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.

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.

Proton deflectometry of laser-driven relativistic electron jet from thin foil target

NASA Astrophysics Data System (ADS)

Huang, Chengkun; Palaniyappan, S.; Gautier, D. C.; Johnson, R. P.; Shimada, T.; Fernandez, J. C.; Tsung, F. S.; Mori, W. B.

2017-10-01

Near critical density relativistic electron jets from laser solid interaction carry currents approaching the Alfvén-limit and tens of kilo-Tesla magnetic fields. Such jets are often found in kinetic simulations with low areal density targets, but have not been confirmed experimentally. They may be used for X/gamma-ray generation and is also important for the understanding of post-transparency plasma dynamics. With a short-pulse probe beam at the Trident laser facility, we employed proton deflectometry to infer the jet's properties, structure and the long-time dynamics. We develop corresponding GEANT4 simulation model of the proton deflectometry, with input from the kinetic PIC simulations in 2D and quasi-3D geometry, to compare with the experimental radiography images. Detail comparison of the experimental and simulation features in the deflectometry will be discussed. Work supported by the LDRD program at LANL.

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

Demonstration of Efficient Core Heating of Magnetized Fast Ignition in FIREX project

NASA Astrophysics Data System (ADS)

Johzaki, Tomoyuki

2017-10-01

Extensive theoretical and experimental research in the FIREX ``I project over the past decade revealed that the large angular divergence of the laser generated electron beam is one of the most critical problems inhibiting efficient core heating in electron-driven fast ignition. To solve this problem, beam guiding using externally applied kilo-tesla class magnetic field was proposed, and its feasibility has recently been numerically demonstrated. In 2016, integrated experiments at ILE Osaka University demonstrated core heating efficiencies reaching > 5 % and heated core temperatures of 1.7 keV. In these experiments, a kilo-tesla class magnetic field was applied to a cone-attached Cu(II) oleate spherical solid target by using a laser-driven capacitor-coil. The target was then imploded by G-XII laser and heated by the PW-class LFEX laser. The heating efficiency was evaluated by measuring the number of Cu-K- α photons emitted. The heated core temperature was estimated by the X-ray intensity ratio of Cu Li-like and He-like emission lines. To understand the detailed dynamics of the core heating process, we carried out integrated simulations using the FI3 code system. Effects of magnetic fields on the implosion and electron beam transport, detailed core heating dynamics, and the resultant heating efficiency and core temperature will be presented. I will also discuss the prospect for an ignition-scale design of magnetized fast ignition using a solid ball target. This work is partially supported by JSPA KAKENHI Grant Number JP16H02245, JP26400532, JP15K21767, JP26400532, JP16K05638 and is performed with the support and the auspices of the NIFS Collaboration Research program (NIFS12KUGK057, NIFS15KUGK087).

Active mirror amplifiers for HiPER kiloJoule beamlines

NASA Astrophysics Data System (ADS)

Chanteloup, J.-C.; Lucianetti, A.

2013-11-01

A major challenge the HiPER [1] project is facing is to derive laser architectures satisfying simultaneously all HiPER requirements; among them, high wall-plug efficiency (15 to 20%) and repetition rate (around 10 Hz) are the most challenging constraints. Several groups over the world are actively pursuing research in the field of High average power Diode Pumped Solid State Lasers (DPSSL) [2]. We propose a comprehensive solution for a 1 kJ DPSSL beamline as the unit brick of a 12 beams bundle.

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.

Study on the quality assurance of diagnostic X-ray machines and assessment of the absorbed dose to patients

NASA Astrophysics Data System (ADS)

Hassan, G. M.; Rabie, N.; Mustafa, K. A.; Abdel-Khalik, S. S.

2012-09-01

Radiation exposure and image quality in X-ray diagnostic radiology provide a clear understanding of the relationship between the radiation dose delivered to a patient and image quality in optimizing medical diagnostic radiology. Because a certain amount of radiation is unavoidably delivered to patients, this should be as low as reasonably achievable. Several X-ray diagnostic machines were used at different medical diagnostic centers in Egypt for studying the beam quality and the dose delivered to the patient. This article studies the factors affecting the beam quality, such as the kilo-volt peak (kVp), exposure time (mSc), tube current (mAs) and the absorbed dose in (μGy) for different examinations. The maximum absorbed dose measured per mAs was 594±239 and 12.5±3.7 μGy for the abdomen and the chest, respectively, while the absorbed dose at the elbow was 18±6 μGy, which was the minimum dose recorded. The compound and expanded uncertainties accompanying these measurements were 4±0.35% and 8±0.7%, respectively. The measurements were done through quality control tests as acceptance procedures.

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.

Optimization-based reconstruction for reduction of CBCT artifact in IGRT

NASA Astrophysics Data System (ADS)

Xia, Dan; Zhang, Zheng; Paysan, Pascal; Seghers, Dieter; Brehm, Marcus; Munro, Peter; Sidky, Emil Y.; Pelizzari, Charles; Pan, Xiaochuan

2016-04-01

Kilo-voltage cone-beam computed tomography (CBCT) plays an important role in image guided radiation therapy (IGRT) by providing 3D spatial information of tumor potentially useful for optimizing treatment planning. In current IGRT CBCT system, reconstructed images obtained with analytic algorithms, such as FDK algorithm and its variants, may contain artifacts. In an attempt to compensate for the artifacts, we investigate optimization-based reconstruction algorithms such as the ASD-POCS algorithm for potentially reducing arti- facts in IGRT CBCT images. In this study, using data acquired with a physical phantom and a patient subject, we demonstrate that the ASD-POCS reconstruction can significantly reduce artifacts observed in clinical re- constructions. Moreover, patient images reconstructed by use of the ASD-POCS algorithm indicate a contrast level of soft-tissue improved over that of the clinical reconstruction. We have also performed reconstructions from sparse-view data, and observe that, for current clinical imaging conditions, ASD-POCS reconstructions from data collected at one half of the current clinical projection views appear to show image quality, in terms of spatial and soft-tissue-contrast resolution, higher than that of the corresponding clinical reconstructions.

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.

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.

33 CFR 100.718 - Annual Suncoast Kilo Run; Sarasota Bay, Sarasota, FL.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 33 Navigation and Navigable Waters 1 2011-07-01 2011-07-01 false Annual Suncoast Kilo Run; Sarasota Bay, Sarasota, FL. 100.718 Section 100.718 Navigation and Navigable Waters COAST GUARD, DEPARTMENT... Suncoast Kilo Run; Sarasota Bay, Sarasota, FL. (a) Regulated area. The regulated area is established in...

Technical Note: Procedure for the calibration and validation of kilo-voltage cone-beam CT models

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

Vilches-Freixas, Gloria; Létang, Jean Michel; Rit,

2016-09-15

Purpose: The aim of this work is to propose a general and simple procedure for the calibration and validation of kilo-voltage cone-beam CT (kV CBCT) models against experimental data. Methods: The calibration and validation of the CT model is a two-step procedure: the source model then the detector model. The source is described by the direction dependent photon energy spectrum at each voltage while the detector is described by the pixel intensity value as a function of the direction and the energy of incident photons. The measurements for the source consist of a series of dose measurements in air performedmore » at each voltage with varying filter thicknesses and materials in front of the x-ray tube. The measurements for the detector are acquisitions of projection images using the same filters and several tube voltages. The proposed procedure has been applied to calibrate and assess the accuracy of simple models of the source and the detector of three commercial kV CBCT units. If the CBCT system models had been calibrated differently, the current procedure would have been exclusively used to validate the models. Several high-purity attenuation filters of aluminum, copper, and silver combined with a dosimeter which is sensitive to the range of voltages of interest were used. A sensitivity analysis of the model has also been conducted for each parameter of the source and the detector models. Results: Average deviations between experimental and theoretical dose values are below 1.5% after calibration for the three x-ray sources. The predicted energy deposited in the detector agrees with experimental data within 4% for all imaging systems. Conclusions: The authors developed and applied an experimental procedure to calibrate and validate any model of the source and the detector of a CBCT unit. The present protocol has been successfully applied to three x-ray imaging systems. The minimum requirements in terms of material and equipment would make its implementation suitable in most clinical environments.« less

Wideband low-noise variable-gain BiCMOS transimpedance amplifier

NASA Astrophysics Data System (ADS)

Meyer, Robert G.; Mack, William D.

1994-06-01

A new monolithic variable gain transimpedance amplifier is described. The circuit is realized in BiCMOS technology and has measured gain of 98 kilo ohms, bandwidth of 128 MHz, input noise current spectral density of 1.17 pA/square root of Hz and input signal-current handling capability of 3 mA.

NASA Sees Typhoon Kilo Maintaining its Eye

NASA Image and Video Library

2017-12-08

Typhoon Kilo continues to thrive in the Northwestern Pacific and imagery from NASA's Terra satellite late on September 7 showed that the storm still maintained a clear eye. The MODIS or Moderate Resolution Imaging Spectroradiometer instrument that flies aboard Terra provided a visible-light image of Kilo on September 7 at 23:50 UTC (7:50 p.m. EDT). The image showed thick bands of thunderstorms wrapping around the eastern and northern quadrants of the visible eye. At 0900 UTC (5 a.m. EDT) on September 9, Typhoon Kilo had maximum sustained winds near 65 knots (74.8 mph/120.4 kph). Kilo is expected to strengthen to 75 knots (86.3 mph/ 138.9 kph) later in the day before weakening. It was centered near 26.8 North latitude and 158.5 East longitude, about 289 nautical miles northeast of Minami Tori Shima, Japan. Kilo was moving to the west-northwest at 18 knots (20.7 mph/33.3 kph). The Joint Typhoon Warning Center noted that Kilo is expected to take more of a northerly track by September 10. Thereafter, Kilo is expected to become extra-tropical and curve to the northeast near the Kuril Islands in Russia's Sakhalin Oblast region. The islands form an 808 mile (1,300 kilometer) volcanic archipelago that stretches northeast from Hokkaido, Japan, to Kamchatka, Russia. For updated watches and warnings from the Japan Meteorological Agency, visit: www.jma.go.jp/en/warn/ NASA image use policy. NASA Goddard Space Flight Center enables NASA’s mission through four scientific endeavors: Earth Science, Heliophysics, Solar System Exploration, and Astrophysics. Goddard plays a leading role in NASA’s accomplishments by contributing compelling scientific knowledge to advance the Agency’s mission. Follow us on Twitter Like us on Facebook Find us on Instagram

The effects of resonant magnetic perturbations on fast ion confinement in the Mega Amp Spherical Tokamak

NASA Astrophysics Data System (ADS)

McClements, K. G.; Akers, R. J.; Boeglin, W. U.; Cecconello, M.; Keeling, D.; Jones, O. M.; Kirk, A.; Klimek, I.; Perez, R. V.; Shinohara, K.; Tani, K.

2015-07-01

The effects of resonant magnetic perturbations (RMPs) on the confinement of energetic (neutral beam) ions in the Mega Amp Spherical Tokamak (MAST) are assessed experimentally using measurements of neutrons, fusion protons and fast ion Dα (FIDA) light emission. In single null-diverted (SND) MAST pulses with relatively low plasma current (400 kA), the total neutron emission dropped by approximately a factor of two when RMPs with toroidal mode number n = 3 were applied. The measured neutron rate during RMPs was much lower than that calculated using the TRANSP plasma simulation code, even when non-classical (but axisymmetric) ad hoc fast ion transport was taken into account in the latter. Sharp drops in spatially-resolved neutron rates, fusion proton rates and FIDA emission were also observed. First principles-based simulations of RMP-induced fast ion transport in MAST, using the F3D-OFMC code, show similar losses for two alternative representations of the MAST first wall, with and without full orbit effects taken into account; for n = 6 RMPs in a 600 kA plasma, the additional loss of beam power due to the RMPs was found in the simulations to be approximately 11%.

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.

Algorithm-enabled exploration of image-quality potential of cone-beam CT in image-guided radiation therapy

NASA Astrophysics Data System (ADS)

Han, Xiao; Pearson, Erik; Pelizzari, Charles; Al-Hallaq, Hania; Sidky, Emil Y.; Bian, Junguo; Pan, Xiaochuan

2015-06-01

Kilo-voltage (KV) cone-beam computed tomography (CBCT) unit mounted onto a linear accelerator treatment system, often referred to as on-board imager (OBI), plays an increasingly important role in image-guided radiation therapy. While the FDK algorithm is currently used for reconstructing images from clinical OBI data, optimization-based reconstruction has also been investigated for OBI CBCT. An optimization-based reconstruction involves numerous parameters, which can significantly impact reconstruction properties (or utility). The success of an optimization-based reconstruction for a particular class of practical applications thus relies strongly on appropriate selection of parameter values. In the work, we focus on tailoring the constrained-TV-minimization-based reconstruction, an optimization-based reconstruction previously shown of some potential for CBCT imaging conditions of practical interest, to OBI imaging through appropriate selection of parameter values. In particular, for given real data of phantoms and patient collected with OBI CBCT, we first devise utility metrics specific to OBI-quality-assurance tasks and then apply them to guiding the selection of parameter values in constrained-TV-minimization-based reconstruction. The study results show that the reconstructions are with improvement, relative to clinical FDK reconstruction, in both visualization and quantitative assessments in terms of the devised utility metrics.

Development of Kilo-Pixel Arrays of Transition-Edge Sensors for X-Ray Spectroscopy

NASA Technical Reports Server (NTRS)

Adams, J. S.; Bandler, S. R.; Busch, S. E.; Chervenak, J. A.; Chiao, M. P.; Eckart, M. E.; Ewin, A. J.; Finkbeiner, F. M.; Kelley, R. L.; Kelly, D. P.;

Positron-Induced Luminescence.

PubMed

Stenson, E V; Hergenhahn, U; Stoneking, M R; Pedersen, T Sunn

2018-04-06

We report on the observation that low-energy positrons incident on a phosphor screen produce significantly more luminescence than electrons do. For two different wide-band-gap semiconductor phosphors (ZnS:Ag and ZnO:Zn), we compare the luminescent response to a positron beam with the response to an electron beam. For both phosphors, the positron response is significantly brighter than the electron response, by a factor that depends strongly on incident energy (0-5 keV). Positrons with just a few tens of electron-volts of energy (for ZnS:Ag) or less (for ZnO:Zn) produce as much luminescence as is produced by electrons with several kilo-electron-volts. We attribute this effect to valence band holes and excited electrons produced by positron annihilation and subsequent Auger processes. These results demonstrate a valuable approach for addressing long-standing questions about luminescent materials.

Positron-Induced Luminescence

NASA Astrophysics Data System (ADS)

Stenson, E. V.; Hergenhahn, U.; Stoneking, M. R.; Pedersen, T. Sunn

2018-04-01

We report on the observation that low-energy positrons incident on a phosphor screen produce significantly more luminescence than electrons do. For two different wide-band-gap semiconductor phosphors (ZnS:Ag and ZnO:Zn), we compare the luminescent response to a positron beam with the response to an electron beam. For both phosphors, the positron response is significantly brighter than the electron response, by a factor that depends strongly on incident energy (0-5 keV). Positrons with just a few tens of electron-volts of energy (for ZnS:Ag) or less (for ZnO:Zn) produce as much luminescence as is produced by electrons with several kilo-electron-volts. We attribute this effect to valence band holes and excited electrons produced by positron annihilation and subsequent Auger processes. These results demonstrate a valuable approach for addressing long-standing questions about luminescent materials.

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.

Fast ignition realization experiment with high-contrast kilo-joule peta-watt LFEX laser and strong external magnetic field

NASA Astrophysics Data System (ADS)

Fujioka, Shinsuke; Arikawa, Yasunobu; Kojima, Sadaoki; Johzaki, Tomoyuki; Nagatomo, Hideo; Sawada, Hiroshi; Lee, Seung Ho; Shiroto, Takashi; Ohnishi, Naofumi; Morace, Alessio; Vaisseau, Xavier; Sakata, Shohei; Abe, Yuki; Matsuo, Kazuki; Farley Law, King Fai; Tosaki, Shota; Yogo, Akifumi; Shigemori, Keisuke; Hironaka, Yoichiro; Zhang, Zhe; Sunahara, Atsushi; Ozaki, Tetsuo; Sakagami, Hitoshi; Mima, Kunioki; Fujimoto, Yasushi; Yamanoi, Kohei; Norimatsu, Takayoshi; Tokita, Shigeki; Nakata, Yoshiki; Kawanaka, Junji; Jitsuno, Takahisa; Miyanaga, Noriaki; Nakai, Mitsuo; Nishimura, Hiroaki; Shiraga, Hiroyuki; Kondo, Kotaro; Bailly-Grandvaux, Mathieu; Bellei, Claudio; Santos, João Jorge; Azechi, Hiroshi

2016-05-01

A petawatt laser for fast ignition experiments (LFEX) laser system [N. Miyanaga et al., J. Phys. IV France 133, 81 (2006)], which is currently capable of delivering 2 kJ in a 1.5 ps pulse using 4 laser beams, has been constructed beside the GEKKO-XII laser facility for demonstrating efficient fast heating of a dense plasma up to the ignition temperature under the auspices of the Fast Ignition Realization EXperiment (FIREX) project [H. Azechi et al., Nucl. Fusion 49, 104024 (2009)]. In the FIREX experiment, a cone is attached to a spherical target containing a fuel to prevent a corona plasma from entering the path of the intense heating LFEX laser beams. The LFEX laser beams are focused at the tip of the cone to generate a relativistic electron beam (REB), which heats a dense fuel core generated by compression of a spherical deuterized plastic target induced by the GEKKO-XII laser beams. Recent studies indicate that the current heating efficiency is only 0.4%, and three requirements to achieve higher efficiency of the fast ignition (FI) scheme with the current GEKKO and LFEX systems have been identified: (i) reduction of the high energy tail of the REB; (ii) formation of a fuel core with high areal density using a limited number (twelve) of GEKKO-XII laser beams as well as a limited energy (4 kJ of 0.53-μm light in a 1.3 ns pulse); (iii) guiding and focusing of the REB to the fuel core. Laser-plasma interactions in a long-scale plasma generate electrons that are too energetic to efficiently heat the fuel core. Three actions were taken to meet the first requirement. First, the intensity contrast of the foot pulses to the main pulses of the LFEX was improved to >109. Second, a 5.5-mm-long cone was introduced to reduce pre-heating of the inner cone wall caused by illumination of the unconverted 1.053-μm light of implosion beam (GEKKO-XII). Third, the outside of the cone wall was coated with a 40-μm plastic layer to protect it from the pressure caused by imploding plasma. Following the above improvements, conversion of 13% of the LFEX laser energy to a low energy portion of the REB, whose slope temperature is 0.7 MeV, which is close to the ponderomotive scaling value, was achieved. To meet the second requirement, the compression of a solid spherical ball with a diameter of 200-μm to form a dense core with an areal density of ˜0.07 g/cm2 was induced by a laser-driven spherically converging shock wave. Converging shock compression is more hydrodynamically stable compared to shell implosion, while a hot spot cannot be generated with a solid ball target. Solid ball compression is preferable also for compressing an external magnetic field to collimate the REB to the fuel core, due to the relatively small magnetic Reynolds number of the shock compressed region. To meet the third requirement, we have generated a strong kilo-tesla magnetic field using a laser-driven capacitor-coil target. The strength and time history of the magnetic field were characterized with proton deflectometry and a B-dot probe. Guidance of the REB using a 0.6-kT field in a planar geometry has been demonstrated at the LULI 2000 laser facility. In a realistic FI scenario, a magnetic mirror is formed between the REB generation point and the fuel core. The effects of the strong magnetic field on not only REB transport but also plasma compression were studied using numerical simulations. According to the transport calculations, the heating efficiency can be improved from 0.4% to 4% by the GEKKO and LFEX laser system by meeting the three requirements described above. This efficiency is scalable to 10% of the heating efficiency by increasing the areal density of the fuel core.

Fast ignition realization experiment with high-contrast kilo-joule peta-watt LFEX laser and strong external magnetic field

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

Fujioka, Shinsuke, E-mail: sfujioka@ile.osaka-u.ac.jp; Arikawa, Yasunobu; Kojima, Sadaoki

A petawatt laser for fast ignition experiments (LFEX) laser system [N. Miyanaga et al., J. Phys. IV France 133, 81 (2006)], which is currently capable of delivering 2 kJ in a 1.5 ps pulse using 4 laser beams, has been constructed beside the GEKKO-XII laser facility for demonstrating efficient fast heating of a dense plasma up to the ignition temperature under the auspices of the Fast Ignition Realization EXperiment (FIREX) project [H. Azechi et al., Nucl. Fusion 49, 104024 (2009)]. In the FIREX experiment, a cone is attached to a spherical target containing a fuel to prevent a corona plasma frommore » entering the path of the intense heating LFEX laser beams. The LFEX laser beams are focused at the tip of the cone to generate a relativistic electron beam (REB), which heats a dense fuel core generated by compression of a spherical deuterized plastic target induced by the GEKKO-XII laser beams. Recent studies indicate that the current heating efficiency is only 0.4%, and three requirements to achieve higher efficiency of the fast ignition (FI) scheme with the current GEKKO and LFEX systems have been identified: (i) reduction of the high energy tail of the REB; (ii) formation of a fuel core with high areal density using a limited number (twelve) of GEKKO-XII laser beams as well as a limited energy (4 kJ of 0.53-μm light in a 1.3 ns pulse); (iii) guiding and focusing of the REB to the fuel core. Laser–plasma interactions in a long-scale plasma generate electrons that are too energetic to efficiently heat the fuel core. Three actions were taken to meet the first requirement. First, the intensity contrast of the foot pulses to the main pulses of the LFEX was improved to >10{sup 9}. Second, a 5.5-mm-long cone was introduced to reduce pre-heating of the inner cone wall caused by illumination of the unconverted 1.053-μm light of implosion beam (GEKKO-XII). Third, the outside of the cone wall was coated with a 40-μm plastic layer to protect it from the pressure caused by imploding plasma. Following the above improvements, conversion of 13% of the LFEX laser energy to a low energy portion of the REB, whose slope temperature is 0.7 MeV, which is close to the ponderomotive scaling value, was achieved. To meet the second requirement, the compression of a solid spherical ball with a diameter of 200-μm to form a dense core with an areal density of ∼0.07 g/cm{sup 2} was induced by a laser-driven spherically converging shock wave. Converging shock compression is more hydrodynamically stable compared to shell implosion, while a hot spot cannot be generated with a solid ball target. Solid ball compression is preferable also for compressing an external magnetic field to collimate the REB to the fuel core, due to the relatively small magnetic Reynolds number of the shock compressed region. To meet the third requirement, we have generated a strong kilo-tesla magnetic field using a laser-driven capacitor-coil target. The strength and time history of the magnetic field were characterized with proton deflectometry and a B-dot probe. Guidance of the REB using a 0.6-kT field in a planar geometry has been demonstrated at the LULI 2000 laser facility. In a realistic FI scenario, a magnetic mirror is formed between the REB generation point and the fuel core. The effects of the strong magnetic field on not only REB transport but also plasma compression were studied using numerical simulations. According to the transport calculations, the heating efficiency can be improved from 0.4% to 4% by the GEKKO and LFEX laser system by meeting the three requirements described above. This efficiency is scalable to 10% of the heating efficiency by increasing the areal density of the fuel core.« less

Drop of coherence of the lower kilo-Hz QPO in neutron stars: Is there a link with the innermost stable circular orbit?

NASA Astrophysics Data System (ADS)

Barret, D.; Olive, J.-F.; Miller, M. Coleman

2005-11-01

Using all available archival data from the Rossi X-ray Timing Explorer (RXTE), we follow the frequency of the kilo-Hz QPOs in three low luminosity neutron star low mass X-ray binaries; namely 4U 1636-536, 4U 1608-522, and 4U 1735-44. Following earlier work by Barret et al. (2005a,b), we focus our analysis on the lower kilo-Hz QPO, for which we study the dependency of its quality factor (Q=\

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.

A comprehensive system for dosimetric commissioning and Monte Carlo validation for the small animal radiation research platform

PubMed Central

Tryggestad, E; Armour, M; Iordachita, I; Verhaegen, F; Wong, J W

2011-01-01

Our group has constructed the small animal radiation research platform (SARRP) for delivering focal, kilo-voltage radiation to targets in small animals under robotic control using cone-beam CT guidance. The present work was undertaken to support the SARRP’s treatment planning capabilities. We have devised a comprehensive system for characterizing the radiation dosimetry in water for the SARRP and have developed a Monte Carlo dose engine with the intent of reproducing these measured results. We find that the SARRP provides sufficient therapeutic dose rates ranging from 102 to 228 cGy min−1 at 1 cm depth for the available set of high-precision beams ranging from 0.5 to 5 mm in size. In terms of depth–dose, the mean of the absolute percentage differences between the Monte Carlo calculations and measurement is 3.4% over the full range of sampled depths spanning 0.5–7.2 cm for the 3 and 5 mm beams. The measured and computed profiles for these beams agree well overall; of note, good agreement is observed in the profile tails. Especially for the smallest 0.5 and 1 mm beams, including a more realistic description of the effective x-ray source into the Monte Carlo model may be important. PMID:19687532

A comprehensive system for dosimetric commissioning and Monte Carlo validation for the small animal radiation research platform.

PubMed

Tryggestad, E; Armour, M; Iordachita, I; Verhaegen, F; Wong, J W

2009-09-07

Our group has constructed the small animal radiation research platform (SARRP) for delivering focal, kilo-voltage radiation to targets in small animals under robotic control using cone-beam CT guidance. The present work was undertaken to support the SARRP's treatment planning capabilities. We have devised a comprehensive system for characterizing the radiation dosimetry in water for the SARRP and have developed a Monte Carlo dose engine with the intent of reproducing these measured results. We find that the SARRP provides sufficient therapeutic dose rates ranging from 102 to 228 cGy min(-1) at 1 cm depth for the available set of high-precision beams ranging from 0.5 to 5 mm in size. In terms of depth-dose, the mean of the absolute percentage differences between the Monte Carlo calculations and measurement is 3.4% over the full range of sampled depths spanning 0.5-7.2 cm for the 3 and 5 mm beams. The measured and computed profiles for these beams agree well overall; of note, good agreement is observed in the profile tails. Especially for the smallest 0.5 and 1 mm beams, including a more realistic description of the effective x-ray source into the Monte Carlo model may be important.

Electrostatic Inflation of Membrane Space Structures

NASA Astrophysics Data System (ADS)

Stiles, Laura A.

Membrane space structures provide a lightweight and cost effective alternative to traditional mechanical systems. The low-mass and high deployed-to-stored volume ratios allow for larger structures to be launched, expanding on-orbit science and technology capabilities. This research explores a novel method for deployment of membrane space structures using electrostatic pressure as the inflation mechanism. Applying electric charge to a layered gossamer structure provides an inflationary pressure due to the repulsive electrostatic forces between the charged layers. The electrostatic inflation of membrane structures (EIMS) concept is particularly applicable to non-precision structures such as sunshields or drag de-orbiting devices. This research addresses three fundamental topics: necessary conditions for EIMS in a vacuum, necessary conditions for EIMS in a plasma, and charging methods. Vacuum demonstrations show that less than 10 kiloVolts are required for electrostatic inflation of membrane structures in 1-g. On-orbit perturbation forces can be much smaller, suggesting feasible voltage requirements. Numerical simulation enables a relationship between required inflation pressure (to offset disturbances) and voltage. 100's of Volts are required for inflation in geosynchronous orbits (GEO) and a few kiloVolts in low Earth orbit (LEO). While GEO plasma has a small impact on the EIMS performance, Debye shielding at LEO reduces the electrostatic pressure. The classic Debye shielding prediction is far worse than actual shielding, raising the `effective' Debye length to the meter scale in LEO, suggesting feasibility for EIMS in LEO. Charged particle emission and remote charging methods are explored as inflation mechanisms. Secondary electron emission characteristics of EIMS materials were determined experimentally. Nonlinear fits to the Sternglass curve determined a maximum yield of 1.83 at 433 eV for Aluminized Kapton and a maximum yield of 1.78 at 511 eV for Aluminized Mylar. Remote charging was demonstrated to -500 V with a 5 keV electron beam. Charge emission power levels are below 1 Watt in GEO and from 10's of Watt to a kiloWatt in LEO.

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.

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.

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.

JPRS Report East Asia Southeast Asia

DTIC Science & Technology

1987-06-24

cashew nut , orange, and lemon. Many provinces increased their industrial crops by 10 to 15 percent and 15 to 20 percent in terms of area and...Evaporated Milk (1 Small Tin) . Fish/Meat/Poultry (1 Kilo) Eggs (3 Pieces) Dried Beans and Nuts . (100 grams) Cereals (2 Kilos) Kamote/Potatoes (1

KiloPower Program

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

McClure, Patrick Ray

2016-08-04

These are the slides for a phone interview with Aerospace America magazine of the AIAA. It goes over the KiloPower Program at Los Alamos National Laboratory (LANL), and covers the following: 1 kWe Kilopower, 10 kWe Kilopower, Kilopower Reactor Using Stirling Technology (KRUSTY) Integration Test (DAF), Reactor Configuration, and Platen Positions.

Mega-Amp Opening Switch with Nested Electrodes/Pulsed Generator of Ion and Ion Cluster Beams

DTIC Science & Technology

1987-07-30

The use of a plasma focus as a mega-amp opening switch has been demonstrated by two modes of operation: (a) Single shot mode; (b) Repetitive Mode...energy level and under the same voltage and filling-pressure conditions but without field distortion elements. Misfirings of the plasma focus machine...are also virtually eliminated by using FDE at the coaxial electrode breech. The tests (based on about 10000 shots and five plasma focus machines

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.

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.

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.

Uniformity of cylindrical imploding underwater shockwaves at very small radii

NASA Astrophysics Data System (ADS)

Yanuka, D.; Rososhek, A.; Bland, S. N.; Krasik, Ya. E.

2017-11-01

We compare the convergent shockwaves generated from underwater, cylindrical arrays of copper wire exploded by multiple kilo-ampere current pulses on nanosecond and microsecond scales. In both cases, the pulsed power devices used for the experiments had the same stored energy (˜500 J) and the wire mass was adjusted to optimize energy transfer to the shockwave. Laser backlit framing images of the shock front were achieved down to the radius of 30 μm. It was found that even in the case of initial azimuthal non-symmetry, the shock wave self-repairs in the final stages of its motion, leading to a highly uniform implosion. In both these and previous experiments, interference fringes have been observed in streak and framing images as the shockwave approached the axis. We have been able to accurately model the origin of the fringes, which is due to the propagation of the laser beam diffracting off the uniform converging shock front. The dynamics of the shockwave and its uniformity at small radii indicate that even with only 500 J stored energies, this technique should produce pressures above 1010 Pa on the axis, with temperatures and densities ideal for warm dense matter research.

