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Sample records for 2-10 ns pulse

  1. A ns-Pulse Laser Microthruster

    SciTech Connect

    Phipps, Claude R.; Luke, James R.

    2006-05-02

    We have developed a prototype device which demonstrates the feasibility of using ns-duration laser pulses in a laser microthruster. Relative to the ms-duration thrusters which we have demonstrated in the past, this change offers the use of any target material, the use of reflection-mode target illumination, and adjustable specific impulse. Specific impulse is adjusted by varying laser intensity on target. In this way, we were able to vary specific impulse from 200s to 3,200s on gold. We used a Concepts Research, Inc. microchip laser with 170mW average optical power, 8kHz repetition rate and 20{mu}J pulse energy for many of the measurements. Thrust was in the 100nN - 1{mu}N range for all the work, requiring development of an extremely sensitive, low-noise thrust stand. We will discuss the design of metallic fuel delivery systems. Ablation efficiency near 100% was observed. Results obtained on metallic fuel systems agreed with simulations. We also report time-of-flight measurements on ejected metal ions, which gave velocities up to 80km/s.

  2. Note: A rectangular pulse generator for 50 kV voltage, 0.8 ns rise time, and 10 ns pulse width based on polymer-film switch.

    PubMed

    Wu, Hanyu; Zhang, Xinjun; Sun, Tieping; Zeng, Zhengzhong; Cong, Peitian; Zhang, Shaoguo

    2015-10-01

    In this article, we describe a rectangular pulse generator, consisting of a polymer-film switch, a tri-plate transmission line, and parallel post-shaped ceramic resistor load, for 50-kV voltage, 0.8-ns rise time, and 10-ns width. The switch and resistors are arranged in atmospheric air and the transmission line can work in atmospheric air or in transformer oil to change the pulse width from 6.7 ns to 10 ns. The fast switching and low-inductance characteristics of the polymer-film switch ensure the fast rising wavefront of <1 ns. This generator can be applied in the calibration of nanosecond voltage dividers and used for electromagnetic pulse tests as a fast-rising current injection source. PMID:26521006

  3. Degradation of Dye Wastewater by ns-Pulse DBD Plasma

    NASA Astrophysics Data System (ADS)

    Gao, Jin; Gu, Pingdao; Yuan, Li; Zhong, Fangchuan

    2013-09-01

    Two plasma reactors have been developed and used to degrade dye wastewater agents. The configuration of one plasma reactor is a comb-like extendable unit module consisting of 5 electrodes covered with a quartz tube and the other one is an array reactor which is extended from the unit module. The decomposition of wastewater by ns pulse dielectric barrier discharge (DBD) plasma have been carried out by atomizing the dyeing solutions into the reactors. During experiments, the indigo carmine has been treated as the waste agent. The measurements of UV-VIS absorption spectroscopy and the chemical oxygen demand (COD) are carried out to demonstrate the decomposition effect on the wastewater. It shows that the decoloration rate of 99% and the COD degradation rate of 65% are achieved with 15 min treatment in the unit reactor. The effect of electrical parameters on degradation has been studied in detail. Results from the array reactor indicate that it has a better degradation effect than the unit one. It can not only totally remove the chromogenic bond of the indigo carmine solution, but also effectively degrade unsaturated bonds. The decoloration rate reaches 99% after 10 min treatment, the decomposition rate of the unsaturated bond reaches 83% after 60 min treatment, and the COD degradation rate is nearly 74%.

  4. Optimising the efficiency of pulsed diode pumped Yb:YAG laser amplifiers for ns pulse generation.

    PubMed

    Ertel, K; Banerjee, S; Mason, P D; Phillips, P J; Siebold, M; Hernandez-Gomez, C; Collier, J C

    2011-12-19

    We present a numerical model of a pulsed, diode-pumped Yb:YAG laser amplifier for the generation of high energy ns-pulses. This model is used to explore how optical-to-optical efficiency depends on factors such as pump duration, pump spectrum, pump intensity, doping concentration, and operating temperature. We put special emphasis on finding ways to achieve high efficiency within the practical limitations imposed by real-world laser systems, such as limited pump brightness and limited damage fluence. We show that a particularly advantageous way of improving efficiency within those constraints is operation at cryogenic temperature. Based on the numerical findings we present a concept for a scalable amplifier based on an end-pumped, cryogenic, gas-cooled multi-slab architecture.

  5. Plasma Membrane Permeabilization by 60- and 600-ns Electric Pulses Is Determined by the Absorbed Dose

    PubMed Central

    Ibey, Bennett L.; Xiao, Shu; Schoenbach, Karl H.; Murphy, Michael R.; Pakhomov, Andrei G.

    2008-01-01

    We explored how the effect of plasma membrane permeabilization by nanosecond-duration electric pulses (nsEP) depends on the physical characteristics of exposure. The resting membrane resistance (Rm) and membrane potential (MP) were measured in cultured GH3 and CHO cells by conventional whole-cell patch-clamp technique. Intact cells were exposed to a single nsEP (60 or 600 ns duration, 0-22 kV/cm), followed by patch-clamp measurements after a 2-3 min delay. Consistent with earlier findings, nsEP caused long-lasting Rm decrease, accompanied by the loss of MP. The threshold for these effects was about 6 kV/cm for 60 ns pulses, and about 1 kV/cm for 600 ns pulses. Further analysis established that it was neither pulse duration nor the E-field amplitude per se, but the absorbed dose that determined the magnitude of the biological effect. In other words, exposure to nsEP at either pulse duration caused equal effects if the absorbed doses were equal. The threshold absorbed dose to produce plasma membrane effects in either GH3 or CHO cells at either pulse duration was found to be at or below 10 mJ/g. Despite being determined by the dose, the nsEP effect clearly is not thermal, as the maximum heating at the threshold dose is less than 0.01 °C. The use of the absorbed dose as a universal exposure metric may help to compare and quantify nsEP sensitivity of different cell types and of cells in different physiological conditions. The absorbed dose may also prove to be a more useful metric than the incident E-field in determining safety limits for high peak, lowaverage power EMF emissions. PMID:18839412

  6. Raising the avermectins production in Streptomyces avermitilis by utilizing nanosecond pulsed electric fields (nsPEFs)

    NASA Astrophysics Data System (ADS)

    Guo, Jinsong; Ma, Ruonan; Su, Bo; Li, Yinglong; Zhang, Jue; Fang, Jing

    2016-05-01

    Avermectins, a group of anthelmintic and insecticidal agents produced from Streptomyces avermitilis, are widely used in agricultural, veterinary, and medical fields. This study presents the first report on the potential of using nanosecond pulsed electric fields (nsPEFs) to improve avermectin production in S. avermitilis. The results of colony forming units showed that 20 pulses of nsPEFs at 10 kV/cm and 20 kV/cm had a significant effect on proliferation, while 100 pulses of nsPEFs at 30 kV/cm exhibited an obvious effect on inhibition of agents. Ultraviolet spectrophotometry assay revealed that 20 pulses of nsPEFs at 15 kV/cm increased avermectin production by 42% and reduced the time for reaching a plateau in fermentation process from 7 days to 5 days. In addition, the decreased oxidation reduction potential (ORP) and increased temperature of nsPEFs-treated liquid were evidenced to be closely associated with the improved cell growth and fermentation efficiency of avermectins in S. avermitilis. More importantly, the real-time RT-PCR analysis showed that nsPEFs could remarkably enhance the expression of aveR and malE in S. avermitilis during fermentation, which are positive regulator for avermectin biosynthesis. Therefore, the nsPEFs technology presents an alternative strategy to be developed to increase avermectin output in fermentation industry.

  7. Raising the avermectins production in Streptomyces avermitilis by utilizing nanosecond pulsed electric fields (nsPEFs)

    PubMed Central

    Guo, Jinsong; Ma, Ruonan; Su, Bo; Li, Yinglong; Zhang, Jue; Fang, Jing

    2016-01-01

    Avermectins, a group of anthelmintic and insecticidal agents produced from Streptomyces avermitilis, are widely used in agricultural, veterinary, and medical fields. This study presents the first report on the potential of using nanosecond pulsed electric fields (nsPEFs) to improve avermectin production in S. avermitilis. The results of colony forming units showed that 20 pulses of nsPEFs at 10 kV/cm and 20 kV/cm had a significant effect on proliferation, while 100 pulses of nsPEFs at 30 kV/cm exhibited an obvious effect on inhibition of agents. Ultraviolet spectrophotometry assay revealed that 20 pulses of nsPEFs at 15 kV/cm increased avermectin production by 42% and reduced the time for reaching a plateau in fermentation process from 7 days to 5 days. In addition, the decreased oxidation reduction potential (ORP) and increased temperature of nsPEFs-treated liquid were evidenced to be closely associated with the improved cell growth and fermentation efficiency of avermectins in S. avermitilis. More importantly, the real-time RT-PCR analysis showed that nsPEFs could remarkably enhance the expression of aveR and malE in S. avermitilis during fermentation, which are positive regulator for avermectin biosynthesis. Therefore, the nsPEFs technology presents an alternative strategy to be developed to increase avermectin output in fermentation industry. PMID:27181521

  8. Supression of laser breakdown by pulsed nonequilibrium ns discharge

    NASA Astrophysics Data System (ADS)

    Starikovskiy, A. Y.; Semenov, I. E.; Shneider, M. N.

    2016-10-01

    The avalanche ionization induced by infrared laser pulses was investigated in a pre-ionized argon gas. Pre-ionization was created by a high-voltage pulsed nanosecond discharge developed in the form of a fast ionization wave. Then, behind the front of ionization wave additional avalanche ionization was initiated by the focused Nd-YAG laser pulse. It was shown that the gas pre-ionization inhibits the laser spark generation. It was demonstrated that the suppression of laser spark development in the case of strong gas pre-ionization is because of fast electron energy transfer from the laser beam focal region. The main mechanism of this energy transfer is free electrons diffusion.

  9. Induction of Cell Death Mechanisms and Apoptosis by Nanosecond Pulsed Electric Fields (nsPEFs)

    PubMed Central

    Beebe, Stephen J.; Sain, Nova M.; Ren, Wei

    2013-01-01

    Pulse power technology using nanosecond pulsed electric fields (nsPEFs) offers a new stimulus to modulate cell functions or induce cell death for cancer cell ablation. New data and a literature review demonstrate fundamental and basic cellular mechanisms when nsPEFs interact with cellular targets. NsPEFs supra-electroporate cells creating large numbers of nanopores in all cell membranes. While nsPEFs have multiple cellular targets, these studies show that nsPEF-induced dissipation of ΔΨm closely parallels deterioration in cell viability. Increases in intracellular Ca2+ alone were not sufficient for cell death; however, cell death depended of the presence of Ca2+. When both events occur, cell death ensues. Further, direct evidence supports the hypothesis that pulse rise-fall times or high frequency components of nsPEFs are important for decreasing ΔΨm and cell viability. Evidence indicates in Jurkat cells that cytochrome c release from mitochondria is caspase-independent indicating an absence of extrinsic apoptosis and that cell death can be caspase-dependent and –independent. The Ca2+ dependence of nsPEF-induced dissipation of ΔΨm suggests that nanoporation of inner mitochondria membranes is less likely and effects on a Ca2+-dependent protein(s) or the membrane in which it is embedded are more likely a target for nsPEF-induced cell death. The mitochondria permeability transition pore (mPTP) complex is a likely candidate. Data demonstrate that nsPEFs can bypass cancer mutations that evade apoptosis through mechanisms at either the DISC or the apoptosome. PMID:24709649

  10. 200 ns pulse high-voltage supply for terahertz field emission.

    PubMed

    Welsh, Gregor H; Turton, David A; Jones, David R; Jaroszynski, Dino A; Wynne, Klaas

    2007-04-01

    We present a method of generating 200 ns high-voltage (up to 40 kV) pulses operating at repetition rates of up to 100 kHz, which may be synchronized with laser pulses. These supplies are simple to make and were developed for ultrafast terahertz pulse generation from GaAs photoconductive antennas using a high-repetition-rate regeneratively amplified laser. We also show an improvement in signal-to-noise ratio over a continuous dc bias field and application of the supply to terahertz pulse generation. PMID:17477645

  11. The Nature of Emission from Optical Breakdown Induced by Pulses of fs and ns Duration

    SciTech Connect

    Carr, C W; Feit, M D; Rubenchik, A M; Demange, P; Kucheyev, S; Shirk, M D; Radousky, H B; Demos, S G

    2004-11-09

    Spectral emission from optical breakdown in the bulk of a transparent dielectric contains information about the nature of the breakdown medium. We have made time resolved measurements of the breakdown induced emission caused by nanosecond and femtosecond infrared laser pulses. We previously demonstrated that the emission due to ns pulses is blackbody in nature allowing determination of the fireball temperature and pressure during and after the damage event. The emission due to femtosecond pulse breakdown is not blackbody in nature; two different spectral distributions being noted. In one case, the peak spectral distribution occurs at the second harmonic of the incident radiation, in the other the distribution is broader and flatter and presumably due to continuum generation. The differences between ns and fs breakdown emission can be explained by the differing breakdown region geometries for the two pulse durations. The possibility to use spectral emission as a diagnostic of the emission region morphology will be discussed.

  12. An all solid-state high-voltage ns trigger generator based on magnetic pulse compression and transmission line transformer.

    PubMed

    Lin, Jiajin; Yang, Jianhua; Zhang, Jiande; Chen, Xinbing

    2013-09-01

    Innovative design of an all solid-state high-voltage ns trigger generator, based on magnetic pulse compression and transmission line transformer, is presented. The repetitive trigger pulse generator was developed to trigger a 700 kV trigatron, which has been used to pulse a repetitive intense electron beam accelerator with Tesla transformer charged double pulse forming lines (PFLs). Experimental results show that the trigger pulse generator could produce 180 kV 65 ns duration pulses with a rise time of 20 ns. The repetitive trigger pulses have nice uniform in the voltage waveform. The control time jitter is less then 3 ns. Owing to its good stability and low time jitter, the high-voltage trigger generator is an excellent candidate to trigger the repetitive accelerator.

  13. Laser-spectroscopic electric field measurements in a ns-pulsed microplasma in nitrogen

    NASA Astrophysics Data System (ADS)

    Boehm, Patrick; Luggenhoelscher, Dirk; Czarnetzki, Uwe; 1123 Research Group Collaboration

    2013-09-01

    In this work for the first time ns-pulsed discharges in nitrogen at near atmospheric pressures are investigated by laser-spectroscopic electric field measurements, ultra-fast optical emission spectroscopy, current and voltage measurements. The discharge is operated with kV-pulses of about 150 ns duration between two parallel plate electrodes with a 1.2 mm gap. The laser technique for electric field measurement is based on a four-wave mixing process similar to Coherent anti-Stokes Raman Scattering (CARS). Here the static electric field acts effectively as the third wave with a zero frequency. The frequency of the generated anti-Stokes wave is in the IR regime and the amplitude is proportional to the electric field strength. By measuring the intensity of the IR- and anti-Stokes-signal it is now possible to determine the static electric field. Due to the short pulse-length of the lasers a temporal resolution in the ns range and a typical sensitivity of 50 - 100 V/mm in pure nitrogen is achieved (p > 50 mbar). Field-measurements are accompanied by emission measurements using a streak-camera with sub-ns resolutions. Further, current and voltage measurements combined with the electric field measurements allow determination of the plasma density. Funding by DFG through FOR 1123.

  14. Characterization of Pressure Transients Generated by Nanosecond Electrical Pulse (nsEP) Exposure

    PubMed Central

    Roth, Caleb C.; Barnes Jr., Ronald A.; Ibey, Bennett L.; Beier, Hope T.; Christopher Mimun, L.; Maswadi, Saher M.; Shadaram, Mehdi; Glickman, Randolph D.

    2015-01-01

    The mechanism(s) responsible for the breakdown (nanoporation) of cell plasma membranes after nanosecond pulse (nsEP) exposure remains poorly understood. Current theories focus exclusively on the electrical field, citing electrostriction, water dipole alignment and/or electrodeformation as the primary mechanisms for pore formation. However, the delivery of a high-voltage nsEP to cells by tungsten electrodes creates a multitude of biophysical phenomena, including electrohydraulic cavitation, electrochemical interactions, thermoelastic expansion, and others. To date, very limited research has investigated non-electric phenomena occurring during nsEP exposures and their potential effect on cell nanoporation. Of primary interest is the production of acoustic shock waves during nsEP exposure, as it is known that acoustic shock waves can cause membrane poration (sonoporation). Based on these observations, our group characterized the acoustic pressure transients generated by nsEP and determined if such transients played any role in nanoporation. In this paper, we show that nsEP exposures, equivalent to those used in cellular studies, are capable of generating high-frequency (2.5 MHz), high-intensity (>13 kPa) pressure transients. Using confocal microscopy to measure cell uptake of YO-PRO®-1 (indicator of nanoporation of the plasma membrane) and changing the electrode geometry, we determined that acoustic waves alone are not responsible for poration of the membrane. PMID:26450165

  15. Characterization of Pressure Transients Generated by Nanosecond Electrical Pulse (nsEP) Exposure.

    PubMed

    Roth, Caleb C; Barnes, Ronald A; Ibey, Bennett L; Beier, Hope T; Christopher Mimun, L; Maswadi, Saher M; Shadaram, Mehdi; Glickman, Randolph D

    2015-10-09

    The mechanism(s) responsible for the breakdown (nanoporation) of cell plasma membranes after nanosecond pulse (nsEP) exposure remains poorly understood. Current theories focus exclusively on the electrical field, citing electrostriction, water dipole alignment and/or electrodeformation as the primary mechanisms for pore formation. However, the delivery of a high-voltage nsEP to cells by tungsten electrodes creates a multitude of biophysical phenomena, including electrohydraulic cavitation, electrochemical interactions, thermoelastic expansion, and others. To date, very limited research has investigated non-electric phenomena occurring during nsEP exposures and their potential effect on cell nanoporation. Of primary interest is the production of acoustic shock waves during nsEP exposure, as it is known that acoustic shock waves can cause membrane poration (sonoporation). Based on these observations, our group characterized the acoustic pressure transients generated by nsEP and determined if such transients played any role in nanoporation. In this paper, we show that nsEP exposures, equivalent to those used in cellular studies, are capable of generating high-frequency (2.5 MHz), high-intensity (>13 kPa) pressure transients. Using confocal microscopy to measure cell uptake of YO-PRO®-1 (indicator of nanoporation of the plasma membrane) and changing the electrode geometry, we determined that acoustic waves alone are not responsible for poration of the membrane.

  16. Characterization of Pressure Transients Generated by Nanosecond Electrical Pulse (nsEP) Exposure

    NASA Astrophysics Data System (ADS)

    Roth, Caleb C.; Barnes, Ronald A., Jr.; Ibey, Bennett L.; Beier, Hope T.; Christopher Mimun, L.; Maswadi, Saher M.; Shadaram, Mehdi; Glickman, Randolph D.

    2015-10-01

    The mechanism(s) responsible for the breakdown (nanoporation) of cell plasma membranes after nanosecond pulse (nsEP) exposure remains poorly understood. Current theories focus exclusively on the electrical field, citing electrostriction, water dipole alignment and/or electrodeformation as the primary mechanisms for pore formation. However, the delivery of a high-voltage nsEP to cells by tungsten electrodes creates a multitude of biophysical phenomena, including electrohydraulic cavitation, electrochemical interactions, thermoelastic expansion, and others. To date, very limited research has investigated non-electric phenomena occurring during nsEP exposures and their potential effect on cell nanoporation. Of primary interest is the production of acoustic shock waves during nsEP exposure, as it is known that acoustic shock waves can cause membrane poration (sonoporation). Based on these observations, our group characterized the acoustic pressure transients generated by nsEP and determined if such transients played any role in nanoporation. In this paper, we show that nsEP exposures, equivalent to those used in cellular studies, are capable of generating high-frequency (2.5 MHz), high-intensity (>13 kPa) pressure transients. Using confocal microscopy to measure cell uptake of YO-PRO®-1 (indicator of nanoporation of the plasma membrane) and changing the electrode geometry, we determined that acoustic waves alone are not responsible for poration of the membrane.

  17. A 4 V, ns-range pulse generator for the test of Cherenkov Telescopes readout electronics

    NASA Astrophysics Data System (ADS)

    Antoranz, P.; Vegas, I.; Miranda, J. M.

    2010-08-01

    We present in this paper the design, fabrication and verification of a ns-range pulse generator based on a Step Recovery Diode (SRD). This device needs only a 5 V DC power supply, delivers 1 ns pulses with peak amplitudes in excess of 4 V and features state of the art jitter figures. In addition, the pulser contains a trigger channel. The long standing problem of the SRD simulation via circuital analysis is addressed. It is shown that the dynamic properties of the Step Recovery Diode can accurately be reproduced via a small signal circuital simulation for the rise times needed in a ns-range pulser. It is also demonstrated that strong inaccuracies in the pulse shape prediction are obtained if the wave propagation through the lines typically used in this type of circuits is simulated by a simple Transverse Electromagnetic Mode (TEM) line model. Instead, it is necessary to account for non-TEM effects. By means of broadband resistive power splitters and high dynamic range amplifiers, a prototype of 4 channels was also fabricated. This prototype is particularly useful for testing the readout electronics of Cherenkov Telescopes, but additional applications to other large-scale experiments are expected, any of those where calibration or verification with compact ns-range pulsers featuring low jitter, large dynamic ranges and multichannel operation is needed. In addition, the fabrication cost of this pulser is almost negligible as compared with bulky, commercially available waveform generators, which rarely deliver ns pulses in excess of 3 V. Furthermore, the small size of the pulser presented here and its low power consumption allow an easy integration into more complex systems.

  18. Thermoreflectance imaging of sub 100 ns pulsed cooling in high-speed thermoelectric microcoolers

    NASA Astrophysics Data System (ADS)

    Vermeersch, Bjorn; Bahk, Je-Hyeong; Christofferson, James; Shakouri, Ali

    2013-03-01

    Miniaturized thin film thermoelectric coolers have received considerable attention as potential means to locally address hot spots in microprocessors. Given the highly dynamic workload in complex integrated circuits, the need arises for a thorough understanding of the high-speed thermal behavior of microcoolers. Although some prior work on transient Peltier cooling in pulsed operation is available, these studies mostly focus on theoretical modeling and typically deal with relatively large modules with time constants well into the millisecond range. In this paper, we present an extensive experimental characterization of 30×30 μm2 high-speed coplanar SiGe superlattice microcoolers subjected to 300 ns wide current pulses at ≈ 300 kHz repetition rate. Using thermoreflectance imaging microscopy, we obtain 2D maps of the transient surface temperature and constituent Peltier and Joule components over the 50-750 ns time range with submicron spatial and 50 ns temporal resolutions. Net cooling of 1 K-1.5 K is achieved within 100-300 ns, well over an order of magnitude faster compared to previous reports on microcoolers in high-speed operation. We also point out ambiguities in separating Peltier and Joule signals during the device turn-off. Overall, our measurements provide substantial insight into ultrafast turn-on and turn-off dynamics in thin film thermoelectrics.

  19. Comparing ablation induced by fs, ps, and ns XUV-laser pulses

    NASA Astrophysics Data System (ADS)

    Bittner, Michal; Juha, Libor; Chvostova, Dagmar; Letal, Vit; Krasa, Josef; Otcenasek, Zdenek; Kozlova, Michaela; Polan, Jiri; Praeg, Ansgar R.; Rus, Bedrich; Stupka, Michal; Krzywinski, Jacek; Andrejczuk, Andrzej; Pelka, Jerzy B.; Sobierajski, Ryszard; Feldhaus, Josef; Boody, Frederick P.; Grisham, Michael E.; Vaschenko, Georgiy O.; Menoni, Carmen S.; Rocca, Jorge J.

    2004-09-01

    Ablation thresholds, etch rates, and quality of ablated structures often differ dramatically if a conventional, UV-Vis-IR laser delivers radiation energy onto a material surface in a short (nanosecond) or ultra-short (picosecond/femtosecond) pulses. Various short-wavelength (λ < 100 nm) lasers emitting pulses with durations ranging from ~ 10 fs to ~ 1 ns have recently been put into a routine operation. This makes possible to investigate how the ablation characteristics depends on the pulse duration in the XUV spectral region. 1.2-ns pulses of 46.9-nm radiation delivered from a capillary-discharge Ne-like Ar laser, focused by a spherical Sc/Si multilayer-coated mirror were used for an ablation of organic polymers and silicon. Various materials were irradiated with an ellipsoidal-mirror-focused XUV radiation (λ = 86 nm, τ = 30-100 fs) generated by the free-electron laser (FEL) operated at the TESLA Test Facility (TTF1 FEL) in Hamburg. The beam of the Ne-like Zn XUV laser (λ = 21.2 nm, τ < 100 ps) driven by the Prague Asterix Laser System (PALS) was also successfully focused by a spherical Si/Mo multilayer-coated mirror to ablate various materials. Based on the results of the experiment the etch rates for three different pulse durations are compared using the XUV-ABLATOR code to compensate for the wavelength difference. Comparing the values of etch rates calculated for short pulses with the measured ones for ultrashort pulses we may study the influence of pulse duration on the XUV ablation efficiency.

  20. A multiphase model for pulsed ns-laser ablation of copper in an ambient gas

    SciTech Connect

    Autrique, D.; Chen, Z.; Alexiades, V.; Bogaerts, A.; Rethfeld, B.

    2012-07-30

    Laser ablation in an ambient gas is nowadays used in a growing number of applications, such as chemical analysis and pulsed laser deposition. Despite the many applications, the technique is still poorly understood. Therefore models describing the material evolution in time during short pulse laser irradiation can be helpful to unravel the puzzle and finally result in the optimization of the related applications. In the present work, a copper target is immersed in helium, initially set at atmospheric pressure and room temperature. Calculations are performed for a Gaussian-shaped laser pulse with a wavelength of 532 nm, full width at half maximum of 6 ns, and laser fluences up to 10 J/cm{sup 2}. In order to describe the transient behaviour in and above the copper target, hydrodynamic equations are solved. An internal energy method accounting for pressure relaxation is applied for the description of the target. In the plume domain a set of conservation equations is solved, assuming local thermodynamic equilibrium. Calculated crater depths and transmission profiles are compared with experimental results and similar trends are found. Our calculations indicate that for the laser fluence regime under study, explosive boiling could play a fundamental role in the plasma formation of metals under ns-pulsed laser irradiation.

  1. Analysis of Influenza A Virus NS1 Dimer Interfaces in Solution by Pulse EPR Distance Measurements

    PubMed Central

    2014-01-01

    Pulsed electron–electron double resonance (PELDOR) is an electron paramagnetic resonance (EPR) spectroscopy technique for nanometer distance measurements between paramagnetic centers such as radicals. PELDOR has been recognized as a valuable tool to approach structural questions in biological systems. In this manuscript, we demonstrate the value of distance measurements for differentiating competing structural models on the dimerization of the effector domain (ED) of the non-structural protein 1 (NS1) of the influenza A virus. Our results show NS1 to be well amenable to nanometer distance measurements by EPR, yielding high quality data. In combination with mutants perturbing protein dimerization and in silico prediction based on crystal structures, we can exclude one of two potential dimerization interfaces. Furthermore, our results lead to a viable hypothesis of a NS1 ED:ED interface which is flexible through rotation around the vector interconnecting the two native cysteines. These results prove the high value of pulse EPR as a complementary method for structural biology. PMID:25148246

  2. Characterization of a Surface-Flashover Ion Source with 10 - 250 ns Pulse Width

    SciTech Connect

    Falabella, S; Guethlein, G; Kerr, P L; Meyer, G A; Sampayan, S E; Tang, V; Morse, J D

    2008-08-05

    As a step towards developing an ultra compact D-D neutron source for various defense and homeland security applications, a compact ion source is needed. Towards that end, we are testing a pulsed, surface flashover source, with deuterated titanium films deposited on alumina substrates as the electrodes. An electrochemically-etched mask was used to define the electrode areas on the substrate during the sputtered deposition of the titanium films. Deuterium loading of the films was performed in an all metal-sealed vacuum chamber containing a heated stage. Deuterium ion current from the source was determined by measuring the neutrons produced when the ions impacted a deuterium-loaded target held at -90 kV. As the duration of the arc current is varied, it was observed that the integrated deuteron current per pulse initially increases rapidly, then reaches a maximum near a pulse length of 100 ns.

  3. The Role of Pulse Repetition Rate in nsPEF-Induced Electroporation: A Biological and Numerical Investigation.

    PubMed

    Lamberti, Patrizia; Romeo, Stefania; Sannino, Anna; Zeni, Luigi; Zeni, Olga

    2015-09-01

    The impact of pulse repetition rate (PRR) in modulating electroporation (EP) induced by nanosecond pulsed electric fields (nsPEFs) in mammalian cells was approached here by performing both biological and numerical analysis. Plasma membrane permeabilization and viability of Jurkat cells were analyzed after exposure to 500, 1.3 MV/m, 40 ns PEFs with variable PRR (2-30 Hz). A finite-element model was used to investigate EP dynamics in a single cell under the same pulsing conditions, by looking at the time course of transmembrane voltage and pore density on the ns time scale. The biological observations showed an increased EP and reduced viability of the exposed cells at lower PRR in the considered range. The numerical analysis resulted in different dynamics of plasma membrane response when ns pulses were delivered with different PRR, consistently with a phenomenon of electrodesensitization recently hypothesized by another research group. PMID:25850084

  4. Effect of focus position of ns pulse laser on damage characteristics of K9 glass

    NASA Astrophysics Data System (ADS)

    Pan, Yunxiang; Zhang, Hongchao; Li, Mengmeng; Shen, Zhonghua; Lu, Jian; Ni, Xiaowu

    2015-05-01

    Laser-induced damage of optical glasses has been investigated for more than fifty years. Due to the residual scratches, inclusions and other forms of defects at surfaces of optical glasses after the processes of grinding and polishing, it is well known that the sample surface can be damaged more easily than bulk. In order to get the relationship between the damage threshold and the location of the laser spot, we carried out damage experiments on K9 glasses with a 7ns pulse laser. Since ns pulse laser-induced damage of optical glasses always accompanies with the generation of the plasma, a optical microscope connected with a CCD camera was used to observe the plasma flash, which can provide a real time detection of damage sites. The laser pulse was first focused into the bulk, then the spot was moved toward the direction of incident laser beam step by step until the beam was completely focused in ambient air. Damage threshold curves were measured for each focus position, and low thresholds and high thresholds were extracted from those curves. Finally, the relationship between damage thresholds and focus position was analyzed.

  5. A new low-cost 10 ns pulsed K(a)-band radar.

    PubMed

    Eskelinen, Pekka; Ylinen, Juhana

    2011-07-01

    Two Gunn oscillators, conventional intermediate frequency building blocks, and a modified GaAs diode detector are combined to form a portable monostatic 10 ns instrumentation radar for outdoor K(a)-band radar cross section measurements. At 37.8 GHz the radar gives +20 dBm output power and its tangential sensitivity is -76 dBm. Processing bandwidth is 125 MHz, which also allows for some frequency drift in the Gunn devices. Intra-pulse frequency chirp is less than 15 MHz. All functions are steered by a microcontroller. First measurements convince that the construction has a reasonable ability to reduce close-to-ground surface clutter and gives an effective way of resolving target detail. This is beneficial especially when amplitude fluctuations disturb measurements with longer pulses. The new unit operates on 12 V dc, draws a current of less than 3 A, and weighs 5 kg.

  6. Design and construction of a PW ultrashort laser facility with ns, ps, and fs outputting pulses

    NASA Astrophysics Data System (ADS)

    Zhu, Qihua; Huang, Xiaojun; Wang, Xiao; Zeng, Xiaoming; Xie, Xudong; Wang, Fang; Wang, Fengrui; Lin, Donghui; Jiang, Dongbin; Wang, Xiaodong; Zhou, Kainan; Zuo, Yanlei; Zhang, Ying; Deng, Ying; Wei, Xiaofeng; Fan, Dianyuan

    2007-06-01

    A petawatt laser facility with three beams for fast ignition research and strong-field physics applications has been designed and is being constructed. The first beam (referred as SILEX-I) is a Ti:sapphire femto-second laser which pulse width is 30 fs, and till now, output power has reached to 330 TW. The other two beams are Nd 3+:glass lasers which output energy are larger than 1kJ and pulse width are about 1ps and 1ns respectively. By using the technology of OPA pumped by 800nm femtosecond laser and seeded by super-continuum white light (SWL), the three beams are synchronized with each other without jitter time. Tiled multilayer dielectric coating gratings are used for the compressor of the PW beam.

  7. Emission properties of ns and ps laser-induced soft x-ray sources using pulsed gas jets.

    PubMed

    Müller, Matthias; Kühl, Frank-Christian; Großmann, Peter; Vrba, Pavel; Mann, Klaus

    2013-05-20

    The influcence of the pulse duration on the emission characteristics of nearly debris-free laser-induced plasmas in the soft x-ray region (λ ≈ 1-5 nm) was investigated, using six different target gases from a pulsed jet. Compared to ns pulses of the same energy, a ps laser generates a smaller, more strongly ionized plasma, being about 10 times brighter than the ns laser plasma. Moreover, the spectra are considerably shifted towards shorter wavelengths. Electron temperatures and densities of the plasma are obtained by comparing the spectra with model calculations using a magneto-hydrodynamic code.

