference Atlas (MegaSaura). I. The Sample and the Spectra

NASA Astrophysics Data System (ADS)

Rigby, J. R.; Bayliss, M. B.; Sharon, K.; Gladders, M. D.; Chisholm, J.; Dahle, H.; Johnson, T.; Paterno-Mahler, R.; Wuyts, E.; Kelson, D. D.

2018-03-01

We introduce Project MEGaSaURA: the Magellan Evolution of Galaxies Spectroscopic and Ultraviolet Reference Atlas. MEGaSaURA comprises medium-resolution, rest-frame ultraviolet spectroscopy of N = 15 bright gravitationally lensed galaxies at redshifts of 1.68 < z < 3.6, obtained with the MagE spectrograph on the Magellan telescopes. The spectra cover the observed-frame wavelength range 3200 < λ o < 8280 Å the average spectral resolving power is R = 3300. The median spectrum has a signal-to-noise ratio (S/N) = 21 per resolution element at 5000 Å. As such, the MEGaSaURA spectra have superior S/N and wavelength coverage compared to what COS/HST provides for starburst galaxies in the local universe. This paper describes the sample, the observations, and the data reduction. We compare the measured redshifts for the stars, the ionized gas as traced by nebular lines, and the neutral gas as traced by absorption lines; we find the expected bulk outflow of the neutral gas, and no systemic offset between the redshifts measured from nebular lines and the redshifts measured from the stellar continuum. We provide the MEGaSaURA spectra to the astronomical community through a data release.

Implantation of Martian Materials in the Inner Solar System by a Mega Impact on Mars

NASA Astrophysics Data System (ADS)

Hyodo, Ryuki; Genda, Hidenori

2018-04-01

Observations and meteorites indicate that the Martian materials are enigmatically distributed within the inner solar system. A mega impact on Mars creating a Martian hemispheric dichotomy and the Martian moons can potentially eject Martian materials. A recent work has shown that the mega-impact-induced debris is potentially captured as the Martian Trojans and implanted in the asteroid belt. However, the amount, distribution, and composition of the debris has not been studied. Here, using hydrodynamic simulations, we report that a large amount of debris (∼1% of Mars’ mass), including Martian crust/mantle and the impactor’s materials (∼20:80), are ejected by a dichotomy-forming impact, and distributed between ∼0.5–3.0 au. Our result indicates that unmelted Martian mantle debris (∼0.02% of Mars’ mass) can be the source of Martian Trojans, olivine-rich asteroids in the Hungarian region and the main asteroid belt, and some even hit the early Earth. The evidence of a mega impact on Mars would be recorded as a spike of 40Ar–39Ar ages in meteorites. A mega impact can naturally implant Martian mantle materials within the inner solar system.

Surfzone vorticity in the presence of extreme bathymetric variability

NASA Astrophysics Data System (ADS)

Clark, D.; Elgar, S.; Raubenheimer, B.

2014-12-01

Surfzone vorticity was measured at Duck, NC using a novel 5-m diameter vorticity sensor deployed in 1.75 m water depth. During the 4-week deployment the initially alongshore uniform bathymetry developed 200-m long mega-cusps with alongshore vertical changes of 1.5 m or more. When waves were small and the vorticity sensor was seaward of the surfzone, vorticity variance and mean vorticity varied with the tidally modulated water depth, consistent with a net seaward flux of surfzone-generated vorticity. Vorticity variance increased with incident wave heights up to 2-m. However, vorticity variance remained relatively constant for incident wave heights above 2-m, and suggests that eddy energy may become saturated in the inner surfzone during large wave events. In the presence of mega-cusps the mean vorticity (shear) is often large and generated by bathymetrically controlled rip currents, while vorticity variance remains strongly correlated with the incident wave height. Funded by NSF, ASD(R&E), and WHOI Coastal Ocean Institute.

Trypanosoma mega (Kinetoplastida) from Bufo viridis in Siwah Oasis, Egypt.

PubMed

Ashour, A A; Gaafar, N A

1997-04-01

A large pleomorphic trypanosome, identified as Trypanosoma mega, is described from the toad Bufo viridis collected from Siwah Oasis at the Western Desert of Egypt. The prevalence of the trypanosome is 83.3%. Three trypanosome forms are described, small, intermediate and large stumpy form. Observations were also made on the lysed (diffused) trypanosomes. This is the first record of T. mega from B. viridis in Egypt which represents a new host and new geographical location. The measurements of the present trypanosome are given and compared with related forms previously described from Egypt.

Wire-positioning algorithm for coreless Hall array sensors in current measurement

NASA Astrophysics Data System (ADS)

Chen, Wenli; Zhang, Huaiqing; Chen, Lin; Gu, Shanyun

2018-05-01

This paper presents a scheme of circular-arrayed, coreless Hall-effect current transformers. It can satisfy the demands of wide dynamic range and bandwidth current in the distribution system, as well as the demand of AC and DC simultaneous measurements. In order to improve the signal to noise ratio (SNR) of the sensor, a wire-positioning algorithm is proposed, which can improve the measurement accuracy based on the post-processing of measurement data. The simulation results demonstrate that the maximum errors are 70%, 6.1% and 0.95% corresponding to Ampère’s circuital method, approximate positioning algorithm and precise positioning algorithm, respectively. It is obvious that the accuracy of the positioning algorithm is significantly improved when compared with that of the Ampère’s circuital method. The maximum error of the positioning algorithm is smaller in the experiment.

Hyperpolarization-activated current (I(h)) in vestibular calyx terminals: characterization and role in shaping postsynaptic events.

PubMed

Meredith, Frances L; Benke, Tim A; Rennie, Katherine J

2012-12-01

Calyx afferent terminals engulf the basolateral region of type I vestibular hair cells, and synaptic transmission across the vestibular type I hair cell/calyx is not well understood. Calyces express several ionic conductances, which may shape postsynaptic potentials. These include previously described tetrodotoxin-sensitive inward Na(+) currents, voltage-dependent outward K(+) currents and a K(Ca) current. Here, we characterize an inwardly rectifying conductance in gerbil semicircular canal calyx terminals (postnatal days 3-45), sensitive to voltage and to cyclic nucleotides. Using whole-cell patch clamp, we recorded from isolated calyx terminals still attached to their type I hair cells. A slowly activating, noninactivating current (I(h)) was seen with hyperpolarizing voltage steps negative to the resting potential. External Cs(+) (1-5 mM) and ZD7288 (100 μM) blocked the inward current by 97 and 83 %, respectively, confirming that I(h) was carried by hyperpolarization-activated, cyclic nucleotide gated channels. Mean half-activation voltage of I(h) was -123 mV, which shifted to -114 mV in the presence of cAMP. Activation of I(h) was well described with a third order exponential fit to the current (mean time constant of activation, τ, was 190 ms at -139 mV). Activation speeded up significantly (τ=136 and 127 ms, respectively) when intracellular cAMP and cGMP were present, suggesting that in vivo I(h) could be subject to efferent modulation via cyclic nucleotide-dependent mechanisms. In current clamp, hyperpolarizing current steps produced a time-dependent depolarizing sag followed by either a rebound afterdepolarization or an action potential. Spontaneous excitatory postsynaptic potentials (EPSPs) became larger and wider when I(h) was blocked with ZD7288. In a three-dimensional mathematical model of the calyx terminal based on Hodgkin-Huxley type ionic conductances, removal of I(h) similarly increased the EPSP, whereas cAMP slightly decreased simulated EPSP size and width.

Probability Assessment of Mega-thrust Earthquakes in Global Subduction Zones　-from the View of Slip Deficit-

NASA Astrophysics Data System (ADS)

Ikuta, R.; Mitsui, Y.; Ando, M.

2014-12-01

We studied inter-plate slip history for about 100 years using earthquake catalogs. On assumption that each earthquake has stick-slip patch centered in its centroid, we regard cumulative seismic slips around the centroid as representing the inter-plate dislocation. We evaluated the slips on the stick-slip patches of over-M5-class earthquakes prior to three recent mega-thrust earthquakes, the 2004 Sumatra (Mw9.2), the 2010 Chile (Mw8.8), and the 2011 Tohoku (Mw9.0) around them. Comparing the cumulative seismic slips with the plate convergence, the slips before the mega-thrust events are significantly short in large area corresponding to the size of the mega-thrust events. We also researched cumulative seismic slips after other three mega-thrust earthquakes occurred in this 100 years, the 1952 Kamchatka (Mw9.0), the 1960 Chile (Mw9.5), the 1964 Alaska (Mw9.2). The cumulative slips have been significantly short in and around the focal area after their occurrence. The result should reflect persistency of the strong or/and large inter-plate coupled area capable of mega-thrust earthquakes. We applied the same procedure to global subduction zones to find that 21 regions including the focal area of above mega-thrust earthquakes show slip deficit over large area corresponding to the size of M9-class earthquakes. Considering that at least six M9-class earthquakes occurred in this 100 years and each recurrence interval should be 500-1000 years, it would not be surprised that from five to ten times of the already known regions (30 to 60 regions) are capable of M9 class earthquakes. The 21 regions as expected M9 class focal areas in our study is less than 5 to 10 times of the known 6, some of these regions may be divided into a few M9 class focal area because they extend to much larger area than typical M9 class focal area.

June 2017: The Earliest European Summer Mega-heatwave of Reanalysis Period

NASA Astrophysics Data System (ADS)

Sánchez-Benítez, A.; García-Herrera, R.; Barriopedro, D.; Sousa, P. M.; Trigo, R. M.

2018-02-01

This paper examines the characteristics of the heatwave that affected western and central Europe in June 2017. Using a novel algorithm, we show that its extension, intensity, and persistence were comparable to those of other European mega-heatwaves, but it occurred earlier in the summer. The most affected area was Iberia, which experienced devastating forest fires with human casualties and the warmest temperatures of the reanalysis period from daily to seasonal scales. The peak of the mega-heatwave displayed an unprecedented warm air intrusion due to a record-breaking subtropical ridge with signatures closer to those of July and August. The atmospheric circulation was the main triggering factor of the event. However, thermodynamical changes of the last decades made a substantial contribution to the event, by increasing the likelihood of surpassing high-temperature thresholds. This episode could be a good example of a coming future, with high-summer mega-heatwaves occurring earlier.

Marching Microbes

NASA Technical Reports Server (NTRS)

1999-01-01

Under an SBIR contract with Marshall Space Flight Center, Micro-Bac International developed a new system for the treatment of wastewater based on the metabolic activity of photorphic bacteria. These microorganisms are now being sold as a liquid product called Mega-Bac TF. It is currently used for septic systems and wastewater ponds, lakes and lagoons to degrade fat, oil, fecal matter and other biologically derived wastes. Potential applications include homes, agriculture, food processors and chemical manufacturing.

77 FR 61797 - Self-Regulatory Organizations; EDGX Exchange, Inc.; Notice of Filing and Immediate Effectiveness...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-10-11

..., MM, RP, 3, or 4 and removal flags are defined as Flags BB, MT, N, W, PI, PR, or 6. Where a Member..., BB and PI where they satisfy the volume tier requirements for the Mega Tier in Footnote 1. Currently... removing liquidity and the rate for Flags N, W, 6, BB, and PI subject to the volume thresholds in Footnotes...

Evaluation of Enterococcus faecalis clinical isolates with 'penicillin-resistant, ampicillin-susceptible' phenotype as reported by Vitek-2 Compact system.

PubMed

Tan, Yen Ee; Ng, Lily S Y; Tan, Thean Yen

2014-10-01

It has been recently reported that ampicillin susceptibility cannot accurately predict piperacillin and imipenem susceptibilities in penicillin-resistant, ampicillin-susceptible (Pen-R, Amp-S) Enterococcus faecalis isolates, contrary to the current Clinical and Laboratory Standards Institute (CLSI) recommendations. This has important therapeutic implications. Such isolates were noted after the use of Vitek-2 Compact system AST-GP67 susceptibility cards in a Singapore general hospital and they were increasing in numbers. The primary aim of this study was to evaluate these clinical isolates against microbroth dilution (MBD) technique and other commonly used antimicrobial susceptibility test (AST) methods for penicillin and ampicillin. The secondary aim was to evaluate whether ampicillin susceptibility could indeed be a reliable surrogate marker for piperacillin and imipenem susceptibilities in E. faecalis isolates that were confirmed Pen-R, Amp-S.From 2009 to 2013, a total of 49 isolates (5%) of 983 non-duplicate E. faecalis tested by Vitek-2 displayed the 'Pen-R, Amp-S' phenotype in a general hospital in Singapore. These were tested against MBD which was the reference method, Etest and disc diffusion for penicillin and ampicillin. Susceptibilities to piperacillin and imipenem were also tested using MBD. In addition, β-lactamase production test was performed. Forty E. faecalis isolates with penicillin-susceptible, ampicillin-susceptible (Pen-S, Amp-S) phenotype were included for comparative purposes.The categorical agreement rate was 100% for all AST methods in ampicillin reporting for the 'Pen-R, Amp-S' group of E. faecalis isolates. However, a large number of isolates (46 isolates, 93.9%) fell into the major error category for penicillin testing by the Vitek-2 system. Penicillin minimum inhibitory concentrations (MICs) generated by the Vitek-2 system for the majority of these isolates were two doubling dilutions higher compared to those obtained by the reference test. The Etest method correlated well with the MBD method. Thirty-two isolates (65.3%) were in categorical agreement with the MBD method when tested by the disc diffusion method for penicillin. Only three E. faecalis isolates (6.1%) were confirmed to have the uncommon penicillin resistance phenotype, with two of them showing resistance to piperacillin and intermediate to imipenem. β-lactamase production test was negative for all isolates. Among the Pen-S, Amp-S E. faecalis isolates, the categorical agreement was 100% for penicillin and ampicillin in all the tested methods.Enterococcus faecalis with 'Pen-R, Amp-S' phenotype reported by the Vitek-2 system using AST-GP67 susceptibility cards must be confirmed with a reference test, the Etest method being a good alternative. The Vitek-2 system generated higher penicillin MIC readings compared to MBD in this study. The actual prevalence of this uncommon penicillin resistance phenotype in E. faecalis was found to be low in this institution. More studies are required to confirm the reliability of ampicillin as a surrogate marker for piperacillin and imipenem susceptibilities in these isolates.

In Vivo Cardiovascular Pharmacology of 2′,3′-cAMP, 2′-AMP, and 3′-AMP in the Rat

PubMed Central

Mi, Zaichuan

2013-01-01

The naturally occurring purine 2′,3′-cAMP is metabolized in vitro to 2′-AMP and 3′-AMP, which are subsequently metabolized to adenosine. Whether in vivo 2′,3′-cAMP, 2′-AMP, or 3′-AMP are rapidly converted to adenosine and exert rapid effects via adenosine receptors is unknown. To address this question, we compared the cardiovascular and renal effects of 2′,3′-cAMP, 2′-AMP, 3′-AMP, 3′,5′-cAMP, 5′-AMP, and adenosine in vivo in the rat. Purines were infused intravenously while monitoring mean arterial blood pressure (MABP), heart rate (HR), cardiac output, and renal and mesenteric blood flows. Total peripheral (TPR), renal vascular (RVR), and mesenteric vascular (MVR) resistances were calculated. Urine was collected for determination of urine excretion rate [urine volume (UV)]. When sufficient urine was available, the sodium excretion rate (Na+ER) and glomerular filtration rate (GFR) were determined. 2′,3′-cAMP, 2′-AMP, and 3′-AMP dose-dependently and profoundly reduced MABP, HR, TPR, and MVR with efficacy and potency similar to adenosine and 5′-AMP. These effects of 2′,3′-cAMP, 2′-AMP, and 3′-AMP were attenuated by blockade of adenosine receptors with 1,3-dipropyl-8-(p-sulfophenyl)xanthine. 2′,3′-cAMP, 2′-AMP, 3′-AMP, adenosine, and 5′-AMP variably affected RVR, but profoundly (nearly 100%) decreased UV at higher doses. GFR and Na+ER could be measured at the lower doses and were suppressed by 2′,3′-cAMP, 2′-AMP, and 3′-AMP, but not by adenosine or 5′-AMP. 2′,3′-cAMP increased urinary excretion rates of 2′-AMP, 3′-AMP, and adenosine. 3′,5′-cAMP exerted no adverse hemodynamic effects yet increased urinary adenosine as efficiently as 2′,3′-cAMP. Conclusions: In vivo 2′,3′-cAMP is rapidly converted to adenosine. Because both cAMPs increase adenosine in the urinary compartment, these agents may provide unique therapeutic opportunities. PMID:23759508

2′,3′-cAMP, 3′-AMP, and 2′-AMP inhibit human aortic and coronary vascular smooth muscle cell proliferation via A2B receptors

PubMed Central

Ren, Jin; Gillespie, Delbert G.

2011-01-01

Rat vascular smooth muscle cells (VSMCs) from renal microvessels metabolize 2′,3′-cAMP to 2′-AMP and 3′-AMP, and these AMPs are converted to adenosine that inhibits microvascular VSMC proliferation via A2B receptors. The goal of this study was to test whether this mechanism also exists in VSMCs from conduit arteries and whether it is similarly expressed in human vs. rat VSMCs. Incubation of rat and human aortic VSMCs with 2′,3′-cAMP concentration-dependently increased levels of 2′-AMP and 3′-AMP in the medium, with a similar absolute increase in 2′-AMP vs. 3′-AMP. In contrast, in human coronary VSMCs, 2′,3′-cAMP increased 2′-AMP levels yet had little effect on 3′-AMP levels. In all cell types, 2′,3′-cAMP increased levels of adenosine, but not 5′-AMP, and 2′,3′-AMP inhibited cell proliferation. Antagonism of A2B receptors (MRS-1754), but not A1 (1,3-dipropyl-8-cyclopentylxanthine), A2A (SCH-58261), or A3 (VUF-5574) receptors, attenuated the antiproliferative effects of 2′,3′-cAMP. In all cell types, 2′-AMP, 3′-AMP, and 5′-AMP increased adenosine levels, and inhibition of ecto-5′-nucleotidase blocked this effect of 5′-AMP but not that of 2′-AMP nor 3′-AMP. Also, 2′-AMP, 3′-AMP, and 5′-AMP, like 2′,3′-cAMP, exerted antiproliferative effects that were abolished by antagonism of A2B receptors with MRS-1754. In conclusion, VSMCs from conduit arteries metabolize 2′,3′-cAMP to AMPs, which are metabolized to adenosine. In rat and human aortic VSMCs, both 2′-AMP and 3′-AMP are involved in this process, whereas, in human coronary VSMCs, 2′,3′-cAMP is mainly converted to 2′-AMP. Because adenosine inhibits VSMC proliferation via A2B receptors, local vascular production of 2′,3′-cAMP may protect conduit arteries from atherosclerosis. PMID:21622827

Molecular Basis of Ion Channels and Receptors Involved in Nerve Excitation, Synaptic Transmission and Muscle Contraction

DTIC Science & Technology

1993-12-20

shows the effect of minoxidil sulphate on CFTR Cl currents; similar results were obtained with BRL 38227 and diazoxide. As was observed for the...dependent; halt-maximal inhibition occurred at about 40 l±M minoxidil sulphate, 50 pM BRI. 38227, and 250 p.M diazoxide. This effect was weaker than...their stimulation of K-ATP channels in vascular smooth muscle."’ 280 ANNALS NEW YORK ACADEMY OF SCIENCES +50 mV -90 mV A ~Bi cAMP cAMP + minoxidil

PAndAS' Progeny: Extending the M31 Dwarf Galaxy Cabal

NASA Astrophysics Data System (ADS)

Richardson, Jenny C.; Irwin, Mike J.; McConnachie, Alan W.; Martin, Nicolas F.; Dotter, Aaron L.; Ferguson, Annette M. N.; Ibata, Rodrigo A.; Chapman, Scott C.; Lewis, Geraint F.; Tanvir, Nial R.; Rich, R. Michael

2011-05-01

We present the discovery of five new dwarf galaxies, Andromeda XXIII-XXVII, located in the outer halo of M31. These galaxies were discovered during the second year of data from the Pan-Andromeda Archaeological Survey (PAndAS), a photometric survey of the M31/M33 subgroup conducted with the MegaPrime/MegaCam wide-field camera on the Canada-France-Hawaii Telescope. The current PAndAS survey now provides an almost complete panoramic view of the M31 halo out to an average projected radius of ~150 kpc. Here we present for the first time the metal-poor stellar density map for this whole region, not only as an illustration of the discovery space for satellite galaxies, but also as a birds-eye view of the ongoing assembly process of an L * disk galaxy. Four of the newly discovered satellites appear as well-defined spatial overdensities of stars lying on the expected locus of metal-poor (-2.5 < [Fe/H] < -1.3) red giant branch stars at the distance of M31. The fifth overdensity, And XXVII, is embedded in an extensive stream of such stars and is possibly the remnant of a strong tidal disruption event. Based on distance estimates from horizontal branch magnitudes, all five have metallicities typical of dwarf spheroidal galaxies ranging from [Fe/H] =-1.7 ± 0.2 to [Fe/H] =-1.9 ± 0.2 and absolute magnitudes ranging from MV = -7.1 ± 0.5 to MV = -10.2 ± 0.5. These five additional satellites bring the number of dwarf spheroidal galaxies in this region to 25 and continue the trend whereby the brighter dwarf spheroidal satellites of M31 generally have much larger half-light radii than their Milky Way counterparts. With an extended sample of M31 satellite galaxies, we also revisit the spatial distribution of this population and in particular we find that, within the current projected limits of the PAndAS survey, the surface density of satellites is essentially constant out to 150 kpc. This corresponds to a radial density distribution of satellites varying as r -1, a result seemingly in conflict with the predictions of cosmological simulations. Based on observations obtained with the MegaPrime/MegaCam, a joint project of the Canada-France-Hawaii Telescope (CFHT) and CEA/DAPNIA, at CFHT which is operated by the National Research Council (NRC) of Canada, the Institut National des Science de l'Univers of the Centre National de la Recherche Scientifique (CNRS) of France, and the University of Hawaii.

The Mega Mesospheric Parachute

NASA Technical Reports Server (NTRS)

Kloesel, Kurt J.; Oberto, Robert; Kinsey, Robert

2005-01-01

The current understanding and modeling of the upper reaches of the atmosphere is incomplete. Upper atmospheric interactions with the lower atmosphere, effects of ionizing radiation, high altitude cloud phenomena, and the dynamical interaction with the magnetosphere require greater definition. The scientific objective of obtaining a greater understanding of the upper atmosphere can be achieved by designing, implementing, testing, and utilizing a facility that provides long period in-situ measurements of the mesosphere. Current direct sub-sonic measurements of the upper atmosphere are hampered by the approximately one minute sub-sonic observation window of a ballistic sounding rocket regardless of the launch angle. In-situ measurements at greater than transonic speeds impart energy into the molecular atmospheric system and distort the true atmospheric chemistry. A long duration, sub-sonic capability will significantly enhance our ability to observe and measure: (1) mesospheric lightning phenomena (sprites and blue jets) (2) composition, structure and stratification of noctilucent clouds (3) physics of seasonal radar echoes, gravity wave phenomena (4) chemistry of mesospheric gaseous ratio mixing (5) mesospheric interaction of ionizing radiation (6) dynamic electric and magnetic fields This new facility will also provide local field measurements which complement those that can be obtained through external measurements from satellite and ground-based platforms. The 400 foot (approximately 130 meter) diameter lightweight mega-mesospheric parachute system, deployed with a sounding rocket, is proposed herein as a method to increase sub-sonic mesospheric measurement time periods by more than an order of magnitude. The report outlines a multi-year evolving science instrumentation suite in parallel with the development of the mega meso-chute facility. The developmental issues surrounding the meso-chute are chiefly materials selection (thermal and structural) and deployment mechanism physics. Three mission cases were conceived and developed to include cost and schedules estimates. Each scenario has increasing scientific utility with paralleling launch weight, parachute hang-time, deployment altitude, and parachute size: (1) Case #1: $8.4M@24 months, 6kg payload, 20 min., 50km alt., 80 m. dia. (2) Case #2: $10.4M@24 months, 6kg payload, 20 min., 60km alt, 130m. dia. (3) Case #3: $13.6M@36 months, 30kg payload, 30 min., 90km alt., 200m. dia. The initial breakout cost for the parachute system is approximately $2M@24 months. This report identifies that although the challenges of the mega-meso-chute may be difficult, they can be surmounted and valuable results can be achieved.

The antioxidant effect of Green Tea Mega EGCG against electromagnetic radiation-induced oxidative stress in the hippocampus and striatum of rats.

PubMed

Ahmed, Nawal A; Radwan, Nasr M; Aboul Ezz, Heba S; Salama, Noha A

2017-01-01

Electromagnetic radiation (EMR) of cellular phones may affect biological systems by increasing free radicals and changing the antioxidant defense systems of tissues, eventually leading to oxidative stress. Green tea has recently attracted significant attention due to its health benefits in a variety of disorders, ranging from cancer to weight loss. Thus, the aim of the present study was to investigate the effect of EMR (frequency 900 MHz modulated at 217 Hz, power density 0.02 mW/cm 2 , SAR 1.245 W/kg) on different oxidative stress parameters in the hippocampus and striatum of adult rats. This study also extends to evaluate the therapeutic effect of green tea mega EGCG on the previous parameters in animals exposed to EMR after and during EMR exposure. The experimental animals were divided into four groups: EMR-exposed animals, animals treated with green tea mega EGCG after 2 months of EMR exposure, animals treated with green tea mega EGCG during EMR exposure and control animals. EMR exposure resulted in oxidative stress in the hippocampus and striatum as evident from the disturbances in oxidant and antioxidant parameters. Co-administration of green tea mega EGCG at the beginning of EMR exposure for 2 and 3 months had more beneficial effect against EMR-induced oxidative stress than oral administration of green tea mega EGCG after 2 months of exposure. This recommends the use of green tea before any stressor to attenuate the state of oxidative stress and stimulate the antioxidant mechanism of the brain.

Accuracy and stability of measuring GABA, glutamate, and glutamine by proton magnetic resonance spectroscopy: A phantom study at 4 Tesla

PubMed Central

Henry, Michael E.; Lauriat, Tara L.; Shanahan, Meghan; Renshaw, Perry F.; Jensen, J. Eric

2015-01-01

Proton magnetic resonance spectroscopy has the potential to provide valuable information about alterations in gamma-aminobutyric acid (GABA), glutamate (Glu), and glutamine (Gln) in psychiatric and neurological disorders. In order to use this technique effectively, it is important to establish the accuracy and reproducibility of the methodology. In this study, phantoms with known metabolite concentrations were used to compare the accuracy of 2D J-resolved MRS, single-echo 30 ms PRESS, and GABA-edited MEGA-PRESS for measuring all three aforementioned neurochemicals simultaneously. The phantoms included metabolite concentrations above and below the physiological range and scans were performed at baseline, 1 week, and 1 month time-points. For GABA measurement, MEGA-PRESS proved optimal with a measured-to-target correlation of R2 = 0.999, with J-resolved providing R2 = 0.973 for GABA. All three methods proved effective in measuring Glu with R2 = 0.987 (30 ms PRESS), R2 = 0.996 (J-resolved) and R2 = 0.910 (MEGA-PRESS). J-resolved and MEGA-PRESS yielded good results for Gln measures with respective R2 = 0.855 (J-resolved) and R2 = 0.815 (MEGA-PRESS). The 30 ms PRESS method proved ineffective in measuring GABA and Gln. When measurement stability at in vivo concentration was assessed as a function of varying spectral quality, J-resolved proved the most stable and immune to signal-to-noise and linewidth fluctuation compared to MEGA-PRESS and 30 ms PRESS. PMID:21130670

Effect of positive pulse charge waveforms on cycle life of nickel-zinc cells

NASA Technical Reports Server (NTRS)

Smithrick, J. J.

1980-01-01

Five amp-hour nickel-zinc cells were life cycled to evaluate four different charge methods. Three of the four waveforms investigated were 120 Hz full wave rectified sinusoidal (FWRS), 120 Hz silicon controlled rectified (SCR), and 1 kHz square wave (SW). The fourth, a constant current method, was used as a baseline of comparison. Three sealed Ni-Zn cells connected in series were cycled. Each series string was charged at an average c/20 rate, and discharged at a c/2.5 rate to a 75% rated depth. Results indicate that the relatively inexpensive 120 Hz FWRS charger appears feasible for charging 5 amp-hour nickel-zinc cells with no significant loss in average cycle life when compared to constant current charging. The 1-kHz SW charger could also be used with no significant loss in average cycle life, and suggests the possibility of utilizing the existing electric vehicle chopper controller circuitry for an on-board charger. There was an apparent difference using the 120 Hz SCR charger compared to the others, however, this difference could be due to an inadvertent severe overcharge, which occurred prior to cell failure. The remaining two positive pulse charging waveforms, FWRS and 1 kHz, did not improve the cycle life of 5 amp-hour nickel-zinc cells over that of constant current charging.

Best Practices from WisDOT Mega and ARRA Projects

DOT National Transportation Integrated Search

2012-03-01

Since 2004 WisDOT has developed a number of new techniques, methods, processes and procedures for management of two new : types of transportation projects: Mega projects and projects funded through the American Recovery and Reinvestment Act of ...

Best practices from WisDOT mega and ARRA projects.

DOT National Transportation Integrated Search

2012-03-01

Since 2004 WisDOT has developed a number of new techniques, methods, processes and procedures for management of two new types of transportation projects: "Mega projects" and projects funded through the American Recovery and Reinvestment Act of 2009 (...

Bridge Approach Remedies Implemented at Western Mega Site

DOT National Transportation Integrated Search

2017-09-01

As part of the heavy axle load (HAL) revenue service mega site testing program, the Transportation Technology Center, Inc. (TTCI) has worked closely with the Union Pacific Railroad (UP) to address bridge approach problems under HAL operations. The te...

A role for Piezo2 in EPAC1-dependent mechanical allodynia

PubMed Central

Eijkelkamp, N; Linley, J.E.; Torres, J.M.; Bee, L.; Dickenson, A.H.; Gringhuis, M.; Minett, M.S.; Hong, G.S.; Lee, E.; Oh, U.; Ishikawa, Y.; Zwartkuis, F.J.; Cox, J.J.; Wood, J.N.