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.

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

Computational modelling of the cerebral cortical microvasculature: effect of x-ray microbeams versus broad beam irradiation

NASA Astrophysics Data System (ADS)

Merrem, A.; Bartzsch, S.; Laissue, J.; Oelfke, U.

2017-05-01

Microbeam Radiation Therapy is an innovative pre-clinical strategy which uses arrays of parallel, tens of micrometres wide kilo-voltage photon beams to treat tumours. These x-ray beams are typically generated on a synchrotron source. It was shown that these beam geometries allow exceptional normal tissue sparing from radiation damage while still being effective in tumour ablation. A final biological explanation for this enhanced therapeutic ratio has still not been found, some experimental data support an important role of the vasculature. In this work, the effect of microbeams on a normal microvascular network of the cerebral cortex was assessed in computer simulations and compared to the effect of homogeneous, seamless exposures at equal energy absorption. The anatomy of a cerebral microvascular network and the inflicted radiation damage were simulated to closely mimic experimental data using a novel probabilistic model of radiation damage to blood vessels. It was found that the spatial dose fractionation by microbeam arrays significantly decreased the vascular damage. The higher the peak-to-valley dose ratio, the more pronounced the sparing effect. Simulations of the radiation damage as a function of morphological parameters of the vascular network demonstrated that the distribution of blood vessel radii is a key parameter determining both the overall radiation damage of the vasculature and the dose-dependent differential effect of microbeam irradiation.

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.

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.

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.

TOLERANCE TO AMINO ACID MIXTURES AND CASEIN DIGESTS GIVEN INTRAVENOUSLY

PubMed Central

Madden, S. C.; Woods, R. R.; Shull, F. W.; Remington, J. H.; Whipple, G. H.

1945-01-01

Several synthetic mixtures of natural and racemic crystalline amino acids suitable for the daily nitrogen requirement are tested in dogs for their tolerance upon intravenous injection. Certain mixtures of the ten essential amino acids plus non-essential amino acids exclusive of glutamic acid are accepted without any obvious sign of disturbance even at rates above 10 mg. nitrogen per kilo per minute for quantities greater than 300 mg. per kilo. One such mixture consists in parts per 100 of dl-threonine 7, dl-valine 15, l(-)-leucine 10.9, dl-isoleucine 9.9, l(+)-lysine· HCl·H2O 10.9, dl-tryptophane 3, dl-phenylalanine 9.9, dl-methionine 6, l(+)-histidine·HCl·H2O 5, l(+)-arginine-HCl 5, glycine 9.9, dl-α-alanine 4, dl-serine 2, l(-)-cystine 0.5, and l(-)-tyrosine 1. In addition other well tolerated mixtures included the prolines. When glutamic acid, natural or racemic, is included in similar mixtures vomiting reactions frequently occur at nitrogen rates above 4 mg. per kilo per minute. Vomiting almost always occurs on the first daily injection containing glutamic acid and usually on any subsequent injection containing more than 100 mg. glutamic acid per kilo unless given very slowly. Upon the addition of glycine certain mixtures of the ten essential amino acids show an improved tolerance. Two casein digests tested usually produced vomiting at injection rates above 2 mg. nitrogen per kilo per minute, probably because of their glutamic acid content. No serious reaction has ever occurrred to any mixture of amino acids or casein digest tested. Elimination of minor reactions such as vomiting appears possible and desirable for greater usefulness of these solutions in parenteral feeding. PMID:19871468

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

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

Estimates of fluid and energy balances of Apollo 17

NASA Technical Reports Server (NTRS)

Johnson, P. C.; Leach, C. S.; Rambaut, P. C.

1973-01-01

Fluid and caloric balance has been calculated for the Apollo 17 crew. This included measurement of nitrogen, water, and caloric value of the ingested food and the volume and nitrogen content of the excreted urine and feces. Body composition changes were determined from total body water and extracellular fluid volume differences. The body composition measurements made it possible to divide the weight loss into lean body mass and adipose tissue losses. From this division a caloric equivalent was calculated. These tissue losses indicated that the caloric requirements of the mission were considerably greater than the actual caloric intake. The 3.3 kilo mean loss of body weight represented 1 kilo of lean body mass and 2.3 kilos of adipose tissue. Calculated fluid balance was more positive during the mission than during the control period. These changes are unlike the body composition and fluid balance changes reported in bedrested subjects.

High throughput film dosimetry in homogeneous and heterogeneous media for a small animal irradiator

PubMed Central

Wack, L.; Ngwa, W.; Tryggestad, E.; Tsiamas, P.; Berbeco, R.; Ng, S.K.; Hesser, J.

2013-01-01

Purpose We have established a high-throughput Gafchromic film dosimetry protocol for narrow kilo-voltage beams in homogeneous and heterogeneous media for small-animal radiotherapy applications. The kV beam characterization is based on extensive Gafchromic film dosimetry data acquired in homogeneous and heterogeneous media. An empirical model is used for parameterization of depth and off-axis dependence of measured data. Methods We have modified previously published methods of film dosimetry to suit the specific tasks of the study. Unlike film protocols used in previous studies, our protocol employs simultaneous multichannel scanning and analysis of up to nine Gafchromic films per scan. A scanner and background correction were implemented to improve accuracy of the measurements. Measurements were taken in homogeneous and inhomogeneous phantoms at 220 kVp and a field size of 5 × 5 mm2. The results were compared against Monte Carlo simulations. Results Dose differences caused by variations in background signal were effectively removed by the corrections applied. Measurements in homogeneous phantoms were used to empirically characterize beam data in homogeneous and heterogeneous media. Film measurements in inhomogeneous phantoms and their empirical parameterization differed by about 2%–3%. The model differed from MC by about 1% (water, lung) to 7% (bone). Good agreement was found for measured and modelled off-axis ratios. Conclusions EBT2 films are a valuable tool for characterization of narrow kV beams, though care must be taken to eliminate disturbances caused by varying background signals. The usefulness of the empirical beam model in interpretation and parameterization of film data was demonstrated. PMID:23510532

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

Americium-241 Decorporation Model

DTIC Science & Technology

2014-10-01

doses compared Radiation Dose Convert mass to activity if needed Calculate critical organ doses/ effective whole body dose (Christy and Eckerman...compartments over time with and without treatment, excretion rates, and radiation doses to critical organs. Calculations from the model may be used to...268 x E + 2 newton-meter (N/m) pound-force/foot2 4.788 026 x E – 2 kilo pascal (kPa) pound-force/inch2 (psi) 6.894 757 kilo pascal (kPa) pound- mass

System Modeling of kJ-class Petawatt Lasers at LLNL

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

Shverdin, M Y; Rushford, M; Henesian, M A

2010-04-14

Advanced Radiographic Capability (ARC) project at the National Ignition Facility (NIF) is designed to produce energetic, ultrafast x-rays in the range of 70-100 keV for backlighting NIF targets. The chirped pulse amplification (CPA) laser system will deliver kilo-Joule pulses at an adjustable pulse duration from 1 ps to 50 ps. System complexity requires sophisticated simulation and modeling tools for design, performance prediction, and comprehension of experimental results. We provide a brief overview of ARC, present our main modeling tools, and describe important performance predictions. The laser system (Fig. 1) consists of an all-fiber front end, including chirped-fiber Bragg grating (CFBG)more » stretchers. The beam after the final fiber amplifier is split into two apertures and spatially shaped. The split beam first seeds a regenerative amplifier and is then amplified in a multi-pass Nd:glass amplifier. Next, the preamplified chirped pulse is split in time into four identical replicas and injected into one NIF Quad. At the output of the NIF beamline, each of the eight amplified pulses is compressed in an individual, folded, four-grating compressor. Compressor grating pairs have slightly different groove densities to enable compact folding geometry and eliminate adjacent beam cross-talk. Pulse duration is adjustable with a small, rack-mounted compressor in the front-end. We use non-sequential ray-tracing software, FRED for design and layout of the optical system. Currently, our FRED model includes all of the optical components from the output of the fiber front end to the target center (Fig. 2). CAD designed opto-mechanical components are imported into our FRED model to provide a complete system description. In addition to incoherent ray tracing and scattering analysis, FRED uses Gaussian beam decomposition to model coherent beam propagation. Neglecting nonlinear effects, we can obtain a nearly complete frequency domain description of the ARC beam at different stages in the system. We employ 3D Fourier based propagation codes: MIRO, Virtual Beamline (VBL), and PROP for time-domain pulse analysis. These codes simulate nonlinear effects, calculate near and far field beam profiles, and account for amplifier gain. Verification of correct system set-up is a major difficulty to using these codes. VBL and PROP predictions have been extensively benchmarked to NIF experiments, and the verified descriptions of specific NIF beamlines are used for ARC. MIRO has the added capability of treating bandwidth specific effects of CPA. A sample MIRO model of the NIF beamline is shown in Fig. 3. MIRO models are benchmarked to VBL and PROP in the narrow bandwidth mode. Developing a variety of simulation tools allows us to cross-check predictions of different models and gain confidence in their fidelity. Preliminary experiments, currently in progress, are allowing us to validate and refine our models, and help guide future experimental campaigns.« 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.

The status of Fast Ignition Realization Experiment (FIREX) and prospects for inertial fusion energy

NASA Astrophysics Data System (ADS)

Azechi, H.; FIREX Project Team

2016-05-01

Here we report recent progress for the fast ignition inertial confinement fusion demonstration. The fraction of low energy (< 1 MeV) component of the relativistic electron beam (REB), which efficiently heats the fuel core, increases by a factor of 4 by enhancing pulse contrast of heating laser and removing preformed plasma sources. Kilo-tesla magnetic field is studied to guide the diverging REB to the fuel core. The transport simulation of the REB accelerated by the heating laser in the externally applied and compressed magnetic field indicates that the REB can be guided efficiently to the fuel core. The integrated simulation shows > 4% of the heating efficiency and > 4 keV of ion temperature are achievable by using GEKKO-XII and LFEX, properly designed cone-fuel and an external magnetic field.

Integrated simulation of magnetic-field-assist fast ignition laser fusion

NASA Astrophysics Data System (ADS)

Johzaki, T.; Nagatomo, H.; Sunahara, A.; Sentoku, Y.; Sakagami, H.; Hata, M.; Taguchi, T.; Mima, K.; Kai, Y.; Ajimi, D.; Isoda, T.; Endo, T.; Yogo, A.; Arikawa, Y.; Fujioka, S.; Shiraga, H.; Azechi, H.

2017-01-01

To enhance the core heating efficiency in fast ignition laser fusion, the concept of relativistic electron beam guiding by external magnetic fields was evaluated by integrated simulations for FIREX class targets. For the cone-attached shell target case, the core heating performance deteriorates by applying magnetic fields since the core is considerably deformed and most of the fast electrons are reflected due to the magnetic mirror formed through the implosion. On the other hand, in the case of a cone-attached solid ball target, the implosion is more stable under the kilo-tesla-class magnetic field. In addition, feasible magnetic field configuration is formed through the implosion. As a result, the core heating efficiency doubles by magnetic guiding. The dependence of core heating properties on the heating pulse shot timing was also investigated for the solid ball target.

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.

Generation and Characterization of Electron Bunches with Ramped Current Profiles in a Dual-Frequency Superconducting Linear Accelerator

DOE PAGES

Piot, P.; Behrens, C.; Gerth, C.; ...

2011-09-07

We report on the successful experimental generation of electron bunches with ramped current profiles. The technique relies on impressing nonlinear correlations in the longitudinal phase space using a superconducing radiofrequency linear accelerator operating at two frequencies and a current-enhancing dispersive section. The produced {approx} 700-MeV bunches have peak currents of the order of a kilo-Ampere. Data taken for various accelerator settings demonstrate the versatility of the method and in particular its ability to produce current profiles that have a quasi-linear dependency on the longitudinal (temporal) coordinate. The measured bunch parameters are shown, via numerical simulations, to produce gigavolt-per-meter peak acceleratingmore » electric fields with transformer ratios larger than 2 in dielectric-lined waveguides.« less

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.

Diffusion of Innovation: Factors Promoting Interest in Solar Photovoltaic Generation Systems Within Air Force Installations

DTIC Science & Technology

2007-03-01

KMO Kaiser-Meyer-Olkin KW Kilo-watts KwH Kilo-watt-hour MAJCOM Major Command MSR Million Solar Roofs MW Mega-watts MWH/yr Mega-watt...direct oblimin rotation and factor restriction for each analysis. A Kaiser-Meyer-Olkin ( KMO ) value of .315 was calculated for the items related to...knowledge, experience, and familiarity, while a KMO value of .389 was calculated for the items related to the two variables of motivation and interest

46 CFR Appendix II to Part 153 - Metric Units Used in Part 153

Code of Federal Regulations, 2011 CFR

2011-10-01

... common metric Force Newton N 0.225 lbs. Length Meter m 39.37 in. Centimeter cm .3937 in. Pressure Pascal Pa 1.450×10−4 lbs/in 2. Kilo-Pascal (1,000 Pascals) kPa 0.145 lbs/in 2. Kilo-Pascal kPa 1.02×10−2 kg/cm2. ......do kPa 1×10 3 N/m 2. Temperature Degree Celsius °C 5/9 (°F-32). Viscosity milli-Pascal...

46 CFR Appendix II to Part 153 - Metric Units Used in Part 153

Code of Federal Regulations, 2010 CFR

2010-10-01

... common metric Force Newton N 0.225 lbs. Length Meter m 39.37 in. Centimeter cm .3937 in. Pressure Pascal Pa 1.450×10−4 lbs/in 2. Kilo-Pascal (1,000 Pascals) kPa 0.145 lbs/in 2. Kilo-Pascal kPa 1.02×10−2 kg/cm2. ......do kPa 1×10 3 N/m 2. Temperature Degree Celsius °C 5/9 (°F-32). Viscosity milli-Pascal...

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

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.

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.

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.

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.

Evaluation of Military Range Berm Effectiveness in Protecting Red-cockaded Woodpecker Foraging and Nesting Habitat

DTIC Science & Technology

2011-04-01

Benning – Malone 5 Malone 5 is an unbermed SA machine gun (firing 7.62 mm or smaller caliber rounds) range with elevated firing and target boxes (~1...plots, not originally allocated. Fort Stewart – Kilo The Kilo range on Fort Stewart is an unbermed SA machine gun (firing 7.62 mm or smaller...is a bermed SA machine gun (firing 7.62 mm or smaller caliber rounds) range with elevated firing boxes and targets (~1-m high; Figures 6 and 7). The

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.

Conceptual design of sub-exa-watt system by using optical parametric chirped pulse amplification

NASA Astrophysics Data System (ADS)

Kawanaka, J.; Tsubakimoto, K.; Yoshida, H.; Fujioka, K.; Fujimoto, Y.; Tokita, S.; Jitsuno, T.; Miyanaga, N.; Gekko-EXA Design Team

2016-03-01

A 50 PW ultrahigh-peak-power laser has been conceptually designed, which is based on optical parametric chirped pulse amplification (OPCPA). A 250 J DPSSL and a flash- lamp-pumped kJ laser are adopted as new repeatable pump source. The existed LFEX-laser with more than ten kilo joules are used in the final amplifier stage and the OPCPA with the 2x2 tiled pump beams in random phase has been proposed with several ten centimeter aperture. A pulse duration of amplified pulses is set at less than 10 fs. A broadband OPCPA with ∼500 nm of the gain spectral width near 1 μm is required. A partially deuterated KDP (p-DKDP) crystal is one of the most promising nonlinear crystals and our numerical calculation ensured such ultra-broad gain width. p-DKDP crystals with several deuteration ratio have been successfully grown.

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.

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.

[The scientific basis of current official dietary recommendations in relation to pregnancy].

PubMed

Olsen, Sjúrour F; Dragsted, Lars O; Hansen, Harald S; Michaelsen, Kim Fleischer; Milman, Nils; Nielsen, Mie Julin; Ovesen, Lars; Petersen, Tove; Tabor, Ann

2005-06-20

The Danish Nutrition Council has examined the latest scientific literature on nutrition during pregnancy to evaluate the basis for the existing official recommendations. The recommendation to overweight women to gain only eight kilo should be accompanied with a recommendation to lose weight pre-conceptionally. Individualised recommendations should be provided in the prevention of iron deficiency, and the recommendation for calcium should include information on quantity. The recommendation of periconceptional folic acid supplementation does not benefit unplanned pregnancies. Arguments exist for adding a recommendation for vitamin D.

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.

Geotourism of Batu Dinding Kilo Tiga, Amurang District, South Minahasa Regency, North Sulawesi - Indonesia

NASA Astrophysics Data System (ADS)

Elvien Kristian, V. A.; Ridho, Ahmad; Diaz Alffi, Febriany

2018-03-01

Start your abstract Batu Dinding Kilo Tiga or famously called Batu Dinding is one of tourist destinations in Kilo Tiga village, Amurang district, South Minahasa regency, North Sulawesi. In terms of Geology, Batu Dinding is a rock cliff with columnar structure and constituted in the form of andesitic thrakit rocks which is one of intermediate igneous rocks of volcanic aged Late Tertiary until Early Quarter, precisely during the Pleistocene. The structure and appearance of Batu Dinding was like a ladder, make Batu Dinding in demand as a destination for wall climbing or cliff hanger. The area around the Batu Dinding, there are Pamurapa River that at a time when it was high tide, can be used for rafting. Unfortunately, the accommodation and accessibility of the Amurang Batu Dinding are poor, causing Batu Dinding rarely to visit. The aim of the paper is to introduce as well as media publications of Batu Dinding tourism in order to increase local income and in addition it can be as a geological site for learning purposes.

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.

Beam energy considerations for gold nano-particle enhanced radiation treatment.

PubMed

Van den Heuvel, F; Locquet, Jean-Pierre; Nuyts, S

2010-08-21

A novel approach using nano-technology enhanced radiation modalities is investigated. The proposed methodology uses antibodies labeled with organically inert metals with a high atomic number. Irradiation using photons with energies in the kilo-electron volt (keV) range shows an increase in dose due to a combination of an increase in photo-electric interactions and a pronounced generation of Auger and/or Coster-Krönig (A-CK) electrons. The dependence of the dose deposition on various factors is investigated using Monte Carlo simulation models. The factors investigated include agent concentration, spectral dependence looking at mono-energetic sources as well as classical bremsstrahlung sources. The optimization of the energy spectrum is performed in terms of physical dose enhancement as well as the dose deposited by Auger and/or Coster-Krönig electrons and their biological effectiveness. A quasi-linear dependence on concentration and an exponential decrease within the target medium is observed. The maximal dose enhancement is dependent on the position of the target in the beam. Apart from irradiation with low-photon energies (10-20 keV) there is no added benefit from the increase in generation of Auger electrons. Interestingly, a regular 110 kVp bremsstrahlung spectrum shows a comparable enhancement in comparison with the optimized mono-energetic sources. In conclusion we find that the use of enhanced nano-particles shows promise to be implemented quite easily in regular clinics on a physical level due to the advantageous properties in classical beams.

Beam energy considerations for gold nano-particle enhanced radiation treatment

NASA Astrophysics Data System (ADS)

Van den Heuvel, F.; Locquet, Jean-Pierre; Nuyts, S.

2010-08-01

A novel approach using nano-technology enhanced radiation modalities is investigated. The proposed methodology uses antibodies labeled with organically inert metals with a high atomic number. Irradiation using photons with energies in the kilo-electron volt (keV) range shows an increase in dose due to a combination of an increase in photo-electric interactions and a pronounced generation of Auger and/or Coster-Krönig (A-CK) electrons. The dependence of the dose deposition on various factors is investigated using Monte Carlo simulation models. The factors investigated include agent concentration, spectral dependence looking at mono-energetic sources as well as classical bremsstrahlung sources. The optimization of the energy spectrum is performed in terms of physical dose enhancement as well as the dose deposited by Auger and/or Coster-Krönig electrons and their biological effectiveness. A quasi-linear dependence on concentration and an exponential decrease within the target medium is observed. The maximal dose enhancement is dependent on the position of the target in the beam. Apart from irradiation with low-photon energies (10-20 keV) there is no added benefit from the increase in generation of Auger electrons. Interestingly, a regular 110 kVp bremsstrahlung spectrum shows a comparable enhancement in comparison with the optimized mono-energetic sources. In conclusion we find that the use of enhanced nano-particles shows promise to be implemented quite easily in regular clinics on a physical level due to the advantageous properties in classical beams.

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

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.

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

Finding strong gravitational lenses in the Kilo Degree Survey with Convolutional Neural Networks

NASA Astrophysics Data System (ADS)

Petrillo, C. E.; Tortora, C.; Chatterjee, S.; Vernardos, G.; Koopmans, L. V. E.; Verdoes Kleijn, G.; Napolitano, N. R.; Covone, G.; Schneider, P.; Grado, A.; McFarland, J.

2017-11-01

The volume of data that will be produced by new-generation surveys requires automatic classification methods to select and analyse sources. Indeed, this is the case for the search for strong gravitational lenses, where the population of the detectable lensed sources is only a very small fraction of the full source population. We apply for the first time a morphological classification method based on a Convolutional Neural Network (CNN) for recognizing strong gravitational lenses in 255 deg2 of the Kilo Degree Survey (KiDS), one of the current-generation optical wide surveys. The CNN is currently optimized to recognize lenses with Einstein radii ≳1.4 arcsec, about twice the r-band seeing in KiDS. In a sample of 21 789 colour-magnitude selected luminous red galaxies (LRGs), of which three are known lenses, the CNN retrieves 761 strong-lens candidates and correctly classifies two out of three of the known lenses. The misclassified lens has an Einstein radius below the range on which the algorithm is trained. We down-select the most reliable 56 candidates by a joint visual inspection. This final sample is presented and discussed. A conservative estimate based on our results shows that with our proposed method it should be possible to find ∼100 massive LRG-galaxy lenses at z ≲ 0.4 in KiDS when completed. In the most optimistic scenario, this number can grow considerably (to maximally ∼2400 lenses), when widening the colour-magnitude selection and training the CNN to recognize smaller image-separation lens systems.

BURDEN OF TUBERCULOSIS AMONG STUDENTS IN TWO ETHIOPIAN UNIVERSITIES

PubMed Central

Mekonnen, Abiyu; Petros, Beyene

2017-01-01

Introduction Tuberculosis outbreaks emerge occasionally in long-term care facilities and various educational establishments. This study was designed to determine the five year overall prevalence and trend of tuberculosis and associated factors among students at Adama Science and Technology University and Addis Ababa University Sidist Kilo campus. Methods A five-year retrospective study was conducted on students medical records of tuberculosis Directly Observed Treatment Short Course clinics from September 2009 – July 2014. The overall prevalence and the trend of smear positive, smear negative and extra pulmonary tuberculosis cases was determined. Odds ratio with 95 percent confidence interval was calculated for categorical variables using a multivariate logistic regression model to assess the strength of association. Results A total of 112 and 263 tuberculos cases were recorded in Addis Ababa University Sidist Kilo campus and Adama Science and Technology University, respectively. The mean proportion of tuberculosis cases of all types among the total number of students enrolled at Adama Science and Technology University and Addis Ababa University Sidist Kilo campus was 1098.1 and 511.7 cases per 100,000 population, respectively. There was a statistically significant difference in prevalence of tuberculosis among students in Adama Science and Technology University compared to that in Addis Ababa University Sidist Kilo campus [adjusted odds ration: 2.881, 95% CI (1.76–4.71)]. The trend of tuberculosis prevalence showed a steady decline from the first to the last year of the study period. Conclusion The number of tuberculosis cases observed among university students in this study was high. Governmental and nongovernmental agencies involved in tuberculosis control must consider higher education institutions as focal points for prevention and elimination of tuberculosis in Ethiopia. PMID:29115116

BURDEN OF TUBERCULOSIS AMONG STUDENTS IN TWO ETHIOPIAN UNIVERSITIES.

PubMed

Mekonnen, Abiyu; Petros, Beyene

2016-10-01

Tuberculosis outbreaks emerge occasionally in long-term care facilities and various educational establishments. This study was designed to determine the five year overall prevalence and trend of tuberculosis and associated factors among students at Adama Science and Technology University and Addis Ababa University Sidist Kilo campus. A five-year retrospective study was conducted on students’ medical records of tuberculosis Directly Observed Treatment Short Course clinics from September 2009– July 2014. The overall prevalence and the trend of smear positive, smear negative and extra pulmonary tuberculosis cases was determined. Odds ratio with 95 percent confidence interval was calculated for categorical variables using a multivariate logistic regression model to assess the strength of association. A total of 112 and 263 tuberculos cases were recorded in Addis Ababa University Sidist Kilo campus and Adama Science and Technology University, respectively. The mean proportion of tuberculosis cases of all types among the total number of students enrolled at Adama Science and Technology University and Addis Ababa University Sidist Kilo campus was 1098.1 and 511.7 cases per 100,000 population, respectively. There was a statistically significant difference in prevalence of tuberculosis among students in Adama Science and Technology University compared to that in Addis Ababa University Sidist Kilo campus [adjusted odds ration: 2.881, 95% CI (1.76-4.71)]. The trend of tuberculosis prevalence showed a steady decline from the first to the last year of the study period. The number of tuberculosis cases observed among university students in this study was high. Governmental and nongovernmental agencies involved in tuberculosis control must consider higher education institutions as focal points for prevention and elimination of tuberculosis in Ethiopia.

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.

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.

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

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.

Hurricanes Kilo, Ignacio and Jimena Surround Hawaii

NASA Image and Video Library

2017-12-08

Major Hurricane Kilo is located around 1220 miles west of Honolulu, Hurricane Ignacio is located around 315 miles east of Hilo and Major Hurricane Jimena is located around 1425 miles east of Hilo, Hawaii. This image was taken by GOES West on August 31, 2015. Credit: NASA/NOAA via NOAA Environmental Visualization Laboratory NASA image use policy. NASA Goddard Space Flight Center enables NASA’s mission through four scientific endeavors: Earth Science, Heliophysics, Solar System Exploration, and Astrophysics. Goddard plays a leading role in NASA’s accomplishments by contributing compelling scientific knowledge to advance the Agency’s mission. Follow us on Twitter Like us on Facebook Find us on Instagram

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

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.

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

Simulation study of core heating properties for recent FIREX-I experiments

NASA Astrophysics Data System (ADS)

Johzaki, Tomoyuki; Kai, Yusuke; Endo, Takuma; Nagatomo, Hideo; Sunahara, Atsushi; Sentoku, Yasuhiko; Taguchi, Toshihiro; Fujioka, Shinsuke; Shiraga, Hiroyuki; Azechi, Hiroshi; Firex Project Team

2016-10-01

The demonstration of efficient core heating is the main purpose of FIREX-I project, where Au cone-attached solid ball CD target is used. For the guiding of fast electron beam generated by relativistic laser plasma interactions, the kilo-Tesla-class longitudinal magnetic field is applied by a capacitor-coil target and kJ-class ns-durration high power laser. In addition, to reduce the collisional effect (energy loss and scattering of fast electrons) during propagation in the Au cone tip, we introduced opened-tip cone (tipless cone). To evaluate the core heating properties, we carried out the integrated simulations, which shows the enhancement of core heating efficiency due to the magnetic guiding and opened-tip cone by a factor of three. These simulation results will be shown and be compared with the experimental results. JSPS KAKENHI (26400532, 15H03758, 16H02245, 15K21767), NIFS Collaboration Research program (NIFS12KUGK05, NIFS14KNSS054), and FIREX project.

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

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

Zhou, L; Bai, S; Zhang, Y

Purpose: To systematically evaluate imaging doses and cancer risks to organs-at-risk as a Result of cumulative doses from various radiological imaging procedures in image-guided radiotherapy (IGRT) in a large cohort of cancer patients. Methods: With IRB approval, imaging procedures (computed tomography, kilo-voltage portal imaging, megavoltage portal imaging and kilo-voltage cone-beam computed tomography) of 4832 cancer patients treated during 4.5 years were collected with their gender, age and circumference. Correlations between patient’s circumference and Monte Carlo simulated-organ dose were applied to estimate organ doses while the cancer risks were reported as 1+ERR using BEIR VII models. Results: 80 cGy or moremore » doses were deposited to brain, lungs and RBM in 273 patients (maximum 136, 278 and 267 cGy, respectively), due largely to repetitive imaging procedures and non-personalized imaging settings. Regardless of gender, relative cancer risk estimates for brain, lungs, and RBM were 3.4 (n = 55), 2.6 (n = 49), 1.8 (n = 25) for age group of 0–19; 1.2 (n = 87), 1.4 (n = 98), 1.3 (n = 51) for age group of 20–39; 1.0 (n = 457), 1.1 (n = 880), 1.8 (n=360) for age group of 40–59; 1.0 (n = 646), 1.1 (n = 1400), 2.3 (n = 716) for age group of 60–79 and 1.0 (n = 108),1.1 (n = 305),1.6 (n = 147) for age group of 80–99. Conclusion: The cumulative imaging doses and associated cancer risks from multi-imaging procedures were patient-specific and site-dependent, with up to 2.7 Gy imaging dose deposited to critical structures in some pediatric patients. The associated cancer risks in brain and lungs for children of age 0 to 19 were 2–3 times larger than those for adults. This study indicated a pressing need for personalized imaging protocol to maximize its clinical benefits while reducing associated cancer risks. Sichuan University Scholarship.« less

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…

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.

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.

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.

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.

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.

Lightning Reporting at 45th Weather Squadron: Recent Improvements

NASA Technical Reports Server (NTRS)

Finn, Frank C.; Roeder, William P.; Buchanan, Michael D.; McNamara, Todd M.; McAllenan, Michael; Winters, Katherine A.; Fitzpatrick, Michael E.; Huddleston, Lisa L.