  8. Shielding properties of laser-induced breakdown in water for pulse durations from 5 ns to 125 fs.

    PubMed

    Hammer, D X; Jansen, E D; Frenz, M; Noojin, G D; Thomas, R J; Noack, J; Vogel, A; Rockwell, B A; Welch, A J

    1997-08-01

    The shielding effectiveness of laser-induced breakdown from focused, visible laser pulses from 5 ns to 125 fs is determined from measurements of transmission of energy through the focal volume. The shielding efficiency decreases as a function of pulse duration from 5 ns to 300 fs and increases from 300 fs to 125 fs. The results are compared with past studies at similar pulse durations. The results of the measurements support laser-induced breakdown models and may lead to an optimization of laser-induced breakdown in ophthalmic surgery by reduction of collateral effects. PMID:18259389

  9. Progress on developing a PW ultrashort laser facility with ns, ps, and fs outputting pulses

    NASA Astrophysics Data System (ADS)

    Zhu, Qihua; Huang, Xiaojun; Wang, Xiao; Zeng, Xiaoming; Xie, Xudong; Wang, Fang; Wang, Fengrui; Lin, Donghui; Wang, Xiaodong; Zhou, Kainan; Jiang, Dongbin; Deng, Wu; Zuo, Yanlei; Zhang, Ying; Deng, Ying; Wei, Xiaofeng; Zhang, Xiaomin; Fan, Dianyuan

    2008-03-01

    A petawatt laser facility with three beams for fast ignition research and strong-field physics applications has been designed and is being constructed. The first beam (referred as SILEX-I) is a Ti:sapphire femto-second laser which pulse width is 30 fs, and till now, output power has reached to 330 TW. The other two beams are Nd 3+:glass lasers which output energy are larger than 1kJ and pulse width are about 1ps and 1ns respectively. By using the technology of OPA pumped by 800nm femtosecond laser and seeded by super-continuum spectrum white light, the three beams are synchronized with each other without jitter time. By using the seeds from OPA pumped by femtosecond laser, and by using the pre-amplification stage of OPCPA, the signal to noise ratio of the Nd 3+:glass petawatt laser will reach to 10 8. Active methods are taken to control the gain narrowing effect of the Nd 3+:glass amplifiers, giving the option to compress the chirped pulse to ultrashort pulse with width less than 400fs. Tiled multilayer dielectric coating gratings are used for the compressor of the PW beam, which has been successfully demonstrated on a 100J picosecond Nd 3+:glass laser system.

  10. Nanosecond pulsed electric fields (nsPEF) induce direct electric field effects and biological effects on human colon carcinoma cells.

    PubMed

    Hall, Emily H; Schoenbach, Karl H; Beebe, Stephen J

    2005-05-01

    Nanosecond pulsed electric fields (nsPEFs) are ultrashort pulses with high electric field intensity (kV/cm) and high power (megawatts), but low energy density (mJ/cc). To determine roles for p53 in response to nsPEFs, HCT116 cells (p53+/+ and p53-/-) were exposed to nsPEF and analyzed for membrane integrity, phosphatidylserine externalization, caspase activation, and cell survival. Decreasing plasma membrane effects were observed in both HCT116p53+/+ and p53-/- cells with decreasing pulse durations and/or decreasing electric fields. However, addition of ethidium homodimer-1 and Annexin-V-FITC post-pulse demonstrated greater fluorescence in p53-/- versus p53+/+ cells, suggesting a postpulse p53-dependent biological effect at the plasma membrane. Caspase activity was significantly higher than nonpulsed cells only in the p53-/- cells. HCT116 cells exhibited greater survival in response to nsPEFs than HL-60 and Jurkat cells, but survival was more evident for HCT116p53+/+ cells than for HCT116p53-/- cells. These results indicate that nsPEF effects on HCT116 cells include (1) apparent direct electric field effects, (2) biological effects that are p53-dependent and p53-independent, (3) actions on mechanisms that originate at the plasma membranes and at intracellular structures, and (4) an apparent p53 protective effect. NsPEF applications provide a means to explore intracellular structures and functions that can reveal mechanisms in health and disease.

  11. Effects of nanosecond pulsed electrical fields (nsPEFs) on the cell cycle of CHO and Jurkat cells

    NASA Astrophysics Data System (ADS)

    Mahlke, Megan A.; Navara, Christopher; Ibey, Bennett L.

    2014-03-01

    Exposure to nano-second pulsed electrical fields (nsPEFs) can cause poration of external and internal cell membranes, DNA damage, and disassociation of cytoskeletal components, all of which are capable of disrupting a cell's ability to replicate. Variations between cell lines in membrane and cytoskeletal structure as well as in survival of nsPEF exposure should correspond to unique line-dependent cell cycle effects. Additionally, phase of cell cycle during exposure may be linked to differential sensitivities to nsPEFs across cell lines, as DNA structure, membrane elasticity, and cytoskeletal structure change dramatically during the cell cycle. Populations of Jurkat and Chinese Hamster Ovary (CHO) cells were examined post-exposure (10 ns pulse trains at 150kV/cm) by analysis of DNA content via propidium iodide staining and flow cytometric analysis at various time points (1, 6, and 12h post-exposure) to determine population distribution in cell cycle phases. Additionally, CHO and Jurkat cells were synchronized in G1/S and G2/M phases, pulsed, and analyzed to evaluate role of cell cycle phase in survival of nsPEFs. CHO populations recovered similarly to sham populations postnsPEF exposure and did not exhibit a phase-specific change in response. Jurkat cells exhibited considerable apoptosis/necrosis in response to nsPEF exposure and were unable to recover and proliferate in a manner similar to sham exposed cells. Additionally, Jurkat cells appear to be more sensitive to nsPEFs in G2/M phases than in G1/S phases. Recovery of CHO populations suggests that nsPEFs do not inhibit proliferation in CHO cells; however, inhibition of Jurkat cells post-nsPEF exposure coupled with preferential cell death in G2/M phases suggest that cell cycle phase during exposure may be an important factor in determining nsPEF toxicity in certain cell lines. Interestingly, CHO cells have a more robust and rigid cytoskeleton than Jurkat cells which is thought to contribute to their ability to

  12. Nanosecond pulsed platelet-rich plasma (nsPRP) improves mechanical and electrical cardiac function following myocardial reperfusion injury.

    PubMed

    Hargrave, Barbara; Varghese, Frency; Barabutis, Nektarios; Catravas, John; Zemlin, Christian

    2016-02-01

    Ischemia and reperfusion (I/R) of the heart is associated with biochemical and ionic changes that result in cardiac contractile and electrical dysfunction. In rabbits, platelet-rich plasma activated using nanosecond pulsed electric fields (nsPRP) has been shown to improve left ventricular pumping. Here, we demonstrate that nsPRP causes a similar improvement in mouse left ventricular function. We also show that nsPRP injection recovers electrical activity even before reperfusion begins. To uncover the mechanism of nsPRP action, we studied whether the enhanced left ventricular function in nsPRP rabbit and mouse hearts was associated with increased expression of heat-shock proteins and altered mitochondrial function under conditions of oxidative stress. Mouse hearts underwent 30 min of global ischemia and 1 h of reperfusion in situ. Rabbit hearts underwent 30 min of ischemia in vivo and were reperfused for 14 days. Hearts treated with nsPRP expressed significantly higher levels of Hsp27 and Hsp70 compared to hearts treated with vehicle. Also, pretreatment of cultured H9c2 cells with nsPRP significantly enhanced the "spare respiratory capacity (SRC)" also referred to as "respiratory reserve capacity" and ATP production in response to the uncoupler FCCP. These results suggest a cardioprotective effect of nsPRP on the ischemic heart during reperfusion. PMID:26908713

  13. Nanosecond pulsed electric field (nsPEF) enhance cytotoxicity of cisplatin to hepatocellular cells by microdomain disruption on plasma membrane.

    PubMed

    Yin, Shengyong; Chen, Xinhua; Xie, Haiyang; Zhou, Lin; Guo, Danjing; Xu, Yuning; Wu, Liming; Zheng, Shusen

    2016-08-15

    Previous studies showed nanosecond pulsed electric field (nsPEF) can ablate solid tumors including hepatocellular carcinoma (HCC) but its effect on cell membrane is not fully understood. We hypothesized nsPEF disrupt the microdomains on outer-cellular membrane with direct mechanical force and as a result the plasma membrane permeability increases to facilitate the small molecule intake. Three HCC cells were pulsed one pulse per minute, an interval longer than nanopore resealing time. The cationized ferritin was used to mark up the electronegative microdomains, propidium iodide (PI) for membrane permeabilization, energy dispersive X-ray spectroscopy (EDS) for the negative cell surface charge and cisplatin for inner-cellular cytotoxicity. We demonstrated that the ferritin marked-microdomain and negative cell surface charge were disrupted by nsPEF caused-mechanical force. The cell uptake of propidium and cytotoxicity of DNA-targeted cisplatin increased with a dose effect. Cisplatin gains its maximum inner-cellular cytotoxicity when combining with nsPEF stimulation. We conclude that nsPEF disrupt the microdomains on the outer cellular membrane directly and increase the membrane permeabilization for PI and cisplatin. The microdomain disruption and membrane infiltration changes are caused by the mechanical force from the changes of negative cell surface charge. PMID:27375200

  14. Efficient generation of mode-locked pulses in Nd:YVO4 with a pulse duration adjustable between 34 ps and 1 ns.

    PubMed

    Lührmann, Markus; Theobald, Christian; Wallenstein, Richard; L'huillier, Johannes A

    2009-04-13

    We report on the generation of highly stable active continuous mode-locked pulses in diode pumped Nd:YVO(4) with an adjustable pulse duration between 34 ps and 1 ns. With this laser an average output power of up to 7.3 W with an excellent stability and beam quality with a M(2)-value of < 1.1 is obtained. For all pulse durations the pulses were within a factor of 1.15 above the Fourier limit. Due to these characteristics the presented system is an attractive oscillator for OPCPA concepts.

  15. Evaluation of the Genetic Response of U937 and Jurkat Cells to 10-Nanosecond Electrical Pulses (nsEP)

    PubMed Central

    Glickman, Randolph D.; Tolstykh, Gleb P.; Estlack, Larry E.; Moen, Erick K.; Echchgadda, Ibtissam; Beier, Hope T.; Barnes, Ronald A.; Ibey, Bennett L.

    2016-01-01

    Nanosecond electrical pulse (nsEP) exposure activates signaling pathways, produces oxidative stress, stimulates hormone secretion, causes cell swelling and induces apoptotic and necrotic death. The underlying biophysical connection(s) between these diverse cellular reactions and nsEP has yet to be elucidated. Using global genetic analysis, we evaluated how two commonly studied cell types, U937 and Jurkat, respond to nsEP exposure. We hypothesized that by studying the genetic response of the cells following exposure, we would gain direct insight into the stresses experienced by the cell and in turn better understand the biophysical interaction taking place during the exposure. Using Ingenuity Systems software, we found genes associated with cell growth, movement and development to be significantly up-regulated in both cell types 4 h post exposure to nsEP. In agreement with our hypothesis, we also found that both cell lines exhibit significant biological changes consistent with mechanical stress induction. These results advance nsEP research by providing strong evidence that the interaction of nsEPs with cells involves mechanical stress. PMID:27135944

  16. Synthesis of arbitrary pulse waveforms in QCL-seeded ns-pulse CO2 laser for optimization of an LPP EUV source.

    PubMed

    Nowak, Krzysztof M; Kurosawa, Yoshiaki; Suganuma, Takashi; Kawasuji, Yasufumi; Nakarai, Hiroaki; Saito, Takashi; Fujimoto, Junichi; Mizoguchi, Hakaru

    2016-07-01

    One of the unique features of the quantum-cascade-laser-seeded, nanosecond-pulse CO2 laser, invented for the purpose of generation of extreme UV by laser-produced-plasma, is a robust synthesis of arbitrary pulse waveforms. In the present Letter we report on experimental results that are, to our best knowledge, the first demonstration of such functionality obtainable from nanosecond-pulse CO2 laser technology. An online pulse duration adjustment within 10-40 ns was demonstrated, and a few exemplary pulse waveforms were synthesized, such as "tophat," "tailspike," and "leadspike" shapes. Such output characteristics may be useful to optimize the performance of LPP EUV source. PMID:27367116

  17. Synthesis of arbitrary pulse waveforms in QCL-seeded ns-pulse CO2 laser for optimization of an LPP EUV source.

    PubMed

    Nowak, Krzysztof M; Kurosawa, Yoshiaki; Suganuma, Takashi; Kawasuji, Yasufumi; Nakarai, Hiroaki; Saito, Takashi; Fujimoto, Junichi; Mizoguchi, Hakaru

    2016-07-01

    One of the unique features of the quantum-cascade-laser-seeded, nanosecond-pulse CO2 laser, invented for the purpose of generation of extreme UV by laser-produced-plasma, is a robust synthesis of arbitrary pulse waveforms. In the present Letter we report on experimental results that are, to our best knowledge, the first demonstration of such functionality obtainable from nanosecond-pulse CO2 laser technology. An online pulse duration adjustment within 10-40 ns was demonstrated, and a few exemplary pulse waveforms were synthesized, such as "tophat," "tailspike," and "leadspike" shapes. Such output characteristics may be useful to optimize the performance of LPP EUV source.

  18. Pulsed Yb:fiber system capable of >250kW peak power with tunable pulses in the 50ps to 1.5ns range

    NASA Astrophysics Data System (ADS)

    McComb, Timothy S.; Lowder, Tyson L.; Leadbetter, Vickie; Reynolds, Mitch; Saracco, Matthieu J.; Hutchinson, Joel; Green, Jared; McCal, Dennis; Burkholder, Gary; Kutscha, Tim; Dittli, Adam; Hamilton, Chuck; Kliner, Dahv A. V.; Randall, Matthew; Fanning, Geoff; Bell, Jake

    2013-03-01

    We have demonstrated a pulsed 1064 nm PM Yb:fiber laser system incorporating a seed source with a tunable pulse repetition rate and pulse duration and a multistage fiber amplifier, ending in a large core (>650 μm2 mode field area), tapered fiber amplifier. The amplifier chain is all-fiber, with the exception of the final amplifier's pump combiner, allowing robust, compact packaging. The air-cooled laser system is rated for >60 W of average power and beam quality of M2 < 1.3 at repetition rates below 100 kHz to 10's of MHz, with pulses discretely tunable over a range spanning 50 ps to greater than 1.5 ns. Maximum pulse energies, limited by the onset of self phase modulation and stimulated Raman scattering, are greater than 12.5 μJ at 50 ps and 375 μJ at 1.5 ns , corresponding to >250 kW peak power across the pulse tuning range. We present frequency conversion to 532 nm with efficiency greater than 70% and conversion to UV via frequency tripling, with initial feasibility experiments showing >30% UV conversion efficiency. Application results of the laser in scribing, thin film removal and micro-machining will be discussed.

  19. Histopathological follow-up by tissue micro-array in a survival study after melanoma treated by nanosecond pulsed electric fields (nsPEF).

    PubMed

    Chen, Xinhua; Chen, Xinmei; Swanson, R James; Schoenbach, Karl H; Yin, Shengyong; Zheng, Shusen

    2011-06-01

    A recent study has shown that nanosecond pulsed electric fields (nsPEF) can affect the intracellular structures of melanoma within weeks. nsPEF is a non-drug, non-thermal treatment using ultrashort, intense pulsed electric fields with nanosecond durations. In the current study we followed up melanoma histopathology and metastasis with tissue micro-array 5 months post-nsPEF. After nsPEF treatment, tumor growth, tumor histology, metastasis, peri-tumor vessel and micro-vessel density were examined for the effect of nsPEF treatment on melanoma in vivo. The 17 nsPEF-treated mice were tumor-free for 169 days, significantly longer than those 19 control mice bearing melanoma without nsPEF. Histopathology follow-up showed that melanoma did not recur to the primary injection place after complete elimination. Compared with the control tumor, nsPEF-treated tumors present decreased micro-vessel density in a time-course manner in this survival study. Treatment with nsPEF caused continuous histopathological changes in melanomas, eliminated melanoma without recurrence at the primary site and prolonged animal survival time by inhibiting tumor blood supply and leading to tumor infarction. Thus, nsPEF could be applied in a non-ionizing therapeutic approach, without other agents, to locally treat tumors within a defined boundary.

  20. 600 ns pulse electric field-induced phosphatidylinositol4,5-bisphosphate depletion.

    PubMed

    Tolstykh, Gleb P; Beier, Hope T; Roth, Caleb C; Thompson, Gary L; Ibey, Bennett L

    2014-12-01

    The interaction between nsPEF-induced Ca(2+) release and nsPEF-induced phosphatidylinositol4,5-bisphosphate (PIP2) hydrolysis is not well understood. To better understand this interrelation we monitored intracellular calcium changes, in cells loaded with Calcium Green-1 AM, and generation of PIP2 hydrolysis byproducts (inositol-1,4,5-trisphosphate (IP3) and diacylglycerol (DAG)) in cells transfected with one of two fluorescent reporter genes: PLCδ-PH-EGFP or GFP-C1-PKCγ-C1a. The percentage fluorescence differences (ΔF %) after exposures were determined. Upon nsPEF impact, we found that in the absence of extracellular Ca(2+) the population of IP3 liberated during nsPEF exposure (ΔF 6%±3, n=22), is diminished compared to the response in the presence of calcium (ΔF 84%±15, n=20). The production of DAG in the absence of extracellular Ca(2+) (ΔF 29%±5, n=25), as well as in cells exposed to thapsigargin (ΔF 40%±12, n=15), was not statistically different from cells exposed in the presence of extracellular calcium (ΔF 22±6%, n=18). This finding suggests that the change in intracellular calcium concentration is not solely driving the observed response. Interestingly, the DAG produced in the absence of Ca(2+) is the strongest near the membrane regions facing the electrodes, whereas the presence of extracellular Ca(2+) leads to a whole cell response. The reported observations of Ca(2+) dynamics combined with IP3 and DAG production suggest that nsPEF may cause a direct effect on the phospholipids within the plasma membrane.

  1. Nanosecond pulsed electric fields (nsPEFs) low cost generator design using power MOSFET and Cockcroft-Walton multiplier circuit as high voltage DC source

    NASA Astrophysics Data System (ADS)

    Sulaeman, M. Y.; Widita, R.

    2014-09-01

    Purpose: Non-ionizing radiation therapy for cancer using pulsed electric field with high intensity field has become an interesting field new research topic. A new method using nanosecond pulsed electric fields (nsPEFs) offers a novel means to treat cancer. Not like the conventional electroporation, nsPEFs able to create nanopores in all membranes of the cell, including membrane in cell organelles, like mitochondria and nucleus. NsPEFs will promote cell death in several cell types, including cancer cell by apoptosis mechanism. NsPEFs will use pulse with intensity of electric field higher than conventional electroporation, between 20-100 kV/cm and with shorter duration of pulse than conventional electroporation. NsPEFs requires a generator to produce high voltage pulse and to achieve high intensity electric field with proper pulse width. However, manufacturing cost for creating generator that generates a high voltage with short duration for nsPEFs purposes is highly expensive. Hence, the aim of this research is to obtain the low cost generator design that is able to produce a high voltage pulse with nanosecond width and will be used for nsPEFs purposes. Method: Cockcroft-Walton multiplier circuit will boost the input of 220 volt AC into high voltage DC around 1500 volt and it will be combined by a series of power MOSFET as a fast switch to obtain a high voltage with nanosecond pulse width. The motivation using Cockcroft-Walton multiplier is to acquire a low-cost high voltage DC generator; it will use capacitors and diodes arranged like a step. Power MOSFET connected in series is used as voltage divider to share the high voltage in order not to damage them. Results: This design is expected to acquire a low-cost generator that can achieve the high voltage pulse in amount of -1.5 kV with falltime 3 ns and risetime 15 ns into a 50Ω load that will be used for nsPEFs purposes. Further detailed on the circuit design will be explained at presentation.

  2. Nanosecond pulsed electric fields (nsPEFs) low cost generator design using power MOSFET and Cockcroft-Walton multiplier circuit as high voltage DC source

    SciTech Connect

    Sulaeman, M. Y.; Widita, R.

    2014-09-30

    Purpose: Non-ionizing radiation therapy for cancer using pulsed electric field with high intensity field has become an interesting field new research topic. A new method using nanosecond pulsed electric fields (nsPEFs) offers a novel means to treat cancer. Not like the conventional electroporation, nsPEFs able to create nanopores in all membranes of the cell, including membrane in cell organelles, like mitochondria and nucleus. NsPEFs will promote cell death in several cell types, including cancer cell by apoptosis mechanism. NsPEFs will use pulse with intensity of electric field higher than conventional electroporation, between 20–100 kV/cm and with shorter duration of pulse than conventional electroporation. NsPEFs requires a generator to produce high voltage pulse and to achieve high intensity electric field with proper pulse width. However, manufacturing cost for creating generator that generates a high voltage with short duration for nsPEFs purposes is highly expensive. Hence, the aim of this research is to obtain the low cost generator design that is able to produce a high voltage pulse with nanosecond width and will be used for nsPEFs purposes. Method: Cockcroft-Walton multiplier circuit will boost the input of 220 volt AC into high voltage DC around 1500 volt and it will be combined by a series of power MOSFET as a fast switch to obtain a high voltage with nanosecond pulse width. The motivation using Cockcroft-Walton multiplier is to acquire a low-cost high voltage DC generator; it will use capacitors and diodes arranged like a step. Power MOSFET connected in series is used as voltage divider to share the high voltage in order not to damage them. Results: This design is expected to acquire a low-cost generator that can achieve the high voltage pulse in amount of −1.5 kV with falltime 3 ns and risetime 15 ns into a 50Ω load that will be used for nsPEFs purposes. Further detailed on the circuit design will be explained at presentation.

  3. ns or fs pulsed laser ablation of a bulk InSb target in liquids for nanoparticles synthesis.

    PubMed

    Semaltianos, N G; Hendry, E; Chang, H; Wears, M L; Monteil, G; Assoul, M; Malkhasyan, V; Blondeau-Patissier, V; Gauthier-Manuel, B; Moutarlier, V

    2016-05-01

    Laser ablation of bulk target materials in liquids has been established as an alternative method for the synthesis of nanoparticles colloidal solutions mainly due to the fact that the synthesized nanoparticles have bare, ligand-free surfaces since no chemical precursors are used for their synthesis. InSb is a narrow band gap semiconductor which has the highest carrier mobility of any known semiconductor and nanoparticles of this material are useful in optoelectronic device fabrication. In this paper a bulk InSb target was ablated in deionized (DI) water or ethanol using a nanosecond (20 ns) or a femtosecond (90 fs) pulsed laser source, for nanoparticles synthesis. In all four cases the largest percentage of the nanoparticles are of InSb in the zincblende crystal structure with fcc lattice. Oxides of either In or Sb are also formed in the nanoparticles ensembles in the case of ns or fs ablation, respectively. Formation of an oxide of either element from the two elements of the binary bulk alloy is explained based on the difference in the ablation mechanism of the material in the case of ns or fs pulsed laser irradiation in which the slow or fast deposition of energy into the material results to mainly melting or vaporization, respectively under the present conditions of ablation, in combination with the lower melting point but higher vaporization enthalpy of In as compared to Sb. InSb in the metastable phase with orthorhombic lattice is also formed in the nanoparticles ensembles in the case of fs ablation in DI water (as well as oxide of InSb) which indicates that the synthesized nanoparticles exhibit polymorphism controlled by the type of the laser source used for their synthesis. The nanoparticles exhibit absorption which is observed to be extended in the infrared region of the spectrum.

  4. Comparison of soft and hard tissue ablation with sub-ps and ns pulse lasers

    SciTech Connect

    Da Silva, L.B.; Stuart, B.C.; Celliers, P.M.; Feit, M.D.; Glinsky, M.E.; Heredia, N.J.; Herman, S.; Lane, S.M.; London, R.A.; Matthews, D.L.; Perry, M.D.; Rubenchik, A.M.; Chang, T.D.; Neev, J.

    1996-05-01

    Tissue ablation with ultrashort laser pulses offers several unique advantages. The nonlinear energy deposition is insensitive to tissue type, allowing this tool to be used for soft and hard tissue ablation. The localized energy deposition lead to precise ablation depth and minimal collateral damage. This paper reports on efforts to study and demonstrate tissue ablation using an ultrashort pulse laser. Ablation efficiency and extent of collateral damage for 0.3 ps and 1000 ps duration laser pulses are compared. Temperature measurements of the rear surface of a tooth section is also presented.

  5. High-power ns-pulse fiber laser sources for remote sensors

    NASA Astrophysics Data System (ADS)

    Di Teodoro, Fabio; Belden, Paul; Ionov, Pavel; Werner, Nicolette

    2014-12-01

    The development of fiber-based laser sources for space-borne remote sensors must meet many concurrent requirements including high pulse energy/peak power, excellent beam quality, narrow spectral linewidth, simple thermal management, small volume and mass, low power consumption, rugged packaging, and long-term reliability. To address these requirements, many aspects of pulse fiber laser technology must be advanced beyond the state of the art of traditional optical sources used in telecommunications and materials processing. In this article, we discuss component and solutions that enable pulsed fiber laser sources to support remote sensing from space. We also describe several examples of such sources and characterize their performance.

  6. Cellular regulation of extension and retraction of pseudopod-like blebs produced by nanosecond pulsed electric field (nsPEF).

    PubMed

    Rassokhin, Mikhail A; Pakhomov, Andrei G

    2014-07-01

    Recently we described a new phenomenon of anodotropic pseudopod-like blebbing in U937 cells exposed to nanosecond pulsed electric field (nsPEF). In Ca(2+)-free buffer such exposure initiates formation of pseudopod-like blebs (PLBs), protrusive cylindrical cell extensions that are distinct from apoptotic and necrotic blebs. PLBs nucleate predominantly on anode-facing cell pole and extend toward anode during nsPEF exposure. Bleb extension depends on actin polymerization and availability of actin monomers. Inhibition of intracellular Ca(2+), cell contractility, and RhoA produced no effect on PLB initiation. Meanwhile, inhibition of WASP by wiskostatin causes dose-dependent suppression of PLB growth. Soon after the end of nsPEF exposure PLBs lose directionality of growth and then retract. Microtubule toxins nocodazole and paclitaxel did not show immediate effect on PLBs; however, nocodazole increased mobility of intracellular components during PLB extension and retraction. Retraction of PLBs is produced by myosin activation and the corresponding increase in PLB cortex contractility. Inhibition of myosin by blebbistatin reduces retraction while inhibition of RhoA-ROCK pathway by Y-27632 completely prevents retraction. Contraction of PLBs can produce cell translocation resembling active cell movement. Overall, the formation, properties, and life cycle of PLBs share common features with protrusions associated with ameboid cell migration. PLB life cycle may be controlled through activation of WASP by its upstream effectors such as Cdc42 and PIP2, and main ROCK activator-RhoA. Parallels between pseudopod-like blebbing and motility blebbing may provide new insights into their underlying mechanisms.

  7. Dynamics of noise-like pulsing at sub-ns scale in a passively mode-locked fiber laser.

    PubMed

    Santiago-Hernandez, H; Pottiez, O; Duran-Sanchez, M; Alvarez-Tamayo, R I; Lauterio-Cruz, J P; Hernandez-Garcia, J C; Ibarra-Escamilla, B; Kuzin, E A

    2015-07-27

    We report an original noise-like pulse dynamics observed in a figure-eight fiber laser, in which fragments are continually released from a main waveform that circulates in the cavity. Particularly, we report two representative cases of the dynamics: in the first case the released fragments drift away from the main bunch and decay over a fraction of the round-trip time, and then vanish suddenly; in the second case, the sub-packets drift without decaying over the complete cavity round-trip time, until they eventually merge again with the main waveform. The most intriguing result is that these fragments, as well as the main waveform, are formed of units with sub-ns duration and roughly the same energy. PMID:26367548

  8. Generation of 1.6 ns Q-switched pulses based on Yb:YAG/Cr:YAG microchip laser

    NASA Astrophysics Data System (ADS)

    Šulc, Jan; Jelínková, Helena; Nejezchleb, Karel; Škoda, Václav

    2015-05-01

    The highly-stable Q-switched longitudinally diode-pumped microchip laser, emitting radiation at wavelength 1031 nm, was designed and realized. This laser was based on monolith crystal which combines in one piece an active laser part (YAG crystal doped with Yb3+ ions, 10 at.% Yb/Y, 3mm long) and saturable absorber (YAG crystal doped with Cr3+ ions, 1.36mm long). The diameter of the diffusion bonded monolith was 3 mm. The initial transmission of the Cr:YAG part was 90% @ 1031 nm. The microchip resonator consisted of dielectric mirrors directly deposited on the monolith surfaces. The pump mirror (HT for pump radiation, HR for generated radiation) was placed on the Yb:YAG part. The output coupler with reflection 55% for the generated wavelength was placed on the Cr3+-doped part. Q-switched microchip laser was tested under CW diode pumping. For longitudinal pumping of Yb:YAG part, a fibre coupled (core diameter 100 μm, NA= 0.22) laser diode, operating at wavelength 968 nm, was used. The laser threshold was 3.3W. The laser slope efficiency calculated for output mean power in respect to incident CW pumping was 17%. The wavelength of linearly polarized laser emission was fixed to 1031 nm. The generated transversal intensity beam profile was close to the fundamental Gaussian mode. The generated pulse length was equal to 1.6 ns (FWHM). This value was mostly stable and independent on investigated pumping powers in the range from the threshold up to 9.3W. The single pulse energy was linearly increasing with the pumping power. Close to the laser threshold the generated pulse energy was 45 μJ. For maximum investigated CW pumping 9.3W the pulse energy was stabilized to 74 μJ which corresponds to the Q-switched pulse peak power 46 kW. The corresponding Q-switched pulses repetition rate was 13.6 kHz. The maximum Yb:YAG/Cr:YAG microchip laser mean output power of 1W was reached without observable thermal roll-over.

  9. Application of sub-ns pulsed LEDs in fluorescence lifetime spectroscopy

    NASA Astrophysics Data System (ADS)

    Wahl, Michael; Ortmann, Uwe; Lauritsen, Kristian; Erdmann, Rainer

    2002-04-01

    Lifetime analysis of laser induced fluorescence by means of Time-Correlated Single Photon Counting (TCSPC) provides a powerful discrimination method to distinguish molecules of interest from background and other species. This has made the technique extremely valuable for sensitive analysis down to the single molecule level. We have developed the first complete range of compact picosecond to nanosecond excitation sources for fluorescence lifetime measurements based on laser diodes and LEDs. Using a common driver with interchangeable LED and laser heads the system is adaptable to almost all of the needs for sensitive chemical and biochemical analysis. The sources provide pulse durations under one nanosecond and repetition rates up to 80 MHz. These features qualify them for use in fast TCSPC applications, in particular where short data acquisition time is crucial. The sources can be used in combination with common inexpensive single photon detectors such as Photomultiplier Tubes and Single Photon Avalanche Photodiodes. Compact, low cost and easy to use fluorescence lifetime spectrometers can be built from these sources together with integrated TCSPC electronics. We will demonstrate the performance of the sources and complete systems in terms of power, repetition rate, stability, IRF and fluorescence decay fit quality in various setups and with different fluorescent materials.

  10. High peak- and average-power pulse shaped fiber laser in the ns-regime applying step-index XLMA gain fibers

    NASA Astrophysics Data System (ADS)

    Dinger, R.; Grundmann, F.-P.; Hapke, C.; Ruppik, S.

    2014-03-01

    Pulsed fiber lasers and continuous-wave (cw) fiber lasers have become the tool of choice in more and more laser based industrial applications like metal cutting and welding mainly because of their robustness, compactness, high brightness, high efficiency and reasonable costs. However, to further increase the productivity with those laser types there is a great demand for even higher laser power specifications. In this context we demonstrate a pulsed high peak- and averagepower fiber laser in a Master Oscillator Power Amplifier (MOPA) configuration with selectable pulse durations between 1 ns and several hundred nanoseconds. To overcome fiber nonlinearities such as stimulated Raman scattering (SRS) and self-phase-modulation (SPM) flexible Ytterbium doped extra-large mode area (XLMA) step index fibers, prepared by novel powder-sinter technology, have been used as gain fibers. As an example, for 12 ns pulses with a repetition rate of 10 kHz, a pump power limited average laser output power of more than 400 W in combination with peak powers of more than 3.5 MW (close to self-focusing-threshold) has been achieved in stable operation. The potentials of this laser system have been further explored towards longer pulse durations in order to achieve even higher pulse energies by means of pulse shaping techniques. In addition, investigations have been conducted with reduced pulse energies and repetition rates up to 500 kHz and average powers of more than 500 W at nearly diffraction limited beam quality.

  11. Analysis of output surface damage resulting from single 351 nm, 3 ns pulses on sub-nanosecond laser conditioned KD2PO4 crystals

    SciTech Connect

    Jarboe, J; Adams, J J; Hackel, R

    2007-10-31

    We observe that by conditioning DKDP using 500 ps laser pulses, the bulk damage threshold becomes essentially equivalent to the surface damage threshold. We report here the findings of our study of laser initiated output surface damage on 500 ps laser conditioned DKDP for test pulses at 351 nm, 3 ns. The relation between surface damage density and damaging fluence (r(f)) is presented for the first time and the morphologies of the surface sites are discussed. The results of this study suggest a surface conditioning effect resulting from exposure to 500 ps laser pulses.

  12. Effect of surrounding gas condition on surface integrity in micro-drilling of SiC by ns pulsed laser

    NASA Astrophysics Data System (ADS)

    Okamoto, Yasuhiro; Asako, Kiichi; Nishi, Norio; Sakagawa, Tomokazu; Okada, Akira

    2015-06-01

    The influence of the surrounding gas conditions on the surface integrity in the micro-drilling of silicon carbide was experimentally investigated using ns pulsed laser of 266 nm wavelength. Moreover, micro-machining characteristics were observed using high-speed shutter and video cameras in the micro-drilling of silicon carbide. The size and intensity of the laser-induced plasma were larger, and the plasma affected area was larger and deeper in argon than that in air. Although the intensity of the plasma was lower in helium than that in other gases, the surface around the drilled hole was roughened by the spread of the plasma in the vicinity of the drilled hole. Debris was removed along the flow field generated by laser shot in the opposite direction to the laser irradiation. The gas flow behavior and the spectrum and intensity of the laser-induced plasma were influenced by the surrounding gas type and pressure. The appearance of plasma generation affected the surface integrity at the circumference of the drilled hole, and the surface integrity was improved by reducing the pressure.

  13. X-ray contact microscopy using a plasma source generated by long and short (120ns and 10ns) excimer laser pulses

    SciTech Connect

    Cotton, R.; Bollanti, S.; Di Lazzaro, P.