2013-01-01

Aberrant mechanosensation has an important role in different pain states. Here we show that Epac1 (cyclic AMP sensor) potentiation of Piezo2-mediated mechanotransduction contributes to mechanical allodynia. Dorsal root ganglia Epac1 mRNA levels increase during neuropathic pain, and nerve damage-induced allodynia is reduced in Epac1−/− mice. The Epac-selective cAMP analogue 8-pCPT sensitizes mechanically evoked currents in sensory neurons. Human Piezo2 produces large mechanically gated currents that are enhanced by the activation of the cAMP-sensor Epac1 or cytosolic calcium but are unaffected by protein kinase C or protein kinase A and depend on the integrity of the cytoskeleton. In vivo, 8-pCPT induces long-lasting allodynia that is prevented by the knockdown of Epac1 and attenuated by mouse Piezo2 knockdown. Piezo2 knockdown also enhanced thresholds for light touch. Finally, 8-pCPT sensitizes responses to innocuous mechanical stimuli without changing the electrical excitability of sensory fibres. These data indicate that the Epac1–Piezo2 axis has a role in the development of mechanical allodynia during neuropathic pain. PMID:23575686

Mega-precovery and data mining of near-Earth asteroids and other Solar System objects

NASA Astrophysics Data System (ADS)

Popescu, M.; Vaduvescu, O.; Char, F.; Curelaru, L.; Euronear Team

2014-07-01

The vast collection of CCD images and photographic plate archives available from the world-wide archives and telescopes is still insufficiently exploited. Within the EURONEAR project we designed two data mining software with the purpose to search very large collections of archives for images which serendipitously include known asteroids or comets in their field, with the main aims to extend the arc and improve the orbits. In this sense, ''Precovery'' (published in 2008, aiming to search all known NEAs in few archives via IMCCE's SkyBoT server) and ''Mega-Precovery'' (published in 2010, querying the IMCCE's Miriade server) were made available to the community via the EURONEAR website (euronear.imcce.fr). Briefly, Mega-Precovery aims to search one or a few known asteroids or comets in a mega-collection including millions of images from some of the largest observatory archives: ESO (15 instruments served by ESO Archive including VLT), NVO (8 instruments served by U.S. NVO Archive), CADC (11 instruments, including HST and Gemini), plus other important instrument archives: SDSS, CFHTLS, INT-WFC, Subaru-SuprimeCam and AAT-WFI, adding together 39 instruments and 4.3 million images (Mar 2014), and our Mega-Archive is growing. Here we present some of the most important results obtained with our data-mining software and some new planned search options of Mega-Precovery. Particularly, the following capabilities will be added soon: the ING archive (all imaging cameras) will be included and new search options will be made available (such as query by orbital elements and by observations) to be able to target new Solar System objects such as Virtual Impactors, bolides, planetary satellites, TNOs (besides the comets added recently). In order to better characterize the archives, we introduce the ''AOmegaA'' factor (archival etendue) proportional to the AOmega (etendue) and the number of images in an archive. With the aim to enlarge the Mega-Archive database, we invite the observatories (particularly those storing their images online and also those that own plate archives which could be scanned on request) to contact us in order to add their instrument archives (consisting of an ASCII file with telescope pointings in a simple format) to our Mega-Precovery open project. We intend for the future to synchronise our service with the Virtual Observatory.

Extracellular 2′,3′-cAMP-adenosine pathway in proximal tubular, thick ascending limb, and collecting duct epithelial cells

PubMed Central

Gillespie, Delbert G.

2013-01-01

In a previous study, we demonstrated that human proximal tubular epithelial cells obtained from a commercial source metabolized extracellular 2′,3′-cAMP to 2′-AMP and 3′-AMP and extracellular 2′-AMP and 3′-AMP to adenosine (the extracellular 2′,3′-cAMP-adenosine pathway; extracellular 2′,3′-cAMP → 2′-AMP + 3′-AMP → adenosine). The purpose of this study was to investigate the metabolism of extracellular 2′,3′-cAMP in proximal tubular vs. thick ascending limb vs. collecting duct epithelial cells freshly isolated from their corresponding nephron segments obtained from rat kidneys. In epithelial cells from all three nephron segments, 1) extracellular 2′,3′-cAMP was metabolized to 2′-AMP and 3′-AMP, with 2′-AMP > 3′-AMP, 2) the metabolism of extracellular 2′,3′-cAMP to 2′-AMP and 3′-AMP was not inhibited by either 3-isobutyl-1-methylxanthine (phosphodiesterase inhibitor) or 1,3-dipropyl-8-p-sulfophenylxanthine (ecto-phosphodiesterase inhibitor), 3) extracellular 2′,3′-cAMP increased extracellular adenosine levels, 4) 3′-AMP and 2′-AMP were metabolized to adenosine with an efficiency similar to that of 5′-AMP, and 5) the metabolism of 5′-AMP, 3′-AMP, and 2′-AMP was not inhibited by α,β-methylene-adenosine-5′-diphosphate (CD73 inhibitor). These results support the conclusion that renal epithelial cells all along the nephron can metabolize extracellular 2′,3′-cAMP to 2′-AMP and 3′-AMP and can efficiently metabolize extracellular 2′-AMP and 3′-AMP to adenosine and that the metabolic enzymes involved are not the classical phosphodiesterases nor ecto-5′-nucleotidase (CD73). Because 2′,3′-cAMP is released by injury and because previous studies demonstrate that the extracellular 2′,3′-cAMP-adenosine pathway stimulates epithelial cell proliferation via adenosine A2B receptors, the present results suggest that the extracellular 2′,3′-cAMP-adenosine pathway may help restore epithelial cells along the nephron following kidney injury. PMID:23077101

The Brain In Vivo Expresses the 2′,3′-cAMP-Adenosine Pathway

PubMed Central

Verrier, Jonathan D.; Jackson, Travis C.; Bansal, Rashmi; Kochanek, Patrick M.; Puccio, Ava M.; Okonkwo, David O.; Jackson, Edwin K.

2012-01-01

Although multiple biochemical pathways produce adenosine, studies suggest that the 2′,3′-cAMP-adenosine pathway (2′,3′-cAMP → 2′-AMP/3′-AMP → adenosine) contributes to adenosine production in some cells/tissues/organs. To determine whether the 2′,3′-cAMP-adenosine pathway exists in vivo in the brain, we delivered to the brain (gray matter and white matter separately) via the inflow perfusate of a microdialysis probe either 2′,3′-cAMP, 3′,5′-cAMP, 2′-AMP, 3′-AMP, or 5′-AMP and measured the recovered metabolites in the microdialysis outflow perfusate with mass spectrometry. In both gray and white matter, 2′,3′-cAMP increased 2′-AMP, 3′-AMP and adenosine, and 3′,5′-cAMP increased 5′-AMP and adenosine. In both brain regions, 2′-AMP, 3-AMP and 5′-AMP were converted to adenosine. Microdialysis experiments in 2′,3′-cyclic nucleotide-3′-phosphodiesterase (CNPase) wild-type mice demonstrated that traumatic brain injury (TBI; controlled cortical impact model) activated the brain 2,3′-cAMP-adenosine pathway; similar experiments in CNPase knockout mice indicated that CNPase was involved in the metabolism of endogenous 2′,3′-cAMP to 2′-AMP and to adenosine. In CSF from TBI patients, 2′,3′-cAMP was significantly increased in the initial 12 hours after injury and strongly correlated with CSF levels of 2′-AMP, 3′-AMP, adenosine and inosine. We conclude that in vivo, 2′,3′-cAMP is converted to 2′-AMP/3′-AMP, and these AMPs are metabolized to adenosine. This pathway exists endogenously in both mice and humans. PMID:22360621

Cellular cAMP uptake as trigger for electrotaxis

NASA Astrophysics Data System (ADS)

Guido, Isabella; Bodenschatz, Eberhard

Cells have the ability to detect continuous current electric fields and respond to them with a directed migratory movement. Dictyostelium discoideum cells, a key model organism for the study of eukaryotic chemotaxis, orient and migrate toward the cathode under the influence of an electric field. The underlying sensing mechanism and whether it is shared by the chemotactic response pathway remains unknown. By investigating the migration in the electric field of cell strains unable to migrate chemotactically (Amib-null) and with defective cAMP relay (ACA-null) we show that the starvation-induced transcription of a set of genes involved in the early developmental stage is not necessary for electrotaxis. However, the analysis of electrotaxis of vegetative cells as well as shortly starved cells shows that cells need to be stimulated with cAMP in order for them to migrate electrotactically. Indeed 30 minutes stimulation with cAMP pulses is enough to let cells orienting with the electric field although during this time the expression of receptors and the beginning of the development has not happened yet. We believe that the reason for this observed phenomenon lies on the endocytosis of the external cAMP which triggers electrotaxis as long as endocytosis and exocytosis are not balanced. This work is part of the MaxSynBio Consortium which is jointly funded by the Federal Ministry of Education and Research of Germany and the Max Planck Society.

An Inorganic Microsphere Composite for the Selective Removal of Cesium 137 from Acidic Nuclear Waste Solutions - Parts 1 and 2

DOE Office of Scientific and Technical Information (OSTI.GOV)

T. J. Tranter; T. A. Vereschchagina; V. Utgikar

2009-03-01

A new inorganic ion exchange composite for removing radioactive cesium from acidic waste streams has been developed. The new material consists of ammonium molybdophosphate, (NH4)3P(Mo3O10)4•3H2O (AMP), synthesized within hollow aluminosilicate microspheres (AMP-C), which are produced as a by-product from coal combustion. The selective cesium exchange capacity of this inorganic composite was evaluated in bench-scale column tests using simulated sodium bearing waste solution as a surrogate for the acidic tank waste currently stored at the Idaho National Laboratory (INL). Total cesium loading on the columns at saturation agreed very well with equilibrium values predicted from isotherm experiments performed previously. A numericalmore » algorithm for solving the governing partial differential equations (PDE) for cesium uptake was developed using the intraparticle mass transfer coefficient obtained from previous batch kinetic experiments. Solutions to the governing equations were generated to obtain the cesium concentration at the column effluent as a function of throughput volume using the same conditions as those used for the actual column experiments. The numerical solutions of the PDE fit the column break through data quite well for all the experimental conditions in the study. The model should therefore provide a reliable prediction of column performance at larger scales. A new inorganic ion exchange composite consisting of ammonium molybdophosphate, (NH4)3P(Mo3O10)4•3H2O (AMP), synthesized within hollow aluminosilicate microspheres (AMP-C) has been developed. Two different batches of the sorbent were produced resulting in 20% and 25% AMP loading for two and three loading cycles, respectively. The selective cesium exchange capacity of this inorganic composite was evaluated using simulated sodium bearing waste solution as a surrogate for the acidic tank waste currently stored at the Idaho National Laboratory (INL). Equilibrium isotherms obtained from these experiments were very favorable for cesium uptake and indicated maximum cesium loading of approximately 9 % by weight of dry AMP. Batch kinetic experiments were also performed to obtain the necessary data to estimate the effective diffusion coefficient for cesium in the sorbent particle. These experiments resulted in effective intraparticle cesium diffusivity coefficients of 4.99 x 10-8 cm2/min and 4.72 x 10-8 cm2/min for the 20% and 25 % AMP-C material, respectively.« less

Efficient numerical method of freeform lens design for arbitrary irradiance shaping

NASA Astrophysics Data System (ADS)

Wojtanowski, Jacek

2018-05-01

A computational method to design a lens with a flat entrance surface and a freeform exit surface that can transform a collimated, generally non-uniform input beam into a beam with a desired irradiance distribution of arbitrary shape is presented. The methodology is based on non-linear elliptic partial differential equations, known as Monge-Ampère PDEs. This paper describes an original numerical algorithm to solve this problem by applying the Gauss-Seidel method with simplified boundary conditions. A joint MATLAB-ZEMAX environment is used to implement and verify the method. To prove the efficiency of the proposed approach, an exemplary study where the designed lens is faced with the challenging illumination task is shown. An analysis of solution stability, iteration-to-iteration ray mapping evolution (attached in video format), depth of focus and non-zero étendue efficiency is performed.

National Ignition Facility Project: An Update

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hogan, W J; Moses, E; Warner, B

2000-12-07

The National Ignition Facility (NIF) consists of 192 forty-centimeter-square laser beams and a 10-m-diameter target chamber. Physical construction began in 1997. The Laser and Target Area Building and the Optics Assembly Building were the first major construction activities, and despite several unforeseen obstacles, the buildings are now 92% complete and have been done on time and within cost. Prototype component development and testing has proceeded in parallel. Optics vendors have installed full-scale production lines and have done prototype production runs. The assembly and integration of the beampath infrastructure has been reconsidered and a new approach has been developed. This papermore » will discuss the status of the NIF project and the plans for completion. It will also include summary information on Laser MegaJoule (LMJ) provided by M. Andre, LMJ Project Director.« less

Potentiation of angiogenic switch in capillary endothelial cells by cAMP: A cross-talk between up-regulated LLO biosynthesis and the HSP-70 expression.

PubMed

Martínez, Juan A; Tavárez, José J; Oliveira, Caroline M; Banerjee, Dipak K

2006-05-01

During tumor growth and invasion, the endothelial cells from a relatively quiescent endothelium start proliferating. The exact mechanism of switching to a new angiogenic phenotype is currently unknown. We have examined the role of intracellular cAMP in this process. When a non-transformed capillary endothelial cell line was treated with 2 mM 8Br-cAMP, cell proliferation was enhanced by approximately 70%. Cellular morphology indicated enhanced mitosis after 32-40 h with almost one-half of the cell population in the S phase. Bcl-2 expression and caspase-3, -8, and -9 activity remained unaffected. A significant increase in the Glc(3)Man(9)GlcNAc(2)-PP-Dol biosynthesis and turnover, Factor VIIIC N-glycosylation, and cell surface expression of N-glycans was observed in cells treated with 8Br-cAMP. Dol-P-Man synthase activity in the endoplasmic reticulum membranes also increased. A 1.4-1.6-fold increase in HSP-70 and HSP-90 expression was also observed in 8Br-cAMP treated cells. On the other hand, the expression of GRP-78/Bip was 2.3-fold higher compared to that of GRP-94 in control cells, but after 8Br-cAMP treatment for 32 h, it was reduced by 3-fold. GRP-78/Bip expression in untreated cells was 1.2-1.5-fold higher when compared with HSP-70 and HSP-90, whereas that of the GRP-94 was 1.5-1.8-fold lower. After 8Br-cAMP treatment, GRP-78/Bip expression was reduced 4.5-4.8-fold, but the GRP-94 was reduced by 1.5-1.6-fold only. Upon comparison, a 2.9-fold down-regulation of GRP-78/Bip was observed compared to GRP-94. We, therefore, conclude that a high level of Glc(3)Man(9)GlcNAc(2)-PP-Dol, resulting from 8Br-cAMP stimulation up-regulated HSP-70 expression and down-regulated that of the GRP-78/Bip, maintained adequate protein folding, and reduced endoplasmic reticulum stress. As a result capillary endothelial cell proliferation was induced.

Pharmacological analysis of epithelial chloride secretion mechanisms in adult murine airways.

PubMed

Gianotti, Ambra; Ferrera, Loretta; Philp, Amber R; Caci, Emanuela; Zegarra-Moran, Olga; Galietta, Luis J V; Flores, Carlos A

2016-06-15

Defective epithelial chloride secretion occurs in humans with cystic fibrosis (CF), a genetic defect due to loss of function of CFTR, a cAMP-activated chloride channel. In the airways, absence of an active CFTR causes a severe lung disease. In mice, genetic ablation of CFTR function does not result in similar lung pathology. This may be due to the expression of an alternative chloride channel which is activated by calcium. The most probable protein performing this function is TMEM16A, a calcium-activated chloride channel (CaCC). Our aim was to assess the relative contribution of CFTR and TMEM16A to chloride secretion in adult mouse trachea. For this purpose we tested pharmacological inhibitors of chloride channels in normal and CF mice. The amplitude of the cAMP-activated current was similar in both types of animals and was not affected by a selective CFTR inhibitor. In contrast, a CaCC inhibitor (CaCCinh-A01) strongly blocked the cAMP-activated current as well as the calcium-activated chloride secretion triggered by apical UTP. Although control experiments revealed that CaCCinh-A01 also shows inhibitory activity on CFTR, our results indicate that transepithelial chloride secretion in adult mouse trachea is independent of CFTR and that another channel, possibly TMEM16A, performs both cAMP- and calcium-activated chloride transport. The prevalent function of a non-CFTR channel may explain the absence of a defect in chloride transport in CF mice. Copyright © 2016. Published by Elsevier B.V.

Spontaneous formation of structurally diverse membrane channel architectures from a single antimicrobial peptide

NASA Astrophysics Data System (ADS)

Wang, Yukun; Chen, Charles H.; Hu, Dan; Ulmschneider, Martin B.; Ulmschneider, Jakob P.

2016-11-01

Many antimicrobial peptides (AMPs) selectively target and form pores in microbial membranes. However, the mechanisms of membrane targeting, pore formation and function remain elusive. Here we report an experimentally guided unbiased simulation methodology that yields the mechanism of spontaneous pore assembly for the AMP maculatin at atomic resolution. Rather than a single pore, maculatin forms an ensemble of structurally diverse temporarily functional low-oligomeric pores, which mimic integral membrane protein channels in structure. These pores continuously form and dissociate in the membrane. Membrane permeabilization is dominated by hexa-, hepta- and octamers, which conduct water, ions and small dyes. Pores form by consecutive addition of individual helices to a transmembrane helix or helix bundle, in contrast to current poration models. The diversity of the pore architectures--formed by a single sequence--may be a key feature in preventing bacterial resistance and could explain why sequence-function relationships in AMPs remain elusive.

The future of EPAC-targeted therapies: agonism versus antagonism.

PubMed

Parnell, Euan; Palmer, Timothy M; Yarwood, Stephen J

2015-04-01

Pharmaceutical manipulation of cAMP levels exerts beneficial effects through the regulation of the exchange protein activated by cAMP (EPAC) and protein kinase A (PKA) signalling routes. Recent attention has turned to the specific regulation of EPAC isoforms (EPAC1 and EPAC2) as a more targeted approach to cAMP-based therapies. For example, EPAC2-selective agonists could promote insulin secretion from pancreatic β cells, whereas EPAC1-selective agonists may be useful in the treatment of vascular inflammation. By contrast, EPAC1 and EPAC2 antagonists could both be useful in the treatment of heart failure. Here we discuss whether the best way forward is to design EPAC-selective agonists or antagonists and the current strategies being used to develop isoform-selective, small-molecule regulators of EPAC1 and EPAC2 activity. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Testing of wide-gap welds at eastern mega site.

DOT National Transportation Integrated Search

2013-08-01

In 2005, Transportation Technology Center, Inc. (TTCI) and Norfolk Southern Railway (NS) began a test of wide-gap welds (WGWs) at the eastern mega site near Bluefield, WV. : WGWs enable the repair of weld or railhead defects with a single weld instea...

Kinin effects on electrogenic ion transport in primary cultures of pig renal papillary collecting tubule cells.

PubMed

Cuthbert, A W; George, A M; MacVinish, L

1985-09-01

Confluent monolayers of pig renal papillary collecting tubule (RPCT) cells were formed on Millipore filters coated with collagen. They were clamped in Ussing-type chambers and used to measure short-circuit current (SCC). The monolayers had low potentials (0.1 mV) with the basolateral side positive. Small inward currents flowed under short-circuit conditions. Increases in SCC were obtained following addition of a number of agents. Receptors associated with SCC changes were disposed as follows: for kinins (e.g., lysyl-bradykinin) they were present on both sides of the tissue, while those for arginine vasopressin and norepinephrine were present on the basolateral side only. Epithelia responded to PGE2 added to the apical or basolateral face of the tissue; application to one side prevented the response from the contralateral side. The tissues also responded to forskolin, an activator of adenylate cyclase, with a sustained inward current that was sensitive to furosemide. Similar sustained inward currents were recorded following exposure to 8-bromoadenosine-3',5'-cyclic monophosphate (BrcAMP). Responses to kinins were attenuated by inhibition of fatty acid cyclooxygenase with either indomethacin or piroxicam or by replacing chloride with impermeant ions. If the SCC was first increased with forskolin, BrcAMP, or norepinephrine, the kinin effects on SCC were either abolished or reversed. It is concluded that kinin can cause chloride secretion in RPCT monolayers, possibly via a prostaglandin or a prostaglandin-adenylate cyclase mechanism. Secondary effects of kinin, exposed by first raising tissue cAMP levels, are not precluded.

Controlling hollow relativistic electron beam orbits with an inductive current divider

DOE PAGES

Swanekamp, S. B.; Richardson, A. S.; Angus, J. R.; ...

2015-02-06

A passive method for controlling the trajectory of an intense, hollow electron beam is proposed using a vacuum structure that inductively splits the beam's return current. A central post carries a portion of the return current (I 1), while the outer conductor carries the remainder (I 2). An envelope equation appropriate for a hollow electron beam is derived and applied to the current divider. The force on the beam trajectory is shown to be proportional to (I 2-I 1), while the average force on the envelope (the beam width) is proportional to the beam current I b = (I 2more » + I 1). The values of I 1 and I 2 depend on the inductances in the return-current path geometries. Proper choice of the return-current geometries determines these inductances and offers control over the beam trajectory. As a result, solutions using realistic beam parameters show that, for appropriate choices of the return-current-path geometry, the inductive current divider can produce a beam that is both pinched and straightened so that it approaches a target at near-normal incidence with a beam diameter that is on the order of a few mm.« less

Management of patients brought in by ambulance to the emergency department: role of the Advanced Musculoskeletal Physiotherapist.

PubMed

Kinsella, Rita; Collins, Tom; Shaw, Bridget; Sayer, James; Cary, Belinda; Walby, Andrew; Cowan, Sallie

2017-05-09

Objective The aim of the present study was to evaluate the role of the Advanced Musculoskeletal Physiotherapist (AMP) in managing patients brought in by ambulance to the emergency department (ED). Methods This study was a dual-centre observational study. Patients brought in by ambulance to two Melbourne hospitals over a 12-month period and seen by an AMP were compared with a matched group seen by other ED staff. Primary outcome measures were wait time and length of stay (LOS) in the ED. Results Data from 1441 patients within the Australasian Triage Scale (ATS) Categories 3-5 with musculoskeletal complaints were included in the analysis. Subgroup analysis of 825 patients aged ≤65 years demonstrated that for Category 4 (semi-urgent) patients, the median wait time to see the AMP was 9.5min (interquartile range (IQR) 3.25-18.00min) compared with 25min (IQR 10.00-56.00min) to see other ED staff (P ≤ 0.05). LOS analysis was undertaken on patients discharged home and demonstrated that there was a 1.20 greater probability (95% confidence interval 1.07-1.35) that ATS Category 4 patients managed by the AMP were discharged within the 4-hour public hospital target compared with patients managed by other ED staff: 87.04% (94/108) of patients managed by the AMPs met this standard compared with 72.35% (123/170) of patients managed by other ED staff (P=0.002). Conclusions Patients aged ≤65 years with musculoskeletal complaints brought in by ambulance to the ED and triaged to ATS Category 4 are likely to wait less time to be seen and are discharged home more quickly when managed by an AMP. This study has added to the evidence that AMPs improve patient flow in the ED, freeing up time for other ED staff to see higher-acuity, more complex patients. What is known about the topic? There is a growing body of evidence establishing that AMPs improve the flow of patients presenting with musculoskeletal conditions to the ED through reduced wait times and LOS and, at the same time, providing good-quality care and enhanced patient satisfaction. What does this paper add? Within their primary contact capacity, AMPs also manage patients who are brought in by ambulance presenting with musculoskeletal conditions. To the authors' knowledge, there is currently no available literature documenting the performance of AMPs in the management of this cohort of patients. What are the implications for practitioners? This study has added to the body of evidence that AMPs improve patient flow in the ED and illustrates that AMPs, by seeing patients brought in by ambulance, are able to have a positive impact on the pressures increasingly facing the Victorian Ambulance Service and emergency hospital care.

Comparison of low-light nonmydriatic digital imaging with 35-mm ETDRS seven-standard field stereo color fundus photographs and clinical examination.

PubMed

Silva, Paolo S; Walia, Saloni; Cavallerano, Jerry D; Sun, Jennifer K; Dunn, Cheri; Bursell, Sven-Erik; Aiello, Lloyd M; Aiello, Lloyd Paul

2012-09-01

To compare agreement between diagnosis of clinical level of diabetic retinopathy (DR) and diabetic macular edema (DME) derived from nonmydriatic fundus images using a digital camera back optimized for low-flash image capture (MegaVision) compared with standard seven-field Early Treatment Diabetic Retinopathy Study (ETDRS) photographs and dilated clinical examination. Subject comfort and image acquisition time were also evaluated. In total, 126 eyes from 67 subjects with diabetes underwent Joslin Vision Network nonmydriatic retinal imaging. ETDRS photographs were obtained after pupillary dilation, and fundus examination was performed by a retina specialist. There was near-perfect agreement between MegaVision and ETDRS photographs (κ=0.81, 95% confidence interval [CI] 0.73-0.89) for clinical DR severity levels. Substantial agreement was observed with clinical examination (κ=0.71, 95% CI 0.62-0.80). For DME severity level there was near-perfect agreement with ETDRS photographs (κ=0.92, 95% CI 0.87-0.98) and moderate agreement with clinical examination (κ=0.58, 95% CI 0.46-0.71). The wider MegaVision 45° field led to identification of nonproliferative changes in areas not imaged by the 30° field of ETDRS photos. Field area unique to ETDRS photographs identified proliferative changes not visualized with MegaVision. Mean MegaVision acquisition time was 9:52 min. After imaging, 60% of subjects preferred the MegaVision lower flash settings. When evaluated using a rigorous protocol, images captured using a low-light digital camera compared favorably with ETDRS photography and clinical examination for grading level of DR and DME. Furthermore, these data suggest the importance of more extensive peripheral images and suggest that utilization of wide-field retinal imaging may further improve accuracy of DR assessment.

ICESpy009, a Conjugative Genetic Element Carrying mef(E) in Streptococcus pyogenes.

PubMed

Del Grosso, Maria; Camilli, Romina; Rizzi, Ermanno; Pietrelli, Alessandro; De Bellis, Gianluca; Pantosti, Annalisa

2016-07-01

Efflux-mediated macrolide resistance due to mef(E) and mel, carried by the mega element, is common in Streptococcus pneumoniae, for which it was originally characterized, but it is rare in Streptococcus pyogenes In S. pyogenes, mega was previously found to be enclosed in Tn2009, a composite genetic element of the Tn916 family containing tet(M) and conferring erythromycin and tetracycline resistance. In this study, S. pyogenes isolates containing mef(E), apparently not associated with other resistance determinants, were examined to characterize the genetic context of mega. By whole-genome sequencing of one isolate, MB56Spyo009, we identified a novel composite integrative and conjugative element (ICE) carrying mega, designated ICESpy009, belonging to the ICESa2603 family. ICESpy009 was 55 kb long, contained 61 putative open reading frames (ORFs), and was found to be integrated into hylA, a novel integration site for the ICESa2603 family. The modular organization of the ICE was similar to that of members of the ICESa2603 family carried by different streptococcal species. In addition, a novel cluster of accessory resistance genes was found inside a region that encloses mega. PCR mapping targeting ICESpy009 revealed the presence of a similar ICE in five other isolates under study. While in three isolates the integration site was the same as that of ICESpy009, in two isolates the ICE was integrated into rplL, the typical integration site of the ICESa2603 family. ICESpy009 was able to transfer macrolide resistance by conjugation to both S. pyogenes and S. pneumoniae, showing the first evidence of the transferability of mega from S. pyogenes. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

ICESpy009, a Conjugative Genetic Element Carrying mef(E) in Streptococcus pyogenes

PubMed Central

Camilli, Romina; Rizzi, Ermanno; Pietrelli, Alessandro; De Bellis, Gianluca; Pantosti, Annalisa

2016-01-01

Efflux-mediated macrolide resistance due to mef(E) and mel, carried by the mega element, is common in Streptococcus pneumoniae, for which it was originally characterized, but it is rare in Streptococcus pyogenes. In S. pyogenes, mega was previously found to be enclosed in Tn2009, a composite genetic element of the Tn916 family containing tet(M) and conferring erythromycin and tetracycline resistance. In this study, S. pyogenes isolates containing mef(E), apparently not associated with other resistance determinants, were examined to characterize the genetic context of mega. By whole-genome sequencing of one isolate, MB56Spyo009, we identified a novel composite integrative and conjugative element (ICE) carrying mega, designated ICESpy009, belonging to the ICESa2603 family. ICESpy009 was 55 kb long, contained 61 putative open reading frames (ORFs), and was found to be integrated into hylA, a novel integration site for the ICESa2603 family. The modular organization of the ICE was similar to that of members of the ICESa2603 family carried by different streptococcal species. In addition, a novel cluster of accessory resistance genes was found inside a region that encloses mega. PCR mapping targeting ICESpy009 revealed the presence of a similar ICE in five other isolates under study. While in three isolates the integration site was the same as that of ICESpy009, in two isolates the ICE was integrated into rplL, the typical integration site of the ICESa2603 family. ICESpy009 was able to transfer macrolide resistance by conjugation to both S. pyogenes and S. pneumoniae, showing the first evidence of the transferability of mega from S. pyogenes. PMID:27067338

Optimization of a cAMP response element signal pathway reporter system.

PubMed

Shan, Qiang; Storm, Daniel R

2010-08-15

A sensitive cAMP response element (CRE) reporter system is essential for studying the cAMP/protein kinase A/cAMP response element binding protein signal pathway. Here we have tested a few CRE promoters and found one with high sensitivity to external stimuli. Using this optimal CRE promoter and the enhanced green fluorescent protein as the reporter, we have established a CRE reporter cell line. This cell line can be used to study the signal pathway by fluorescent microscope, fluorescence-activated cell analysis and luciferase assay. This cell line's sensitivity to forskolin, using the technique of fluorescence-activated cell sorting, was increased to approximately seven times that of its parental HEK 293 cell line, which is currently the most commonly used cell line in the field for the signal pathway study. Therefore, this newly created cell line is potentially useful for studying the signal pathway's modulators, which generally have weaker effect than its mediators. Our research has also established a general procedure for optimizing transcription-based reporter cell lines, which might be useful in performing the same task when studying many other transcription-based signal pathways. (c) 2010 Elsevier B.V. All rights reserved.

Application of graphene-ionic liquid-chitosan composite-modified carbon molecular wire electrode for the sensitive determination of adenosine-5'-monophosphate.