2010-01-01

The 45th Weather Squadron (45 WS) provides daily lightning reports to space launch customers at CCAFS/KSC. These reports are provided to assess the need to inspect the electronics of satellite payloads, space launch vehicles, and ground support equipment for induced current damage from nearby lightning strokes. The 45 WS has made several improvements to the lightning reports during 2008-2009. The 4DLSS, implemented in April 2008, provides all lightning strokes as opposed to just one stroke per flash as done by the previous system. The 45 WS discovered that the peak current was being truncated to the nearest kilo amp in the database used to generate the daily lightning reports, which led to an up to 4% underestimate in the peak current for average lightning. This error was corrected and led to elimination of this underestimate. The 45 WS and their mission partners developed lightning location error ellipses for 99% and 95% location accuracies tailored to each individual stroke and began providing them in the spring of 2009. The new procedure provides the distance from the point of interest to the best location of the stroke (the center of the error ellipse) and the distance to the closest edge of the ellipse. This information is now included in the lightning reports, along with the peak current of the stroke. The initial method of calculating the error ellipses could only be used during normal duty hours, i.e. not during nights, weekends, or holidays. This method was improved later to provide lightning reports in near real-time, 24/7. The calculation of the distance to the closest point on the ellipse was also significantly improved later. Other improvements were also implemented. A new method to calculate the probability of any nearby lightning stroke. being within any radius of any point of interest was developed and is being implemented. This may supersede the use of location error ellipses. The 45 WS is pursuing adding data from nine NLDN sensors into 4DLSS in real-time. This will overcome the problem of 4DLSS missing some of the strong local strokes. This will also improve the location accuracy, reduce the size and eccentricity of the location error ellipses, and reduce the probability of nearby strokes being inside the areas of interest when few of the 4DLSS sensors are used in the stroke solution. This will not reduce 4DLSS performance when most of the 4DLSS sensors are used in the stroke solution. Finally, several possible future improvements were discussed, especially for improving the peak current estimate and the error estimate for peak current, and upgrading the 4DLSS. Some possible approaches for both of these goals were discussed.

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.

Monochromatic x-ray radiography of laser-driven spherical targets using high-energy, picoseconds LFEX laser

NASA Astrophysics Data System (ADS)

Sawada, Hiroshi; Fujioka, S.; Lee, S.; Arikawa, Y.; Shigemori, K.; Nagatomo, H.; Nishimura, H.; Sunahara, A.; Theobald, W.; Perez, F.; Patel, P. K.; Beg, F. N.

2015-11-01

Formation of a high density fusion fuel is essential in both conventional and advanced Inertial Confinement Fusion (ICF) schemes for the self-sustaining fusion process. In cone-guided Fast Ignition (FI), a metal cone is attached to a spherical target to maintain the path for the injection of an intense short-pulse ignition laser from blow-off plasma created when nanoseconds compression lasers drive the target. We have measured a temporal evolution of a compressed deuterated carbon (CD) sphere using 4.5 keV K-alpha radiography with the Kilo-Joule, picosecond LFEX laser at the Institute of Laser Engineering. A 200 μm CD sphere attached to the tip of a Au cone was directly driven by 9 Gekko XII beams with 300 J/beam in a 1.3 ns Gaussian pulse. The LFEX laser irradiated on a Ti foil to generate 4.51 Ti K-alpha x-ray. By varying the delay between the compression and backlighter lasers, the measured radiograph images show an increase of the areal density of the imploded target. The detail of the quantitative analyses to infer the areal density and comparisons to hydrodynamics simulations will be presented. This work was performed with the support and under the auspices of the NIFS Collaboration Research program (NIFS13KUGK072). H.S. was supported by the UNR's International Activities Grant program.

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.

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

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.

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.

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

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.

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.

Mega-Amp Opening Switch with Nested Electrodes/Pulsed Generator of Ion and Ion Cluster Beams.

DTIC Science & Technology

1985-07-01

i.e., noncollisiona].) resistivity which controls the "~switch opening" function (specifically, the rate of disintergration of the PF pinch where...unaffected the pinch field Be and then disassemble in a light (D) component and other heavy components. Production and propagation of-neutrals (from...emission, production and - evaporation would imply a distorsion of the pinholeimage-because of B -which is not p.-.. observed (our pinhole resolution is 150

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.

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

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.

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

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.

Fabrication and functionalization of carbon nanotube field effect transistors for bio-sensing applications

NASA Astrophysics Data System (ADS)

Zhou, Jianyun

Single walled carbon nanotube based field effect transistors are fabricated using photolithography and electron beam lithography techniques. First catalyst islands are deposited onto the substrate using standard optical lithographic techniques, and the nanotubes are grown by catalytic chemical vapor deposition from the pre-patterned catalyst islands. After imaging the grown nanotubes, the metal contact electrodes are patterned using lithography, followed by metal deposition using a sputtering technique. Both single nanotube devices and nanotube film devices are fabricated using this method. The single nanotube devices can be semiconducting, ambipolar, or metallic, with the resistance ranging from tens of kilo ohms to a few mega ohms, while the film devices are generally metallic, with only a few kilo ohms of resistance. Semiconducting single nanotube devices are functionalized for sensor applications. An electrodeposition technique was developed to functionalize the nanotube with a few materials, including avidin, chitosan, and metal nanoparticles. Among them, metal nanoparticle deposition is the most successful, and both gold and silver nanoparticles have been successfully deposited onto the sidewalls of the nanotubes from an "in situ" sacrificial electrode. The size and density of the nanoparticles, to some extent, can be tailored by controlling the deposition voltage. The gold nanoparticles are generally spherical, while the silver nanoparticles have branching snowflake shapes. These nanoparticles change the ON-state conductance of the nanotube while maintaining its semiconducting characteristics. The gold nanoparticles on the nanotube sidewalls can serve as anchoring sites for thiol-terminated biomolecules to functionalize the device for biosensing purposes. Results have shown that the thiol-terminated molecules can bind to the Au nanoparticles; however, nonspecific binding to the SiO2 surface is still abundant. Therefore, a self assembled monolayer (SAM) of protein-resistant polyethylene glycol (PEG) is deposited onto the SiO 2 surface to provide protein resistance, which results in selective immobilization of bio-receptors to the gold nanoparticles on the nanotube only. This reduces possible noise signals from the nonspecific substrate binding, and is expected to improve the device sensitivity.

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

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.

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.

Electrical Characteristics of 10-kV 4H-SiC MPS Rectifiers with High Schottky Barrier Height

NASA Astrophysics Data System (ADS)

Jiang, Yifan; Sung, Woongje; Baliga, Jayant; Wang, Sizhen; Lee, Bongmook; Huang, Alex

2018-02-01

This paper reports the study of the fabrication and characterization results of 10-kilo-volt (kV) 4H-SiC merged PiN/Schottky rectifiers. A metal contact process was developed to make the Schottky contact on n-type SiC and ohmic contact on p-type SiC at the same time. The diodes with different Schottky contact width were fabricated and characterized for comparison. With the improvement quality of the Schottky contact and the passivation layer, the devices show low leakage current up to 10 kV. The on-state characteristics from room temperature to elevated temperature (423 K) were demonstrated and compared between structures with different Schottky contact width.

X-ray backlighting of imploding aluminium liners on PTS facility

NASA Astrophysics Data System (ADS)

Yang, Qingguo; Liu, Dongbing; Mu, Jian; Huang, Xianbin; Dan, Jiakun; Xie, Xudong; Deng, Wu; Feng, Shuping; Wang, Meng; Ye, Yan; Peng, Qixian; Li, Zeren

2016-09-01

The x-ray backlighting systems, including a 1.865 keV (Si Heα line) spherically bent crystal imaging system and an ˜8.3 keV (Cu Heα line) point-projection imaging system, newly fielded on the Primary Test Stand facility are introduced and its preliminary experimental results in radiography of the aluminium (Al) liners with seeded sinusoidal perturbations are presented. The x-ray backlighter source is created using a 1 TW, 1 kJ Nd: glass high power laser, kilo-joule laser system, recently constructed at China Academy of Engineering Physics. The ablation melt and instability of the imploding Al liner outer edge under the driving current of ˜7.5 MA are successfully observed using these two backlighting systems, respectively.

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.

46 CFR 199.175 - Survival craft and rescue boat equipment.

Code of Federal Regulations, 2011 CFR

2011-10-01

... and must provide at least 10,000 kiloJoules (2,390 calories). Individual provision packages may... hatchet counts towards this requirement in rigid rescue boats. 5 Oars are not required on a free-fall...

33 CFR 100.718 - Annual Suncoast Kilo Run; Sarasota Bay, Sarasota, FL.

Code of Federal Regulations, 2010 CFR

2010-07-01

... datum: NAD 83. (b) Special local regulations. (1) In accordance with these regulations, the regulated... referenced use datum: NAD 83. (3) Entry into the regulated area shall be in accordance with this regulation...

Molecular physics. Production of trilobite Rydberg molecule dimers with kilo-Debye permanent electric dipole moments.

PubMed

Booth, D; Rittenhouse, S T; Yang, J; Sadeghpour, H R; Shaffer, J P

2015-04-03

Permanent electric dipole moments are important for understanding symmetry breaking in molecular physics, control of chemical reactions, and realization of strongly correlated many-body quantum systems. However, large molecular permanent electric dipole moments are challenging to realize experimentally. We report the observation of ultralong-range Rydberg molecules with bond lengths of ~100 nanometers and kilo-Debye permanent electric dipole moments that form when an ultracold ground-state cesium (Cs) atom becomes bound within the electronic cloud of an extended Cs electronic orbit. The electronic character of this hybrid class of "trilobite" molecules is dominated by degenerate Rydberg manifolds, making them difficult to produce by conventional photoassociation. We used detailed coupled-channel calculations to reproduce their properties quantitatively. Our findings may lead to progress in ultracold chemistry and strongly correlated many-body physics. Copyright © 2015, American Association for the Advancement of Science.

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.

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

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

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

Energetic particles in spherical tokamak plasmas

NASA Astrophysics Data System (ADS)

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

2017-05-01

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 with 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. Ion acceleration has also been observed during merging-compression start-up in MAST.

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.

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.

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

Alfven Wave Reflection Model of Field-Aligned Currents at Mercury

NASA Technical Reports Server (NTRS)

Lyatsky, Wladislaw; Khazanov, George V.; Slavin, James

2010-01-01

An Alfven Wave Reflection (AWR) model is proposed that provides closure for strong field-aligned currents (FACs) driven by the magnetopause reconnection in the magnetospheres of planets having no significant ionospheric and surface electrical conductance. The model is based on properties of the Alfven waves, generated at high altitudes and reflected from the low-conductivity surface of the planet. When magnetospheric convection is very slow, the incident and reflected Alfven waves propagate along approximately the same path. In this case, the net field-aligned currents will be small. However, as the convection speed increases. the reflected wave is displaced relatively to the incident wave so that the incident and reflected waves no longer compensate each other. In this case, the net field-aligned current may be large despite the lack of significant ionospheric and surface conductivity. Our estimate shows that for typical solar wind conditions at Mercury, the magnitude of Region 1-type FACs in Mercury's magnetosphere may reach hundreds of kilo-Amperes. This AWR model of field-aligned currents may provide a solution to the long-standing problem of the closure of FACs in the Mercury's magnetosphere. c2009 Elsevier Inc. All rights reserved.

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.

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.

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

Progress toward an aberration-corrected low energy electron microscope for DNA sequencing and surface analysis.

PubMed

Mankos, Marian; Shadman, Khashayar; N'diaye, Alpha T; Schmid, Andreas K; Persson, Henrik H J; Davis, Ronald W

2012-11-01

Monochromatic, aberration-corrected, dual-beam low energy electron microscopy (MAD-LEEM) is a novel imaging technique aimed at high resolution imaging of macromolecules, nanoparticles, and surfaces. MAD-LEEM combines three innovative electron-optical concepts in a single tool: a monochromator, a mirror aberration corrector, and dual electron beam illumination. The monochromator reduces the energy spread of the illuminating electron beam, which significantly improves spectroscopic and spatial resolution. The aberration corrector is needed to achieve subnanometer resolution at landing energies of a few hundred electronvolts. The dual flood illumination approach eliminates charging effects generated when a conventional, single-beam LEEM is used to image insulating specimens. The low landing energy of electrons in the range of 0 to a few hundred electronvolts is also critical for avoiding radiation damage, as high energy electrons with kilo-electron-volt kinetic energies cause irreversible damage to many specimens, in particular biological molecules. The performance of the key electron-optical components of MAD-LEEM, the aberration corrector combined with the objective lens and a magnetic beam separator, was simulated. Initial results indicate that an electrostatic electron mirror has negative spherical and chromatic aberration coefficients that can be tuned over a large parameter range. The negative aberrations generated by the electron mirror can be used to compensate the aberrations of the LEEM objective lens for a range of electron energies and provide a path to achieving subnanometer spatial resolution. First experimental results on characterizing DNA molecules immobilized on Au substrates in a LEEM are presented. Images obtained in a spin-polarized LEEM demonstrate that high contrast is achievable at low electron energies in the range of 1-10 eV and show that small changes in landing energy have a strong impact on the achievable contrast. The MAD-LEEM approach promises to significantly improve the performance of a LEEM for a wide range of applications in the biosciences, material sciences, and nanotechnology where nanometer scale resolution and analytical capabilities are required. In particular, the microscope has the potential of delivering images of unlabeled DNA strands with nucleotide-specific contrast. This simplifies specimen preparation and significantly eases the computational complexity needed to assemble the DNA sequence from individual reads.

Progress toward an aberration-corrected low energy electron microscope for DNA sequencing and surface analysis

PubMed Central

Mankos, Marian; Shadman, Khashayar; N'Diaye, Alpha T.; Schmid, Andreas K.; Persson, Henrik H. J.; Davis, Ronald W.

2012-01-01

Monochromatic, aberration-corrected, dual-beam low energy electron microscopy (MAD-LEEM) is a novel imaging technique aimed at high resolution imaging of macromolecules, nanoparticles, and surfaces. MAD-LEEM combines three innovative electron–optical concepts in a single tool: a monochromator, a mirror aberration corrector, and dual electron beam illumination. The monochromator reduces the energy spread of the illuminating electron beam, which significantly improves spectroscopic and spatial resolution. The aberration corrector is needed to achieve subnanometer resolution at landing energies of a few hundred electronvolts. The dual flood illumination approach eliminates charging effects generated when a conventional, single-beam LEEM is used to image insulating specimens. The low landing energy of electrons in the range of 0 to a few hundred electronvolts is also critical for avoiding radiation damage, as high energy electrons with kilo-electron-volt kinetic energies cause irreversible damage to many specimens, in particular biological molecules. The performance of the key electron–optical components of MAD-LEEM, the aberration corrector combined with the objective lens and a magnetic beam separator, was simulated. Initial results indicate that an electrostatic electron mirror has negative spherical and chromatic aberration coefficients that can be tuned over a large parameter range. The negative aberrations generated by the electron mirror can be used to compensate the aberrations of the LEEM objective lens for a range of electron energies and provide a path to achieving subnanometer spatial resolution. First experimental results on characterizing DNA molecules immobilized on Au substrates in a LEEM are presented. Images obtained in a spin-polarized LEEM demonstrate that high contrast is achievable at low electron energies in the range of 1–10 eV and show that small changes in landing energy have a strong impact on the achievable contrast. The MAD-LEEM approach promises to significantly improve the performance of a LEEM for a wide range of applications in the biosciences, material sciences, and nanotechnology where nanometer scale resolution and analytical capabilities are required. In particular, the microscope has the potential of delivering images of unlabeled DNA strands with nucleotide-specific contrast. This simplifies specimen preparation and significantly eases the computational complexity needed to assemble the DNA sequence from individual reads. PMID:23847748

Chemical oxygen-iodine laser (COIL) for the dismantlement of nuclear facilities

NASA Astrophysics Data System (ADS)

Hallada, Marc R.; Seiffert, Stephan L.; Walter, Robert F.; Vetrovec, John

2000-05-01

The dismantlement of obsolete nuclear facilities is a major challenge for both the US Department of Energy and nuclear power utilities. Recent demonstrations have shown that lasers can be highly effective for size reduction cutting, especially for the efficient storage and recycling of materials. However, the full benefits of lasers can only be realized with high average power beams that can be conveniently delivered, via fiber optics, to remote and/or confined areas. Industrial lasers that can meet these requirements are not available now or for the foreseeable future. However, a military weapon laser, a Chemical Oxygen Iodine Laser (COIL), which has been demonstrated at over a hundred kilo Watts, could be adapted to meet these needs and enable entirely new industrial applications. An 'industrialized' COIL would enable rapid sectioning of thick and complex structures, such as glove boxes, reactor vessels, and steam generators, accelerating dismantlement schedules and reducing worker hazards. The full advantages of lasers in dismantlement could finally be realized with a portable COIL which is integrated with sophisticated robotics. It could be built and deployed in less than two years, breaking the paradigm of labor-intensive dismantlement operations and cutting processing times and costs dramatically.

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

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.

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

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.

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.

The density matrix renormalization group algorithm on kilo-processor architectures: Implementation and trade-offs

NASA Astrophysics Data System (ADS)

Nemes, Csaba; Barcza, Gergely; Nagy, Zoltán; Legeza, Örs; Szolgay, Péter

2014-06-01

In the numerical analysis of strongly correlated quantum lattice models one of the leading algorithms developed to balance the size of the effective Hilbert space and the accuracy of the simulation is the density matrix renormalization group (DMRG) algorithm, in which the run-time is dominated by the iterative diagonalization of the Hamilton operator. As the most time-dominant step of the diagonalization can be expressed as a list of dense matrix operations, the DMRG is an appealing candidate to fully utilize the computing power residing in novel kilo-processor architectures. In the paper a smart hybrid CPU-GPU implementation is presented, which exploits the power of both CPU and GPU and tolerates problems exceeding the GPU memory size. Furthermore, a new CUDA kernel has been designed for asymmetric matrix-vector multiplication to accelerate the rest of the diagonalization. Besides the evaluation of the GPU implementation, the practical limits of an FPGA implementation are also discussed.

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.

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

microRNA and mRNA profiles in ventral tegmental area relevant to stress-induced depression and resilience.

PubMed

Sun, Xiaoyan; Song, Zhenhua; Si, Yawei; Wang, Jin-Hui

2018-06-01

Chronic stress with lack of reward presumably may impair brain reward circuit, leading to major depressive disorder (MDD). Most individuals experiencing chronic stress do not suffer from MDD, i.e., resilience, implying the presence of endogenous anti-depression in the brain. Molecular mechanisms underlying stress-induced depression versus resilience were investigated. Mice were treated by chronic unpredictable mild stress (CUMS) for four weeks. Their mood state was assessed by behavioral tasks, such as sucrose preference, Y-maze and forced swimming testes. To reveal comprehensive molecular profiles of major depression versus resilience, mRNA and microRNA profiles were analyzed by high-throughput sequencing in the ventral tegmental area (VTA) harvested from control, CUMS-susceptible and CUMS-resilience mice. In data analyses of control versus CUMS-susceptible mice as well as control versus CUMS-resilience mice, 1.5 fold ratio in reads per kilo-base per million reads was set as the threshold to judge the involvement of mRNAs and microRNAs in the CUMS, depression or resilience. The downregulation of synaptic vesicle cycle, neurotrophin, GABAergic synapse and morphine addiction as well as the upregulation of transmitter release, calcium signal and cAMP-dependent response element binding are associated to CUMS-susceptibility. The downregulation of tyrosine metabolism and protein process in endoplasmic reticulum as well as the upregulation of amino acid biosynthesis, neuroactive ligand-receptor interaction and dopaminergic synapse are associated to CUMS-resilience. Therefore, the impairment of neurons and GABA/dopaminergic synapses in the VTA is associated with major depression. The upregulation of these entities is associated with resilience. Consistent results obtained from analyzing mRNAs and microRNAs as well as using different approaches strengthen our finding and conclusion. Copyright © 2018. Published by Elsevier Inc.

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.

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

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.

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

Determinants of Successful Weight Loss After Using a Commercial Web-Based Weight Reduction Program for Six Months: Cohort Study

PubMed Central

Postrach, Elisa; Aspalter, Rosa; Elbelt, Ulf; Koller, Michael; Longin, Rita; Schulzke, Jörg-Dieter

2013-01-01

Background The Internet is widely available and commonly used for health information; therefore, Web-based weight loss programs could provide support to large parts of the population in self-guided weight loss. Previous studies showed that Web-based weight loss interventions can be effective, depending on the quality of the program. The most effective program tools are visual progress charts or tools for the self-monitoring of weight, diet, and exercises. KiloCoach, a commercial program currently available in German-speaking countries, incorporates these features. A previous investigation showed that the program effectively supports users in losing weight. Objective We investigated weight loss dynamics stratified by weight loss success after 6-month use of KiloCoach. Furthermore, we analyzed possible associations between intensity of program use and weight loss. The results are intended for tailoring user recommendations for weight-loss Internet platforms. Methods Datasets of KiloCoach users (January 1, 2008 to December 31, 2011) who actively used the platform for 6 months or more were assigned to this retrospective analysis. Users (N=479) were 42.2% men, mean age of 44.0 years (SD 11.7), with a mean body mass index (BMI) of 31.7 kg/m2 (SD 3.2). Based on the weight loss achieved after 6 months, 3 success groups were generated. The unsuccessful group lost <5%, the moderate success group lost 5%-9.9%, and the high success group lost ≥10% of their baseline body weight. At baseline, the unsuccessful (n=261, 54.5%), moderate success (n=133, 27.8%), and high success (n=85, 17.8%) groups were similar in age, weight, BMI, and gender distribution. Results After 6 months, the unsuccessful group lost 1.2% (SD 2.4), the moderate success group lost 7.4% (SD 1.5), and the high success group lost 14.2% (SD 3.8) of their initial weight (P<.001). Multivariate regression showed that early weight loss (weeks 3-4), the total number of dietary protocols, and the total number of weight entries were independent predictors for 6-month weight reduction (all P<.001) explaining 52% of the variance in weight reduction. Sensitivity analysis by baseline carried forward method confirmed all independent predictors of 6-month weight loss and reduced the model fit by only 11%. The high success group lost weight faster and maintained weight loss more efficiently than the other groups (P<.001). Early weight loss was associated with weight maintenance after 1 year and 2 years (both P<.001). Weight dynamics did not differ between men and women over 6 months when adjusted for baseline and usage parameters (P=.91). The percentage of male long-term users was unusually high (42.2%). Conclusions Our results suggest that early weight loss and close program adherence (ie, 5 dietary protocols per week and weekly entering of current weight), especially in the early phase of program usage, can improve weight loss outcome. PMID:24126250

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.

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.

Ecological Impacts During the Deepwater Horizon Oil Spill Response

EPA Science Inventory

The Deepwater Horizon (DWH) oil spill was the largest environmental disaster and response effort in U.S. history, with nearly 800 million liters of crude oil spilled. Vast areas of the Gulf of Mexico were contaminated with oil, including deep-ocean communities and over 1,600 kilo...

WHOI Hawaii Ocean Timeseries Station (WHOTS): WHOTS-5 2008 Mooring Turnaround Cruise Report

DTIC Science & Technology

2009-04-01

deposition. The anti-bird wire is constructed of 316 stainless steel and is 4 inches high and 4 inches wide and has no less than 120 wire points per...11 4-3 R/V Kilo Moana diagram ...12 5-1 WHOTS-4 mooring diagram

[A patient with depression due to digitalis poisoning].

PubMed

Schouten, J; van der Aa, G C

1984-04-01

A 85 year old lady suffering from depression is described. The depression was caused by digoxin intoxication. At first this was not recognized because of the low level of creatinine in the serum. This was the result of the decreased lean body mass, the patient weighing only 40 kilo!

33 CFR 161.18 - Reporting requirements.

Code of Federal Regulations, 2010 CFR

2010-07-01

... call. H HOTEL Date, time and point of entry system Entry time expressed as in (B) and into the entry... KILO Date, time and point of exit from system Exit time expressed as in (B) and exit position expressed....; for a dredge or floating plant: configuration of pipeline, mooring configuration, number of assist...

21 CFR 579.22 - Ionizing radiation for treatment of animal diets.

Code of Federal Regulations, 2012 CFR

2012-04-01

... SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IRRADIATION IN THE PRODUCTION, PROCESSING... radiation is used or intended for use in single treatment as follows: Food for irradiation Limitations Use... dose: Not to exceed 50 kiloGrays. Feeds and feed ingredients treated by irradiation should be...

21 CFR 579.22 - Ionizing radiation for treatment of animal diets.

Code of Federal Regulations, 2010 CFR

2010-04-01

... SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IRRADIATION IN THE PRODUCTION, PROCESSING... radiation is used or intended for use in single treatment as follows: Food for irradiation Limitations Use... dose: Not to exceed 50 kiloGrays. Feeds and feed ingredients treated by irradiation should be...

21 CFR 579.22 - Ionizing radiation for treatment of animal diets.

Code of Federal Regulations, 2011 CFR

2011-04-01

... SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IRRADIATION IN THE PRODUCTION, PROCESSING... radiation is used or intended for use in single treatment as follows: Food for irradiation Limitations Use... dose: Not to exceed 50 kiloGrays. Feeds and feed ingredients treated by irradiation should be...

21 CFR 579.22 - Ionizing radiation for treatment of animal diets.

Code of Federal Regulations, 2014 CFR

2014-04-01

... SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IRRADIATION IN THE PRODUCTION, PROCESSING... radiation is used or intended for use in single treatment as follows: Food for irradiation Limitations Use... dose: Not to exceed 50 kiloGrays. Feeds and feed ingredients treated by irradiation should be...

21 CFR 579.22 - Ionizing radiation for treatment of animal diets.

Code of Federal Regulations, 2013 CFR

2013-04-01

... SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IRRADIATION IN THE PRODUCTION, PROCESSING... radiation is used or intended for use in single treatment as follows: Food for irradiation Limitations Use... dose: Not to exceed 50 kiloGrays. Feeds and feed ingredients treated by irradiation should be...

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

Acceleration modules in linear induction accelerators

NASA Astrophysics Data System (ADS)

Wang, Shao-Heng; Deng, Jian-Jun

2014-05-01

The Linear Induction Accelerator (LIA) is a unique type of accelerator that is capable of accelerating kilo-Ampere charged particle current to tens of MeV energy. The present development of LIA in MHz bursting mode and the successful application into a synchrotron have broadened LIA's usage scope. Although the transformer model is widely used to explain the acceleration mechanism of LIAs, it is not appropriate to consider the induction electric field as the field which accelerates charged particles for many modern LIAs. We have examined the transition of the magnetic cores' functions during the LIA acceleration modules' evolution, distinguished transformer type and transmission line type LIA acceleration modules, and re-considered several related issues based on transmission line type LIA acceleration module. This clarified understanding should help in the further development and design of LIA acceleration modules.

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.

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

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

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.

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.

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

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.

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.

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.

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

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.

Energy Conservation Education for New York State. Interdisciplinary Learning Activities. Grades 7-12.

ERIC Educational Resources Information Center

New York State Education Dept., Albany.

Provided in this document are 18 energy conservation activities designed to supplement regular classroom learning activities. A matrix correlating activity number with grade level and subject areas is included. Titles of activities are: puzzles; energy quiz; energy-related careers; reading a meter; trading calories for kilo-watts; conserving home…

Dew Point Evaporative Comfort Cooling

DTIC Science & Technology

2013-07-01

efficiency ratio kBtu kilo British thermal unit kW kilowatt kWh kilowatt-hour M-Cycle Maisotsenko Cycle MCDB mean coincident dry bulb mi2 square...the foothills of the Rocky Mountains. The base covers more than 8.7 square miles ( mi2 ) and includes more than 11 million ft2 of building area

Frequency Allocation; The Radio Spectrum.

ERIC Educational Resources Information Center

Federal Communications Commission, Washington, DC.

The Federal Communications Commission (FCC) assigns segments of the radio spectrum to categories of users, and specific frequencies within each segment to individual users. Since demand for channel space exceeds supply, the process is complex. The radio spectrum can be compared to a long ruler: the portion from 10-540 kiloHertz has been set aside…

Detonation of Meta-stable Clusters

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

Kuhl, Allen; Kuhl, Allen L.; Fried, Laurence E.

2008-05-31

We consider the energy accumulation in meta-stable clusters. This energy can be much larger than the typical chemical bond energy (~;;1 ev/atom). For example, polymeric nitrogen can accumulate 4 ev/atom in the N8 (fcc) structure, while helium can accumulate 9 ev/atom in the excited triplet state He2* . They release their energy by cluster fission: N8 -> 4N2 and He2* -> 2He. We study the locus of states in thermodynamic state space for the detonation of such meta-stable clusters. In particular, the equilibrium isentrope, starting at the Chapman-Jouguet state, and expanding down to 1 atmosphere was calculated with the Cheetahmore » code. Large detonation pressures (3 and 16 Mbar), temperatures (12 and 34 kilo-K) and velocities (20 and 43 km/s) are a consequence of the large heats of detonation (6.6 and 50 kilo-cal/g) for nitrogen and helium clusters respectively. If such meta-stable clusters could be synthesized, they offer the potential for large increases in the energy density of materials.« less

Implementation of ground penetrating radar and electrical resistivity tomography for inspecting the Greco-Roman Necropolis at Kilo 6 of the Golden Mummies Valley, Bahariya Oasis, Egypt

NASA Astrophysics Data System (ADS)

Abbas, Abbas M.; Ghazala, Hosni H.; Mesbah, Hany S.; Atya, Magdy A.; Radwan, Ali; Hamed, Diaa E.

2016-06-01

Bahariya Oasis is one of the lately inspected spots in Egypt and has a long historical record extending from the old kingdom till the emergence of Islam. Since June 1999, the Valley of the Golden Mummies near Bawiti (at kilometer 6 on the road leads to Farafra Oasis) became significant due to the discoveries of amazing mummies of gelded faces. The archeologists believe that the Valley has more valuable tombs that still unrevealed. Also, the possibility that the Greco-Roman Necropolis extends to areas other than Kilo-6 is sustainable. The ground penetrating radar and electrical resistivity tomography are two geophysical tools that have successful applications in archeological assessment. The two techniques were used in integration plan to assert the archeological potentiality of the studied site and to map the feasible tombs. Sum of 798 GPR profiles and 19 ERT cross sections was carried out over the study area. The results of them were analyzed to envisage these results in archeological terms.

The galaxy environment in GAMA G3C groups using the Kilo Degree Survey Data Release 3

NASA Astrophysics Data System (ADS)

Costa-Duarte, M. V.; Viola, M.; Molino, A.; Kuijken, K.; , L. Sodré, Jr.; Bilicki, M.; Brouwer, M. M.; Buddelmeijer, H.; Grado, A.; de Jong, J. T. A.; Napolitano, N.; Puddu, E.; Radovich, M.; Vakili, M.