    1995-12-31

    Soft X-ray contact microscopy (SXCM), using a pulsed X-ray source, offers the possibility of imaging the ultrastructure of living biological systems at sub-50nm resolution. The authors have developed a pulsed plasma X-ray source for this application, generated by the large volume XeCl laser Hercules. Various unstable optical resonator configurations were employed to achieve a high laser intensity to increase the conversion efficiency to water window X-rays (280--530 eV). Optimum plasma conditions for SXCM are discussed, including the effect of pulse duration on image resolution. Soft X-ray contact images of Chlamydomonas dysosmos (unicellular alga) and the cyanobacteria Leptolyngbya are shown. In addition, the potential of producing a movie film of the development of X-ray images within the photoresist (acting as the recording medium) is discussed, following the resist development while viewing by atomic force microscopy.

  14. A 4 MA, 500 ns pulsed power generator CQ-4 for characterization of material behaviors under ramp wave loading

    NASA Astrophysics Data System (ADS)

    Wang, Guiji; Luo, Binqiang; Zhang, Xuping; Zhao, Jianheng; Sun, Chengwei; Tan, Fuli; Chong, Tao; Mo, Jianjun; Wu, Gang; Tao, Yanhui

    2013-01-01

    A pulsed power generator CQ-4 was developed to characterize dynamic behaviors of materials under ramp wave loading, and to launch high velocity flyer plates for shock compression and hypervelocity impact experiments of materials and structures at Institute of Fluid Physics, China Academy of Engineering Physics. CQ-4 is composed of twenty capacitor and primary discharge switch modules with total capacitance of 32μF and rated charging voltage of 100 kV, and the storage energy is transmitted by two top and bottom parallel aluminum plates insulated by twelve layers of polyester film with total thickness of 1.2 mm. Between capacitor bank and chamber, there are 72 peaking capacitors with total capacitance of 7.2 μF and rated voltage of 120 kV in parallel, which are connected with the capacitor bank in parallel. Before the load, there is a group of seven secondary self-breaking down switches connected with the total circuit in series. The peaking capacitors and secondary switches are used to shape the discharging current waveforms. For short-circuit, the peak current of discharging can be up to 3 ˜ 4 MA and rise time varies from 470 ns to 600 ns when the charging voltages of the generator are from 75 kV to 85 kV. With CQ-4 generator, some quasi-isentropic compression experiments under ramp wave loadings are done to demonstrate the ability of CQ-4 generator. And some experiments of launching high velocity flyer plates are also done on CQ-4. The experimental results show that ramp wave loading pressure of several tens of GPa on copper and aluminum samples can be realized and the velocity of aluminum flyer plate with size of 10 mm × 6 mm × 0.35 mm can be accelerated to about 11 km/s and the velocity of aluminum flyer plate with size of 10 mm × 6 mm × 0.6 mm can be up to about 9 km/s, which show that CQ-4 is a good and versatile tool to realize ramp wave loading and shock compression for shock physics.

  15. A 4 MA, 500 ns pulsed power generator CQ-4 for characterization of material behaviors under ramp wave loading.

    PubMed

    Wang, Guiji; Luo, Binqiang; Zhang, Xuping; Zhao, Jianheng; Sun, Chengwei; Tan, Fuli; Chong, Tao; Mo, Jianjun; Wu, Gang; Tao, Yanhui

    2013-01-01

    A pulsed power generator CQ-4 was developed to characterize dynamic behaviors of materials under ramp wave loading, and to launch high velocity flyer plates for shock compression and hypervelocity impact experiments of materials and structures at Institute of Fluid Physics, China Academy of Engineering Physics. CQ-4 is composed of twenty capacitor and primary discharge switch modules with total capacitance of 32 μF and rated charging voltage of 100 kV, and the storage energy is transmitted by two top and bottom parallel aluminum plates insulated by twelve layers of polyester film with total thickness of 1.2 mm. Between capacitor bank and chamber, there are 72 peaking capacitors with total capacitance of 7.2 μF and rated voltage of 120 kV in parallel, which are connected with the capacitor bank in parallel. Before the load, there is a group of seven secondary self-breaking down switches connected with the total circuit in series. The peaking capacitors and secondary switches are used to shape the discharging current waveforms. For short-circuit, the peak current of discharging can be up to 3 ~ 4 MA and rise time varies from 470 ns to 600 ns when the charging voltages of the generator are from 75 kV to 85 kV. With CQ-4 generator, some quasi-isentropic compression experiments under ramp wave loadings are done to demonstrate the ability of CQ-4 generator. And some experiments of launching high velocity flyer plates are also done on CQ-4. The experimental results show that ramp wave loading pressure of several tens of GPa on copper and aluminum samples can be realized and the velocity of aluminum flyer plate with size of 10 mm × 6 mm × 0.35 mm can be accelerated to about 11 km/s and the velocity of aluminum flyer plate with size of 10 mm × 6 mm × 0.6 mm can be up to about 9 km/s, which show that CQ-4 is a good and versatile tool to realize ramp wave loading and shock compression for shock physics. PMID:23387705

  16. A 4 MA, 500 ns pulsed power generator CQ-4 for characterization of material behaviors under ramp wave loading.

    PubMed

    Wang, Guiji; Luo, Binqiang; Zhang, Xuping; Zhao, Jianheng; Sun, Chengwei; Tan, Fuli; Chong, Tao; Mo, Jianjun; Wu, Gang; Tao, Yanhui

    2013-01-01

    A pulsed power generator CQ-4 was developed to characterize dynamic behaviors of materials under ramp wave loading, and to launch high velocity flyer plates for shock compression and hypervelocity impact experiments of materials and structures at Institute of Fluid Physics, China Academy of Engineering Physics. CQ-4 is composed of twenty capacitor and primary discharge switch modules with total capacitance of 32 μF and rated charging voltage of 100 kV, and the storage energy is transmitted by two top and bottom parallel aluminum plates insulated by twelve layers of polyester film with total thickness of 1.2 mm. Between capacitor bank and chamber, there are 72 peaking capacitors with total capacitance of 7.2 μF and rated voltage of 120 kV in parallel, which are connected with the capacitor bank in parallel. Before the load, there is a group of seven secondary self-breaking down switches connected with the total circuit in series. The peaking capacitors and secondary switches are used to shape the discharging current waveforms. For short-circuit, the peak current of discharging can be up to 3 ~ 4 MA and rise time varies from 470 ns to 600 ns when the charging voltages of the generator are from 75 kV to 85 kV. With CQ-4 generator, some quasi-isentropic compression experiments under ramp wave loadings are done to demonstrate the ability of CQ-4 generator. And some experiments of launching high velocity flyer plates are also done on CQ-4. The experimental results show that ramp wave loading pressure of several tens of GPa on copper and aluminum samples can be realized and the velocity of aluminum flyer plate with size of 10 mm × 6 mm × 0.35 mm can be accelerated to about 11 km/s and the velocity of aluminum flyer plate with size of 10 mm × 6 mm × 0.6 mm can be up to about 9 km/s, which show that CQ-4 is a good and versatile tool to realize ramp wave loading and shock compression for shock physics.

  17. Er-doped high-aspect-ratio core rectangular fiber producing 5 mJ, 13 ns pulses at 1572 nm.

    PubMed

    Khitrov, Victor; Shkunov, Vladimir V; Rockwell, David A; Zakharenkov, Yuri A; Strohkendl, Friedrich

    2012-10-01

    We have produced 5 mJ, 13 ns pulses using a very large-mode-area rectangular fiber containing a high-aspect-ratio core with dimensions of ~30 μm×580 μm. The rectangular fiber design retains a thin cladding dimension ~0.5 mm, which is compatible with a compact coiled package. We have developed a theoretical model that achieves good agreement with the experimental data. This model indicates that an optimized fiber design can be scaled to pulse energies of several tens of millijoules. We also discuss a strategy for maintaining good beam quality in both transverse dimensions of this fiber. PMID:23027246

  18. Analysis of the photosystem II by modelling the fluorescence yield transients during 10 seconds after a 10 ns pulse

    NASA Astrophysics Data System (ADS)

    Belyaeva, Natalya E.; Schmitt, Franz-Josef; Paschenko, Vladimir Z.; Riznichenko, Galina Yu.; Rubin, Andrew B.

    2014-10-01

    The dynamics of the photosystem II (PS II) redox states is imitated over nine orders of magnitude in time. Our simulations focus on the information of the chlorophyll a fluorescence induced by a 10 ns laser flash. The PS II model analyzes differences in the PS II reaction between leaves (A. Thaliana, spinach) and thermophilic Chlorella cells.

  19. Macrospin modeling of sub-ns pulse switching of perpendicularly magnetized free layer via spin-orbit torques for cryogenic memory applications

    SciTech Connect

    Park, Junbo; Rowlands, G. E.; Lee, O. J.; Buhrman, R. A.; Ralph, D. C.

    2014-09-08

    We model, using the macrospin approximation, the magnetic reversal of a perpendicularly magnetized nanostructured free layer formed on a normal, heavy-metal nanostrip, subjected to spin-orbit torques (SOTs) generated by short (≤0.5 ns) current pulses applied to the nanostrip, to examine the potential for SOT-based fast, efficient cryogenic memory. Due to thermal fluctuations, if solely an anti-damping torque is applied, then, for a device with sufficiently low anisotropy (H{sub anis}{sup 0} ∼ 1 kOe) suitable for application in cryogenic memory, a high magnetic damping parameter (α∼0.1−0.2) is required for reliable switching over a significant variation of pulse current. The additional presence of a substantial field-like torque improves switching reliability even for low damping (α≤0.03).

  20. Study of the integrated fluence threshold condition for the formation of β-Bi2O3 on Bi thin films by using ns laser pulses

    NASA Astrophysics Data System (ADS)

    Venegas-Castro, A.; Reyes-Contreras, A.; Camacho-López, M.; Olea-Mejía, O.; Camacho-López, S.; Esparza-García, A.

    2016-07-01

    The formation of β-Bi2O3 through laser irradiation of a bismuth (Bi) thin film is reported. The bismuth thin films were irradiated in atmospheric air using Nd:YAG laser pulses of 7 ns duration and 1064 nm wavelength. A set of irradiations was done on the samples varying the total irradiation time (i. e. the number of pulses) for a fix per pulse laser fluence of 25 mJ/cm2. The laser processed regions were characterized by optical microscopy (OM), scanning electron microscopy (SEM) and microRaman spectroscopy (mRS). OM results show that the laser modified cross section on the film is smaller than the laser beam cross section, which means a thermally confined interaction; SEM micrographs reveled the formation of submicron sized particles as a result of the multi-pulse laser irradiation; using microRaman spectroscopy characterization we were able to determine the formation of the β-Bi2O3 crystalline phase within the laser irradiated spot on the sample.

  1. Single-pulse laser ablation threshold of borosilicate, fused silica, sapphire, and soda-lime glass for pulse widths of 500  fs, 10  ps, 20  ns.

    PubMed

    Nieto, Daniel; Arines, Justo; O'Connor, Gerard M; Flores-Arias, María Teresa

    2015-10-10

    In this work, we report a comparative study of the laser ablation threshold of borosilicate, fused silica, sapphire, and soda-lime glass as a function of the pulse width and for IR laser wavelengths. We determine the ablation threshold for three different pulse durations: τ=500  fs, 10 ps, and 20 ns. Experiments have been performed using a single laser pulse per shot in an ambient (air) environment. The results show a significant difference, of two orders of magnitude, between the group of ablation thresholds obtained for femtosecond, picosecond, and nanosecond pulses. This difference is reduced to 1 order of magnitude in the soda-lime substrate with tin impurities, pointing out the importance of the incubation effect. The morphology of the marks generated over the different glass materials by one single pulse of different pulse durations has been analyzed using a scanning electron microscope (FESEM ULTRA Plus). Our results are important for practical purposes, providing the ablation threshold data of four commonly used substrates at three different pulse durations in the infrared regime (1030-1064 nm) and complete data for increasing the understanding of the differences in the mechanism's leading ablation in the nanosecond, picosecond, and femtosecond regimes.

  2. CQ-4: a 4 MA, 500ns Compact Pulsed Power Generator Dedicated to Magnetically Driven Quasi-isentropic Compression Experiments (ICE) and Hypervelocity Flyer Plates

    NASA Astrophysics Data System (ADS)

    Wang, Guiji; Zhao, Jianheng; Sun, Chengwei; Kuai, Bin; Mo, Jianjun; Wu, Gang

    2011-06-01

    Compact pulsed power generators have been widely used to produce high magnetic pressure to study dynamic behaviors of materials and do some hypervelocity impact experiments. After the compact pulsed power generator CQ-1.5 developed by us, a larger current and shorter rise time compact pulsed power generator CQ-4 has been designed and being constructed. The generator CQ-4 is composed of 20 energy-storage modules in parallel, of which is constituted by a 1.6 μF, 100 kV capacitor and a coaxial field-distortion spark gas switch with inductance of 25 nH. The energy is transmitted by the aluminum strip transmission lines insulated by 16 layers of Mylar films, of which is 0.1 mm in thickness. Before the short-circuit load, 72 peaking capacitors in parallel with the energy-storage capacitors are used to shape the discharging current waveforms in load. Each peaking capacitor is with rated capacitance of 0.1 μF and rated voltage of 120 kV. When the capacitor is charged to 70-80 kV, the peak current can reach 4-5MA, and the rise time is 400-500 ns (0-100%). The expected magnetic pressure can be up to 100GPa on the metallic loads and a hypervelocity of 12-15 km/s can be reached for the aluminum flyer plates with size of 10 mm in diameter and 1.0 mm in thickness.

  3. Generation of 25-ns pulses with a peak power of over 10 kW from a gain-switched, 2-mm Tm-doped fibre laser and amplifier system

    SciTech Connect

    Swiderski, J; Michalska, M; Pichola, W; Mamajek, M

    2014-04-28

    We report on an all-fibre, gain-switched, Tm{sup 3+}-doped silica fibre laser and amplifier system generating a train of pulses at a wavelength of 1994.4 nm. When operating at a pulse repetition frequency f=''100'' kHz, it delivered the maximum average power as high as 9.03 W with a slope efficiency of 36.4%. At f = 26 kHz, stable 25-ns pulses with an energy of 0.28 mJ corresponding to a peak power of 10.5 kW were obtained. The performance of the laser system is described. (lasers)

  4. Impact of 532 nm 6 ns laser pulses on (104) oriented zinc single crystal: surface morphology, phase transformation, and structure hardness relationship

    NASA Astrophysics Data System (ADS)

    Zakria Butt, Muhammad; Waqas Khaliq, Muhammad; Mannan Majeed, Abdul; Ali, Dilawar

    2016-09-01

    Specimens of (104) oriented Zn single crystal were irradiated in vacuum ˜10-3 Torr with pulsed Nd:YAG laser (λ = 532 nm, E = 50 mJ, τ = 6 ns) at a repetition rate 10 Hz. The number of laser shots was varied from 1 to 100. The laser fluence and laser intensity at the one laser shot irradiation spot on the target surface were 97.2 J cm-2 and 1.6 × 1010 W cm-2, respectively. Crater geometry of laser-irradiated specimens was examined by optical microscope. Crater area was found to increase with the increase in number of laser shots. The data points were encompassed by sigmoidal (Boltzmann) fit showing that crater area increases rapidly to begin with up to 50 laser shots and later on rather slowly till 100 laser shots. Surface morphology was examined by SEM and AFM, which revealed ripple patterns, cavities, trenches, ridges, nanohillocks, microcones, droplets, and solid flakes etc. Structural parameters, namely crystallite size and lattice strain were evaluated by Williamson-Hall analysis of x-ray diffraction patterns. Surface hardness was found to increase up to 50 laser shots and later on it decreased progressively till 100 laser shots. Correlation between surface hardness and crystallite size was also examined, and was found to obey inverse Hall-Petch relation.

  5. 50-kHz, 50-ns UV pulse generation by diode-pumped frequency doubling Pr3+:YLF Q-switch laser with a Cr4+:YAG saturable absorber.

    PubMed

    Tanaka, Hiroki; Kariyama, Ryosuke; Iijima, Kodai; Kannari, Fumihiko

    2016-08-10

    We demonstrate intracavity second-harmonic generation at 320 nm of a diode-pumped praseodymium-doped YLF laser Q-switched by a Cr4+:YAG crystal. By employing two 3.5-W high-power blue InGaN diode lasers as the pump source, we obtained 50-ns Q-switched pulses with a pulse energy of 1.54 μJ at a repetition rate of 50 kHz. A rate equation analysis shows good agreement with the experimental results. PMID:27534459

  6. Generation of spectrally stable continuous-wave emission and ns pulses with a peak power of 4 W using a distributed Bragg reflector laser and a ridge-waveguide power amplifier.

    PubMed

    Klehr, A; Wenzel, H; Fricke, J; Bugge, F; Erbert, G

    2014-10-01

    We have developed a diode-laser based master oscillator power amplifier (MOPA) light source which emits high-power spectrally stabilized and nearly-diffraction limited optical pulses in the nanoseconds range as required by many applications. The MOPA consists of a distributed Bragg reflector (DBR) laser as master oscillator driven by a constant current and a ridge waveguide power amplifier (PA) which can be driven by a constant current (DC) or by rectangular current pulses with a width of 5 ns at a repetition frequency of 200 kHz. Under pulsed operation the amplifier acts as an optical gate, converting the CW input beam emitted by the DBR laser into a train of short amplified optical pulses. With this experimental MOPA arrangement no relaxation oscillations occur. A continuous wave power of 1 W under DC injection and a pulse power of 4 W under pulsed operation are reached. For both operational modes the optical spectrum of the emission of the amplifier exhibits a peak at a constant wavelength of 973.5 nm with a spectral width < 10 pm.

  7. Amplification of 1 ps Pulse Length Beam by Stimulated Raman Scattering of a 1 ns Beam in a Low Density Plasma

    SciTech Connect

    Dewald, E; Kirkwood, R K; Niemann, C; Meezan, N; Wilks, S C; Divol, L; Berger, R L; Landen, O L; Wurtele, J; Charman, A E; Hur, M S; Lindberg, R; Fisch, N; Malkin, V M

    2005-06-12

    The compression of a laser pulse by amplification of an ultra short pulse beam which seeds the stimulated Raman scatter of the first beam has been long been discussed in the context of solid and gas media. We investigate the possibility of using intersecting beams in a plasma to compress nanosecond pulses to picosecond duration by scattering from driven electron waves. Recent theoretical studies have shown the possibility of efficient compression with large amplitude, non-linear Langmuir waves driven either by SRS [1] or non-resonantly [2]. We describe experiments in which a plasma suitable for pulse compression is created, and amplification of an ultra short pulse beam is demonstrated.

  8. Generation of spectrally-stable continuous-wave emission and ns pulses at 800 nm and 975 nm with a peak power of 4 W using a distributed Bragg reflector laser and a ridge-waveguide power amplifier

    NASA Astrophysics Data System (ADS)

    Klehr, A.; Wenzel, H.; Fricke, J.; Bugge, F.; Liero, A.; Hoffmann, Th.; Erbert, G.; Tränkle, G.

    2015-03-01

    Semiconductor based sources which emit high-power spectrally stable nearly diffraction-limited optical pulses in the nanosecond range are ideally suited for a lot of applications, such as free-space communications, metrology, material processing, seed lasers for fiber or solid state lasers, spectroscopy, LIDAR and frequency doubling. Detailed experimental investigations of 975 nm and 800 nm diode lasers based on master oscillator power amplifier (MOPA) light sources are presented. The MOPA systems consist of distributed Bragg reflector lasers (DBR) as master oscillators driven by a constant current and ridge waveguide power amplifiers which can be driven DC and by current pulses. In pulse regime the amplifiers modulated with rectangular current pulses of about 5 ns width and a repetition frequency of 200 kHz act as optical gates, converting the continuous wave (CW) input beam emitted by the DBR lasers into a train of short optical pulses which are amplified. With these experimental MOPA arrangements no relaxation oscillations in the pulse power occur. With a seed power of about 5 mW at a wavelength of 973 nm output powers behind the amplifier of about 1 W under DC injection and 4 W under pulsed operation, corresponding to amplification factors of 200 (amplifier gain 23 dB) and 800 (gain 29 dB) respectively, are reached. At 800 nm a CW power of 1 W is obtained for a seed power of 40 mW. The optical spectra of the emission of the amplifiers exhibit a single peak at a constant wavelength with a line width < 10 pm in the whole investigated current ranges. The ratios between laser and ASE levels were > 50 dB. The output beams are nearly diffraction limited with beam propagation ratios M2lat ~ 1.1 and M2ver ~ 1.2 up to 4 W pulse power.

  9. Study of x-rays produced from debris-free sources with Ar, Kr and Kr/Ar mixture linear gas jets irradiated by UNR Leopard laser beam with fs and ns pulse duration

    NASA Astrophysics Data System (ADS)

    Kantsyrev, V. L.; Schultz, K. A.; Shlyaptseva, V. V.; Safronova, A. S.; Shrestha, I. K.; Petrov, G. M.; Moschella, J. J.; Petkov, E. E.; Stafford, A.; Cooper, M. C.; Weller, M. E.; Cline, W.; Wiewior, P.; Chalyy, O.

    2016-06-01

    Experiments of x-ray emission from Ar, Kr, and Ar/Kr gas jet mixture were performed at the UNR Leopard Laser Facility operated with 350 fs pulses at laser intensity of 2 × 1019 W/cm2 and 0.8 ns pulses at an intensity of 1016 W/cm2. Debris free x-ray source with supersonic linear nozzle generated clusters/monomer jet with an average density of ≥1019 cm-3 was compared to cylindrical tube subsonic nozzle, which produced only monomer jet with average density 1.5-2 times higher. The linear (elongated) cluster/gas jet provides the capability to study x-ray yield anisotropy and laser beam self-focusing with plasma channel formation that are interconnecting with efficient x-ray generation. Diagnostics include x-ray diodes, pinhole cameras and spectrometers. It was observed that the emission in the 1-9 keV spectral region was strongly anisotropic depending on the directions of laser beam polarization for sub-ps laser pulse and supersonic linear jet. The energy yield in the 1-3 keV region produced by a linear nozzle was an order of magnitude higher than from a tube nozzle. Non-LTE models and 3D molecular dynamic simulations of Ar and Kr clusters irradiated by sub-ps laser pulses have been implemented to analyze obtained data. A potential evidence of electron beam generation in jets' plasma was discussed. Note that the described debris-free gas-puff x-ray source can generate x-ray pulses in a high repetition regime. This is a great advantage compared to solid laser targets.

  10. Three-year aging of prototype flight laser at 10 kHz and 1 ns pulses with external frequency doubler for ICESat-2 mission

    NASA Astrophysics Data System (ADS)

    Konoplev, Oleg A.; Chiragh, Furqan L.; Vasilyev, Aleksey A.; Edwards, Ryan; Stephen, Mark A.; Troupaki, Elisavet; Yu, Anthony W.; Krainak, Michael A.; Sawruk, Nick; Hovis, Floyd; Culpepper, Charles F.; Strickler, Kathy

    2016-05-01

    We present the results of a three-year operational-aging test of a specially designed prototype flight laser operating at 1064 nm, 10 kHz, 1ns, 15W average power and externally frequency-doubled. Fibertek designed and built the q-switched, 1064nm laser and this laser was in a sealed container of dry air pressurized to 1.3 atm. The external frequency doubler was in a clean room at a normal air pressure. The goal of the experiment was to measure degradation modes at 1064 and 532 nm separately. The external frequency doubler consisted of a Lithium triborate, LiB3O5, non-critically phase-matched crystal. After some 1064 nm light was diverted for diagnostics, 13.7W of fundamental power was available to pump the doubling crystal. Between 8.5W and 10W of 532nm power was generated, depending on the level of stress and degradation. The test consisted of two stages, the first at 0.3 J/cm2 for almost 1 year, corresponding to expected operational conditions, and the second at 0.93 J/cm2 for the remainder of the experiment, corresponding to accelerated optical stress testing. We observed no degradation at the first stress-level and linear degradation at the second stress-level. The linear degradation was linked to doubler crystal output surface changes from laser-assisted contamination. We estimate the expected lifetime for the flight laser at 532 nm using fluence as the stress parameter. This work was done for NASA's Ice, Cloud, and land Elevation Satellite-2 (ICESat-2) LIDAR at Goddard Space Flight Center in Greenbelt, MD with the goal of 1 trillion shots lifetime.

  11. Three Three-Year Aging of Prototype Flight Laser at 10 kHz and 1 ns Pulses With External Frequency Doubler for ICESat-2 Mission

    NASA Technical Reports Server (NTRS)

    Konoplev, Oleg A.; Chiragh, Furqan L.; Vasilyev, Aleksey A.; Edwards, Ryan; Stephen, Mark A.; Troupaki, Elisavet; Yu, Anthony W.; Krainak, Michael A.; Sawruk, Nick; Hovis, Floyd; Culpepper, Charles F.; Strickler, Kathy

    2016-01-01

    We present the results of three year life-aging of a specially designed prototype flight source laser operating at 1064 nm, 10 kHz, 1ns, 15W average power and external frequency doubler. The Fibertek-designed, slightly pressurized air, enclosed-container source laser operated at 1064 nm in active Q-switching mode. The external frequency doubler was set in a clean room at a normal air pressure. The goal of the experiment was to measure degradation modes at 1064 and 532 nm discreetly. The external frequency doubler consisted of a Lithium triborate, LiB3O5, crystal operated at non-critical phase-matching. Due to 1064 nm diagnostic needs, the amount of fundamental frequency power available for doubling was 13.7W. The power generated at 532 nm was between 8.5W and 10W, depending on the level of stress and degradation. The life-aging consisted of double stress-step operation for doubler crystal, at 0.35 Jcm2 for almost 1 year, corresponding to normal conditions, and then at 0.93 Jcm2 for the rest of the experiment, corresponding to accelerated testing. We observed no degradation at the first step and linear degradation at the second step. The linear degradation at the second stress-step was related to doubler crystal output surface changes and linked to laser-assisted contamination. We discuss degradation model and estimate the expected lifetime for the flight laser at 532 nm. This work was done within the laser testing for NASAs Ice, Cloud, and land Elevation Satellite-2 (ICESat-2) LIDAR at Goddard Space Flight Center in Greenbelt, MD with the goal of 1 trillion shots lifetime.

  12. Three Year Aging of Prototype Flight Laser at 10 Khz and 1 Ns Pulses with External Frequency Doubler for the Icesat-2 Mission

    NASA Technical Reports Server (NTRS)

    Konoplev, Oleg A.; Chiragh, Furqan L.; Vasilyev, Aleksey A.; Edwards, Ryan; Stephen, Mark A.; Troupaki, Elisavet; Yu, Anthony W.; Krainak, Michael A.; Sawruk, Nick; Hovis, Floyd; Culpepper, Charles F.; Strickler, Kathy

    2016-01-01

    We present the results of three year life-aging of a specially designed prototype flight source laser operating at 1064 nm, 10 kHz, 1ns, 15W average power and external frequency doubler. The Fibertek-designed, slightly pressurized air, enclosed-container source laser operated at 1064 nm in active Q-switching mode. The external frequency doubler was set in a clean room at a normal air pressure. The goal of the experiment was to measure degradation modes at 1064 and 532 nm discreetly. The external frequency doubler consisted of a Lithium triborate, LiB3O5, crystal operated at non-critical phase-matching. Due to 1064 nm diagnostic needs, the amount of fundamental frequency power available for doubling was 13.7W. The power generated at 532 nm was between 8.5W and 10W, depending on the level of stress and degradation. The life-aging consisted of double stress-step operation for doubler crystal, at 0.35 J/cm2 for almost 1 year, corresponding to normal conditions, and then at 0.93 J/cm2 for the rest of the experiment, corresponding to accelerated testing. We observed no degradation at the first step and linear degradation at the second step. The linear degradation at the second stress-step was related to doubler crystal output surface changes and linked to laser-assisted contamination. We discuss degradation model and estimate the expected lifetime for the flight laser at 532 nm. This work was done within the laser testing for NASA's Ice, Cloud, and land Elevation Satellite-2 (ICESat-2) LIDAR at Goddard Space Flight Center in Greenbelt, MD with the goal of 1 trillion shots lifetime.

  13. Pulse

    MedlinePlus

    ... resting for at least 10 minutes. Take the exercise heart rate while you are exercising. ... pulse rate can help determine if the patient's heart is pumping. ... rate gives information about your fitness level and health.

  14. Laser parametric instability experiments of a 3ω, 15 kJ, 6-ns laser pulse in gas-filled hohlraums at the Ligne d'Intégration Laser facility

    SciTech Connect

    Rousseaux, C.; Huser, G.; Loiseau, P.; Casanova, M.; Alozy, E.; Villette, B.; Wrobel, R.; Henry, O.; Raffestin, D.

    2015-02-15

    Experimental investigation of stimulated Raman (SRS) and Brillouin (SBS) scattering have been obtained at the Ligne-d'Intégration-Laser facility (LIL, CEA-Cesta, France). The parametric instabilities (LPI) are driven by firing four laser beamlets (one quad) into millimeter size, gas-filled hohlraum targets. A quad delivers energy on target of 15 kJ at 3ω in a 6-ns shaped laser pulse. The quad is focused by means of 3ω gratings and is optically smoothed with a kinoform phase plate and with smoothing by spectral dispersion-like 2 GHz and/or 14 GHz laser bandwidth. Open- and closed-geometry hohlraums have been used, all being filled with 1-atm, neo-pentane (C{sub 5}H{sub 12}) gas. For SRS and SBS studies, the light backscattered into the focusing optics is analyzed with spectral and time resolutions. Near-backscattered light at 3ω and transmitted light at 3ω are also monitored in the open geometry case. Depending on the target geometry (plasma length and hydrodynamic evolution of the plasma), it is shown that, at maximum laser intensity about 9 × 10{sup 14} W/cm{sup 2}, Raman reflectivity noticeably increases up to 30% in 4-mm long plasmas while SBS stays below 10%. Consequently, laser transmission through long plasmas drops to about 10% of incident energy. Adding 14 GHz bandwidth to the laser always reduces LPI reflectivities, although this reduction is not dramatic.

  15. Characterization of the magnetization reversal of perpendicular Nanomagnetic Logic clocked in the ns-range

    NASA Astrophysics Data System (ADS)

    Ziemys, Grazvydas; Trummer, Christian; Gamm, Stephan Breitkreutz-v.; Eichwald, Irina; Schmitt-Landsiedel, Doris; Becherer, Markus

    2016-05-01

    We have investigated the magnetization reversal of fabricated Co/Pt nanomagnets with perpendicular anisotropy within a wide range of magnetic field pulse widths. This experiment covers the pulse lengths from 700 ms to 20 ns. We observed that the commonly used Arrhenius model fits very well the experimental data with a single parameter set for pulse times above 100 ns (tp > 100 ns). However, below 100 ns (tp < 100 ns), a steep increase of the switching field amplitude is observed and the deviation from the Arrhenius model becomes unacceptable. For short pulse times the model can be adjusted by the reversal time term for the dynamic switching field which is only dependent on the pulse amplitude and not on temperature anymore. Precise modeling of the magnetization reversal in the sub-100 ns-range is crucially important to ensure reliable operation in the favored GHz-range as well as to explore and design new kinds of Nanomagnetic Logic circuits and architectures.

  16. In vitro processing of dengue virus type 2 nonstructural proteins NS2A, NS2B, and NS3.

    PubMed Central

    Preugschat, F; Yao, C W; Strauss, J H

    1990-01-01

    We have tested the hypothesis that the flavivirus nonstructural protein NS3 is a viral proteinase that generates the termini of several nonstructural proteins by using an efficient in vitro expression system and monospecific antisera directed against the nonstructural proteins NS2B and NS3. A series of cDNA constructs was transcribed by using T7 RNA polymerase, and the RNA was translated in reticulocyte lysates. The resulting protein patterns indicated that proteolytic processing occurred in vitro to generate NS2B and NS3. The amino termini of NS2B and NS3 produced in vitro were found to be the same as the termini of NS2B and NS3 isolated from infected cells. Deletion analysis of cDNA constructs localized the protease domain within NS3 to the first 184 amino acids but did not eliminate the possibility that sequences within NS2B were also required for proper cleavage. Kinetic analysis of processing events in vitro and experiments to examine the sensitivity of processing to dilution suggested that an intramolecular cleavage between NS2A and NS2B preceded an intramolecular cleavage between NS2B and NS3. The data from these expression experiments confirm that NS3 is the viral proteinase responsible for cleavage events generating the amino termini of NS2B and NS3 and presumably for cleavages generating the termini of NS4A and NS5 as well. Images PMID:2143543

  17. A compact nanosecond pulse modulator

    NASA Astrophysics Data System (ADS)

    Sha, Jizhang; Xue, Jianchao; Qiang, Bohan

    Two circuits of nanosecond pulse modulator which generate two different width rectangular pulses respectively are described. The basic configuration of the modulator is the Marx circuit, in which avalanche transistors are used as switching devices. In order to obtain the rectangular pulses a pulse-forming network (PFN) is introduced and fitted into the Marx. A multi-parallel arrangement of the Marx is used to satisfy the broad pulse requirement. Experiments have shown that the two different width rectangular pulses which have 130 V amplitudes and 30 and 200 ns widths respectively can be obtained at a 50 ohms load. The two pulses have steep front edges (3.6 ns and 10 ns respectively) and flat tops with less than + or - 5 percent ripples. Therefore, the modulator can meet the requirements of the nanosecond pulse radar.

  18. [System of ns time-resolved spectroscopy diagnosis and radioprotection].