PubMed

Shi, Fan; Gong, Shixing; Xu, Li; Zhu, Huanhuan; Sun, Zhenfan; Sun, Wei

2013-12-01

In this paper, a graphene (GR) ionic liquid (IL) 1-octyl-3-methylimidazolium hexafluorophosphate and chitosan composite-modified carbon molecular wire electrode (CMWE) was fabricated by a drop-casting method and further applied to the sensitive electrochemical detection of adenosine-5'-monophosphate (AMP). CMWE was prepared with diphenylacetylene (DPA) as the modifier and the binder. The properties of modified electrode were examined by scanning electron microscopy, cyclic voltammetry and electrochemical impedance spectroscopy. Electrochemical behaviors of AMP was carefully investigated with enhanced responses appeared, which was due to the presence of GR-IL composite on the electrode surface with excellent electrocatalytic ability. A well-defined oxidation peak of AMP appeared at 1.314 V and the electrochemical parameters were calculated by electrochemical methods. Under the selected conditions, the oxidation peak current of AMP was proportional to its concentration in the range from 0.01 μM to 80.0 μM with the detection limit as 3.42 nM (3σ) by differential pulse voltammetry. The proposed method exhibited good selectivity and was applied to the detection of vidarabine monophosphate injection samples with satisfactory results. © 2013.

Stable, sensitive, fluorescence-based method for detecting cAMP.

PubMed

Hesley, Jayne; Daijo, Janet; Ferguson, Anne T

2002-09-01

cAMP is a universal secondary messenger that connects changes in the extracellular environment, as detected by cell surface receptors, to transcriptional changes in the nucleus. Since cAMP-mediated signal transduction plays a role in critical cell functions and human diseases, monitoring its activity can aid in understanding these responses and the process of drug discovery. This report examines the performance of a fluorescence-based competitive immunoassay in 384-well microplate format. Using purified cAMP as a competitor the estimated detection limit was determined to be 0.1 nM and Z'-factor was greater than 0.83, which indicates that the assay is of high quality and one of the most sensitive assays currently on the market. Of note, the results obtained were similar whether the reaction was allowed to proceed for 10 min or up to 60 min. Next, HEK 293 cells were treated with the promiscuous adenylate cyclase activator, forskolin, and the beta-adrenoceptor agonist, isoproterenol. The resultant average EC50 values were 11 microM and 123 nM, respectively, which correspond to those found in the literature. Together, these results demonstrate that this assay is afast, accurate, non-radioactive method that is ideal for high-throughput screening.

Amplified biosensing using the horseradish peroxidase-mimicking DNAzyme as an electrocatalyst.

PubMed

Pelossof, Gilad; Tel-Vered, Ran; Elbaz, Johann; Willner, Itamar

2010-06-01

The hemin/G-quadruplex horseradish peroxidase-mimicking DNAzyme is assembled on Au electrodes. It reveals bioelectrocatalytic properties and electrocatalyzes the reduction of H(2)O(2). The bioelectrocatalytic functions of the hemin/G-quadruplex DNAzyme are used to develop electrochemical sensors that follow the activity of glucose oxidase and biosensors for the detection of DNA or low-molecular-weight substrates (adenosine monophosphate, AMP). Hairpin nucleic structures that include the G-quadruplex sequence in a caged configuration and the nucleic acid sequence complementary to the analyte DNA, or the aptamer sequence for AMP, are immobilized on Au-electrode surfaces. In the presence of the DNA analyte, or AMP, the hairpin structures are opened, and the hemin/G-quadruplex horseradish peroxidase-mimicking DNAzyme structures are generated on the electrode surfaces. The bioelectrocatalytic cathodic currents generated by the functionalized electrodes, upon the electrochemical reduction of H(2)O(2), provide a quantitative measure for the detection of the target analytes. The DNA target was analyzed with a detection limit of 1 x 10(-12) M, while the detection limit for analyzing AMP was 1 x 10(-6) M. Methods to regenerate the sensing surfaces are presented.

Development of a Poly-ε-Lysine Contact Lens as a Drug Delivery Device for the Treatment of Fungal Keratitis.

PubMed

Gallagher, Andrew G; McLean, Keri; Stewart, Rosalind M K; Wellings, Don A; Allison, Heather E; Williams, Rachel L

2017-09-01

The purpose of this study was to develop a more efficient drug delivery device to overcome the limitations of current drop therapy for the treatment of fungal keratitis. Amphotericin B (AmpB), 0 to 30 μg/mL, was associated with a poly-ε-lysine (pεK) hydrogel. Fungicidal effect against Candida albicans was assessed at 18 and 42 hours by optical density (OD600) and growth on agar. Tear film dilution effect was mimicked by storage of AmpB pεK gels in 3.4 mL sterile PBS for 24 hours prior to fungal incubation. Drug elution over 96 hours was evaluated by HPLC, and drug stability was tested while associated with the gel by OD600 up to 48 hours. Lack of cytotoxicity toward the HCE-T corneal epithelial cell line was assessed over 7 days. AmpB pεK gels show fungicidal activity in normal conditions (0.057 OD600, SD 0.003, P < 0.005) and in the presence of horse serum (0.048 OD600, SD 0.028 P < 0.005) at 18 hours. The drug release profile was above therapeutic levels (0.188 μg/mL) for up to 72 hours. Tear dilution had no significant effect at higher concentrations of AmpB (3 to 10 μg/mL). AmpB pεK gels were not cytotoxic to the HCE-T cell line. We demonstrated that AmpB pεK gels confer sustained therapeutic antifungal activity for at least 48 hours without corneal epithelial cell line cytotoxicity, suggesting their potential for in vivo use as an antifungal bandage contact lens. This could avoid the need for intensive topical medication in the treatment of fungal keratitis.

Beam Development_V6MP

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gilpatrick, John D.

2014-03-24

This presentation includes slides on Conditions; Sternglass states; H+ beam interacts with a W sense wire – Sternglass theory for SE current; Observed H+ beam at 03WS001 location; Jan 23 data; H- beam at 03WS001 location, Jan 23 data, Sternglass theory for SE current; H- beam at 03WS001 location; Jan 23 data; H+ beam at 04WS001 location, Jan 23 data, Sternglass theory for SE current; H+ beam at 04WS001 location; Jan 23 data; H- beam at 10WS001 location, Nov 17, 2013 data, Sternglass theory for SE current; H- beam at 10WS001 location; Nov 17, 2013 data; H- beam at 11WS001more » location, Nov 17, 2013 data, Sternglass theory for SE current; and lastly H- beam at 11WS001 location; Nov 17, 2013 data.« less

Fundamental Research of Molecular Beam Epitaxy for Device Applications.

DTIC Science & Technology

1980-11-01

Mitsui, J. Crys. Growth 45, 302 (1978). 8. A. Y. Cho and I. Hayashi , Met. Trans., 2, 777 (1971). 9. T. Shimanoe, T. Murotani, M. Nakatani, M. Otsubo...London, 1976). nual Conference on Gas and Related Compounds,St.Louis, 1978 (Institute "A. Y. Cho and 1. Hayashi , Metall. Trans. 2. 777 (1971). of...Physics, London, 1979). ’ 2C. E. C. Wood, L. Rathbun, and H. Ohno , J. Cryst. Growth (to be 6C. B. C. Wood, Appl. Phys. Lett. 33, 770 (1978). published). 382 AMp!. Pflys. Lett. 37(4j, 15 August 1980 382

Molluscan mega-hemocyanin: an ancient oxygen carrier tuned by a ~550 kDa polypeptide

PubMed Central

2010-01-01

Background The allosteric respiratory protein hemocyanin occurs in gastropods as tubular di-, tri- and multimers of a 35 × 18 nm, ring-like decamer with a collar complex at one opening. The decamer comprises five subunit dimers. The subunit, a 400 kDa polypeptide, is a concatenation of eight paralogous functional units. Their exact topology within the quaternary structure has recently been solved by 3D electron microscopy, providing a molecular model of an entire didecamer (two conjoined decamers). Here we study keyhole limpet hemocyanin (KLH2) tridecamers to unravel the exact association mode of the third decamer. Moreover, we introduce and describe a more complex type of hemocyanin tridecamer discovered in fresh/brackish-water cerithioid snails (Leptoxis, Melanoides, Terebralia). Results The "typical" KLH2 tridecamer is partially hollow, whereas the cerithioid tridecamer is almost completely filled with material; it was therefore termed "mega-hemocyanin". In both types, the staggering angle between adjoining decamers is 36°. The cerithioid tridecamer comprises two typical decamers based on the canonical 400 kDa subunit, flanking a central "mega-decamer" composed of ten unique ~550 kDa subunits. The additional ~150 kDa per subunit substantially enlarge the internal collar complex. Preliminary oxygen binding measurements indicate a moderate hemocyanin oxygen affinity in Leptoxis (p50 ~9 mmHg), and a very high affinity in Melanoides (~3 mmHg) and Terebralia (~2 mmHg). Species-specific and individual variation in the proportions of the two subunit types was also observed, leading to differences in the oligomeric states found in the hemolymph. Conclusions In cerithioid hemocyanin tridecamers ("mega-hemocyanin") the collar complex of the central decamer is substantially enlarged and modified. The preliminary O2 binding curves indicate that there are species-specific functional differences in the cerithioid mega-hemocyanins which might reflect different physiological tolerances of these gill-breathing animals. The observed differential expression of the two subunit types of mega-hemocyanin might allow individual respiratory acclimatization. We hypothesize that mega-hemocyanin is a key character supporting the adaptive radiation and invasive capacity of cerithioid snails. PMID:20465844

Current-limited electron beam injection

NASA Technical Reports Server (NTRS)

Stenzel, R. L.

1977-01-01

The injection of an electron beam into a weakly collisional, magnetized background plasma was investigated experimentally. The injected beam was energetic and cold, the background plasma was initially isothermal. Beam and plasma dimensions were so large that the system was considered unbounded. The temporal and spatial evolution of the beam-plasma system was dominated by collective effects. High-frequency electrostatic instabilities rapidly thermalized the beam and heated the background electrons. The injected beam current was balanced by a return current consisting of background electrons drifting toward the beam source. The drift between electrons and ions gave rise to an ion acoustic instability which developed into strong three-dimensional turbulence. It was shown that the injected beam current was limited by the return current which is approximately given by the electron saturation current. Non-Maxwellian electron distribution functions were observed.

If Maxwell had worked between Ampère and Faraday: An historical fable with a pedagogical moral

NASA Astrophysics Data System (ADS)

Jammer, Max; Stachel, John

1980-01-01

If one drops the Faraday induction term from Maxwell's equations, they become exactly Galilei invariant. This suggests that if Maxwell had worked between Ampère and Faraday, he could have developed this Galilei-invariant electromagnetic theory so that Faraday's discovery would have confronted physicists with the dilemma: give up the Galileian relativity principle for electromagnetism (ether hypothesis), or modify it (special relativity). This suggests a new pedagogical approach to electromagnetic theory, in which the displacement current and the Galileian relativity principle are introduced before the induction term is discussed.

Construction and performance of MEGAs low-mass, high-rate cylindrical MWPCs

NASA Astrophysics Data System (ADS)

Cooper, M. D.; Armijo, V.; Black, J. K.; Bolton, R. D.; Carius, S.; Espinoza, C.; Hart, G.; Hogan, G. E.; Gonzales, A.; Kroupa, M. A.; Mischke, R. E.; Sandoval, J.; Schilling, S.; Sena, J.; Suazo, G.; Whitehouse, D. A.; Wilkinson, C. A.; Stantz, K.; Szymanski, J. J.; Jui, C. C.; Gagliardi, C. A.; Tribble, R. E.; Tu, X.-L.; Fisk, R. J.; Koetke, D. D.; Manweiler, R. W.; Nord, P. M.; Stanislaus, S.; Piilonen, L. E.; Zhang, Y. D.

A design for extremely low mass, high-resolution multiwire proportional chambers (MWPC) was achieved by the MEGA collaboration in its experiment to search for the lepton family number violating decay μ→eγ. To extend the present branching ratio limit by over an order of magnitude, these MWPCs were operated in high particle fluxes. They showed minimal effects of aging, and evidenced spatial and energy resolutions for the orbiting positrons from muon decay which were consistent with our design parameters. The unique features of these chambers, their assembly into the MEGA positron spectrometer, and their performance during the experiment are described in this paper.

Controlling hollow relativistic electron beam orbits with an inductive current divider

DOE Office of Scientific and Technical Information (OSTI.GOV)

Swanekamp, S. B.; Richardson, A. S.; Angus, J. R.

2015-02-15

A passive method for controlling the trajectory of an intense, hollow electron beam is proposed using a vacuum structure that inductively splits the beam's return current. A central post carries a portion of the return current (I{sub 1}), while the outer conductor carries the remainder (I{sub 2}). An envelope equation appropriate for a hollow electron beam is derived and applied to the current divider. The force on the beam trajectory is shown to be proportional to (I{sub 2}-I{sub 1}), while the average force on the envelope (the beam width) is proportional to the beam current I{sub b} = (I{sub 2} + I{sub 1}). Themore » values of I{sub 1} and I{sub 2} depend on the inductances in the return-current path geometries. Proper choice of the return-current geometries determines these inductances and offers control over the beam trajectory. Solutions using realistic beam parameters show that, for appropriate choices of the return-current-path geometry, the inductive current divider can produce a beam that is both pinched and straightened so that it approaches a target at near-normal incidence with a beam diameter that is on the order of a few mm.« less

Electron-Beam-Induced Current | Materials Science | NREL

Science.gov Websites

Electron-Beam-Induced Current Electron-Beam-Induced Current Photo of a GaAsP-on-Si solar cell. EBIC measure electron-beam-induced current (EBIC). In presence of an electrostatic field (p-n junction

Method for measuring and controlling beam current in ion beam processing

DOEpatents

Kearney, Patrick A.; Burkhart, Scott C.

2003-04-29

A method for producing film thickness control of ion beam sputter deposition films. Great improvements in film thickness control is accomplished by keeping the total current supplied to both the beam and suppressor grids of a radio frequency (RF) in beam source constant, rather than just the current supplied to the beam grid. By controlling both currents, using this method, deposition rates are more stable, and this allows the deposition of layers with extremely well controlled thicknesses to about 0.1%. The method is carried out by calculating deposition rates based on the total of the suppressor and beam currents and maintaining the total current constant by adjusting RF power which gives more consistent values.

Past Strategies and Future Directions for Identifying AMP-Activated Protein Kinase (AMPK) Modulators

PubMed Central

Sinnett, Sarah E.; Brenman, Jay E.

2014-01-01

AMP-activated protein kinase (AMPK) is a promising therapeutic target for cancer, type II diabetes, and other illnesses characterized by abnormal energy utilization. During the last decade, numerous labs have published a range of methods for identifying novel AMPK modulators. The current understanding of AMPK structure and regulation, however, has propelled a paradigm shift in which many researchers now consider ADP to be an additional regulatory nucleotide of AMPK. How can the AMPK community apply this new understanding of AMPK signaling to translational research? Recent insights into AMPK structure, regulation, and holoenzyme-sensitive signaling may provide the hindsight needed to clearly evaluate the strengths and weaknesses of past AMPK drug discovery efforts. Improving future strategies for AMPK drug discovery will require pairing the current understanding of AMPK signaling with improved experimental designs. PMID:24583089

Prostaglandin D2 regulates human colonic ion transport via the DP1 receptor.

PubMed

Medani, M; Collins, D; Mohan, H M; Walsh, E; Winter, D C; Baird, A W

2015-02-01

Prostaglandin D2 is released by mast cells and is important in allergies. Its role in gastrointestinal function is not clearly defined. This study aimed to determine the effect of exogenous PGD2 on ion transport in ex vivo normal human colonic mucosa. Mucosal sheets were mounted in Ussing chambers and voltage clamped to zero electric potential. Ion transport was quantified as changes in short-circuit current. In separate experiments epithelial monolayers or colonic crypts, isolated by calcium chelation, were treated with PGD2 and cAMP levels determined by ELISA or calcium levels were determined by fluorimetry. PGD2 caused a sustained, concentration-dependent rise in short-circuit current by increasing chloride secretion (EC50=376nM). This effect of PGD2 is mediated by the DP1 receptor, as the selective DP1 receptor antagonist BW A686C inhibited PGD2-induced but not PGE2-induced rise in short-circuit current. PGD2 also increased intracellular cAMP in isolated colonic crypts with no measurable influence on cytosolic calcium. PGD2 induces chloride secretion in isolated human colonic mucosa in a concentration-dependent manner with concomitant elevation of cytoplasmic cAMP in epithelial cells. The involvement of DP2 receptor subtypes has not previously been considered in regulation of ion transport in human intestine. Since inflammatory stimuli may induce production of eicosanoids, selective regulation of these pathways may be pivotal in determining therapeutic strategies and in understanding disease. Copyright © 2014. Published by Elsevier Inc.

Amphetamine fails to alter cued recollection of emotional images: study of encoding, retrieval, and state-dependency.

PubMed

Weafer, Jessica; Gallo, David A; de Wit, Harriet

2014-01-01

Stimulant drugs facilitate both encoding and retrieval of salient information in laboratory animals, but less is known about their effects on memory for emotionally salient visual images in humans. The current study investigated dextroamphetamine (AMP) effects on memory for emotional pictures in healthy humans, by administering the drug only at encoding, only at retrieval, or at both encoding and retrieval. During the encoding session, all participants viewed standardized positive, neutral, and negative pictures from the International Affective Picture System (IAPS). 48 hours later they attended a retrieval session testing their cued recollection of these stimuli. Participants were randomly assigned to one of four conditions (N=20 each): condition AP (20 mg AMP at encoding and placebo (PL) at retrieval); condition PA (PL at encoding and AMP at retrieval); condition AA (AMP at encoding and retrieval); or condition PP (PL at encoding and retrieval). Amphetamine produced its expected effects on physiological and subjective measures, and negative pictures were recollected more frequently than neutral pictures. However, contrary to hypotheses, AMP did not affect recollection for positive, negative, or neutral stimuli, whether it was administered at encoding, retrieval, or at both encoding and retrieval. Moreover, recollection accuracy was not state-dependent. Considered in light of other recent drug studies in humans, this study highlights the sensitivity of drug effects to memory testing conditions and suggests future strategies for translating preclinical findings to human behavioral laboratories.

Amphetamine Fails to Alter Cued Recollection of Emotional Images: Study of Encoding, Retrieval, and State-Dependency

PubMed Central

Weafer, Jessica; Gallo, David A.; de Wit, Harriet

2014-01-01

Stimulant drugs facilitate both encoding and retrieval of salient information in laboratory animals, but less is known about their effects on memory for emotionally salient visual images in humans. The current study investigated dextroamphetamine (AMP) effects on memory for emotional pictures in healthy humans, by administering the drug only at encoding, only at retrieval, or at both encoding and retrieval. During the encoding session, all participants viewed standardized positive, neutral, and negative pictures from the International Affective Picture System (IAPS). 48 hours later they attended a retrieval session testing their cued recollection of these stimuli. Participants were randomly assigned to one of four conditions (N = 20 each): condition AP (20 mg AMP at encoding and placebo (PL) at retrieval); condition PA (PL at encoding and AMP at retrieval); condition AA (AMP at encoding and retrieval); or condition PP (PL at encoding and retrieval). Amphetamine produced its expected effects on physiological and subjective measures, and negative pictures were recollected more frequently than neutral pictures. However, contrary to hypotheses, AMP did not affect recollection for positive, negative, or neutral stimuli, whether it was administered at encoding, retrieval, or at both encoding and retrieval. Moreover, recollection accuracy was not state-dependent. Considered in light of other recent drug studies in humans, this study highlights the sensitivity of drug effects to memory testing conditions and suggests future strategies for translating preclinical findings to human behavioral laboratories. PMID:24587355

Purification, characterization, and sequencing of antimicrobial peptides, Cy-AMP1, Cy-AMP2, and Cy-AMP3, from the Cycad (Cycas revoluta) seeds.

PubMed

Yokoyama, Seiya; Kato, Kouji; Koba, Atsuko; Minami, Yuji; Watanabe, Keiichi; Yagi, Fumio

2008-12-01

Novel antimicrobial peptides (AMP), designated Cy-AMP1, Cy-AMP2, and Cy-AMP3, were purified from seeds of the cycad (Cycas revoluta) by a CM cellulofine column, ion-exchange HPLC on SP COSMOGEL, and reverse-phase HPLC. They had molecular masses of 4583.2 Da, 4568.9 Da and 9275.8 Da, respectively, by MALDI-TOF MS analysis. Half of the amino acid residues of Cy-AMP1 and Cy-AMP2 were cysteine, glycine and proline, and their sequences were similar. The sequence of Cy-AMP3 showed high homology to various lipid transfer proteins. For Cy-AMP1 and Cy-AMP2, the concentrations of peptides required for 50% inhibition (IC(50)) of the growth of plant pathogenic fungi, Gram-positive and Gram-negative bacteria were 7.0-8.9 microg/ml. The Cy-AMP3 had weak antimicrobial activity. The structural and antimicrobial characteristics of Cy-AMP1 and Cy-AMP2 indicated that they are a novel type of antimicrobial peptide belonging to a plant defensin family.

Evaluation of high-energy lithium thionyl chloride primary cells

NASA Technical Reports Server (NTRS)

Frank, H. A.

1980-01-01

An advanced commercial primary lithium cell (LiSoCl2) was evaluated in order to establish baseline data for improved lithium batteries for aerospace applications. The cell tested had nominal capacity of 6 Ah. Maximum energy density at low rates (less than C/30, where C is the cell capacity in amp-hrs and 30 corresponds to a 30 hr discharge time) was found to be near 300 Wh/kg. An equation which predicts the operating voltage of these cells as a function of current and state of charge is presented. Heat generation rates of these cells were determined as a function of current in a calorimeter. It was found that heat rates could be theoretically predicted with some degree of accuracy at currents less than 1 amp or the C/6 rate. No explosions were observed in the cells during the condition of overdischarge or reversal nor during high rate discharge. It was found, however, that the cells can vent when overdischarge currents are greater than C/30 and when discharge rates are greater than 1.5C.

Conventional chemotherapy (CHOEP-14) with rituximab or high-dose chemotherapy (MegaCHOEP) with rituximab for young, high-risk patients with aggressive B-cell lymphoma: an open-label, randomised, phase 3 trial (DSHNHL 2002-1).

PubMed

Schmitz, Norbert; Nickelsen, Maike; Ziepert, Marita; Haenel, Mathias; Borchmann, Peter; Schmidt, Christian; Viardot, Andreas; Bentz, Martin; Peter, Norma; Ehninger, Gerhard; Doelken, Gottfried; Ruebe, Christian; Truemper, Lorenz; Rosenwald, Andreas; Pfreundschuh, Michael; Loeffler, Markus; Glass, Bertram

2012-12-01

High-dose therapy (HDT) followed by transplantation of autologous haemopoietic stem cells is frequently done as part of first-line therapy in young patients with high-risk aggressive B-cell lymphoma. We investigated whether HDT with cytotoxic agents identical to those used for conventional therapy followed by autologous stem-cell transplantation (ASCT) improved survival outcome compared with conventional chemotherapy when rituximab was added to both modalities. We did an open-label, randomised trial comparing conventional chemotherapy (cyclophosphamide, doxorubicin, vincristine, etoposide, prednisone) and rituximab (R-CHOEP-14) with dose-escalated sequential HDT and rituximab (R-MegaCHOEP) followed by repetitive ASCT in high-risk (age-adjusted International Prognostic Index [IPI] 2 or 3) patients aged 18-60 years with aggressive B-cell lymphoma. Eligible patients received radiotherapy for bulky, extranodal disease, or both. Randomisation (1:1) used the Pocock minimisation algorithm; patients were stratified by age-adjusted IPI factors, bulky disease, and centre. The primary endpoint was event-free survival. All analyses were done on the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT00129090. 136 patients were randomly assigned to R-CHOEP-14 and 139 to R-MegaCHOEP. 130 patients in the R-CHOEP-14 group and 132 in the R-MegaCHOEP group were included in the intention-to-treat population. After a median of 42 months (IQR 29-59), 3-year event-free survival was 69·5% (95% CI 61·3-77·7) in the R-CHOEP-14 group and 61·4% (52·8-70·0) in the R-MegaCHOEP group (p=0·14; hazard ratio 1·3, 95% CI 0·9-2·0). All 128 evaluable patients treated with R-MegaCHOEP had grade 4 leucopenia, as did 48 (58·5%) of 82 patients with documented blood counts in the R-CHOEP-14 group. All 128 evaluable patients in the R-MegaCHOEP group had grade 3-4 thrombocytopenia, as did 26 (33·8%) of 77 patients in the R-CHOEP-14 group with documented blood counts. The most important non-haematological grade 3 or 4 adverse event was infection, which occurred in 96 (75·0%) of 128 patients treated with R-MegaCHOEP and in 40 (31·3%) of 128 patients treated with R-CHOEP-14. In young patients with high-risk aggressive B-cell lymphoma, R-MegaCHOEP was not superior to conventional R-CHOEP therapy and was associated with significantly more toxic effects. R-CHOEP-14 with or without radiotherapy remains a treatment option for these patients, with encouraging efficacy. Deutsche Krebshilfe. Copyright © 2012 Elsevier Ltd. All rights reserved.

First demonstration of simultaneous measurement of beam current, beam position, and beam tilt on induction linac using combined B-dot monitor

NASA Astrophysics Data System (ADS)

He, Xiaozhong; Pang, Jian; Chen, Nan; Li, Qin; Dai, Wenhua; Ma, Chaofan; Zhao, Liangchao; Gao, Feng; Dai, Zhiyong

2017-06-01

The authors previously reported that the axial B-dots can be used to directly measure the beam tilt and demonstrated that the axial B-dots are applicable to a coaxial calibration stand. In this study, a combined B-dot monitor composed of four axial B-dot loops and four azimuthal ones is tested for the simultaneous measurement of the time-varying beam current, beam offset, and beam tilt at the output of the injector of the DRAGON-I induction linac. In the experiments, the beam offset and beam tilt at the position of the monitor are proportionally adjusted using a pair of steering coils. Eight waveforms acquired from the B-dot monitor are analyzed to reconstruct the time-varying beam current, beam offset, and beam tilt. The original signals of both the azimuthal B-dot and the axial B-dot ports change significantly with respect to the current applied to the steering coils. The measured beam tilt is linearly dependent on the current applied to the steering coils and agrees well with the measured beam offset.

2',3'-cAMP, 3'-AMP, 2'-AMP and adenosine inhibit TNF-α and CXCL10 production from activated primary murine microglia via A2A receptors.

PubMed

Newell, Elizabeth A; Exo, Jennifer L; Verrier, Jonathan D; Jackson, Travis C; Gillespie, Delbert G; Janesko-Feldman, Keri; Kochanek, Patrick M; Jackson, Edwin K

2015-01-12

Some cells, tissues and organs release 2',3'-cAMP (a positional isomer of 3',5'-cAMP) and convert extracellular 2',3'-cAMP to 2'-AMP plus 3'-AMP and convert these AMPs to adenosine (called the extracellular 2',3'-cAMP-adenosine pathway). Recent studies show that microglia have an extracellular 2',3'-cAMP-adenosine pathway. The goal of the present study was to investigate whether the extracellular 2',3'-cAMP-adenosine pathway could have functional consequences on the production of cytokines/chemokines by activated microglia. Experiments were conducted in cultures of primary murine microglia. In the first experiment, the effect of 2',3'-cAMP, 3'-AMP, 2'-AMP and adenosine on LPS-induced TNF-α and CXCL10 production was determined. In the next experiment, the first protocol was replicated but with the addition of 1,3-dipropyl-8-p-sulfophenylxanthine (DPSPX) (0.1 μM; antagonist of adenosine receptors). The last experiment compared the ability of 2-chloro-N(6)-cyclopentyladenosine (CCPA) (10 μM; selective A1 agonist), 5'-N-ethylcarboxamide adenosine (NECA) (10 μM; agonist for all adenosine receptor subtypes) and CGS21680 (10 μM; selective A2A agonist) to inhibit LPS-induced TNF-α and CXCL10 production. (1) 2',3'-cAMP, 3'-AMP, 2'-AMP and adenosine similarly inhibited LPS-induced TNF-α and CXCL10 production; (2) DPSPX nearly eliminated the inhibitory effects of 2',3'-cAMP, 3'-AMP, 2'-AMP and adenosine on LPS-induced TNF-α and CXCL10 production; (3) CCPA did not affect LPS-induced TNF-α and CXCL10; (4) NECA and CGS21680 similarly inhibited LPS-induced TNF-α and CXCL10 production. 2',3'-cAMP and its metabolites (3'-AMP, 2'-AMP and adenosine) inhibit LPS-induced TNF-α and CXCL10 production via A2A-receptor activation. Adenosine and its precursors, via A2A receptors, likely suppress TNF-α and CXCL10 production by activated microglia in brain diseases. Copyright © 2014 Elsevier B.V. All rights reserved.

Bacterial Signal Transduction by Cyclic Di-GMP and Other Nucleotide Second Messengers

PubMed Central

Gründling, Angelika; Jenal, Urs; Ryan, Robert; Yildiz, Fitnat

2015-01-01

The first International Symposium on c-Di-GMP Signaling in Bacteria (22 to 25 March 2015, Harnack-Haus, Berlin, Germany) brought together 131 molecular microbiologists from 17 countries to discuss recent progress in our knowledge of bacterial nucleotide second messenger signaling. While the focus was on signal input, synthesis, degradation, and the striking diversity of the modes of action of the current second messenger paradigm, i.e., cyclic di-GMP (c-di-GMP), “classics” like cAMP and (p)ppGpp were also presented, in novel facets, and more recent “newcomers,” such as c-di-AMP and c-AMP-GMP, made an impressive appearance. A number of clear trends emerged during the 30 talks, on the 71 posters, and in the lively discussions, including (i) c-di-GMP control of the activities of various ATPases and phosphorylation cascades, (ii) extensive cross talk between c-di-GMP and other nucleotide second messenger signaling pathways, and (iii) a stunning number of novel effectors for nucleotide second messengers that surprisingly include some long-known master regulators of developmental pathways. Overall, the conference made it amply clear that second messenger signaling is currently one of the most dynamic fields within molecular microbiology, with major impacts in research fields ranging from human health to microbial ecology. PMID:26055111

Intracellular tortuosity underlies slow cAMP diffusion in adult ventricular myocytes.