2018-04-01

We aim to investigate the galaxy environment in GAMA Galaxy Groups Catalogue (G3C) using a volume-limited galaxy sample from the Kilo Degree Survey Data Release 3. The k-Nearest Neighbour technique is adapted to take into account the probability density functions (PDFs) of photometric redshifts in our calculations. This algorithm was tested on simulated KiDS tiles, showing its capability of recovering the relation between galaxy colour, luminosity and local environment. The characterization of the galaxy environment in G3C groups shows systematically steeper density contrasts for more massive groups. The red galaxy fraction gradients in these groups is evident for most of group mass bins. The density contrast of red galaxies is systematically higher at group centers when compared to blue galaxy ones. In addition, distinct group center definitions are used to show that our results are insensitive to center definitions. These results confirm the galaxy evolution scenario which environmental mechanisms are responsible for a slow quenching process as galaxies fall into groups and clusters, resulting in a smooth observed colour gradients in galaxy systems.

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.

The Primordial Inflation Explorer (PIXIE) Mission

NASA Technical Reports Server (NTRS)

Kogut, Alan J.; Chuss, David T.; Dotson, Jessie L.; Fixsen, Dale J.; Halpern, Mark; Hinshaw, Gary F.; Meyer, Stephan M.; Moseley, S. Harvey; Seiffert, Michael D.; Spergel, David N.;

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.

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

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.

Signals of ENPEMF Used in Earthquake Prediction

NASA Astrophysics Data System (ADS)

Hao, G.; Dong, H.; Zeng, Z.; Wu, G.; Zabrodin, S. M.

2012-12-01

The signals of Earth's natural pulse electromagnetic field (ENPEMF) is a combination of the abnormal crustal magnetic field pulse affected by the earthquake, the induced field of earth's endogenous magnetic field, the induced magnetic field of the exogenous variation magnetic field, geomagnetic pulsation disturbance and other energy coupling process between sun and earth. As an instantaneous disturbance of the variation field of natural geomagnetism, ENPEMF can be used to predict earthquakes. This theory was introduced by A.A Vorobyov, who expressed a hypothesis that pulses can arise not only in the atmosphere but within the Earth's crust due to processes of tectonic-to-electric energy conversion (Vorobyov, 1970; Vorobyov, 1979). The global field time scale of ENPEMF signals has specific stability. Although the wave curves may not overlap completely at different regions, the smoothed diurnal ENPEMF patterns always exhibit the same trend per month. The feature is a good reference for observing the abnormalities of the Earth's natural magnetic field in a specific region. The frequencies of the ENPEMF signals generally locate in kilo Hz range, where frequencies within 5-25 kilo Hz range can be applied to monitor earthquakes. In Wuhan, the best observation frequency is 14.5 kilo Hz. Two special devices are placed in accordance with the S-N and W-E direction. Dramatic variation from the comparison between the pulses waveform obtained from the instruments and the normal reference envelope diagram should indicate high possibility of earthquake. The proposed detection method of earthquake based on ENPEMF can improve the geodynamic monitoring effect and can enrich earthquake prediction methods. We suggest the prospective further researches are about on the exact sources composition of ENPEMF signals, the distinction between noise and useful signals, and the effect of the Earth's gravity tide and solid tidal wave. This method may also provide a promising application in mineral deposits detecting, surface relics pipeline surveying and safety resonance monitoring on reservoir dam.

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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

The E and B EXperiment: EBEX

NASA Astrophysics Data System (ADS)

Helson, Kyle R.

2015-08-01

We report on the status of the E and B Experiment (EBEX) a balloon-borne polarimeter designed to measure the polarization of the cosmic microwave background radiation. The instrument employs a 1.5 meter Gregorian Mizuguchi-Dragone telescope providing 8 arc-minute resolution at three bands centered on 150, 250, and 410 GHz. A continuously rotating achromatic half wave plate, mounted on a superconducting magnetic bearing, and a polarizing grid give EBEX polarimetric capabilities. Radiation is detected with a kilo-pixel array of transition edge sensor (TES) bolometers that are cooled to 0.25 K. The detectors are readout using SQUID current amplifiers and a digital frequency-domain multiplexing system in which 16 detectors are readout simultaneously with two wires. EBEX is the first instrument to implement TESs and such readout system on board a balloon-borne platform. EBEX was launched from the Antarctic in December 2012 on an 11-day long-duration balloon flight. This presentation will provide an overview of the instrument and discuss the flight and status of the data analysis. We also discuss the next generation of EBEX called EBEX10k, currently in development.

Development of X-Ray Microcalorimeter Imaging Spectrometers for the X-Ray Surveyor Mission Concept

NASA Technical Reports Server (NTRS)

Bandler, Simon R.; Adams, Joseph S.; Chervenak, James A.; Datesman, Aaron M.; Eckart, Megan E.; Finkbeiner, Fred M.; Kelley, Richard L.; Kilbourne, Caroline A.; Betncourt-Martinez, Gabriele; Miniussi, Antoine R.;

A sandwich-like differential B-dot based on EACVD polycrystalline diamond slice

NASA Astrophysics Data System (ADS)

Xu, P.; Yu, Y.; Xu, L.; Zhou, H. Y.; Qiu, C. J.

2018-06-01

In this article, we present a method of mass production of a standardized high-performance differential B-dot magnetic probe together with the magnetic field measurement in a pulsed current device with the current up to hundreds of kilo-Amperes. A polycrystalline diamond slice produced in an Electron Assisted Chemical Vapor Deposition device is used as the base and insulating material to imprint two symmetric differential loops for the magnetic field measurement. The SP3 carbon bond in the cubic lattice structure of diamond is confirmed by Raman spectra. The thickness of this slice is 20 μm. A gold loop is imprinted onto each surface of the slice by using the photolithography technique. The inner diameter, width, and thickness of each loop are 0.8 mm, 50 μm, and 1 μm, respectively. It provides a way of measuring the pulsed magnetic field with a high spatial and temporal resolution, especially in limited space. This differential magnetic probe has demonstrated a very good common-mode rejection rate through the pulsed magnetic field measurement.

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.

Photovoltaic investigation of minority carrier lifetime in the heavily-doped emitter layer of silicon junction solar cell

NASA Technical Reports Server (NTRS)

Ho, C.-T.

1982-01-01

The results of experiments on the recombination lifetime in a phosphorus diffused N(+) layer of a silicon solar cell are reported. The cells studied comprised three groups of Czochralski grown crystals: boron doped to one ohm-cm, boron doped to 6 ohm-cm, and aluminum doped to one ohm-cm, all with a shunt resistance exceeding 500 kilo-ohms. The characteristic bulk diffusion length of a cell sample was determined from the short circuit current response to light at a wavelength of one micron. The recombination rates were obtained by measurement of the open circuit voltage as a function of the photogeneration rate. The recombination rate was found to be dependent on the photoinjection level, and is positive-field controlled at low photoinjection, positive-field influence Auger recombination at a medium photoinjection level, and negative-field controlled Auger recombination at a high photoinjection level.

A Review of Some Superconducting Technologies for AtLAST: Parametric Amplifiers, Kinetic Inductance Detectors, and On-Chip Spectrometers

NASA Astrophysics Data System (ADS)

Noroozian, Omid

2018-01-01

The current state of the art for some superconducting technologies will be reviewed in the context of a future single-dish submillimeter telescope called AtLAST. The technologies reviews include: 1) Kinetic Inductance Detectors (KIDs), which have now been demonstrated in large-format kilo-pixel arrays with photon background-limited sensitivity suitable for large field of view cameras for wide-field imaging. 2) Parametric amplifiers - specifically the Traveling-Wave Kinetic Inductance (TKIP) amplifier - which has enormous potential to increase sensitivity, bandwidth, and mapping speed of heterodyne receivers, and 3) On-chip spectrometers, which combined with sensitive direct detectors such as KIDs or TESs could be used as Multi-Object Spectrometers on the AtLAST focal plane, and could provide low-medium resolution spectroscopy of 100 objects at a time in each field of view.

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

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.

Searching for galaxy clusters in the Kilo-Degree Survey

NASA Astrophysics Data System (ADS)

Radovich, M.; Puddu, E.; Bellagamba, F.; Roncarelli, M.; Moscardini, L.; Bardelli, S.; Grado, A.; Getman, F.; Maturi, M.; Huang, Z.; Napolitano, N.; McFarland, J.; Valentijn, E.; Bilicki, M.

2017-02-01

Aims: In this paper, we present the tools used to search for galaxy clusters in the Kilo Degree Survey (KiDS), and our first results. Methods: The cluster detection is based on an implementation of the optimal filtering technique that enables us to identify clusters as over-densities in the distribution of galaxies using their positions on the sky, magnitudes, and photometric redshifts. The contamination and completeness of the cluster catalog are derived using mock catalogs based on the data themselves. The optimal signal to noise threshold for the cluster detection is obtained by randomizing the galaxy positions and selecting the value that produces a contamination of less than 20%. Starting from a subset of clusters detected with high significance at low redshifts, we shift them to higher redshifts to estimate the completeness as a function of redshift: the average completeness is 85%. An estimate of the mass of the clusters is derived using the richness as a proxy. Results: We obtained 1858 candidate clusters with redshift 0

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

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

19 CFR 159.22 - Net weights and tares.

Code of Federal Regulations, 2013 CFR

2013-04-01

... tins imported from Spain: The following schedule drained weight shall be used as the Customs dutiable... in tins and such drained weight being the allowance made in liquidation for tare for water: Size can Drained weight 3 kilo 13.6 kilograms-case of 6 tins. 794 grams 16.7 kilograms-case of 24 tins. 425 grams 8...

19 CFR 159.22 - Net weights and tares.

Code of Federal Regulations, 2012 CFR

2012-04-01

... tins imported from Spain: The following schedule drained weight shall be used as the Customs dutiable... in tins and such drained weight being the allowance made in liquidation for tare for water: Size can Drained weight 3 kilo 13.6 kilograms-case of 6 tins. 794 grams 16.7 kilograms-case of 24 tins. 425 grams 8...

19 CFR 159.22 - Net weights and tares.

Code of Federal Regulations, 2014 CFR

2014-04-01

... tins imported from Spain: The following schedule drained weight shall be used as the Customs dutiable... in tins and such drained weight being the allowance made in liquidation for tare for water: Size can Drained weight 3 kilo 13.6 kilograms-case of 6 tins. 794 grams 16.7 kilograms-case of 24 tins. 425 grams 8...

19 CFR 159.22 - Net weights and tares.

Code of Federal Regulations, 2010 CFR

2010-04-01

... tins imported from Spain: The following schedule drained weight shall be used as the Customs dutiable... in tins and such drained weight being the allowance made in liquidation for tare for water: Size can Drained weight 3 kilo 13.6 kilograms-case of 6 tins. 794 grams 16.7 kilograms-case of 24 tins. 425 grams 8...

19 CFR 159.22 - Net weights and tares.

Code of Federal Regulations, 2011 CFR

2011-04-01

... tins imported from Spain: The following schedule drained weight shall be used as the Customs dutiable... in tins and such drained weight being the allowance made in liquidation for tare for water: Size can Drained weight 3 kilo 13.6 kilograms-case of 6 tins. 794 grams 16.7 kilograms-case of 24 tins. 425 grams 8...

Diesel Engine Air Emissions Reduction Technologies

DTIC Science & Technology

2010-04-01

Hour GC/MS Gas Chromatography /Mass Spectroscopy GC/FID Gas Chromatography /Flame Ionization Detector g/mile Gram per Mile HAP Hazardous Air...Pollutant HC Hydrocarbon HPLC/UV High Performance Liquid Chromatography / Ultraviolet KPa Kilo-Pascals NDIR Non Dispersive Infrared... Chromatography (GC) where the samples were collected on DNPH cartridges. Portable versions of these instruments were available and employed for

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.

Construction, Deployment and Data Analysis of the E and B EXperiment: A Cosmic Microwave Background Polarimeter

NASA Astrophysics Data System (ADS)

Didier, Joy

The E and B EXperiment (EBEX) is a pointed balloon-borne telescope designed to measure the polarization of the cosmic microwave background (CMB) as well as that from Galactic dust. The instrument is equipped with a 1.5 meter aperture Gregorian-Dragone telescope, providing an 8' beam at three frequency bands centered on 150, 250 and 410 GHz. The telescope is designed to measure or place an upper limit on inflationary B-mode signals and to probe B-modes originating from gravitationnal lensing of the CMB. The higher EBEX frequencies are designed to enable the measurement and removal of polarized Galactic dust foregrounds which currently limit the measurement of inflationary B-modes. Polarimetry is achieved by rotating an achromatic half-wave plate (HWP) on a superconducting magnetic bearing. In January 2013, EBEX completed 11 days of observations in a flight over Antarctica covering 6,000 square degrees of the southern sky. This marks the first time that kilo-pixel TES bolometer arrays have made science observations on a balloon-borne platform. In this thesis we report on the construction, deployment and data analysis of EBEX. We review the development of the pointing sensors and software used for real-time attitude determination and control, including pre-flight testing and calibration. We then report on the 2013 long duration flight (LD2013) and review all the major stages of the analysis pipeline used to transform the ˜1 TB of raw data into polarized sky maps. We review "LEAP", the software framework developed to support the analysis pipeline. We discuss in detail the novel program developed to reconstruct the attitude post-flight and estimate the effect of attitude errors on measured B-mode signals. We describe the bolometer time-stream cleaning procedure including removing the HWP-synchronous signal, and we detail the map making procedure. Finally we present a novel method to measure and subtract instrumental polarization, after which we show Galaxy and CMB maps.

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.

5D imaging approaches reveal the formation of distinct intracellular cAMP spatial gradients

NASA Astrophysics Data System (ADS)

Rich, Thomas C.; Annamdevula, Naga; Trinh, Kenny; Britain, Andrea L.; Mayes, Samuel A.; Griswold, John R.; Deal, Joshua; Hoffman, Chase; West, Savannah; Leavesley, Silas J.

2017-02-01

Cyclic AMP (cAMP) is a ubiquitous second messenger known to differentially regulate many cellular functions. Several lines of evidence suggest that the distribution of cAMP within cells is not uniform. However, to date, no studies have measured the kinetics of 3D cAMP distributions within cells. This is largely due to the low signal-tonoise ratio of FRET-based probes. We previously reported that hyperspectral imaging improves the signal-to-noise ratio of FRET measurements. Here we utilized hyperspectral imaging approaches to measure FRET signals in five dimensions (5D) - three spatial (x, y, z), wavelength (λ), and time (t) - allowing us to visualize cAMP gradients in pulmonary endothelial cells. cAMP levels were measured using a FRET-based sensor (H188) comprised of a cAMP binding domain sandwiched between FRET donor and acceptor - Turquoise and Venus fluorescent proteins. We observed cAMP gradients in response to 0.1 or 1 μM isoproterenol, 0.1 or 1 μM PGE1, or 50 μM forskolin. Forskolin- and isoproterenol-induced cAMP gradients formed from the apical (high cAMP) to basolateral (low cAMP) face of cells. In contrast, PGE1-induced cAMP gradients originated from both the basolateral and apical faces of cells. Data suggest that 2D (x,y) studies of cAMP compartmentalization may lead to erroneous conclusions about the existence of cAMP gradients, and that 3D (x,y,z) studies are required to assess mechanisms of signaling specificity. Results demonstrate that 5D imaging technologies are powerful tools for measuring biochemical processes in discrete subcellular domains.

Inhibition of basolateral cAMP permeability in the toad urinary bladder.

PubMed

Boom, A; Golstein, P E; Frerotte, M; Sande, J V; Beauwens, R

2000-10-01

1. The effect of sulphonylurea drugs on hydrosmotic flow across toad urinary bladder epithelium was re-evaluated in the present study. Glibenclamide, added to the basolateral medium, significantly enhanced the osmotic flow induced by low doses of antidiuretic hormone (ADH) or forskolin (FK), while it inhibited the effect of exogenous cyclic adenosine monophosphate (cAMP) or its non-hydrolysable bromo derivative, 8-Br-cAMP, added to the basolateral medium. These opposite effects of glibenclamide on the transepithelial osmotic flow can be explained by a reduction of cAMP permeability across the basolateral membrane of the epithelium. The decrease in cAMP permeability leads, according to the direction of the cAMP gradient, to firstly an enhanced osmotic flow when cAMP is generated intracellularly by addition of ADH and FK, glibenclamide reducing cAMP exit from the cell, and secondly a decreased osmotic flow in response to cAMP (and 8-Br-cAMP) added to the basolateral medium, glibenclamide inhibiting, in this case, their entry into the cell. 2. The demonstration that glibenclamide actually inhibits the basolateral cAMP permeability rests on the fact that firstly it decreases the release of cAMP into the basolateral medium by about 40 %, at each concentration of ADH or forskolin tested, secondly it increases the cAMP content of paired hemibladders incubated in the presence of ADH or FK, when intracellular degradation was prevented by phosphodiesterase inhibition, and thirdly it decreases also the uptake of basolateral 8-Br-[3H]cAMP into paired toad hemibladders. 3. Taken together, the present data demonstrate that glibenclamide inhibits the toad urinary bladder basolateral membrane permeability to cAMP, most probably by a direct interaction with a membrane protein not yet indentified but distinct from the sulphonylurea receptor.

AmpA protein functions by different mechanisms to influence early cell type specification and to modulate cell adhesion and actin polymerization in Dictyostelium discoideum

PubMed Central

Cost, Hoa N.; Noratel, Elizabeth F.; Blumberg, Daphne D.

2013-01-01

The Dictyostelium discoideum ampA gene encodes a multifunctional regulator protein that modulates cell–cell and cell–substrate adhesions and actin polymerization during growth and is necessary for correct cell type specification and patterning during development. Insertional inactivation of the ampA gene results in defects that define two distinct roles for the ampA gene during development. AmpA is necessary in a non-cell autonomous manner to prevent premature expression of a prespore gene marker. It is also necessary in a cell autonomous manner for the anterior like cells, which express the ampA gene, to migrate to the upper cup during culmination. It is also necessary to prevent excessive cell–cell agglutination when cells are developed in a submerged suspension culture. Here, we demonstrate that a supernatant source of AmpA protein, added extracellularly, can prevent the premature mis-expression of the prespore marker. Synthetic oligopeptides are used to identify the domain of the AmpA protein that is important for preventing cells from mis-expressing the prespore gene. We further demonstrate that a factor capable of inducing additional cells to express the prespore gene marker accumulates extracellularly in the absence of AmpA protein. While the secreted AmpA acts extracellularly to suppress prespore gene expression, the effects of AmpA on cell agglutination and on actin polymerization in growing cells are not due to an extracellular role of secreted AmpA protein. Rather, these effects appear to reflect a distinct cell autonomous role of the ampA gene. Finally, we show that secretion of AmpA protein is brought about by elevating the levels of expression of ampA so that the protein accumulates to an excessive level. PMID:23911723

Parallel Allostery by cAMP and PDE Coordinates Activation and Termination Phases in cAMP Signaling.

PubMed

Krishnamurthy, Srinath; Tulsian, Nikhil Kumar; Chandramohan, Arun; Anand, Ganesh S

2015-09-15

The second messenger molecule cAMP regulates the activation phase of the cAMP signaling pathway through high-affinity interactions with the cytosolic cAMP receptor, the protein kinase A regulatory subunit (PKAR). Phosphodiesterases (PDEs) are enzymes responsible for catalyzing hydrolysis of cAMP to 5' AMP. It was recently shown that PDEs interact with PKAR to initiate the termination phase of the cAMP signaling pathway. While the steps in the activation phase are well understood, steps in the termination pathway are unknown. Specifically, the binding and allosteric networks that regulate the dynamic interplay between PKAR, PDE, and cAMP are unclear. In this study, PKAR and PDE from Dictyostelium discoideum (RD and RegA, respectively) were used as a model system to monitor complex formation in the presence and absence of cAMP. Amide hydrogen/deuterium exchange mass spectrometry was used to monitor slow conformational transitions in RD, using disordered regions as conformational probes. Our results reveal that RD regulates its interactions with cAMP and RegA at distinct loci by undergoing slow conformational transitions between two metastable states. In the presence of cAMP, RD and RegA form a stable ternary complex, while in the absence of cAMP they maintain transient interactions. RegA and cAMP each bind at orthogonal sites on RD with resultant contrasting effects on its dynamics through parallel allosteric relays at multiple important loci. RD thus serves as an integrative node in cAMP termination by coordinating multiple allosteric relays and governing the output signal response. Copyright © 2015 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Fibroblast growth factor and cyclic AMP (cAMP) synergistically activate gene expression at a cAMP response element.

PubMed Central

Tan, Y; Low, K G; Boccia, C; Grossman, J; Comb, M J

1994-01-01

Growth factors and cyclic AMP (cAMP) are known to activate distinct intracellular signaling pathways. Fibroblast growth factor (FGF) activates ras-dependent kinase cascades, resulting in the activation of MAP kinases, whereas cAMP activates protein kinase A. In this study, we report that growth factors and cAMP act synergistically to stimulate proenkephalin gene expression. Positive synergy between growth factor- and cAMP-activated signaling pathways on gene expression has not been previously reported, and we suggest that these synergistic interactions represent a useful model for analyzing interactions between these pathways. Transfection and mutational studies indicate that both FGF-dependent gene activation and cAMP-dependent gene activation require cAMP response element 2 (CRE-2), a previously characterized cAMP-dependent regulatory element. Furthermore, multiple copies of this element are sufficient to confer FGF regulation upon a minimal promoter, indicating that FGF and cAMP signaling converge upon transcription factors acting at CRE-2. Among many different ATF/AP-1 factors tested, two factors, ATF-3 and c-Jun, stimulate proenkephalin transcription in an FGF- or Ras-dependent fashion. Finally, we show that ATF-3 and c-Jun form heterodimeric complexes in SK-N-MC cells and that the levels of both proteins are increased in response to FGF but not cAMP. Together, these results indicate that growth factor- and cAMP-dependent signaling pathways converge at CRE-2 to synergistically stimulate gene expression and that ATF-3 and c-Jun regulate proenkephalin transcription in response to both growth factor- and cAMP-dependent intracellular signaling pathways. Images PMID:7935470

The cAMP analogs have potent anti-proliferative effects on medullary thyroid cancer cell lines.

PubMed

Dicitore, Alessandra; Grassi, Elisa Stellaria; Caraglia, Michele; Borghi, Maria Orietta; Gaudenzi, Germano; Hofland, Leo J; Persani, Luca; Vitale, Giovanni

2016-01-01

The oncogenic activation of the rearranged during transfection (RET) proto-oncogene has a main role in the pathogenesis of medullary thyroid cancer (MTC). Several lines of evidence suggest that RET function could be influenced by cyclic AMP (cAMP)-dependent protein kinase A (PKA) activity. We evaluated the in vitro anti-tumor activity of 8-chloroadenosine-3',5'-cyclic monophosphate (8-Cl-cAMP) and PKA type I-selective cAMP analogs [equimolar combination of the 8-piperidinoadenosine-3',5'-cyclic monophosphate (8-PIP-cAMP) and 8-hexylaminoadenosine-3',5'-cyclic monophosphate (8-HA-cAMP) in MTC cell lines (TT and MZ-CRC-1)]. 8-Cl-cAMP and the PKA I-selective cAMP analogs showed a potent anti-proliferative effect in both cell lines. In detail, 8-Cl-cAMP blocked significantly the transition of TT cell population from G2/M to G0/G1 phase and from G0/G1 to S phase and of MZ-CRC-1 cells from G0/G1 to S phase. Moreover, 8-Cl-cAMP induced apoptosis in both cell lines, as demonstrated by FACS analysis for annexin V-FITC/propidium iodide, the activation of caspase-3 and PARP cleavage. On the other hand, the only effect induced by PKA I-selective cAMP analogs was a delay in G0/G1-S and S-G2/M progression in TT and MZ-CRC-1 cells, respectively. In conclusion, these data demonstrate that cAMP analogs, particularly 8-Cl-cAMP, significantly suppress in vitro MTC proliferation and provide rationale for a potential clinical use of cAMP analogs in the treatment of advanced MTC.

Atmospheric, Magnetospheric and Plasmas in Space (AMPS) spacelab payload definition study. Volume 3: Interface control documents. Part 2: AMPS payload to spacelab ICD

NASA Technical Reports Server (NTRS)

1976-01-01

The AMPS to Spacelab Interface Control Document which is to be used as a guide for format and information content in generating specific AMPS Mission ICDs is presented. This document is meant to supplement the Spacelab Payload Accommodations Handbook in that it only defines interfaces which are not discussed in the handbook to the level required for design purposes. The AMPS Top Level Requirements Tree, illustrates this ICD by a shaded area and its relationship to the other AMPS technical documents. Other interface documents shown are the Level II, AMPS to Space Shuttle Vehicle ICD and the Level III, AMPS to Instruments ICD.

Transverse field focused system

DOEpatents

Anderson, O.A.

1983-06-01

It is an object of the invention to provide a transport apparatus for a high current negative-ion beam which will bend the beam around corners through a baffled path in a differential pump or a neutron trap. It is another object of the invention to provide a transport apparatus for a high current negative-ion beam which will allow gas molecules in the beam to exit outwardly from the transport apparatus. A further object of the invention is to provide a multi-stage accelerator for a high current negative-ion beam which will enable acceleration of the beam to very high energy levels with a minimum loss of current carrying capacity. A still further object of the invention is to provide an apparatus for transport or accelertion of a sheet beam of negative ions which is shaped to confine the beam against divergence or expansion.

Regulation of Maltodextrin Phosphorylase Synthesis in Escherichia coli by Cyclic Adenosine 3′, 5′-Monophosphate and Glucose1

PubMed Central

Chao, Julie; Weathersbee, Carolyn J.

1974-01-01

Cyclic adenosine 3′, 5′-monophosphate (AMP) stimulates maltodextrin phosphorylase synthesis in Escherichia coli cells induced with maltose. A maximal effect occurs at 2 to 3 mM cyclic AMP. The action of cyclic AMP is specific, inasmuch as adenosine triphosphate, 3′-AMP, 5′-AMP, adenosine, and dibutyryl cyclic AMP are inactive. Glucose, α-methyl glucoside, 2-deoxyglucose, and pyridoxal 5′-phosphate repress maltodextrin phosphorylase synthesis. This repression is reversed by cyclic AMP. The action of cyclic AMP appears to be at the transcriptional level, since cyclic AMP fails to stimulate phosphorylase production in induced cells in which messenger ribonucleic acid synthesis has been arrested by rifampin or by inducer removal. The two other enzymes involved in the metabolism of maltose, amylomaltase and maltose permease, are also induced in this strain of E. coli and affected by glucose and cyclic AMP in a manner similar to phosphorylase. PMID:4358043

The Alzheimer's Disease-Associated Amyloid β-Protein Is an Antimicrobial Peptide

PubMed Central

Soscia, Stephanie J.; Kirby, James E.; Washicosky, Kevin J.; Tucker, Stephanie M.; Ingelsson, Martin; Hyman, Bradley; Burton, Mark A.; Goldstein, Lee E.; Duong, Scott; Tanzi, Rudolph E.; Moir, Robert D.

2010-01-01

Background The amyloid β-protein (Aβ) is believed to be the key mediator of Alzheimer's disease (AD) pathology. Aβ is most often characterized as an incidental catabolic byproduct that lacks a normal physiological role. However, Aβ has been shown to be a specific ligand for a number of different receptors and other molecules, transported by complex trafficking pathways, modulated in response to a variety of environmental stressors, and able to induce pro-inflammatory activities. Methodology/Principal Findings Here, we provide data supporting an in vivo function for Aβ as an antimicrobial peptide (AMP). Experiments used established in vitro assays to compare antimicrobial activities of Aβ and LL-37, an archetypical human AMP. Findings reveal that Aβ exerts antimicrobial activity against eight common and clinically relevant microorganisms with a potency equivalent to, and in some cases greater than, LL-37. Furthermore, we show that AD whole brain homogenates have significantly higher antimicrobial activity than aged matched non-AD samples and that AMP action correlates with tissue Aβ levels. Consistent with Aβ-mediated activity, the increased antimicrobial action was ablated by immunodepletion of AD brain homogenates with anti-Aβ antibodies. Conclusions/Significance Our findings suggest Aβ is a hitherto unrecognized AMP that may normally function in the innate immune system. This finding stands in stark contrast to current models of Aβ-mediated pathology and has important implications for ongoing and future AD treatment strategies. PMID:20209079

Binder of Sperm Proteins 1 and 5 have contrasting effects on the capacitation of ram spermatozoa.

PubMed

Pini, Taylor; de Graaf, Simon P; Druart, Xavier; Tsikis, Guillaume; Labas, Valerie; Teixeira-Gomes, Ana Paula; Gadella, Barend M; Leahy, Tamara

2018-06-01

Binder of Sperm Proteins (BSPs) are the most abundant seminal plasma protein family in the ram and bull. They have been extensively studied in the bull but less is known about their function in ovine seminal plasma and current knowledge suggests that BSPs may have different effects in these two species. In the bull, they facilitate capacitation and destabilize the sperm membrane during in vitro handling, whereas in the ram, they appear to stabilize the sperm membrane and prevent cryopreservation-induced capacitation-like changes. Further investigation into the effects of BSPs on ram spermatozoa under capacitating conditions is required to further clarify their physiological roles in the ram. We investigated the effects of Binder of Sperm Proteins 1 and 5 on epididymal ram spermatozoa in conditions of low, moderate, and high cAMP. BSPs had minimal effects on sperm function in low-cAMP conditions, but caused significant changes under cAMP upregulation. BSP1 stabilized the membrane and qualitatively reduced protein tyrosine phosphorylation, but significantly increased cholesterol efflux and induced spontaneous acrosome reactions. BSP5 slightly increased spontaneous acrosome reactions and caused sperm necrosis. However, BSP5 had minimal effects on membrane lipid order and cholesterol efflux and did not inhibit protein tyrosine phosphorylation. These findings demonstrate that under maximal cAMP upregulation, BSP1 affected ram spermatozoa in a manner comparable to bull spermatozoa, while BSP5 did not.

cAMP-dependent chloride secretion mediates tubule enlargement and cyst formation by cultured mammalian collecting duct cells.