    PubMed

    Yao, Wei-Bo; Guo, Jian-Ming; Zhang, Yong-min; Tang, Jun-Ping; Cheng, Liang; Xu, Qi-fuo

    2014-06-01

    Cathode plasma of high current electron beam diode is an important research on high power microwave and strong pulsed radio accelerator. It is a reliable method to study cathode plasma by diagnosing the cathode plasma parameters with non-contact spectroscopy measurement system. The present paper introduced the work principle, system composition and performance of the nanosecond (ns) time-resolved spectroscopy diagnosis system. Furthermore, it introduced the implementing method and the temporal relation of lower jitter synchronous trigger system. Simultaneously, the authors designed electromagnetic and radio shield room to protect the diagnosis system due to the high electromagnetic and high X-ray and γ-ray radiation, which seriously interferes with the system. Time-resolved spectroscopy experiment on brass (H62) cathode shows that, the element and matter composition of cathode plasma is clearly increase with the increase in the diode pulsed voltage and current magnitude. The spectroscopy diagnosis system could be of up to 10 ns time resolve capability. It's least is 2 ns. Synchronous trigger system's jitter is less than 4 ns. The spectroscopy diagnosis system will open a new way to study the cathode emission mechanism in depth. PMID:25358142

  19. NS&T Management Observations

    SciTech Connect

    Gianotto, David

    2014-09-01

    The INL Management Observation Program (MOP) is designed to improve managers and supervisors understanding of work being performed by employees and the barriers impacting their success. The MOP also increases workers understanding of managements’ expectations as they relate to safety, security, quality, and work performance. Management observations (observations) are designed to improve the relationship and trust between employees and managers through increased engagement and interactions between managers and researchers in the field. As part of continuous improvement, NS&T management took initiative to focus on the participation and quality of observations in FY 14. This quarterly report is intended to (a) summarize the participation and quality of management’s observations, (b) assess observations for commonalities or trends related to facility or process barriers impacting research, and (c) provide feedback and make recommendations for improvements NS&T’s MOP.

  20. A versatile pulse programmer for pulsed nuclear magnetic resonance spectroscopy.

    NASA Technical Reports Server (NTRS)

    Tarr, C. E.; Nickerson, M. A.

    1972-01-01

    A digital pulse programmer producing the standard pulse sequences required for pulsed nuclear magnetic resonance spectroscopy is described. In addition, a 'saturation burst' sequence, useful in the measurement of long relaxation times in solids, is provided. Both positive and negative 4 V trigger pulses are produced that are fully synchronous with a crystal-controlled time base, and the pulse programmer may be phase-locked with a maximum pulse jitter of 3 ns to the oscillator of a coherent pulse spectrometer. Medium speed TTL integrated circuits are used throughout.

  1. Cell electrofusion using nanosecond electric pulses

    PubMed Central

    Rems, Lea; Ušaj, Marko; Kandušer, Maša; Reberšek, Matej; Miklavčič, Damijan; Pucihar, Gorazd

    2013-01-01

    Electrofusion is an efficient method for fusing cells using short-duration high-voltage electric pulses. However, electrofusion yields are very low when fusion partner cells differ considerably in their size, since the extent of electroporation (consequently membrane fusogenic state) with conventionally used microsecond pulses depends proportionally on the cell radius. We here propose a new and innovative approach to fuse cells with shorter, nanosecond (ns) pulses. Using numerical calculations we demonstrate that ns pulses can induce selective electroporation of the contact areas between cells (i.e. the target areas), regardless of the cell size. We then confirm experimentally on B16-F1 and CHO cell lines that electrofusion of cells with either equal or different size by using ns pulses is indeed feasible. Based on our results we expect that ns pulses can improve fusion yields in electrofusion of cells with different size, such as myeloma cells and B lymphocytes in hybridoma technology. PMID:24287643

  2. Widely tunable repetition-rate and pulse-duration nanosecond pulses from two spectral beam combined fiber amplifiers

    NASA Astrophysics Data System (ADS)

    Hu, Man; Zheng, Ye; Yang, Yifeng; Chen, Xiaolong; Zhao, Chun; Liu, Kai; Wang, Jianhua; Qi, Yunfeng; He, Bing; Zhou, Jun

    2016-10-01

    Nanosecond pulses with a widely tunable repetition-rate and pulse-duration at 1 μm wavelength are obtained by spectrally combining two pulse fiber amplifiers using a home-made polarization-independent multilayer dielectric reflective diffraction grating. The width of the combined pulses can be tuned from 4 ns to 800 ns, and the pulse repetition-rate can be ranged from 1 MHz to 200 MHz. Thanks to the spectral beam combining system, the maximum repetition-rate and pulse-duration of the combined pulses are doubled, compared to the single pulse fiber amplifier, by setting a proper temporal delay between the two pulse channels.

  3. GENIE Production Release 2.10.0

    SciTech Connect

    Alam, M.; Andreopoulos, C.; Athar, M.; Bodek, A.; Christy, E.; Coopersmith, B.; Dennis, S.; Dytman, S.; Gallagher, H.; Geary, N.; Golan, T.; Hatcher, R.; Hoshina, K.; Liu, J.; Mahn, K.; Marshall, C.; Morrison, J.; Nirkko, M.; Nowak, J.; Perdue, G. N.; Yarba, J.

    2015-12-25

    GENIE is a neutrino Monte Carlo event generator that simulates the primary interaction of a neutrino with a nuclear target, along with the subsequent propagation of the reaction products through the nuclear medium. It additionally contains libraries for fully-featured detector geometries and for managing various types of neutrino flux. This note details recent updates to GENIE, in particular, changes introduced into the newest production release, version 2.10.0.

  4. Monoclonal Antibodies Against NS3 and NS5 Proteins of Japanese Encephalitis Virus

    PubMed Central

    Chen, Zheng; Shao, Lin; Ye, Jing; Li, Yongmao; Huang, Shaomei; Chen, Huanchun

    2012-01-01

    Non-structural proteins NS3 and NS5 of Japanese encephalitis virus (JEV) were expressed in Escherichia coli and purified by dialysis. Two monoclonal antibodies (MAbs) named 1H7 and 2D4 against NS3 protein and three MAbs named 3C4, 3H7, and 3F10 against NS5 protein were generated by fusing mouse myeloma cell line SP2/0 with spleen lymphocytes from NS3 or NS5 protein immunized mice. Then activity of MAbs was characterized by enzyme-linked immunosorbent assay (ELISA), Western blot analysis, and indirect immunofluorescent assays (IFA). Our results demonstrated that all the MAbs showed high specificity and sensitivity in IFA at 1:100 dilution and in Western blot analysis at 1:500 dilution, which indicated that these MAbs against NS3 and NS5 proteins of JEV may be used as valuable tools for analysis of the protein functions and pathogenesis of JEV. PMID:22509919

  5. Kilovolt Blumlein pulse generator with variable pulse duration and polarity

    NASA Astrophysics Data System (ADS)

    de Angelis, Andrea; Kolb, Juergen F.; Zeni, Luigi; Schoenbach, Karl H.

    2008-04-01

    A Blumlein pulse generator which utilizes the superposition of electrical pulses launched from two individually switched pulse forming lines has been designed and tested. By using a power metal-oxide-semiconductor field-effect transistor as a switch on each end of the Blumlein line, we were able to generate pulses with amplitudes of 1kV across a 100Ω load. Pulse duration and polarity can be controlled by the temporal delay in the triggering of the two switches. Using this technique, we have demonstrated the generation of pulses with durations between 8 and 60ns. The lower limit in pulse duration was determined by the switch closing time and the upper limit by the length of the pulse forming line. A further advantage of the concept is that pulse distortions caused by the non-negligible on-resistance of a line with a single switch can be eliminated by using switches with identical characteristics.

  6. Kilovolt Blumlein pulse generator with variable pulse duration and polarity.

    PubMed

    de Angelis, Andrea; Kolb, Juergen F; Zeni, Luigi; Schoenbach, Karl H

    2008-04-01

    A Blumlein pulse generator which utilizes the superposition of electrical pulses launched from two individually switched pulse forming lines has been designed and tested. By using a power metal-oxide-semiconductor field-effect transistor as a switch on each end of the Blumlein line, we were able to generate pulses with amplitudes of 1 kV across a 100 Omega load. Pulse duration and polarity can be controlled by the temporal delay in the triggering of the two switches. Using this technique, we have demonstrated the generation of pulses with durations between 8 and 60 ns. The lower limit in pulse duration was determined by the switch closing time and the upper limit by the length of the pulse forming line. A further advantage of the concept is that pulse distortions caused by the non-negligible on-resistance of a line with a single switch can be eliminated by using switches with identical characteristics.

  7. Classical swine fever virus NS5B protein suppresses the inhibitory effect of NS5A on viral translation by binding to NS5A.

    PubMed

    Sheng, Chun; Wang, Jing; Xiao, Jing; Xiao, Jun; Chen, Yan; Jia, Lin; Zhi, Yimiao; Li, Guangyuan; Xiao, Ming

    2012-05-01

    In order to investigate molecular mechanisms of internal ribosome entry site (IRES)-mediated translation in classical swine fever virus (CSFV), an important pathogen of pigs, the expression level of NS3 was evaluated in the context of genomic RNAs and reporter RNA fragments. All data showed that the NS5A protein has an inhibitory effect on IRES-mediated translation and that NS5B proteins suppress the inhibitory effect of NS5A on viral translation, but CSFV NS5B GDD mutants do not. Furthermore, glutathione S-transferase pull-down assay and immunoprecipitation analysis, associated with deletion and alanine-scanning mutations, were performed. Results showed that NS5B interacts with NS5A and that the region aa 390-414, located in the C-terminal half of NS5A, is important for binding of NS5B to NS5A. Furthermore, amino acids K399, T401, E406 and L413 in the region were found to be essential for NS5A-NS5B interaction, virus rescue and infection. The above-mentioned region and four amino acids were observed to overlap with the site responsible for inhibition of IRES-mediated translation by the NS5A protein. We also found that aa 63-72, aa 637-653 and the GDD motif of NS5B were necessary for the interaction between NS5A and NS5B. These findings suggest that the repression activity of the NS5B protein toward the role of NS5A in translation might be achieved by NS5A-NS5B interaction, for which aa 390-414 of NS5A and aa 63-72, aa 637-653 and the GDD motif of NS5B are indispensable. This is important for understanding the role of NS5A-NS5B interaction in the virus life cycle. PMID:22258858

  8. Dengue 2 virus NS2B and NS3 form a stable complex that can cleave NS3 within the helicase domain.

    PubMed

    Arias, C F; Preugschat, F; Strauss, J H

    1993-04-01

    Flavivirus genomic RNA is translated into a large polyprotein that is processed into structural and nonstructural proteins. The N-termini of several nonstructural proteins are produced by cleavage at dibasic sites by a two-component viral proteinase consisting of NS2B and NS3. NS3 contains a trypsin-like serine proteinase domain at its N-terminus, whereas the function of NS2B in proteolysis is yet to be determined. We have used an NS3-specific antiserum, under nondenaturing conditions, to demonstrate that NS2B and NS3 form a complex both in vitro and in vivo. The N-terminal 184 residues of NS3 are sufficient to form the complex with NS2B. The complex forms efficiently when the NS2B and NS3 are translated from two different mRNAs as well as when NS2B and NS3 are translated as a polyprotein from the same mRNA. A chimeric complex can be formed between yellow fever NS2B and a chimeric yellow fever-dengue 2 NS3. Using anti-NS3 antisera, we also found that a 50-kDa fragment of NS3, consisting of the N-terminal approximately 460 residues, is produced in infected mammalian cells. This fragment is not produced in infected mosquito cells, but will form in Triton X-100 lysates of mosquito cells. The cleavage of NS3 to form this fragment is catalyzed by the NS3 proteinase itself and proteolysis requires NS2B. Examination of the amino acid sequence of NS3 reveals a potential conserved cleavage site that resembles other sites cleaved by the NS3/NS2B proteinase; this site occurs within a conserved RNA helicase sequence motif. The importance of this alternatively processed form of NS3 and its role in the replication cycle of dengue virus remain to be determined.

  9. Allosteric inhibition of the NS2B-NS3 protease from dengue virus.

    PubMed

    Yildiz, Muslum; Ghosh, Sumana; Bell, Jeffrey A; Sherman, Woody; Hardy, Jeanne A

    2013-12-20

    Dengue virus is the flavivirus that causes dengue fever, dengue hemorrhagic disease, and dengue shock syndrome, which are currently increasing in incidence worldwide. Dengue virus protease (NS2B-NS3pro) is essential for dengue virus infection and is thus a target of therapeutic interest. To date, attention has focused on developing active-site inhibitors of NS2B-NS3pro. The flat and charged nature of the NS2B-NS3pro active site may contribute to difficulties in developing inhibitors and suggests that a strategy of identifying allosteric sites may be useful. We report an approach that allowed us to scan the NS2B-NS3pro surface by cysteine mutagenesis and use cysteine reactive probes to identify regions of the protein that are susceptible to allosteric inhibition. This method identified a new allosteric site utilizing a circumscribed panel of just eight cysteine variants and only five cysteine reactive probes. The allosterically sensitive site is centered at Ala125, between the 120s loop and the 150s loop. The crystal structures of WT and modified NS2B-NS3pro demonstrate that the 120s loop is flexible. Our work suggests that binding at this site prevents a conformational rearrangement of the NS2B region of the protein, which is required for activation. Preventing this movement locks the protein into the open, inactive conformation, suggesting that this site may be useful in the future development of therapeutic allosteric inhibitors. PMID:24164286

  10. The C-terminal 50 amino acid residues of dengue NS3 protein are important for NS3-NS5 interaction and viral replication.

    PubMed

    Tay, Moon Y F; Saw, Wuan Geok; Zhao, Yongqian; Chan, Kitti W K; Singh, Daljit; Chong, Yuwen; Forwood, Jade K; Ooi, Eng Eong; Grüber, Gerhard; Lescar, Julien; Luo, Dahai; Vasudevan, Subhash G

    2015-01-23

    Dengue virus multifunctional proteins NS3 protease/helicase and NS5 methyltransferase/RNA-dependent RNA polymerase form part of the viral replication complex and are involved in viral RNA genome synthesis, methylation of the 5'-cap of viral genome, and polyprotein processing among other activities. Previous studies have shown that NS5 residue Lys-330 is required for interaction between NS3 and NS5. Here, we show by competitive NS3-NS5 interaction ELISA that the NS3 peptide spanning residues 566-585 disrupts NS3-NS5 interaction but not the null-peptide bearing the N570A mutation. Small angle x-ray scattering study on NS3(172-618) helicase and covalently linked NS3(172-618)-NS5(320-341) reveals a rigid and compact formation of the latter, indicating that peptide NS5(320-341) engages in specific and discrete interaction with NS3. Significantly, NS3:Asn-570 to alanine mutation introduced into an infectious DENV2 cDNA clone did not yield detectable virus by plaque assay even though intracellular double-stranded RNA was detected by immunofluorescence. Detection of increased negative-strand RNA synthesis by real time RT-PCR for the NS3:N570A mutant suggests that NS3-NS5 interaction plays an important role in the balanced synthesis of positive- and negative-strand RNA for robust viral replication. Dengue virus infection has become a global concern, and the lack of safe vaccines or antiviral treatments urgently needs to be addressed. NS3 and NS5 are highly conserved among the four serotypes, and the protein sequence around the pinpointed amino acids from the NS3 and NS5 regions are also conserved. The identification of the functionally essential interaction between the two proteins by biochemical and reverse genetics methods paves the way for rational drug design efforts to inhibit viral RNA synthesis.

  11. Nitrogen oxide removal dynamic process through 15 Ns DBD technique

    NASA Astrophysics Data System (ADS)

    Wang, Xiaojun; Zhang, Lianshui; Lai, Weidong; Liu, Fengliang

    2015-05-01

    Nitrogen oxides exhaust gas assumes the important responsibility on air pollution by forming acid rain. This paper discusses the NO removal mechanism in 15 ns pulse dielectric barrier discharge (DBD) plasma through experimental and simulating method. Emission spectra collected from plasma are evaluated as sourced from N+ and O(3P). The corresponding zero-dimensional model is established and verified through comparing the simulated concentration evolution and the experimental time-resolved spectra of N+. The electron impact ionization plays major role on NO removal and the produced NO+ are further decomposed into N+ and O(3P) through electron impact dissociative excitation rather than the usual reported dissociative recombination process. Simulation also indicates that the removal process can be accelerated by NO inputted at lower initial concentration or electrons streamed at higher concentration, due to the heightened electron impact probability on NO molecules. The repetitive pulse discharge is a benefit for improving the NO removal efficiency by effectively utilizing the radicals generated from the previous pulse under the condition that the pulse period should be shorter enough to ignore the spatial diffusion of radicals. Finally, slight attenuation on NO removal has been experimentally and simulatively observed after N2 mixed, due to the competitive consumption of electrons.

  12. Dynamic Imaging of the Hepatitis C Virus NS5A Protein during a Productive Infection

    PubMed Central

    Eyre, Nicholas S.; Fiches, Guillaume N.; Aloia, Amanda L.; Helbig, Karla J.; McCartney, Erin M.; McErlean, Christopher S. P.; Li, Kui; Aggarwal, Anupriya; Turville, Stuart G.

    2014-01-01

    ABSTRACT Hepatitis C virus (HCV) NS5A is essential for viral genome replication within cytoplasmic replication complexes and virus assembly at the lipid droplet (LD) surface, although its definitive functions are poorly understood. We developed approaches to investigate NS5A dynamics during a productive infection. We report here that NS5A motility and efficient HCV RNA replication require the microtubule network and the cytoplasmic motor dynein and demonstrate that both motile and relatively static NS5A-positive foci are enriched with host factors VAP-A and Rab5A. Pulse-chase imaging revealed that newly synthesized NS5A foci are small and distinct from aged foci, while further studies using a unique dual fluorescently tagged infectious HCV chimera showed a relatively stable association of NS5A foci with core-capped LDs. These results reveal new details about the dynamics and maturation of NS5A and the nature of potential sites of convergence of HCV replication and assembly pathways. IMPORTANCE Hepatitis C virus (HCV) is a major cause of serious liver disease worldwide. An improved understanding of the HCV replication cycle will enable development of novel and improved antiviral strategies. Here we have developed complementary fluorescent labeling and imaging approaches to investigate the localization, traffic and interactions of the HCV NS5A protein in living, virus-producing cells. These studies reveal new details as to the traffic, composition and biogenesis of NS5A foci and the nature of their association with putative sites of virus assembly. PMID:24429364

  13. Spin Complicates Eccentric BH-NS Mergers

    NASA Astrophysics Data System (ADS)

    Kohler, Susanna

    2015-08-01

    When a neutron star (NS) has a glancing encounter with a black hole (BH), its spin has a significant effect on the outcome, according to new simulations run by William East of Stanford University and his collaborators. Spotting an Eccentric Merger. In a traditional BH-NS merger, the two objects orbit each other quasi-circularly as they spiral in. But there's another kind of merger that's possible in high-density environments like galactic nuclei or globular clusters: a dynamical capture merger, in which a NS and BH pass each other just close enough that the gravity of the black hole "catches" the NS, leading the two objects to merge with very eccentric orbits. During an eccentric merger, the NS can be torn apart -- at which point some fraction of the tidally-disrupted material will escape the system, while some fraction instead accretes back onto the BH. Knowing these fractions is important for being able to model the expected electromagnetic signatures for the merger: the unbound material can power transients like kilonovae, whereas the accreting material may be the cause of short gamma-ray bursts. The amount of material available for events like these would change their observable strengths. Testing the Effects of Spin. To see whether NS spin has an impact on the behavior of the merger, East and collaborators use a general-relativistic hydrodynamic code to simulate the glancing encounter of a BH and a NS with dimensionless spin between a=0 (non-spinning) and a=0.756 (rotation period of 1 ms). They also vary the separation of the first encounter. The group finds that changing the NS's spin can change a number of outcomes of the merger. To start with, it can affect whether the NS is captured by the BH, or if the encounter is glancing and then both objects carry on their merry way. And if the NS is trapped by the BH and torn apart, then the higher the NS's spin, the more matter outside of the BH ends up unbound, instead of getting trapped into an accretion disk

  14. Rationalizing meat consumption. The 4Ns.

    PubMed

    Piazza, Jared; Ruby, Matthew B; Loughnan, Steve; Luong, Mischel; Kulik, Juliana; Watkins, Hanne M; Seigerman, Mirra

    2015-08-01

    Recent theorizing suggests that the 4Ns - that is, the belief that eating meat is natural, normal, necessary, and nice - are common rationalizations people use to defend their choice of eating meat. However, such theorizing has yet to be subjected to empirical testing. Six studies were conducted on the 4Ns. Studies 1a and 1b demonstrated that the 4N classification captures the vast majority (83%-91%) of justifications people naturally offer in defense of eating meat. In Study 2, individuals who endorsed the 4Ns tended also to objectify (dementalize) animals and included fewer animals in their circle of moral concern, and this was true independent of social dominance orientation. Subsequent studies (Studies 3-5) showed that individuals who endorsed the 4Ns tend not to be motivated by ethical concerns when making food choices, are less involved in animal-welfare advocacy, less driven to restrict animal products from their diet, less proud of their animal-product decisions, tend to endorse Speciesist attitudes, tend to consume meat and animal products more frequently, and are highly committed to eating meat. Furthermore, omnivores who strongly endorsed the 4Ns tended to experience less guilt about their animal-product decisions, highlighting the guilt-alleviating function of the 4Ns. PMID:25865663

  15. Rationalizing meat consumption. The 4Ns.

    PubMed

    Piazza, Jared; Ruby, Matthew B; Loughnan, Steve; Luong, Mischel; Kulik, Juliana; Watkins, Hanne M; Seigerman, Mirra

    2015-08-01

    Recent theorizing suggests that the 4Ns - that is, the belief that eating meat is natural, normal, necessary, and nice - are common rationalizations people use to defend their choice of eating meat. However, such theorizing has yet to be subjected to empirical testing. Six studies were conducted on the 4Ns. Studies 1a and 1b demonstrated that the 4N classification captures the vast majority (83%-91%) of justifications people naturally offer in defense of eating meat. In Study 2, individuals who endorsed the 4Ns tended also to objectify (dementalize) animals and included fewer animals in their circle of moral concern, and this was true independent of social dominance orientation. Subsequent studies (Studies 3-5) showed that individuals who endorsed the 4Ns tend not to be motivated by ethical concerns when making food choices, are less involved in animal-welfare advocacy, less driven to restrict animal products from their diet, less proud of their animal-product decisions, tend to endorse Speciesist attitudes, tend to consume meat and animal products more frequently, and are highly committed to eating meat. Furthermore, omnivores who strongly endorsed the 4Ns tended to experience less guilt about their animal-product decisions, highlighting the guilt-alleviating function of the 4Ns.

  16. Experimental study on double-pulse laser ablation of steel upon multiple parallel-polarized ultrashort-pulse irradiations

    NASA Astrophysics Data System (ADS)

    Schille, Joerg; Schneider, Lutz; Kraft, Sebastian; Hartwig, Lars; Loeschner, Udo

    2016-07-01

    In this paper, double-pulse laser processing is experimentally studied with the aim to explore the influence of ultrashort pulses with very short time intervals on ablation efficiency and quality. For this, sequences of 50 double pulses of varied energy and inter-pulse delay, as adjusted between 400 fs and 18 ns by splitting the laser beam into two optical paths of different length, were irradiated to technical-grade stainless steel. The depth and the volume of the craters produced were measured in order to evaluate the efficiency of the ablation process; the crater quality was analyzed by SEM micrographs. The results obtained were compared with craters produced with sequences of 50 single pulses and energies equal to the double pulse. It is demonstrated that double-pulse processing cannot exceed the ablation efficiency of single pulses of optimal fluence, but the ablation crater surface formed smoother if inter-pulse delay was in the range between 10 ns and 18 ns. In addition, the influence of pulse duration and energy distribution between the individual pulses of the double pulse on ablation was studied. For very short inter-pulse delay, no significant effect of energy variation within the double pulse on removal rate was found, indicating that the double pulse acts as a big single pulse of equal energy. Further, the higher removal efficiency was achieved when double-pulse processing using femtosecond pulses instead of picosecond pulses.

  17. Bipolar nanosecond electric pulses are less efficient at electropermeabilization and killing cells than monopolar pulses

    PubMed Central

    Ibey, Bennett L.; Ullery, Jody; Pakhomova, Olga N.; Roth, Caleb C.; Semenov, Iurri; Beier, Hope T.; Tarango, Melissa; Xiao, Shu; Schoenbach, Karl; Pakhomov, Andrei G.

    2014-01-01

    Multiple studies have shown that bipolar (BP) electric pulses in the microsecond range are more effective at permeabilizing cells while maintaining similar cell survival rates as compared to monopolar (MP) pulse equivalents. In this paper, we investigated whether the same advantage existed for BP nanosecond-pulsed electric fields (nsPEF) as compared to MP nsPEF. To study permeabilization effectiveness, MP or BP pulses were delivered to single Chinese hamster ovary (CHO) cells and the response of three dyes, Calcium Green-1, Propidium Iodide (PI), and FM1-43, was measured by confocal microscopy. Results show that BP pulses were less effective at increasing intracellular calcium concentration or PI uptake and cause less membrane reorganization (FM1-43) than MP pulses. Twenty-four hour survival was measured in three cell lines (Jurkat, U937, CHO) and over ten times more BP pulses were required to induce death as compared to MP pulses of similar magnitude and duration. Flow cytometry analysis of CHO cells after exposure (15 minutes) revealed that to achieve positive FITC-Annexin V and PI expression, ten times more BP pulses were required than MP pulses. Overall, unlike longer pulse exposures, BP nsPEF exposures proved far less effective at both membrane permeabilization and cell killing than MP nsPEF. PMID:24332942

  18. Bipolar nanosecond electric pulses are less efficient at electropermeabilization and killing cells than monopolar pulses.

    PubMed

    Ibey, Bennett L; Ullery, Jody C; Pakhomova, Olga N; Roth, Caleb C; Semenov, Iurii; Beier, Hope T; Tarango, Melissa; Xiao, Shu; Schoenbach, Karl H; Pakhomov, Andrei G

    2014-01-10

    Multiple studies have shown that bipolar (BP) electric pulses in the microsecond range are more effective at permeabilizing cells while maintaining similar cell survival rates as compared to monopolar (MP) pulse equivalents. In this paper, we investigated whether the same advantage existed for BP nanosecond-pulsed electric fields (nsPEF) as compared to MP nsPEF. To study permeabilization effectiveness, MP or BP pulses were delivered to single Chinese hamster ovary (CHO) cells and the response of three dyes, Calcium Green-1, propidium iodide (PI), and FM1-43, was measured by confocal microscopy. Results show that BP pulses were less effective at increasing intracellular calcium concentration or PI uptake and cause less membrane reorganization (FM1-43) than MP pulses. Twenty-four hour survival was measured in three cell lines (Jurkat, U937, CHO) and over ten times more BP pulses were required to induce death as compared to MP pulses of similar magnitude and duration. Flow cytometry analysis of CHO cells after exposure (at 15 min) revealed that to achieve positive FITC-Annexin V and PI expression, ten times more BP pulses were required than MP pulses. Overall, unlike longer pulse exposures, BP nsPEF exposures proved far less effective at both membrane permeabilization and cell killing than MP nsPEF.

  19. The Effects of Intense Submicrosecond Electrical Pulses on Cells

    PubMed Central

    Deng, Jingdong; Schoenbach, Karl H.; Buescher, E. Stephen; Hair, Pamela S.; Fox, Paula M.; Beebe, Stephen J.

    2003-01-01

    A simple electrical model for living cells predicts an increasing probability for electric field interactions with intracellular substructures of both prokaryotic and eukaryotic cells when the electric pulse duration is reduced into the sub-microsecond range. The validity of this hypothesis was verified experimentally by applying electrical pulses (durations 100 μs–60 ns, electric field intensities 3–150 kV/cm) to Jurkat cells suspended in physiologic buffer containing propidium iodide. Effects on Jurkat cells were assessed by means of temporally resolved fluorescence and light microscopy. For the longest applied pulses, immediate uptake of propidium iodide occurred consistent with electroporation as the cause of increased surface membrane permeability. For nanosecond pulses, more delayed propidium iodide uptake occurred with significantly later uptake of propidium iodide occurring after 60 ns pulses compared to 300 ns pulses. Cellular swelling occurred rapidly following 300 ns pulses, but was minimal following 60 ns pulses. These data indicate that submicrosecond pulses achieve temporally distinct effects on living cells compared to microsecond pulses. The longer pulses result in rapid permeability changes in the surface membrane that are relatively homogeneous across the cell population, consistent with electroporation, while shorter pulses cause surface membrane permeability changes that are temporally delayed and heterogeneous in their magnitude. PMID:12668479

  20. Hepatitis C virus core, NS3, NS4B and NS5A are the major immunogenic proteins in humoral immunity in chronic HCV infection

    PubMed Central

    Sillanpää, Maarit; Melén, Krister; Porkka, Päivi; Fagerlund, Riku; Nevalainen, Kaisu; Lappalainen, Maija; Julkunen, Ilkka

    2009-01-01

    Background The viral genome of hepatitis C virus constitutes a 9.6-kb single-stranded positive-sense RNA which encodes altogether 11 viral proteins. In order to study the humoral immune responses against different HCV proteins in patients suffering from chronic HCV infection, we produced three structural (core, E1 and E2) and six nonstructural proteins (NS2, NS3, NS4A, NS4B, NS5A and NS5B) in Sf9 insect cells by using the baculovirus expression system. Results The recombinant HCV core, E1, E2, NS2, NS3, NS4A, NS4B, NS5A and NS5B proteins were purified and used in Western blot analysis to determine antibody responses against individual HCV protein in 68 HCV RNA and antibody positive human sera that were obtained from patients suffering from genotype 1, 2, 3 or 4 infection. These sera were also analysed with INNO-LIA Score test for HCV antibodies against core, NS3, NS4AB and NS5A, and the results were similar to the ones obtained by Western blot method. Based on our Western blot analyses we found that the major immunogenic HCV antigens were the core, NS4B, NS3 and NS5A proteins which were recognized in 97%, 86%, 68% and 53% of patient sera, respectively. There were no major genotype specific differences in antibody responses to individual HCV proteins. A common feature within the studied sera was that all except two sera recognized the core protein in high titers, whereas none of the sera recognized NS2 protein and only three sera (from genotype 3) recognised NS5B. Conclusion The data shows significant variation in the specificity in humoral immunity in chronic HCV patients. PMID:19549310

  1. Nucleocytoplasmic transport: the influenza virus NS1 protein regulates the transport of spliced NS2 mRNA and its precursor NS1 mRNA.

    PubMed

    Alonso-Caplen, F V; Nemeroff, M E; Qiu, Y; Krug, R M

    1992-02-01

    Influenza virus unspliced NS1 mRNA, like retroviral pre-mRNAs, is efficiently exported from the nucleus and translated in the cytoplasm of infected cells. With human immunodeficiency virus (HIV), the transport of viral pre-mRNAs is facilitated by the viral Rev protein. We tested the possibility that the influenza virus NS1 protein, a nuclear protein that is encoded by unspliced NS1 mRNA, has the same function as the HIV Rev protein. Surprisingly, using transient transfection assays, we found that rather than facilitating the nucleocytoplasmic transport of unspliced NS1 mRNA, the NS1 protein inhibited the transport of NS2 mRNA, the spliced mRNA generated from NS1 mRNA. The efficient transport of NS2 mRNA from the nucleus to the cytoplasm occurred only when the synthesis of the NS1 protein was abrogated by amber mutations. The NS1 protein down-regulated the export of NS2 mRNA whether or not it was generated by splicing, indicating that the NS1 protein acted directly on transport. Actinomycin D chase experiments verified that the NS1 protein acted on the transport and not on the differential stability of NS2 mRNA in the nucleus as compared to the cytoplasm. In addition, the NS1 protein inhibited the transport of NS1 mRNA itself, which contains all of the sequences in NS2 mRNA, particularly when NS1 mRNA was released from the splicing machinery by mutating its 3'-splice site. Our results indicate that the NS1 protein-mediated inhibition of transport requires sequences in NS2 mRNA. The transport of the viral PB1 protein, nucleocapsid protein, hemagglutinin, membrane protein, and M2 mRNAs was not affected by the NS1 protein. When the NS2 mRNA sequence was covalently attached to the PB1 mRNA, the transport of the chimeric mRNA was inhibited by the NS1 protein. Our results identify a novel function of the influenza virus NS1 protein and demonstrate that post-transcriptional control of gene expression can also occur at the level of the nucleocytoplasmic transport of a

  2. A novel recombinant single-chain hepatitis C virus NS3-NS4A protein with improved helicase activity.

    PubMed Central

    Howe, A. Y.; Chase, R.; Taremi, S. S.; Risano, C.; Beyer, B.; Malcolm, B.; Lau, J. Y.

    1999-01-01

    Hepatitis C virus (HCV) nonstructural protein 3 (NS3) has been shown to possess protease and helicase activities and has also been demonstrated to spontaneously associate with nonstructural protein NS4A (NS4A) to form a stable complex. Previous attempts to produce the NS3/NS4A complex in recombinant baculovirus resulted in a protein complex that aggregated and precipitated in the absence of nonionic detergent and high salt. A single-chain form of the NS3/NS4A complex (His-NS4A21-32-GSGS-NS3-631) was constructed in which the NS4A core peptide is fused to the N-terminus of the NS3 protease domain as previously described (Taremi et al., 1998). This protein contains a histidine tagged NS4A peptide (a.a. 21-32) fused to the full-length NS3 (a.a. 3-631) through a flexible tetra amino acid linker. The recombinant protein was expressed to high levels in Escherichia coli, purified to homogeneity, and examined for NTPase, nucleic acid unwinding, and proteolytic activities. The single-chain recombinant NS3-NS4A protein possesses physiological properties equivalent to those of the NS3/NS4A complex except that this novel construct is stable, soluble and sixfold to sevenfold more active in unwinding duplex RNA. Comparison of the helicase activity of the single-chain recombinant NS3-NS4A with that of the full-length NS3 (without NS4A) and that of the helicase domain alone suggested that the presence of the protease domain and at least the NS4A core peptide are required for optimal unwinding activity. PMID:10386883

  3. Temporal Behavior of the Pump Pulses, Residual Pump Pulses, and THz Pulses for D2O Gas Pumped by a TEA CO2 Laser

    NASA Astrophysics Data System (ADS)

    Geng, Lijie; Zhang, Zhifeng; Zhai, Yusheng; Su, Yuling; Zhou, Fanghua; Qu, Yanchen; Zhao, Weijiang

    2016-08-01

    Temporal behavior of the pump pulses, residual pump pulses, and THz pulses for optically pumped D2O gas molecules was investigated by using a tunable TEA CO2 laser as the pumping source. The pulse profiles of pump laser pulses, residual pump pulses, and the THz output pulses were measured, simultaneously, at several different gas pressures. For THz pulse, the pulse delay between the THz pulse and the pump pulse was observed and the delay time was observed to increase from 40 to 70 ns with an increase in gas pressure from 500 to 1700 Pa. Both THz pulse broadening and compression were observed, and the pulse broadening effect transformed to the compression effect with increasing the gas pressure. For the residual pump pulse, the full width at half maximum (FWHM) of the main pulse decreased with increasing gas pressure, and the main pulse disappeared at high gas pressures. The secondary pulses were observed at high gas pressure, and the time intervals of about 518 and 435 ns were observed between the THz output pulse and the secondary residual pump pulse at the pressure of 1400 Pa and 1700 Pa, from which the vibrational relaxation time constants of about 5.45 and 5.55 μs Torr were obtained.