PubMed

Richards, Mark; Lomas, Oliver; Jalink, Kees; Ford, Kerrie L; Vaughan-Jones, Richard D; Lefkimmiatis, Konstantinos; Swietach, Pawel

2016-06-01

3',5'-Cyclic adenosine monophosphate (cAMP) signals in the heart are often confined to concentration microdomains shaped by cAMP diffusion and enzymatic degradation. While the importance of phosphodiesterases (degradative enzymes) in sculpting cAMP microdomains is well established in cardiomyocytes, less is known about cAMP diffusivity (DcAMP) and factors affecting it. Many earlier studies have reported fast diffusivity, which argues against sharply defined microdomains. [cAMP] dynamics in the cytoplasm of adult rat ventricular myocytes were imaged using a fourth generation genetically encoded FRET-based sensor. The [cAMP]-response to the addition and removal of isoproterenol (β-adrenoceptor agonist) quantified the rates of cAMP synthesis and degradation. To obtain a read out of DcAMP, a stable [cAMP] gradient was generated using a microfluidic device which delivered agonist to one half of the myocyte only. After accounting for phosphodiesterase activity, DcAMP was calculated to be 32 µm(2)/s; an order of magnitude lower than in water. Diffusivity was independent of the amount of cAMP produced. Saturating cAMP-binding sites with the analogue 6-Bnz-cAMP did not accelerate DcAMP, arguing against a role of buffering in restricting cAMP mobility. cAMP diffused at a comparable rate to chemically unrelated but similar sized molecules, arguing for a common physical cause of restricted diffusivity. Lower mitochondrial density and order in neonatal cardiac myocytes allowed for faster diffusion, demonstrating the importance of mitochondria as physical barriers to cAMP mobility. In adult cardiac myocytes, tortuosity due to physical barriers, notably mitochondria, restricts cAMP diffusion to levels that are more compatible with microdomain signalling. © The Author 2016. Published by Oxford University Press on behalf of the European Society of Cardiology.

Metformin and phenformin activate AMP-activated protein kinase in the heart by increasing cytosolic AMP concentration.

PubMed

Zhang, Li; He, Huamei; Balschi, James A

2007-07-01

AMP-activated protein kinase (AMPK) acts as a cellular energy sensor: it responds to an increase in AMP concentration ([AMP]) or the AMP-to-ATP ratio (AMP/ATP). Metformin and phenformin, which are biguanides, have been reported to increase AMPK activity without increasing AMP/ATP. This study tests the hypothesis that these biguanides increase AMPK activity in the heart by increasing cytosolic [AMP]. Groups of isolated rat hearts (n = 5-7 each) were perfused with Krebs-Henseleit buffer with or without 0.2 mM phenformin or 10 mM metformin, and (31)P-NMR-measured phosphocreatine, ATP, and intracellular pH were used to calculate cytosolic [AMP]. At various times, hearts were freeze-clamped and assayed for AMPK activity, phosphorylation of Thr(172) on AMPK-alpha, and phosphorylation of Ser(79) on acetyl-CoA carboxylase, an AMPK target. In hearts treated with phenformin for 18 min and then perfused for 20 min with Krebs-Henseleit buffer, [AMP] began to increase at 26 min and AMPK activity was elevated at 36 min. In hearts treated with metformin, [AMP] was increased at 50 min and AMPK activity, phosphorylated AMPK, and phosphorylated acetyl-CoA carboxylase were elevated at 61 min. In metformin-treated hearts, HPLC-measured total AMP content and total AMP/ATP did not increase. In summary, phenformin and metformin increase AMPK activity and phosphorylation in the isolated heart. The increase in AMPK activity was always preceded by and correlated with increased cytosolic [AMP]. Total AMP content and total AMP/ATP did not change. Cytosolic [AMP] reported metabolically active AMP, which triggered increased AMPK activity, but measures of total AMP did not.

Understanding the current state of infection preventionists through competency, role, and activity self-assessment.

PubMed

Kalp, Ericka L; Marx, James F; Davis, James

2017-06-01

The Association for Professionals in Infection Control and Epidemiology (APIC) MegaSurvey, administered in 2015, was completed by approximately 4,079 APIC members. The survey sought to gain a better understanding the current state of 4 components of infection prevention practice: demographic characteristics, compensation, organizational structure, and practice and competency. The data for this analysis come from the APIC MegaSurvey Practice and Competency domain. Descriptive statistics and χ 2 analyses were conducted to examine differences in infection preventionist (IP) competency, roles, and activity self-assessments. The majority of IPs self-assessed their competency as Proficient compared with Novice or Expert for each of the 8 IP core competency activities. Forty percent of IPs self-rated their competency as Expert in the Preventing/Controlling the Transmission of Infectious Agents/HAIs component. IPs reported Novice competency in Employee/Occupational Health (29%); Cleaning, Sterilization, Disinfection, and Asepsis (23%); and Education and Research categories (22%). Differences in self-rated competency among IPs by discipline type (public health, nurse, and laboratory) were identified. Differences in self-rated competency were identified for each of the 8 IP core competency activities. IPs report using various resource types to gain competency. Future research is needed to identify opportunities to increase competency levels in the weakest-rated competency activities. Copyright © 2017 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.

The glutamate carboxypeptidase AMP1 mediates abscisic acid and abiotic stress responses in Arabidopsis.

PubMed

Shi, Yiting; Wang, Zheng; Meng, Pei; Tian, Siqi; Zhang, Xiaoyan; Yang, Shuhua

2013-07-01

ALTERED MERISTEM PROGRAM1 (AMP1) encodes a glutamate carboxypeptidase that plays an important role in shoot apical meristem development and phytohormone homeostasis. We isolated a new mutant allele of AMP1, amp1-20, from a screen for abscisic acid (ABA) hypersensitive mutants and characterized the function of AMP1 in plant stress responses. amp1 mutants displayed ABA hypersensitivity, while overexpression of AMP1 caused ABA insensitivity. Moreover, endogenous ABA concentration was increased in amp1-20- and decreased in AMP1-overexpressing plants under stress conditions. Application of ABA reduced the AMP1 protein level in plants. Interestingly, amp1 mutants accumulated excess superoxide and displayed hypersensitivity to oxidative stress. The hypersensitivity of amp1 to ABA and oxidative stress was partially rescued by reactive oxygen species (ROS) scavenging agent. Furthermore, amp1 was tolerant to freezing and drought stress. The ABA hypersensitivity and freezing tolerance of amp1 was dependent on ABA signaling. Moreover, amp1 had elevated soluble sugar content and showed hypersensitivity to high concentrations of sugar. By contrast, the contents of amino acids were changed in amp1 mutant compared to the wild-type. This study suggests that AMP1 modulates ABA, oxidative and abotic stress responses, and is involved in carbon and amino acid metabolism in Arabidopsis. © 2013 The Authors. New Phytologist © 2013 New Phytologist Trust.

Innovative real-time and non-destructive method of beam profile measurement under large beam current irradiation for BNCT

NASA Astrophysics Data System (ADS)

Takada, M.; Kamada, S.; Suda, M.; Fujii, R.; Nakamura, M.; Hoshi, M.; Sato, H.; Endo, S.; Hamano, T.; Arai, S.; Higashimata, A.

2012-10-01

We developed a real-time and non-destructive method of beam profile measurement on a target under large beam current irradiation, and without any complex radiation detectors or electrical circuits. We measured the beam profiles on a target by observing the target temperature using an infrared-radiation thermometer camera. The target temperatures were increased and decreased quickly by starting and stopping the beam irradiation within 1 s in response speed. Our method could trace beam movements rapidly. The beam size and position were calibrated by measuring O-ring heat on the target. Our method has the potential to measure beam profiles at beam current over 1 mA for proton and deuteron with the energy around 3 MeV and allows accelerator operators to adjust the beam location during beam irradiation experiments without decreasing the beam current.

Signalling mechanism for somatostatin receptor 5-mediated suppression of AMPA responses in rat retinal ganglion cells.

PubMed

Deng, Qin-Qin; Sheng, Wen-Long; Zhang, Gong; Weng, Shi-Jun; Yang, Xiong-Li; Zhong, Yong-Mei

2016-08-01

Somatostatin (SRIF) is involved in a variety of physiological functions via the activation of five subtypes of specific receptors (sst1-5). Here, we investigated the effects of SRIF on AMPA receptor (AMPAR)-mediated currents (AMPA currents) in isolated rat retinal ganglion cells (GCs) using patch-clamp techniques. Immunofluorescence double labelling demonstrated the expression of sst5 in rat GCs. Consistent to this, whole cell AMPA currents of GCs were dose-dependently suppressed by SRIF, and the effect was reversed by the sst5 antagonist BIM-23056. Intracellular dialysis of GDP-β-S or pre-incubation with the Gi/o inhibitor pertussis toxin (PTX) abolished the SRIF effect. The SRIF effect was mimicked by the administration of either 8-Br-cAMP or forskolin, but was eliminated by the protein kinase A (PKA) antagonists H-89/KT5720/Rp-cAMP. Moreover, SRIF increased intracellular Ca(2+) levels and did not suppress the AMPA currents when GCs were infused with an intracellular Ca(2+)-free solution or in the presence of ryanodine receptor modulators caffeine/ryanodine. Furthermore, the SRIF effect was eliminated when the activity of calmodulin (CaM), calcineurin and protein phosphatase 1 (PP1) was blocked with W-7, FK-506 and okadaic acid, respectively. SRIF persisted to suppress the AMPA currents when cGMP-protein kinase G (PKG) and phosphatidylinositol (PI)-/phosphatidylcholine (PC)-phospholipase C (PLC) signalling pathways were blocked. In rat flat-mount retinas, SRIF suppressed AMPAR-mediated light-evoked excitatory postsynaptic currents (L-EPSCs) in GCs. We conclude that a distinct Gi/o/cAMP-PKA/ryanodine/Ca(2+)/CaM/calcineurin/PP1 signalling pathway comes into play due to the activation of sst5 to mediate the SRIF effect on GCs. Copyright © 2016 Elsevier Ltd. All rights reserved.

Schwann Cells Metabolize Extracellular 2′,3′-cAMP to 2′-AMP

PubMed Central

Verrier, Jonathan D.; Kochanek, Patrick M.

2015-01-01

The 3′,5′-cAMP–adenosine pathway (3′,5′-cAMP→5′-AMP→adenosine) and the 2′,3′-cAMP–adenosine pathway (2′,3′-cAMP→2′-AMP/3′-AMP→adenosine) are active in the brain. Oligodendrocytes participate in the brain 2′,3′-cAMP–adenosine pathway via their robust expression of 2′,3′-cyclic nucleotide 3′-phosphodiesterase (CNPase; converts 2′,3′-cAMP to 2′-AMP). Because Schwann cells also express CNPase, it is conceivable that the 2′,3′-cAMP–adenosine pathway exists in the peripheral nervous system. To test this and to compare the 2′,3′-cAMP–adenosine pathway to the 3′,5′-cAMP–adenosine pathway in Schwann cells, we examined the metabolism of 2′,3′-cAMP, 2′-AMP, 3′-AMP, 3′,5′-cAMP, and 5′-AMP in primary rat Schwann cells in culture. Addition of 2′,3′-cAMP (3, 10, and 30 µM) to Schwann cells increased levels of 2′-AMP in the medium from 0.006 ± 0.002 to 21 ± 2, 70 ± 3, and 187 ± 10 nM/µg protein, respectively; in contrast, Schwann cells had little ability to convert 2′,3′-cAMP to 3′-AMP or 3′,5′-cAMP to either 3′-AMP or 5′-AMP. Although Schwann cells slightly converted 2′,3′-cAMP and 2′-AMP to adenosine, they did so at very modest rates (e.g., 5- and 3-fold, respectively, more slowly compared with our previously reported studies in oligodendrocytes). Using transected myelinated rat sciatic nerves in culture medium, we observed a time-related increase in endogenous intracellular 2′,3′-cAMP and extracellular 2′-AMP. These findings indicate that Schwann cells do not have a robust 3′,5′-cAMP–adenosine pathway but do have a 2′,3′-cAMP–adenosine pathway; however, because the pathway mostly involves 2′-AMP formation rather than 3′-AMP, and because the conversion of 2′-AMP to adenosine is slow, metabolism of 2′,3′-cAMP mostly results in the accumulation of 2′-AMP. Accumulation of 2′-AMP in peripheral nerves postinjury could have pathophysiological consequences. PMID:25998049

Particle-in-cell simulations of electron beam control using an inductive current divider

DOE PAGES

Swanekamp, S. B.; Angus, J. R.; Cooperstein, G.; ...

2015-11-18

Kinetic, time-dependent, electromagnetic, particle-in-cell simulations of the inductive current divider are presented. The inductive current divider is a passive method for controlling the trajectory of an intense, hollow electron beam using a vacuum structure that inductively splits the beam’s return current. The current divider concept was proposed and studied theoretically in a previous publication [Phys. Plasmas 22, 023107 (2015)] A central post carries a portion of the return current (I 1) while the outer conductor carries the remainder (I 2) with the injected beam current given by I b=I 1+I 2. The simulations are in agreement with the theory whichmore » predicts that the total force on the beam trajectory is proportional to (I 2-I 1) and the force on the beam envelope is proportional to I b. For a fixed central post, the beam trajectory is controlled by varying the outer conductor radius which changes the inductance in the return-current path. The simulations show that the beam emittance is approximately constant as the beam propagates through the current divider to the target. As a result, independent control over both the current density and the beam angle at the target is possible by choosing the appropriate return-current geometry.« less

Indirectly sensing accelerator beam currents for limiting maximum beam current magnitude

DOEpatents

Bogaty, J.M.; Clifft, B.E.; Bollinger, L.M.

1995-08-08

A beam current limiter is disclosed for sensing and limiting the beam current in a particle accelerator, such as a cyclotron or linear accelerator, used in scientific research and medical treatment. A pair of independently operable capacitive electrodes sense the passage of charged particle bunches to develop an RF signal indicative of the beam current magnitude produced at the output of a bunched beam accelerator. The RF signal produced by each sensing electrode is converted to a variable DC voltage indicative of the beam current magnitude. The variable DC voltages thus developed are compared to each other to verify proper system function and are further compared to known references to detect beam currents in excess of pre-established limits. In the event of a system malfunction, or if the detected beam current exceeds pre-established limits, the beam current limiter automatically inhibits further accelerator operation. A high Q tank circuit associated with each sensing electrode provides a narrow system bandwidth to reduce noise and enhance dynamic range. System linearity is provided by injecting, into each sensing electrode, an RF signal that is offset from the bunching frequency by a pre-determined beat frequency to ensure that subsequent rectifying diodes operate in a linear response region. The system thus provides a large dynamic range in combination with good linearity. 6 figs.

Indirectly sensing accelerator beam currents for limiting maximum beam current magnitude

DOEpatents

Bogaty, John M.; Clifft, Benny E.; Bollinger, Lowell M.

1995-01-01

A beam current limiter for sensing and limiting the beam current in a particle accelerator, such as a cyclotron or linear accelerator, used in scientific research and medical treatment. A pair of independently operable capacitive electrodes sense the passage of charged particle bunches to develop an RF signal indicative of the beam current magnitude produced at the output of a bunched beam accelerator. The RF signal produced by each sensing electrode is converted to a variable DC voltage indicative of the beam current magnitude. The variable DC voltages thus developed are compared to each other to verify proper system function and are further compared to known references to detect beam currents in excess of pre-established limits. In the event of a system malfunction, or if the detected beam current exceeds pre-established limits, the beam current limiter automatically inhibits further accelerator operation. A high Q tank circuit associated with each sensing electrode provides a narrow system bandwidth to reduce noise and enhance dynamic range. System linearity is provided by injecting, into each sensing electrode, an RF signal that is offset from the bunching frequency by a pre-determined beat frequency to ensure that subsequent rectifying diodes operate in a linear response region. The system thus provides a large dynamic range in combination with good linearity.

Effects of cigarette smoke on methacholine- and AMP-induced air trapping in asthmatics.

PubMed

Prieto, Luis; Palop, Julio; Llusar, Ruth; Herrera, Susana; Perez-Frances, Carmen; Lanuza, Amparo; Aguilar, Daniela

2015-02-01

Abstract Objective: No information is available on the effect of cigarette smoke on bronchoconstrictor-induced air trapping in asthma. The aim of this study was to evaluate the additional influence of smoking on methacholine- and adenosine 5'-monophosphate (AMP)-induced air trapping in subjects with asthma. Airway responsiveness to methacholine and AMP, bronchial (J'awNO) and alveolar (CANO) nitric oxide (NO) and exhaled breath condensate pH were measured in 68 adults (23 current smokers with asthma, 23 non-smokers with asthma and 22 current or former smokers with chronic obstructive pulmonary disease; COPD). The degree of air trapping induced by each bronchoconstrictor agent was expressed by the percent fall in forced vital capacity (FVC) at a 20% fall in forced expiratory volume in 1 s relative to FVC after saline inhalation (ΔFVC%). The ΔFVC% for AMP was higher in both smokers with asthma and patients with COPD than in non-smokers with asthma (p<0.001). By contrast, ΔFVC% for methacholine was similar in the three groups of subjects (p=0.69). In smokers with asthma, but not in the other two groups, there was a correlation between the residual volume/total lung capacity at baseline and the ΔFVC% induced by each bronchoconstrictor agent. Mean values for J'awNO were higher in non-smokers with asthma than in the other two groups (p<0.05). The results of this study suggest that factors underlying bronchoconstriction induced by indirect agonists are different in smokers and non-smokers with asthma. These observations might be clinically relevant, because triggers that frequently induce bronchial obstruction in the real world act by an indirect mechanism.

Development of in-situ control diagnostics for application of epitaxial superconductor and buffer layers

DOE Office of Scientific and Technical Information (OSTI.GOV)

B.C. Winkleman; T.V. Giel; Jason Cunningham

1999-07-30

The recent achievements of critical currents in excess of 1 x 10{sup 6} amp/cm{sup 2} at 77 K in YBCO deposited over suitably textured buffer/substrate composites have stimulated interest in the potential fabrication of these coated conductors as wire. Numerous approaches and manufacturing schemes for producing coated conductor wire are currently being developed. Recently, under the US DOE's sponsorship, the University of Tennessee Space Institute performed an extensive evaluation of leading coated conductor processing options. In general, it is their feeling that the science and chemistry that are being developed in the coated conductor wire program now need proper engineeringmore » evaluation to define the most viable options for a commercial fabrication process. All fabrication processes will need process control measurements. This report provides a specific review of the needs and available technologies for process control for many of the coated conductor processing options. This report also addresses generic process monitoring areas in which additional research and development is needed. The concentration is on the two different approaches for obtaining the textured substrates that have been identified as viable candidates. These are the Los Alamos National Laboratory's ion-beam assisted deposition, called IBAD, to obtain a highly textured yttria-stabilized zirconia (YSZ) buffer on nickel alloy strips, and Oak Ridge National Laboratory's rolling assisted, bi-axially textured substrate option called RABiTS{trademark}.« less

High-Energy Two-Stage Pulsed Plasma Thruster

NASA Technical Reports Server (NTRS)

Markusic, Tom

2003-01-01

A high-energy (28 kJ per pulse) two-stage pulsed plasma thruster (MSFC PPT-1) has been constructed and tested. The motivation of this project is to develop a high power (approximately 500 kW), high specific impulse (approximately 10000 s), highly efficient (greater than 50%) thruster for use as primary propulsion in a high power nuclear electric propulsion system. PPT-1 was designed to overcome four negative characteristics which have detracted from the utility of pulsed plasma thrusters: poor electrical efficiency, poor propellant utilization efficiency, electrode erosion, and reliability issues associated with the use of high speed gas valves and high current switches. Traditional PPTs have been plagued with poor efficiency because they have not been operated in a plasma regime that fully exploits the potential benefits of pulsed plasma acceleration by electromagnetic forces. PPTs have generally been used to accelerate low-density plasmas with long current pulses. Operation of thrusters in this plasma regime allows for the development of certain undesirable particle-kinetic effects, such as Hall effect-induced current sheet canting. PPT-1 was designed to propel a highly collisional, dense plasma that has more fluid-like properties and, hence, is more effectively pushed by a magnetic field. The high-density plasma loading into the second stage of the accelerator is achieved through the use of a dense plasma injector (first stage). The injector produces a thermal plasma, derived from a molten lithium propellant feed system, which is subsequently accelerated by the second stage using mega-amp level currents, which eject the plasma at a speed on the order of 100 kilometers per second. Traditional PPTs also suffer from dynamic efficiency losses associated with snowplow loading of distributed neutral propellant. The twostage scheme used in PPT-I allows the propellant to be loaded in a manner which more closely approximates the optimal slug loading. Lithium propellant was chosen to test whether or not the reduced electrode erosion found in the Lithium Lorentz Force Accelerator (LiLFA) could also be realized in a pulsed plasma thruster. The use of the molten lithium dense plasma injector also eliminates the need for a gas valve and electrical switch; the injector design fulfills both roles, and uses no moving parts to provide, in principle, a highly reliable propellant feed and electrical switching system. Experimental results reported in this paper include: second-stage current traces, high-speed photographic and holographic imaging of the thruster exit plume, and internal mapping of the discharge chamber magnetic field from B-dot probe data. The magnetic field data is used to create a two-dimensional description of the evolution of the current sheet inside the thruster.

Particle-in-cell simulations of electron beam control using an inductive current divider

DOE Office of Scientific and Technical Information (OSTI.GOV)

Swanekamp, S. B.; Angus, J. R.; Cooperstein, G.

2015-11-15

Kinetic, time-dependent, electromagnetic, particle-in-cell simulations of the inductive current divider are presented. The inductive current divider is a passive method for controlling the trajectory of an intense, hollow electron beam using a vacuum structure that inductively splits the beam's return current. The current divider concept was proposed and studied theoretically in a previous publication [Swanekamp et al., Phys. Plasmas 22, 023107 (2015)]. A central post carries a portion of the return current (I{sub 1}), while the outer conductor carries the remainder (I{sub 2}) with the injected beam current given by I{sub b} = I{sub 1} + I{sub 2}. The simulations are in agreement withmore » the theory which predicts that the total force on the beam trajectory is proportional to (I{sub 2}−I{sub 1}) and the force on the beam envelope is proportional to I{sub b}. Independent control over both the current density and the beam angle at the target is possible by choosing the appropriate current-divider geometry. The root-mean-square (RMS) beam emittance (ε{sub RMS}) varies as the beam propagates through the current divider to the target. For applications where control of the beam trajectory is desired and the current density at the target is similar to the current density at the entrance foil, there is a modest 20% increase in ε{sub RMS} at the target. For other applications where the beam is pinched to a current density ∼5 times larger at the target, ε{sub RMS} is 2–3 times larger at the target.« less

Attenuated response of L-type calcium current to nitric oxide in atrial fibrillation.

PubMed

Rozmaritsa, Nadiia; Christ, Torsten; Van Wagoner, David R; Haase, Hannelore; Stasch, Johannes-Peter; Matschke, Klaus; Ravens, Ursula

2014-03-01

Nitric oxide (NO) synthesized by cardiomyocytes plays an important role in the regulation of cardiac function. Here, we studied the impact of NO signalling on calcium influx in human right atrial myocytes and its relation to atrial fibrillation (AF). Right atrial appendages (RAAs) were obtained from patients in sinus rhythm (SR) and AF. The biotin-switch technique was used to evaluate endogenous S-nitrosylation of the α1C subunit of L-type calcium channels. Comparing SR to AF, S-nitrosylation of Ca(2+) channels was similar. Direct effects of the NO donor S-nitroso-N-acetyl-penicillamine (SNAP) on L-type calcium current (ICa,L) were studied in cardiomyocytes with standard voltage-clamp techniques. In SR, ICa,L increased with SNAP (100 µM) by 48%, n/N = 117/56, P < 0.001. The SNAP effect on ICa,L involved activation of soluble guanylate cyclase and protein kinase A. Specific inhibition of phosphodiesterase (PDE)3 with cilostamide (1 µM) enhanced ICa,L to a similar extent as SNAP. However, when cAMP was elevated by PDE3 inhibition or β-adrenoceptor stimulation, SNAP reduced ICa,L, pointing to cGMP-cAMP cross-regulation. In AF, the stimulatory effect of SNAP on ICa,L was attenuated, while its inhibitory effect on isoprenaline- or cilostamide-stimulated current was preserved. cGMP elevation with SNAP was comparable between the SR and AF group. Moreover, the expression of PDE3 and soluble guanylate cyclase was not reduced in AF. NO exerts dual effects on ICa,L in SR with an increase of basal and inhibition of cAMP-stimulated current, and in AF NO inhibits only stimulated ICa,L. We conclude that in AF, cGMP regulation of PDE2 is preserved, but regulation of PDE3 is lost.

Method of automatic measurement and focus of an electron beam and apparatus therefore

DOEpatents

Giedt, W.H.; Campiotti, R.

1996-01-09

An electron beam focusing system, including a plural slit-type Faraday beam trap, for measuring the diameter of an electron beam and automatically focusing the beam for welding is disclosed. Beam size is determined from profiles of the current measured as the beam is swept over at least two narrow slits of the beam trap. An automated procedure changes the focus coil current until the focal point location is just below a workpiece surface. A parabolic equation is fitted to the calculated beam sizes from which optimal focus coil current and optimal beam diameter are determined. 12 figs.

Method of automatic measurement and focus of an electron beam and apparatus therefor

DOEpatents

Giedt, Warren H.; Campiotti, Richard

1996-01-01

An electron beam focusing system, including a plural slit-type Faraday beam trap, for measuring the diameter of an electron beam and automatically focusing the beam for welding. Beam size is determined from profiles of the current measured as the beam is swept over at least two narrow slits of the beam trap. An automated procedure changes the focus coil current until the focal point location is just below a workpiece surface. A parabolic equation is fitted to the calculated beam sizes from which optimal focus coil current and optimal beam diameter are determined.

Development of a decision support system for monitoring, reporting and forecasting ecological conditions of the Appalachian Trail

USGS Publications Warehouse

Wang, Yeqiao; Nemani, Ramakrishna; Dieffenbach, Fred; Stolte, Kenneth; Holcomb, Glenn B.; Robinson, Matt; Reese, Casey C.; McNiff, Marcia; Duhaime, Roland; Tierney, Geri; Mitchell, Brian; August, Peter; Paton, Peter; LaBash, Charles

2010-01-01

This paper introduces a collaborative multi-agency effort to develop an Appalachian Trail (A.T.) MEGA-Transect Decision Support System (DSS) for monitoring, reporting and forecasting ecological conditions of the A.T. and the surrounding lands. The project is to improve decisionmaking on management of the A.T. by providing a coherent framework for data integration, status reporting and trend analysis. The A.T. MEGA-Transect DSS is to integrate NASA multi-platform sensor data and modeling through the Terrestrial Observation and Prediction System (TOPS) and in situ measurements from A.T. MEGA-Transect partners to address identified natural resource priorities and improve resource management decisions.

The Long-Baseline Neutrino Facility: Building the Future

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fermilab

The Long-Baseline Neutrino Facility (LBNF) will be the world’s flagship science project to unlock the mysteries of neutrinos, the particles that could be the key to explaining why matter exists in our universe. It will house the infrastructure and particle detectors for the Deep Underground Neutrino Experiment (DUNE) and will use the world’s most intense neutrino beam. LBNF will be hosted at the U.S. Department of Energy’s Fermi National Accelerator Laboratory in Illinois and the Sanford Underground Research Facility in South Dakota. About 1,000 scientists from more than 160 laboratories and universities in 30 countries are contributing to this internationalmore » mega-science project. In addition to direct economic benefits to the states of Illinois and South Dakota, LBNF will foster STEM education nationwide and keep the United States at the leading edge of global science and innovation.« less

VizieR Online Data Catalog: SL2S galaxy-scale sample of lens candidates (Gavazzi+, 2014)

NASA Astrophysics Data System (ADS)

Gavazzi, R.; Marshall, P. J.; Treu, T.; Sonnenfeld, A.

2017-06-01

The CFHTLS5 is a major photometric survey of more than 450 nights over 5 yr (started on 2003 June 1) using the MegaCam wide-field imager, which covers ~1 deg2 on the sky, with a pixel size of 0.186". The CFHTLS has two components aimed at extragalactic studies: a Deep component consisting of four pencil-beam fields of 1 deg2 and a wide component consisting of four mosaics covering 150 deg2 in total. Both surveys are imaged through five broadband filters. The data are pre-reduced at CFHT with the Elixir pipeline (http://www.cfht.hawaii.edu/Instruments/Elixir/), which removes the instrumental artifacts in individual exposures. The CFHTLS images are then astrometrically calibrated, photometrically inter-calibrated, resampled and stacked by the Terapix group at the Institut d'Astrophysique de Paris, and finally archived at the Canadian Astronomy Data Centre. (2 data files).

Laser-plasma interactions in magnetized environment

NASA Astrophysics Data System (ADS)

Shi, Yuan; Qin, Hong; Fisch, Nathaniel J.

2018-05-01

Propagation and scattering of lasers present new phenomena and applications when the plasma medium becomes strongly magnetized. With mega-Gauss magnetic fields, scattering of optical lasers already becomes manifestly anisotropic. Special angles exist where coherent laser scattering is either enhanced or suppressed, as we demonstrate using a cold-fluid model. Consequently, by aiming laser beams at special angles, one may be able to optimize laser-plasma coupling in magnetized implosion experiments. In addition, magnetized scattering can be exploited to improve the performance of plasma-based laser pulse amplifiers. Using the magnetic field as an extra control variable, it is possible to produce optical pulses of higher intensity, as well as compress UV and soft x-ray pulses beyond the reach of other methods. In even stronger giga-Gauss magnetic fields, laser-plasma interaction enters a relativistic-quantum regime. Using quantum electrodynamics, we compute a modified wave dispersion relation, which enables correct interpretation of Faraday rotation measurements of strong magnetic fields.

Aggressiveness of contemporary self-etching adhesives. Part II: etching effects on unground enamel.

PubMed

Pashley, D H; Tay, F R

2001-09-01

The aggressiveness of three self-etching adhesives on unground enamel was investigated. Ultrastructural features and microtensile bond strength were examined, first using these adhesives as both the etching and resin-infiltration components, and then examining their etching efficacy alone through substitution of the proprietary resins with the same control resins. For SEM examination, buccal, mid-coronal, unground enamel from human extracted bicuspids were etched with either Clearfil Mega Bond (Kuraray), Non-Rinse Conditioner (NRC; Dentsply DeTrey) or Prompt L-Pop (ESPE). Those in the control group were etched with 32% phosphoric acid (Bisco) for 15s. They were all rinsed off prior to examination of the etching efficacy. For TEM examination, the self-etching adhesives were used as recommended. Unground enamel treated with NRC were further bonded using Prime&Bond NT (Dentsply), while those in the etched, control group were bonded using All-Bond 2 (Bisco). Completely demineralized, resin replicas were embedded in epoxy resin for examination of the extent of resin infiltration. For microtensile bond strength evaluation, specimens were first etched and bonded using the self-etching adhesives. A second group of specimens were etched with the self-etching adhesives, rinsed but bonded using a control adhesive. Following restoration with Z100 (3M Dental Products), they were sectioned into beams of uniform cross-sectional areas and stressed to failure. Etching patterns of aprismatic enamel, as revealed by SEM, and the subsurface hybrid layer morphology, as revealed by TEM, varied according to the aggressiveness of the self-etching adhesives. Clearfil Mega Bond exhibited the mildest etching patterns, while Prompt L-Pop produced an etching effect that approached that of the total-etch control group. Microtensile bond strength of the three experimental groups were all significantly lower than the control group, but not different from one another. When the self-etching adhesives were replaced with the control adhesive after etching, bond strengths of NRC/Prime&Bond NT and Prompt L-Pop were not significantly different from that of the control group, but were significantly higher than that of Clearfil Mega Bond. Both etching efficacy and strength of the resins are important contributing factors in bonding of self-etching adhesives to unground enamel.