PubMed

Montesano, Roberto; Ghzili, Hafida; Carrozzino, Fabio; Rossier, Bernard C; Féraille, Eric

2009-02-01

Polycystic kidney diseases result from disruption of the genetically defined program that controls the size and geometry of renal tubules. Cysts which frequently arise from the collecting duct (CD) result from cell proliferation and fluid secretion. From mCCD(cl1) cells, a differentiated mouse CD cell line, we isolated a clonal subpopulation (mCCD-N21) that retains morphogenetic capacity. When grown in three-dimensional gels, mCCD-N21 cells formed highly organized tubular structures consisting of a palisade of polarized epithelial cells surrounding a cylindrical lumen. Subsequent addition of cAMP-elevating agents (forskolin or cholera toxin) or of membrane-permeable cAMP analogs (CPT-cAMP) resulted in rapid and progressive dilatation of existing tubules, leading to the formation of cystlike structures. When grown on filters, mCCD-N21 cells exhibited a high transepithelial resistance as well as aldosterone- and/or vasopressin-induced amiloride-sensitive and -insensitive current. The latter was in part inhibited by Na(+)-K(+)-2Cl(-) cotransporter (bumetanide) and chloride channel (NPPB) inhibitors. Real-time PCR analysis confirmed the expression of NKCC1, the ubiquitous Na(+)-K(+)-2Cl(-) cotransporter and cystic fibrosis transmembrane regulator (CFTR) in mCCD-N21 cells. Tubule enlargement and cyst formation were prevented by inhibitors of Na(+)-K(+)-2Cl(-) cotransporters (bumetanide or ethacrynic acid) or CFTR (NPPB or CFTR inhibitor-172). These results further support the notion that cAMP signaling plays a key role in renal cyst formation, at least in part by promoting chloride-driven fluid secretion. This new in vitro model of tubule-to-cyst conversion affords a unique opportunity for investigating the molecular mechanisms that govern the architecture of epithelial tubes, as well as for dissecting the pathophysiological processes underlying cystic kidney diseases.

A double blind, randomized, active controlled study to assess the safety, tolerability and immunogenicity of measles, mumps rubella, and varicella vaccine (MMRV) manufactured using an alternative process.

PubMed

Marshall, Gary S; Senders, Shelly D; Shepard, Julie; Twiggs, Jerry D; Gardner, Julie; Hille, Darcy; Hartzel, Jonathan; Valenzuela, Rowan; Stek, Jon E; Helmond, Frans A

2016-08-02

Vaccination against measles, mumps, rubella, and varicella is recommended for all children in the US. Limitations manufacturing Oka/Merck strain varicella-zoster virus have hampered the availability of the combination vaccine (MMRV) against these 4 viruses, which drove the need to investigate an alternative manufacturing process. Healthy children 12-to-23 months of age at 71 US sites were randomized (1:1) to receive MMRV manufactured using an alternative process (MMRV AMP ) or the currently licensed MMRV. Subjects received 2 0.5 mL doses 3 months apart. Sera were collected before and 6 weeks after Dose-1. Adverse experiences (AEs) were collected for 42 d after each dose and serious AEs and events of special interest for 180 d after Dose-2. Overall, 706 subjects were randomized to MMRV AMP and 706 to MMRV and 698 and 702 received at least 1 dose of study vaccine, respectively. The risk difference in response rates and geometric mean concentrations of antibody to measles, mumps, rubella, and varicella viruses 6 weeks after Dose-1 met non-inferiority criteria for MMRV AMP versus, MMRV. Response rates met acceptability criteria for each virus, and the seroconversion rate to varicella-zoster virus was 99.5% in both groups. Vaccine-related AEs were mostly mild-to-moderate in intensity and somewhat more common after MMRV AMP . Febrile seizures occurred at similar rates in both groups during the first 42 d after each vaccine dose. MMRV AMP is non-inferior to MMRV and represents an important advancement in maintaining an adequate supply of vaccines against these diseases.

cAMP-dependent insulin modulation of synaptic inhibition in neurons of the dorsal motor nucleus of the vagus is altered in diabetic mice

PubMed Central

Blake, Camille B.

2014-01-01

Pathologies in which insulin is dysregulated, including diabetes, can disrupt central vagal circuitry, leading to gastrointestinal and other autonomic dysfunction. Insulin affects whole body metabolism through central mechanisms and is transported into the brain stem dorsal motor nucleus of the vagus (DMV) and nucleus tractus solitarius (NTS), which mediate parasympathetic visceral regulation. The NTS receives viscerosensory vagal input and projects heavily to the DMV, which supplies parasympathetic vagal motor output. Normally, insulin inhibits synaptic excitation of DMV neurons, with no effect on synaptic inhibition. Modulation of synaptic inhibition in DMV, however, is often sensitive to cAMP-dependent mechanisms. We hypothesized that an effect of insulin on GABAergic synaptic transmission may be uncovered by elevating resting cAMP levels in GABAergic terminals. We used whole cell patch-clamp recordings in brain stem slices from control and diabetic mice to identify insulin effects on inhibitory neurotransmission in the DMV in the presence of forskolin to elevate cAMP levels. In the presence of forskolin, insulin decreased the frequency of inhibitory postsynaptic currents (IPSCs) and the paired-pulse ratio of evoked IPSCs in DMV neurons from control mice. This effect was blocked by brefeldin-A, a Golgi-disrupting agent, or indinavir, a GLUT4 blocker, indicating that protein trafficking and glucose transport were involved. In streptozotocin-treated, diabetic mice, insulin did not affect IPSCs in DMV neurons in the presence of forskolin. Results suggest an impairment of cAMP-induced insulin effects on GABA release in the DMV, which likely involves disrupted protein trafficking in diabetic mice. These findings provide insight into mechanisms underlying vagal dysregulation associated with diabetes. PMID:24990858

A Novel Peptide to Treat Oral Mucositis Blocks Endothelial and Epithelial Cell Apoptosis

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

Wu Xiaoyan; Chen Peili; Sonis, Stephen T.

2012-07-01

Purpose: No effective agents currently exist to treat oral mucositis (OM) in patients receiving chemoradiation for the treatment of head-and-neck cancer. We identified a novel 21-amino acid peptide derived from antrum mucosal protein-18 that is cytoprotective, mitogenic, and motogenic in tissue culture and animal models of gastrointestinal epithelial cell injury. We examined whether administration of antrum mucosal protein peptide (AMP-p) could protect against and/or speed recovery from OM. Methods and Materials: OM was induced in established hamster models by a single dose of radiation, fractionated radiation, or fractionated radiation together with cisplatin to simulate conventional treatments of head-and-neck cancer. Results:more » Daily subcutaneous administration of AMP-p reduced the occurrence of ulceration and accelerated mucosal recovery in all three models. A delay in the onset of erythema after irradiation was observed, suggesting that a protective effect exists even before injury to mucosal epithelial cells occurs. To test this hypothesis, the effects of AMP-p on tumor necrosis factor-{alpha}-induced apoptosis were studied in an endothelial cell line (human dermal microvascular endothelial cells) as well as an epithelial cell line (human adult low-calcium, high-temperature keratinocytes; HaCaT) used to model the oral mucosa. AMP-p treatment, either before or after cell monolayers were exposed to tumor necrosis factor-{alpha}, protected against development of apoptosis in both cell types when assessed by annexin V and propidium iodide staining followed by flow cytometry or ligase-mediated polymerase chain reaction. Conclusions: These observations suggest that the ability of AMP-p to attenuate radiation-induced OM could be attributable, at least in part, to its antiapoptotic activity.« less

Adenosine 3′,5′-cyclic monophosphate (cAMP)-dependent phosphoregulation of mitochondrial complex I is inhibited by nucleoside reverse transcriptase inhibitors

PubMed Central

Lund, Kaleb C.; Wallace, Kendall B.

2008-01-01

Nucleoside analog reverse transcriptase inhibitors (NRTI) are known to directly inhibit mitochondrial complex I activity as well as various mitochondrial kinases. Recent observations that complex I activity and superoxide production are modulated through cAMP-dependent phosphorylation suggests a mechanism through which NRTIs may affect mitochondrial respiration via kinase-dependent protein phosphorylation. In the current study we examine the potential for NRTIs to inhibit the cAMP-dependent phosphorylation of complex I and the associated NADH:CoQ oxidoreductase activities and rates of superoxide production using HepG2 cells. Phosphoprotein staining of immunocaptured complex I revealed that 3′-azido-3′-deoxythymidine (AZT; 10 and 50 μM), AZT monophosphate (150 μM), and 2′,3′-dideoxycytidine (ddC; 1μM) prevented the phosphorylation of the NDUFB11 subunit of complex I. This was associated with a decrease in complex I activity with AZT and AZT monophosphate only. In the presence of succinate, superoxide production was increased with 2′,3′-dideoxyinosine (ddI; 10 μM) and ddC (1 μM). In the presence of succinate + cAMP AZT showed an inverse dose-dependent effect on superoxide production. None of the NRTIs examined inhibit PKA activity suggesting that the observed effects are due to a direct interaction with complex I. These data demonstrate a direct effect of NRTIs on cAMP-dependent regulation of mitochondrial bioenergetics independent of DNA polymerase-γ activity; in the case of AZT these observations may provide a mechanism for the observed long-term toxicity with this drug. PMID:17904600

Synergistic action of cyclic adenosine monophosphate- and calcium-mediated chloride secretion in a colonic epithelial cell line.

PubMed Central

Cartwright, C A; McRoberts, J A; Mandel, K G; Dharmsathaphorn, K

1985-01-01

Vasoactive intestinal polypeptide (VIP) and the calcium ionophore A23187 caused dose-dependent changes in the potential difference and the short circuit current (Isc) across confluent T84 cell monolayers mounted in modified Ussing chambers. Both VIP and A23187 stimulated net chloride secretion without altering sodium transport. Net chloride secretion accounted for the increase in Isc. When A23187 was tested in combination with VIP, net chloride secretion was significantly greater than predicted from the calculated sum of their individual responses indicating a synergistic effect. VIP increased cellular cyclic AMP (cAMP) production in a dose-dependent manner, whereas A23187 had no effect on cellular cAMP. We then determined whether VIP and A23187 activated different transport pathways. Earlier studies suggest that VIP activates a basolaterally localized, barium-sensitive potassium channel as well as an apically localized chloride conductance pathway. In this study, stimulation of basolateral membrane potassium efflux by A23187 was documented by preloading the monolayers with 86Rb+. Stimulation of potassium efflux by A23187 was additive to the VIP-stimulated potassium efflux. By itself, 0.3 microM A23187 did not alter transepithelial chloride permeability, and its stimulation of basolateral membrane potassium efflux caused only a relatively small amount of chloride secretion. However, in the presence of an increased transepithelial chloride permeability induced by VIP, the effectiveness of A23187 on chloride secretion was greatly augmented. Our studies suggest that cAMP and calcium each activate basolateral potassium channels, but cAMP also activates an apically localized chloride channel. Synergism results from cooperative interaction of potassium channels and the chloride channel. PMID:2997291

Regulation of basal and reserve cardiac pacemaker function by interactions of cAMP mediated PKA-dependent Ca2+ cycling with surface membrane channels

PubMed Central

Vinogradova, Tatiana M.; Lakatta, Edward G.

2009-01-01

Decades of intensive research of primary cardiac pacemaker, the sinoatrial node, have established potential roles of specific membrane channels in the generation of the diastolic depolarization, the major mechanism allowing sinoatrial node cells generate spontaneous beating. During the last three decades, multiple studies made either in the isolated sinoatrial node or sinoatrial node cells have demonstrated a pivotal role of Ca2+ and, specifically Ca2+-release from sarcoplasmic reticulum, for spontaneous beating of cardiac pacemaker. Recently, spontaneous, rhythmic local subsarcolemmal Ca2+ releases from ryanodine receptors during late half of the diastolic depolarization have been implicated as a vital factor in the generation of sinoatrial node cells spontaneous firing. Local Ca2+ releases are driven by a unique combination of high basal cAMP production by adenylyl cyclases, high basal cAMP degradation by phosphodiesterases and a high level of cAMP-mediated PKA-dependent phosphorylation. These local Ca2+ releases activate an inward Na+-Ca2+ exchange current which accelerates the terminal diastolic depolarization rate and, thus, controls the spontaneous pacemaker firing. Both the basal primary pacemaker beating rate and its modulation via β-adrenergic receptor stimulation appear to be critically dependent upon intact RyR function and local subsarcolemmal sarcoplasmic reticulum generated Ca2+ releases. This review aspires to integrate the traditional viewpoint that has emphasized the supremacy of the ensemble of surface membrane ion channels in spontaneous firing of the primary cardiac pacemaker, and these novel perspectives of cAMP-mediated PKA-dependent Ca2+ cycling in regulation of the heart pacemaker clock, both in the basal state and during β-adrenergic receptor stimulation. PMID:19573534

The N Terminus of Phosphodiesterase TbrPDEB1 of Trypanosoma brucei Contains the Signal for Integration into the Flagellar Skeleton ▿

PubMed Central

Luginbuehl, Edith; Ryter, Damaris; Schranz-Zumkehr, Judith; Oberholzer, Michael; Kunz, Stefan; Seebeck, Thomas

2010-01-01

The precise subcellular localization of the components of the cyclic AMP (cAMP) signaling pathways is a crucial aspect of eukaryotic intracellular signaling. In the human pathogen Trypanosoma brucei, the strict control of cAMP levels by cAMP-specific phosphodiesterases is essential for parasite survival, both in cell culture and in the infected host. Among the five cyclic nucleotide phosphodiesterases identified in this organism, two closely related isoenzymes, T. brucei PDEB1 (TbrPDEB1) (PDEB1) and TbrPDEB2 (PDEB2) are predominantly responsible for the maintenance of cAMP levels. Despite their close sequence similarity, they are distinctly localized in the cell. PDEB1 is mostly located in the flagellum, where it forms an integral part of the flagellar skeleton. PDEB2 is mainly located in the cell body, and only a minor part of the protein localizes to the flagellum. The current study, using transfection of procyclic trypanosomes with green fluorescent protein (GFP) reporters, demonstrates that the N termini of the two enzymes are essential for determining their final subcellular localization. The first 70 amino acids of PDEB1 are sufficient to specifically direct a GFP reporter to the flagellum and to lead to its detergent-resistant integration into the flagellar skeleton. In contrast, the analogous region of PDEB2 causes the GFP reporter to reside predominantly in the cell body. Mutagenesis of selected residues in the N-terminal region of PDEB2 demonstrated that single amino acid changes are sufficient to redirect the reporter from a cell body location to stable integration into the flagellar skeleton. PMID:20693305

Transportation of high-current ion and electron beams in the accelerator drift gap in the presence of an additional electron background

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

Karas’, V. I., E-mail: karas@kipt.kharkov.ua; Kornilov, E. A.; Manuilenko, O. V.

2015-12-15

The dynamics of a high-current ion beam propagating in the drift gap of a linear induction accelerator with collective focusing is studied using 3D numerical simulations in the framework of the full system of the Vlasov–Maxwell equations (code KARAT). The ion beam is neutralized by a comoving electron beam in the current density and, partially, in space charge, since the velocities of electrons and ions differ substantially. The dynamics of the high-current ion beam is investigated for different versions of additional neutralization of its space charge. It is established that, for a given configuration of the magnetic field and inmore » the presence of a specially programmed injection of additional electrons from the boundary opposite to the ion injection boundary, the angular divergence of the ion beam almost vanishes, whereas the current of the ion beam at the exit from the accelerator drift gap changes insignificantly and the beam remains almost monoenergetic.« less

Transportation of high-current ion and electron beams in the accelerator drift gap in the presence of an additional electron background

NASA Astrophysics Data System (ADS)

Karas', V. I.; Kornilov, E. A.; Manuilenko, O. V.; Tarakanov, V. P.; Fedorovskaya, O. V.

2015-12-01

The dynamics of a high-current ion beam propagating in the drift gap of a linear induction accelerator with collective focusing is studied using 3D numerical simulations in the framework of the full system of the Vlasov-Maxwell equations (code KARAT). The ion beam is neutralized by a comoving electron beam in the current density and, partially, in space charge, since the velocities of electrons and ions differ substantially. The dynamics of the high-current ion beam is investigated for different versions of additional neutralization of its space charge. It is established that, for a given configuration of the magnetic field and in the presence of a specially programmed injection of additional electrons from the boundary opposite to the ion injection boundary, the angular divergence of the ion beam almost vanishes, whereas the current of the ion beam at the exit from the accelerator drift gap changes insignificantly and the beam remains almost monoenergetic.

Adsorption characteristics of green 5-arylaminomethylene pyrimidine-2,4,6-triones on mild steel surface in acidic medium: Experimental and computational approach

NASA Astrophysics Data System (ADS)

Verma, Chandrabhan; Olasunkanmi, Lukman O.; Ebenso, Eno E.; Quraishi, M. A.

2018-03-01

The effect of electron withdrawing nitro (-NO2) and electron releasing hydroxyl (-OH) groups on corrosion inhibition potentials of 5-arylaminomethylenepyrimidine-2,4,6-trione (AMP) had been studied. Four AMPs tagged AMP-1, AMP-2, AMP-3 and AMP-4 were studied for their ability to inhibit mild steel corrosion in 1 M HCl using experimental and theoretical methods. Gravimetric results showed that inhibition efficiency of the studied inhibitors increases with increasing concentration. The results further revealed that that electron withdrawing nitro (-NO2) group decreases the inhibition efficiency of AMP, while electron donating hydroxyl (-OH) group increases the inhibition efficiency of AMP. SEM and AFM studies showed that the studied compounds inhibit mild steel corrosion by adsorbing at the metal/electrolyte interface and their adsorption obeyed the Temkin adsorption isotherm. Potentiodynamic polarization study revealed that studied inhibitors act as mixed type inhibitors with predominant effect on cathodic reaction. The inhibitive strength of the compounds might have direct relationship electron donating ability of the molecules as revealed by quantum chemical parameters. The order of interaction energies derived from Monte Carlo simulations is AMP-4 > AMP-3 > AMP-2 > AMP-1, which is in agreement with the order of inhibition efficiencies obtained from experimental measurements.

Gene Expression Patterns Define Key Transcriptional Events InCell-Cycle Regulation By cAMP And Protein Kinase A

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

Zambon, Alexander C.; Zhang, Lingzhi; Minovitsky, Simon

Although a substantial number of hormones and drugs increase cellular cAMP levels, the global impact of cAMP and its major effector mechanism, protein kinase A (PKA), on gene expression is not known. Here we show that treatment of murine wild-type S49 lymphoma cells for 24 h with 8-(4-chlorophenylthio)-cAMP (8-CPTcAMP), a PKA-selective cAMP analog, alters the expression of approx equal to 4,500 of approx. equal to 13,600 unique genes. By contrast, gene expression was unaltered in Kin- S49 cells (that lack PKA) incubated with 8-CPTcAMP. Changes in mRNA and protein expression of several cell cycle regulators accompanied cAMP-induced G1-phase cell-cycle arrestmore » of wild-type S49 cells. Within 2h, 8-CPT-cAMP altered expression of 152 genes that contain evolutionarily conserved cAMP-response elements within 5 kb of transcriptional start sites, including the circadian clock gene Per1. Thus, cAMP through its activation of PKA produces extensive transcriptional regulation in eukaryotic cells. These transcriptional networks include a primary group of cAMP-response element-containing genes and secondary networks that include the circadian clock.« less

Dual contradictory roles of cAMP signaling pathways in hydroxyl radical production in the rat striatum.

PubMed

Hara, Shuichi; Kobayashi, Masamune; Kuriiwa, Fumi; Mukai, Toshiji; Mizukami, Hajime

2012-03-15

Studies have suggested that cAMP signaling pathways may be associated with the production of reactive oxygen species. In this study, we examined how modifications in cAMP signaling affected the production of hydroxyl radicals in rat striatum using microdialysis to measure extracellular 2,3-dihydroxybenzoic acid (2,3-DHBA), which is a hydroxyl radical adduct of salicylate. Up to 50 nmol of the cell-permeative cAMP mimetic 8-bromo-cAMP (8-Br-cAMP) increased 2,3-DHBA in a dose-dependent manner (there was no additional increase in 2,3-DHBA at 100 nmol). Another cAMP mimetic, dibutyryl cAMP (db-cAMP), caused a nonsignificant increase in 2,3-DHBA at 50 nmol and a significant decrease at 100 nmol. Up to 20 nmol of forskolin, which is a direct activator of adenylyl cyclase, increased 2,3-DHBA, similar to the effect of 8-Br-cAMP; however, forskolin resulted in a much greater increase in 2,3-DHBA. A potent inhibitor of protein kinase A (PKA), H89 (500 μM), potentiated the 8-Br-cAMP- and forskolin-induced increases in 2,3-DHBA and antagonized the inhibitory effect of 100 nmol of db-cAMP. Interestingly, the administration of 100 nmol of 8-bromo-cGMP alone or in combination with H89 had no significant effect on 2,3-DHBA levels. Doses of 100 nmol of a preferential PKA activator (6-phenyl-cAMP) or a preferential PKA inhibitor (8-bromoadenosine-3',5'-cyclic monophosphorothionate, Rp-isomer; Rp-8-Br-cAMPS), which also inhibits the cAMP-mediated activation of Epac (the exchange protein directly activated by cAMP), suppressed or enhanced, respectively, the formation of 2,3-DHBA. Up to 100 nmol of 8-(4-chlorophenylthio)-2'-O-methyladenosine-cAMP, which is a selective activator of Epac, dose-dependently stimulated the formation of 2,3-DHBA. These findings suggest that cAMP signaling plays contradictory roles (stimulation and inhibition) in the production of hydroxyl radicals in rat striatum by differential actions of Epac and PKA. These roles might contribute to the production of hydroxyl radicals concomitant with cAMP in carbon monoxide poisoning, because the formation of 2,3-DHBA was potentiated by the PKA inhibitor H89 and suppressed by Rp-8-Br-cAMPS, which inhibits PKA and Epac. Copyright © 2012 Elsevier Inc. All rights reserved.

Selective blockade of a slowly inactivating potassium current in striatal neurons by (+/-) 6-chloro-APB hydrobromide (SKF82958).

PubMed

Nisenbaum, E S; Mermelstein, P G; Wilson, C J; Surmeier, D J

1998-07-01

The ion channels of rat striatal neurons are known to be modulated by stimulation of D1 dopamine receptors. The susceptibility of depolarization-activated K+ currents to be modulated by the D1 agonist, 6-chloro-7,8-dihydroxy-3-allyl-1-phenyl-2,3,4,5-tetra-hydro-1H-3-benzaze pine (APB) was investigated using whole-cell voltage-clamp recording techniques from acutely isolated neurons. APB (0.01-100 microM) produced a concentration-dependent reduction in the total K+ current. At intermediate concentrations (ca. 10 microM), APB selectively depressed the slowly inactivating A-current (I(As)). A similar effect was produced by application of the D1 agonist, 7,8-dihydroxy-1-phenyl-2,3,4,5-tetrahydro-1-H-2-benzazepine (SKF38393, 10 microM). APB reduced I(As) rapidly, having onset and recovery time constants of 1.2 sec and 1.6 sec, respectively. Unexpectedly, the effect of APB could not be mimicked by application of Sp-adenosine 3',5'-cyclic monophosphothioate triethylamine (Sp-cAMPS, 100-200 microM), a membrane-permeable analog of cyclic AMP (cAMP), or by pretreatment with forskolin (25 microM), an activator of adenylyl cyclase. The reduction in I(As) also was not blocked by pretreatment with the D1 receptor antagonist, R(+)-SCH23390 hydrochloride (SCH23390, 10-20 microM). In addition, intracellular dialysis with guanosine-5'-O-(2-thiodiphosphate (GDP-beta-S, 200 microM) did not preclude the APB-induced inhibition of I(As), nor did dialysis with guanosine-5'-O-(3-thiotriphosphate (GTP-gamma-S, 400 microM) prevent reversal of the effect. The effect of APB was produced by a reduction in the maximal conductance of I(As) without changing the voltage-dependence of the current. Collectively, these results argue that APB does not inhibit I(As) through D1 receptors coupled to stimulation of adenylyl cyclase, but rather by allosterically regulating or blocking the channels giving rise to this current.

A multiple gap plasma cathode electron gun and its electron beam analysis in self and trigger breakdown modes.

PubMed

Kumar, Niraj; Pal, Dharmendra Kumar; Jadon, Arvind Singh; Pal, Udit Narayan; Rahaman, Hasibur; Prakash, Ram

2016-03-01

In the present paper, a pseudospark discharge based multiple gap plasma cathode electron gun is reported which has been operated separately in self and trigger breakdown modes using two different gases, namely, argon and hydrogen. The beam current and beam energy have been analyzed using a concentric ring diagnostic arrangement. Two distinct electron beams are clearly seen with hollow cathode and conductive phases. The hollow cathode phase has been observed for ∼50 ns where the obtained electron beam is having low beam current density and high energy. While in conductive phase it is high current density and low energy electron beam. It is inferred that in the hollow cathode phase the beam energy is more for the self breakdown case whereas the current density is more for the trigger breakdown case. The tailor made operation of the hollow cathode phase electron beam can play an important role in microwave generation. Up to 30% variation in the electron beam energy has been achieved keeping the same gas and by varying the breakdown mode operations. Also, up to 32% variation in the beam current density has been achieved for the trigger breakdown mode at optimized trigger position by varying the gas type.

A multiple gap plasma cathode electron gun and its electron beam analysis in self and trigger breakdown modes

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

Kumar, Niraj; Pal, Udit Narayan; Prakash, Ram

In the present paper, a pseudospark discharge based multiple gap plasma cathode electron gun is reported which has been operated separately in self and trigger breakdown modes using two different gases, namely, argon and hydrogen. The beam current and beam energy have been analyzed using a concentric ring diagnostic arrangement. Two distinct electron beams are clearly seen with hollow cathode and conductive phases. The hollow cathode phase has been observed for ∼50 ns where the obtained electron beam is having low beam current density and high energy. While in conductive phase it is high current density and low energy electronmore » beam. It is inferred that in the hollow cathode phase the beam energy is more for the self breakdown case whereas the current density is more for the trigger breakdown case. The tailor made operation of the hollow cathode phase electron beam can play an important role in microwave generation. Up to 30% variation in the electron beam energy has been achieved keeping the same gas and by varying the breakdown mode operations. Also, up to 32% variation in the beam current density has been achieved for the trigger breakdown mode at optimized trigger position by varying the gas type.« less

Non-perturbative measurement of low-intensity charged particle beams

NASA Astrophysics Data System (ADS)

Fernandes, M.; Geithner, R.; Golm, J.; Neubert, R.; Schwickert, M.; Stöhlker, T.; Tan, J.; Welsch, C. P.

2017-01-01

Non-perturbative measurements of low-intensity charged particle beams are particularly challenging to beam diagnostics due to the low amplitude of the induced electromagnetic fields. In the low-energy antiproton decelerator (AD) and the future extra low energy antiproton rings at CERN, an absolute measurement of the beam intensity is essential to monitor the operation efficiency. Superconducting quantum interference device (SQUID) based cryogenic current comparators (CCC) have been used for measuring slow charged beams in the nA range, showing a very good current resolution. But these were unable to measure fast bunched beams, due to the slew-rate limitation of SQUID devices and presented a strong susceptibility to external perturbations. Here, we present a CCC system developed for the AD machine, which was optimised in terms of its current resolution, system stability, ability to cope with short bunched beams, and immunity to mechanical vibrations. This paper presents the monitor design and the first results from measurements with a low energy antiproton beam obtained in the AD in 2015. These are the first CCC beam current measurements ever performed in a synchrotron machine with both coasting and short bunched beams. It is shown that the system is able to stably measure the AD beam throughout the entire cycle, with a current resolution of 30 {nA}.

Discovery of novel antimicrobial peptides with unusual cysteine motifs in dandelion Taraxacum officinale Wigg. flowers.

PubMed

Astafieva, A A; Rogozhin, E A; Odintsova, T I; Khadeeva, N V; Grishin, E V; Egorov, Ts A

2012-08-01

Three novel antimicrobial peptides designated ToAMP1, ToAMP2 and ToAMP3 were purified from Taraxacum officinale flowers. Their amino acid sequences were determined. The peptides are cationic and cysteine-rich and consist of 38, 44 and 42 amino acid residues for ToAMP1, ToAMP2 and ToAMP3, respectively. Importantly, according to cysteine motifs, the peptides are representatives of two novel previously unknown families of plant antimicrobial peptides. ToAMP1 and ToAMP2 share high sequence identity and belong to 6-Cys-containing antimicrobial peptides, while ToAMP3 is a member of a distinct 8-Cys family. The peptides were shown to display high antimicrobial activity both against fungal and bacterial pathogens, and therefore represent new promising molecules for biotechnological and medicinal applications. Crown Copyright © 2012. Published by Elsevier Inc. All rights reserved.

A continuous spectrophotometric assay for monitoring adenosine 5'-monophosphate production.

PubMed

First, Eric A

2015-08-15

A number of biologically important enzymes release adenosine 5'-monophosphate (AMP) as a product, including aminoacyl-tRNA synthetases, cyclic AMP (cAMP) phosphodiesterases, ubiquitin and ubiquitin-like ligases, DNA ligases, coenzyme A (CoA) ligases, polyA deadenylases, and ribonucleases. In contrast to the abundance of assays available for monitoring the conversion of adenosine 5'-triphosphate (ATP) to ADP, there are relatively few assays for monitoring the conversion of ATP (or cAMP) to AMP. In this article, we describe a homogeneous assay that continuously monitors the production of AMP. Specifically, we have coupled the conversion of AMP to inosine 5'-monophosphate (IMP) (by AMP deaminase) to the oxidation of IMP (by IMP dehydrogenase). This results in the reduction of oxidized nicotine adenine dinucleotide (NAD(+)) to reduced nicotine adenine dinucleotide (NADH), allowing AMP formation to be monitored by the change in the absorbance at 340 nm. Changes in AMP concentrations of 5 μM or more can be reliably detected. The ease of use and relatively low expense make the AMP assay suitable for both high-throughput screening and kinetic analyses. Copyright © 2015 Elsevier Inc. All rights reserved.

A novel cysteine-rich antifungal peptide ToAMP4 from Taraxacum officinale Wigg. flowers.