  4. 29 CFR 2.10 - Scope and purpose.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 29 Labor 1 2010-07-01 2010-07-01 true Scope and purpose. 2.10 Section 2.10 Labor Office of the Secretary of Labor GENERAL REGULATIONS Audiovisual Coverage of Administrative Hearings § 2.10 Scope and purpose. This subpart defines the scope of audiovisual coverage of departmental administrative...

  5. Non-structural protein NS3/NS3a is required for propagation of bluetongue virus in Culicoides sonorensis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background: Bluetongue virus (BTV) causes non-contagious haemorrhagic disease in ruminants and is transmitted by Culicoides spp. biting midges. BTV encodes four non-structural proteins of which NS3/NS3a is functional in virus release. NS3/NS3a is not essential for in vitro virus replication. However...

  6. Progress on New Hepatitis C Virus Targets: NS2 and NS5A

    NASA Astrophysics Data System (ADS)

    Marcotrigiano, Joseph

    Hepatitis C virus (HCV) is a major global health problem, affecting about 170 million people worldwide. Chronic infection can lead to cirrhosis and liver cancer. The replication machine of HCV is a multi-subunit membrane associated complex, consisting of nonstructural proteins (NS2-5B), which replicate the viral RNA genome. The structures of NS5A and NS2 were recently determined. NS5A is an essential replicase component that also modulates numerous cellular processes ranging from innate immunity to cell growth and survival. The structure reveals a novel protein fold, a new zinc coordination motif, a disulfide bond and a dimer interface. Analysis of molecular surfaces suggests the location of the membrane interaction surface of NS5A, as well as hypothetical protein and RNA binding sites. NS2 is one of two virally encoded proteases that are required for processing the viral polyprotein into the mature nonstructural proteins. NS2 is a dimeric cysteine protease with two composite active sites. For each active site, the catalytic histidine and glutamate residues are contributed by one monomer and the nucleophilic cysteine by the other. The C-terminal residues remain coordinated in the two active sites, predicting an inactive post-cleavage form. The structure also reveals possible sites of membrane interaction, a rare cis-proline residue, and highly conserved dimer contacts. The novel features of both structures have changed the current view of HCV polyprotein replication and present new opportunities for antiviral drug design.

  7. The two-component NS2B-NS3 proteinase represses DNA unwinding activity of the West Nile virus NS3 helicase.

    PubMed

    Chernov, Andrei V; Shiryaev, Sergey A; Aleshin, Alexander E; Ratnikov, Boris I; Smith, Jeffrey W; Liddington, Robert C; Strongin, Alex Y

    2008-06-20

    Similar to many flavivirus types including Dengue and yellow fever viruses, the nonstructural NS3 multifunctional protein of West Nile virus (WNV) with an N-terminal serine proteinase domain and an RNA triphosphatase, an NTPase domain, and an RNA helicase in the C-terminal domain is implicated in both polyprotein processing and RNA replication and is therefore a promising drug target. To exhibit its proteolytic activity, NS3 proteinase requires the presence of the cofactor encoded by the upstream NS2B sequence. During our detailed investigation of the biology of the WNV helicase, we characterized the ATPase and RNA/DNA unwinding activities of the full-length NS2B-NS3 proteinase-helicase protein as well as the individual NS3 helicase domain lacking both the NS2B cofactor and the NS3 proteinase sequence and the individual NS3 proteinase-helicase lacking only the NS2B cofactor. We determined that both the NS3 helicase and NS3 proteinase-helicase constructs are capable of unwinding both the DNA and the RNA templates. In contrast, the full-length NS2B-NS3 proteinase-helicase unwinds only the RNA templates, whereas its DNA unwinding activity is severely repressed. Our data suggest that the productive, catalytically competent fold of the NS2B-NS3 proteinase moiety represents an essential component of the RNA-DNA substrate selectivity mechanism in WNV and, possibly, in other flaviviruses. Based on our data, we hypothesize that the mechanism we have identified plays a role yet to be determined in WNV replication occurring both within the virus-induced membrane-bound replication complexes in the host cytoplasm and in the nuclei of infected cells.

  8. Coherent combining of pulsed fiber amplifiers in the nonlinear chirp regime with intra-pulse phase control.

    PubMed

    Palese, Stephen; Cheung, Eric; Goodno, Gregory; Shih, Chun-Ching; Di Teodoro, Fabio; McComb, Timothy; Weber, Mark

    2012-03-26

    Two high pulse contrast (> 95 dB) polarization maintaining all-fiber amplifier chains were coherently combined to generate 0.42 mJ, 1 ns 25 kHz pulses with 79% efficiency despite 38 radians of intra-pulse phase distortion. A recursive intra-pulse phase compensation method was utilized to correct for the large nonlinear chirp providing a path for improved coherent waveform control of nanosecond pulse trains.

  9. Sensitivity of NIF-scale backlit thin shell implosions to hohlraum symmetry in the foot of the ignition drive pulse

    SciTech Connect

    Kirkwood, R K; Milovich, J; Bradley, D K; Schmitt, M; Goldman, S R; Kalantar, D H; Meeker, D; Jones, O S; Pollaine, S M; Amendt, P A; Dewald, E; Edwards, J; Landen, O L; Nikroo, A

    2008-07-28

    A necessary condition for igniting indirectly-driven inertial confinement fusion (ICF) spherical capsules on the National Ignition Facility (NIF) is controlling drive flux asymmetry to the 1% level time-integrated over the pulse and with < 10%/ns swings during the pulse [J. D. Lindl et al., 'The Physics Basis for Ignition using Indirect Drive Targets on the National Ignition Facility', Physics of Plasmas 11, 339 (2003)]. While drive symmetry during the first 2 ns of the pulse can be inferred by using the re-emission pattern from a surrogate high Z sphere [E. Dewald et al. to be published in Rev. Sci. Inst.] and symmetry during the last 5 ns inferred from the shape of fully imploded capsules [A. Hauer, N. Delamater, D. Ress et al. Rev. Sci. Instrum. 66, 672-7 (1995)], the midportion ({approx} 2-10 ns) has been shown to be amenable to detection by the in-flight shape of x-ray backlit thin shell capsules [Pollaine et. al., Physics of Plasmas 8 2357 (2001)]. In this paper, we present sensitivity studies conducted on the University of Rochester's OMEGA laser of the thin shell symmetry measurement technique at near NIF-scale for two candidate capsule ablator materials, Ge-doped CH and Cu-doped Be. These experiments use both point and area backlighting to cast 4.7 keV radiographs of thin 1.4 mm initial-diameter Ge-doped CH and Cu-doped Be shells when converged a factor of {approx} 0.5 x in radius. Distortions in the position of the transmission limb of the shells resulting from drive asymmetries are measured to an accuracy of a few {micro}ms, meeting requirements. The promising results to date allow us to compare measured and predicted distortions and by inference drive asymmetries for the first 4 asymmetry modes as a function of hohlraum illumination conditions.

  10. Characterization of methicillin-resistant coagulase-negative staphylococci (MRCoNS) in retail meat.

    PubMed

    Bhargava, Kanika; Zhang, Yifan

    2014-09-01

    This study was to understand the extent of methicillin-resistant coagulase-negative staphylococci (MRCoNS) serving as a mecA reservoir in retail meat. MRCoNS were isolated from retail meat (beef, chicken, and turkey) in Detroit and characterized by sodA gene sequencing for species identification, staphylococcal cassette chromosome mec (SCCmec) typing, and pulsed-field gel electrophoresis (PFGE). Unique MRCoNS isolates recovered from 25 meat samples were comprised of Staphylococcus sciuri (n = 13), Staphylococcus fleuretti (n = 4), Staphylococcus lentus (n = 3), Staphylococcus epidermidis (n = 2), Staphylococcus vitulinus (n = 1), Staphylococcus saprophyticus (n = 1) and Staphylococcus pasteuri (n = 1). Heterogeneous and composite SCCmec types, including I, III, IV, V, I + V and III + V were identified in 16 isolates. Same SCCmec types were recovered in different staphylococcal species and meat sources. Indistinguishable PFGE patterns were also observed in S. sciuri isolated from beef, chicken, and turkey, and with different SCCmec types. In conclusion, multiple CoNS species can serve as reservoirs for mecA. In addition to the clonal transmission of MRCoNS in meat, horizontal occurrence of SCCmec is observed in staphylococcal species.

  11. Characterization of methicillin-resistant coagulase-negative staphylococci (MRCoNS) in retail meat.

    PubMed

    Bhargava, Kanika; Zhang, Yifan

    2014-09-01

    This study was to understand the extent of methicillin-resistant coagulase-negative staphylococci (MRCoNS) serving as a mecA reservoir in retail meat. MRCoNS were isolated from retail meat (beef, chicken, and turkey) in Detroit and characterized by sodA gene sequencing for species identification, staphylococcal cassette chromosome mec (SCCmec) typing, and pulsed-field gel electrophoresis (PFGE). Unique MRCoNS isolates recovered from 25 meat samples were comprised of Staphylococcus sciuri (n = 13), Staphylococcus fleuretti (n = 4), Staphylococcus lentus (n = 3), Staphylococcus epidermidis (n = 2), Staphylococcus vitulinus (n = 1), Staphylococcus saprophyticus (n = 1) and Staphylococcus pasteuri (n = 1). Heterogeneous and composite SCCmec types, including I, III, IV, V, I + V and III + V were identified in 16 isolates. Same SCCmec types were recovered in different staphylococcal species and meat sources. Indistinguishable PFGE patterns were also observed in S. sciuri isolated from beef, chicken, and turkey, and with different SCCmec types. In conclusion, multiple CoNS species can serve as reservoirs for mecA. In addition to the clonal transmission of MRCoNS in meat, horizontal occurrence of SCCmec is observed in staphylococcal species. PMID:24929717

  12. D-terms from generalized NS-NS fluxes in type II

    NASA Astrophysics Data System (ADS)

    Robbins, Daniel; Wrase, Timm

    2007-12-01

    Orientifolds of type II string theory admit a certain set of generalized NS-NS fluxes, including not only the three-form field strength H, but also metric and non-geometric fluxes, which are related to H by T-duality. We describe in general how these fluxes appear as parameters of an effective Script N = 1 supergravity theory in four dimensions, and in particular how certain generalized NS-NS fluxes can act as charges for R-R axions, leading to D-term contributions to the effective scalar potential. We illustrate these phenomena in type IIB with the example of a certain orientifold of T6/Bbb Z4.

  13. Generation of high-power nanosecond pulses from laser diode-pumped Nd:YAG lasers

    NASA Technical Reports Server (NTRS)

    Chan, Kinpui

    1988-01-01

    Simulation results are used to compare the pulse energy levels and pulse energy widths that can be achieved with LD-pumped Nd:YAG lasers for both the pulse-transmission mode (PTM) and pulse-reflection mode (PRM) Q-switching methods for pulse energy levels up to hundreds of microjoules and pulse widths as short as 1 ns. It is shown that high-power pulses with pulse widths as short as 1 ns can be generated with PTM Q-switched in LD-pumped Nd:YAG lasers. With the PRM Q-switching method, pulse widths as short as 2 ns and pulse energy at the level of a few hundred microjoules can also be achieved but require pumping with 8-10-mJ AlGaAs laser diode arrays.

  14. NetSim Project contributions to ns-3

    2012-05-01

    ns-3 is an external (non-LLNL) open-source framework for modeling computer networks. The LLNL NetSim project uses the ns-3 framework to address specific questions in computer network design, operation, and security. As part of the NetSim work, we develop bug fixes, deature enhancements, and new capabilities for the ns-3 framework. The virtual package referenced here, ns-3-contrib, consists of those developments we have (or will) contribute back to the ns-3 project in source code form, for inclusionmore » in future releases of ns-3.« less

  15. Monomeric nature of dengue virus NS3 helicase and thermodynamic analysis of the interaction with single-stranded RNA

    PubMed Central

    Gebhard, Leopoldo G.; Incicco, J. Jeremías; Smal, Clara; Gallo, Mariana; Gamarnik, Andrea V.; Kaufman, Sergio B.

    2014-01-01

    Dengue virus nonstructural protein 3 (NS3) is a multifunctional protein formed by a superfamily-2 RNA helicase linked to a protease domain. In this work, we report results from in vitro experiments designed to determine the oligomeric state of dengue virus NS3 helicase (NS3h) and to characterize fundamental properties of the interaction with single-stranded (ss)RNA. Pulsed field gradient-NMR spectroscopy was used to determine the effective hydrodynamic radius of NS3h, which was constant over a wide range of protein concentrations in the absence and presence of ssRNA. Size exclusion chromatography-static light scattering experiments showed that NS3h eluted as a monomeric molecule even in the presence of ssRNA. Binding of NS3h to ssRNA was studied by quantitative fluorescence titrations using fluorescein-labeled and unlabeled ssRNA oligonucleotides of different lengths, and the effect of the fluorescein label on the interaction parameters was also analyzed. Experimental results were well described by a statistical thermodynamic model based on the theory of non-specific interactions of large ligands to a one-dimensional lattice. We found that binding of NS3h to ssRNA oligonucleotides and to poly(A) is characterized by minimum and occluded binding site sizes both of 10 nucleotides and by a weak positive cooperativity between adjacent proteins. PMID:25223789

  16. Laser Pulse-Stretching Using Multiple Optical Ring-Cavities

    NASA Technical Reports Server (NTRS)

    Kojima, Jun; Nguyen, Quang-Viet; Lee, Chi-Ming (Technical Monitor)

    2002-01-01

    We describe a simple and passive nanosecond-long (ns-long) laser 'pulse-stretcher' using multiple optical ring-cavities. We present a model of the pulse-stretching process for an arbitrary number of optical ring-cavities. Using the model, we optimize the design of a pulse-stretcher for use in a spontaneous Raman scattering excitation system that avoids laser-induced plasma spark problems. From the optimized design, we then experimentally demonstrate and verify the model with a 3-cavity pulse-stretcher system that converts a 1000 mJ, 8.4 ns-long input laser pulse into an approximately 75 ns-long (FWHM) output laser pulse with a peak power reduction of 0.10X, and an 83% efficiency.

  17. 28 CFR 2.10 - Date service of sentence commences.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 28 Judicial Administration 1 2013-07-01 2013-07-01 false Date service of sentence commences. 2.10 Section 2.10 Judicial Administration DEPARTMENT OF JUSTICE PAROLE, RELEASE, SUPERVISION AND RECOMMITMENT... absconded from parole supervision; or (4) Comes within the provisions of paragraph (b) of this section....

  18. 28 CFR 2.10 - Date service of sentence commences.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 28 Judicial Administration 1 2011-07-01 2011-07-01 false Date service of sentence commences. 2.10 Section 2.10 Judicial Administration DEPARTMENT OF JUSTICE PAROLE, RELEASE, SUPERVISION AND RECOMMITMENT... absconded from parole supervision; or (4) Comes within the provisions of paragraph (b) of this section....

  19. 28 CFR 2.10 - Date service of sentence commences.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 28 Judicial Administration 1 2012-07-01 2012-07-01 false Date service of sentence commences. 2.10 Section 2.10 Judicial Administration DEPARTMENT OF JUSTICE PAROLE, RELEASE, SUPERVISION AND RECOMMITMENT... absconded from parole supervision; or (4) Comes within the provisions of paragraph (b) of this section....

  20. 28 CFR 2.10 - Date service of sentence commences.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 28 Judicial Administration 1 2014-07-01 2014-07-01 false Date service of sentence commences. 2.10 Section 2.10 Judicial Administration DEPARTMENT OF JUSTICE PAROLE, RELEASE, SUPERVISION AND RECOMMITMENT... absconded from parole supervision; or (4) Comes within the provisions of paragraph (b) of this section....

  1. 10 CFR 960.5-2-10 - Hydrology.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 10 Energy 4 2010-01-01 2010-01-01 false Hydrology. 960.5-2-10 Section 960.5-2-10 Energy DEPARTMENT OF ENERGY GENERAL GUIDELINES FOR THE PRELIMINARY SCREENING OF POTENTIAL SITES FOR A NUCLEAR WASTE REPOSITORY Preclosure Guidelines Ease and Cost of Siting, Construction, Operation, and Closure §...

  2. 46 CFR 2.10-101 - Annual vessel inspection fee.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... listed in table 2.10-101 for its vessel category. (2) A vessel certificated for more than one service must pay only the higher of the two applicable fees in table 2.10-101 of this section. (b) The vessel... Inspection, reinspections (annual and periodic inspections), hull (drydock) inspections,...

  3. 46 CFR 2.10-101 - Annual vessel inspection fee.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... listed in table 2.10-101 for its vessel category. (2) A vessel certificated for more than one service must pay only the higher of the two applicable fees in table 2.10-101 of this section. (b) The vessel... Inspection, reinspections (annual and periodic inspections), hull (drydock) inspections,...

  4. 10 CFR 960.5-2-10 - Hydrology.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 10 Energy 4 2014-01-01 2014-01-01 false Hydrology. 960.5-2-10 Section 960.5-2-10 Energy DEPARTMENT OF ENERGY GENERAL GUIDELINES FOR THE PRELIMINARY SCREENING OF POTENTIAL SITES FOR A NUCLEAR WASTE REPOSITORY Preclosure Guidelines Ease and Cost of Siting, Construction, Operation, and Closure §...

  5. 21 CFR 2.10 - Examination and investigation samples.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 1 2013-04-01 2013-04-01 false Examination and investigation samples. 2.10 Section 2.10 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL... samples. (a)(1) When any officer or employee of the Department collects a sample of a food, drug,...

  6. 21 CFR 2.10 - Examination and investigation samples.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 1 2014-04-01 2014-04-01 false Examination and investigation samples. 2.10 Section 2.10 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL... samples. (a)(1) When any officer or employee of the Department collects a sample of a food, drug,...

  7. 21 CFR 2.10 - Examination and investigation samples.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 1 2012-04-01 2012-04-01 false Examination and investigation samples. 2.10 Section 2.10 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL... samples. (a)(1) When any officer or employee of the Department collects a sample of a food, drug,...

  8. 28 CFR 2.10 - Date service of sentence commences.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 28 Judicial Administration 1 2010-07-01 2010-07-01 false Date service of sentence commences. 2.10 Section 2.10 Judicial Administration DEPARTMENT OF JUSTICE PAROLE, RELEASE, SUPERVISION AND RECOMMITMENT OF PRISONERS, YOUTH OFFENDERS, AND JUVENILE DELINQUENTS United States Code Prisoners and Parolees §...

  9. A new pulse width reduction technique for pulsed electron paramagnetic resonance spectroscopy.

    PubMed

    Ohba, Yasunori; Nakazawa, Shigeaki; Kazama, Shunji; Mizuta, Yukio

    2008-03-01

    We present a new technique for a microwave pulse modulator that generates a short microwave pulse of approximately 1ns for use in an electron paramagnetic resonance (EPR) spectrometer. A quadruple-frequency multiplier that generates a signal of 16-20GHz from an input of 4-5GHz was employed to reduce the rise and fall times of the pulse prepared by a PIN diode switch. We examined the transient response characteristics of a commercial frequency multiplier and found that the device can function as a multiplier for pulsed signal even though it was designed for continuous wave operation. We applied the technique to a Ku band pulsed EPR spectrometer and successfully observed a spin echo signal with a broad excitation bandwidth of approximately 1.6mT using 80 degrees pulses of 1.5ns. PMID:18248828

  10. Splicing of influenza A virus NS1 mRNA is independent of the viral NS1 protein.

    PubMed

    Robb, Nicole C; Jackson, David; Vreede, Frank T; Fodor, Ervin

    2010-09-01

    RNA segment 8 (NS) of influenza A virus encodes two proteins. The NS1 protein is translated from the unspliced primary mRNA transcript, whereas the second protein encoded by this segment, NS2/NEP, is translated from a spliced mRNA. Splicing of influenza NS1 mRNA is thought to be regulated so that the levels of NS2 spliced transcripts are approximately 10 % of total NS mRNA. Regulation of splicing of the NS1 mRNA has been studied at length, and a number of often-contradictory control mechanisms have been proposed. In this study, we used (32)P-labelled gene-specific primers to investigate influenza A NS1 mRNA splicing regulation. It was found that the efficiency of splicing of NS1 mRNA was maintained at similar levels in both virus infection and ribonucleoprotein-reconstitution assays, and NS2 mRNA comprised approximately 15 % of total NS mRNA in both assays. The effect of NS1 protein expression on the accumulation of viral NS2 mRNA and spliced cellular beta-globin mRNA was analysed, and it was found that NS1 protein expression reduced spliced beta-globin mRNA levels, but had no effect on the accumulation of NS2 mRNA. We conclude that the NS1 protein specifically inhibits the accumulation of cellular RNA polymerase II-driven mRNAs, but does not affect the splicing of its own viral NS1 mRNA.

  11. Using shaped pulses to probe energy deposition during laser-induced damage of SiO2 surfaces

    SciTech Connect

    Carr, C W; Cross, D; Feit, M D; Bude, J D

    2008-10-24

    Laser-induced damage initiation in silica has been shown to follow a power-law behavior with respect to pulse-length. Models based on thermal diffusion physics can successfully predict this scaling and the effect of pulse shape for pulses between about 3ns and 10ns. In this work we use sophisticated new measurement techniques and novel pulse shape experiments to test the limits of this scaling. We show that simple pulse length scaling fails for pulses below about 3ns. Furthermore, double pulse initiation experiments suggest that energy absorbed by the first pulse is lost on time scales much shorter than would be predicted for thermal diffusion. This time scale for energy loss can be strongly modulated by maintaining a small but non-zero intensity between the pulses. By producing damage with various pulse shapes and pulse trains it is demonstrated that the properties of any hypothetical thermal absorber become highly constrained.

  12. A compact high-voltage pulse generator based on pulse transformer with closed magnetic core.

    PubMed

    Zhang, Yu; Liu, Jinliang; Cheng, Xinbing; Bai, Guoqiang; Zhang, Hongbo; Feng, Jiahuai; Liang, Bo

    2010-03-01

    A compact high-voltage nanosecond pulse generator, based on a pulse transformer with a closed magnetic core, is presented in this paper. The pulse generator consists of a miniaturized pulse transformer, a curled parallel strip pulse forming line (PFL), a spark gap, and a matched load. The innovative design is characterized by the compact structure of the transformer and the curled strip PFL. A new structure of transformer windings was designed to keep good insulation and decrease distributed capacitance between turns of windings. A three-copper-strip structure was adopted to avoid asymmetric coupling of the curled strip PFL. When the 31 microF primary capacitor is charged to 2 kV, the pulse transformer can charge the PFL to 165 kV, and the 3.5 ohm matched load can deliver a high-voltage pulse with a duration of 9 ns, amplitude of 84 kV, and rise time of 5.1 ns. When the load is changed to 50 ohms, the output peak voltage of the generator can be 165 kV, the full width at half maximum is 68 ns, and the rise time is 6.5 ns.

  13. Purification and crystallization of dengue and West Nile virus NS2B–NS3 complexes

    SciTech Connect

    D’Arcy, Allan Chaillet, Maxime; Schiering, Nikolaus; Villard, Frederic; Lim, Siew Pheng; Lefeuvre, Peggy; Erbel, Paul

    2006-02-01

    Crystals of dengue serotype 2 and West Nile virus NS2B–NS3 protease complexes have been obtained and the crystals of both diffract to useful resolution. Sample homogeneity was essential for obtaining X-ray-quality crystals of the dengue protease. Controlled proteolysis produced a crystallizable fragment of the apo West Nile virus NS2B–NS3 and crystals were also obtained in the presence of a peptidic inhibitor. Both dengue and West Nile virus infections are an increasing risk to humans, not only in tropical and subtropical areas, but also in North America and parts of Europe. These viral infections are generally transmitted by mosquitoes, but may also be tick-borne. Infection usually results in mild flu-like symptoms, but can also cause encephalitis and fatalities. Approximately 2799 severe West Nile virus cases were reported this year in the United States, resulting in 102 fatalities. With this alarming increase in the number of West Nile virus infections in western countries and the fact that dengue virus already affects millions of people per year in tropical and subtropical climates, there is a real need for effective medicines. A possible therapeutic target to combat these viruses is the protease, which is essential for virus replication. In order to provide structural information to help to guide a lead identification and optimization program, crystallizations of the NS2B–NS3 protease complexes from both dengue and West Nile viruses have been initiated. Crystals that diffract to high resolution, suitable for three-dimensional structure determinations, have been obtained.

  14. Histopathology of ultrashort-laser-pulse retinal damage

    NASA Astrophysics Data System (ADS)

    Toth, Cynthia A.; Narayan, Drew G.; Osborne, Catherine; Rockwell, Benjamin A.; Stein, Cindy D.; Amnotte, Rodney E.; DiCarlo, Cheryl D.; Roach, William P.; Noojin, Gary D.; Cain, Clarence P.

    1996-05-01

    Recent studies of retinal damage due to ultrashort laser pulses have shown interesting behavior. Laser induced retinal damage for ultrashort (i.e. less than 1 ns) laser pulses is produced at lower energies than in the nanosecond to microsecond laser pulse regime and the energy required for hemorrhagic lesions is much greater times greater for the nanosecond regime. We investigated the tissue effects exhibited in histopathology of retinal tissues exposed to ultrashort laser pulses.

  15. Ns-scale time-resolved laser induced fluorescence imaging for detection of fecal contamination on apples

    NASA Astrophysics Data System (ADS)

    Kim, Moon S.; Lefcourt, Alan M.; Chen, Yud-Ren

    2004-11-01

    Our laboratory has been utilizing fluorescence techniques as a potential means for detection of quality and wholesomeness of food products. A system with a short pulse light source such as a laser coupled with a gated detector can be used to harvest fluorescence in ambient light conditions from biological samples with relatively low fluorescence yields. We present a versatile multispectral laser-induced fluorescence (LIF) imaging system capable of ns-scale time resolved fluorescence. The system is equipped with a tunable pulse laser system that emits in the visible range from 410 nm to 690 nm. Ns-scale, time-dependent multispectral fluorescence emissions of apples contaminated with a range of diluted cow feces were acquired. Four spectral bands, F670, F680, F685 and F730, centered near the emission peak wavelengths of the major constituents responsible for the red fluorescence emissions from apples artificially contaminated with cow feces were examined to determine a suitable single red fluorescence band and optimal ns-gate window for detection of fecal contamination on apples. The results based on the ns decay curves showed that 670 nm with 10 nm full width at half maximum (FWHM) at a gate-delay of 4 ns from the laser excitation peak provided the greatest differences in time-dependent fluorescence responses between feces contaminated spots and apples surfaces.

  16. Nanosecond Pulsed Electric Field Stimulation of Reactive Oxygen Species in Human Pancreatic Cancer Cells is Ca2+-Dependent

    PubMed Central

    Nuccitelli, Richard; Lui, Kaying; Kreis, Mark; Athos, Brian; Nuccitelli, Pamela

    2013-01-01

    The cellular response to 100 ns pulsed electric fields (nsPEF) exposure includes the formation of transient nanopores in the plasma membrane and organelle membranes, an immediate increase in intracellular Ca2+, an increase in reactive oxygen species (ROS), DNA fragmentation and caspase activation. 100 ns, 30 kV/cm nsPEF stimulates an increase in ROS proportional to the pulse number. This increase is inhibited by the anti-oxidant, Trolox, as well as the presence of Ca2+ chelators in the intracellular and extracellular media. This suggests that the nsPEF-triggered Ca2+ increase is required for ROS generation. PMID:23680664

  17. Autonomous portable pulsed-periodical generator of high-power radiofrequency-pulses based on gas discharge with hollow cathode.

    PubMed

    Bulychev, Sergey V; Dubinov, Alexander E; L'vov, Igor L; Popolev, Vyacheslav L; Sadovoy, Sergey A; Sadchikov, Eugeny A; Selemir, Victor D; Valiulina, Valeria K; Vyalykh, Dmitry V; Zhdanov, Victor S

    2016-05-01

    Portable autonomous generator of high-power RF-pulses based on the gas discharge with hollow cathode has been designed, fabricated, and tested. Input and output characteristics are the following: discharge current amplitude is 800 A, duration of generated RF-pulses is 350 ns, carrier frequency is ∼90 MHz, power in RF-pulse is 0.5 MW, pulse repetition rate is 0.5 kHz, and device efficiency is ∼25%.

  18. Autonomous portable pulsed-periodical generator of high-power radiofrequency-pulses based on gas discharge with hollow cathode

    NASA Astrophysics Data System (ADS)

    Bulychev, Sergey V.; Dubinov, Alexander E.; L'vov, Igor L.; Popolev, Vyacheslav L.; Sadovoy, Sergey A.; Sadchikov, Eugeny A.; Selemir, Victor D.; Valiulina, Valeria K.; Vyalykh, Dmitry V.; Zhdanov, Victor S.

    2016-05-01

    Portable autonomous generator of high-power RF-pulses based on the gas discharge with hollow cathode has been designed, fabricated, and tested. Input and output characteristics are the following: discharge current amplitude is 800 A, duration of generated RF-pulses is 350 ns, carrier frequency is ˜90 MHz, power in RF-pulse is 0.5 MW, pulse repetition rate is 0.5 kHz, and device efficiency is ˜25%.

  19. Mechanistic and kinetic characterization of hepatitis C virus NS3 protein interactions with NS4A and protease inhibitors.

    PubMed

    Geitmann, Matthis; Dahl, Göran; Danielson, U Helena

    2011-01-01

    The mechanism and kinetics of the interactions between ligands and immobilized full-length hepatitis C virus (HCV) genotype 1a NS3 have been characterized by SPR biosensor technology. The NS3 interactions for a series of NS3 protease inhibitors as well as for the NS4A cofactor, represented by a peptide corresponding to the sequence interacting with the enzyme, were found to be heterogeneous. It may represent interactions with two stable conformations of the protein. The NS3-NS4A interaction consisted of a high-affinity (K(D) = 50 nM) and a low-affinity (K(D) = 2 µM) interaction, contributing equally to the overall binding. By immobilizing NS3 alone or together with NS4A it was shown that all inhibitors had a higher affinity for NS3 in the presence of NS4A. NS4A thus has a direct effect on the binding of inhibitors to NS3 and not only on catalysis. As predicted, the mechanism-based inhibitor VX 950 exhibited a time-dependent interaction with a slow formation of a stable complex. BILN 2061 or ITMN-191 showed no signs of time-dependent interactions, but ITMN-191 had the highest affinity of the tested compounds, with both the slowest dissociation (k(off)) and fastest association rate, closely followed by BILN 2061. The k(off) for the inhibitors correlated strongly with their NS3 protease inhibitory effect as well as with their effect on replication of viral proteins in replicon cell cultures, confirming the relevance of the kinetic data. This approach for obtaining kinetic and mechanistic data for NS3 protease inhibitor and cofactor interactions is expected to be of importance for understanding the characteristics of HCV NS3 functionality as well as for anti-HCV lead discovery and optimization. PMID:21194118

  20. Long implosion time (240 ns) Z-pinch experiments with a large diameter (12 cm) double-shell nozzle

    NASA Astrophysics Data System (ADS)

    Levine, J. S.; Banister, J. W.; Failor, B. H.; Qi, N.; Song, Y.; Sze, H. M.; Fisher, A.

    2004-05-01

    Recently, an 8 cm diameter double-shell nozzle has produced argon Z pinches with high K-shell yields with implosion time of 210 ns. To produce even longer implosion time Z pinches for facilities such as Decade Quad [D. Price, et al., "Electrical and Mechanical Design of the Decade Quad in PRS Mode," in Proceedings of the 12th IEEE Pulsed Power Conference, Monterey, CA, edited by C. Stallings and H. Kirbie (IEEE, New York, 1999), p. 489] (9 MA short circuit current at 300 ns), a larger nozzle (12 cm outer diameter) was designed and fabricated. During initial testing on Double-EAGLE [P. Sincerny et al., Proceedings of the 5th IEEE Pulsed Power Conference, Arlington, VA, edited by M. F. Rose and P. J. Turchi (IEEE, New York, 1985), p. 151], 9 kJ of argon K-shell radiation in a 6 ns full width at half maximum pulse was produced with a 240 ns implosion. The initial gas distributions produced by various nozzle configurations have been measured and their impact on the final radiative characteristics of the pinch are presented. The addition of a central jet to increase the initial gas density near the axis is observed to enhance the pinch quality, increasing K-shell yield by 17% and power by 40% in the best configuration tested.