Role of CNPase in the Oligodendrocytic Extracellular 2′,3′-cAMP-Adenosine Pathway

PubMed Central

Verrier, Jonathan D.; Jackson, Travis C.; Gillespie, Delbert G.; Janesko-Feldman, Keri; Bansal, Rashmi; Goebbels, Sandra; Nave, Klaus-Armin; Kochanek, Patrick M.; Jackson, Edwin K.

2014-01-01

Extracellular adenosine 3′,5′-cyclic monophosphate (3′,5′-cAMP) is an endogenous source of localized adenosine production in many organs. Recent studies suggest that extracellular 2′,3′-cAMP (positional isomer of 3′,5′-cAMP) is also a source of adenosine, particularly in the brain in vivo post-injury. Moreover, in vitro studies show that both microglia and astrocytes can convert extracellular 2′,3′-cAMP to adenosine. Here we examined the ability of primary mouse oligodendrocytes and neurons to metabolize extracellular 2′,3′-cAMP and their respective adenosine monophosphates (2′-AMP and 3′-AMP). Cells were also isolated from mice deficient in 2′,3′-cyclic nucleotide-3′-phosphodiesterase (CNPase). Oligodendrocytes metabolized 2′,3′-cAMP to 2′-AMP with 10-fold greater efficiency than did neurons (and also more than previously examined microglia and astrocytes); whereas, the production of 3′-AMP was minimal in both oligodendrocytes and neurons. The production of 2′-AMP from 2′,3′-cAMP was reduced by 65% in CNPase -/- versus CNPase +/+ oligodendrocytes. Oligodendrocytes also converted 2′-AMP to adenosine, and this was also attenuated in CNPase -/- oligodendrocytes. Inhibition of classic 3′,5′-cAMP-3′-phosphodiesterases with 3-isobutyl-1-methylxanthine did not block metabolism of 2′,3′-cAMP to 2′-AMP and inhibition of classic ecto-5′-nucleotidase (CD73) with α,β-methylene-adenosine-5′-diphosphate did not attenuate the conversion of 2′-AMP to adenosine. These studies demonstrate that oligodendrocytes express the extracellular 2′,3′-cAMP-adenosine pathway (2′,3′-cAMP → 2′-AMP → adenosine). This pathway is more robustly expressed in oligodendrocytes than in all other CNS cell types because CNPase is the predominant enzyme that metabolizes 2′,3′-cAMP to 2-AMP in CNS cells. By reducing levels of 2′,3′-cAMP (a mitochondrial toxin) and increasing levels of adenosine (a neuroprotectant), oligodendrocytes may protect axons from injury. PMID:23922219

2’,3’-cAMP, 3’-AMP, 2’-AMP and Adenosine Inhibit TNF-α and CXCL10 Production From Activated Primary Murine Microglia via A2A Receptors

PubMed Central

Newell, Elizabeth A.; Exo, Jennifer L.; Verrier, Jonathan D.; Jackson, Travis C.; Gillespie, Delbert G.; Janesko-Feldman, Keri; Kochanek, Patrick M.

2014-01-01

Background Some cells, tissues and organs release 2’,3’-cAMP (a positional isomer of 3’,5’-cAMP) and convert extracellular 2’,3’-cAMP to 2’-AMP plus 3’-AMP and convert these AMPs to adenosine (called the extracellular 2’,3’-cAMP-adenosine pathway). Recent studies show that microglia have an extracellular 2’,3’-cAMP-adenosine pathway. The goal of the present study was to investigate whether the extracellular 2’,3’-cAMP-adenosine pathway could have functional consequences on the production of cytokines/chemokines by activated microglia. Methods Experiments were conducted in cultures of primary murine microglia. In the first experiment, the effect of 2’,3’-cAMP, 3’-AMP, 2’-AMP and adenosine on LPS-induced TNF-α and CXCL10 production was determined. In the next experiment, the first protocol was replicated but with the addition of 1,3-dipropyl-8-p-sulfophenylxanthine (DPSPX) (0.1 µM; antagonist of adenosine receptors). The last experiment compared the ability of 2-chloro-N6-cyclopentyladenosine (CCPA) (10 µM; selective A1 agonist), 5’-N-ethylcarboxamide adenosine (NECA) (10 µM; agonist for all adenosine receptor subtypes) and CGS21680 (10 µM; selective A2A agonist) to inhibit LPS-induced TNF-α and CXCL10 production. Results 1) 2’,3’-cAMP, 3’-AMP, 2’-AMP and adenosine similarly inhibited LPS-induced TNF-α and CXCL10 production; 2) DPSPX nearly eliminated the inhibitory effects of 2’,3’-cAMP, 3’-AMP, 2’-AMP and adenosine on LPS-induced TNF-α and CXCL10 production; 3) CCPA did not affect LPS-induced TNF-α and CXCL10; 4) NECA and CGS21680 similarly inhibited LPS-induced TNF-α and CXCL10 production. Conclusions 2’,3’-cAMP and its metabolites (3’-AMP, 2’-AMP and adenosine) inhibit LPS-induced TNF-α and CXCL10 production via A2A-receptor activation. Adenosine and its precursors, via A2A receptors, likely suppress TNF-α and CXCL10 production by activated microglia in brain diseases. PMID:25451117

The 2′,3′-cAMP-adenosine pathway

PubMed Central

2011-01-01

Our recent studies employing HPLC-tandem mass spectrometry to analyze venous perfusate from isolated, perfused kidneys demonstrate that intact kidneys produce and release into the extracellular compartment 2′,3′-cAMP, a positional isomer of the second messenger 3′,5′-cAMP. To our knowledge, this represents the first detection of 2′,3′-cAMP in any cell/tissue/organ/organism. Nuclear magnetic resonance experiments with isolated RNases and experiments in isolated, perfused kidneys suggest that 2′,3′-cAMP likely arises from RNase-mediated transphosphorylation of mRNA. Both in vitro and in vivo kidney experiments demonstrate that extracellular 2′,3′-cAMP is efficiently metabolized to 2′-AMP and 3′-AMP, both of which can be further metabolized to adenosine. This sequence of reactions is called the 2′,3′-cAMP-adenosine pathway (2′,3′-cAMP → 2′-AMP/3′-AMP → adenosine). Experiments in rat and mouse kidneys show that metabolic poisons increase extracellular levels of 2′,3′-cAMP, 2′-AMP, 3′-AMP, and adenosine; however, little is known regarding the pharmacology of 2′,3′-cAMP, 2′-AMP, and 3′-AMP. What is known is that 2′,3′-cAMP facilitates activation of mitochondrial permeability transition pores, a process that can lead to apoptosis and necrosis, and inhibits proliferation of vascular smooth muscle cells and glomerular mesangial cells. In summary, there is mounting evidence that at least some types of cellular injury, by triggering mRNA degradation, engage the 2′,3′-cAMP-adenosine pathway, and therefore this pathway should be added to the list of biochemical pathways that produce adenosine. Although speculative, it is possible that the 2′,3′-cAMP-adenosine pathway may protect against some forms of acute organ injury, for example acute kidney injury, by both removing an intracellular toxin (2′,3′-cAMP) and increasing an extracellular renoprotectant (adenosine). PMID:21937608

Optical monitoring of ion beam Y-Ba-Cu-O sputtering

NASA Astrophysics Data System (ADS)

Klein, J. D.; Yen, A.

1990-11-01

The emission spectra resulting from ion beam sputtering a Y-Ba-Cu-O target were observed as a function of beam voltage and beam current. The spectra were relatively clean with several peaks readily attributed to each of Y, Ba, and Ar. Monitoring of copper and oxygen was more difficult with a single CuO peak and one O peak evident. The intensities of the cation peaks were linear with respect to beam voltage above 400 V. Since target current was found not to be directly proportional to beam current, target power was defined as the product of beam voltage and target current. The response of cation peak height to changes in target power was linear and similar for variations of either beam voltage or target current.

Mega-Universities and Knowledge Media: Technology Strategies for Higher Education.

ERIC Educational Resources Information Center

Daniel, John S

This book explores the essentials of distance education and reviews issues facing large open universities (mega-universities) worldwide. It uses examples from industry and the knowledge media, to show how technology-based learning can be made attractive both to students and to institutions. The book's eight chapters, including 10 figures and 5…

Unemployment, Entrepreneurial Education and Mega Universities: Challenges to Expanding Access in Education in Nigeria University

ERIC Educational Resources Information Center

Undie, John Atewhoble; Okafor, Victor

2014-01-01

In fundamental economics, individuals acquired education for two broad reasons, as an investment and as consumption. The investment function of education has continued to create tension for job search leading to cases of unemployment. Entrepreneurship education and establishment of mega universities have been identified as panaceas. This paper…

Mega-Planning in Population

ERIC Educational Resources Information Center

Clark, Sarah C.; Murray, Margo

2005-01-01

Clark and Murray examine the six Critical Performance Factors for Mega planning in an example drawn from the five-year history of the population program of a major west coast philanthropy. In this article, the authors describe the salience and scope of the population issue as it is relates to other global trends; the steps the foundation took to…

From Teacher to Teacher: A True School and Home Collaboration that Works.

ERIC Educational Resources Information Center

Brim, Judy

1998-01-01

MegaSkills are attitudes, behaviors, and habits that determine a child's achievement in school and throughout life. This paper describes the MegaSkills Parent Workshops and Classroom Essentials Programs, which empower parents, and introduce, develop, and reinforce crucial living skills for success in and out of school. The paper also offers…

Nurturing the Educational Leader within You! Knowing, Building, and Using Your Adult MegaSkills.

ERIC Educational Resources Information Center

Rich, Dorothy

This handbook is designed to identify, build, maintain, and expand teachers' personal and professional effectiveness using "MegaSkills." Section 1, "Knowing Your Leadership Strengths," focuses on identifying strengths, exploring how adults learn, and considering new dimensions for successful education. It also discusses seven habits of good…

Can interpreting sediment toxicity tests a mega sites benefit from novel approaches to normalization to address batching of tests?

EPA Science Inventory

Sediment toxicity tests are a key tool used in Ecological Risk Assessments for contaminated sediment sites. Interpreting test results and defining toxicity is often a challenge. This is particularly true at mega sites where the testing regime is large, and by necessity performed ...

Ground-level air pollution changes during a boreal wildland mega-fire

Treesearch

Andrzej Bytnerowicz; Yu-Mei Hsu; Kevin Percy; Allan Legge; Mark E. Fenn; Susan Schilling; Witold Frączek; Diane Alexander

2016-01-01

The 2011 Richardson wildland mega-fire in the Athabasca Oil Sands Region (AOSR) in northern Alberta, Canada had large effects on air quality. At a receptor site in the center of the AOSR ambient PM2.5, O3, NO, NO2, SO2, NH3, HONO, HNO3...

Inhibition of Gαs/cAMP Signaling Decreases TCR-Stimulated IL-2 transcription in CD4(+) T Helper Cells.

PubMed

Hynes, Thomas R; Yost, Evan A; Yost, Stacy M; Hartle, Cassandra M; Ott, Braden J; Berlot, Catherine H

2015-07-06

The role of cAMP in regulating T cell activation and function has been controversial. cAMP is generally known as an immunosuppressant, but it is also required for generating optimal immune responses. As the effect of cAMP is likely to depend on its cellular context, the current study investigated whether the mechanism of activation of Gαs and adenylyl cyclase influences their effect on T cell receptor (TCR)-stimulated interleukin-2 (IL-2) mRNA levels. The effect of blocking Gs-coupled receptor (GsPCR)-mediated Gs activation on TCR-stimulated IL-2 mRNA levels in CD4(+) T cells was compared with that of knocking down Gαs expression or inhibiting adenylyl cyclase activity. The effect of knocking down Gαs expression on TCR-stimulated cAMP accumulation was compared with that of blocking GsPCR signaling. ZM-241385, an antagonist to the Gs-coupled A2A adenosine receptor (A2AR), enhanced TCR-stimulated IL-2 mRNA levels in primary human CD4(+) T helper cells and in Jurkat T cells. A dominant negative Gαs construct, GαsDN3, also enhanced TCR-stimulated IL-2 mRNA levels. Similar to GsPCR antagonists, GαsDN3 blocked GsPCR-dependent activation of both Gαs and Gβγ. In contrast, Gαs siRNA and 2',5'-dideoxyadenosine (ddA), an adenylyl cyclase inhibitor, decreased TCR-stimulated IL-2 mRNA levels. Gαs siRNA, but not GαsDN3, decreased TCR-stimulated cAMP synthesis. Potentiation of IL-2 mRNA levels by ZM-241385 required at least two days of TCR stimulation, and addition of ddA after three days of TCR stimulation enhanced IL-2 mRNA levels. GsPCRs play an inhibitory role in the regulation of TCR-stimulated IL-2 mRNA levels whereas Gαs and cAMP can play a stimulatory one. Additionally, TCR-dependent activation of Gαs does not appear to involve GsPCRs. These results suggest that the context of Gαs/cAMP activation and the stage of T cell activation and differentiation determine the effect on TCR-stimulated IL-2 mRNA levels.

Communicating mega-projects in the face of uncertainties: Israeli mass media treatment of the Dead Sea Water Canal.

PubMed

Fischhendler, Itay; Cohen-Blankshtain, Galit; Shuali, Yoav; Boykoff, Max

2015-10-01

Given the potential for uncertainties to influence mega-projects, this study examines how mega-projects are deliberated in the public arena. The paper traces the strategies used to promote the Dead Sea Water Canal. Findings show that the Dead Sea mega-project was encumbered by ample uncertainties. Treatment of uncertainties in early coverage was dominated by economics and raised primarily by politicians, while more contemporary media discourses have been dominated by ecological uncertainties voiced by environmental non-governmental organizations. This change in uncertainty type is explained by the changing nature of the project and by shifts in societal values over time. The study also reveals that 'uncertainty reduction' and to a lesser degree, 'project cancellation', are still the strategies most often used to address uncertainties. Statistical analysis indicates that although uncertainties and strategies are significantly correlated, there may be other intervening variables that affect this correlation. This research also therefore contributes to wider and ongoing considerations of uncertainty in the public arena through various media representational practices. © The Author(s) 2013.

Dynamic characteristics of a 30-centimeter mercury ion thruster

NASA Technical Reports Server (NTRS)

Serafini, J. S.; Mantenieks, M. A.; Rawlin, V. K.

1975-01-01

The present work reports on measurements of the fluctuations in the beam current, discharge current, neutralizer keeper current, and discharge voltage of a 30-cm ion thruster made with 60Hz laboratory-type power supplies. The intensities of the fluctuations (ratio of the root-mean-square magnitude to time-average quantity) were found to depend significantly on the beam and magnetic baffle currents. The shape of the frequency spectra of the discharge plasma fluctuations was related to the beam and magnetic baffle currents. The predominant peaks of the beam and discharge current spectra occurred at frequencies less than 30 kilohertz. This discharge chamber resonance could be attributable to ion-acoustic wave phenomena. Cross-correlations of the discharge and beam currents indicated that the dependence on the magnetic baffle current was strong. The measurements revealed that the discharge current fluctuations directly contribute to the beam current fluctuations and that the power supply characteristics can modify these fluctuations.

A Measurement of the Force between Two Current-Carrying Wires

ERIC Educational Resources Information Center

Straulino, S.; Cartacci, A.

2014-01-01

The measurement of the force acting between two parallel, current-carrying wires is known as Ampère's experiment. A mechanical balance was historically employed to measure that force. We report a simple experiment based on an electronic precision balance that is useful in clearly showing students the existence of this interaction and how to…

Dietary effects of adenosine monophosphate to enhance growth, digestibility, innate immune responses and stress resistance of juvenile red sea bream, Pagrus major.

PubMed

Hossain, Md Sakhawat; Koshio, Shunsuke; Ishikawa, Manabu; Yokoyama, Saichiro; Sony, Nadia Mahjabin

2016-09-01

Our study explored the dietary effects of adenosine monophosphate (AMP) to enhance growth, digestibility, innate immune responses and stress resistance of juvenile red sea bream. A semi-purified basal diet supplemented with 0% (Control), 0.1% (AMP-0.1), 0.2% (AMP-0.2), 0.4% (AMP-0.4) and 0.8% (AMP-0.8) purified AMP to formulate five experimental diets. Each diet was randomly allocated to triplicate groups of fish (mean initial weight 3.4 g) for 56 days. The results indicated that dietary AMP supplements tended to improve growth performances. One of the best ones was found in diet group AMP-0.2, followed by diet groups AMP-0.1, AMP-0.4 and AMP-0.8. The Apparent digestibility coefficients (dry matter, protein and lipid) also improved by AMP supplementation and the significantly highest dry matter digestibility was observed in diet group AMP-0.2. Fish fed diet groups AMP-0.2 and AMP-0.4 had significantly higher peroxidase and bactericidal activities than fish fed the control diet. Nitro-blue-tetrazolium (NBT) activity was found to be significantly (P < 0.05) greater in fish fed diet groups AMP-0.4 and AMP-0.8. Total serum protein, lysozyme activity and agglutination antibody titer were also increased (P > 0.05) by dietary supplementation. In contrast, catalase activity decreased with AMP supplementation. Moreover, the fish fed AMP supplemented diets had better improvement (P < 0.05) in body lipid contents, condition factor, hematocrit content and glutamyl oxaloacetic transaminase (GOT) level than the control group. Supplementation also improved both freshwater and oxidative stress resistances. Interestingly, the fish fed diet groups AMP-0.2 and AMP-0.4 showed the least oxidative stress condition. Finally it is concluded that, dietary AMP supplementation enhanced the growth, digestibility, immune response and stress resistance of red sea bream. The regression analysis revealed that a dietary AMP supplementation between 0.2 and 0.4% supported weight gain and lysozyme activity as a marker of immune functions for red sea bream, which is also inline with the most of the growth and health performance parameters of fish under present experimental conditions. Copyright © 2016 Elsevier Ltd. All rights reserved.

Comparisons of spectral aerosol single scattering albedo in Seoul, South Korea

NASA Astrophysics Data System (ADS)

Mok, Jungbin; Krotkov, Nickolay A.; Torres, Omar; Jethva, Hiren; Li, Zhanqing; Kim, Jhoon; Koo, Ja-Ho; Go, Sujung; Irie, Hitoshi; Labow, Gordon; Eck, Thomas F.; Holben, Brent N.; Herman, Jay; Loughman, Robert P.; Spinei, Elena; Lee, Seoung Soo; Khatri, Pradeep; Campanelli, Monica

2018-04-01

Quantifying aerosol absorption at ultraviolet (UV) wavelengths is important for monitoring air pollution and aerosol amounts using current (e.g., Aura/OMI) and future (e.g., TROPOMI, TEMPO, GEMS, and Sentinel-4) satellite measurements. Measurements of column average atmospheric aerosol single scattering albedo (SSA) are performed on the ground by the NASA AERONET in the visible (VIS) and near-infrared (NIR) wavelengths and in the UV-VIS-NIR by the SKYNET networks. Previous comparison studies have focused on VIS and NIR wavelengths due to the lack of co-incident measurements of aerosol and gaseous absorption properties in the UV. This study compares the SKYNET-retrieved SSA in the UV with the SSA derived from a combination of AERONET, MFRSR, and Pandora (AMP) retrievals in Seoul, South Korea, in spring and summer 2016. The results show that the spectrally invariant surface albedo assumed in the SKYNET SSA retrievals leads to underestimated SSA compared to AMP values at near UV wavelengths. Re-processed SKYNET inversions using spectrally varying surface albedo, consistent with the AERONET retrieval improve agreement with AMP SSA. The combined AMP inversions allow for separating aerosol and gaseous (NO2 and O3) absorption and provide aerosol retrievals from the shortest UVB (305 nm) through VIS to NIR wavelengths (870 nm).

Antimicrobial Peptides and Nanotechnology, Recent Advances and Challenges.

PubMed

Biswaro, Lubhandwa S; da Costa Sousa, Mauricio G; Rezende, Taia M B; Dias, Simoni C; Franco, Octavio L

2018-01-01

Antimicrobial peptides are sequences of amino acids, which present activity against microorganisms. These peptides were discovered over 70 years ago, and are abundant in nature from soil bacteria, insects, amphibians to mammals and plants. They vary in amino acids number, the distance between amino acids within individual peptide structure, net charge, solubility and other physical chemical properties as well as differ in mechanism of action. These peptides may provide an alternative treatment to conventional antibiotics, which encounter resistance such as the peptide nisin applied in treating methicillin resistant Staphylococcus aureus (MRSA) or may behave synergistically with known antibiotics against parasites for instance, nisin Z when used in synergy with ampicillin reported better activity against Pseudomonas fluorescens than when the antibiotic was alone. AMPs are known to be active against viruses, bacteria, fungi and protozoans. Nanotechnology is an arena which explores the synthesis, characterization and application of an array of delivery systems at a one billionth of meter scale. Such systems are implemented to deliver drugs, proteins, vaccines, and peptides. The role of nanotechnology in delivering AMPs is still at its early development stage. There are challenges of incorporating AMPs into drug delivery system. This review intends to explore in depth, the role of nanotechnology in delivering AMPs as well as presenting the current advances and accompanying challenges of the technology.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bockris, J.O.; Devanathan, M.A.V.

The galvanostatic double charging method was applied to determine the coverage of Ni cathodes with adsorbed atomic H in 2 N NaOH solutions. Anodic current densities were varied from 0.05 to 1.8 amp/sq cm. The plateau indicating absence of readsorption was between 0.6 and 1.8 amp/sq cm, for a constant cathodic c.d. of 1/10,000 amp/sq cm. The variation of the adsorbed H over cathodic c.d.'s ranging from 10 to the -6th power to 1/10 at a constant anodic c.d. of 1 amp/sq cm were calculated and the coverage calculated. The mechanism of the H evolution reaction was elucidated. The ratemore » determining step is discharge from a water molecules followed by rapid Tafel recombination. The rate constants for these processes and the rate constant for the ionisation, calculated with the extrapolated value of coverage for the reversible H electrode, were determined. A modification of the Tafel equation which takes into account both coverage and ionisation is in harmony with the results. A new method for the determination of coverage suitable for corrodible metals is described which involves the measurement of the rate of permeation of H by electrochemical techniques which enhances the sensitivity of the method. (Author)« less

Increased production of omega-3 fatty acids protects retinal ganglion cells after optic nerve injury in mice.

PubMed

Peng, Shanshan; Shi, Zhe; Su, Huanxing; So, Kwok-Fai; Cui, Qi

2016-07-01

Injury to the central nervous system causes progressive degeneration of injured axons, leading to loss of the neuronal bodies. Neuronal survival after injury is a prerequisite for successful regeneration of injured axons. In this study, we investigated the effects of increased production of omega-3 fatty acids and elevation of cAMP on retinal ganglion cell (RGC) survival and axonal regeneration after optic nerve (ON) crush injury in adult mice. We found that increased production of omega-3 fatty acids in mice enhanced RGC survival, but not axonal regeneration, over a period of 3 weeks after ON injury. cAMP elevation promoted RGC survival in wild type mice, but no significant difference in cell survival was seen in mice over-producing omega-3 fatty acids and receiving intravitreal injections of CPT-cAMP, suggesting that cAMP elevation protects RGCs after injury but does not potentiate the actions of the omega-3 fatty acids. The observed omega-3 fatty acid-mediated neuroprotection is likely achieved partially through ERK1/2 signaling as inhibition of this pathway by PD98059 hindered, but did not completely block, RGC protection. Our study thus enhances our current understanding of neural repair after CNS injury, including the visual system. Copyright © 2016 Elsevier Ltd. All rights reserved.

Using ERPs to Investigate Valence Processing in the Affect Misattribution Procedure

PubMed Central

Von Gunten, Curtis D.; Bartholow, Bruce D.; Scherer, Laura D.

2016-01-01

The construct validity of the Affect Misattribution Procedure (AMP) has been challenged by theories proposing that the task does not actually measure affect misattribution. The current study tested the validity of the AMP as a measure of affect misattribution by examining three components of the event-related potential (ERP) known to be associated with the allocation of motivated attention. Results revealed that ERP amplitudes varied in response to affectively ambiguous targets as a function of the valence of preceding primes. Furthermore, differences in ERP responses to the targets were largely similar to differences in ERPs elicited by the primes. The existence of valence differentiation in both the prime-locked and the target-locked ERPs, along with the similarity in this differentiation, provides evidence that the affective content of the primes is psychologically registered, and that this content influences the processing of the subsequent, evaluatively ambiguous targets, both of which are required if the priming effects found in the AMP are the result of affect misattribution. However, the behavioral priming effect was uncorrelated with ERP amplitudes, leaving some question as to the locus of this effect in the information-processing system. Findings are discussed in light of the strengths and weaknesses of using ERPs to understand the priming effects in the AMP. PMID:27754548

Air-water exchange of PAHs and OPAHs at a superfund mega-site.

PubMed

Tidwell, Lane G; Blair Paulik, L; Anderson, Kim A

2017-12-15

Chemical fate is a concern at environmentally contaminated sites, but characterizing that fate can be difficult. Identifying and quantifying the movement of chemicals at the air-water interface are important steps in characterizing chemical fate. Superfund sites are often suspected sources of air pollution due to legacy sediment and water contamination. A quantitative assessment of polycyclic aromatic hydrocarbons (PAHs) and oxygenated PAH (OPAHs) diffusive flux in a river system that contains a Superfund Mega-site, and passes through residential, urban and agricultural land, has not been reported before. Here, passive sampling devices (PSDs) were used to measure 60 polycyclic aromatic hydrocarbons (PAHs) and 22 oxygenated PAH (OPAHs) in air and water. From these concentrations the magnitude and direction of contaminant flux between these two compartments was calculated. The magnitude of PAH flux was greater at sites near or within the Superfund Mega-site than outside of the Superfund Mega-site. The largest net individual PAH deposition at a single site was naphthalene at a rate of -14,200 (±5780) (ng/m 2 )/day. The estimated one-year total flux of phenanthrene was -7.9×10 5 (ng/m 2 )/year. Human health risk associated with inhalation of vapor phase PAHs and dermal exposure to PAHs in water were assessed by calculating benzo[a]pyrene equivalent concentrations. Excess lifetime cancer risk estimates show potential increased risk associated with exposure to PAHs at sites within and in close proximity to the Superfund Mega-site. Specifically, estimated excess lifetime cancer risk associated with dermal exposure and inhalation of PAHs was above 1 in 1 million within the Superfund Mega-site. The predominant depositional flux profile observed in this study suggests that the river water in this Superfund site is largely a sink for airborne PAHs, rather than a source. Copyright © 2017 Elsevier B.V. All rights reserved.

Dynamic Simulations for the Seismic Behavior on the Shallow Part of the Fault Plane in the Subduction Zone during Mega-Thrust Earthquakes

NASA Astrophysics Data System (ADS)

Tsuda, K.; Dorjapalam, S.; Dan, K.; Ogawa, S.; Watanabe, T.; Uratani, H.; Iwase, S.

2012-12-01

The 2011 Tohoku-Oki earthquake (M9.0) produced some distinct features such as huge slips on the order of several ten meters around the shallow part of the fault and different areas with radiating seismic waves for different periods (e.g., Lay et al., 2012). These features, also reported during the past mega-thrust earthquakes in the subduction zone such as the 2004 Sumatra earthquake (M9.2) and the 2010 Chile earthquake (M8.8), get attentions as the distinct features if the rupture of the mega-thrust earthquakes reaches to the shallow part of the fault plane. Although various kinds of observations for the seismic behavior (rupture process and ground motion characteristics etc.) on the shallow part of the fault plane during the mega-trust earthquakes have been reported, the number of analytical or numerical studies based on dynamic simulation is still limited. Wendt et al. (2009), for example, revealed that the different distribution of initial stress produces huge differences in terms of the seismic behavior and vertical displacements on the surface. In this study, we carried out the dynamic simulations in order to get a better understanding about the seismic behavior on the shallow part of the fault plane during mega-thrust earthquakes. We used the spectral element method (Ampuero, 2009) that is able to incorporate the complex fault geometry into simulation as well as to save computational resources. The simulation utilizes the slip-weakening law (Ida, 1972). In order to get a better understanding about the seismic behavior on the shallow part of the fault plane, some parameters controlling seismic behavior for dynamic faulting such as critical slip distance (Dc), initial stress conditions and friction coefficients were changed and we also put the asperity on the fault plane. These understandings are useful for the ground motion prediction for future mega-thrust earthquakes such as the earthquakes along the Nankai Trough.

Weak gravitational lensing effects on the determination of Omega_mega_m and Omega_mega Lambda from SNeIa

NASA Astrophysics Data System (ADS)

Valageas, P.

2000-02-01

In this article we present an analytical calculation of the probability distribution of the magnification of distant sources due to weak gravitational lensing from non-linear scales. We use a realistic description of the non-linear density field, which has already been compared with numerical simulations of structure formation within hierarchical scenarios. Then, we can directly express the probability distribution P(mu ) of the magnification in terms of the probability distribution of the density contrast realized on non-linear scales (typical of galaxies) where the local slope of the initial linear power-spectrum is n=-2. We recover the behaviour seen by numerical simulations: P(mu ) peaks at a value slightly smaller than the mean < mu >=1 and it shows an extended large mu tail (as described in another article our predictions also show a good quantitative agreement with results from N-body simulations for a finite smoothing angle). Then, we study the effects of weak lensing on the derivation of the cosmological parameters from SNeIa. We show that the inaccuracy introduced by weak lensing is not negligible: {cal D}lta Omega_mega_m >~ 0.3 for two observations at z_s=0.5 and z_s=1. However, observations can unambiguously discriminate between Omega_mega_m =0.3 and Omega_mega_m =1. Moreover, in the case of a low-density universe one can clearly distinguish an open model from a flat cosmology (besides, the error decreases as the number of observ ed SNeIa increases). Since distant sources are more likely to be ``demagnified'' the most probable value of the observed density parameter Omega_mega_m is slightly smaller than its actual value. On the other hand, one may obtain some valuable information on the properties of the underlying non-linear density field from the measure of weak lensing distortions.

A parallel input composite transimpedance amplifier.

PubMed

Kim, D J; Kim, C

2018-01-01

A new approach to high performance current to voltage preamplifier design is presented. The design using multiple operational amplifiers (op-amps) has a parasitic capacitance compensation network and a composite amplifier topology for fast, precision, and low noise performance. The input stage consisting of a parallel linked JFET op-amps and a high-speed bipolar junction transistor (BJT) gain stage driving the output in the composite amplifier topology, cooperating with the capacitance compensation feedback network, ensures wide bandwidth stability in the presence of input capacitance above 40 nF. The design is ideal for any two-probe measurement, including high impedance transport and scanning tunneling microscopy measurements.