PubMed

Astafieva, A A; Rogozhin, Eugene A; Andreev, Yaroslav A; Odintsova, T I; Kozlov, S A; Grishin, Eugene V; Egorov, Tsezi A

2013-09-01

A novel peptide named ToAMP4 was isolated from Taraxacum officinale Wigg. flowers by a combination of acetic acid extraction and different types of chromatography: affinity, size-exclusion, and RP-HPLC. The amino acid sequence of ToAMP4 was determined by automated Edman degradation. The peptide is basic, consists of 41 amino acids, and incorporates three disulphide bonds. Due to the unusual cysteine spacing pattern, ToAMP4 does not belong to any known plant AMP family, but classifies together with two other antimicrobial peptides ToAMP1 and ToAMP2 previously isolated from the dandelion flowers. To study the biological activity of ToAMP4, it was successfully produced in a prokaryotic expression system as a fusion protein with thioredoxin. The recombinant peptide was shown to be identical to the native ToAMP4 by chromatographic behavior, molecular mass, and N-terminal amino acid sequence. The peptide displays broad-spectrum antifungal activity against important phytopathogens. Two ToAMP4-mediated inhibition strategies depending on the fungus were demonstrated. The results obtained add to our knowledge on the structural and functional diversity of AMPs in plants. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

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

Koh, S.K.; Song, S.K.; Choi, W.K.

A Kaufman-type 5 cm convex gridded ion-beam source is characterized in terms of angle-resolved ion-beam current density and beam uniformity at various discharge currents, electromagnet currents, and acceleration potentials. {copyright} {ital 1995} {ital American} {ital Institute} {ital of} {ital Physics}.

Measurement of Minority Charge Carrier Diffusion Length in Gallium Nitride Nanowires Using Electron Beam Induced Current (EBIC)

DTIC Science & Technology

2009-12-01

MINORITY CHARGE CARRIER DIFFUSION LENGTH IN GALLIUM NITRIDE NANOWIRES USING ELECTRON BEAM INDUCED CURRENT (EBIC) by Chiou Perng Ong December... Gallium Nitride Nanowires Using Electron Beam Induced Current (EBIC) 6. AUTHOR(S) Ong, Chiou Perng 5. FUNDING NUMBERS DMR 0804527 7. PERFORMING...CARRIER DIFFUSION LENGTH IN GALLIUM NITRIDE NANOWIRES USING ELECTRON BEAM INDUCED CURRENT (EBIC) Chiou Perng Ong Major, Singapore Armed Forces B

Altered ion transport by thyroid epithelia from CFTR−/− pigs suggests mechanisms for hypothyroidism in Cystic Fibrosis

PubMed Central

Li, Hui; Ganta, Suhasini; Fong, Peying

2010-01-01

Subclinical hypothyroidism has been linked to Cystic Fibrosis (CF), and the cystic fibrosis transmembrane conductance regulator (CFTR) shown to be expressed in the thyroid. The thyroid epithelium secretes Cl− and absorbs Na+ in response to cAMP. Chloride secretion may provide a counter-ion for the SLC26A4 (Pendrin)-mediated I− secretion which is required for the first step of thyroid hormonogenesis, thyroglobulin iodination. In contrast, few models exist to explain a role for Na+ absorption. Whether CFTR mediates the secretory Cl− current in thyroid epithelium has not been directly addressed. We used thyroids from a novel pig CFTR−/− model, generated primary pig thyroid epithelial cell cultures (pThECs), analyzed these cultures for preservation of thyroid-specific transcripts and proteins, and monitored 1) the Cl− secretory response to the cAMP agonist, isoproterenol and 2) the amiloride-sensitive Na+ current. Baseline short-circuit current (Isc) did not differ between CFTR+/+ and CFTR−/− cultures. Serosal isoproterenol increased Isc in CFTR+/+, but not CFTR−/−, monolayers. Compared to CFTR+/+ thyroid cultures, amiloride-sensitive Na+ absorption measured in CFTR−/− pThECs represented a greater fraction of the resting Isc. However, levels of transcripts encoding ENaC subunits did not differ between CFTR+/+ and CFTR−/− pThECs. Immunoblot analysis verified ENaC subunit protein expression, but quantification indicated no difference in expression levels. Our studies definitively demonstrate that CFTR mediates cAMP-stimulated Cl− secretion in a well-differentiated thyroid culture model, and that knockout of CFTR promotes increased Na+ absorption by a mechanism other than increased ENaC expression. These findings suggest several models for the mechanism of CF-associated hypothyroidism. PMID:20729267

M1-Muscarinic Receptors Promote Fear Memory Consolidation via Phospholipase C and the M-Current

PubMed Central

Young, Matthew B.

2014-01-01

Neuromodulators released during and after a fearful experience promote the consolidation of long-term memory for that experience. Because overconsolidation may contribute to the recurrent and intrusive memories of post-traumatic stress disorder, neuromodulatory receptors provide a potential pharmacological target for prevention. Stimulation of muscarinic receptors promotes memory consolidation in several conditioning paradigms, an effect primarily associated with the M1 receptor (M1R). However, neither inhibiting nor genetically disrupting M1R impairs the consolidation of cued fear memory. Using the M1R agonist cevimeline and antagonist telenzepine, as well as M1R knock-out mice, we show here that M1R, along with β2-adrenergic (β2AR) and D5-dopaminergic (D5R) receptors, regulates the consolidation of cued fear memory by redundantly activating phospholipase C (PLC) in the basolateral amygdala (BLA). We also demonstrate that fear memory consolidation in the BLA is mediated in part by neuromodulatory inhibition of the M-current, which is conducted by KCNQ channels and is known to be inhibited by muscarinic receptors. Manipulating the M-current by administering the KCNQ channel blocker XE991 or the KCNQ channel opener retigabine reverses the effects on consolidation caused by manipulating β2AR, D5R, M1R, and PLC. Finally, we show that cAMP and protein kinase A (cAMP/PKA) signaling relevant to this stage of consolidation is upstream of these neuromodulators and PLC, suggesting an important presynaptic role for cAMP/PKA in consolidation. These results support the idea that neuromodulatory regulation of ion channel activity and neuronal excitability is a critical mechanism for promoting consolidation well after acquisition has occurred. PMID:24478341

M1-muscarinic receptors promote fear memory consolidation via phospholipase C and the M-current.

PubMed

Young, Matthew B; Thomas, Steven A

2014-01-29

Neuromodulators released during and after a fearful experience promote the consolidation of long-term memory for that experience. Because overconsolidation may contribute to the recurrent and intrusive memories of post-traumatic stress disorder, neuromodulatory receptors provide a potential pharmacological target for prevention. Stimulation of muscarinic receptors promotes memory consolidation in several conditioning paradigms, an effect primarily associated with the M1 receptor (M1R). However, neither inhibiting nor genetically disrupting M1R impairs the consolidation of cued fear memory. Using the M1R agonist cevimeline and antagonist telenzepine, as well as M1R knock-out mice, we show here that M1R, along with β2-adrenergic (β2AR) and D5-dopaminergic (D5R) receptors, regulates the consolidation of cued fear memory by redundantly activating phospholipase C (PLC) in the basolateral amygdala (BLA). We also demonstrate that fear memory consolidation in the BLA is mediated in part by neuromodulatory inhibition of the M-current, which is conducted by KCNQ channels and is known to be inhibited by muscarinic receptors. Manipulating the M-current by administering the KCNQ channel blocker XE991 or the KCNQ channel opener retigabine reverses the effects on consolidation caused by manipulating β2AR, D5R, M1R, and PLC. Finally, we show that cAMP and protein kinase A (cAMP/PKA) signaling relevant to this stage of consolidation is upstream of these neuromodulators and PLC, suggesting an important presynaptic role for cAMP/PKA in consolidation. These results support the idea that neuromodulatory regulation of ion channel activity and neuronal excitability is a critical mechanism for promoting consolidation well after acquisition has occurred.

Virtual cathode formations in nested-well configurations

NASA Astrophysics Data System (ADS)

Stephens, K. F.; Ordonez, C. A.; Peterkin, R. E.

1999-12-01

Complete transmission of an electron beam through a cavity is not possible if the current exceeds the space-charge limited current. The formation of a virtual cathode reflects some of the beam electrons and reduces the current transmitted through the cavity. Transients in the injected current have been shown to lower the transmitted current below the value predicted by the electrostatic Child-Langmuir law. The present work considers the propagation of an electron beam through a nested-well configuration. Electrostatic particle-in-cell simulations are used to demonstrate that ions can be trapped in the electric potential depression of an electron beam. Furthermore, the trapped ions can prevent the formation of a virtual cathode for beam currents exceeding the space-charge limit.

Use of a wire scanner for monitoring residual gas ionization in Soreq Applied Research Accelerator Facility 20 keV/u proton/deuteron low energy beam transport beam line

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

Vainas, B.; Eliyahu, I.; Weissman, L.

2012-02-15

The ion source end of the Soreq Applied Research Accelerator Facility accelerator consists of a proton/deuteron ECR ion source and a low energy beam transport (LEBT) beam line. An observed reduction of the radio frequency quadrupole transmission with increase of the LEBT current prompted additional study of the LEBT beam properties. Numerous measurements have been made with the LEBT bream profiler wire biased by a variable voltage. Current-voltage characteristics in presence of the proton beam were measured even when the wire was far out of the beam. The current-voltage characteristic in this case strongly resembles an asymmetric diodelike characteristic, whichmore » is typical of Langmuir probes monitoring plasma. The measurement of biased wire currents, outside the beam, enables us to estimate the effective charge density in vacuum.« less

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, Jr.; J. Cunningham

1999-06-30

The recent achievements of critical currents in excess of 1x10{sup 6}amp/cm{sup 2} at 77K 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 U. S. Department of Energy (DOE's) sponsorship, the University of Tennessee Space Institute (UTSI) performed an extensive evaluation of leading coated conductor processing options. In general, it is our feeling that the science and chemistry that are being developed in the coated conductor wire program now need propermore » engineering 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 (LANL) 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 (ORNL) rolling assisted, bi-axially textured substrate option called RABiTS{trademark}.« less

AmpC β-lactamases in nosocomial isolates of Klebsiella pneumoniae from India

PubMed Central

Gupta, Varsha; Kumarasamy, Karthikeyan; Gulati, Neelam; Garg, Ritu; Krishnan, Padma; Chander, Jagdish

2012-01-01

Background & objectives: AmpC β-lactamases are clinically significant since these confer resistance to cephalosporins in the oxyimino group, 7-α methoxycephalosporins and are not affected by available β-lactamase inhibitors. In this study we looked for both extended spectrum β-lactamases (ESBL) and AmpC β-lactamases in Klebsiella pneumoniae clinical isolates. Methods: One hundred consecutive, non-duplicate clinical isolates of K. pneumoniae collected over a period of one year (June 2008 - June 2009) were included in the study. An antibiotic susceptibility method was used with 10 antibiotics for Gram-negative infections which helped in screening for ESBL and AmpC β-lactamases and also in confirmation of ESBL production. The detection of AmpC β-lactamases was done based on screening and confirmatory tests. For screening, disc diffusion zones of cefoxitin <18 mm was taken as cefoxitin resistant. All cefoxitin resistant isolates were tested further by AmpC disk test and modified three dimensional test. Multiplex-PCR was performed for screening the presence of plasmid-mediated AmpC genes. Results: Of the 100 isolates of K. pneumoniae studied, 48 were resistant to cefoxitin on screening. AmpC disk test was positive in 32 (32%) isolates. This was also confirmed with modified three dimensional test. Indentation indicating strong AmpC producer was observed in 25 isolates whereas little distortion (weak AmpC) was observed in 7 isolates. ESBL detection was confirmed by a modification of double disk synergy test in 56 isolates. Cefepime was the best cephalosporin in synergy with tazobactam for detecting ESBL production in isolates co-producing AmpC β-lactamases. The subsets of isolates phenotypically AmpC β-lactamase positive were subjected to amplification of six different families of AmpC gene using multiplex PCR. The sequence analysis revealed 12 CMY-2 and eight DHA-1 types. Interpretation & conclusions: Tazobactam was the best β-lactamase inhibitor for detecting ESBL in presence of AmpC β-lactamase as this is a very poor inducer of AmpC gene. Amongst cephalosporins, cefepime was the best cephalosporin in detecting ESBL in presence of AmpC β-lactamase as it is least hydrolyzed by AmpC enzymes. Cefepime-tazobactam combination disk test would be a simple and best method in detection of ESBLs in Enterobacteriaceae co-producing AmpC β-lactamase in the routine diagnostic microbiology laboratories. PMID:22960890

Antimicrobial peptides with selective antitumor mechanisms: prospect for anticancer applications.

PubMed

Deslouches, Berthony; Di, Y Peter

2017-07-11

In the last several decades, there have been significant advances in anticancer therapy. However, the development of resistance to cancer drugs and the lack of specificity related to actively dividing cells leading to toxic side effects have undermined these achievements. As a result, there is considerable interest in alternative drugs with novel antitumor mechanisms. In addition to the recent approach using immunotherapy, an effective but much cheaper therapeutic option of pharmaceutical drugs would still provide the best choice for cancer patients as the first line treatment. Ribosomally synthesized cationic antimicrobial peptides (AMPs) or host defense peptides (HDP) display broad-spectrum activity against bacteria based on electrostatic interactions with negatively charged lipids on the bacterial surface. Because of increased proportions of phosphatidylserine (negatively charged) on the surface of cancer cells compared to normal cells, cationic amphipathic peptides could be an effective source of anticancer agents that are both selective and refractory to current resistance mechanisms. We reviewed herein the prospect for AMP application to cancer treatment, with a focus on modes of action of cationic AMPs.

Assessing program efficiency: a time and motion study of the Mental Health Emergency Care - Rural Access Program in NSW Australia.

PubMed

Saurman, Emily; Lyle, David; Kirby, Sue; Roberts, Russell

2014-07-31

The Mental Health Emergency Care-Rural Access Program (MHEC-RAP) is a telehealth solution providing specialist emergency mental health care to rural and remote communities across western NSW, Australia. This is the first time and motion (T&M) study to examine program efficiency and capacity for a telepsychiatry program. Clinical services are an integral aspect of the program accounting for 6% of all activities and 50% of the time spent conducting program activities, but half of this time is spent completing clinical paperwork. This finding emphasizes the importance of these services to program efficiency and the need to address variability of service provision to impact capacity. Currently, there is no efficiency benchmark for emergency telepsychiatry programs. Findings suggest that MHEC-RAP could increase its activity without affecting program responsiveness. T&M studies not only determine activity and time expenditure, but have a wider application assessing program efficiency by understanding, defining, and calculating capacity. T&M studies can inform future program development of MHEC-RAP and similar telehealth programs, both in Australia and overseas.

Role of calcium signaling in epithelial bicarbonate secretion.

PubMed

Jung, Jinsei; Lee, Min Goo

2014-06-01

Transepithelial bicarbonate secretion plays a key role in the maintenance of fluid and protein secretion from epithelial cells and the protection of the epithelial cell surface from various pathogens. Epithelial bicarbonate secretion is mainly under the control of cAMP and calcium signaling. While the physiological roles and molecular mechanisms of cAMP-induced bicarbonate secretion are relatively well defined, those induced by calcium signaling remain poorly understood in most epithelia. The present review summarizes the current status of knowledge on the role of calcium signaling in epithelial bicarbonate secretion. Specifically, this review introduces how cytosolic calcium signaling can increase bicarbonate secretion by regulating membrane transport proteins and how it synergizes with cAMP-induced mechanisms in epithelial cells. In addition, tissue-specific variations in the pancreas, salivary glands, intestines, bile ducts, and airways are discussed. We hope that the present report will stimulate further research into this important topic. These studies will provide the basis for future medicines for a wide spectrum of epithelial disorders including cystic fibrosis, Sjögren's syndrome, and chronic pancreatitis. Copyright © 2014 Elsevier Ltd. All rights reserved.

Insect antimicrobial peptides: potential tools for the prevention of skin cancer.

PubMed

Tonk, Miray; Vilcinskas, Andreas; Rahnamaeian, Mohammad

2016-09-01

Antimicrobial peptides/proteins (AMPs) are biologically active molecules with diverse structural properties that are produced by mammals, plants, insects, ticks, and microorganisms. They have a range of antibacterial, antifungal, antiviral, and even anticancer activities, and their biological properties could therefore be exploited for therapeutic and prophylactic applications. Cancer and cancer drug resistance are significant current health challenges, so the development of innovative cancer drugs with minimal toxicity toward normal cells and novel modes of action that can evade resistance may provide a new direction for anticancer therapy. The skin is the first line of defense against heat, sunlight, injury, and infection, and skin cancer is thus the most common type of cancer. The skin that has been exposed to sunlight is particularly susceptible, but lesions can occur anywhere on the body. Skin cancer awareness and self-efficacy are necessary to improve sun protection behavior, but more effective preventative approaches are also required. AMPs may offer a new prophylactic approach against skin cancer. In this mini review, we draw attention to the potential use of insect AMPs for the prevention and treatment of skin cancer.

The Popeye domain containing protein family--A novel class of cAMP effectors with important functions in multiple tissues.

PubMed

Schindler, Roland F R; Brand, Thomas

2016-01-01

Popeye domain containing (Popdc) proteins are a unique family, which combine several different properties and functions in a surprisingly complex fashion. They are expressed in multiple tissues and cell types, present in several subcellular compartments, interact with different classes of proteins, and are associated with a variety of physiological and pathophysiological processes. Moreover, Popdc proteins bind the second messenger cAMP with high affinity and it is thought that they act as a novel class of cAMP effector proteins. Here, we will review the most important findings about the Popdc family, which accumulated since its discovery about 15 years ago. We will be focussing on Popdc protein interaction and function in striated muscle tissue. However, as a full picture only emerges if all aspects are taken into account, we will also describe what is currently known about the role of Popdc proteins in epithelial cells and in various types of cancer, and discuss these findings with regard to their relevance for cardiac and skeletal muscle. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Trends in primary and revision anterior cruciate ligament reconstruction among National Basketball Association team physicians.

PubMed

Mall, Nathan A; Abrams, Geoffrey D; Azar, Frederick M; Traina, Steve M; Allen, Answorth A; Parker, Richard; Cole, Brian J

2014-06-01

Anterior cruciate ligament (ACL) tears are common in athletes. Techniques and methods of treatment for these injuries continue to vary among surgeons. Thirty National Basketball Association (NBA) team physicians were surveyed during the NBA Pre-Draft Combine. Survey questions involved current and previous practice methods of primary and revision ACL reconstruction, including technique, graft choice, rehabilitation, and treatment of combined ACL and medial collateral ligament injuries. Descriptive parametric statistics, Fisher exact test, and logistic regression were used, and significance was set at α = 0.05. All 30 team physicians completed the survey. Eighty-seven percent indicated they use autograft (81% bone-patellar tendon-bone) for primary ACL reconstruction in NBA athletes, and 43% indicated they use autograft for revision cases. Fourteen surgeons (47%) indicated they use an anteromedial portal (AMP) for femoral tunnel drilling, whereas 5 years earlier only 4 (13%) used this technique. There was a significant (P = .009) positive correlation between fewer years in practice and AMP use. NBA team physicians' use of an AMP for femoral tunnel drilling has increased over the past 5 years.

Specific Sirt1 Activator-mediated Improvement in Glucose Homeostasis Requires Sirt1-Independent Activation of AMPK.

PubMed

Park, Sung-Jun; Ahmad, Faiyaz; Um, Jee-Hyun; Brown, Alexandra L; Xu, Xihui; Kang, Hyeog; Ke, Hengming; Feng, Xuesong; Ryall, James; Philp, Andrew; Schenk, Simon; Kim, Myung K; Sartorelli, Vittorio; Chung, Jay H

2017-04-01

The specific Sirt1 activator SRT1720 increases mitochondrial function in skeletal muscle, presumably by activating Sirt1. However, Sirt1 gain of function does not increase mitochondrial function, which raises a question about the central role of Sirt1 in SRT1720 action. Moreover, it is believed that the metabolic effects of SRT1720 occur independently of AMP-activated protein kinase (AMPK), an important metabolic regulator that increases mitochondrial function. Here, we show that SRT1720 activates AMPK in a Sirt1-independent manner and SRT1720 activates AMPK by inhibiting a cAMP degrading phosphodiesterase (PDE) in a competitive manner. Inhibiting the cAMP effector protein Epac prevents SRT1720 from activating AMPK or Sirt1 in myotubes. Moreover, SRT1720 does not increase mitochondrial function or improve glucose tolerance in AMPKα2 knockout mice. Interestingly, weight loss induced by SRT1720 is not sufficient to improve glucose tolerance. Therefore, contrary to current belief, the metabolic effects produced by SRT1720 require AMPK, which can be activated independently of Sirt1. Published by Elsevier B.V.

Antimicrobial peptides with selective antitumor mechanisms: prospect for anticancer applications

PubMed Central

Deslouches, Berthony; Di, Y. Peter

2017-01-01

In the last several decades, there have been significant advances in anticancer therapy. However, the development of resistance to cancer drugs and the lack of specificity related to actively dividing cells leading to toxic side effects have undermined these achievements. As a result, there is considerable interest in alternative drugs with novel antitumor mechanisms. In addition to the recent approach using immunotherapy, an effective but much cheaper therapeutic option of pharmaceutical drugs would still provide the best choice for cancer patients as the first line treatment. Ribosomally synthesized cationic antimicrobial peptides (AMPs) or host defense peptides (HDP) display broad-spectrum activity against bacteria based on electrostatic interactions with negatively charged lipids on the bacterial surface. Because of increased proportions of phosphatidylserine (negatively charged) on the surface of cancer cells compared to normal cells, cationic amphipathic peptides could be an effective source of anticancer agents that are both selective and refractory to current resistance mechanisms. We reviewed herein the prospect for AMP application to cancer treatment, with a focus on modes of action of cationic AMPs. PMID:28422728

AmpH, a bifunctional DD-endopeptidase and DD-carboxypeptidase of Escherichia coli.

PubMed

González-Leiza, Silvia M; de Pedro, Miguel A; Ayala, Juan A

2011-12-01

In Escherichia coli, low-molecular-mass penicillin-binding proteins (LMM PBPs) are important for correct cell morphogenesis. These enzymes display DD-carboxypeptidase and/or dd-endopeptidase activities associated with maturation and remodeling of peptidoglycan (PG). AmpH has been classified as an AmpH-type class C LMM PBP, a group closely related to AmpC β-lactamases. AmpH has been associated with PG recycling, although its enzymatic activity remained uncharacterized until now. Construction and purification of His-tagged AmpH from E. coli permitted a detailed study of its enzymatic properties. The N-terminal export signal of AmpH is processed, but the protein remains membrane associated. The PBP nature of AmpH was demonstrated by its ability to bind the β-lactams Bocillin FL (a fluorescent penicillin) and cefmetazole. In vitro assays with AmpH and specific muropeptides demonstrated that AmpH is a bifunctional DD-endopeptidase and DD-carboxypeptidase. Indeed, the enzyme cleaved the cross-linked dimers tetrapentapeptide (D45) and tetratetrapeptide (D44) with efficiencies (k(cat)/K(m)) of 1,200 M(-1) s(-1) and 670 M(-1) s(-1), respectively, and removed the terminal D-alanine from muropeptides with a C-terminal D-Ala-D-Ala dipeptide. Both DD-peptidase activities were inhibited by 40 μM cefmetazole. AmpH also displayed a weak β-lactamase activity for nitrocefin of 1.4 × 10(-3) nmol/μg protein/min, 1/1,000 the rate obtained for AmpC under the same conditions. AmpH was also active on purified sacculi, exhibiting the bifunctional character that was seen with pure muropeptides. The wide substrate spectrum of the DD-peptidase activities associated with AmpH supports a role for this protein in PG remodeling or recycling.

AmpH, a Bifunctional dd-Endopeptidase and dd-Carboxypeptidase of Escherichia coli▿

PubMed Central

González-Leiza, Silvia M.; de Pedro, Miguel A.; Ayala, Juan A.

2011-01-01

In Escherichia coli, low-molecular-mass penicillin-binding proteins (LMM PBPs) are important for correct cell morphogenesis. These enzymes display dd-carboxypeptidase and/or dd-endopeptidase activities associated with maturation and remodeling of peptidoglycan (PG). AmpH has been classified as an AmpH-type class C LMM PBP, a group closely related to AmpC β-lactamases. AmpH has been associated with PG recycling, although its enzymatic activity remained uncharacterized until now. Construction and purification of His-tagged AmpH from E. coli permitted a detailed study of its enzymatic properties. The N-terminal export signal of AmpH is processed, but the protein remains membrane associated. The PBP nature of AmpH was demonstrated by its ability to bind the β-lactams Bocillin FL (a fluorescent penicillin) and cefmetazole. In vitro assays with AmpH and specific muropeptides demonstrated that AmpH is a bifunctional dd–endopeptidase and dd-carboxypeptidase. Indeed, the enzyme cleaved the cross-linked dimers tetrapentapeptide (D45) and tetratetrapeptide (D44) with efficiencies (kcat/Km) of 1,200 M−1 s−1 and 670 M−1 s−1, respectively, and removed the terminal d-alanine from muropeptides with a C-terminal d-Ala-d-Ala dipeptide. Both dd-peptidase activities were inhibited by 40 μM cefmetazole. AmpH also displayed a weak β-lactamase activity for nitrocefin of 1.4 × 10−3 nmol/μg protein/min, 1/1,000 the rate obtained for AmpC under the same conditions. AmpH was also active on purified sacculi, exhibiting the bifunctional character that was seen with pure muropeptides. The wide substrate spectrum of the dd-peptidase activities associated with AmpH supports a role for this protein in PG remodeling or recycling. PMID:22001512

Antimicrobial susceptibilities of Proteus mirabilis: a longitudinal nationwide study from the Taiwan surveillance of antimicrobial resistance (TSAR) program.

PubMed

Wang, Jann-Tay; Chen, Pei-Chen; Chang, Shan-Chwen; Shiau, Yih-Ru; Wang, Hui-Ying; Lai, Jui-Fen; Huang, I-Wen; Tan, Mei-Chen; Lauderdale, Tsai-Ling Yang

2014-09-05

Longitudinal nationwide data on antimicrobial susceptibility in Proteus mirabilis from different sources are rare. The effects of the revised Clinical and Laboratory Standards Institute (CLSI) β-lactam breakpoints on susceptibility rates and on detecting extended-spectrum β-lactamase (ESBL) and AmpC β-lactamase-producers in this species are also seldom evaluated. The present study analyzed data from the Taiwan Surveillance of Antimicrobial Resistance program to address these issues. Isolates were collected biennially between 2002 and 2012 from 25 to 28 hospitals in Taiwan. Minimum inhibitory concentrations (MIC) were determined by reference broth microdilution method. All isolates with aztreonam, ceftazidime, or cefotaxime MIC ≥ 2 mg/L were checked for the presence of ESBL by CLSI confirmatory test and subjected to ESBL and AmpC β-lactamases gene detection by PCR. Univariate and multivariate analyses were performed. Between 2002 and 2012, a total of 1157 P. mirabilis were studied. Susceptibility to cefotaxime, ceftazidime, and ciprofloxacin decreased significantly during the past decade, from 92.6% to 81.7%, 100% to 95.2%, and 80.1% to 53.8%, respectively (P < 0.01). The revised CLSI breakpoints had significant impact on susceptibility to cefazolin (2009 vs. current breakpoints, 71.9% vs. 0.9%) and imipenem (99.8% vs. 55.1%) (P < 0.001 for both). However, using the 2014 cefazolin breakpoints for urinary tract infections, 81.2% of the urine isolates were susceptible. Susceptibilities of isolates from different specimen types were mostly similar but outpatient isolates were more susceptible than inpatient isolates. The overall prevalence of ESBL- and AmpC- producers was 8.2% and 4.7%, respectively, but AmpC carriage increased significantly over the years (from 0 to 7.0%, P < 0.001). ESBL and AmpC β-lactamase-producers were more likely to be found in elderly and ICU patients. The predominant ESBL and AmpC β-lactamase genes were CTX-M- and CMY- types, respectively. A significant decrease in susceptibility to 3rd-generation cephalosporins and ciprofloxacin occurred in P. mirabilis from Taiwan in the past decade. The prevalence of ESBL remained stable but AmpC β-lactamase-producing P. mirabilis increased significantly. Cefotaxime was a better surrogate than ceftazidime for predicting the presence of these β-lactamases. Continuous surveillance on antimicrobial resistance and associated resistance mechanisms in P. mirabilis is warranted.

Identification of second messenger mediating signal transduction in the olfactory receptor cell.

PubMed

Takeuchi, Hiroko; Kurahashi, Takashi

2003-11-01

One of the biggest controversial issues in the research of olfaction has been the mechanism underlying response generation to odorants that have been shown to fail to produce cAMP when tested by biochemical assays with olfactory ciliary preparations. Such observations are actually the original source proposing a possibility for the presence of multiple and parallel transduction pathways. In this study the activity of transduction channels in the olfactory cilia was recorded in cells that retained their abilities of responding to odorants that have been reported to produce InsP3 (instead of producing cAMP, and therefore tentatively termed "InsP3 odorants"). At the same time, the cytoplasmic cNMP concentration ([cNMP]i) was manipulated through the photolysis of caged compounds to examine their real-time interactions with odorant responses. Properties of responses induced by both InsP3 odorants and cytoplasmic cNMP resembled each other in their unique characteristics. Reversal potentials of currents were 2 mV for InsP3 odorant responses and 3 mV for responses induced by cNMP. Current and voltage (I-V) relations showed slight outward rectification. Both responses showed voltage-dependent adaptation when examined with double pulse protocols. When brief pulses of the InsP3 odorant and cytoplasmic cNMP were applied alternatively, responses expressed cross-adaptation with each other. Furthermore, both responses were additive in a manner as predicted quantitatively by the theory that signal transduction is mediated by the increase in cytoplasmic cAMP. With InsP3 odorants, actually, remarkable responses could be detected in a small fraction of cells ( approximately 2%), explaining the observation for a small production of cAMP in ciliary preparations obtained from the entire epithelium. The data will provide evidence showing that olfactory response generation and adaptation are regulated by a uniform mechanism for a wide variety of odorants.

MRI signal intensity of anterior cruciate ligament graft after transtibial versus anteromedial portal technique (TRANSIG): design of a randomized controlled clinical trial.