  1. Supergiant pulses from extragalactic neutron stars

    NASA Astrophysics Data System (ADS)

    Cordes, J. M.; Wasserman, Ira

    2016-03-01

    We consider radio bursts that originate from extragalactic neutron stars (NSs) by addressing three questions about source distances. What are the physical limitations on coherent radiation at GHz frequencies? Do they permit detection at cosmological distances? How many bursts per NS are needed to produce the inferred burst rate ˜103-104sky-1 d-1? The burst rate is comparable to the NS formation rate in a Hubble volume, requiring only one per NS if they are bright enough. Radiation physics suggests a closer population, requiring more bursts per NS and increasing the chances for repeats. Bursts comprise sub-ns, coherent shot pulses superposed incoherently to produce ms-duration ˜1 Jy amplitudes; each shot pulse can be much weaker than 1 Jy, placing less restrictive requirements on the emission process. None the less, single shot pulses are similar to the extreme, unresolved (<0.4 ns) MJy shot pulse seen from the Crab pulsar, consistent with coherent curvature radiation emitted near the light cylinder by an almost neutral clump with net charge ˜± 1021e and total energy ≳ 1023 erg. Bursts from Gpc distances require incoherent superposition of {˜ } 10^{12}d_Gpc^2 shot pulses or a total energy ≳ 10^{35} d_Gpc^2 erg. The energy reservoir near the light cylinder limits the detection distance to ≲ few × 100 Mpc for a fluence ˜1 Jy ms unless conditions are more extreme than for the Crab pulsar, such as in magnetars. We discuss contributions to dispersion measures from galaxy clusters and we propose tests for the overall picture presented.

  2. Determinants of Dengue Virus NS4A Protein Oligomerization

    PubMed Central

    Lee, Chia Min; Xie, Xuping; Zou, Jing; Li, Shi-Hua; Lee, Michelle Yue Qi; Dong, Hongping; Qin, Cheng-Feng; Kang, Congbao

    2015-01-01

    ABSTRACT Flavivirus NS4A protein induces host membrane rearrangement and functions as a replication complex component. The molecular details of how flavivirus NS4A exerts these functions remain elusive. Here, we used dengue virus (DENV) as a model to characterize and demonstrate the biological relevance of flavivirus NS4A oligomerization. DENV type 2 (DENV-2) NS4A protein forms oligomers in infected cells or when expressed alone. Deletion mutagenesis mapped amino acids 50 to 76 (spanning the first transmembrane domain [TMD1]) of NS4A as the major determinant for oligomerization, while the N-terminal 50 residues contribute only slightly to the oligomerization. Nuclear magnetic resonance (NMR) analysis of NS4A amino acids 17 to 80 suggests that residues L31, L52, E53, G66, and G67 could participate in oligomerization. Ala substitution for 15 flavivirus conserved NS4A residues revealed that these amino acids are important for viral replication. Among the 15 mutated NS4A residues, 2 amino acids (E50A and G67A) are located within TMD1. Both E50A and G67A attenuated viral replication, decreased NS4A oligomerization, and reduced NS4A protein stability. In contrast, NS4A oligomerization was not affected by the replication-defective mutations (R12A, P49A, and K80A) located outside TMD1. trans complementation experiments showed that expression of wild-type NS4A alone was not sufficient to rescue the replication-lethal NS4A mutants. However, the presence of DENV-2 replicons could partially restore the replication defect of some lethal NS4A mutants (L26A and K80A), but not others (L60A and E122A), suggesting an unidentified mechanism governing the outcome of complementation in a mutant-dependent manner. Collectively, the results have demonstrated the importance of TMD1-mediated NS4A oligomerization in flavivirus replication. IMPORTANCE We report that DENV NS4A forms oligomers. Such NS4A oligomerization is mediated mainly through amino acids 50 to 76 (spanning the first

  3. Alternative method for gas detection using pulsed quantum-cascade-laser spectrometers.

    PubMed

    Grouiez, Bruno; Parvitte, Bertrand; Joly, Lilian; Zeninari, Virginie

    2009-01-15

    Pulsed quantum-cascade-laser (QCL) spectrometers are usually used to detect atmospheric gases with either the interpulse technique (short pulses, typically 5-20 ns) or the intrapulse technique (long pulses, typically 500-800 ns). Each of these techniques has many drawbacks, which we present. Particularly the gas absorption spectra are generally distorted. We demonstrate the possibility to use intermediate pulses (typically 50-100 ns) for gas detection using pulsed QCL spectrometers. IR spectra of ammonia recorded in the 10 microm region are presented in various conditions of pulse emission. These experiences demonstrate the large influence of the pulse shape on the recorded spectrum and the importance to use our alternative method for gas detection with pulsed QCL spectrometers.

  4. Nanosecond pulsed electric field ablation of hepatocellular carcinoma.

    PubMed

    Beebe, Stephen J; Chen, Xinhua; Liu, Jie A; Schoenbach, Karl H

    2011-01-01

    Hepatocellular carcinoma often evades effective therapy and recurrences are frequent. Recently, nanosecond pulsed electric field (nsPEF) ablation using pulse power technology has emerged as a local-regional, non-thermal, and non-drug therapy for skin cancers. In the studies reported here we use nsPEFs to ablate murine, rat and human HCCs in vitro and an ectopic murine Hepa 1-6 HCC in vivo. Using pulses with 60 or 300 ns and electric fields as high as 60 kV/cm, murine Hepa 1-6, rat N1S1 and human HepG2 HCC are readily eliminated with changes in caspase-3 activity. Interestingly caspase activities increase in the mouse and human model and decrease in the rat model as electric field strengths are increased. In vivo, while sham treated control mice survived an average of 15 days after injection and before humane euthanasia, Hepa 1-6 tumors were eliminated for longer than 50 days with 3 treatments using one hundred pulses with 100 ns at 55 kV/cm. Survival was 40% in mice treated with 30 ns pulses at 55 kV/cm. This study demonstrates that nsPEF ablation is not limited to effectively treating skin cancers and provides a rationale for treating orthotopic hepatocellular carcinoma in pre-clinical applications and ultimately in clinical trials.

  5. Wavelength stabilized ns-MOPA diode laser system with 16 W peak power and a spectral line width below 10 pm

    NASA Astrophysics Data System (ADS)

    Nghiem Vu, Thi; Klehr, Andreas; Sumpf, Bernd; Wenzel, Hans; Erbert, Götz; Tränkle, Günther

    2014-03-01

    A master oscillator power amplifier system for the generation of ns-pulses with high peak power, stabilized wavelength and narrow spectral line width will be presented. The master oscillator is a distributed feedback (DFB) ridge waveguide (RW) laser. The tapered amplifier consists of three RW sections and one flared gain-guided section. The DFB laser is operated in continuous wave mode and emits at 1064 nm with a spectral line width below 10 pm. One RW section of the amplifier acts as an optical gate for pulse selection. The tapered section amplifies the generated optical pulse. By adjusting the delay time between the current pulses injected into the picker and into the tapered section, respectively, the power of the amplified spontaneous emission was reduced below 1% of the average laser power. For an optical pulse length of 2 ns, a peak power of 16 W was obtained. A side mode suppression ratio better than 46 dB was observed.

  6. The role of mass removal mechanisms in the onset of ns-laser induced plasma formation

    SciTech Connect

    Autrique, D.; Clair, G.; L'Hermite, D.; Alexiades, V.; Bogaerts, A.; Rethfeld, B.

    2013-07-14

    The present study focuses on the role of mass removal mechanisms in ns-laser ablation. A copper sample is placed in argon, initially set at standard pressure and temperature. Calculations are performed for a 6 ns laser pulse with a wavelength of 532 nm and laser fluences up to 10 J/cm{sup 2}. The transient behavior in and above the copper target is described by a hydrodynamic model. Transmission profiles and ablation depths are compared with experimental results and similar trends are found. Our calculations reveal an interesting self-inhibiting mechanism: volumetric mass removal in the supercritical region triggers plasma shielding and therefore stops proceeding. This self-limiting process indicates that volumetric mass removal does not necessarily result in large ablation depths.

  7. The role of mass removal mechanisms in the onset of ns-laser induced plasma formation

    NASA Astrophysics Data System (ADS)

    Autrique, D.; Clair, G.; L'Hermite, D.; Alexiades, V.; Bogaerts, A.; Rethfeld, B.

    2013-07-01

    The present study focuses on the role of mass removal mechanisms in ns-laser ablation. A copper sample is placed in argon, initially set at standard pressure and temperature. Calculations are performed for a 6 ns laser pulse with a wavelength of 532 nm and laser fluences up to 10 J/cm2. The transient behavior in and above the copper target is described by a hydrodynamic model. Transmission profiles and ablation depths are compared with experimental results and similar trends are found. Our calculations reveal an interesting self-inhibiting mechanism: volumetric mass removal in the supercritical region triggers plasma shielding and therefore stops proceeding. This self-limiting process indicates that volumetric mass removal does not necessarily result in large ablation depths.

  8. Compact pulse forming line using barium titanate ceramic material.

    PubMed

    Kumar Sharma, Surender; Deb, P; Shukla, R; Prabaharan, T; Shyam, A

    2011-11-01

    Ceramic material has very high relative permittivity, so compact pulse forming line can be made using these materials. Barium titanate (BaTiO(3)) has a relative permittivity of 1200 so it is used for making compact pulse forming line (PFL). Barium titanate also has piezoelectric effects so it cracks during high voltages discharges due to stresses developed in it. Barium titanate is mixed with rubber which absorbs the piezoelectric stresses when the PFL is charged and regain its original shape after the discharge. A composite mixture of barium titanate with the neoprene rubber is prepared. The relative permittivity of the composite mixture is measured to be 85. A coaxial pulse forming line of inner diameter 120 mm, outer diameter 240 mm, and length 350 mm is made and the composite mixture of barium titanate and neoprene rubber is filled between the inner and outer cylinders. The PFL is charged up to 120 kV and discharged into 5 Ω load. The voltage pulse of 70 kV, 21 ns is measured across the load. The conventional PFL is made up of oil or plastics dielectrics with the relative permittivity of 2-10 [D. R. Linde, CRC Handbook of Chemistry and Physics, 90th ed. (CRC, 2009); Xia et al., Rev. Sci. Instrum. 79, 086113 (2008); Yang et al., Rev. Sci. Instrum. 81, 43303 (2010)], which increases the length of PFL. We have reported the compactness in length achieved due to increase in relative permittivity of composite mixture by adding barium titanate in neoprene rubber. PMID:22129008

  9. Compact pulse forming line using barium titanate ceramic material.

    PubMed

    Kumar Sharma, Surender; Deb, P; Shukla, R; Prabaharan, T; Shyam, A

    2011-11-01

    Ceramic material has very high relative permittivity, so compact pulse forming line can be made using these materials. Barium titanate (BaTiO(3)) has a relative permittivity of 1200 so it is used for making compact pulse forming line (PFL). Barium titanate also has piezoelectric effects so it cracks during high voltages discharges due to stresses developed in it. Barium titanate is mixed with rubber which absorbs the piezoelectric stresses when the PFL is charged and regain its original shape after the discharge. A composite mixture of barium titanate with the neoprene rubber is prepared. The relative permittivity of the composite mixture is measured to be 85. A coaxial pulse forming line of inner diameter 120 mm, outer diameter 240 mm, and length 350 mm is made and the composite mixture of barium titanate and neoprene rubber is filled between the inner and outer cylinders. The PFL is charged up to 120 kV and discharged into 5 Ω load. The voltage pulse of 70 kV, 21 ns is measured across the load. The conventional PFL is made up of oil or plastics dielectrics with the relative permittivity of 2-10 [D. R. Linde, CRC Handbook of Chemistry and Physics, 90th ed. (CRC, 2009); Xia et al., Rev. Sci. Instrum. 79, 086113 (2008); Yang et al., Rev. Sci. Instrum. 81, 43303 (2010)], which increases the length of PFL. We have reported the compactness in length achieved due to increase in relative permittivity of composite mixture by adding barium titanate in neoprene rubber.

  10. Dengue virus NS1 triggers endothelial permeability and vascular leak that is prevented by NS1 vaccination.

    PubMed

    Beatty, P Robert; Puerta-Guardo, Henry; Killingbeck, Sarah S; Glasner, Dustin R; Hopkins, Kaycie; Harris, Eva

    2015-09-01

    The four dengue virus serotypes (DENV1 to DENV4) are mosquito-borne flaviviruses that cause up to ~100 million cases of dengue annually worldwide. Severe disease is thought to result from immunopathogenic processes involving serotype cross-reactive antibodies and T cells that together induce vasoactive cytokines, causing vascular leakage that leads to shock. However, no viral proteins have been directly implicated in triggering endothelial permeability, which results in vascular leakage. DENV nonstructural protein 1 (NS1) is secreted and circulates in patients' blood during acute infection; high levels of NS1 are associated with severe disease. We show that inoculation of mice with DENV NS1 alone induces both vascular leakage and production of key inflammatory cytokines. Furthermore, simultaneous administration of NS1 with a sublethal dose of DENV2 results in a lethal vascular leak syndrome. We also demonstrate that NS1 from DENV1, DENV2, DENV3, and DENV4 triggers endothelial barrier dysfunction, causing increased permeability of human endothelial cell monolayers in vitro. These pathogenic effects of physiologically relevant amounts of NS1 in vivo and in vitro were blocked by NS1-immune polyclonal mouse serum or monoclonal antibodies to NS1, and immunization of mice with NS1 from DENV1 to DENV4 protected against lethal DENV2 challenge. These findings add an important and previously overlooked component to the causes of dengue vascular leak, identify a new potential target for dengue therapeutics, and support inclusion of NS1 in dengue vaccines. PMID:26355030

  11. NMR analysis of a novel enzymatically active unlinked dengue NS2B-NS3 protease complex.

    PubMed

    Kim, Young Mee; Gayen, Shovanlal; Kang, CongBao; Joy, Joma; Huang, Qiwei; Chen, Angela Shuyi; Wee, John Liang Kuan; Ang, Melgious Jin Yan; Lim, Huichang Annie; Hung, Alvin W; Li, Rong; Noble, Christian G; Lee, Le Tian; Yip, Andy; Wang, Qing-Yin; Chia, Cheng San Brian; Hill, Jeffrey; Shi, Pei-Yong; Keller, Thomas H

    2013-05-01

    The dengue virus (DENV) is a mosquito-borne pathogen responsible for an estimated 100 million human infections annually. The viral genome encodes a two-component trypsin-like protease that contains the cofactor region from the nonstructural protein NS2B and the protease domain from NS3 (NS3pro). The NS2B-NS3pro complex plays a crucial role in viral maturation and has been identified as a potential drug target. Using a DENV protease construct containing NS2B covalently linked to NS3pro via a Gly4-Ser-Gly4 linker ("linked protease"), previous x-ray crystal structures show that the C-terminal fragment of NS2B is remote from NS3pro and exists in an open state in the absence of an inhibitor; however, in the presence of an inhibitor, NS2B complexes with NS3pro to form a closed state. This linked enzyme produced NMR spectra with severe signal overlap and line broadening. To obtain a protease construct with a resolved NMR spectrum, we expressed and purified an unlinked protease complex containing a 50-residue segment of the NS2B cofactor region and NS3pro without the glycine linker using a coexpression system. This unlinked protease complex was catalytically active at neutral pH in the absence of glycerol and produced dispersed cross-peaks in a (1)H-(15)N heteronuclear single quantum correlation spectrum that enabled us to conduct backbone assignments using conventional techniques. In addition, titration with an active-site peptide aldehyde inhibitor and paramagnetic relaxation enhancement studies demonstrated that the unlinked DENV protease exists predominantly in a closed conformation in solution. This protease complex can serve as a useful tool for drug discovery against DENV.

  12. Cooperative pulses

    NASA Astrophysics Data System (ADS)

    Braun, Michael; Glaser, Steffen J.

    2010-11-01

    We introduce the concept of cooperative (COOP) pulses which are designed to compensate each other's imperfections. In multi-scan experiments, COOP pulses can cancel undesired signal contributions, complementing and generalizing phase cycles. COOP pulses can be efficiently optimized using an extended version of the optimal-control-based gradient ascent pulse engineering (GRAPE) algorithm. The advantage of the COOP approach is experimentally demonstrated for broadband and band-selective pulses.

  13. Low-noise detector and amplifier design for 100 ns direct detection CO{sub 2} LIDAR receiver

    SciTech Connect

    Cafferty, M.M.; Cooke, B.J.; Laubscher, B.E.; Olivas, N.L.; Fuller, K.

    1997-06-01

    The development and test results of a prototype detector/amplifier design for a background limited, pulsed 100 ns, 10--100 kHz repetition rate LIDAR/DIAL receiver system are presented. Design objectives include near-matched filter detection of received pulse amplitude and round trip time-of-flight, and the elimination of excess correlated detector/amplifier noise for optimal pulse averaging. A novel pole-zero cancellation amplifier, coupled with a state-of-the-art SBRC (Santa Barbara Research Center) infrared detector was implemented to meet design objectives. The pole-zero cancellation amplifier utilizes a tunable, pseudo-matched filter technique to match the width of the laser pulse to the shaping time of the filter for optimal SNR performance. Low frequency correlated noise, (l/f and drift noise) is rejected through a second order high gain feedback loop. The amplifier also employs an active detector bias stage minimizing detector drift. Experimental results will be provided that demonstrate near-background limited, 100 ns pulse detection performance given a 8.5--11.5 {micro}m (300 K B.B.) radiant background, with the total noise floor spectrally white for optimal pulse averaging efficiency.

  14. A Closer Look at the NS1 of Influenza Virus

    PubMed Central

    Dundon, William G.; Capua, Ilaria

    2009-01-01

    The Non-Structural 1 (NS1) protein is a multifactorial protein of type A influenza viruses that plays an important role in the virulence of the virus. A large amount of what we know about this protein has been obtained from studies using human influenza isolates and, consequently, the human NS1 protein. The current global interest in avian influenza, however, has highlighted a number of sequence and functional differences between the human and avian NS1. This review discusses these differences in addition to describing potential uses of NS1 in the management and control of avian influenza outbreaks. PMID:21994582

  15. 36 CFR 2.10 - Camping and food storage.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 36 Parks, Forests, and Public Property 1 2012-07-01 2012-07-01 false Camping and food storage. 2... RESOURCE PROTECTION, PUBLIC USE AND RECREATION § 2.10 Camping and food storage. (a) The superintendent may... revocation of the permit. (d) Food storage. The superintendent may designate all or a portion of a park...

  16. 36 CFR 2.10 - Camping and food storage.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 36 Parks, Forests, and Public Property 1 2014-07-01 2014-07-01 false Camping and food storage. 2... RESOURCE PROTECTION, PUBLIC USE AND RECREATION § 2.10 Camping and food storage. (a) The superintendent may... revocation of the permit. (d) Food storage. The superintendent may designate all or a portion of a park...

  17. 36 CFR 2.10 - Camping and food storage.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 36 Parks, Forests, and Public Property 1 2013-07-01 2013-07-01 false Camping and food storage. 2... RESOURCE PROTECTION, PUBLIC USE AND RECREATION § 2.10 Camping and food storage. (a) The superintendent may... revocation of the permit. (d) Food storage. The superintendent may designate all or a portion of a park...

  18. 36 CFR 2.10 - Camping and food storage.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 36 Parks, Forests, and Public Property 1 2010-07-01 2010-07-01 false Camping and food storage. 2... RESOURCE PROTECTION, PUBLIC USE AND RECREATION § 2.10 Camping and food storage. (a) The superintendent may... revocation of the permit. (d) Food storage. The superintendent may designate all or a portion of a park...

  19. 36 CFR 2.10 - Camping and food storage.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 36 Parks, Forests, and Public Property 1 2011-07-01 2011-07-01 false Camping and food storage. 2... RESOURCE PROTECTION, PUBLIC USE AND RECREATION § 2.10 Camping and food storage. (a) The superintendent may... revocation of the permit. (d) Food storage. The superintendent may designate all or a portion of a park...

  20. Anthracene-based inhibitors of dengue virus NS2B-NS3 protease.

    PubMed

    Tomlinson, Suzanne M; Watowich, Stanley J

    2011-02-01

    Dengue virus (DENV) is a mosquito-borne flavivirus that has strained global healthcare systems throughout tropical and subtropical regions of the world. In addition to plaguing developing nations, it has re-emerged in several developed countries with recent outbreaks in the USA (CDC, 2010), Australia (Hanna et al., 2009), Taiwan (Kuan et al., 2010) and France (La Ruche et al., 2010). DENV infection can cause significant disease, including dengue fever, dengue hemorrhagic fever, dengue shock syndrome, and death. There are no approved vaccines or antiviral therapies to prevent or treat dengue-related illnesses. However, the viral NS2B-NS3 protease complex provides a strategic target for antiviral drug development since NS3 protease activity is required for virus replication. Recently, we reported two compounds with inhibitory activity against the DENV protease in vitro and antiviral activity against dengue 2 (DEN2V) in cell culture (Tomlinson et al., 2009a). Analogs of one of the lead compounds were purchased, tested in protease inhibition assays, and the data evaluated with detailed kinetic analyses. A structure activity relationship (SAR) identified key atomic determinants (i.e. functional groups) important for inhibitory activity. Four "second series" analogs were selected and tested to validate our SAR and structural models. Here, we report improvements to inhibitory activity ranging between ∼2- and 60-fold, resulting in selective low micromolar dengue protease inhibitors.

  1. Ultrashort electric pulse induced changes in cellular dielectric properties.

    PubMed

    Garner, Allen L; Chen, George; Chen, Nianyong; Sridhara, Viswanadham; Kolb, Juergen F; Swanson, R James; Beebe, Stephen J; Joshi, Ravindra P; Schoenbach, Karl H

    2007-10-12

    The interaction of nanosecond duration pulsed electric fields (nsPEFs) with biological cells, and the models describing this behavior, depend critically on the electrical properties of the cells being pulsed. Here, we used time domain dielectric spectroscopy to measure the dielectric properties of Jurkat cells, a malignant human T-cell line, before and after exposure to five 10ns, 150kV/cm electrical pulses. The cytoplasm and nucleoplasm conductivities decreased dramatically following pulsing, corresponding to previously observed rises in cell suspension conductivity. This suggests that electropermeabilization occurred, resulting in ion transport from the cell's interior to the exterior. A delayed decrease in cell membrane conductivity after the nsPEFs possibly suggests long-term ion channel damage or use dependence due to repeated membrane charging and discharging. This data could be used in models describing the phenomena at work.

  2. Effect of Pulse Length on Engraving Efficiency in Nanosecond Pulsed Laser Engraving of Stainless Steel

    NASA Astrophysics Data System (ADS)

    Manninen, Matti; Hirvimäki, Marika; Poutiainen, Ilkka; Salminen, Antti

    2015-10-01

    Dependency of laser pulse length on the effectiveness of laser engraving 304 stainless steel with nanosecond pulses was investigated. Ytterbium fiber laser with pulse lengths from 4 to 200 ns was used at a constant average power of 20 W. Measured criteria for effective laser engraving were high material removal rate (MRR), good visual quality of the engraved surface, and low processing temperature. MRR was measured by weighing the samples prior and after the engraving process. Visual quality was evaluated from magnified images. Surface temperature of the samples was measured by two laser spot-welded K-type thermocouples near the laser-processed area. It was noticed that MRR increases significantly with longer pulse lengths, while the quality decreases and processing temperature increases. Some peculiar process behavior was noticed. With short pulses (<20 ns), the process temperature steadily increased as the engraving process continued, whereas with longer pulses the process temperature started to decrease after initially jumping to a specific level. From visually analyzing the samples, it was noticed that the melted and resolidified bottom structure had cracks and pores on the surface when 50 ns or longer pulse lengths were used.

  3. Balance of RNA sequence requirement and NS3/NS3a expression of segment 10 of orbiviruses.

    PubMed

    Feenstra, Femke; van Gennip, René G P; Schreuder, Myrte; van Rijn, Piet A

    2016-02-01

    Orbiviruses are insect-transmitted, non-enveloped viruses with a ten-segmented dsRNA genome of which the bluetongue virus (BTV) is the prototype. Viral non-structural protein NS3/NS3a is encoded by genome segment 10 (Seg-10), and is involved in different virus release mechanisms. This protein induces specific release via membrane disruptions and budding in both insect and mammalian cells, but also the cytopathogenic release that is only seen in mammalian cells. NS3/NS3a is not essential for virus replication in vitro with BTV Seg-10 containing RNA elements essential for virus replication, even if protein is not expressed. Recently, new BTV serotypes with distinct NS3/NS3a sequence and cell tropism have been identified. Multiple studies have hinted at the importance of Seg-10 in orbivirus replication, but the exact prerequisites are still unknown. Here, more insight is obtained with regard to the needs for orbivirus Seg-10 and the balance between protein expression and RNA elements. Multiple silent mutations in the BTV NS3a ORF destabilized Seg-10, resulting in deletions and sequences originating from other viral segments being inserted, indicating strong selection at the level of RNA during replication in mammalian cells in vitro. The NS3a ORFs of other orbiviruses were successfully exchanged in BTV1 Seg-10, resulting in viable chimeric viruses. NS3/NS3a proteins in these chimeric viruses were generally functional in mammalian cells, but not in insect cells. NS3/NS3a of the novel BTV serotypes 25 and 26 affected virus release from Culicoides cells, which might be one of the reasons for their distinct cell tropism. PMID:26644214

  4. Pulsed cathodoluminescence of diamond, calcite, spodumene, and fluorite under the action of subnanosecond electron beam

    NASA Astrophysics Data System (ADS)

    Baksht, E. Kh.; Burachenko, A. G.; Tarasenko, V. F.

    2010-11-01

    Amplitude and temporal characteristics of pulsed cathodoluminescence (PCL) of diamond (natural and synthetic), calcite, spodumene, and fluorite have been studied at a temporal resolution of ˜0.3 ns. The PCL was generated by electron beam pulses with a full width at half maximum (FWHM) of 0.1, 0.25, and 0.65 ns. The PCL spectra have been measured for the emission induced by 0.1- and 0.25-ns pulses at a beam current density of ˜90 A/cm2.

  5. Brazilian Flavivirus phylogeny based on NS5.

    PubMed

    Baleotti, Flúvia Graciela; Moreli, Marcos Lázaro; Figueiredo, Luiz Tadeu Moraes

    2003-04-01

    In this work, a comprehensive phylogenetic study based on 600 base pair nucleotide and on putative 200 amino acid sequences of NS5 was carried out in order to establish genetic relationships among 15 strains of 10 Brazilian flaviviruses: Bussuquara, Cacipacore, dengue type 1, 2 and 4, Iguape, Ilheus, Rocio, Saint Louis encephalitis (SLE), and yellow fever. Phylogenetic trees were created by neighbor-joining and maximum parsimony methods. These trees showed Brazilian flaviviruses grouped into three main branches: yellow fever branch, dengue branch subdivided in types 1, 2 and 4 branches, and Japanese encephalitis virus (JEV) complex branch including SLE virus strains, Cacipacore, Iguape, Rocio, Ilheus and Bussuquara. Viruses transmitted by Aedes mosquitoes, such as dengue and urban yellow fever, that are also the only Flavivirus causing hemorrhagic fevers in Brazil, were grouped in the same cluster. Encephalitis associated viruses, transmitted by Culex mosquitoes such as JEV complex branch including SLE virus strains, Cacipacore, Iguape, Rocio, Ilheus and Bussuquara were also grouped in the same clade.

  6. Synergistic Activity of Combined NS5A Inhibitors

    PubMed Central

    Nower, Peter T.; Gao, Min; Fridell, Robert; Wang, Chunfu; Hewawasam, Piyasena; Lopez, Omar; Tu, Yong; Meanwell, Nicholas A.; Belema, Makonen; Roberts, Susan B.; Cockett, Mark; Sun, Jin-Hua

    2015-01-01

    Daclatasvir (DCV) is a first-in-class hepatitis C virus (HCV) nonstructural 5A replication complex inhibitor (NS5A RCI) that is clinically effective in interferon-free combinations with direct-acting antivirals (DAAs) targeting alternate HCV proteins. Recently, we reported NS5A RCI combinations that enhance HCV inhibitory potential in vitro, defining a new class of HCV inhibitors termed NS5A synergists (J. Sun, D. R. O’Boyle II, R. A. Fridell, D. R. Langley, C. Wang, S. Roberts, P. Nower, B. M. Johnson F. Moulin, M. J. Nophsker, Y. Wang, M. Liu, K. Rigat, Y. Tu, P. Hewawasam, J. Kadow, N. A. Meanwell, M. Cockett, J. A. Lemm, M. Kramer, M. Belema, and M. Gao, Nature 527:245–248, 2015, doi:10.1038/nature15711). To extend the characterization of NS5A synergists, we tested new combinations of DCV and NS5A synergists against genotype (gt) 1 to 6 replicons and gt 1a, 2a, and 3a viruses. The kinetics of inhibition in HCV-infected cells treated with DCV, an NS5A synergist (NS5A-Syn), or a combination of DCV and NS5A-Syn were distinctive. Similar to activity observed clinically, DCV caused a multilog drop in HCV, followed by rebound due to the emergence of resistance. DCV–NS5A-Syn combinations were highly efficient at clearing cells of viruses, in line with the trend seen in replicon studies. The retreatment of resistant viruses that emerged using DCV monotherapy with DCV–NS5A-Syn resulted in a multilog drop and rebound in HCV similar to the initial decline and rebound observed with DCV alone on wild-type (WT) virus. A triple combination of DCV, NS5A-Syn, and a DAA targeting the NS3 or NS5B protein cleared the cells of viruses that are highly resistant to DCV. Our data support the observation that the cooperative interaction of DCV and NS5A-Syn potentiates both the genotype coverage and resistance barrier of DCV, offering an additional DAA option for combination therapy and tools for explorations of NS5A function. PMID:26711745

  7. Generation and dynamics of single-electrode nanosecond pulsed microplasma jets

    NASA Astrophysics Data System (ADS)

    Jiang, Chunqi; Lane, Jamie; Song, Shutong; Plasma; Pulsed Power Lab at ODU-CBE Team

    2015-11-01

    Several millimeter long, 160 - 260 micrometer-in-width, helium plasma jets were generated in ambient atmosphere when a needle electrode was excited with nanosecond high voltage pulses at single shot or up to 500 Hz. This single-electrode system does not require the use of ground electrode for plasma generation, and thus has advantages in simplicity and small-dimension for a variety of biomedical applications. Dynamics of the microplasma jet powered by high voltage pulses with two different nanosecond pulses - 5 ns and 164 ns, was studied with high speed imaging, and spatiotemporally resolved optical emission spectroscopy. Whereas the plasma jet exhibits three different modes including a positive-streamer mode, a stochastic transition, and a negative streamer-like mode when it was excited with 164 ns kilovolt pulses, such modes and transitions in the plasma development were not observed for the 5 ns pulsed excitation. Shorter pulses with shorter rise times allowed higher energy deposition into the plasma and promote rapid acceleration of the plasma wavefronts; 5 ns pulsed excitation resulted in 4 times increase in the wavefront velocity compared with the 164 ns pulsed excitation. Importantly, the production of excited atomic oxygen increased by a factor of 2 for the 5 ns pulsed plasma jet when compared with that for a 164 ns pulsed plasma jet, whereas the other excited species including He, O, H, OH, N2(C-B) and N2+(B-X) were produced at comparable rates for the two plasma jets. Work supported by the Air Force Office of Scientific Research (AFOSR Award No. FA9550-11-1-0190).

  8. An improved rolled strip pulse forming line

    NASA Astrophysics Data System (ADS)

    Li, Song; Qian, Bao-Liang; Yang, Han-Wu; Gao, Jing-Ming; Liu, Zhao-Xi

    2013-06-01

    The rolled strip pulse forming line (RSPFL) has advantages of compactness, portability, and long pulse achievability which could well meet the requirements of industrial application of the pulse power technology. In this paper, an improved RSPFL with an additional insulator between the grounded conductors is investigated numerically and experimentally. Results demonstrate that the jitter on the flat-top of the output voltage waveform is reduced to 3.8% due to the improved structure. Theoretical analysis shows that the electromagnetic coupling between the conductors of the RSPFL strongly influences the output voltage waveform. Therefore, the new structure was designed to minimize the detrimental effect of the electromagnetic coupling. Simulation results show that the electromagnetic coupling can be efficiently reduced in the improved RSPFL. Experimental results illustrate that the improved RSPFL, with dimensions and weight of Φ 290 × 250 mm and 16 kg, when used as a simple pulse forming line, could generate a well shaped quasi-square pulse with output power of hundreds of MW and pulse duration of 250 ns. Importantly, the improved RSPFL was successfully used as a Blumlein pulse forming line, and a 10.8 kV, 260 ns quasi-square pulse was obtained on a 2 Ω dummy load. Experiments show reasonable agreement with numerical analysis.

  9. PULSE SORTER

    DOEpatents

    Wade, E.J.

    1958-07-29

    An apparatus is described for counting and recording the number of electrical pulses occurring in each of a timed sequence of groups of pulses. The particular feature of the invention resides in a novel timing circuit of the univibrator type which provides very accurately timed pulses for opening each of a series of coincidence channels in sequence. The univibrator is shown incorporated in a pulse analyzing system wherein a series of pulse counting channels are periodically opened in order, one at a time, for a predetermtned open time interval, so that only one channel will be open at the time of occurrence of any of the electrical pulses to be sorted.

  10. Effect of inter-pulse delay time on production and size properties of colloidal nanoparticles prepared by collinear double-pulse laser ablation in liquid

    NASA Astrophysics Data System (ADS)

    Fattahi, Behzad; Mahdieh, Mohammah Hossein

    2016-08-01

    The influence of inter-pulse delay times (0–20 ns) between two collinear sequential nanosecond pulses on the production and size properties (mean size and size distribution) of colloidal nanoparticles prepared by pulsed laser ablation of a silver target in a distilled water medium has been studied. Various laser fluences at different inter-pulse delay times between two collinear pulses were used. Furthermore, for a better understanding of the effect of the double-pulse and single-pulse mode, experiments were performed. The characterization of the synthesized colloidal nanoparticles was investigated using scanning electron microscopy (SEM) and UV–vis absorption spectroscopy. Our results showed that 5 ns time-delayed double-pulse laser ablation results in the production of nanoparticles with the highest concentration among the other time-delayed ablation experiments and even more than single-pulse-mode experiments. It also found that using a double-pulse approach with inter-pulse delay times in the range of 0–20 ns leads to the production of nanoparticles with smaller mean sizes and narrower size distributions in comparison to single-pulse-mode laser ablation. The effect of time overlapping between two pulses in the case of double-pulse ablation was analyzed.