A parallel input composite transimpedance amplifier

NASA Astrophysics Data System (ADS)

Kim, D. J.; Kim, C.

2018-01-01

A new approach to high performance current to voltage preamplifier design is presented. The design using multiple operational amplifiers (op-amps) has a parasitic capacitance compensation network and a composite amplifier topology for fast, precision, and low noise performance. The input stage consisting of a parallel linked JFET op-amps and a high-speed bipolar junction transistor (BJT) gain stage driving the output in the composite amplifier topology, cooperating with the capacitance compensation feedback network, ensures wide bandwidth stability in the presence of input capacitance above 40 nF. The design is ideal for any two-probe measurement, including high impedance transport and scanning tunneling microscopy measurements.

Zinc-oxygen battery development program

NASA Technical Reports Server (NTRS)

Bourland, Deborah S.

1991-01-01

The purpose of this Zinc-Oxygen development program is to incorporate the improved air/oxygen cathode and zinc anode technology developed in recent years into relatively large cells (150-200 amp/hr, 25-100 hour rate) and smaller high rate cells (9-12 amp/hr, 3-12 hour rate). Existing commercial cells manufactured by Duracell and Rayovac are currently being utilized on the Space Shuttle Orbiter in a mini-oscilloscope, the crew radio, and other crew equipment. These applications provide a basis for other Orbiter systems that require portable, storable, electrical power as well as emergency power for the Space Station major payload systems power and for Space Station equipment applications.

Development and planning and design of equipment pumping generator of semiconductor lasers

NASA Technical Reports Server (NTRS)

Popkov, A. V.

1974-01-01

The schematic of a multidimensional current pulse generator is studied. A MTKh-90 cold cathode thyratron is used as the current commutator. In the autooscillation mode on a frequency of 380 hertz the generator creates a current to 100 amps per pulse in a control resistance of 1 ohm. The pulse duration is regulated within the limits from 0.1 to 3.0 microseconds.

Antimicrobial proteins: From old proteins, new tricks.

PubMed

Smith, Valerie J; Dyrynda, Elisabeth A

2015-12-01

This review describes the main types of antimicrobial peptides (AMPs) synthesised by crustaceans, primarily those identified in shrimp, crayfish, crab and lobster. It includes an overview of their range of microbicidal activities and the current landscape of our understanding of their gene expression patterns in different body tissues. It further summarises how their expression might change following various types of immune challenges. The review further considers proteins or protein fragments from crustaceans that have antimicrobial properties but are more usually associated with other biological functions, or are derived from such proteins. It discusses how these unconventional AMPs might be generated at, or delivered to, sites of infection and how they might contribute to crustacean host defence in vivo. It also highlights recent work that is starting to reveal the extent of multi-functionality displayed by some decapod AMPs, particularly their participation in other aspects of host protection. Examples of such activities include proteinase inhibition, phagocytosis, antiviral activity and haematopoiesis. Copyright © 2015 Elsevier Ltd. All rights reserved.

Low Concentrations of Metformin Suppress Glucose Production in Hepatocytes through AMP-activated Protein Kinase (AMPK)*♦

PubMed Central

Cao, Jia; Meng, Shumei; Chang, Evan; Beckwith-Fickas, Katherine; Xiong, Lishou; Cole, Robert N.; Radovick, Sally; Wondisford, Fredric E.; He, Ling

2014-01-01

Metformin is a first-line antidiabetic agent taken by 150 million people across the world every year, yet its mechanism remains only partially understood and controversial. It was proposed that suppression of glucose production in hepatocytes by metformin is AMPK-independent; however, unachievably high concentrations of metformin were employed in these studies. In the current study, we find that metformin, via an AMP-activated protein kinase (AMPK)-dependent mechanism, suppresses glucose production and gluconeogenic gene expression in primary hepatocytes at concentrations found in the portal vein of animals (60–80 μm). Metformin also inhibits gluconeogenic gene expression in the liver of mice administered orally with metformin. Furthermore, the cAMP-PKA pathway negatively regulates AMPK activity through phosphorylation at Ser-485/497 on the α subunit, which in turn reduces net phosphorylation at Thr-172. Because diabetic patients often have hyperglucagonemia, AMPKα phosphorylation at Ser-485/497 is a therapeutic target to improve metformin efficacy. PMID:24928508

Input-output Transfer Function Analysis of a Photometer Circuit Based on an Operational Amplifier.

PubMed

Hernandez, Wilmar

2008-01-09

In this paper an input-output transfer function analysis based on the frequencyresponse of a photometer circuit based on operational amplifier (op amp) is carried out. Opamps are universally used in monitoring photodetectors and there are a variety of amplifierconnections for this purpose. However, the electronic circuits that are usually used to carryout the signal treatment in photometer circuits introduce some limitations in theperformance of the photometers that influence the selection of the op amps and otherelectronic devices. For example, the bandwidth, slew-rate, noise, input impedance and gain,among other characteristics of the op amp, are often the performance limiting factors ofphotometer circuits. For this reason, in this paper a comparative analysis between twophotodiode amplifier circuits is carried out. One circuit is based on a conventional currentto-voltage converter connection and the other circuit is based on a robust current-to-voltageconverter connection. The results are satisfactory and show that the photodiode amplifierperformance can be improved by using robust control techniques.

Anchored phosphatases modulate glucose homeostasis

PubMed Central

Hinke, Simon A; Navedo, Manuel F; Ulman, Allison; Whiting, Jennifer L; Nygren, Patrick J; Tian, Geng; Jimenez-Caliani, Antonio J; Langeberg, Lorene K; Cirulli, Vincenzo; Tengholm, Anders; Dell'Acqua, Mark L; Santana, L Fernando; Scott, John D

2012-01-01

Endocrine release of insulin principally controls glucose homeostasis. Nutrient-induced exocytosis of insulin granules from pancreatic β-cells involves ion channels and mobilization of Ca2+ and cyclic AMP (cAMP) signalling pathways. Whole-animal physiology, islet studies and live-β-cell imaging approaches reveal that ablation of the kinase/phosphatase anchoring protein AKAP150 impairs insulin secretion in mice. Loss of AKAP150 impacts L-type Ca2+ currents, and attenuates cytoplasmic accumulation of Ca2+ and cAMP in β-cells. Yet surprisingly AKAP150 null animals display improved glucose handling and heightened insulin sensitivity in skeletal muscle. More refined analyses of AKAP150 knock-in mice unable to anchor protein kinase A or protein phosphatase 2B uncover an unexpected observation that tethering of phosphatases to a seven-residue sequence of the anchoring protein is the predominant molecular event underlying these metabolic phenotypes. Thus anchored signalling events that facilitate insulin secretion and glucose homeostasis may be set by AKAP150 associated phosphatase activity. PMID:22940692

Imaging of persistent cAMP signaling by internalized G protein-coupled receptors.

PubMed

Calebiro, Davide; Nikolaev, Viacheslav O; Lohse, Martin J

2010-07-01

G protein-coupled receptors (GPCRs) are the largest family of plasma membrane receptors. They mediate the effects of several endogenous cues and serve as important pharmacological targets. Although many biochemical events involved in GPCR signaling have been characterized in great detail, little is known about their spatiotemporal dynamics in living cells. The recent advent of optical methods based on fluorescent resonance energy transfer allows, for the first time, to directly monitor GPCR signaling in living cells. Utilizing these methods, it has been recently possible to show that the receptors for two protein/peptide hormones, the TSH and the parathyroid hormone, continue signaling to cAMP after their internalization into endosomes. This type of intracellular signaling is persistent and apparently triggers specific cellular outcomes. Here, we review these recent data and explain the optical methods used for such studies. Based on these findings, we propose a revision of the current model of the GPCR-cAMP signaling pathway to accommodate receptor signaling at endosomes.

Comparative evolutionary diversity and phylogenetic structure across multiple forest dynamics plots: a mega-phylogeny approach

PubMed Central

Erickson, David L.; Jones, Frank A.; Swenson, Nathan G.; Pei, Nancai; Bourg, Norman A.; Chen, Wenna; Davies, Stuart J.; Ge, Xue-jun; Hao, Zhanqing; Howe, Robert W.; Huang, Chun-Lin; Larson, Andrew J.; Lum, Shawn K. Y.; Lutz, James A.; Ma, Keping; Meegaskumbura, Madhava; Mi, Xiangcheng; Parker, John D.; Fang-Sun, I.; Wright, S. Joseph; Wolf, Amy T.; Ye, W.; Xing, Dingliang; Zimmerman, Jess K.; Kress, W. John

2014-01-01

Forest dynamics plots, which now span longitudes, latitudes, and habitat types across the globe, offer unparalleled insights into the ecological and evolutionary processes that determine how species are assembled into communities. Understanding phylogenetic relationships among species in a community has become an important component of assessing assembly processes. However, the application of evolutionary information to questions in community ecology has been limited in large part by the lack of accurate estimates of phylogenetic relationships among individual species found within communities, and is particularly limiting in comparisons between communities. Therefore, streamlining and maximizing the information content of these community phylogenies is a priority. To test the viability and advantage of a multi-community phylogeny, we constructed a multi-plot mega-phylogeny of 1347 species of trees across 15 forest dynamics plots in the ForestGEO network using DNA barcode sequence data (rbcL, matK, and psbA-trnH) and compared community phylogenies for each individual plot with respect to support for topology and branch lengths, which affect evolutionary inference of community processes. The levels of taxonomic differentiation across the phylogeny were examined by quantifying the frequency of resolved nodes throughout. In addition, three phylogenetic distance (PD) metrics that are commonly used to infer assembly processes were estimated for each plot [PD, Mean Phylogenetic Distance (MPD), and Mean Nearest Taxon Distance (MNTD)]. Lastly, we examine the partitioning of phylogenetic diversity among community plots through quantification of inter-community MPD and MNTD. Overall, evolutionary relationships were highly resolved across the DNA barcode-based mega-phylogeny, and phylogenetic resolution for each community plot was improved when estimated within the context of the mega-phylogeny. Likewise, when compared with phylogenies for individual plots, estimates of phylogenetic diversity in the mega-phylogeny were more consistent, thereby removing a potential source of bias at the plot-level, and demonstrating the value of assessing phylogenetic relationships simultaneously within a mega-phylogeny. An unexpected result of the comparisons among plots based on the mega-phylogeny was that the communities in the ForestGEO plots in general appear to be assemblages of more closely related species than expected by chance, and that differentiation among communities is very low, suggesting deep floristic connections among communities and new avenues for future analyses in community ecology. PMID:25414723

First experiment on LMJ facility: pointing and synchronisation qualification, sequences qualification

NASA Astrophysics Data System (ADS)

Henry, Olivier; Raffestin, Didier; Bretheau, Dominique; Luttmann, Michel; Graillot, Herve; Ferri, Michel; Seguineau, Frederic; Bar, Emmanuel; Patissou, Loic; Canal, Philippe; Sautarel, Françoise; Tranquille-Marques, Yves

2015-11-01

The LMJ (Laser mega Joule) facility at the CESTA site (Aquitaine, France) is a tool designed to deliver up to 1.2 MJ at 351 nm. The experiment system will include plasma diagnostics: UV and X energy balances, imagers (Streak and stripe camera, CCD), spectrometers, and a Visar/pyrometer. The facility must be able to deliver, within the hour following the shot, all the results of the plasma diagnostics, alignment images and laser diagnostic measurements. Part of the end of 2014 was devoted to the qualification of system pointing on target and synchronization within and between beams. The shots made with one chain (divided in 2 quads - 8 laser beams) have achieved 50 μm of misalignment accuracy and a synchronization accuracy in the order of 50 ps. The performances achieved for plasma diagnostic (in the order of less 100 μm of alignment and timing accuracy less than 150 ps) comply with expectations. At the same time the first automatic sequences were tested. They allowed a shot on target every 6h:30 and in some case twice a day by reducing preparation actions, leading to a sequence of 4h:00. These shooting sequences are managed by an operating team of 7 people helped by 3 people for security aspects.

First experiment on LMJ facility: pointing and synchronisation qualification

NASA Astrophysics Data System (ADS)

Henry, Olivier; Raffestin, Didier; Bretheau, Dominique; Luttmann, Michel; Graillot, Herve; Ferri, Michel; Seguineau, Frederic; Bar, Emmanuel; Patissou, Loic; Canal, Philippe; Sautarel, Franöise; Tranquille-Marques, Yves

2017-10-01

The LMJ (Laser mega Joule) facility at the CESTA site (Aquitaine, France) is a tool designed to deliver up to 1.2 MJ at 351 nm for plasma experiments. The experiment system will include 11 diagnostics: UV and X energy balances, imagers (Streak and stripe camera, CCD), spectrometers, and a Visar/pyrometer. The facility must be able to deliver, within the hour following the shot, all the results of the plasma diagnostics, alignment images and laser diagnostic measurements. These results have to be guaranteed in terms of conformity to the request and quality of measurement. The end of 2016 was devoted to the qualification of system pointing on target and synchronization within and between beams. The shots made with two chains (divided in 4 quads - 8 laser beams) have achieved 50 µm of misalignment accuracy (chain and quad channel) and a synchronization accuracy in the order of 50 ps . The performances achieved for plasma diagnostic (in the order of less 100 µm of alignment and timing accuracy less than 150 ps) comply with expectations. At the same time the first automatic sequences were tested. They allowed a shot on target every 6h:30 and in some case twice a day by reducing preparation actions, leading to a sequence of 4h:00.

Multifocal multiphoton microscopy with adaptive optical correction

NASA Astrophysics Data System (ADS)

Coelho, Simao; Poland, Simon; Krstajic, Nikola; Li, David; Monypenny, James; Walker, Richard; Tyndall, David; Ng, Tony; Henderson, Robert; Ameer-Beg, Simon

2013-02-01

Fluorescence lifetime imaging microscopy (FLIM) is a well established approach for measuring dynamic signalling events inside living cells, including detection of protein-protein interactions. The improvement in optical penetration of infrared light compared with linear excitation due to Rayleigh scattering and low absorption have provided imaging depths of up to 1mm in brain tissue but significant image degradation occurs as samples distort (aberrate) the infrared excitation beam. Multiphoton time-correlated single photon counting (TCSPC) FLIM is a method for obtaining functional, high resolution images of biological structures. In order to achieve good statistical accuracy TCSPC typically requires long acquisition times. We report the development of a multifocal multiphoton microscope (MMM), titled MegaFLI. Beam parallelization performed via a 3D Gerchberg-Saxton (GS) algorithm using a Spatial Light Modulator (SLM), increases TCSPC count rate proportional to the number of beamlets produced. A weighted 3D GS algorithm is employed to improve homogeneity. An added benefit is the implementation of flexible and adaptive optical correction. Adaptive optics performed by means of Zernike polynomials are used to correct for system induced aberrations. Here we present results with significant improvement in throughput obtained using a novel complementary metal-oxide-semiconductor (CMOS) 1024 pixel single-photon avalanche diode (SPAD) array, opening the way to truly high-throughput FLIM.

Special section introduction on MicroMars to MegaMars

USGS Publications Warehouse

Bridges, Nathan T.; Dundas, Colin M.; Edgar, Lauren

2016-01-01

The study of Earth's surface and atmosphere evolved from local investigations to the incorporation of remote sensing on a global scale. The study of Mars has followed the opposite progression, beginning with telescopic observations, followed by flyby and orbital missions, landers, and finally rover missions in the last ∼20 years. This varied fleet of spacecraft (seven of which are currently operating as of this writing) provides a rich variety of datasets at spatial scales ranging from microscopic images to synoptic orbital remote sensing.

Dynamic characteristic of a 30-cm mercury ion thruster

NASA Technical Reports Server (NTRS)

Serafini, J. S.; Mantenieks, M. A.; Rawlin, V. K.

1975-01-01

Measurements of the fluctuations of the discharge and beam plasmas of a 30 centimeter ion thruster were performed using 60 Hertz laboratory type power supplies. The time-varying properties of the discharge voltage and current, the ion beam current, and neutralizer keeper current were measured. The intensities of the fluctuations were found to depend on the beam and magnetic baffle currents. The shape of the frequency spectra of the discharge plasma fluctuations was found to be related to the beam and magnetic baffle currents. The measurements indicated that the discharge current fluctuations directly contribute to the beam current fluctuations and that the power supply characteristics modify these fluctuations.

Twin plants from supernumerary egg cells in Arabidopsis.

PubMed

Kong, Jixiang; Lau, Steffen; Jürgens, Gerd

2015-01-19

Sexual reproduction of flowering plants is distinguished by double fertilization—the two sperm cells delivered by a pollen tube fuse with the two gametic cells of the female gametophyte, the egg and the central cell—inside the ovule to give rise to the embryo and the nutritive endosperm, respectively. The pollen tube is attracted by nongametic synergid cells, and how these two cells of the female gametophyte are specified is currently unclear. Here, we show that ALTERED MERISTEM PROGRAM 1 (AMP1), encoding a protein associated with the endoplasmic reticulum, is required for synergid cell fate during Arabidopsis female gametophyte development. Loss of AMP1 function leads to supernumerary egg cells at the expense of synergids, enabling the generation of dizygotic twins. However, if twin embryos are formed, endosperm formation is prevented, eventually resulting in ovule abortion. The latter can be overcome by the delivery of supernumerary sperm cells in tetraspore (tes) pollen, enabling the formation of twin plants. Thus, both primary and supernumerary egg cells are fully functional in amp1 mutant plants. Sporophytic AMP1 expression is sufficient to prevent cell-fate change of synergids, indicating that one or more AMP1-dependent mobile signals from outside the female gametophyte can contribute to its patterning, in addition to the previously reported lateral inhibition between gametophytic cells. Our results provide insight into the mechanism of synergid fate specification and emphasize the importance of specifying only one egg cell within the female gametophyte to ensure central-cell fertilization by the second sperm cell. Copyright © 2015 Elsevier Ltd. All rights reserved.

Preliminary measurements of plasma fluctuations in an 8-cm mercury ion thruster

NASA Technical Reports Server (NTRS)

Serafini, J. S.; Nakanishi, S.

1975-01-01

The rms magnitude, spectra, and cross correlations for the fluctuations in the beam current, the neutralizer keeper current, and the discharge current and voltage were measured for an 8-cm diameter, dished grid ion thruster for a beam current of 72 milliamps. The ratio of the rms magnitude of the fluctuations to the time-mean neutralizer keeper current was found to depend significantly on the neutralizer time-mean keeper current, the flow rate, and keeper hold diameter. The maxima of the spectra of the beam current fluctuations did not depend on the discharge fluctuations. It was found that: (1) the discharge current fluctuations do not directly contribute to the beam current fluctuations; and (2) the neutralizer contributions to the beam fluctuations are small (for good neutralizer-to-beam coupling) but not negligible and appear mostly in the higher frequency range measured.

Active spectroscopy upgrades and neutral beam injection on LTX- β

NASA Astrophysics Data System (ADS)

Elliott, Drew; Biewer, Theodore; Canik, John; Reinke, Matthew; Bell, Ronald; Boyle, Dennis; Guttenfelder, Walter; Kaita, Robert; Kozub, Thomas; Majeski, Richard; Merino, Enrique

2017-10-01

The LTX- β upgrade includes the addition of neutral beam injection (NBI) and increased active spectroscopy. Typical plasmas have been and are expected to remain inboard limited, at 14 cm with minor radii of 18-23 cm. The NBI, 35 Amps of 20 keV particles, will enable active diagnosis of ion velocity distribution profiles through charge exchange (CHERS). 18 CHERS views will cover more than a full minor radius, each sampling 2 cm of major radius. The system has both a set of beam directed ``active'' views and a symmetric set of views pointing away from the beam for stray light subtraction. Along with measuring ion temperatures and impurity transport, the CHERS diagnostic will measure the plasma rotation profiles. The recently described low recycling regime is predicted to allow for high rotational velocities due to the low neutral drag. The planned NBI has been predicted to give on axis velocities near 100 km/s. Flow shear is expected to increase confinement in this regime by suppressing trapped electron mode and other microturbulence enhanced transport. Upgrades to the Thomson scattering system, including an array of polychromators and a new camera, will assist in diagnosing the low density hot edge in this low recycling regime. Supported by US DOE contracts DE-AC02-09CH11466 and DE-AC05-00OR22725.

AMPS data management requirements study, appendix 1. [user manuals (computer programs)/display devices - computerized simulation/experimentation/ionosphere

NASA Technical Reports Server (NTRS)

1975-01-01

Flow charts and display formats for the simulation of five experiments are given. The experiments are: (1) electromagnetic wave transmission; (2) passive observations of ambient plasma; (3) ionospheric measurements with subsatellite; (4) electron accelerator beam measurements; and (5) measurement of acoustical gravity waves in the sodium layer using lasers. A detailed explanation of the simulation procedure, definition of variables, and an explanation of how the experimenter makes display choices is also presented. A functional description is included on each flow chart and the assumptions and definitions of terms and scope of the flow charts and displays are presented.

Characterisation and novel applications of glass beads as dosimeters in radiotherapy

NASA Astrophysics Data System (ADS)

Jafari, Shakardokht

The intent of external beam radiotherapy is to deliver as high a radiation dose as possible to tumour volume whilst minimizing the dose to surrounding normal tissues. Recent development of techniques such as intensity modulated radiation therapy (IMRT) and stereotactic ablative body radiotherapy (SABR) aim to extend this capability. The main feature of these techniques is to use beams which often contain small fields and very steep dose gradients. These present several dosimetric challenges including loss of charge particle equilibrium (CPE), partial occlusion of the direct-beam source and steep fall-off in dose in the penumbra. Dosimeters which are small in size relative to the radiation field dimensions are recommended for such conditions. The particular glass beads studied herein have several potentially favourable physical characteristics; they are small in size (1 to 3 mm diameter), chemically inert, inexpensive, readily available and reusable. The dosimetric characterisation of glass beads has been obtained by irradiating them in various radiotherapy beams of kilo-voltage and mega-voltage photons, megavoltage electrons, protons and carbon ions. They exhibit minimal fading compared with commercial LiF thermo-luminescent (TL) dosimeters, have high TL light transparency, high sensitivity and a large dynamic dose range that remains linear from 1 cGy to 100 Gy They have also been shown to be independent of dose rate and beam incidence angle, as well as having a low variation in response with energy over a range of megavoltage photon and electron beams. The latter characteristic is of importance, where spectral changes may occur as a function of field size and off axis location and for the use of dosimeters in postal audit situations where each institution may have slightly different quality index (QI) for their respective photon energies thus ensuring that the calibration is still valid. These properties suggest their practical use as TL dosimeters for radiotherapy dosimetry. Investigations have been performed to evaluate the feasibility of using glass beads in treatment plan verification, small field radiation dosimetry and postal dosimetry audit.

Exchange protein activated by cAMP (Epac) induces vascular relaxation by activating Ca2+-sensitive K+ channels in rat mesenteric artery

PubMed Central

Roberts, Owain Llŷr; Kamishima, Tomoko; Barrett-Jolley, Richard; Quayle, John M; Dart, Caroline

2013-01-01

Vasodilator-induced elevation of intracellular cyclic AMP (cAMP) is a central mechanism governing arterial relaxation but is incompletely understood due to the diversity of cAMP effectors. Here we investigate the role of the novel cAMP effector exchange protein directly activated by cAMP (Epac) in mediating vasorelaxation in rat mesenteric arteries. In myography experiments, the Epac-selective cAMP analogue 8-pCPT-2′-O-Me-cAMP-AM (5 μm, subsequently referred to as 8-pCPT-AM) elicited a 77.6 ± 7.1% relaxation of phenylephrine-contracted arteries over a 5 min period (mean ± SEM; n= 6). 8-pCPT-AM induced only a 16.7 ± 2.4% relaxation in arteries pre-contracted with high extracellular K+ over the same time period (n= 10), suggesting that some of Epac's relaxant effect relies upon vascular cell hyperpolarization. This involves Ca2+-sensitive, large-conductance K+ (BKCa) channel opening as iberiotoxin (100 nm) significantly reduced the ability of 8-pCPT-AM to reverse phenylephrine-induced contraction (arteries relaxed by only 35.0 ± 8.5% over a 5 min exposure to 8-pCPT-AM, n= 5; P < 0.05). 8-pCPT-AM increased Ca2+ spark frequency in Fluo-4-AM-loaded mesenteric myocytes from 0.045 ± 0.008 to 0.103 ± 0.022 sparks s-1μm-1 (P < 0.05) and reversibly increased both the frequency (0.94 ± 0.25 to 2.30 ± 0.72 s−1) and amplitude (23.9 ± 3.3 to 35.8 ± 7.7 pA) of spontaneous transient outward currents (STOCs) recorded in isolated mesenteric myocytes (n= 7; P < 0.05). 8-pCPT-AM-activated STOCs were sensitive to iberiotoxin (100 nm) and to ryanodine (30 μm). Current clamp recordings of isolated myocytes showed a 7.9 ± 1.0 mV (n= 10) hyperpolarization in response to 8-pCPT-AM that was sensitive to iberiotoxin (n= 5). Endothelial disruption suppressed 8-pCPT-AM-mediated relaxation in phenylephrine-contracted arteries (24.8 ± 4.9% relaxation after 5 min of exposure, n= 5; P < 0.05), as did apamin and TRAM-34, blockers of Ca2+-sensitive, small- and intermediate-conductance K+ (SKCa and IKCa) channels, respectively, and NG-nitro-l-arginine methyl ester, an inhibitor of nitric oxide synthase (NOS). In Fluo-4-AM-loaded mesenteric endothelial cells, 8-pCPT-AM induced a sustained increase in global Ca2+. Our data suggest that Epac hyperpolarizes smooth muscle by (1) increasing localized Ca2+ release from ryanodine receptors (Ca2+ sparks) to activate BKCa channels, and (2) endothelial-dependent mechanisms involving the activation of SKCa/IKCa channels and NOS. Epac-mediated smooth muscle hyperpolarization will limit Ca2+ entry via voltage-sensitive Ca2+ channels and represents a novel mechanism of arterial relaxation. PMID:23959673

Start-Up Mega Planning--A Case History

ERIC Educational Resources Information Center

Forbes, Ronald; Forbes, Dylan; Hoskins, Peter

2005-01-01

Social Responsibility is becoming a key issue for organizations today. They talk about it and they make social contributions, but how do we know if anything is being achieved? A framework is required and has existed at least since 1992. Roger Kaufman's Mega Planning has slowly gathered momentum in organizations worldwide. For a faster take-up we…

Treasure Chase: Mega Gifts Are Down--But Are They out?

ERIC Educational Resources Information Center

Mayer, Caroline E.

2010-01-01

Just a few years ago, the University of Notre Dame averaged about six mega gifts--$10 million or more--a year. Last year, however, the Fighting Irish received only one such donation. "That multimillion donation has become more difficult to obtain," says Lou Nanni, vice president for university relations at the Indiana institution.…

Mega Thinking and Planning: An Introduction to Defining and Delivering Individual and Organizational Success

ERIC Educational Resources Information Center

Kaufman, Roger

2009-01-01

All organizations are means to societal ends, and thus Mega thinking and planning starts with a primary focus on adding value for all stakeholders, including our shared society. It is pragmatic, realistic, practical, and ethical. Defining and achieving continual organizational success is possible. It relies on three basic elements: (1) a societal…

Defining and Delivering Measurable Value: A Mega Thinking and Planning Primer

ERIC Educational Resources Information Center

Kaufman, Roger

2005-01-01

Mega planning has a primary focus on adding value for all stakeholders. It is realistic, practical, and ethical. Denning and then achieving sustained organizational success is possible. It relies on three basic elements: (1) "A societal value-added "frame of mind" or paradigm": your perspective about your organization, people, and our world. It…

OER on the Asian Mega Universities: Developments, Motives, Openness, and Sustainability

ERIC Educational Resources Information Center

Farisi, Mohammad Imam

2013-01-01

The OER movement originated and integrated into ODE developments. Mega Universities (MUs) are among the most important of ODE providers worldwide should be to be the primary organizations for providing access to OER. So far, however, in-depth studies on OER developments in the Asian MUs were very limited. This study focuses on the developments,…

Why Academics Choose to Publish in a Mega-Journal

ERIC Educational Resources Information Center

Shopovski, Jovan; Marolov, Dejan

2017-01-01

With their broad scope, high publishing volume, a peer review process based on the scientific soundness of the content, and an open access model, mega journals have become an important part of scholarly publishing. The main aim of this paper is to determine the most important factor that influenced researchers' decisions to submit their academic…

Comparison of mega-voltage cone-beam computed tomography prostate localization with online ultrasound and fiducial markers methods

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gayou, Olivier; Miften, Moyed

2008-02-15

The online image-guided localization data from 696 ultrasound (United States), 598 mega-voltage cone-beam computed tomography (MV-CBCT), and 393 seed markers (SMs) couch alignments for patients undergoing intensity modulation radiotherapy of the prostate were analyzed. Daily US, MV-CBCT and SM images were acquired for 19, 17 and 12 patients, respectively, after each patient was immobilized in a vacuum cradle and setup to skin markers as the center of mass. The couch shifts applied in the lateral (left-right/LR), vertical (anterior-posterior/AP), and longitudinal (superior-inferior/SI) directions, along with the magnitude of the three-dimensional (3D) shift vector, were analyzed and compared for all three methods.more » The percentage of shifts larger than 5 mm in all directions was also compared. Clinical target volume-planning target volume (CTV-to-PTV) expansion margins were estimated based on the localization data with US, CB, and SM image guidance. Results show the US data have greater variability. Systematic and random shifts were -1.2{+-}6.8 mm (LR), -2.8{+-}5.1 mm (SI) and -1.0{+-}5.9 mm (AP) for US, 1.0{+-}3.9 mm (LR), -1.3{+-}2.5 mm (SI) and -0.3{+-}3.9 mm (AP) for CB, and -1.0{+-}3.4 mm (LR), 0.0{+-}3.4 mm (SI) and 0.5{+-}4.1 mm (AP) for SM. The mean 3D shift distance was larger using US (8.8{+-}6.2 mm) compared to CB and SM (5.3{+-}3.4 mm and 5.2{+-}3.7 mm, respectively). The percentage of US shifts larger than 5 mm were 34%, 31%, and 38% in the LR, SI, and AP directions, respectively, compared to 18%, 6%, and 16% for CB and 14%, 10%, and 20% for SM. MV-CBCT and SM localization data suggest a different distribution of prostate center-of-mass shifts with smaller variability, compared to US. The online MV-CBCT and SM image-guidance data show that for treatments that do not include daily prostate localization, one can use a CTV-to-PTV margin that is 4 mm smaller than the one suggested by US data, hence allowing more rectum and bladder sparing and potentially improving the therapeutic ratio.« less

Plasma fluctuations in a Kaufman thruster. [root mean square magnitude, spectra and cross correlation

NASA Technical Reports Server (NTRS)

Serafini, J. S.; Terdan, F. F.