PubMed

Ruiter, Simeon J S; Brouwer, Reinoud W; Meys, Tim W G M; Slump, Cornelis H; van Raay, Jos J A M

2016-08-10

There are two primary surgical techniques to reconstruct the anterior cruciate ligament (ACL), transtibial (TT) technique and anteromedial portal (AMP) technique. Currently, there is no consensus which surgical technique elicits the best clinical and functional outcomes. MRI-derived measures of the signal intensity (SI) of the ACL graft have been described as an independent predictor of graft properties. The purpose of this study is to compare the MRI derived SI measurements of the ACL graft one year after ACL reconstruction, in order to compare the outcomes of both the AMP and TT ACL reconstruction technique. Thirty-six patients will be included in a randomized controlled trial. Patients who are admitted for primary unilateral ACL reconstruction will be included in the study. Exclusion criteria are a history of previous surgery on the ipsilateral knee, re-rupture of the ipsilateral ACL graft, associated ligamentous injuries or meniscal tear of the ipsilateral knee, unhealthy contralateral knee, contra-indications for MRI and a preference for one of the two surgical techniques and/or orthopaedic surgeon. Primary outcome is MRI Signal intensity ratio (SIR) of the ACL graft. Secondary outcome measures are the International Knee Documentation Committee (IKDC) Knee Examination Form,the Knee injury and Osteoarthritis Outcome Scores (KOOS) and the Anterior Cruciate Ligament OsteoArthritis Score (ACLOAS). Differences between MRI SIR assessment with the current MRI protocol (proton density weighted imaging protocol) and the additional T2*-weighted gradient-echo protocol will be assessed. There is no consensus regarding the TT or AMP ACL reconstruction technique. SI measurements with MRI have been used in other clinical studies for evaluation of the ACL graft and maturation after ACL reconstruction compared to clinical and functional outcomes. This randomized controlled trial has been designed to compare the TT technique with the AMP technique with the use of MRI SI of the graft after ACL reconstruction. Netherlands Trial Registry NTR5410 (registered on August 24, 2015).

Identification of Second Messenger Mediating Signal Transduction in the Olfactory Receptor Cell

PubMed Central

Takeuchi, Hiroko; Kurahashi, Takashi

2003-01-01

One of the biggest controversial issues in the research of olfaction has been the mechanism underlying response generation to odorants that have been shown to fail to produce cAMP when tested by biochemical assays with olfactory ciliary preparations. Such observations are actually the original source proposing a possibility for the presence of multiple and parallel transduction pathways. In this study the activity of transduction channels in the olfactory cilia was recorded in cells that retained their abilities of responding to odorants that have been reported to produce InsP3 (instead of producing cAMP, and therefore tentatively termed “InsP3 odorants”). At the same time, the cytoplasmic cNMP concentration ([cNMP]i) was manipulated through the photolysis of caged compounds to examine their real-time interactions with odorant responses. Properties of responses induced by both InsP3 odorants and cytoplasmic cNMP resembled each other in their unique characteristics. Reversal potentials of currents were 2 mV for InsP3 odorant responses and 3 mV for responses induced by cNMP. Current and voltage (I-V) relations showed slight outward rectification. Both responses showed voltage-dependent adaptation when examined with double pulse protocols. When brief pulses of the InsP3 odorant and cytoplasmic cNMP were applied alternatively, responses expressed cross-adaptation with each other. Furthermore, both responses were additive in a manner as predicted quantitatively by the theory that signal transduction is mediated by the increase in cytoplasmic cAMP. With InsP3 odorants, actually, remarkable responses could be detected in a small fraction of cells (∼2%), explaining the observation for a small production of cAMP in ciliary preparations obtained from the entire epithelium. The data will provide evidence showing that olfactory response generation and adaptation are regulated by a uniform mechanism for a wide variety of odorants. PMID:14581582

Discovery of a cAMP Deaminase That Quenches Cyclic AMP-Dependent Regulation

PubMed Central

Goble, Alissa M.; Feng, Youjun; Raushel, Frank M.; Cronan, John E.

2013-01-01

An enzyme of unknown function within the amidohydrolase superfamily was discovered to catalyze the hydrolysis of the universal second messenger, cyclic-3’, 5’-adenosine monophosphate (cAMP). The enzyme, which we have named CadD, is encoded by the human pathogenic bacterium Leptospira interrogans. Although CadD is annotated as an adenosine deaminase, the protein specifically deaminates cAMP to cyclic-3’, 5’-inosine monophosphate (cIMP) with a kcat/Km of 2.7 ± 0.4 × 105 M−1 s−1 and has no activity on adenosine, adenine, or 5’-adenosine monophosphate (AMP). This is the first identification of a deaminase specific for cAMP. Expression of CadD in Escherichia coli mimics the loss of adenylate cyclase in that it blocks growth on carbon sources that require the cAMP-CRP transcriptional activator complex for expression of the cognate genes. The cIMP reaction product cannot replace cAMP as the ligand for CRP binding to DNA in vitro and cIMP is a very poor competitor of cAMP activation of CRP for DNA binding. Transcriptional analyses indicate that CadD expression represses expression of several cAMP-CRP dependent genes. CadD adds a new activity to the cAMP metabolic network and may be a useful tool in intracellular study of cAMP-dependent processes. PMID:24074367

Performance of an electron gun for a high-brightness X-ray generator.

PubMed

Sugimura, Takashi; Ohsawa, Satoshi; Ikeda, Mitsuo

2008-05-01

A prototype thermionic electron gun for a high-brightness X-ray generator has been developed. Its extraction voltage and design current are 60 kV and 100 mA (DC), respectively. The X-ray generator aims towards a maximum brilliance of 60 kW mm(-2). The beam sizes at the rotating anticathode must therefore be within 1.0 mm x 0.1 mm and a small beam emittance is required. The fabricated electron gun optimizes an aperture grid and a Whenelt electrode. The performance of the prototype electron gun measured using pulsed-beam tests is as follows: maximum beam current, 85.7 mA; beam focus size at the rotating anticathode, 0.79 mm x 0.13 mm. In DC beam tests, FWHM beam sizes were measured to be 0.65 mm x 0.08 mm at the rotating anticathode with a beam current of 45 mA. The beam current recently reached approximately 60 mA with some thermal problems.

Detection of an electron beam in a high density plasma via an electrostatic probe

NASA Astrophysics Data System (ADS)

Majeski, Stephen; Yoo, Jongsoo; Zweben, Stewart; Yamada, Masaaki

2018-07-01

An electron beam is detected by a 1D floating potential probe array in a relatively high density (1012–1013 cm‑3) and low temperature (∼5 eV) plasma of the Magnetic Reconnection Experiment. Clear perturbations in the floating potential profile by the electron beam are observed. Based on the floating potential profile and a current balance equation to the probe array tips, the effective width of the electron beam is determined, from which we determine the radial and toroidal beam current density profiles. After the profile of the electron beam is specified from the measured beam current, we demonstrate the consistency of the current balance equation and the location of the perturbation is also in agreement with field line mapping. No significant broadening of the electron beam is observed after the beam propagates for tens of centimeters through the high density plasma. These results prove that the field line mapping is, in principle, possible in high density plasmas.

Detection of an electron beam in a high density plasma via an electrostatic probe

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

Majeski, Stephen; Yoo, Jongsoo; Zweben, Stewart

Here, an electron beam is detected by a 1D floating potential probe array in a relatively high density (10 12–10 13 cm -3) and low temperature (~5 eV) plasma of the Magnetic Reconnection Experiment. Clear perturbations in the floating potential profile by the electron beam are observed. Based on the floating potential profile and a current balance equation to the probe array tips, the effective width of the electron beam is determined, from which we determine the radial and toroidal beam current density profiles. After the profile of the electron beam is specified from the measured beam current, we demonstratemore » the consistency of the current balance equation and the location of the perturbation is also in agreement with field line mapping. No significant broadening of the electron beam is observed after the beam propagates for tens of centimeters through the high density plasma. These results prove that the field line mapping is, in principle, possible in high density plasmas.« less

Detection of an electron beam in a high density plasma via an electrostatic probe

DOE PAGES

Majeski, Stephen; Yoo, Jongsoo; Zweben, Stewart; ...

2018-05-08

Here, an electron beam is detected by a 1D floating potential probe array in a relatively high density (10 12–10 13 cm -3) and low temperature (~5 eV) plasma of the Magnetic Reconnection Experiment. Clear perturbations in the floating potential profile by the electron beam are observed. Based on the floating potential profile and a current balance equation to the probe array tips, the effective width of the electron beam is determined, from which we determine the radial and toroidal beam current density profiles. After the profile of the electron beam is specified from the measured beam current, we demonstratemore » the consistency of the current balance equation and the location of the perturbation is also in agreement with field line mapping. No significant broadening of the electron beam is observed after the beam propagates for tens of centimeters through the high density plasma. These results prove that the field line mapping is, in principle, possible in high density plasmas.« less

Cyclic AMP Inhibits the Activity and Promotes the Acetylation of Acetyl-CoA Synthetase through Competitive Binding to the ATP/AMP Pocket.

PubMed

Han, Xiaobiao; Shen, Liqiang; Wang, Qijun; Cen, Xufeng; Wang, Jin; Wu, Meng; Li, Peng; Zhao, Wei; Zhang, Yu; Zhao, Guoping

2017-01-27

The high-affinity biosynthetic pathway for converting acetate to acetyl-coenzyme A (acetyl-CoA) is catalyzed by the central metabolic enzyme acetyl-coenzyme A synthetase (Acs), which is finely regulated both at the transcriptional level via cyclic AMP (cAMP)-driven trans-activation and at the post-translational level via acetylation inhibition. In this study, we discovered that cAMP directly binds to Salmonella enterica Acs (SeAcs) and inhibits its activity in a substrate-competitive manner. In addition, cAMP binding increases SeAcs acetylation by simultaneously promoting Pat-dependent acetylation and inhibiting CobB-dependent deacetylation, resulting in enhanced SeAcs inhibition. A crystal structure study and site-directed mutagenesis analyses confirmed that cAMP binds to the ATP/AMP pocket of SeAcs, and restrains SeAcs in an open conformation. The cAMP contact residues are well conserved from prokaryotes to eukaryotes, suggesting a general regulatory mechanism of cAMP on Acs. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

cAMP enhances BMP2-signaling through PKA and MKP1-dependent mechanisms

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

Ghayor, Chafik; Ehrbar, Martin; Miguel, Blanca San

2009-04-03

Recent studies suggest that the elevation of intracellular cyclic adenosine monophosphate (cAMP) and the activation of the protein kinase A regulate BMP-induced osteogenesis. However, the precise mechanisms underlying the enhancing effect of cAMP on BMP2 signaling were not completely revealed. In this study we investigated the effect of elevated cAMP level and PKA activation on the BMP2-induced osteoblastic differentiation in pluripotent C2C12 cells. Alkaline phosphatase activity and its mRNA were consistently induced by BMP2 treatment. The pretreatment of C2C12 cells with Forskolin, a cAMP generating agent, dbcAMP, an analogue of cAMP, or IBMX (3-isobutyl 1-methyl xanthine), and a nonspecific inhibitormore » of phosphodiesterases elicited further activation of alkaline phosphatase. Furthermore, elevated intracellular cAMP level increased BMP2-induced MKP1. On the other hand, BMP2-induced Erk phosphorylation (p44/p42) and cell proliferation were suppressed in the presence of cAMP. Thus, cAMP might enhance BMP2-induced osteoblastic differentiation by a MKP1-Erk-dependent mechanism.« less

cAMP dependent and independent regulation of thyroglobulin synthesis by two clones of the OVNIS 6H thyroid cell line.

PubMed

Aouani, A; Hovsépian, S; Fayet, G

1987-07-01

The hormonal regulation of thyroglobulin synthesis has been studied using two independent clones of the OVNIS 6H cell line. Insulin, hydrocortisone and TSH were able to stimulate thyroglobulin synthesis, whereas transferrin, somatostatin and glycyl-histidyl-lysine were without effect. Insulin stimulated thyroglobulin synthesis without affecting cAMP production. Hydrocortisone, when combined with insulin was a stimulator too; this stimulation was not accompanied by an increase in cAMP. TSH alone was unable to stimulate either cAMP or thyroglobulin synthesis. The stimulatory effect of TSH on thyroglobulin synthesis took place only when combined with insulin or insulin plus hydrocortisone, and was mediated by cAMP. Consequently, insulin and hydrocortisone stimulated thyroglobulin synthesis by cAMP-independent mechanisms, whereas TSH acted via the cAMP system. Forskolin mimicked TSH effects on cAMP and thyroglobulin synthesis. Calf serum inhibited cAMP and thyroglobulin production. Optimal cAMP and thyroglobulin synthesis as well as TSH responsiveness were obtained in serum-free medium supplemented with 5 micrograms/ml insulin, 100 nM hydrocortisone and 1 mU/ml TSH.

Mechanisms Restricting Diffusion of Intracellular cAMP.

PubMed

Agarwal, Shailesh R; Clancy, Colleen E; Harvey, Robert D

2016-01-22

Although numerous receptors stimulate cAMP production in a wide array of cells, many elicit distinct, highly localized responses, implying that the subcellular distribution of cAMP is not uniform. One often used explanation is that phosphodiesterases, which breakdown cAMP, act as functional barriers limiting diffusion. However, several studies refute the notion that this is sufficient, suggesting that phosphodiesterase-independent movement of cAMP must occur at rates slower than free diffusion. But, until now this has never been demonstrated. Using Raster Image Correlation Spectroscopy (RICS), we measured the diffusion coefficient of a fluorescently-labeled cAMP derivative (φ450-cAMP) as well as other fluorescent molecules in order to investigate the role that molecular size, cell morphology, and buffering by protein kinase A (PKA) play in restricting cAMP mobility in different cell types. Our results demonstrate that cytosolic movement of cAMP is indeed much slower than the rate of free diffusion and that interactions with PKA, especially type II PKA associated with mitochondria, play a significant role. These findings have important implications with respect to cAMP signaling in all cells.

Mechanisms Restricting Diffusion of Intracellular cAMP

PubMed Central

Agarwal, Shailesh R.; Clancy, Colleen E.; Harvey, Robert D.

2016-01-01

Although numerous receptors stimulate cAMP production in a wide array of cells, many elicit distinct, highly localized responses, implying that the subcellular distribution of cAMP is not uniform. One often used explanation is that phosphodiesterases, which breakdown cAMP, act as functional barriers limiting diffusion. However, several studies refute the notion that this is sufficient, suggesting that phosphodiesterase-independent movement of cAMP must occur at rates slower than free diffusion. But, until now this has never been demonstrated. Using Raster Image Correlation Spectroscopy (RICS), we measured the diffusion coefficient of a fluorescently-labeled cAMP derivative (φ450-cAMP) as well as other fluorescent molecules in order to investigate the role that molecular size, cell morphology, and buffering by protein kinase A (PKA) play in restricting cAMP mobility in different cell types. Our results demonstrate that cytosolic movement of cAMP is indeed much slower than the rate of free diffusion and that interactions with PKA, especially type II PKA associated with mitochondria, play a significant role. These findings have important implications with respect to cAMP signaling in all cells. PMID:26795432

Influence of the electrode gap separation on the pseudospark-sourced electron beam generation

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

Zhao, J., E-mail: junping.zhao@qq.com; State Key Laboratory of Electrical Insulation and Power Equipment, West Xianning Road, Xi'an 710049; Department of Physics, SUPA, University of Strathclyde, Glasgow, G4 0NG Scotland

Pseudospark-sourced electron beam is a self-focused intense electron beam which can propagate without any external focusing magnetic field. This electron beam can drive a beam-wave interaction directly or after being post-accelerated. It is especially suitable for terahertz radiation generation due to the ability of a pseudospark discharge to produce small size in the micron range and very high current density and bright electron beams. In this paper, a single-gap pseudospark discharge chamber has been built and tested with several electrode gap separations to explore the dependence of the pseudospark-sourced electron beam current on the discharge voltage and the electrode gapmore » separation. Experimental results show that the beam pulses have similar pulse width and delay time from the distinct drop of the applied voltage for smaller electrode gap separations but longer delay time for the largest gap separation used in the experiment. It has been found that the electron beam only starts to occur when the charging voltage is above a certain value, which is defined as the starting voltage of the electron beam. The starting voltage is different for different electrode gap separations and decreases with increasing electrode gap separation in our pseudospark discharge configuration. The electron beam current increases with the increasing discharge voltage following two tendencies. Under the same discharge voltage, the configuration with the larger electrode gap separation will generate higher electron beam current. When the discharge voltage is higher than 10 kV, the beam current generated at the electrode gap separation of 17.0 mm, is much higher than that generated at smaller gap separations. The ionization of the neutral gas in the main gap is inferred to contribute more to the current increase with increasing electrode gap separation.« less

AMP Affects Intracellular Ca2+ Signaling, Migration, Cytokine Secretion and T Cell Priming Capacity of Dendritic Cells

PubMed Central

Panther, Elisabeth; Dürk, Thorsten; Ferrari, Davide; Di Virgilio, Francesco; Grimm, Melanie; Sorichter, Stephan; Cicko, Sanja; Herouy, Yared; Norgauer, Johannes; Idzko, Marco; Müller, Tobias

2012-01-01

The nucleotide adenosine-5′-monophosphate (AMP) can be released by various cell types and has been shown to elicit different cellular responses. In the extracellular space AMP is dephosphorylated to the nucleoside adenosine which can then bind to adenosine receptors. However, it has been shown that AMP can also activate A1 and A2a receptors directly. Here we show that AMP is a potent modulator of mouse and human dendritic cell (DC) function. AMP increased intracellular Ca2+ concentration in a time and dose dependent manner. Furthermore, AMP stimulated actin-polymerization in human DCs and induced migration of immature human and bone marrow derived mouse DCs, both via direct activation of A1 receptors. AMP strongly inhibited secretion of TNF-α and IL-12p70, while it enhanced production of IL-10 both via activation of A2a receptors. Consequently, DCs matured in the presence of AMP and co-cultivated with naive CD4+CD45RA+ T cells inhibited IFN-γ production whereas secretion of IL-5 and IL-13 was up-regulated. An enhancement of Th2-driven immune response could also be observed when OVA-pulsed murine DCs were pretreated with AMP prior to co-culture with OVA-transgenic naïve OTII T cells. An effect due to the enzymatic degradation of AMP to adenosine could be ruled out, as AMP still elicited migration and changes in cytokine secretion in bone-marrow derived DCs generated from CD73-deficient animals and in human DCs pretreated with the ecto-nucleotidase inhibitor 5′-(alpha,beta-methylene) diphosphate (APCP). Finally, the influence of contaminating adenosine could be excluded, as AMP admixed with adenosine desaminase (ADA) was still able to influence DC function. In summary our data show that AMP when present during maturation is a potent regulator of dendritic cell function and point out the role for AMP in the pathogenesis of inflammatory disorders. PMID:22624049

c-di-AMP: An Essential Molecule in the Signaling Pathways that Regulate the Viability and Virulence of Gram-Positive Bacteria

PubMed Central

Fahmi, Tazin; Port, Gary C.

2017-01-01

Signal transduction pathways enable organisms to monitor their external environment and adjust gene regulation to appropriately modify their cellular processes. Second messenger nucleotides including cyclic adenosine monophosphate (c-AMP), cyclic guanosine monophosphate (c-GMP), cyclic di-guanosine monophosphate (c-di-GMP), and cyclic di-adenosine monophosphate (c-di-AMP) play key roles in many signal transduction pathways used by prokaryotes and/or eukaryotes. Among the various second messenger nucleotides molecules, c-di-AMP was discovered recently and has since been shown to be involved in cell growth, survival, and regulation of virulence, primarily within Gram-positive bacteria. The cellular level of c-di-AMP is maintained by a family of c-di-AMP synthesizing enzymes, diadenylate cyclases (DACs), and degradation enzymes, phosphodiesterases (PDEs). Genetic manipulation of DACs and PDEs have demonstrated that alteration of c-di-AMP levels impacts both growth and virulence of microorganisms. Unlike other second messenger molecules, c-di-AMP is essential for growth in several bacterial species as many basic cellular functions are regulated by c-di-AMP including cell wall maintenance, potassium ion homeostasis, DNA damage repair, etc. c-di-AMP follows a typical second messenger signaling pathway, beginning with binding to receptor molecules to subsequent regulation of downstream cellular processes. While c-di-AMP binds to specific proteins that regulate pathways in bacterial cells, c-di-AMP also binds to regulatory RNA molecules that control potassium ion channel expression in Bacillus subtilis. c-di-AMP signaling also occurs in eukaryotes, as bacterially produced c-di-AMP stimulates host immune responses during infection through binding of innate immune surveillance proteins. Due to its existence in diverse microorganisms, its involvement in crucial cellular activities, and its stimulating activity in host immune responses, c-di-AMP signaling pathway has become an attractive antimicrobial drug target and therefore has been the focus of intensive study in several important pathogens. PMID:28783096

cAMP-secretion coupling is impaired in diabetic GK/Par rat β-cells: a defect counteracted by GLP-1.

PubMed

Dolz, Manuel; Movassat, Jamileh; Bailbé, Danielle; Le Stunff, Hervé; Giroix, Marie-Hélène; Fradet, Magali; Kergoat, Micheline; Portha, Bernard

2011-11-01

cAMP-raising agents with glucagon-like peptide-1 (GLP-1) as the first in class, exhibit multiple actions that are beneficial for the treatment of type 2 diabetic (T2D) patients, including improvement of glucose-induced insulin secretion (GIIS). To gain additional insight into the role of cAMP in the disturbed stimulus-secretion coupling within the diabetic β-cell, we examined more thoroughly the relationship between changes in islet cAMP concentration and insulin release in the GK/Par rat model of T2D. Basal cAMP content in GK/Par islets was significantly higher, whereas their basal insulin release was not significantly different from that of Wistar (W) islets. Even in the presence of IBMX or GLP-1, their insulin release did not significantly change despite further enhanced cAMP accumulation in both cases. The high basal cAMP level most likely reflects an increased cAMP generation in GK/Par compared with W islets since 1) forskolin dose-dependently induced an exaggerated cAMP accumulation; 2) adenylyl cyclase (AC)2, AC3, and G(s)α proteins were overexpressed; 3) IBMX-activated cAMP accumulation was less efficient and PDE-3B and PDE-1C mRNA were decreased. Moreover, the GK/Par insulin release apparatus appears less sensitive to cAMP, since GK/Par islets released less insulin at submaximal cAMP levels and required five times more cAMP to reach a maximal secretion rate no longer different from W. GLP-1 was able to reactivate GK/Par insulin secretion so that GIIS became indistinguishable from that of W. The exaggerated cAMP production is instrumental, since GLP-1-induced GIIS reactivation was lost in the presence the AC blocker 2',5'-dideoxyadenosine. This GLP-1 effect takes place in the absence of any improvement of the [Ca(2+)](i) response and correlates with activation of the cAMP-dependent PKA-dependent pathway.

8-Bromo-cAMP decreases the Ca2+ sensitivity of airway smooth muscle contraction through a mechanism distinct from inhibition of Rho-kinase.

PubMed

Endou, Katsuaki; Iizuka, Kunihiko; Yoshii, Akihiro; Tsukagoshi, Hideo; Ishizuka, Tamotsu; Dobashi, Kunio; Nakazawa, Tsugio; Mori, Masatomo

2004-10-01

To clarify whether cyclic AMP (cAMP)/cAMP-dependent protein kinase (PKA) activation and Rho-kinase inhibition share a common mechanism to decrease the Ca2+ sensitivity of airway smooth muscle contraction, we examined the effects of 8-bromoadenosine 3',5'-cyclic monophosphate (8-BrcAMP), a stable cAMP analog, and (+)-(R)-trans-4-(1-aminoethyl)-N-(4-pyridyl) cyclohexane carboxamide dihydrochloride, monohydrate (Y-27632), a Rho-kinase inhibitor, on carbachol (CCh)-, guanosine 5'-O-(3-thiotriphosphate) (GTPgammaS)-, 4beta-phorbol 12,13-dibutyrate (PDBu)-, and leukotriene D4 (LTD4)-induced Ca2+ sensitization in alpha-toxin-permeabilized rabbit tracheal and human bronchial smooth muscle. In rabbit trachea, CCh-induced smooth muscle contraction was inhibited by 8-BrcAMP and Y-27632 to a similar extent. However, GTPgammaS-induced smooth muscle contraction was resistant to 8-BrcAMP. In the presence of a saturating concentration of Y-27632, PDBu-induced smooth muscle contraction was completely reversed by 8-BrcAMP. Conversely, PDBu-induced smooth muscle contraction was resistant to Y-27632. In the presence of a saturating concentration of 8-BrcAMP, GTPgammaS-induced Ca2+ sensitization was also reversed by Y-27632. The 8-BrcAMP had no effect on the ATP-triggered contraction of tracheal smooth muscle that had been treated with calyculin A in rigor solutions. The 8-BrcAMP and Y-27632 additively accelerated the relaxation rate of PDBu- and GTPgammaS-treated smooth muscle under myosin light chain kinase-inhibited conditions. In human bronchus, LTD4-induced smooth muscle contraction was inhibited by both 8-BrcAMP and Y-27632. We conclude that cAMP/PKA-induced Ca2+ desensitization contains at least two mechanisms: 1) inhibition of the muscarinic receptor signaling upstream from Rho activation and 2) cAMP/PKA's preferential reversal of PKC-mediated Ca2+ sensitization in airway smooth muscle.

Beam brilliance investigation of high current ion beams at GSI heavy ion accelerator facility.

PubMed

Adonin, A A; Hollinger, R

2014-02-01

In this work the emittance measurements of high current Ta-beam provided by VARIS (Vacuum Arc Ion Source) ion source are presented. Beam brilliance as a function of beam aperture at various extraction conditions is investigated. Influence of electrostatic ion beam compression in post acceleration gap on the beam quality is discussed. Use of different extraction systems (single aperture, 7 holes, and 13 holes) in order to achieve more peaked beam core is considered. The possible ways to increase the beam brilliance are discussed.

Activation state of the hyperpolarization-activated current modulates temperature-sensitivity of firing in locus coeruleus neurons from bullfrogs.

PubMed

Santin, Joseph M; Hartzler, Lynn K

2015-06-15

Locus coeruleus neurons of anuran amphibians contribute to breathing control and have spontaneous firing frequencies that, paradoxically, increase with cooling. We previously showed that cooling inhibits a depolarizing membrane current, the hyperpolarization-activated current (I h) in locus coeruleus neurons from bullfrogs, Lithobates catesbeianus (Santin JM, Watters KC, Putnam RW, Hartzler LK. Am J Physiol Regul Integr Comp Physiol 305: R1451-R1464, 2013). This suggests an unlikely role for I h in generating cold activation, but led us to hypothesize that inhibition of I h by cooling functions as a physiological brake to limit the cold-activated response. Using whole cell electrophysiology in brain slices, we employed 2 mM Cs(+) (an I h antagonist) to isolate the role of I h in spontaneous firing and cold activation in neurons recorded with either control or I h agonist (cyclic AMP)-containing artificial intracellular fluid. I h did not contribute to the membrane potential (V m) and spontaneous firing at 20°C. Although voltage-clamp analysis confirmed that cooling inhibits I h, its lack of involvement in setting baseline firing and V m precluded its ability to regulate cold activation as hypothesized. In contrast, neurons dialyzed with cAMP exhibited greater baseline firing frequencies at 20°C due to I h activation. Our hypothesis was supported when the starting level of I h was enhanced by elevating cAMP because cold activation was converted to more ordinary cold inhibition. These findings indicate that situations leading to enhancement of I h facilitate firing at 20°C, yet the hyperpolarization associated with inhibiting a depolarizing cation current by cooling blunts the net V m response to cooling to oppose normal cold-depolarizing factors. This suggests that the influence of I h activation state on neuronal firing varies in the poikilothermic neuronal environment. Copyright © 2015 the American Physiological Society.

Enzymatic Characterization of AMP Phosphorylase and Ribose-1,5-Bisphosphate Isomerase Functioning in an Archaeal AMP Metabolic Pathway

PubMed Central

Aono, Riku; Sato, Takaaki; Yano, Ayumu; Yoshida, Shosuke; Nishitani, Yuichi; Miki, Kunio; Imanaka, Tadayuki

2012-01-01

AMP phosphorylase (AMPpase), ribose-1,5-bisphosphate (R15P) isomerase, and type III ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) have been proposed to constitute a novel pathway involved in AMP metabolism in the Archaea. Here we performed a biochemical examination of AMPpase and R15P isomerase from Thermococcus kodakarensis. R15P isomerase was specific for the α-anomer of R15P and did not recognize other sugar compounds. We observed that activity was extremely low with the substrate R15P alone but was dramatically activated in the presence of AMP. Using AMP-activated R15P isomerase, we reevaluated the substrate specificity of AMPpase. AMPpase exhibited phosphorylase activity toward CMP and UMP in addition to AMP. The [S]-v plot (plot of velocity versus substrate concentration) of the enzyme toward AMP was sigmoidal, with an increase in activity observed at concentrations higher than approximately 3 mM. The behavior of the two enzymes toward AMP indicates that the pathway is intrinsically designed to prevent excess degradation of intracellular AMP. We further examined the formation of 3-phosphoglycerate from AMP, CMP, and UMP in T. kodakarensis cell extracts. 3-Phosphoglycerate generation was observed from AMP alone, and from CMP or UMP in the presence of dAMP, which also activates R15P isomerase. 3-Phosphoglycerate was not formed when 2-carboxyarabinitol 1,5-bisphosphate, a Rubisco inhibitor, was added. The results strongly suggest that these enzymes are actually involved in the conversion of nucleoside monophosphates to 3-phosphoglycerate in T. kodakarensis. PMID:23065974

Analytic Determination of Interference Thresholds for Microwave Landing System Equipment and TACAN/DME Equipment

DTIC Science & Technology

1980-08-01

terminals for the PD channel, in dB, at function level tD /U]lL pea^,, desired-to-average undesired signal power at the phase-locked loop for successful...listed belows MS Receiver Reparation Distance (nmI) estimated Altitude Uetwen Desired & Undesired MS (Kilo feet) Grcnd Nquipment 2.1 42 10 142 20) 1q3

Photon Counting Detectors for the 1.0 - 2.0 Micron Wavelength Range

NASA Technical Reports Server (NTRS)

Krainak, Michael A.

2004-01-01

We describe results on the development of greater than 200 micron diameter, single-element photon-counting detectors for the 1-2 micron wavelength range. The technical goals include quantum efficiency in the range 10-70%; detector diameter greater than 200 microns; dark count rate below 100 kilo counts-per-second (cps), and maximum count rate above 10 Mcps.

The Bean pod mottle virus RNA2-encoded 58-kilodalton protein P58 is required in cis for RNA2 accumulation

USDA-ARS?s Scientific Manuscript database

Bean pod mottle virus (BPMV) is a bipartite, positive sense (+) RNA plant virus in the Secoviridae family. Its RNA1 encodes proteins required for genome replication, whereas RNA2 primarily encodes proteins needed for virion assembly and cell-to-cell movement. However, the function of a 58 kilo-dalto...