  11. Effect of inter-pulse delay time on production and size properties of colloidal nanoparticles prepared by collinear double-pulse laser ablation in liquid

    NASA Astrophysics Data System (ADS)

    Fattahi, Behzad; Mahdieh, Mohammah Hossein

    2016-08-01

    The influence of inter-pulse delay times (0-20 ns) between two collinear sequential nanosecond pulses on the production and size properties (mean size and size distribution) of colloidal nanoparticles prepared by pulsed laser ablation of a silver target in a distilled water medium has been studied. Various laser fluences at different inter-pulse delay times between two collinear pulses were used. Furthermore, for a better understanding of the effect of the double-pulse and single-pulse mode, experiments were performed. The characterization of the synthesized colloidal nanoparticles was investigated using scanning electron microscopy (SEM) and UV-vis absorption spectroscopy. Our results showed that 5 ns time-delayed double-pulse laser ablation results in the production of nanoparticles with the highest concentration among the other time-delayed ablation experiments and even more than single-pulse-mode experiments. It also found that using a double-pulse approach with inter-pulse delay times in the range of 0-20 ns leads to the production of nanoparticles with smaller mean sizes and narrower size distributions in comparison to single-pulse-mode laser ablation. The effect of time overlapping between two pulses in the case of double-pulse ablation was analyzed.

  12. Fast Rise Time and High Voltage Nanosecond Pulses at High Pulse Repetition Frequency

    NASA Astrophysics Data System (ADS)

    Miller, Kenneth E.; Ziemba, Timothy; Prager, James; Picard, Julian; Hashim, Akel

    2015-09-01

    Eagle Harbor Technologies (EHT), Inc. is conducting research to decrease the rise time and increase the output voltage of the EHT Nanosecond Pulser product line, which allows for independently, user-adjustable output voltage (0 - 20 kV), pulse width (20 - 500 ns), and pulse repetition frequency (0 - 100 kHz). The goals are to develop higher voltage pulses (50 - 60 kV), decrease the rise time from 20 to below 10 ns, and maintain the high pulse repetition capabilities. These new capabilities have applications to pseudospark generation, corona production, liquid discharges, and nonlinear transmission line driving for microwave production. This work is supported in part by the US Navy SBIR program.

  13. Hepatitis C Virus NS3 Inhibitors: Current and Future Perspectives

    PubMed Central

    Akimitsu, Nobuyoshi

    2013-01-01

    Currently, hepatitis C virus (HCV) infection is considered a serious health-care problem all over the world. A good number of direct-acting antivirals (DAAs) against HCV infection are in clinical progress including NS3-4A protease inhibitors, RNA-dependent RNA polymerase inhibitors, and NS5A inhibitors as well as host targeted inhibitors. Two NS3-4A protease inhibitors (telaprevir and boceprevir) have been recently approved for the treatment of hepatitis C in combination with standard of care (pegylated interferon plus ribavirin). The new therapy has significantly improved sustained virologic response (SVR); however, the adverse effects associated with this therapy are still the main concern. In addition to the emergence of viral resistance, other targets must be continually developed. One such underdeveloped target is the helicase portion of the HCV NS3 protein. This review article summarizes our current understanding of HCV treatment, particularly with those of NS3 inhibitors. PMID:24282816

  14. Pulse Oximetry

    MedlinePlus

    ... www.thoracic.org amount of gases (oxygen and carbon dioxide) that are in your blood. To get an ... Also, a pulse oximeter does not measure your carbon dioxide level. How accurate is the pulse oximeter? The ...

  15. Ultrastructure of Kunjin virus-infected cells: colocalization of NS1 and NS3 with double-stranded RNA, and of NS2B with NS3, in virus-induced membrane structures.

    PubMed Central

    Westaway, E G; Mackenzie, J M; Kenney, M T; Jones, M K; Khromykh, A A

    1997-01-01

    The subcellular location of the nonstructural proteins NS1, NS2B, and NS3 in Vero cells infected with the flavivirus Kunjin was investigated using indirect immunofluorescence and cryoimmunoelectron microscopy with monospecific antibodies. Comparisons were also made by dual immunolabelling using antibodies to double-stranded RNA (dsRNA), the putative template in the flavivirus replication complex. At 8 h postinfection, the immunofluorescent patterns showed NS1, NS2B, NS3, and dsRNA located in a perinuclear rim with extensions into the peripheral cytoplasm. By 16 h, at the end of the latent period, all patterns had changed to some discrete perinuclear foci associated with a thick cytoplasmic reticulum. By 24 h, this localization in perinuclear foci was more apparent and some foci were dual labelled with antibodies to dsRNA. In immuno-gold-labelled cryosections of infected cells at 24 h, all antibodies were associated with clusters of induced membrane structures in the perinuclear region. Two important and novel observations were made. First, one set of induced membranes comprised vesicle packets of smooth membranes dual labelled with anti-dsRNA and anti-NS1 or anti-NS3 antibodies. Second, adjacent masses of paracrystalline arrays or of convoluted smooth membranes, which appeared to be structurally related, were strongly labelled only with anti-NS2B and anti-NS3 antibodies. Paired membranes similar in appearance to the rough endoplasmic reticulum were also labelled, but less strongly, with antibodies to the three nonstructural proteins. Other paired membranes adjacent to the structures discussed above enclosed accumulated virus particles but were not labelled with any of the four antibodies. The collection of induced membranes may represent virus factories in which translation, RNA synthesis, and virus assembly occur. PMID:9261387

  16. A compact high current pulsed electron gun with subnanosecond electron pulse widths

    NASA Technical Reports Server (NTRS)

    Khakoo, M. A.; Srivastava, S. K.

    1984-01-01

    A magnetically-collimated, double-pulsed electron gun capable of generating electron pulses with a peak instantaneous current of approximately 70 microamps and a temporal width of 0.35 ns (FWHM) has been developed. Calibration is accomplished by measuring the lifetime of the well known 2(1P)-to-1(1S) transition in helium (58.4nm) at a near-threshold electron-impact energy by use of the delayed-coincidence technique.

  17. Pulse generation and preamplification for long pulse beamlines of Orion laser facility.

    PubMed

    Hillier, David I; Winter, David N; Hopps, Nicholas W

    2010-06-01

    We describe the pulse generation, shaping, and preamplification system for the nanosecond beamlines of the Orion laser facility. The system generates shaped laser pulses of up to approximately 1 J of 100 ps-5 ns duration with a programmable temporal profile. The laser has a 30th-power supergaussian spatial profile and is diffraction limited. The system is capable of imposing 2D smoothing by spectral dispersion upon the beam, which will produce a nonuniformity of 10% rms at the target.

  18. Pulsed discharge production Ar* metastables

    NASA Astrophysics Data System (ADS)

    Han, Jiande; Heaven, Michael C.; Emmons, Daniel; Perram, Glen P.; Weeks, David E.; Bailey, William F.

    2016-03-01

    The production of relatively high densities of Ar* metastables (>1012 cm-3) in Ar/He mixtures, at total pressures close to 1 atm, is essential for the efficient operation of an optically pumped Ar* laser. We have used emission spectroscopy and diode laser absorption spectroscopy measurements to observe the production and decay of Ar* in a parallel plate pulsed discharge. With discharge pulses of 1 μs duration we find that metastable production is dominated by processes occurring within the first 100 ns of the gas break-down. Application of multiple, closely spaced discharge pulses yields insights concerning conditions that favor metastable production. This information has been combined with time-resolved measurements of voltage and current. The experimental results and preliminary modeling of the discharge kinetics are presented.

  19. Neodymium glass laser with a pulse energy of 220 J and a pulse repetition rate of 0.02 Hz

    SciTech Connect

    Kuzmin, A A; Kulagin, O V; Khazanov, Efim A; Shaykin, A A

    2013-07-31

    A compact neodymium glass laser with a pulse energy of 220 J and a record-high pulse repetition rate of 0.02 Hz (pulse duration 30 ns) is developed. Thermally induced phase distortions are compensated using wave phase conjugation. The integral depolarisation of radiation is decreased to 0.4% by using linear compensation schemes. The second harmonic of laser radiation can be used for pumping Ti : sapphire multipetawatt complexes. (letters)

  20. Flavonoids as noncompetitive inhibitors of Dengue virus NS2B-NS3 protease: inhibition kinetics and docking studies.

    PubMed

    de Sousa, Lorena Ramos Freitas; Wu, Hongmei; Nebo, Liliane; Fernandes, João Batista; da Silva, Maria Fátima das Graças Fernandes; Kiefer, Werner; Kanitz, Manuel; Bodem, Jochen; Diederich, Wibke E; Schirmeister, Tanja; Vieira, Paulo Cezar

    2015-02-01

    NS2B-NS3 is a serine protease of the Dengue virus considered a key target in the search for new antiviral drugs. In this study flavonoids were found to be inhibitors of NS2B-NS3 proteases of the Dengue virus serotypes 2 and 3 with IC50 values ranging from 15 to 44 μM. Agathisflavone (1) and myricetin (4) turned out to be noncompetitive inhibitors of dengue virus serotype 2 NS2B-NS3 protease with Ki values of 11 and 4.7 μM, respectively. Docking studies propose a binding mode of the flavonoids in a specific allosteric binding site of the enzyme. Analysis of biomolecular interactions of quercetin (5) with NT647-NHS-labeled Dengue virus serotype 3 NS2B-NS3 protease by microscale thermophoresis experiments, yielded a dissociation constant KD of 20 μM. Our results help to understand the mechanism of inhibition of the Dengue virus serine protease by flavonoids, which is essential for the development of improved inhibitors.

  1. Longitudinally Excited CO2 Laser with Short Laser Pulse like TEA CO2 Laser

    NASA Astrophysics Data System (ADS)

    Uno, Kazuyuki; Nakamura, Kenshi; Goto, Tatsumi; Jitsuno, Takahisa

    2009-11-01

    We have developed a longitudinally excited CO2 laser with a short laser pulse similar to that of TEA and Q-switched CO2 lasers. A capacitor transfer circuit with a low shunt resistance provided rapid discharge and a sharp spike pulse with a short pulse tail. Specifically, a circuit with a resistance of 10 M Ω provided a spike pulse width of 103.3 ns and a pulse tail length of 61.9 μs, whereas a circuit with a shunt resistance of 100 Ω provided a laser pulse with a spike pulse width of 96.3 ns and a pulse tail length of 17.2 μs. The laser pulses from this longitudinally excited CO2 laser were used for processing a human tooth without carbonization and for glass marking without cracks.

  2. Effects of high voltage nanosecond electric pulses on eukaryotic cells (in vitro): A systematic review.

    PubMed

    Batista Napotnik, Tina; Reberšek, Matej; Vernier, P Thomas; Mali, Barbara; Miklavčič, Damijan

    2016-08-01

    For this systematic review, 203 published reports on effects of electroporation using nanosecond high-voltage electric pulses (nsEP) on eukaryotic cells (human, animal, plant) in vitro were analyzed. A field synopsis summarizes current published data in the field with respect to publication year, cell types, exposure configuration, and pulse duration. Published data were analyzed for effects observed in eight main target areas (plasma membrane, intracellular, apoptosis, calcium level and distribution, survival, nucleus, mitochondria, stress) and an additional 107 detailed outcomes. We statistically analyzed effects of nsEP with respect to three pulse duration groups: A: 1-10ns, B: 11-100ns and C: 101-999ns. The analysis confirmed that the plasma membrane is more affected with longer pulses than with short pulses, seen best in uptake of dye molecules after applying single pulses. Additionally, we have reviewed measurements of nsEP and evaluations of the electric fields to which cells were exposed in these reports, and we provide recommendations for assessing nanosecond pulsed electric field effects in electroporation studies. PMID:26946156

  3. Effects of high voltage nanosecond electric pulses on eukaryotic cells (in vitro): A systematic review.

    PubMed

    Batista Napotnik, Tina; Reberšek, Matej; Vernier, P Thomas; Mali, Barbara; Miklavčič, Damijan

    2016-08-01

    For this systematic review, 203 published reports on effects of electroporation using nanosecond high-voltage electric pulses (nsEP) on eukaryotic cells (human, animal, plant) in vitro were analyzed. A field synopsis summarizes current published data in the field with respect to publication year, cell types, exposure configuration, and pulse duration. Published data were analyzed for effects observed in eight main target areas (plasma membrane, intracellular, apoptosis, calcium level and distribution, survival, nucleus, mitochondria, stress) and an additional 107 detailed outcomes. We statistically analyzed effects of nsEP with respect to three pulse duration groups: A: 1-10ns, B: 11-100ns and C: 101-999ns. The analysis confirmed that the plasma membrane is more affected with longer pulses than with short pulses, seen best in uptake of dye molecules after applying single pulses. Additionally, we have reviewed measurements of nsEP and evaluations of the electric fields to which cells were exposed in these reports, and we provide recommendations for assessing nanosecond pulsed electric field effects in electroporation studies.

  4. Short pulse generation from a flashlamp-pumped rhodamine 6G ring dye laser using the colliding pulse mode-locking technique

    SciTech Connect

    Singh, S.

    1987-01-01

    The colliding pulse mode-locking (CPM) technique has been applied to a flashlamp-pumped rhodamine 6G dye laser to reliably generate pulses of <1.5 ps. Pulse evolution in the ring cavity has been studied by examining the pulse characteristics at various parts of the pulse train using a Photochron II streak camera. The measured pulse durations in the ring cavity were found to be detector-limited and were shorter than those generated in a linear cavity. The shortest pulses were observed to evolve toward the end of the --600-ns long mode-locked train.

  5. Novel Dengue Virus NS2B/NS3 Protease Inhibitors

    PubMed Central

    Wu, Hongmei; Bock, Stefanie; Snitko, Mariya; Berger, Thilo; Weidner, Thomas; Holloway, Steven; Kanitz, Manuel; Diederich, Wibke E.; Steuber, Holger; Walter, Christof; Hofmann, Daniela; Weißbrich, Benedikt; Spannaus, Ralf; Acosta, Eliana G.; Bartenschlager, Ralf; Engels, Bernd; Schirmeister, Tanja

    2014-01-01

    Dengue fever is a severe, widespread, and neglected disease with more than 2 million diagnosed infections per year. The dengue virus NS2B/NS3 protease (PR) represents a prime target for rational drug design. At the moment, there are no clinical PR inhibitors (PIs) available. We have identified diaryl (thio)ethers as candidates for a novel class of PIs. Here, we report the selective and noncompetitive inhibition of the serotype 2 and 3 dengue virus PR in vitro and in cells by benzothiazole derivatives exhibiting 50% inhibitory concentrations (IC50s) in the low-micromolar range. Inhibition of replication of DENV serotypes 1 to 3 was specific, since all substances influenced neither hepatitis C virus (HCV) nor HIV-1 replication. Molecular docking suggests binding at a specific allosteric binding site. In addition to the in vitro assays, a cell-based PR assay was developed to test these substances in a replication-independent way. The new compounds inhibited the DENV PR with IC50s in the low-micromolar or submicromolar range in cells. Furthermore, these novel PIs inhibit viral replication at submicromolar concentrations. PMID:25487800

  6. PULSE GENERATOR

    DOEpatents

    Roeschke, C.W.

    1957-09-24

    An improvement in pulse generators is described by which there are produced pulses of a duration from about 1 to 10 microseconds with a truly flat top and extremely rapid rise and fall. The pulses are produced by triggering from a separate input or by modifying the current to operate as a free-running pulse generator. In its broad aspect, the disclosed pulse generator comprises a first tube with an anode capacitor and grid circuit which controls the firing; a second tube series connected in the cathode circuit of the first tube such that discharge of the first tube places a voltage across it as the leading edge of the desired pulse; and an integrator circuit from the plate across the grid of the second tube to control the discharge time of the second tube, determining the pulse length.

  7. Monoclonal antibodies against NS1 protein of Goose parvovirus.

    PubMed

    Qiu, Zheng; Tian, Wei; Yu, Tianfei; Li, Li; Ma, Bo; Wang, Junwei

    2012-04-01

    In the present study, monoclonal antibodies (MAbs) against NS1 protein of Goose parvovirus (GPV) were generated. The secreted MAbs were obtained by fusing mouse myeloma cells and spleen cells of BALB/c mice, which were immunized with the plasmid pcDNA3.1-GPV-NS1 and recombinant protein of GPV-NS1. With indirect ELISA, six hybridoma cell lines against GPV-NS1 were screened. The subtypes of the two MAbs were IgG2a; the others were IgM. The light chain was κ. Western blot analysis showed that six MAbs reacted with recombinant protein GPV-NS1. GPV-NS1 was dissected into 15 overlapping epitopes, which were used to react with MAbs in Western blot. Results showed that six MAbs recognized NS1 protein linear B-cell epitopes located at the C-terminus 453-514 aa, 485-542 aa, and 533-598 aa.

  8. Psammaplin A inhibits hepatitis C virus NS3 helicase.

    PubMed

    Salam, Kazi Abdus; Furuta, Atsushi; Noda, Naohiro; Tsuneda, Satoshi; Sekiguchi, Yuji; Yamashita, Atsuya; Moriishi, Kohji; Nakakoshi, Masamichi; Tsubuki, Masayoshi; Tani, Hidenori; Tanaka, Junichi; Akimitsu, Nobuyoshi

    2013-10-01

    Hepatitis C virus (HCV) is the causative agent of hepatitis C, a chronic infectious disease that can lead to development of hepatocellular carcinoma. The NS3 nucleoside triphosphatase (NTPase)/helicase has an essential role in HCV replication, and is therefore an attractive target for direct-acting antiviral strategies. In this study, we employed high-throughput screening using a photo-induced electron transfer (PET) system to identify an inhibitor of NS3 helicase from marine organism extracts. We successfully identified psammaplin A as a novel NS3 inhibitor. The dose-response relationship clearly demonstrates the inhibition of NS3 RNA helicase and ATPase activities by psammaplin A, with IC₅₀ values of 17 and 32 μM, respectively. Psammaplin A has no influence on the apparent Km value (0.4 mM) of NS3 ATPase activity, and acts as a non-competitive inhibitor. Additionally, it inhibits the binding of NS3 to single-stranded RNA in a dose-dependent manner. Furthermore, psammaplin A shows an inhibitory effect on viral replication, with EC₅₀ values of 6.1 and 6.3 μM in subgenomic replicon cells derived from genotypes 1b and 2a, respectively. We postulate that psammaplin A is a potential anti-viral agent through the inhibition of ATPase, RNA binding and helicase activities of NS3. PMID:23359228

  9. Silencing by H-NS Potentiated the Evolution of Salmonella

    PubMed Central

    Rao, Chitong; Leung, Andrea S.; Ngai, David Hon-Man; Ensminger, Alexander W.; Navarre, William Wiley

    2014-01-01

    The bacterial H-NS protein silences expression from sequences with higher AT-content than the host genome and is believed to buffer the fitness consequences associated with foreign gene acquisition. Loss of H-NS results in severe growth defects in Salmonella, but the underlying reasons were unclear. An experimental evolution approach was employed to determine which secondary mutations could compensate for the loss of H-NS in Salmonella. Six independently derived S. Typhimurium hns mutant strains were serially passaged for 300 generations prior to whole genome sequencing. Growth rates of all lineages dramatically improved during the course of the experiment. Each of the hns mutant lineages acquired missense mutations in the gene encoding the H-NS paralog StpA encoding a poorly understood H-NS paralog, while 5 of the mutant lineages acquired deletions in the genes encoding the Salmonella Pathogenicity Island-1 (SPI-1) Type 3 secretion system critical to invoke inflammation. We further demonstrate that SPI-1 misregulation is a primary contributor to the decreased fitness in Salmonella hns mutants. Three of the lineages acquired additional loss of function mutations in the PhoPQ virulence regulatory system. Similarly passaged wild type Salmonella lineages did not acquire these mutations. The stpA missense mutations arose in the oligomerization domain and generated proteins that could compensate for the loss of H-NS to varying degrees. StpA variants most able to functionally substitute for H-NS displayed altered DNA binding and oligomerization properties that resembled those of H-NS. These findings indicate that H-NS was central to the evolution of the Salmonellae by buffering the negative fitness consequences caused by the secretion system that is the defining characteristic of the species. PMID:25375226

  10. The influenza virus NS1 protein as a therapeutic target.

    PubMed

    Engel, Daniel A

    2013-09-01

    Nonstructural protein 1 (NS1) of influenza A virus plays a central role in virus replication and blockade of the host innate immune response, and is therefore being considered as a potential therapeutic target. The primary function of NS1 is to dampen the host interferon (IFN) response through several distinct molecular mechanisms that are triggered by interactions with dsRNA or specific cellular proteins. Sequestration of dsRNA by NS1 results in inhibition of the 2'-5' oligoadenylate synthetase/RNase L antiviral pathway, and also inhibition of dsRNA-dependent signaling required for new IFN production. Binding of NS1 to the E3 ubiquitin ligase TRIM25 prevents activation of RIG-I signaling and subsequent IFN induction. Cellular RNA processing is also targeted by NS1, through recognition of cleavage and polyadenylation specificity factor 30 (CPSF30), leading to inhibition of IFN-β mRNA processing as well as that of other cellular mRNAs. In addition NS1 binds to and inhibits cellular protein kinase R (PKR), thus blocking an important arm of the IFN system. Many additional proteins have been reported to interact with NS1, either directly or indirectly, which may serve its anti-IFN and additional functions, including the regulation of viral and host gene expression, signaling pathways and viral pathogenesis. Many of these interactions are potential targets for small-molecule intervention. Structural, biochemical and functional studies have resulted in hypotheses for drug discovery approaches that are beginning to bear experimental fruit, such as targeting the dsRNA-NS1 interaction, which could lead to restoration of innate immune function and inhibition of virus replication. This review describes biochemical, cell-based and nucleic acid-based approaches to identifying NS1 antagonists.

  11. The influenza virus NS1 protein as a therapeutic target

    PubMed Central

    Engel, Daniel A.

    2015-01-01

    Nonstructural protein 1 (NS1) of influenza A virus plays a central role in virus replication and blockade of the host innate immune response, and is therefore being considered as a potential therapeutic target. The primary function of NS1 is to dampen the host interferon (IFN) response through several distinct molecular mechanisms that are triggered by interactions with dsRNA or specific cellular proteins. Sequestration of dsRNA by NS1 results in inhibition of the 2’-5’ oligoadenylate synthetase/RNase L antiviral pathway, and also inhibition of dsRNA-dependent signaling required for new IFN production. Binding of NS1 to the E3 ubiquitin ligase TRIM25 prevents activation of RIG-I signaling and subsequent IFN induction. Cellular RNA processing is also targeted by NS1, through recognition of cleavage and polyadenylation specificity factor 30 (CPSF30), leading to inhibition of IFN- mRNA processing as well as that of other cellular mRNAs. In addition NS1 binds to and inhibits cellular protein kinase R (PKR), thus blocking an important arm of the IFN system. Many additional proteins have been reported to interact with NS1, either directly or indirectly, which may serve its anti-IFN and additional functions, including the regulation of viral and host gene expression, signaling pathways and viral pathogenesis. Many of these interactions are potential targets for small-molecule intervention. Structural, biochemical and functional studies have resulted in hypotheses for drug discovery approaches that are beginning to bear experimental fruit, such as targeting the dsRNA-NS1 interaction, which could lead to restoration of innate immune function and inhibition of virus replication. This review describes biochemical, cell-based and nucleic acid-based approaches to identifying NS1 antagonists. PMID:23796981

  12. The Influenza A Virus Protein NS1 Displays Structural Polymorphism

    PubMed Central

    Carrillo, Berenice; Choi, Jae-Mun; Bornholdt, Zachary A.; Sankaran, Banumathi; Rice, Andrew P.

    2014-01-01

    ABSTRACT NS1 of influenza A virus is a potent antagonist of host antiviral interferon responses. This multifunctional protein with two distinctive domains, an RNA-binding domain (RBD) and an effector domain (ED) separated by a linker region (LR), is implicated in replication, pathogenesis, and host range. Although the structures of individual domains of NS1 from different strains of influenza viruses have been reported, the only structure of full-length NS1 available to date is from an H5N1 strain (A/Vietnam/1203/2004). By carrying out crystallographic analyses of full-length H6N6-NS1 (A/blue-winged teal/MN/993/1980) and an LR deletion mutant, combined with mutational analysis, we show here that these full-length NS1 structures provide an exquisite structural sampling of various conformational states of NS1 that based on the orientation of the ED with respect to RBD can be summarized as “open,” “semi-open,” and “closed” conformations. Our studies show that preference for these states is clearly dictated by determinants such as linker length, residue composition at position 71, and a mechanical hinge, providing a structural basis for strain-dependent functional variations in NS1. Because of the flexibility inherent in the LR, any particular NS1 could sample the conformational space around these states to engage ED in different quaternary interactions so that it may participate in specific protein-protein or protein-RNA interactions to allow for the known multifunctionality of NS1. We propose that such conformational plasticity provides a mechanism for autoregulating NS1 functions, depending on its temporal distribution, posttranslational modifications, and nuclear or cellular localization, during the course of virus infection. IMPORTANCE NS1 of influenza A virus is a multifunctional protein associated with numerous strain-specific regulatory functions during viral infection, including conferring resistance to antiviral interferon induction, replication

  13. Excimer emission from pulsed microhollow cathode discharges in xenon

    SciTech Connect

    Lee, B.-J.; Nam, S. H.; Rahaman, H.; Iberler, M.; Jacoby, J.; Frank, K.

    2013-12-15

    Direct current (dc) microhollow cathode discharge (MHCD) is an intense source for excimer radiation in vacuum ultraviolet at a wavelength of 172 nm in a high pressure xenon (Xe) gas. The concentration of precursors for the excimer formation, i.e., excited and ionized gas atoms, increases significantly by applying high voltage pulse onto the dc MHCD over the pulse duration range from 20 to 100 ns. The intensity of the excimer emission for the voltage pulse of 20 ns duration exceeds that of the emission intensity obtained from the same MHCD operated only in the dc mode, by one order of magnitude. In addition, the emission intensity increases by one order of magnitude over the pulse duration range from 20 to 100 ns. It can be assumed that the emission intensity of the MHCD source increases as long as the duration of the high voltage pulse is shorter than the electron relaxation time. For the high voltage pulse of 100 ns duration, the emission intensity has been found to be further enhanced by a factor of three when the gas pressure is increased from 200 to 800 mbar.

  14. Excimer emission from pulsed microhollow cathode discharges in xenon

    NASA Astrophysics Data System (ADS)

    Lee, B.-J.; Rahaman, H.; Nam, S. H.; Iberler, M.; Jacoby, J.; Frank, K.

    2013-12-01

    Direct current (dc) microhollow cathode discharge (MHCD) is an intense source for excimer radiation in vacuum ultraviolet at a wavelength of 172 nm in a high pressure xenon (Xe) gas. The concentration of precursors for the excimer formation, i.e., excited and ionized gas atoms, increases significantly by applying high voltage pulse onto the dc MHCD over the pulse duration range from 20 to 100 ns. The intensity of the excimer emission for the voltage pulse of 20 ns duration exceeds that of the emission intensity obtained from the same MHCD operated only in the dc mode, by one order of magnitude. In addition, the emission intensity increases by one order of magnitude over the pulse duration range from 20 to 100 ns. It can be assumed that the emission intensity of the MHCD source increases as long as the duration of the high voltage pulse is shorter than the electron relaxation time. For the high voltage pulse of 100 ns duration, the emission intensity has been found to be further enhanced by a factor of three when the gas pressure is increased from 200 to 800 mbar.

  15. Nanosecond electric pulses penetrate the nucleus and enhance speckle formation

    SciTech Connect

    Chen Nianyong Garner, Allen L.; Chen, George; Jing Yu; Deng Yuping; Swanson, R. James; Kolb, Juergen F.; Beebe, Stephen J.; Joshi, Ravindra P.; Schoenbach, Karl H.

    2007-12-14

    Nanosecond electric pulses generate nanopores in the interior membranes of cells and modulate cellular functions. Here, we used confocal microscopy and flow cytometry to observe Smith antigen antibody (Y12) binding to nuclear speckles, known as small nuclear ribonucleoprotein particles (snRNPs) or intrachromatin granule clusters (IGCs), in Jurkat cells following one or five 10 ns, 150 kV/cm pulses. Using confocal microscopy and flow cytometry, we observed changes in nuclear speckle labeling that suggested a disruption of pre-messenger RNA splicing mechanisms. Pulse exposure increased the nuclear speckled substructures by {approx}2.5-fold above basal levels while the propidium iodide (PI) uptake in pulsed cells was unchanged. The resulting nuclear speckle changes were also cell cycle dependent. These findings suggest that 10 ns pulses directly influenced nuclear processes, such as the changes in the nuclear RNA-protein complexes.

  16. Subcellular effects of nanosecond electrical pulses.

    PubMed

    Schoenbach, Karl H; Joshi, Ravindra; Kolb, J; Buescher, Stephen; Beebe, Stephen

    2004-01-01

    Electrical models for biological cells predict that reducing the duration of applied electrical pulses to values below the charging time of the outer membrane causes a strong increase in the probability for electric field interactions with intracellular structures. For electric field amplitudes exceeding MV/m such pulses are expected to cause electroporation of cell organelles, with the required electric field amplitude scaling linearly with the inverse of pulse duration. Experimental studies where human cells were exposed to pulsed electric field of up to 300 kV/cm amplitude with duration as short as 10 ns, have confirmed this hypothesis. The observed effects include the breaching of intracellular granule membranes without permanent damage to the cell membrane, abrupt rises in intracellular free calcium levels, and enhanced expression of genes. At increased electric fields, the application of nanosecond pulses induces apoptosis in biological cells, an effect that has been shown to reduce the growth of tumors.

  17. Monoclonal Antibodies Against NS2B of Japanese Encephalitis Virus.

    PubMed

    Dong, Qian; Xu, Qiuping; Ruan, Xindi; Huang, Shaomei; Cao, Shengbo

    2015-04-01

    Japanese encephalitis (JE) is one of the most important viral encephalitis, caused by the Japanese encephalitis virus (JEV). The function of non-structural protein 2B (NS2B) mostly remains unclear. In our study, NS2B of Japanese encephalitis virus (JEV) was expressed in Escherichia coli and purified by dialysis. After fusing mouse myeloma cell line SP2/0 with spleen lymphocytes from NS2B protein immunized mice, three clones of monoclonal antibodies (MAbs), named 1B9, 3E12, and 4E6, were generated. The specificity and sensitivity of MAbs were demonstrated by ELISA, indirect immunofluorescence assay, and Western blot. These MAbs will be useful in further exploration of the functions of NS2B and the pathogenesis of Japanese encephalitis virus. PMID:25897607

  18. NS1: A corner piece in the dengue pathogenesis puzzle?

    PubMed

    Thomas, Stephen J

    2015-09-01

    Soluble dengue virus NS1 protein induces proinflammatory immune responses via Toll-like receptor 4 and disrupts endothelial cell integrity, resulting in vascular leakage (Beatty et al. and Modhiran et al., this issue). PMID:26355028

  19. Pulse stretcher

    DOEpatents

    Horton, J.A.

    1994-05-03

    Apparatus for increasing the length of a laser pulse to reduce its peak power without substantial loss in the average power of the pulse is disclosed. The apparatus uses a White cell having a plurality of optical delay paths of successively increasing number of passes between the field mirror and the objective mirrors. A pulse from a laser travels through a multi-leg reflective path between a beam splitter and a totally reflective mirror to the laser output. The laser pulse is also simultaneously injected through the beam splitter to the input mirrors of the optical delay paths. The pulses from the output mirrors of the optical delay paths go simultaneously to the laser output and to the input mirrors of the longer optical delay paths. The beam splitter is 50% reflective and 50% transmissive to provide equal attenuation of all of the pulses at the laser output. 6 figures.

  20. High gain broadband amplification of ultraviolet pulses in optical parametric chirped pulse amplifier.

    PubMed

    Wnuk, Paweł; Stepanenko, Yuriy; Radzewicz, Czesław

    2010-04-12

    We report on a high gain amplification of broadband ultraviolet femtosecond pulses in an optical parametric chirped pulse amplifier. Broadband ultraviolet seed pulses were obtained by an achromatic frequency doubling of the output from a femtosecond Ti:Sapphire oscillator. Stretched seed pulses were amplified in a multipass parametric amplifier with a single BBO crystal pumped by a ns frequency quadrupled Nd:YAG laser. A noncollinear configuration was used for a broadband amplification. The total (after compression) amplification of 2.510(5) was achieved, with compressed pulse energy of 30 microJ and pulse duration of 24 fs. We found that the measured gain was limited by thermal effects induced by the absorption of the pump laser by color centers created in the BBO crystal.

  1. CPLOAS_2 V2.10 verification report.

    SciTech Connect

    Groth, Katrina M.

    2014-07-01

    A series of test cases designed to verify the correct implementation of several features of the CPLOAS_2 program are documented. CPLOAS_2 is used to calculate the probability of loss of assured safety (PLOAS) for a weak link (WL)/strong link (SL) system. CPLOAS_2 takes physical properties (e.g., temperature, pressure, etc.) of a WL/SL system and uses these properties and definitions of link failure properties in probabilistic calculations to determine PLOAS. The features being tested include (i) six aleatory distribution forms, (ii) five numerical procedures for the determination of PLOAS (i.e., one quadrature procedure, two simple random sampling procedures, and two importance sampling procedures), and (iii) time and environmental margin calculations. All tests were performed with CPLOAS_2 version 2.10.

  2. Research and development of RHIC injection kicker upgrade with nano second FID pulse generator

    SciTech Connect

    Zhang W.; Sandberg, J.; Hahn, H.; Fischer, W.; Liaw, C.J.; Pai, C.; Tuozzolo, J.