1973-01-01

Measurements of the RMS magnitude, spectra and cross-correlations for the fluctuations in the beam, discharge and neutralizer keeper currents are presented for a 30-cm diameter dished grid ion thrustor for a range of magnetic baffle currents and up to 2.0 amperes beam current. The ratio of RMS to mean ion beam current varied from 0.04 to 0.23. The spectra of the amplitudes of the beam and discharge current fluctuations were taken up to 9 MHz and show that the predominant amplitudes occur at frequencies of 10 kHz or below. The fall-off with increasing frequency is rapid. Frequencies above 100 kHz the spectral levels are 45 kb or more below the maximum peak amplitudes. The cross-correlations revealed the ion beam fluctuations to have large radial and axial scales which implied that the beam fluctuates as a whole or 'in-phase.' The cross-correlations of the beam and neutralizer keeper current fluctuations indicated the neutralizer contributions to the beam fluctuations to be small, but not negligible. The mode of operation of the thrustor (values of beam and magnetic baffle currents) was significant in determining the RMS magnitude and spectral shape of the beam fluctuations. The major oscillations were not found to be directly dependent on the power conditioner inverter frequencies.

Purification, characterization, and sequencing of novel antimicrobial peptides, Tu-AMP 1 and Tu-AMP 2, from bulbs of tulip (Tulipa gesneriana L.).

PubMed

Fujimura, Masatoshi; Ideguchi, Mineo; Minami, Yuji; Watanabe, Keiichi; Tadera, Kenjiro

2004-03-01

Novel antimicrobial peptides (AMP), designated Tu-AMP 1 and Tu-AMP 2, were purified from the bulbs of tulip (Tulipa gesneriana L.) by chitin affinity chromatography and reverse-phase high-performance liquid chromatography (HPLC). They bind to chitin in a reversible way. They were basic peptides having isoelectric points of over 12. Tu-AMP 1 and Tu-AMP 2 had molecular masses of 4,988 Da and 5,006 Da on MALDI-TOF MS analysis, and their extinction coefficients of 1% aqueous solutions at 280 nm were 3.3 and 3.4, respectively. Half of all amino acid residues of Tu-AMP 1 and Tu-AMP 2 were occupied by cysteine, arginine, lysine, and proline. The concentrations of peptides required for 50% inhibition (IC(50)) of the growth of plant pathogenic bacteria and fungi were 2 to 20 microg/ml. The structural characteristics of Tu-AMP 1 and Tu-AMP 2 indicated that they were novel thionin-like antimicrobial peptides, though Tu-AMP 2 was a heterodimer composes of two short peptides joined with disulfide bonds.

Special Delivery | The UCSB Current

Science.gov Websites

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Current topics in membranes and transport

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kleinzeller, A.

1987-01-01

This book contains 10 chapters. Some of the chapter titles are: Expression of the Oxytocin and Vasopressin Genes; Steroid Effects on Excitable Membranes: The Secretory Vesicle in Processing and Secretion of Neuropeptides: and Steroid Hormone Influences on Cyclic AMP-Generating Systems.

Dynamics of a high-current relativistic electron beam

DOE Office of Scientific and Technical Information (OSTI.GOV)

Strelkov, P. S., E-mail: strelkov@fpl.gpi.ru; Tarakanov, V. P., E-mail: karat@gmail.ru; Ivanov, I. E., E-mail: iei@fpl.gpi.ru

2015-06-15

The dynamics of a high-current relativistic electron beam is studied experimentally and by numerical simulation. The beam is formed in a magnetically insulated diode with a transverse-blade explosive-emission cathode. It is found experimentally that the radius of a 500-keV beam with a current of 2 kA and duration of 500 ns decreases with time during the beam current pulse. The same effect was observed in numerical simulations. This effect is explained by a change in the shape of the cathode plasma during the current pulse, which, according to calculations, leads to a change in the beam parameters, such as themore » electron pitch angle and the spread over the longitudinal electron momentum. These parameters are hard to measure experimentally; however, the time evolution of the radial profile of the beam current density, which can be measured reliably, coincides with the simulation results. This allows one to expect that the behavior of the other beam parameters also agrees with numerical simulations.« less

Role of 2',3'-cyclic nucleotide 3'-phosphodiesterase in the renal 2',3'-cAMP-adenosine pathway.

PubMed

Jackson, Edwin K; Gillespie, Delbert G; Mi, Zaichuan; Cheng, Dongmei; Bansal, Rashmi; Janesko-Feldman, Keri; Kochanek, Patrick M

2014-07-01

Energy depletion increases the renal production of 2',3'-cAMP (a positional isomer of 3',5'-cAMP that opens mitochondrial permeability transition pores) and 2',3'-cAMP is converted to 2'-AMP and 3'-AMP, which in turn are metabolized to adenosine. Because the enzymes involved in this "2',3'-cAMP-adenosine pathway" are unknown, we examined whether 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNPase) participates in the renal metabolism of 2',3'-cAMP. Western blotting and real-time PCR demonstrated expression of CNPase in rat glomerular mesangial, preglomerular vascular smooth muscle and endothelial, proximal tubular, thick ascending limb and collecting duct cells. Real-time PCR established the expression of CNPase in human glomerular mesangial, proximal tubular and vascular smooth muscle cells; and the level of expression of CNPase was greater than that for phosphodiesterase 4 (major enzyme for the metabolism of 3',5'-cAMP). Overexpression of CNPase in rat preglomerular vascular smooth muscle cells increased the metabolism of exogenous 2',3'-cAMP to 2'-AMP. Infusions of 2',3'-cAMP into isolated CNPase wild-type (+/+) kidneys increased renal venous 2'-AMP, and this response was diminished by 63% in CNPase knockout (-/-) kidneys, whereas the conversion of 3',5'-cAMP to 5'-AMP was similar in CNPase +/+ vs. -/- kidneys. In CNPase +/+ kidneys, energy depletion (metabolic poisons) increased kidney tissue levels of adenosine and its metabolites (inosine, hypoxanthine, xanthine, and uric acid) without accumulation of 2',3'-cAMP. In contrast, in CNPase -/- kidneys, energy depletion increased kidney tissue levels of 2',3'-cAMP and abolished the increase in adenosine and its metabolites. In conclusion, kidneys express CNPase, and renal CNPase mediates in part the renal 2',3'-cAMP-adenosine pathway. Copyright © 2014 the American Physiological Society.

Mutating the Conserved Q-loop Glutamine 1291 Selectively Disrupts Adenylate Kinase-dependent Channel Gating of the ATP-binding Cassette (ABC) Adenylate Kinase Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) and Reduces Channel Function in Primary Human Airway Epithelia*

PubMed Central

Dong, Qian; Ernst, Sarah E.; Ostedgaard, Lynda S.; Shah, Viral S.; Ver Heul, Amanda R.; Welsh, Michael J.; Randak, Christoph O.

2015-01-01

The ATP-binding cassette (ABC) transporter cystic fibrosis transmembrane conductance regulator (CFTR) and two other non-membrane-bound ABC proteins, Rad50 and a structural maintenance of chromosome (SMC) protein, exhibit adenylate kinase activity in the presence of physiologic concentrations of ATP and AMP or ADP (ATP + AMP ⇆ 2 ADP). The crystal structure of the nucleotide-binding domain of an SMC protein in complex with the adenylate kinase bisubstrate inhibitor P1,P5-di(adenosine-5′) pentaphosphate (Ap5A) suggests that AMP binds to the conserved Q-loop glutamine during the adenylate kinase reaction. Therefore, we hypothesized that mutating the corresponding residue in CFTR, Gln-1291, selectively disrupts adenylate kinase-dependent channel gating at physiologic nucleotide concentrations. We found that substituting Gln-1291 with bulky side-chain amino acids abolished the effects of Ap5A, AMP, and adenosine 5′-monophosphoramidate on CFTR channel function. 8-Azidoadenosine 5′-monophosphate photolabeling of the AMP-binding site and adenylate kinase activity were disrupted in Q1291F CFTR. The Gln-1291 mutations did not alter the potency of ATP at stimulating current or ATP-dependent gating when ATP was the only nucleotide present. However, when physiologic concentrations of ADP and AMP were added, adenylate kinase-deficient Q1291F channels opened significantly less than wild type. Consistent with this result, we found that Q1291F CFTR displayed significantly reduced Cl− channel function in well differentiated primary human airway epithelia. These results indicate that a highly conserved residue of an ABC transporter plays an important role in adenylate kinase-dependent CFTR gating. Furthermore, the results suggest that adenylate kinase activity is important for normal CFTR channel function in airway epithelia. PMID:25887396

Mutating the Conserved Q-loop Glutamine 1291 Selectively Disrupts Adenylate Kinase-dependent Channel Gating of the ATP-binding Cassette (ABC) Adenylate Kinase Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) and Reduces Channel Function in Primary Human Airway Epithelia.

PubMed

Dong, Qian; Ernst, Sarah E; Ostedgaard, Lynda S; Shah, Viral S; Ver Heul, Amanda R; Welsh, Michael J; Randak, Christoph O

2015-05-29

The ATP-binding cassette (ABC) transporter cystic fibrosis transmembrane conductance regulator (CFTR) and two other non-membrane-bound ABC proteins, Rad50 and a structural maintenance of chromosome (SMC) protein, exhibit adenylate kinase activity in the presence of physiologic concentrations of ATP and AMP or ADP (ATP + AMP ⇆ 2 ADP). The crystal structure of the nucleotide-binding domain of an SMC protein in complex with the adenylate kinase bisubstrate inhibitor P(1),P(5)-di(adenosine-5') pentaphosphate (Ap5A) suggests that AMP binds to the conserved Q-loop glutamine during the adenylate kinase reaction. Therefore, we hypothesized that mutating the corresponding residue in CFTR, Gln-1291, selectively disrupts adenylate kinase-dependent channel gating at physiologic nucleotide concentrations. We found that substituting Gln-1291 with bulky side-chain amino acids abolished the effects of Ap5A, AMP, and adenosine 5'-monophosphoramidate on CFTR channel function. 8-Azidoadenosine 5'-monophosphate photolabeling of the AMP-binding site and adenylate kinase activity were disrupted in Q1291F CFTR. The Gln-1291 mutations did not alter the potency of ATP at stimulating current or ATP-dependent gating when ATP was the only nucleotide present. However, when physiologic concentrations of ADP and AMP were added, adenylate kinase-deficient Q1291F channels opened significantly less than wild type. Consistent with this result, we found that Q1291F CFTR displayed significantly reduced Cl(-) channel function in well differentiated primary human airway epithelia. These results indicate that a highly conserved residue of an ABC transporter plays an important role in adenylate kinase-dependent CFTR gating. Furthermore, the results suggest that adenylate kinase activity is important for normal CFTR channel function in airway epithelia. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Studies of beam injection with a compensated bump and uncompensated bump in a synchrotron

DOE Office of Scientific and Technical Information (OSTI.GOV)

Akbar Fakhri, Ali; Prajapati, S. K.; Ghodke, A. D.

2013-08-15

Synchrotron radiation sources Indus-1 and Indus-2 have a synchrotron as the common injector. A three kicker compensated bump injection scheme was employed for beam injection into this synchrotron. The stored beam current in the synchrotron is higher, when all the three kickers are operated at the same current than when kickers are operated at currents required to generate compensated bump. Beam dynamics studies have been done to understand why this happens. Theoretical studies indicate that higher stored current in the later case is attributed to smaller residual oscillations of injected beam. These studies also reveal that if the angle ofmore » the injected beam during beam injection is kept varying, the performance could be further improved. This is experimentally confirmed by injecting the beam on rising part of the injection septum magnet current pulse.« less

A novel comparison of Møller and Compton electron-beam polarimeters

DOE PAGES

Magee, J. A.; Narayan, A.; Jones, D.; ...

2017-01-19

We have performed a novel comparison between electron-beam polarimeters based on Moller and Compton scattering. A sequence of electron-beam polarization measurements were performed at low beam currents (more » $<$ 5 $$\\mu$$A) during the $$Q_{\\rm weak}$$ experiment in Hall C at Jefferson Lab. These low current measurements were bracketed by the regular high current (180 $$\\mu$$A) operation of the Compton polarimeter. All measurements were found to be consistent within experimental uncertainties of 1% or less, demonstrating that electron polarization does not depend significantly on the beam current. This result lends confidence to the common practice of applying Moller measurements made at low beam currents to physics experiments performed at higher beam currents. Here, the agreement between two polarimetry techniques based on independent physical processes sets an important benchmark for future precision asymmetry measurements that require sub-1% precision in polarimetry.« less

A novel comparison of Møller and Compton electron-beam polarimeters

DOE Office of Scientific and Technical Information (OSTI.GOV)

Magee, J. A.; Narayan, A.; Jones, D.

We have performed a novel comparison between electron-beam polarimeters based on Moller and Compton scattering. A sequence of electron-beam polarization measurements were performed at low beam currents (more » $<$ 5 $$\\mu$$A) during the $$Q_{\\rm weak}$$ experiment in Hall C at Jefferson Lab. These low current measurements were bracketed by the regular high current (180 $$\\mu$$A) operation of the Compton polarimeter. All measurements were found to be consistent within experimental uncertainties of 1% or less, demonstrating that electron polarization does not depend significantly on the beam current. This result lends confidence to the common practice of applying Moller measurements made at low beam currents to physics experiments performed at higher beam currents. Here, the agreement between two polarimetry techniques based on independent physical processes sets an important benchmark for future precision asymmetry measurements that require sub-1% precision in polarimetry.« less

Measurements of high-current electron beams from X pinches and wire array Z pinches.

PubMed

Shelkovenko, T A; Pikuz, S A; Blesener, I C; McBride, R D; Bell, K S; Hammer, D A; Agafonov, A V; Romanova, V M; Mingaleev, A R

2008-10-01

Some issues concerning high-current electron beam transport from the X pinch cross point to the diagnostic system and measurements of the beam current by Faraday cups are discussed. Results of computer simulation of electron beam propagation from the pinch to the Faraday cup give limits for the measured current for beams having different energy spreads. The beam is partially neutralized as it propagates from the X pinch to a diagnostic system, but within a Faraday cup diagnostic, space charge effects can be very important. Experimental results show evidence of such effects.

Loss of absorptive capacity for sodium and chloride in the colon causes diarrhoea in Potomac horse fever.

PubMed

Rikihisa, Y; Johnson, G C; Wang, Y Z; Reed, S M; Fertel, R; Cooke, H J

1992-05-01

Ehrlichia risticii, an obligate intracellular bacterium in the family Rickettsiaceae, causes Potomac horse fever which is often associated with severe watery diarrhoea. The mechanism of the diarrhoea is unknown. The aim of this study was to determine whether sodium and chloride transport, morphology and cyclic adenosine 3', 5'-monophosphate (cyclic AMP) content of colonic mucosa was altered in E risticii-infected horses. Mucosa-submucosa sheets from the large and small colon of nine infected and seven to nine uninfected horses were set up in Ussing chambers for measurement of short-circuit current and transepithelial 22Na and 36Cl fluxes. Uninfected tissues absorbed both sodium and chloride whereas absorption of sodium and chloride was abolished in infected tissues. Bethanechol and histamine evoked a concentration-dependent increase in short-circuit current in both groups, but the responses were attenuated at all concentrations in infected horses. Slight focal degeneration of colonic epithelial cells and loss of microvilli from glandular epithelial cells occurred in infected horses. There was a significant increase in cyclic AMP content in colonic mucosa of infected animals. The results suggest that E risticii infection induces focal microscopic degeneration of epithelial cells and an increase in intracellular cyclic AMP in colonic mucosa. These alterations are associated with malabsorption of sodium and chloride and could cause diarrhoea.

An Improved Zero Potential Circuit for Readout of a Two-Dimensional Resistive Sensor Array

PubMed Central

Wu, Jian-Feng; Wang, Feng; Wang, Qi; Li, Jian-Qing; Song, Ai-Guo

2016-01-01

With one operational amplifier (op-amp) in negative feedback, the traditional zero potential circuit could access one element in the two-dimensional (2-D) resistive sensor array with the shared row-column fashion but it suffered from the crosstalk problem for the non-scanned elements’ bypass currents, which were injected into array’s non-scanned electrodes from zero potential. Firstly, for suppressing the crosstalk problem, we designed a novel improved zero potential circuit with one more op-amp in negative feedback to sample the total bypass current and calculate the precision resistance of the element being tested (EBT) with it. The improved setting non-scanned-electrode zero potential circuit (S-NSE-ZPC) was given as an example for analyzing and verifying the performance of the improved zero potential circuit. Secondly, in the S-NSE-ZPC and the improved S-NSE-ZPC, the effects of different parameters of the resistive sensor arrays and their readout circuits on the EBT’s measurement accuracy were simulated with the NI Multisim 12. Thirdly, part features of the improved circuit were verified with the experiments of a prototype circuit. Followed, the results were discussed and the conclusions were given. The experiment results show that the improved circuit, though it requires one more op-amp, one more resistor and one more sampling channel, can access the EBT in the 2-D resistive sensor array more accurately. PMID:27929410

An Improved Zero Potential Circuit for Readout of a Two-Dimensional Resistive Sensor Array.

PubMed

Wu, Jian-Feng; Wang, Feng; Wang, Qi; Li, Jian-Qing; Song, Ai-Guo

2016-12-06

With one operational amplifier (op-amp) in negative feedback, the traditional zero potential circuit could access one element in the two-dimensional (2-D) resistive sensor array with the shared row-column fashion but it suffered from the crosstalk problem for the non-scanned elements' bypass currents, which were injected into array's non-scanned electrodes from zero potential. Firstly, for suppressing the crosstalk problem, we designed a novel improved zero potential circuit with one more op-amp in negative feedback to sample the total bypass current and calculate the precision resistance of the element being tested (EBT) with it. The improved setting non-scanned-electrode zero potential circuit (S-NSE-ZPC) was given as an example for analyzing and verifying the performance of the improved zero potential circuit. Secondly, in the S-NSE-ZPC and the improved S-NSE-ZPC, the effects of different parameters of the resistive sensor arrays and their readout circuits on the EBT's measurement accuracy were simulated with the NI Multisim 12. Thirdly, part features of the improved circuit were verified with the experiments of a prototype circuit. Followed, the results were discussed and the conclusions were given. The experiment results show that the improved circuit, though it requires one more op-amp, one more resistor and one more sampling channel, can access the EBT in the 2-D resistive sensor array more accurately.

New insight into the binding modes of TNP-AMP to human liver fructose-1,6-bisphosphatase

NASA Astrophysics Data System (ADS)

Han, Xinya; Huang, Yunyuan; Zhang, Rui; Xiao, San; Zhu, Shuaihuan; Qin, Nian; Hong, Zongqin; Wei, Lin; Feng, Jiangtao; Ren, Yanliang; Feng, Lingling; Wan, Jian

2016-08-01

Human liver fructose-1,6-bisphosphatase (FBPase) contains two binding sites, a substrate fructose-1,6-bisphosphate (FBP) active site and an adenosine monophosphate (AMP) allosteric site. The FBP active site works by stabilizing the FBPase, and the allosteric site impairs the activity of FBPase through its binding of a nonsubstrate molecule. The fluorescent AMP analogue, 2‧,3‧-O-(2,4,6-trinitrophenyl)adenosine 5‧-monophosphate (TNP-AMP) has been used as a fluorescent probe as it is able to competitively inhibit AMP binding to the AMP allosteric site and, therefore, could be used for exploring the binding modes of inhibitors targeted on the allosteric site. In this study, we have re-examined the binding modes of TNP-AMP to FBPase. However, our present enzyme kinetic assays show that AMP and FBP both can reduce the fluorescence from the bound TNP-AMP through competition for FBPase, suggesting that TNP-AMP binds not only to the AMP allosteric site but also to the FBP active site. Mutagenesis assays of K274L (located in the FBP active site) show that the residue K274 is very important for TNP-AMP to bind to the active site of FBPase. The results further prove that TNP-AMP is able to bind individually to the both sites. Our present study provides a new insight into the binding mechanism of TNP-AMP to the FBPase. The TNP-AMP fluorescent probe can be used to exam the binding site of an inhibitor (the active site or the allosteric site) using FBPase saturated by AMP and FBP, respectively, or the K247L mutant FBPase.

New insight into the binding modes of TNP-AMP to human liver fructose-1,6-bisphosphatase.

PubMed

Han, Xinya; Huang, Yunyuan; Zhang, Rui; Xiao, San; Zhu, Shuaihuan; Qin, Nian; Hong, Zongqin; Wei, Lin; Feng, Jiangtao; Ren, Yanliang; Feng, Lingling; Wan, Jian

2016-08-05

Human liver fructose-1,6-bisphosphatase (FBPase) contains two binding sites, a substrate fructose-1,6-bisphosphate (FBP) active site and an adenosine monophosphate (AMP) allosteric site. The FBP active site works by stabilizing the FBPase, and the allosteric site impairs the activity of FBPase through its binding of a nonsubstrate molecule. The fluorescent AMP analogue, 2',3'-O-(2,4,6-trinitrophenyl)adenosine 5'-monophosphate (TNP-AMP) has been used as a fluorescent probe as it is able to competitively inhibit AMP binding to the AMP allosteric site and, therefore, could be used for exploring the binding modes of inhibitors targeted on the allosteric site. In this study, we have re-examined the binding modes of TNP-AMP to FBPase. However, our present enzyme kinetic assays show that AMP and FBP both can reduce the fluorescence from the bound TNP-AMP through competition for FBPase, suggesting that TNP-AMP binds not only to the AMP allosteric site but also to the FBP active site. Mutagenesis assays of K274L (located in the FBP active site) show that the residue K274 is very important for TNP-AMP to bind to the active site of FBPase. The results further prove that TNP-AMP is able to bind individually to the both sites. Our present study provides a new insight into the binding mechanism of TNP-AMP to the FBPase. The TNP-AMP fluorescent probe can be used to exam the binding site of an inhibitor (the active site or the allosteric site) using FBPase saturated by AMP and FBP, respectively, or the K247L mutant FBPase. Copyright © 2016 Elsevier B.V. All rights reserved.

Gating, modulation and subunit composition of voltage-gated K+ channels in dendritic inhibitory interneurones of rat hippocampus

PubMed Central

Lien, Cheng-Chang; Martina, Marco; Schultz, Jobst H; Ehmke, Heimo; Jonas, Peter

2002-01-01

GABAergic interneurones are diverse in their morphological and functional properties. Perisomatic inhibitory cells show fast spiking during sustained current injection, whereas dendritic inhibitory cells fire action potentials with lower frequency. We examined functional and molecular properties of K+ channels in interneurones with horizontal dendrites in stratum oriens-alveus (OA) of the hippocampal CA1 region, which mainly comprise somatostatin-positive dendritic inhibitory cells. Voltage-gated K+ currents in nucleated patches isolated from OA interneurones consisted of three major components: a fast delayed rectifier K+ current component that was highly sensitive to external 4-aminopyridine (4-AP) and tetraethylammonium (TEA) (half-maximal inhibitory concentrations < 0.1 mm for both blockers), a slow delayed rectifier K+ current component that was sensitive to high concentrations of TEA, but insensitive to 4-AP, and a rapidly inactivating A-type K+ current component that was blocked by high concentrations of 4-AP, but resistant to TEA. The relative contributions of these components to the macroscopic K+ current were estimated as 57 ± 5, 25 ± 6, and 19 ± 2 %, respectively. Dendrotoxin, a selective blocker of Kv1 channels had only minimal effects on K+ currents in nucleated patches. Coapplication of the membrane-permeant cAMP analogue 8-(4-chlorophenylthio)-adenosine 3′:5′-cyclic monophosphate (cpt-cAMP) and the phosphodiesterase blocker isobutyl-methylxanthine (IBMX) resulted in a selective inhibition of the fast delayed rectifier K+ current component. This inhibition was absent in the presence of the protein kinase A (PKA) inhibitor H-89, implying the involvement of PKA-mediated phosphorylation. Single-cell reverse transcription-polymerase chain reaction (RT-PCR) analysis revealed a high abundance of Kv3.2 mRNA in OA interneurones, whereas the expression level of Kv3.1 mRNA was markedly lower. Similarly, RT-PCR analysis showed a high abundance of Kv4.3 mRNA, whereas Kv4.2 mRNA was undetectable. This suggests that the fast delayed rectifier K+ current and the A-type K+ current component are mediated predominantly by homomeric Kv3.2 and Kv4.3 channels. Selective modulation of Kv3.2 channels in OA interneurones by cAMP is likely to be an important factor regulating the activity of dendritic inhibitory cells in principal neurone-interneurone microcircuits. PMID:11790809

Sensitivity of GBM cells to cAMP agonist-mediated apoptosis correlates with CD44 expression and agonist resistance with MAPK signaling.

PubMed

Daniel, Paul M; Filiz, Gulay; Mantamadiotis, Theo

2016-12-01

In some cell types, activation of the second messenger cAMP leads to increased expression of proapoptotic Bim and subsequent cell death. We demonstrate that suppression of the cAMP pathway is a common event across many cancers and that pharmacological activation of cAMP in glioblastoma (GBM) cells leads to enhanced BIM expression and apoptosis in specific GBM cell types. We identified the MAPK signaling axis as the determinant of cAMP agonist sensitivity in GBM cells, with high MAPK activity corresponding to cAMP resistance and low activity corresponding to sensitization to cAMP-induced apoptosis. Sensitive cells were efficiently killed by cAMP agonists alone, while targeting both the cAMP and MAPK pathways in resistant GBM cells resulted in efficient apoptosis. We also show that CD44 is differentially expressed in cAMP agonist-sensitive and -resistant cells. We thus propose that CD44 may be a useful biomarker for distinguishing tumors that may be sensitive to cAMP agonists alone or cAMP agonists in combination with other pathway inhibitors. This suggests that using existing chemotherapeutic compounds in combination with existing FDA-approved cAMP agonists may fast track trials toward improved therapies for difficult-to-treat cancers, such as GBM.

Study of the VMM1 read-out chip in a neutron irradiation environment

NASA Astrophysics Data System (ADS)

Alexopoulos, T.; Fanourakis, G.; Geralis, T.; Kokkoris, M.; Kourkoumeli-Charalampidi, A.; Papageorgiou, K.; Tsipolitis, G.

2016-05-01

Within 2015, the LHC operated close to the design energy of √s = 13-14 TeV delivering instantaneous luminosities up to Script L = 5 × 1033 cm-2s-1. The ATLAS Phase-I upgrade in 2018/19 will introduce the MicroMEGAS detectors in the area of the small wheel at the end caps. Accompanying new electronics are designed and built such as the VMM front end ASIC, which provides energy, timing and triggering information and allows fast data read-out. The first VMM version (VMM1) has been widely produced and tested in various test beams, whilst the second version (VMM2) is currently being tested. This paper focuses on the VMM1 single event upset studies and more specifically on the response of the configuration registers under harsh radiation environments. Similar conditions are expected at Run III with Script L = 2 × 1034 cm-2s-1 and a mean of 55 interactions per bunch crossing. Two VMM1s were exposed in a neutron irradiation environment using the TANDEM Van Der Graaff accelerator at NSCR Demokritos, Athens, Greece. The results showed a rate of SEU occurrences at a measured cross section of (4.1±0.8)×10-14 cm2/bit for each VMM. Consequently, when extrapolating this value to the luminosity expected in Run III, the occurrence is roughly 6 SEUs/min in all the read-out system comprising 40,000 VMMs installed during the Phase-I upgrade.

Link between mechanical strength and laser damage threshold for antireflective coating made by sol-gel

NASA Astrophysics Data System (ADS)

Avice, J.; Piombini, H.; Boscher, C.; Belleville, P.; Vaudel, G.; Brotons, G.; Ruello, P.; Gusev, V.

2017-11-01

The MegaJoule Laser (LMJ) for inertial confinement fusion experiments is currently in operation at CEA-CESTA in France. All the lenses are coated by an antireflective (AR) layer to optimize the light power transmission. This AR layer is manufactured by sol-gel process, a soft chemical process, associated with a liquid phase coating technique to realize thin film of metal oxide. These optical components are hardened into ammoniac vapors in order to mechanically reinforce the AR coating and to make them more handling. This hardening induces a thickness reduction of the layer so an increase of the stiffness and sometimes a crazing of the layer. As these optical components undergo a high-power laser beam, so, it is important to verify if the AR properties (optical and mechanical) influence the value of the threshold laser damage. A series of coated samples have been manufactured having variable elastic moduli to discuss this point. In that purpose, a homemade Laser Induced Damage Threshold (LIDT) setup has been developed to test the layers under laser flux. We describe the used methods and different results are given. Preliminary results obtained on several coated samples with variable elastic moduli are presented. We show that whatever are the elastic stiffness of the AR coating, an overall decrease of the threshold appears with no noticeable effect of the mechanical properties of the AR coatings. Some possible explanations are given.

Mega-analysis of Odds Ratio: A Convergent Method for a Deep Understanding of the Genetic Evidence in Schizophrenia.

PubMed

Jia, Peilin; Chen, Xiangning; Xie, Wei; Kendler, Kenneth S; Zhao, Zhongming

2018-06-20

Numerous high-throughput omics studies have been conducted in schizophrenia, providing an accumulated catalog of susceptible variants and genes. The results from these studies, however, are highly heterogeneous. The variants and genes nominated by different omics studies often have limited overlap with each other. There is thus a pressing need for integrative analysis to unify the different types of data and provide a convergent view of schizophrenia candidate genes (SZgenes). In this study, we collected a comprehensive, multidimensional dataset, including 7819 brain-expressed genes. The data hosted genome-wide association evidence in genetics (eg, genotyping data, copy number variations, de novo mutations), epigenetics, transcriptomics, and literature mining. We developed a method named mega-analysis of odds ratio (MegaOR) to prioritize SZgenes. Application of MegaOR in the multidimensional data resulted in consensus sets of SZgenes (up to 530), each enriched with dense, multidimensional evidence. We proved that these SZgenes had highly tissue-specific expression in brain and nerve and had intensive interactions that were significantly stronger than chance expectation. Furthermore, we found these SZgenes were involved in human brain development by showing strong spatiotemporal expression patterns; these characteristics were replicated in independent brain expression datasets. Finally, we found the SZgenes were enriched in critical functional gene sets involved in neuronal activities, ligand gated ion signaling, and fragile X mental retardation protein targets. In summary, MegaOR analysis reported consensus sets of SZgenes with enriched association evidence to schizophrenia, providing insights into the pathophysiology underlying schizophrenia.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pak, S.; Sites, J.R.