EXTREME INTENSITY INCREASES OF HIGH-ENERGY PARTICLE RADIATION IN THE EXOSPHERE AS OBSERVED BY SPUTNIK III

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

Knuth, R.

1962-09-01

Two channels in the telemetered data from Sputnik III investigated the intensity of high-energy photons over 35 kilo-electron-volt. The data from the period between May 15 and Aug. 16, 1958 (corresponding to flight altitudes between 220 and 950 kilometers) were analyzed. The extreme intensity increases observed were illustrated and are discussed. (OTS)

Aircraft Electromagnetic Compatibility.

DTIC Science & Technology

1987-06-01

Human Exposure to Radio Frequency Electromagnetic Fields , 300 KiloHertz to 100 GigaHertz." 6. ARINC 429-8, "Digital Information Transfer System (DITS...142 V EXECUTIVE SUMMARY The Aircraft Electromagnetic Compatibility guidelines document deals with electromagnetic compatibility in a... electromagnetic interference paths (figure EI. TYPE PATH 400 Hz Electrostatic MagneticCharge Electric Field Transients 5 R d t Coupling 150/i 300o Wire

76 FR 20509 - Irradiation in the Production, Processing, and Handling of Food

Federal Register 2010, 2011, 2012, 2013, 2014

2011-04-13

.... FDA-1998-F-0072] (Formerly 98F-0165) Irradiation in the Production, Processing, and Handling of Food..., Irradiation in the Production, Processing, and Handling of Food (21 CFR part 179), to provide for the safe use... irradiation of fresh shell eggs for the reduction of Salmonella at doses not to exceed 3.0 kiloGray (kGy...

Mitigation of carbon dioxide from the Indonesia energy system

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

Adi, A.C.; Nurrohim, A.; Hidajat, M.N.

1996-12-31

Energy consumption in Indonesia is growing fast in line with the development of national economy. During (1990 - 1993) the emission of CO{sub 2} gas coming from energy sector increased from 150 million tones to 200 million tones in 1993. Whereas, the total methane emission from the oil, gas and coal sub-sector reached 550 kilo tones in 1991 and increased to 670 kilo tones in 1994. This amount of CO{sub 2} and Methane from energy sector was 26% and 10 % respectively of the total emission of Indonesia. Based on the last two decades of Indonesia`s economic growth experience, asmore » a developing country this high economic growth rate of Indonesia in the future will be kept until reaching the newly industrialized country level, which is more than 6% annually in the next decade. This high growth rate economic projection will also added the level of GHG emission in the future. As a developing country Indonesia is one of the fast growing countries. The GDP growth in the year 1995 was more than 7 percent, therefore growth rate of energy consumption in this country also rose following the economic growth.« less

Anticonvulsant effect of AMP by direct activation of adenosine A1 receptor.

PubMed

Muzzi, Mirko; Coppi, Elisabetta; Pugliese, Anna Maria; Chiarugi, Alberto

2013-12-01

Purinergic neurotransmission mediated by adenosine (Ado) type 1 receptors (A1Rs) plays pivotal roles in negative modulation of epileptic seizures, and Ado is thought to be a key endogenous anticonvulsant. Recent evidence, however, indicates that AMP, the metabolic precursor of Ado, also activate A1Rs. Here, we evaluated the antiepileptic effects of AMP adopting in vitro and in vivo models of epilepsy. We report that AMP reversed the increase in population spike (PS) amplitude and the decrease in PS latency induced by a Mg(2+)-free extracellular solution in CA1 neurons of mouse hippocampal slices. The AMP effects were inhibited by the A1R antagonist DPCPX, but not prevented by inhibiting conversion of AMP into Ado, indicating that AMP inhibited per se sustained hippocampal excitatory neurotransmission by directly activating A1Rs. AMP also reduced seizure severity and mortality in a model of audiogenic convulsion. Of note, the anticonvulsant effects of AMP were potentiated by preventing its conversion into Ado and inhibited by DPCPX. When tested in a model of kainate-induced seizure, AMP prolonged latency of convulsions but had no effects on seizure severity and mortality. Data provide the first evidence that AMP is an endogenous anticonvulsant acting at A1Rs. © 2013.

The relationship between pulsatile GnRH secretion and cAMP production in immortalized GnRH neurons.

PubMed

Frattarelli, John L; Krsmanovic, Lazar Z; Catt, Kevin J

2011-06-01

In perifused immortalized GnRH neurons (GT1-7), simultaneous measurements of GnRH and cAMP revealed that the secretory profiles for both GnRH and cAMP are pulsatile. An analysis of GnRH and cAMP pulses in 16 independent experiments revealed that 25% of pulses coincide. Inversion of the peak and nadir levels was found in 33% and random relationship between GnRH and cAMP found in 42% of analyzed pulses. The random relation between GnRH and cAMP pulse resets to synchronous after an inverse relation between pulses occurred during the major GnRH release, indicating that GnRH acts as a switching mechanism to synchronize cAMP and GnRH release in perifused GT1-7 neurons. Activation of GnRH receptors with increasing agonist concentrations caused a biphasic change in cAMP levels. Low nanomolar concentrations increased cAMP production, but at high concentrations the initial increase was followed by a rapid decline to below the basal level. Blockade of the GnRH receptors by peptide and nonpeptide antagonists generated monotonic nonpulsatile increases in both GnRH and cAMP production. These findings indicate that cAMP positively regulates GnRH secretion but does not participate in the mechanism of pulsatile GnRH release.

Variable energy constant current accelerator structure

DOEpatents

Anderson, O.A.

1988-07-13

A variable energy, constant current ion beam accelerator structure is disclosed comprising an ion source capable of providing the desired ions, a pre-accelerator for establishing an initial energy level, a matching/pumping module having means for focusing means for maintaining the beam current, and at least one main accelerator module for continuing beam focus, with means capable of variably imparting acceleration to the beam so that a constant beam output current is maintained independent of the variable output energy. In a preferred embodiment, quadrupole electrodes are provided in both the matching/pumping module and the one or more accelerator modules, and are formed using four opposing cylinder electrodes which extend parallel to the beam axis and are spaced around the beam at 90/degree/ intervals with opposing electrodes maintained at the same potential. 12 figs., 3 tabs.

Automated pinhole-aperture diagnostic for the current profiling of TWT electron beams

NASA Astrophysics Data System (ADS)

Wei, Yu-Xiang; Huang, Ming-Guang; Liu, Shu-Qing; Liu, Jin-Yue; Hao, Bao-Liang; Du, Chao-Hai; Liu, Pu-Kun

2013-02-01

The measurement system reported here is intended for use in determining the current density distribution of electron beams from Pierce guns for use in TWTs. The system was designed to automatically scan the cross section of the electron beam and collect the high-resolution data with a Faraday cup probe mounted on a multistage manipulator using the LabVIEW program. A 0.06 mm thick molybdenum plate with a pinhole and a Faraday cup mounted as a probe assembly was employed to sample the electron beam current with 0.5 µm space resolution. The thermal analysis of the probe with pulse beam heating was discussed. A 0.45 µP electron gun with the expected minimum beam radius 0.42 mm was measured and the three-dimensional current density distribution, beam envelope and phase space were presented.

High-current fast electron beam propagation in a dielectric target.

PubMed

Klimo, Ondrej; Tikhonchuk, V T; Debayle, A

2007-01-01

Recent experiments demonstrate an efficient transformation of high intensity laser pulse into a relativistic electron beam with a very high current density exceeding 10(12) A cm(-2). The propagation of such a beam inside the target is possible if its current is neutralized. This phenomenon is not well understood, especially in dielectric targets. In this paper, we study the propagation of high current density electron beam in a plastic target using a particle-in-cell simulation code. The code includes both ionization of the plastic and collisions of newborn electrons. The numerical results are compared with a relatively simple analytical model and a reasonable agreement is found. The temporal evolution of the beam velocity distribution, the spatial density profile, and the propagation velocity of the ionization front are analyzed and their dependencies on the beam density and energy are discussed. The beam energy losses are mainly due to the target ionization induced by the self-generated electric field and the return current. For the highest beam density, a two-stream instability is observed to develop in the plasma behind the ionization front and it contributes to the beam energy losses.

The radiated electromagnetic field from collimated gamma rays and electron beams in air

NASA Astrophysics Data System (ADS)

Tumolillo, T. A.; Wondra, J. P.; Hobbs, W. E.; Smith, K.

1980-12-01

Nuclear weapons effects computer codes are used to study the electromagnetic field produced by gamma rays or by highly relativistic electron beams moving through the air. Consideration is given to large-area electron and gamma beams, small-area electron beams, variation of total beam current, variation of pressure in the beam channel, variation of the beam rise time, variation of beam radius, far-field radiated signals, and induced current on a system from a charged-particle beam. The work has application to system EMP coupling from nuclear weapons or charged-particle-beam weapons.

Experiment definition studies for AMPS Spacelab

NASA Technical Reports Server (NTRS)

Liemohn, H.

1975-01-01

The electrical charging of the space shuttle orbiter is discussed in relation to the AMPS Spacelab payload along with an operations research technique for the selection of AMPS Spacelab experiments. Experiments proposed for AMPS include: hydromagnetic wave experiments; bistatic sounder of AMPS wake; and an artificial meteor gun. Experiment objectives and instrument functions are given for all experiments.

Hypercapnia modulates cAMP signalling and cystic fibrosis transmembrane conductance regulator‐dependent anion and fluid secretion in airway epithelia

PubMed Central

Turner, Mark J.; Saint‐Criq, Vinciane; Patel, Waseema; Ibrahim, Salam H.; Verdon, Bernard; Ward, Christopher; Garnett, James P.; Tarran, Robert; Cann, Martin J.

2015-01-01

Key points Raised arterial blood CO2 (hypercapnia) is a feature of many lung diseases.CO2 has been shown to act as a cell signalling molecule in human cells, notably by influencing the levels of cell signalling second messengers: cAMP and Ca2+.Hypercapnia reduced cAMP‐stimulated cystic fibrosis transmembrane conductance regulator‐dependent anion and fluid transport in Calu‐3 cells and primary human airway epithelia but did not affect cAMP‐regulated HCO3 − transport via pendrin or Na+/HCO3 − cotransporters.These results further support the role of CO2 as a cell signalling molecule and suggests CO2‐induced reductions in airway anion and fluid transport may impair innate defence mechanisms of the lungs. Abstract Hypercapnia is clinically defined as an arterial blood partial pressure of CO2 of above 40 mmHg and is a feature of chronic lung disease. In previous studies we have demonstrated that hypercapnia modulates agonist‐stimulated cAMP levels through effects on transmembrane adenylyl cyclase activity. In the airways, cAMP is known to regulate cystic fibrosis transmembrane conductance regulator (CFTR)‐mediated anion and fluid secretion, which contributes to airway surface liquid homeostasis. The aim of the current work was to investigate if hypercapnia could modulate cAMP‐regulated ion and fluid transport in human airway epithelial cells. We found that acute exposure to hypercapnia significantly reduced forskolin‐stimulated elevations in intracellular cAMP as well as both adenosine‐ and forskolin‐stimulated increases in CFTR‐dependent transepithelial short‐circuit current, in polarised cultures of Calu‐3 human airway cells. This CO2‐induced reduction in anion secretion was not due to a decrease in HCO3 − transport given that neither a change in CFTR‐dependent HCO3 − efflux nor Na+/HCO3 − cotransporter‐dependent HCO3 − influx were CO2‐sensitive. Hypercapnia also reduced the volume of forskolin‐stimulated fluid secretion over 24 h, yet had no effect on the HCO3 − content of the secreted fluid. Our data reveal that hypercapnia reduces CFTR‐dependent, electrogenic Cl− and fluid secretion, but not CFTR‐dependent HCO3 − secretion, which highlights a differential sensitivity of Cl− and HCO3 − transporters to raised CO2 in Calu‐3 cells. Hypercapnia also reduced forskolin‐stimulated CFTR‐dependent anion secretion in primary human airway epithelia. Based on current models of airways biology, a reduction in fluid secretion, associated with hypercapnia, would be predicted to have important consequences for airways hydration and the innate defence mechanisms of the lungs. PMID:26574187

Current-Voltage Characteristic of Nanosecond - Duration Relativistic Electron Beam

NASA Astrophysics Data System (ADS)

Andreev, Andrey

2005-10-01

The pulsed electron-beam accelerator SINUS-6 was used to measure current-voltage characteristic of nanosecond-duration thin annular relativistic electron beam accelerated in vacuum along axis of a smooth uniform metal tube immersed into strong axial magnetic field. Results of these measurements as well as results of computer simulations performed using 3D MAGIC code show that the electron-beam current dependence on the accelerating voltage at the front of the nanosecond-duration pulse is different from the analogical dependence at the flat part of the pulse. In the steady-state (flat) part of the pulse), the measured electron-beam current is close to Fedosov current [1], which is governed by the conservation law of an electron moment flow for any constant voltage. In the non steady-state part (front) of the pulse, the electron-beam current is higher that the appropriate, for a giving voltage, steady-state (Fedosov) current. [1] A. I. Fedosov, E. A. Litvinov, S. Ya. Belomytsev, and S. P. Bugaev, ``Characteristics of electron beam formed in diodes with magnetic insulation,'' Soviet Physics Journal (A translation of Izvestiya VUZ. Fizika), vol. 20, no. 10, October 1977 (April 20, 1978), pp.1367-1368.

Generation of a pulsed low-energy electron beam using the channel spark device

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

Elgarhy, M. A. I., E-mail: elgarhy@azhar.edu.eg; Hassaballa, S. E.; Rashed, U. M.

2015-12-15

For the generation of low-energy electron beam, the design and characteristics of channel spark discharge (CSD) operating at a low voltage are presented in this paper. The discharge voltage, discharge current, X-ray emissions, and electron beam current were experimentally determined. The effects of the applied voltage, working gas pressure, and external capacitance on the CSD and beam parameters were measured. At an applied voltage of 11 kV, an oxygen gas pressure of 25 mTorr, and an external capacitance of 16.45 nF, the maximum measured current was 900 A. The discharge current increased with the increase in the pressure and capacitance,more » while its periodic time decreased with the increase in the pressure. Two types of the discharge were identified and recorded: the hollow cathode discharge and the conduction discharge. A Faraday cup was used to measure the beam current. The maximum measured beam current was 120 A, and the beam signal exhibited two peaks. The increase in both the external capacitance and the applied discharge voltage increased the maximum electron beam current. The electron-beam pulse time decreased with the increase in the gas pressure at a constant voltage and increased with the decrease in the applied discharge voltage. At an applied voltage of 11 kV and an oxygen gas pressure of 15 mTorr, the maximum beam energy was 2.8 keV. The X-ray signal intensity decreased with the increase in the gas pressure and increased with the increase in the capacitance.« less

Beam-plasma dielectric tensor with Mathematica

NASA Astrophysics Data System (ADS)

Bret, A.

2007-03-01

We present a Mathematica notebook allowing for the symbolic calculation of the 3×3 dielectric tensor of an electron-beam plasma system in the fluid approximation. Calculation is detailed for a cold relativistic electron beam entering a cold magnetized plasma, and for arbitrarily oriented wave vectors. We show how one can elaborate on this example to account for temperatures, arbitrarily oriented magnetic field or a different kind of plasma. Program summaryTitle of program: Tensor Catalog identifier: ADYT_v1_0 Program summary URL:http://cpc.cs.qub.ac.uk/summaries/ADYT_v1_0 Program obtainable from: CPC Program Library, Queen's University of Belfast, N. Ireland Computer for which the program is designed and others on which it has been tested: Computers: Any computer running Mathematica 4.1. Tested on DELL Dimension 5100 and IBM ThinkPad T42. Installations: ETSI Industriales, Universidad Castilla la Mancha, Ciudad Real, Spain Operating system under which the program has been tested: Windows XP Pro Programming language used: Mathematica 4.1 Memory required to execute with typical data: 7.17 Mbytes No. of bytes in distributed program, including test data, etc.: 33 439 No. of lines in distributed program, including test data, etc.: 3169 Distribution format: tar.gz Nature of the physical problem: The dielectric tensor of a relativistic beam plasma system may be quite involved to calculate symbolically when considering a magnetized plasma, kinetic pressure, collisions between species, and so on. The present Mathematica notebook performs the symbolic computation in terms of some usual dimensionless variables. Method of solution: The linearized relativistic fluid equations are directly entered and solved by Mathematica to express the first-order expression of the current. This expression is then introduced into a combination of Faraday and Ampère-Maxwell's equations to give the dielectric tensor. Some additional manipulations are needed to express the result in terms of the dimensionless variables. Restrictions on the complexity of the problem: Temperature effects are limited to small, i.e. non-relativistic, temperatures. The kinetic counterpart of the present Mathematica will usually not compute the required integrals. Typical running time: About 1 minute on a Intel Centrino 1.5 GHz Laptop with 512 MB of RAM. Unusual features of the program: None.

Persons with allergy symptoms use alternative medicine more often.

PubMed

Kłak, Anna; Raciborski, Filip; Krzych-Fałta, Edyta; Opoczyńska-Świeżewska, Dagmara; Szymański, Jakub; Lipiec, Agnieszka; Piekarska, Barbara; Sybilski, Adam; Tomaszewska, Aneta; Samoliński, Bolesław

2016-01-01

The aim of the study is to indicate the relation between the use of alternative medicine and the occurrence of allergic diseases in the Polish population of adults in the age of 20-44 years. Moreover the additional aim of the study is to define the relation between the sex, age and place of living and the use of alternative medicine. The data from the project Epidemiology of Allergic Diseases in Poland (ECAP) has been used for analysis. This project was a continuation of the European Community Respiratory Health Survey II. The questions on alternative medicine were asked to the group of 4671 respondents in the age of 20-44 years. Additionally outpatient tests were performed in order to confirm the diagnosis of allergic diseases. The total of 22.2% of respondents that participated in the study have ever used alternative medicine (n = 4621). A statistically significant relation between the use of alternative medicine and declaration of allergic diseases and asthma symptoms has been demonstrated (p &amp;amp;amp;amp;amp;lt; 0.001). No statistically significant relation between the use of alternative medicine by persons diagnosed by a doctor with any form of asthma or seasonal allergic rhinitis (p &amp;amp;amp;amp;amp;gt; 0.05) has been demonstrated. The occurrence of allergic diseases and asthma influences the frequency of alternative medicine use. However the frequency of alternative medicine use does not depend on allergic disease or asthma being confirmed by a doctor.

Measured and Simulated Dark J-V Characteristics of a-Si:H Single Junction p-i-n Solar Cells Irradiated with 40 keV Electrons

NASA Technical Reports Server (NTRS)

Lord, Kenneth; Woodyard, James R.

2002-01-01

The effect of 40 keV electron irradiation on a-Si:H p-i-n single-junction solar cells was investigated using measured and simulated dark J-V characteristics. EPRI-AMPS and PC-1D simulators were explored for use in the studies. The EPRI-AMPS simulator was employed and simulator parameters selected to produce agreement with measured J-V characteristics. Three current mechanisms were evident in the measured dark J-V characteristics after electron irradiation, namely, injection, shunting and a term of the form CV(sup m). Using a single discrete defect state level at the center of the band gap, good agreement was achieved between measured and simulated J-V characteristics in the forward-bias voltage region where the dark current density was dominated by injection. The current mechanism of the form CV(sup m) was removed by annealing for two hours at 140 C. Subsequent irradiation restored the CV(sup m) current mechanism and it was removed by a second anneal. Some evidence of the CV(sup m) term is present in device simulations with a higher level of discrete density of states located at the center of the bandgap.

Alternative Fuels Data Center: ampCNG Puts Conventional Fuels Out to

Science.gov Websites

; Steve Josephs, co-founder and director of engineering at ampCNG, Chicago, Illinois When ampCNG isn't the process. ampCNG's Cow-Powered Trucks ampCNG, a CNG station developer based in Chicago, Illinois interest in using more sustainable forms of fuel began in 2010, when the company partnered with Fair Oaks

Antimicrobial Peptides as Mediators of Innate Immunity in Teleosts

PubMed Central

Katzenback, Barbara A.

2015-01-01

Antimicrobial peptides (AMPs) have been identified throughout the metazoa suggesting their evolutionarily conserved nature and their presence in teleosts is no exception. AMPs are short (18–46 amino acids), usually cationic, amphipathic peptides. While AMPs are diverse in amino acid sequence, with no two AMPs being identical, they collectively appear to have conserved functions in the innate immunity of animals towards the pathogens they encounter in their environment. Fish AMPs are upregulated in response to pathogens and appear to have direct broad-spectrum antimicrobial activity towards both human and fish pathogens. However, an emerging role for AMPs as immunomodulatory molecules has become apparent—the ability of AMPs to activate the innate immune system sheds light onto the multifaceted capacity of these small peptides to combat pathogens through direct and indirect means. Herein, this review focuses on the role of teleost AMPs as modulators of the innate immune system and their regulation in response to pathogens or other exogenous molecules. The capacity to regulate AMP expression by exogenous factors may prove useful in modulating AMP expression in fish to prevent disease, particularly in aquaculture settings where crowded conditions and environmental stress pre-dispose these fish to infection. PMID:26426065

Beam-return current systems in solar flares

NASA Technical Reports Server (NTRS)

Spicer, D. S.; Sudan, R. N.

1984-01-01

It is demonstrated that the common assumption made in solar flare beam transport theory that the beam-accompanied return current is purely electrostatically driven is incorrect, and that the return current is both electrostatically and inductively driven, in accordance with Lenz's law, with the inductive effects dominating for times greater than a few plasma periods. In addition, it is shown that a beam can only exist in a solar plasma for a finite time which is much smaller than the inductive return current dissipation time. The importance of accounting for the role of the acceleration mechanism in forming the beam is discussed. In addition, the role of return current driven anomalous resistivity and its subsequent anomalous Joule heating during the flare process is elucidated.

PKA and Epac synergistically inhibit smooth muscle cell proliferation

PubMed Central

Hewer, Richard C.; Sala-Newby, Graciela B.; Wu, Yih-Jer; Newby, Andrew C.; Bond, Mark

2011-01-01

Cyclic AMP signalling promotes VSMC quiescence in healthy vessels and during vascular healing following injury. Cyclic AMP inhibits VSMC proliferation via mechanisms that are not fully understood. We investigated the role of PKA and Epac signalling on cAMP-induced inhibition of VSMC proliferation. cAMP-mediated growth arrest was PKA-dependent. However, selective PKA activation with 6-Benzoyl-cAMP did not inhibit VSMC proliferation, indicating a requirement for additional pathways. Epac activation using the selective cAMP analogue 8-CPT-2′-O-Me-cAMP, did not affect levels of hyperphosphorylated Retinoblastoma (Rb) protein, a marker of G1-S phase transition, or BrdU incorporation, despite activation of the Epac-effector Rap1. However, 6-Benzoyl-cAMP and 8-CPT-2′-O-Me-cAMP acted synergistically to inhibit Rb-hyperphosphorylation and BrdU incorporation, indicating that both pathways are required for growth inhibition. Consistent with this, constitutively active Epac increased Rap1 activity and synergised with 6-Benzoyl-cAMP to inhibit VSMC proliferation. PKA and Epac synergised to inhibit phosphorylation of ERK and JNK. Induction of stellate morphology, previously associated with cAMP-mediated growth arrest, was also dependent on activation of both PKA and Epac. Rap1 inhibition with Rap1GAP or siRNA silencing did not negate forskolin-induced inhibition of Rb-hyperphosphorylation, BrdU incorporation or stellate morphology. This data demonstrates for the first time that Epac synergises with PKA via a Rap1-independent mechanism to mediate cAMP-induced growth arrest in VSMC. This work highlights the role of Epac as a major player in cAMP-dependent growth arrest in VSMC. PMID:20971121

Nephrogenous Cyclic Adenosine Monophosphate as a Parathyroid Function Test

PubMed Central

Broadus, Arthur E.; Mahaffey, Jane E.; Bartter, Frederic C.; Neer, Robert M.

1977-01-01

Nephrogenous cyclic AMP (NcAMP), total cyclic AMP excretion (UcAMP), and plasma immunoreactive parathyroid hormone (iPTH), determined with a multivalent antiserum, were prospectively measured in 55 control subjects, 57 patients with primary hyperparathyroidism (1°HPT), and 10 patients with chronic hypoparathyroidism. In the group with 1° HPT, NcAMP was elevated in 52 patients (91%), and similar elevations were noted in subgroups of 26 patients with mild (serum calcium ≤10.7 mg/dl) or intermittent hypercalcemia, 19 patients with mild renal insufficiency (mean glomerular filtration rate, 64 ml/min), and 10 patients with moderate renal insufficiency (mean glomerular filtration rate, 43 ml/min). Plasma iPTH was increased in 41 patients (73%). The development of a parametric expression for UcAMP was found to be critically important in the clinical interpretation of results for total cAMP excretion. Because of renal impairment in a large number of patients, the absolute excretion rate of cAMP correlated poorly with the hyperparathyroid state. Expressed as a function of creatinine excretion, UcAMP was elevated in 81% of patients with 1° HPT, but the nonparametric nature of the expression led to a number of interpretive difficulties. The expression of cAMP excretion as a function of glomerular filtration rate was developed on the basis of the unique features of cAMP clearance in man, and this expression, which provided elevated values in 51 (89%) of the patients with 1° HPT, avoided entirely the inadequacies of alternative expressions. Results for NcAMP and UcAMP in nonazotemic and azotemic patients with hypoparathyroidism confirmed the validity of the measurements and the expressions employed. PMID:197123

Cardiac Hypertrophy Is Inhibited by a Local Pool of cAMP Regulated by Phosphodiesterase 2.

PubMed

Zoccarato, Anna; Surdo, Nicoletta C; Aronsen, Jan M; Fields, Laura A; Mancuso, Luisa; Dodoni, Giuliano; Stangherlin, Alessandra; Livie, Craig; Jiang, He; Sin, Yuan Yan; Gesellchen, Frank; Terrin, Anna; Baillie, George S; Nicklin, Stuart A; Graham, Delyth; Szabo-Fresnais, Nicolas; Krall, Judith; Vandeput, Fabrice; Movsesian, Matthew; Furlan, Leonardo; Corsetti, Veronica; Hamilton, Graham; Lefkimmiatis, Konstantinos; Sjaastad, Ivar; Zaccolo, Manuela

2015-09-25

Chronic elevation of 3'-5'-cyclic adenosine monophosphate (cAMP) levels has been associated with cardiac remodeling and cardiac hypertrophy. However, enhancement of particular aspects of cAMP/protein kinase A signaling seems to be beneficial for the failing heart. cAMP is a pleiotropic second messenger with the ability to generate multiple functional outcomes in response to different extracellular stimuli with strict fidelity, a feature that relies on the spatial segregation of the cAMP pathway components in signaling microdomains. How individual cAMP microdomains affect cardiac pathophysiology remains largely to be established. The cAMP-degrading enzymes phosphodiesterases (PDEs) play a key role in shaping local changes in cAMP. Here we investigated the effect of specific inhibition of selected PDEs on cardiac myocyte hypertrophic growth. Using pharmacological and genetic manipulation of PDE activity, we found that the rise in cAMP resulting from inhibition of PDE3 and PDE4 induces hypertrophy, whereas increasing cAMP levels via PDE2 inhibition is antihypertrophic. By real-time imaging of cAMP levels in intact myocytes and selective displacement of protein kinase A isoforms, we demonstrate that the antihypertrophic effect of PDE2 inhibition involves the generation of a local pool of cAMP and activation of a protein kinase A type II subset, leading to phosphorylation of the nuclear factor of activated T cells. Different cAMP pools have opposing effects on cardiac myocyte cell size. PDE2 emerges as a novel key regulator of cardiac hypertrophy in vitro and in vivo, and its inhibition may have therapeutic applications. © 2015 American Heart Association, Inc.

Genotypic and Phenotypic Detection of AmpC β-lactamases in Enterobacter spp. Isolated from a Teaching Hospital in Malaysia.

PubMed

Mohd Khari, Fatin Izzati; Karunakaran, Rina; Rosli, Roshalina; Tee Tay, Sun

2016-01-01

The objective of this study was to determine the occurrence of chromosomal and plasmid-mediated β-lactamases (AmpC) genes in a collection of Malaysian isolates of Enterobacter species. Several phenotypic tests for detection of AmpC production of Enterobacter spp. were evaluated and the agreements between tests were determined. Antimicrobial susceptibility profiles for 117 Enterobacter clinical isolates obtained from the Medical Microbiology Diagnostic Laboratory, University Malaya Medical Centre, Malaysia, from November 2012-February 2014 were determined in accordance to CLSI guidelines. AmpC genes were detected using a multiplex PCR assay targeting the MIR/ACT gene (closely related to chromosomal EBC family gene) and other plasmid-mediated genes, including DHA, MOX, CMY, ACC, and FOX. The AmpC β-lactamase production of the isolates was assessed using cefoxitin disk screening test, D69C AmpC detection set, cefoxitin-cloxacillin double disk synergy test (CC-DDS) and AmpC induction test. Among the Enterobacter isolates in this study, 39.3% were resistant to cefotaxime and ceftriaxone and 23.9% were resistant to ceftazidime. Ten (8.5%) of the isolates were resistant to cefepime, and one isolate was resistant to meropenem. Chromosomal EBC family gene was amplified from 36 (47.4%) E. cloacae and three (25%) E. asburiae. A novel blaDHA type plasmid-mediated AmpC gene was identified for the first time from an E. cloacae isolate. AmpC β-lactamase production was detected in 99 (89.2%) of 111 potential AmpC β-lactamase producers (positive in cefoxitin disk screening) using D69C AmpC detection set. The detection rates were lower with CC-DDS (80.2%) and AmpC induction tests (50.5%). There was low agreement between the D69C AmpC detection set and the other two phenotypic tests. Of the 40 isolates with AmpC genes detected in this study, 87.5%, 77.5% and 50.0% of these isolates were positive by the D69C AmpC detection set, CC-DDS and AmpC induction tests, respectively. Besides MIR/ACT gene, a novel plasmid-mediated AmpC gene belonging to the DHA-type was identified in this study. Low agreement was noted between the D69C AmpC detection set and two other phenotypic tests for detection of AmpC production in Enterobacter spp. As plasmid-mediated genes may serve as the reservoir for the emergence of antibiotic resistance in a clinical setting, surveillance and infection control measures are necessary to limit the spread of these genes in the hospital.