A Kaufman-type broad beam ion source, used for sputtering and etching purposes, has been operated with Ar, Kr,O/sub 2/ and N/sub 2/ gas inputs over a wide range of beam energies (200-1200 eV) and gas flow rates (1-10 sccm). The maximum ion beam current density for each gas saturates at about 2.5 mA/sq. cm. as gas flow is increased. The discharge threshold voltage necessary to produce a beam and the beam efficiency (beam current/molecular current), however, varied considerably. Kr had the lowest threshold and highest efficiency, Ar next, then N/sub 2/ and O/sub 2/. The ion beam current varied onlymore » weakly with beam energy for low gas flow rates, but showed a factor of two increase when the gas flow was higher.« less

Unprecedented permafrost thaw dynamics on a decadal time scale: Batagay mega thaw slump development, Yana Uplands, Yakutia, Russia

NASA Astrophysics Data System (ADS)

Günther, F.; Grosse, G.; Jones, B. M.; Schirrmeister, L.; Romanovsky, V. E.; Kunitsky, V.

2016-12-01

Ice-rich permafrost that formed in glacial periods of the Quaternary is highly vulnerable to thaw under ongoing climate warming and anthropogenic disturbance. The mega thaw slump near the village of Batagay (Yakutia, Russia) is an outstanding example of permafrost degradation and demonstrates that thermo-erosion processes may occur in unexpected locations, develop very rapidly in particular after disturbances, and leave behind deep rutted badlands. Retrogressive thaw slumps are particularly frequent along riverbanks and coastlines of regions where buried glacier ice or ice-rich glacial till have been mapped. In East Siberia, syngenetic Late Pleistocene Ice Complex (Yedoma) permafrost deposits accumulate volumetric ground ice contents of up to 80-90% % and extend tens of meters below the ground surface. Beyond the Yedoma main distributional range in the coastal lowlands of the Laptev and East Siberian seas, these deposits are also found on slopes of the Verkhoyan Mountain Range and in valleys of surrounding foothills, providing favorable preconditions for rapid thaw development. The Batagay mega slump exposes a profile of 30m thick Yedoma deposits underlain by ice saturated alluvial sand of around 60 m thickness and another very ice-rich layer at the base. We present data from a multi-sensor remote sensing time series investigation of the mega slump in order to assess the planimetric and volumetric dimensions and its decadal and interannual expansion rates. For ortho-rectification purposes and for volumetric analyses, we photogrammetrically derived highly detailed digital elevation models. The height difference between the headwall and the slump outflow is 145 m along a distance of 2300 m, while the maximum slump width is 840 m. Our analysis does not show any signs of stabilization after several decades (since 1980s) of slump growth, with the headwall retreating with observed rates of generally >10 m and more recently up to 30m per year. Reconstruction of a paleo-surface revealed that the slump has carved into the rolling topography to a depth of up to 73 m. The current size of the slump is >69 ha, while it had thawed >25 × 106 m³ of ice-rich permafrost through 2016. The majority of sediment released from the slump episodically dams up the Batagay River, forming a large temporary lake which then empties catastrophically.

Skeletal muscle expresses the extracellular cyclic AMP–adenosine pathway

PubMed Central

Chiavegatti, T; Costa, V L; Araújo, M S; Godinho, R O

2007-01-01

Background and purpose: cAMP is a key intracellular signalling molecule that regulates multiple processes of the vertebrate skeletal muscle. We have shown that cAMP can be actively pumped out from the skeletal muscle cell. Since in other tissues, cAMP efflux had been associated with extracellular generation of adenosine, in the present study we have assessed the fate of interstitial cAMP and the existence of an extracellular cAMP-adenosine signalling pathway in skeletal muscle. Experimental approach: cAMP efflux and/or its extracellular degradation were analysed by incubating rat cultured skeletal muscle with exogenous cAMP, forskolin or isoprenaline. cAMP and its metabolites were quantified by radioassay or HPLC, respectively. Key results: Incubation of cells with exogenous cAMP was followed by interstitial accumulation of 5′-AMP and adenosine, a phenomenon inhibited by selective inhibitors of ecto-phosphodiesterase (DPSPX) and ecto-nucleotidase (AMPCP). Activation of adenylyl cyclase (AC) in cultured cells with forskolin or isoprenaline increased cAMP efflux and extracellular generation of 5′-AMP and adenosine. Extracellular cAMP-adenosine pathway was also observed after direct and receptor-dependent stimulation of AC in rat extensor muscle ex vivo. These events were attenuated by probenecid, an inhibitor of ATP binding cassette family transporters. Conclusions and implications: Our results show the existence of an extracellular biochemical cascade that converts cAMP into adenosine. The functional relevance of this extracellular signalling system may involve a feedback modulation of cellular response initiated by several G protein-coupled receptor ligands, amplifying cAMP influence to a paracrine mode, through its metabolite, adenosine. PMID:18157164

Cyclic AMP-dependent regulation of P-type calcium channels expressed in Xenopus oocytes.

PubMed

Fournier, F; Bourinet, E; Nargeot, J; Charnet, P

1993-05-01

Xenopus oocytes injected with rat cerebellum mRNA, express voltage-dependent calcium channels (VDCC). These were identified as P-type Ca2+ channels by their insensitivity to dihydropyridines and omega-conotoxin and by their blockade by Agelenopsis aperta venom (containing the funnel-web spider toxins: FTX and omega-Aga-IV-A). Coinjection of cerebellar mRNA and antisense oligonucleotide complementary to the dihydropyridine-resistant brain Ca2+ channel, named BI [Mori Y. et al. (1991) Nature 350:398-402] or rbA [Starr T. V. B. et al. (1991) Proc Natl Acad Sci USA 88:5621-5625], strongly reduced the expressed Ba2+ current suggesting that these clones encode a P-type VDCC. The macroscopic Ca2+ channel activity was increased by direct intraoocyte injection of cAMP. This increase in current amplitude was concomitant with a slowing of current inactivation, and was attributed to activation of protein kinase A, since it could be antagonized by a peptidic inhibitor of this enzyme. Positive regulation of P-type VDCC could be of importance in Purkinje neurons and motor nerve terminals where this channel is predominant.

Electron-beam irradiation-induced gate oxide degradation

NASA Astrophysics Data System (ADS)

Cho, Byung Jin; Chong, Pei Fen; Chor, Eng Fong; Joo, Moon Sig; Yeo, In Seok

2000-12-01

Gate oxide degradation induced by electron-beam irradiation has been studied. A large increase in the low-field excess leakage current was observed on irradiated oxides and this was very similar to electrical stress-induced leakage currents. Unlike conventional electrical stress-induced leakage currents, however, electron-beam induced leakage currents exhibit a power law relationship with fluency without any signs of saturation. It has also been found that the electron-beam neither accelerates nor initiates quasibreakdown of the ultrathin gate oxide. Therefore, the traps generated by electron-beam irradiation do not contribute to quasibreakdown, only to the leakage current.

Responsiveness to a Prospective Student E-Mail Inquiry by Community Colleges in the Nine Mega-States

ERIC Educational Resources Information Center

Shadinger, David A.

2014-01-01

This quantitative study investigated e-mail responsiveness by community colleges in the nine mega-states to an inquiry from a prospective student. Noel-Levitz (2006b) reported that prospective students want to receive an e-mail with information about an institution prior to applying for admission. Specifically, high school juniors and seniors want…

Student Engagement and Completion in Precalculus Precalculus Mega Section: Efficiently Assisting Student Engagement and Completion with Communications and Information Technology

ERIC Educational Resources Information Center

Brusi, Rima; Portnoy, Arturo; Toro, Nilsa

2013-01-01

The Precalculus Mega Section project was developed with the main purpose of improving the overall performance of the student body in Precalculus, an important gatekeeper course that affects student engagement and completion, with typical drop/failure rates of over 50 percent. Strategies such as integration of technology and additional practice…

The Open Education System, Anadolu University, Turkey: E-Transformation in a Mega-University

ERIC Educational Resources Information Center

Latchem, Colin; Ozkul, Ali Ekrem; Aydin, Cengiz Hakan; Mutlu, Mehmet Emin

2006-01-01

Anadolu University in Turkey is one of the world's largest and least known mega-universities. Well over one million students in Turkey, the European Union and Northern Cyprus are enrolled in its Open Education System and yet few accounts of this dual-mode provider appear in the international literature. This article describes the evolution of the…

Educational Planning and Social Responsibility: Eleven Years of Mega Planning at the Sonora Institute of Technology (ITSON)

ERIC Educational Resources Information Center

Guerra, Ingrid J.; Rodriguez, Gonzalo

2005-01-01

The Instituto Tecnologico de Sonora (ITSON), a public and autonomous university in Cuidad Obregon, Sonora in Mexico has, since its inception, maintained a commitment to society and public service. To transform this commitment into valued results, it has used Mega Planning as its framework over the last eleven years. This article illustrates the…

Rp-cAMPS Prodrugs Reveal the cAMP Dependence of First-Phase Glucose-Stimulated Insulin Secretion

PubMed Central

Schwede, Frank; Chepurny, Oleg G.; Kaufholz, Melanie; Bertinetti, Daniela; Leech, Colin A.; Cabrera, Over; Zhu, Yingmin; Mei, Fang; Cheng, Xiaodong; Manning Fox, Jocelyn E.; MacDonald, Patrick E.; Genieser, Hans-G.; Herberg, Friedrich W.

2015-01-01

cAMP-elevating agents such as the incretin hormone glucagon-like peptide-1 potentiate glucose-stimulated insulin secretion (GSIS) from pancreatic β-cells. However, a debate has existed since the 1970s concerning whether or not cAMP signaling is essential for glucose alone to stimulate insulin secretion. Here, we report that the first-phase kinetic component of GSIS is cAMP-dependent, as revealed through the use of a novel highly membrane permeable para-acetoxybenzyl (pAB) ester prodrug that is a bioactivatable derivative of the cAMP antagonist adenosine-3′,5′-cyclic monophosphorothioate, Rp-isomer (Rp-cAMPS). In dynamic perifusion assays of human or rat islets, a step-wise increase of glucose concentration leads to biphasic insulin secretion, and under these conditions, 8-bromoadenosine-3′,5′-cyclic monophosphorothioate, Rp-isomer, 4-acetoxybenzyl ester (Rp-8-Br-cAMPS-pAB) inhibits first-phase GSIS by up to 80%. Surprisingly, second-phase GSIS is inhibited to a much smaller extent (≤20%). Using luciferase, fluorescence resonance energy transfer, and bioluminescence resonance energy transfer assays performed in living cells, we validate that Rp-8-Br-cAMPS-pAB does in fact block cAMP-dependent protein kinase activation. Novel effects of Rp-8-Br-cAMPS-pAB to block the activation of cAMP-regulated guanine nucleotide exchange factors (Epac1, Epac2) are also validated using genetically encoded Epac biosensors, and are independently confirmed in an in vitro Rap1 activation assay using Rp-cAMPS and Rp-8-Br-cAMPS. Thus, in addition to revealing the cAMP dependence of first-phase GSIS from human and rat islets, these findings establish a pAB-based chemistry for the synthesis of highly membrane permeable prodrug derivatives of Rp-cAMPS that act with micromolar or even nanomolar potency to inhibit cAMP signaling in living cells. PMID:26061564

Structural and Functional Characterization of Pseudomonas aeruginosa Global Regulator AmpR

PubMed Central

Caille, Olivier; Zincke, Diansy; Merighi, Massimo; Balasubramanian, Deepak; Kumari, Hansi; Kong, Kok-Fai; Silva-Herzog, Eugenia; Narasimhan, Giri; Schneper, Lisa; Lory, Stephen

2014-01-01

Pseudomonas aeruginosa is a dreaded pathogen in many clinical settings. Its inherent and acquired antibiotic resistance thwarts therapy. In particular, derepression of the AmpC β-lactamase is a common mechanism of β-lactam resistance among clinical isolates. The inducible expression of ampC is controlled by the global LysR-type transcriptional regulator (LTTR) AmpR. In the present study, we investigated the genetic and structural elements that are important for ampC induction. Specifically, the ampC (PampC) and ampR (PampR) promoters and the AmpR protein were characterized. The transcription start sites (TSSs) of the divergent transcripts were mapped using 5′ rapid amplification of cDNA ends-PCR (RACE-PCR), and strong σ54 and σ70 consensus sequences were identified at PampR and PampC, respectively. Sigma factor RpoN was found to negatively regulate ampR expression, possibly through promoter blocking. Deletion mapping revealed that the minimal PampC extends 98 bp upstream of the TSS. Gel shifts using membrane fractions showed that AmpR binds to PampC in vitro whereas in vivo binding was demonstrated using chromatin immunoprecipitation-quantitative PCR (ChIP-qPCR). Additionally, site-directed mutagenesis of the AmpR helix-turn-helix (HTH) motif identified residues critical for binding and function (Ser38 and Lys42) and critical for function but not binding (His39). Amino acids Gly102 and Asp135, previously implicated in the repression state of AmpR in the enterobacteria, were also shown to play a structural role in P. aeruginosa AmpR. Alkaline phosphatase fusion and shaving experiments suggest that AmpR is likely to be membrane associated. Lastly, an in vivo cross-linking study shows that AmpR dimerizes. In conclusion, a potential membrane-associated AmpR dimer regulates ampC expression by direct binding. PMID:25182487

Infection prevention staffing and resources in U.S. acute care hospitals: Results from the APIC MegaSurvey.

PubMed

Pogorzelska-Maziarz, Monika; Gilmartin, Heather; Reese, Sara

2018-06-01

Given the changing nature of infection prevention and control (IPC), appropriate infection preventionist (IP) staffing needs to be established. In this study, we aimed to describe current IP staffing levels and IPC department resources in U.S. acute care hospitals. These data came from the 2015 MegaSurvey conducted by the Association of Professionals in Infection Prevention and Epidemiology. Descriptive statistics and bivariate analyses were conducted to examine differences in respondent, facility, and department characteristics by facility size (average inpatient census ≤100 vs >100). Data from 1623 respondents were included. Most (72%) had single-site responsibilities and dedicated 76%-100% of their job to IPC (68%). The overall median IP staffing was 1.25 IPs per 100 inpatient census (interquartile range = 1.81). Almost half (46%) represented facilities with daily inpatient census ≤100; the average number of IPs in these facilities was 1.1 (standard deviation = 0.7). The reported number of IPs increased steadily with higher patient census. Significant differences were observed in IP staffing, responsibilities, and support to the IPC department between smaller and larger hospitals. This study represents the current snapshot of IP staffing and IPC resources in acute care hospitals. Findings indicate important differences between large and small facilities in staffing and IPC resources. The field of infection prevention would benefit from a comprehensive assessment of IPC department staffing and resource needs. Copyright © 2018 Association for Professionals in Infection Control and Epidemiology, Inc. All rights reserved.

Studies on space charge neutralization and emittance measurement of beam from microwave ion source.

PubMed

Misra, Anuraag; Goswami, A; Sing Babu, P; Srivastava, S; Pandit, V S

2015-11-01

A 2.45 GHz microwave ion source together with a beam transport system has been developed at VECC to study the problems related with the injection of high current beam into a compact cyclotron. This paper presents the results of beam profile measurement of high current proton beam at different degrees of space charge neutralisation with the introduction of neon gas in the beam line using a fine leak valve. The beam profiles have been measured at different pressures in the beam line by capturing the residual gas fluorescence using a CCD camera. It has been found that with space charge compensation at the present current level (∼5 mA at 75 keV), it is possible to reduce the beam spot size by ∼34%. We have measured the variation of beam profile as a function of the current in the solenoid magnet under the neutralised condition and used these data to estimate the rms emittance of the beam. Simulations performed using equivalent Kapchinsky-Vladimirsky beam envelope equations with space charge neutralization factor are also presented to interpret the experimental results.

Studies on space charge neutralization and emittance measurement of beam from microwave ion source

NASA Astrophysics Data System (ADS)

Misra, Anuraag; Goswami, A.; Sing Babu, P.; Srivastava, S.; Pandit, V. S.

2015-11-01

A 2.45 GHz microwave ion source together with a beam transport system has been developed at VECC to study the problems related with the injection of high current beam into a compact cyclotron. This paper presents the results of beam profile measurement of high current proton beam at different degrees of space charge neutralisation with the introduction of neon gas in the beam line using a fine leak valve. The beam profiles have been measured at different pressures in the beam line by capturing the residual gas fluorescence using a CCD camera. It has been found that with space charge compensation at the present current level (˜5 mA at 75 keV), it is possible to reduce the beam spot size by ˜34%. We have measured the variation of beam profile as a function of the current in the solenoid magnet under the neutralised condition and used these data to estimate the rms emittance of the beam. Simulations performed using equivalent Kapchinsky-Vladimirsky beam envelope equations with space charge neutralization factor are also presented to interpret the experimental results.

Dynamic neutral beam current and voltage control to improve beam efficacy in tokamaks

NASA Astrophysics Data System (ADS)

Pace, D. C.; Austin, M. E.; Bardoczi, L.; Collins, C. S.; Crowley, B.; Davis, E.; Du, X.; Ferron, J.; Grierson, B. A.; Heidbrink, W. W.; Holcomb, C. T.; McKee, G. R.; Pawley, C.; Petty, C. C.; Podestà, M.; Rauch, J.; Scoville, J. T.; Spong, D. A.; Thome, K. E.; Van Zeeland, M. A.; Varela, J.; Victor, B.

2018-05-01

An engineering upgrade to the neutral beam system at the DIII-D tokamak [J. L. Luxon, Nucl. Fusion 42, 614 (2002)] enables time-dependent programming of the beam voltage and current. Initial application of this capability involves pre-programmed beam voltage and current injected into plasmas that are known to be susceptible to instabilities that are driven by energetic ( E ≥ 40 keV) beam ions. These instabilities, here all Alfvén eigenmodes (AEs), increase the transport of the beam ions beyond a classical expectation based on particle drifts and collisions. Injecting neutral beam power, P beam ≥ 2 MW, at reduced voltage with increased current reduces the drive for Alfvénic instabilities and results in improved ion confinement. In lower-confinement plasmas, this technique is applied to eliminate the presence of AEs across the mid-radius of the plasmas. Simulations of those plasmas indicate that the mode drive is decreased and the radial extent of the remaining modes is reduced compared to a higher beam voltage case. In higher-confinement plasmas, this technique reduces AE activity in the far edge and results in an interesting scenario of beam current drive improving as the beam voltage reduces from 80 kV to 65 kV.

Dynamic neutral beam current and voltage control to improve beam efficacy in tokamaks

DOE Office of Scientific and Technical Information (OSTI.GOV)

Austin, Max E.; Bardoczi, Laszlo; Collins, Cami S.

Here, an engineering upgrade to the neutral beam system at the DIII-D tokamak enables time-dependent programming of the beam voltage and current. Initial application of this capability involves pre-programmed beam voltage and current injected into plasmas that are known to be susceptible to instabilities that are driven by energetic (E ≥ 40 keV) beam ions. These instabilities, here all Alfvén eigenmodes (AEs), increase the transport of the beam ions beyond a classical expectation based on particle drifts and collisions. Injecting neutral beam power, P beam ≥ 2MW, at reduced voltage with increased current reduces the drive for Alfvénic instabilities andmore » results in improved ion confinement. In lower-confinement plasmas, this technique is applied to eliminate the presence of AEs across the mid-radius of the plasmas. Simulations of those plasmas indicate that the mode drive is decreased and the radial extent of the remaining modes is reduced compared to a higher beam voltage case. In higher-confinement plasmas, this technique reduces AE activity in the far edge and results in an interesting scenario of beam current drive improving as the beam voltage reduces from 80 kV to 65 kV.« less

Dynamic neutral beam current and voltage control to improve beam efficacy in tokamaks

DOE PAGES

Austin, Max E.; Bardoczi, Laszlo; Collins, Cami S.; ...

2018-04-20

Here, an engineering upgrade to the neutral beam system at the DIII-D tokamak enables time-dependent programming of the beam voltage and current. Initial application of this capability involves pre-programmed beam voltage and current injected into plasmas that are known to be susceptible to instabilities that are driven by energetic (E ≥ 40 keV) beam ions. These instabilities, here all Alfvén eigenmodes (AEs), increase the transport of the beam ions beyond a classical expectation based on particle drifts and collisions. Injecting neutral beam power, P beam ≥ 2MW, at reduced voltage with increased current reduces the drive for Alfvénic instabilities andmore » results in improved ion confinement. In lower-confinement plasmas, this technique is applied to eliminate the presence of AEs across the mid-radius of the plasmas. Simulations of those plasmas indicate that the mode drive is decreased and the radial extent of the remaining modes is reduced compared to a higher beam voltage case. In higher-confinement plasmas, this technique reduces AE activity in the far edge and results in an interesting scenario of beam current drive improving as the beam voltage reduces from 80 kV to 65 kV.« less

Mechanism of cAMP Partial Agonism in Protein Kinase G (PKG)*♦

PubMed Central

VanSchouwen, Bryan; Selvaratnam, Rajeevan; Giri, Rajanish; Lorenz, Robin; Herberg, Friedrich W.; Kim, Choel; Melacini, Giuseppe

2015-01-01

Protein kinase G (PKG) is a major receptor of cGMP and controls signaling pathways often distinct from those regulated by cAMP. Hence, the selective activation of PKG by cGMP versus cAMP is critical. However, the mechanism of cGMP-versus-cAMP selectivity is only limitedly understood. Although the C-terminal cyclic nucleotide-binding domain B of PKG binds cGMP with higher affinity than cAMP, the intracellular concentrations of cAMP are typically higher than those of cGMP, suggesting that the cGMP-versus-cAMP selectivity of PKG is not controlled uniquely through affinities. Here, we show that cAMP is a partial agonist for PKG, and we elucidate the mechanism for cAMP partial agonism through the comparative NMR analysis of the apo, cGMP-, and cAMP-bound forms of the PKG cyclic nucleotide-binding domain B. We show that although cGMP activation is adequately explained by a two-state conformational selection model, the partial agonism of cAMP arises from the sampling of a third, partially autoinhibited state. PMID:26370085

Atmospheric, Magnetospheric and Plasmas in space (AMPS) spacelab payload definition study. Volume 4. Part 1, AMPS program specification

NASA Technical Reports Server (NTRS)

Keeley, J. T.

1976-01-01

The AMPS Program Specification delineates the AMPS Program requirements consistent with the resources defined in the AMPS Project Plan. All subsidiary specifications and requirements shall conform to the requirements presented. The requirements hierarchy for the AMPS program is illustrated. A brief description of each of the requirements documents and their intended use is provided.

Role of 2′,3′-cyclic nucleotide 3′-phosphodiesterase in the renal 2′,3′-cAMP-adenosine pathway

PubMed Central

Gillespie, Delbert G.; Mi, Zaichuan; Cheng, Dongmei; Bansal, Rashmi; Janesko-Feldman, Keri; Kochanek, Patrick M.

2014-01-01

Energy depletion increases the renal production of 2′,3′-cAMP (a positional isomer of 3′,5′-cAMP that opens mitochondrial permeability transition pores) and 2′,3′-cAMP is converted to 2′-AMP and 3′-AMP, which in turn are metabolized to adenosine. Because the enzymes involved in this “2′,3′-cAMP-adenosine pathway” are unknown, we examined whether 2′,3′-cyclic nucleotide 3′-phosphodiesterase (CNPase) participates in the renal metabolism of 2′,3′-cAMP. Western blotting and real-time PCR demonstrated expression of CNPase in rat glomerular mesangial, preglomerular vascular smooth muscle and endothelial, proximal tubular, thick ascending limb and collecting duct cells. Real-time PCR established the expression of CNPase in human glomerular mesangial, proximal tubular and vascular smooth muscle cells; and the level of expression of CNPase was greater than that for phosphodiesterase 4 (major enzyme for the metabolism of 3′,5′-cAMP). Overexpression of CNPase in rat preglomerular vascular smooth muscle cells increased the metabolism of exogenous 2′,3′-cAMP to 2′-AMP. Infusions of 2′,3′-cAMP into isolated CNPase wild-type (+/+) kidneys increased renal venous 2′-AMP, and this response was diminished by 63% in CNPase knockout (−/−) kidneys, whereas the conversion of 3′,5′-cAMP to 5′-AMP was similar in CNPase +/+ vs. −/− kidneys. In CNPase +/+ kidneys, energy depletion (metabolic poisons) increased kidney tissue levels of adenosine and its metabolites (inosine, hypoxanthine, xanthine, and uric acid) without accumulation of 2′,3′-cAMP. In contrast, in CNPase −/− kidneys, energy depletion increased kidney tissue levels of 2′,3′-cAMP and abolished the increase in adenosine and its metabolites. In conclusion, kidneys express CNPase, and renal CNPase mediates in part the renal 2′,3′-cAMP-adenosine pathway. PMID:24808540

Cyclic AMP- and (Rp)-cAMPS-induced Conformational Changes in a Complex of the Catalytic and Regulatory (RIα) Subunits of Cyclic AMP-dependent Protein Kinase*

PubMed Central

Anand, Ganesh S.; Krishnamurthy, Srinath; Bishnoi, Tanushree; Kornev, Alexandr; Taylor, Susan S.; Johnson, David A.

2010-01-01

We took a discovery approach to explore the actions of cAMP and two of its analogs, one a cAMP mimic ((Sp)-adenosine cyclic 3′:5′-monophosphorothioate ((Sp)-cAMPS)) and the other a diastereoisomeric antagonist ((Rp)-cAMPS), on a model system of the type Iα cyclic AMP-dependent protein kinase holoenzyme, RIα(91–244)·C-subunit, by using fluorescence spectroscopy and amide H/2H exchange mass spectrometry. Specifically, for the fluorescence experiments, fluorescein maleimide was conjugated to three cysteine single residue substitution mutants, R92C, T104C, and R239C, of RIα(91–244), and the effects of cAMP, (Sp)-cAMPS, and (Rp)-cAMPS on the kinetics of R-C binding and the time-resolved anisotropy of the reporter group at each conjugation site were measured. For the amide exchange experiments, ESI-TOF mass spectrometry with pepsin proteolytic fragmentation was used to assess the effects of (Rp)-cAMPS on amide exchange of the RIα(91–244)·C-subunit complex. We found that cAMP and its mimic perturbed at least parts of the C-subunit interaction Sites 2 and 3 but probably not Site 1 via reduced interactions of the linker region and αC of RIα(91–244). Surprisingly, (Rp)-cAMPS not only increased the affinity of RIα(91–244) toward the C-subunit by 5-fold but also produced long range effects that propagated through both the C- and R-subunits to produce limited unfolding and/or enhanced conformational flexibility. This combination of effects is consistent with (Rp)-cAMPS acting by enhancing the internal entropy of the R·C complex. Finally, the (Rp)-cAMPS-induced increase in affinity of RIα(91–244) toward the C-subunit indicates that (Rp)-cAMPS is better described as an inverse agonist because it decreases the fractional dissociation of the cyclic AMP-dependent protein kinase holoenzyme and in turn its basal activity. PMID:20167947

Cyclic AMP Enhances TGFβ Responses of Breast Cancer Cells by Upregulating TGFβ Receptor I Expression

PubMed Central

Oerlecke, Ilka; Bauer, Elke; Dittmer, Angela; Leyh, Benjamin; Dittmer, Jürgen

2013-01-01

Cellular functions are regulated by complex networks of many different signaling pathways. The TGFβ and cAMP pathways are of particular importance in tumor progression. We analyzed the cross-talk between these pathways in breast cancer cells in 2D and 3D cultures. We found that cAMP potentiated TGFβ-dependent gene expression by enhancing Smad3 phosphorylation. Higher levels of total Smad3, as observed in 3D-cultured cells, blocked this effect. Two Smad3 regulating proteins, YAP (Yes-associated protein) and TβRI (TGFβ receptor 1), were responsive to cAMP. While YAP had little effect on TGFβ-dependent expression and Smad3 phosphorylation, a constitutively active form of TβRI mimicked the cAMP effect on TGFβ signaling. In 3D-cultured cells, which show much higher levels of TβRI and cAMP, TβRI was unresponsive to cAMP. Upregulation of TβRI expression by cAMP was dependent on transcription. A proximal TβRI promoter fragment was moderately, but significantly activated by cAMP suggesting that cAMP increases TβRI expression at least partially by activating TβRI transcription. Neither the cAMP-responsive element binding protein (CREB) nor the TβRI-regulating transcription factor Six1 was required for the cAMP effect. An inhibitor of histone deacetylases alone or together with cAMP increased TβRI expression by a similar extent as cAMP alone suggesting that cAMP may exert its effect by interfering with histone acetylation. Along with an additive stimulatory effect of cAMP and TGFβ on p21 expression an additive inhibitory effect of these agents on proliferation was observed. Finally, we show that mesenchymal stem cells that interact with breast cancer cells can simultaneously activate the cAMP and TGFβ pathways. In summary, these data suggest that combined effects of cAMP and TGFβ, as e.g. induced by mesenchymal stem cells, involve the upregulation of TβRI expression on the transcriptional level, likely due to changes in histone acetylation. As a consequence, cancer cell functions such as proliferation are affected. PMID:23349840

Filamentation instability of a fast electron beam in a dielectric target.

PubMed

Debayle, A; Tikhonchuk, V T

2008-12-01

High-intensity laser-matter interaction is an efficient method for high-current relativistic electron beam production. At current densities exceeding a several kA microm{-2} , the beam propagation is maintained by an almost complete current neutralization by the target electrons. In such a geometry of two oppositely directed flows, beam instabilities can develop, depending on the target and the beam parameters. The present paper proposes an analytical description of the filamentation instability of an electron beam propagating through an insulator target. It is shown that the collisionless and resistive instabilities enter into competition with the ionization instability. This latter process is dominant in insulator targets where the field ionization by the fast beam provides free electrons for the neutralization current.

Analog bus driver and multiplexer

NASA Technical Reports Server (NTRS)

Pain, Bedabrata (Inventor); Hancock, Bruce (Inventor); Cunningham, Thomas J. (Inventor)

2012-01-01

For a source-follower signal chain, the ohmic drop in the selection switch causes unacceptable voltage offset, non-linearity, and reduced small signal gain. For an op amp signal chain, the required bias current and the output noise rises rapidly with increasing the array format due to a rapid increase in the effective capacitance caused by the Miller effect boosting up the contribution of the bus capacitance. A new switched source-follower signal chain circuit overcomes limitations of existing op-amp based or source follower based circuits used in column multiplexers and data readout. This will improve performance of CMOS imagers, and focal plane read-out integrated circuits for detectors of infrared or ultraviolet light.