    2012-05-20

    Our recent effort to test a 50 kV, 1 kA, 50 ns pulse width, 10 ns pulse rise time FID pulse generator with a 250 ft transmission cable, resistive load, and existing RHIC injection kicker magnet has produced unparalleled results. This is the very first attempt to drive a high strength fast kicker magnet with a nano second high pulsed power (50 MVA) generator for large accelerator and colliders. The technology is impressive. We report here the result and future plan of RHIC Injection kicker upgrade.

  3. Transform-limited pulses generated by an actively Q-switched distributed fiber laser.

    PubMed

    Cuadrado-Laborde, C; Pérez-Millán, P; Andrés, M V; Díez, A; Cruz, J L; Barmenkov, Yu O

    2008-11-15

    A single-mode, transform-limited, actively Q-switched distributed-feedback fiber laser is presented, based on a new in-line acoustic pulse generator. Our technique permits a continuous adjustment of the repetition rate that modulates the Q factor of the cavity. Optical pulses of 800 mW peak power, 32 ns temporal width, and up to 20 kHz repetition rates were obtained. The measured linewidth demonstrates that these pulses are transform limited: 6 MHz for a train of pulses of 10 kHz repetition rate, 80 ns temporal width, and 60 mW peak power. Efficient excitation of spontaneous Brillouin scattering is demonstrated.

  4. Pulse Voltammetry

    NASA Astrophysics Data System (ADS)

    Stojek, Zbigniew

    The idea of imposing potential pulses and measuring the currents at the end of each pulse was proposed by Barker in a little-known journal as early as in 1958 [1]. However, the first reliable trouble-free and affordable polarographs offering voltammetric pulse techniques appeared on the market only in the 1970s. This delay was due to some limitations on the electronic side. In the 1990s, again substantial progress in electrochemical pulse instrumentation took place. This was related to the introduction of microprocessors, computers, and advanced software.

  5. A high-impedance attenuator for measurement of high-voltage nanosecond-range pulses.

    PubMed

    Yu, Binxiong; Liu, Jinliang; Zhang, Tianyang; Hong, Zhiqiang

    2013-05-01

    A novel kind of high-impedance cable attenuator for measurement of high-voltage ns-range pulses is investigated in this paper. The input and output ports of the proposed attenuator were both high-impedance ports, and good pulse response characteristics of the proposed attenuator were obtained with pulse response time less than 1 ns. According to the requirement of measurement, two attenuators with lengths at 14 m and 0.7 m were developed with response time of 1 ns and 20 ns, and the attenuation coefficient of 96 and 33.5, respectively. The attenuator with the length of 14 m was used as a secondary-stage attenuator of a capacitive divider to measure the high-voltage pulses at several hundred ns range. The waveform was improved by the proposed attenuator in contrast to the result only measured by the same capacitive divider and a long cable line directly. The 0.7 m attenuator was also used as a secondary-stage attenuator of a standard resistant divider for an accurate measurement of high-voltage pulses at 100 ns range. The proposed cable attenuator can be used to substitute the traditional secondary-stage attenuators for the measurement of high-voltage pulses.

  6. Flavivirus NS1: a multifaceted enigmatic viral protein.

    PubMed

    Rastogi, Meghana; Sharma, Nikhil; Singh, Sunit Kumar

    2016-01-01

    Flaviviruses are emerging arthropod-borne viruses representing an immense global health problem. The prominent viruses of this group include dengue virus, yellow fever virus, Japanese encephalitis virus, West Nile virus tick borne encephalitis virus and Zika Virus. These are endemic in many parts of the world. They are responsible for the illness ranging from mild flu like symptoms to severe hemorrhagic, neurologic and cognitive manifestations leading to death. NS1 is a highly conserved non-structural protein among flaviviruses, which exist in diverse forms. The intracellular dimer form of NS1 plays role in genome replication, whereas, the secreted hexamer plays role in immune evasion. The secreted NS1 has been identified as a potential diagnostic marker for early detection of the infections caused by flaviviruses. In addition to the diagnostic marker, the importance of NS1 has been reported in the development of therapeutics. NS1 based subunit vaccines are at various stages of development. The structural details and diverse functions of NS1 have been discussed in detail in this review.

  7. Flavivirus NS1: a multifaceted enigmatic viral protein.

    PubMed

    Rastogi, Meghana; Sharma, Nikhil; Singh, Sunit Kumar

    2016-01-01

    Flaviviruses are emerging arthropod-borne viruses representing an immense global health problem. The prominent viruses of this group include dengue virus, yellow fever virus, Japanese encephalitis virus, West Nile virus tick borne encephalitis virus and Zika Virus. These are endemic in many parts of the world. They are responsible for the illness ranging from mild flu like symptoms to severe hemorrhagic, neurologic and cognitive manifestations leading to death. NS1 is a highly conserved non-structural protein among flaviviruses, which exist in diverse forms. The intracellular dimer form of NS1 plays role in genome replication, whereas, the secreted hexamer plays role in immune evasion. The secreted NS1 has been identified as a potential diagnostic marker for early detection of the infections caused by flaviviruses. In addition to the diagnostic marker, the importance of NS1 has been reported in the development of therapeutics. NS1 based subunit vaccines are at various stages of development. The structural details and diverse functions of NS1 have been discussed in detail in this review. PMID:27473856

  8. A repetitive long-pulse power generator based on pulse forming network and linear transformer driver.

    PubMed

    Li, Mingjia; Kang, Qiang; Tan, Jie; Zhang, Faqiang; Luo, Min; Xiang, Fei

    2016-06-01

    A compact module for long-pulse power generator, based on Blumlein pulse forming network (PFN), was designed. Two Blumlein PFNs with L-type configuration and 20 Ω characteristic impedance were connected symmetrically to the primary coil of the linear transformer driver (LTD) and driven by an identical high voltage spark switch to ensure two Blumlein PFNs synchronizing operation. The output pulse of the module connected with 10 Ω water load is about 135 kV in amplitude and 200 ns in duration with a rise time of ∼50 ns and a flat top of ∼100 ns. On this basis, a repetitive long-pulse power generator based on PFN-LTD has been developed, which was composed of four modules. The following technical parameters of the generator were achieved on planar diode: output voltage amplitude of ∼560 kV, output current amplitude of ∼10 kA at a repetition rate of 25 Hz. The generator operates stable and outputs more than 10(4) pulses. Meanwhile, the continuous operating time of the generator is up to 60 s. PMID:27370479

  9. A repetitive long-pulse power generator based on pulse forming network and linear transformer driver

    NASA Astrophysics Data System (ADS)

    Li, Mingjia; Kang, Qiang; Tan, Jie; Zhang, Faqiang; Luo, Min; Xiang, Fei

    2016-06-01

    A compact module for long-pulse power generator, based on Blumlein pulse forming network (PFN), was designed. Two Blumlein PFNs with L-type configuration and 20 Ω characteristic impedance were connected symmetrically to the primary coil of the linear transformer driver (LTD) and driven by an identical high voltage spark switch to ensure two Blumlein PFNs synchronizing operation. The output pulse of the module connected with 10 Ω water load is about 135 kV in amplitude and 200 ns in duration with a rise time of ˜50 ns and a flat top of ˜100 ns. On this basis, a repetitive long-pulse power generator based on PFN-LTD has been developed, which was composed of four modules. The following technical parameters of the generator were achieved on planar diode: output voltage amplitude of ˜560 kV, output current amplitude of ˜10 kA at a repetition rate of 25 Hz. The generator operates stable and outputs more than 104 pulses. Meanwhile, the continuous operating time of the generator is up to 60 s.

  10. A repetitive long-pulse power generator based on pulse forming network and linear transformer driver.

    PubMed

    Li, Mingjia; Kang, Qiang; Tan, Jie; Zhang, Faqiang; Luo, Min; Xiang, Fei

    2016-06-01

    A compact module for long-pulse power generator, based on Blumlein pulse forming network (PFN), was designed. Two Blumlein PFNs with L-type configuration and 20 Ω characteristic impedance were connected symmetrically to the primary coil of the linear transformer driver (LTD) and driven by an identical high voltage spark switch to ensure two Blumlein PFNs synchronizing operation. The output pulse of the module connected with 10 Ω water load is about 135 kV in amplitude and 200 ns in duration with a rise time of ∼50 ns and a flat top of ∼100 ns. On this basis, a repetitive long-pulse power generator based on PFN-LTD has been developed, which was composed of four modules. The following technical parameters of the generator were achieved on planar diode: output voltage amplitude of ∼560 kV, output current amplitude of ∼10 kA at a repetition rate of 25 Hz. The generator operates stable and outputs more than 10(4) pulses. Meanwhile, the continuous operating time of the generator is up to 60 s.

  11. Replacement of the respiratory syncytial virus nonstructural proteins NS1 and NS2 by the V protein of parainfluenza virus 5

    SciTech Connect

    Tran, Kim C.; He, Biao; Teng, Michael N.

    2007-11-10

    Paramyxoviruses have been shown to produce proteins that inhibit interferon production and signaling. For human respiratory syncytial virus (RSV), the nonstructural NS1 and NS2 proteins have been shown to have interferon antagonist activity through an unknown mechanism. To understand further the functions of NS1 and NS2, we generated recombinant RSV in which both NS1 and NS2 were replaced by the PIV5 V protein, which has well-characterized IFN antagonist activities ({delta}NS1/2-V). Expression of V was able to partially inhibit IFN responses in {delta}NS1/2-V-infected cells. In addition, the replication kinetics of {delta}NS1/2-V were intermediate between {delta}NS1/2 and wild-type (rA2) in A549 cells. However, expression of V did not affect the ability of {delta}NS1/2-V to activate IRF3 nuclear translocation and IFN{beta} transcription. These data indicate that V was able to replace some of the IFN inhibitory functions of the RSV NS1 and NS2 proteins, but also that NS1 and NS2 have functions in viral replication beyond IFN antagonism.

  12. Double nanosecond pulses generation in ytterbium fiber laser.

    PubMed

    Veiko, V P; Lednev, V N; Pershin, S M; Samokhvalov, A A; Yakovlev, E B; Zhitenev, I Yu; Kliushin, A N

    2016-06-01

    Double pulse generation mode for nanosecond ytterbium fiber laser was developed. Two sequential 60-200 ns laser pulses with variable delay between them were generated by acousto-optic modulator opening with continuous diode pumping. A custom radio frequency generator was developed to produce two sequential "opening" radio pulses with a delay of 0.2-1 μs. It was demonstrated that double pulse generation did not decrease the average laser power while providing the control over the laser pulse power profile. Surprisingly, a greater peak power in the double pulse mode was observed for the second laser pulse. Laser crater studies and plasma emission measurements revealed an improved efficiency of laser ablation in the double pulse mode. PMID:27370433

  13. Double nanosecond pulses generation in ytterbium fiber laser

    NASA Astrophysics Data System (ADS)

    Veiko, V. P.; Lednev, V. N.; Pershin, S. M.; Samokhvalov, A. A.; Yakovlev, E. B.; Zhitenev, I. Yu.; Kliushin, A. N.

    2016-06-01

    Double pulse generation mode for nanosecond ytterbium fiber laser was developed. Two sequential 60-200 ns laser pulses with variable delay between them were generated by acousto-optic modulator opening with continuous diode pumping. A custom radio frequency generator was developed to produce two sequential "opening" radio pulses with a delay of 0.2-1 μs. It was demonstrated that double pulse generation did not decrease the average laser power while providing the control over the laser pulse power profile. Surprisingly, a greater peak power in the double pulse mode was observed for the second laser pulse. Laser crater studies and plasma emission measurements revealed an improved efficiency of laser ablation in the double pulse mode.

  14. Temporal pulse cleaning by a self-diffraction process for ultrashort laser pulses

    NASA Astrophysics Data System (ADS)

    Xie, Na; Zhou, Kainan; Sun, Li; Wang, Xiaodong; Guo, Yi; Li, Qing; Su, Jingqin

    2014-11-01

    Applying the self-diffraction process to clean ultrashort laser pulses temporally is a recently developed effective way to temporal contrast enhancement. In this paper, we attempt to clean ultrashort laser pulses temporally by the self-diffraction process. Experiments were carried out to study the temporal contrast improvement in the front-end system of an ultraintense and ultrashort laser facility, i.e. the super intense laser for experiment on the extremes (SILEX-I). The results show that the maximum conversion efficiency of the first-order self-diffraction (SD1) pulse is 11%. The temporal contrast of the SD1 signal is improved by two orders of magnitude, i.e. to 103, for a 2.4-ns prepulse with initial contrast of ~10. For a 5.5 -ns prepulse with initial contrast of 2×103, the temporal contrast of the SD1 signal is improved by more than three orders of magnitude.

  15. Increasing the RF energy per pulse of an RKO

    SciTech Connect

    Hendricks, K.J.; Haworth, M.D.

    1998-06-01

    The Air Force Research Laboratory RKO source has recently demonstrated the ability to convert electron beam power to RF power until the termination of the electron beam pulse, achieving a power of 1.5 GW at an energy of 170 J. These results represent an increase in power of 25--30% and energy extracted from this source. This paper discusses the principal research areas encountered in lengthening the RF pulse (FWHM) from 50 ns to the present 120 ns and the associated increase in the RF energy.

  16. GaSe damage threshold under IR pulse pumping

    NASA Astrophysics Data System (ADS)

    Guo, Jin; Xie, Ji-Jiang; Zhang, Laiming; Chen, Fei; Jiang, Ke; Alexeev, Sergei V.; Andreev, Yury M.; Kokh, Konstantin A.; Lanskii, Gregory V.; Losev, Valery F.; Lubenko, Dmitry M.; Shaiduko, Anna V.; Svetlichnyi, Valeriy A.

    2012-01-01

    Damage threshold of non-linear GaSe crystals under IR fs (Ti:Sapphiere 800 nm laser and 1.1-2.9μm OPG) and ns (2. 79 Er3+:YSGG and 10.6μm CO2 laser) pulse pumping is studded in details. Local micro defects and field induced effects (GaSe dissociation, multiphoton absorptions and transient transparency origin effects) are identified as responsible for damage threshold in this case. Local (including nano scaled) defects and thermal effects are identified as reason of damage threshold under ns pulse pumping.

  17. Effects of temporal laser profile on the emission spectra for underwater laser-induced breakdown spectroscopy: Study by short-interval double pulses with different pulse durations

    SciTech Connect

    Tamura, Ayaka Matsumoto, Ayumu; Nishi, Naoya; Sakka, Tetsuo; Nakajima, Takashi; Ogata, Yukio H.; Fukami, Kazuhiro

    2015-01-14

    We investigate the effects of temporal laser profile on the emission spectra of laser ablation plasma in water. We use short-interval (76 ns) double pulses with different pulse durations of the composing two pulses for the irradiation of underwater target. Narrow atomic spectral lines in emission spectra are obtained by the irradiation, where the two pulses are wide enough to be merged into a single-pulse-like temporal profile, while deformed spectra are obtained when the two pulses are fully separated. The behavior of the atomic spectral lines for the different pulse durations is consistent with that of the temporal profiles of the optical emission intensities of the plasma. All these results suggest that continuous excitation of the plasma during the laser irradiation for ∼100 ns is a key to obtain narrow emission spectral lines.

  18. Long term survival of mice with hepatocellular carcinoma after pulse power ablation with nanosecond pulsed electric fields.

    PubMed

    Chen, X; Zhuang, J; Kolb, J F; Schoenbach, K H; Beebe, S J

    2012-02-01

    Novel therapies are needed for treating hepatocellular carcinoma (HCC) without recurrence in a single procedure. In this work we evaluated anti-neoplastic effects of a pulse power ablation (PPA) with nanosecond pulsed electric fields (nsPEFs), a non-thermal, non-drug, local, regional method and investigated its molecular mechanisms for hepatocellular carcinoma tumor ablation in vivo. An ectopic tumor model was established using C57BL/6 mice with Hepa1-6 hepatocellular carcinoma cells. Pulses with durations of 30 or 100 ns and fast rise times were delivered by a needle or ring electrode with different electric field strengths (33, 50 and 68 kV/cm), and 900 pulses in three treatment sessions (300 pulses each session) or a single 900 pulse treatment. Treated and control tumor volumes were monitored by ultrasound and apoptosis and angiogenesis markers were evaluated by immunohistochemistry. Seventy five percent of primary hepatocellular carcinoma tumors were eradicated with 900 hundred pulses at 100 ns pulses at 68 kV/cm in a single treatment or in three treatment sessions without recurrence within 9 months. Using quantitative analysis, tumors in treated animals showed nsPEF-mediated nuclear condensation (3 h post-pulse), cell shrinkage (1 h), increases in active executioner caspases (caspase-3 > -7 > -6) and terminal deoxynucleotidyl transferase dUTP nick-end-labeling (1 h) with decreases in vascular endothelial growth factor expression (7d) and micro-vessel density (14d). NsPEF ablation eliminated hepatocellular carcinoma tumors by targeting two therapeutic sites, apoptosis induction and inhibition of angiogenesis, both important cancer hallmarks. These data indicate that PPA with nsPEFs is not limited to treating skin cancers and provide a rationale for continuing to investigate pulse power ablation for hepatocellular carcinoma using other models in pre-clinical applications and ultimately in clinical trials. Based on present treatments for specific HCC stages, it

  19. Proper processing of dengue virus nonstructural glycoprotein NS1 requires the N-terminal hydrophobic signal sequence and the downstream nonstructural protein NS2a.

    PubMed

    Falgout, B; Chanock, R; Lai, C J

    1989-05-01

    Expression of dengue virus gene products involves specific proteolytic cleavages of a precursor polyprotein. To study the flanking sequences required for expression of the dengue virus nonstructural glycoprotein NS1, we constructed a series of recombinant vaccinia viruses that contain the coding sequence for NS1 in combination with various lengths of upstream and downstream sequences. The NS1 products expressed by these viruses in infected CV-1 cells were immune precipitated and analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The data show that the 24-residue hydrophobic sequence preceding NS1 was necessary and sufficient for the production of glycosylated NS1 and that this sequence was cleaved from NS1 in the absence of most dengue virus proteins. This finding is consistent with previous proposals that this hydrophobic sequence serves as an N-terminal signal sequence that is cleaved by signal peptidase. The cleavage between the C terminus of NS1 and the downstream protein NS2a occurred when the complete NS2a was present. Recombinant viruses containing NS1 plus 15 or 49% of NS2a produced proteins larger than authentic NS1, indicating that the cleavage between NS1 and NS2a had not occurred. Failure of cleavage was not corrected by coinfection with a recombinant virus capable of cleavage. These results suggest that NS2a may be a cis-acting protease that cleaves itself from NS1, or NS2a may provide sequences for recognition by a specific cellular protease that cleaves at the NS1-NS2a junction.

  20. Robust Short-Pulse, High-Peak-Power Laser Transmitter for Optical Communications

    NASA Technical Reports Server (NTRS)

    Wright, Malcolm W.

    2009-01-01

    We report on a pulsed fiber based master oscillator power amplifier laser at 1550 nm to support moderate data rates with high peak powers in a compact package suitable for interplanetary optical communications. To accommodate pulse position modulation, the polarization maintaining laser transmitter generates pulses from 0.1 to 1 ns with variable duty cycle over a pulse repetition frequency range of 10 to 100 MHz.

  1. PULSE AMPLIFIER

    DOEpatents

    Johnstone, C.W.

    1958-06-17

    The improvement of pulse amplifiers used with scintillation detectors is described. The pulse amplifier circuit has the advantage of reducing the harmful effects of overloading cause by large signal inputs. In general the pulse amplifier circuit comprises two amplifier tubes with the input pulses applied to one amplifier grid and coupled to the second amplifier tube through a common cathode load. The output of the second amplifier is coupled from the plate circuit to a cathode follower tube grid and a diode tube in connected from grid to cathode of the cathode follower tube. Degenerative feedback is provided in the second amplifier by coupling a signal from the cathode follower cathode to the second amplifier grid. The circuit proqides moderate gain stability, and overload protection for subsequent pulse circuits.

  2. An 8-GW long-pulse generator based on Tesla transformer and pulse forming network

    NASA Astrophysics Data System (ADS)

    Su, Jiancang; Zhang, Xibo; Li, Rui; Zhao, Liang; Sun, Xu; Wang, Limin; Zeng, Bo; Cheng, Jie; Wang, Ying; Peng, Jianchang; Song, Xiaoxin

    2014-06-01

    A long-pulse generator TPG700L based on a Tesla transformer and a series pulse forming network (PFN) is constructed to generate intense electron beams for the purpose of high power microwave (HPM) generation. The TPG700L mainly consists of a 12-stage PFN, a built-in Tesla transformer in a pulse forming line, a three-electrode gas switch, a transmission line with a trigger, and a load. The Tesla transformer and the compact PFN are the key technologies for the development of the TPG700L. This generator can output electrical pulses with a width as long as 200 ns at a level of 8 GW and a repetition rate of 50 Hz. When used to drive a relative backward wave oscillator for HPM generation, the electrical pulse width is about 100 ns on a voltage level of 520 kV. Factors affecting the pulse waveform of the TPG700L are also discussed. At present, the TPG700L performs well for long-pulse HPM generation in our laboratory.

  3. A compact bipolar pulse-forming network-Marx generator based on pulse transformers.

    PubMed

    Zhang, Huibo; Yang, Jianhua; Lin, Jiajin; Yang, Xiao

    2013-11-01

    A compact bipolar pulse-forming network (PFN)-Marx generator based on pulse transformers is presented in this paper. The high-voltage generator consisted of two sets of pulse transformers, 6 stages of PFNs with ceramic capacitors, a switch unit, and a matched load. The design is characterized by the bipolar pulse charging scheme and the compact structure of the PFN-Marx. The scheme of bipolar charging by pulse transformers increased the withstand voltage of the ceramic capacitors in the PFNs and decreased the number of the gas gap switches. The compact structure of the PFN-Marx was aimed at reducing the parasitic inductance in the generator. When the charging voltage on the PFNs was 35 kV, the matched resistive load of 48 Ω could deliver a high-voltage pulse with an amplitude of 100 kV. The full width at half maximum of the load pulse was 173 ns, and its rise time was less than 15 ns.

  4. An 8-GW long-pulse generator based on Tesla transformer and pulse forming network.

    PubMed

    Su, Jiancang; Zhang, Xibo; Li, Rui; Zhao, Liang; Sun, Xu; Wang, Limin; Zeng, Bo; Cheng, Jie; Wang, Ying; Peng, Jianchang; Song, Xiaoxin

    2014-06-01

    A long-pulse generator TPG700L based on a Tesla transformer and a series pulse forming network (PFN) is constructed to generate intense electron beams for the purpose of high power microwave (HPM) generation. The TPG700L mainly consists of a 12-stage PFN, a built-in Tesla transformer in a pulse forming line, a three-electrode gas switch, a transmission line with a trigger, and a load. The Tesla transformer and the compact PFN are the key technologies for the development of the TPG700L. This generator can output electrical pulses with a width as long as 200 ns at a level of 8 GW and a repetition rate of 50 Hz. When used to drive a relative backward wave oscillator for HPM generation, the electrical pulse width is about 100 ns on a voltage level of 520 kV. Factors affecting the pulse waveform of the TPG700L are also discussed. At present, the TPG700L performs well for long-pulse HPM generation in our laboratory.

  5. A compact bipolar pulse-forming network-Marx generator based on pulse transformers

    NASA Astrophysics Data System (ADS)

    Zhang, Huibo; Yang, Jianhua; Lin, Jiajin; Yang, Xiao

    2013-11-01

    A compact bipolar pulse-forming network (PFN)-Marx generator based on pulse transformers is presented in this paper. The high-voltage generator consisted of two sets of pulse transformers, 6 stages of PFNs with ceramic capacitors, a switch unit, and a matched load. The design is characterized by the bipolar pulse charging scheme and the compact structure of the PFN-Marx. The scheme of bipolar charging by pulse transformers increased the withstand voltage of the ceramic capacitors in the PFNs and decreased the number of the gas gap switches. The compact structure of the PFN-Marx was aimed at reducing the parasitic inductance in the generator. When the charging voltage on the PFNs was 35 kV, the matched resistive load of 48 Ω could deliver a high-voltage pulse with an amplitude of 100 kV. The full width at half maximum of the load pulse was 173 ns, and its rise time was less than 15 ns.

  6. An 8-GW long-pulse generator based on Tesla transformer and pulse forming network

    SciTech Connect

    Su, Jiancang; Zhang, Xibo; Li, Rui; Zhao, Liang Sun, Xu; Wang, Limin; Zeng, Bo; Cheng, Jie; Wang, Ying; Peng, Jianchang; Song, Xiaoxin

    2014-06-15

    A long-pulse generator TPG700L based on a Tesla transformer and a series pulse forming network (PFN) is constructed to generate intense electron beams for the purpose of high power microwave (HPM) generation. The TPG700L mainly consists of a 12-stage PFN, a built-in Tesla transformer in a pulse forming line, a three-electrode gas switch, a transmission line with a trigger, and a load. The Tesla transformer and the compact PFN are the key technologies for the development of the TPG700L. This generator can output electrical pulses with a width as long as 200 ns at a level of 8 GW and a repetition rate of 50 Hz. When used to drive a relative backward wave oscillator for HPM generation, the electrical pulse width is about 100 ns on a voltage level of 520 kV. Factors affecting the pulse waveform of the TPG700L are also discussed. At present, the TPG700L performs well for long-pulse HPM generation in our laboratory.

  7. Intense Pulsed Heavy Ion Beam Technology

    NASA Astrophysics Data System (ADS)

    Masugata, Katsumi; Ito, Hiroaki

    Development of intense pulsed heavy ion beam accelerator technology is described for the application of materials processing. Gas puff plasma gun and vacuum arc discharge plasma gun were developed as an active ion source for magnetically insulated pulsed ion diode. Source plasma of nitrogen and aluminum were successfully produced with the gas puff plasma gun and the vacuum arc plasma gun, respectively. The ion diode was successfully operated with gas puff plasma gun at diode voltage 190 kV, diode current 2.2 kA and nitrogen ion beam of ion current density 27 A/cm2 was obtained. The ion composition was evaluated by a Thomson parabola spectrometer and the purity of the nitrogen ion beam was estimated to be 86%. The diode also operated with aluminum ion source of vacuum arc plasma gun. The ion diode was operated at 200 kV, 12 kA, and aluminum ion beam of current density 230 A/cm2 was obtained. The beam consists of aluminum ions (Al(1-3)+) of energy 60-400 keV, and protons (90-130 keV), and the purity was estimated to be 89 %. The development of the bipolar pulse accelerator (BPA) was reported. A double coaxial type bipolar pulse generator was developed as the power supply of the BPA. The generator was tested with dummy load of 7.5 ohm, bipolar pulses of -138 kV, 72 ns (1st pulse) and +130 kV, 70 ns (2nd pulse) were succesively generated. By applying the bipolar pulse to the drift tube of the BPA, nitrogen ion beam of 2 A/cm2 was observed in the cathode, which suggests the bipolar pulse acceleration.

  8. CARS imaging with a single laser pulse

    NASA Astrophysics Data System (ADS)

    Heinrich, Christoph; Bernet, Stefan; Ritsch-Marte, Monika

    2005-09-01

    We report coherent anti-Stokes Raman scattering (CARS) microscopy with ns-pulses. The chosen wide-field geometry allows imaging of the whole field of view at once, without scanning of the sample. Tuning the difference of the two incident laser frequencies overlapping at the sample to a specific vibrational level, one can map the spatial distribution of selected Raman active molecules. Both the CARS signal of the surrounding solvent can be excited (negative contrast) as well as the signal of the structure embedded by the solvent (positive contrast). As a biological sample we used slices of a sunflower seed and tuned to the vibrational transition of its ingredient - linoleic acid - at 2870 cm-1 which corresponds to the strongest C-H stretching vibration. Even with a single pair of laser pulses of 3 ns duration it was possible to acquire a rough, but still meaningful image.

  9. Electromagnetic acceleration of material from a plate hit by a pulsed electron beam

    SciTech Connect

    Garcia, M.

    1998-04-16

    An intense pulsed electron beam traversing a thin metal plate creates a volume of dense plasma. Current flows in this plasma as a result of the charge and magnetic field introduced by the relativistic electrons. A magnetic field may linger after the electron beam pulse because of the conductivity of the material. This field decays by both diffusing out of the conducting matter and causing it to expand. If the magnetized matter is of low density and high conductivity it may expand quickly. Scaling laws for this acceleration are sought by analyzing the idealization of a steady axisymmetric flow. This case simplifies a general formulation based on both Euler`s and Maxwell`s equations. As an example, fluid with conductivity {sigma} = 8 x 10{sup 4} Siemens/m, density {rho} = 8 x 10{sup -3} kg/m{sup 3}, and initially magnetized to B = 1 Tesla can accelerate to v = 10{sup 4} m/s within a distance comparable to L = 1 mm and a time comparable to {sigma}{mu}L{sup 2} = 100 ns, which is the magnetic diffusion time. If instead, {sigma} = 8 x 10{sup 3} Siemens/m and {rho} = 8 x 10{sup -5} kg/m{sup 3} then v = 10{sup 5} m/s with a magnetic diffusion time {sigma}{mu}L{sup 2} = 10 ns. These idealized flows have R{sub M} = {sigma}{mu}vL = 1, where R{sub M} is the magnetic Reynolds number. The target magnetizes by a thermal electric effect.

  10. Nanosecond, high-intensity pulsed electric fields induce apoptosis in human cells.

    PubMed

    Beebe, Stephen J; Fox, Paula M; Rec, Laura J; Willis, E Lauren K; Schoenbach, Karl H

    2003-08-01

    Electroporation by using pulsed electric fields with long durations compared with the charging time of the plasma membrane can induce cell fusion or introduce xenomolecules into cells. Nanosecond pulse power technology generates pulses with high-intensity electric fields, but with such short durations that the charging time of the plasma membrane is not reached, but intracellular membranes are affected. To determine more specifically their effects on cell structure and function, human cells were exposed to high intensity (up to 300 kV/cm) nanosecond (10-300 ns) pulsed electric fields (nsPEF) and were analyzed at the cellular and molecular levels. As the pulse duration decreased, plasma membrane electroporation decreased and appearances of apoptosis markers were delayed. NsPEF induced apoptosis within tens of minutes, depending on the pulse duration. Annexin-V binding, caspase activation, decreased forward light scatter, and cytochrome c release into the cytoplasm were coincident. Apoptosis was caspase- and mitochondria-dependent but independent of plasma membrane electroporation and thermal changes. The results suggest that with decreasing pulse durations, nsPEF modulate cell signaling from the plasma membrane to intracellular structures and functions. NsPEF technology provides a unique, high-power, energy-independent tool to recruit plasma membrane and/or intracellular signaling mechanisms that can delete aberrant cells by apoptosis.

  11. Inactivation of Ricin Toxin by Nanosecond Pulsed Electric Fields Including Evidences from Cell and Animal Toxicity.

    PubMed

    Wei, Kai; Li, Wei; Gao, Shan; Ji, Bin; Zang, Yating; Su, Bo; Wang, Kaile; Yao, Maosheng; Zhang, Jue; Wang, Jinglin

    2016-01-05

    Ricin is one of the most toxic and easily produced plant protein toxin extracted from the castor oil plant, and it has been classified as a chemical warfare agent. Here, nanosecond pulsed electric fields (nsPEFs) at 30 kV/cm (pulse durations: 10 ns, 100 ns, and 300 ns) were applied to inactivating ricin up to 4.2 μg/mL. To investigate the efficacy, cells and mice were tested against the ricin treated by the nsPEFs via direct intraperitoneal injection and inhalation exposure. Results showed that nsPEFs treatments can effectively reduce the toxicity of the ricin. Without the nsPEFs treatment, 100% of mice were killed upon the 4 μg ricin injection on the first day, however 40% of the mice survived the ricin treated by the nsPEFs. Compared to injection, inhalation exposure even with higher ricin dose required longer time to observe mice fatality. Pathological observations revealed damages to heart, lung, kidney, and stomach after the ricin exposure, more pronounced for lung and kidney including severe bleeding. Sodium dodecyl sulfate polyacrylamide gel electrophoresis(SDS-PAGE) and circular dichroism (CD) analyses revealed that although the primary structure of ricin was not altered, its secondary structures (beta-sheet and beta-turn) underwent transition upon the nsPEFs treatment.

  12. Inactivation of Ricin Toxin by Nanosecond Pulsed Electric Fields Including Evidences from Cell and Animal Toxicity

    NASA Astrophysics Data System (ADS)

    Wei, Kai; Li, Wei; Gao, Shan; Ji, Bin; Zang, Yating; Su, Bo; Wang, Kaile; Yao, Maosheng; Zhang, Jue; Wang, Jinglin

    2016-01-01

    Ricin is one of the most toxic and easily produced plant protein toxin extracted from the castor oil plant, and it has been classified as a chemical warfare agent. Here, nanosecond pulsed electric fields (nsPEFs) at 30 kV/cm (pulse durations: 10 ns, 100 ns, and 300 ns) were applied to inactivating ricin up to 4.2 μg/mL. To investigate the efficacy, cells and mice were tested against the ricin treated by the nsPEFs via direct intraperitoneal injection and inhalation exposure. Results showed that nsPEFs treatments can effectively reduce the toxicity of the ricin. Without the nsPEFs treatment, 100% of mice were killed upon the 4 μg ricin injection on the first day, however 40% of the mice survived the ricin treated by the nsPEFs. Compared to injection, inhalation exposure even with higher ricin dose required longer time to observe mice fatality. Pathological observations revealed damages to heart, lung, kidney, and stomach after the ricin exposure, more pronounced for lung and kidney including severe bleeding. Sodium dodecyl sulfate polyacrylamide gel electrophoresis(SDS-PAGE) and circular dichroism (CD) analyses revealed that although the primary structure of ricin was not altered, its secondary structures (beta-sheet and beta-turn) underwent transition upon the nsPEFs treatment.

  13. Inactivation of Ricin Toxin by Nanosecond Pulsed Electric Fields Including Evidences from Cell and Animal Toxicity

    PubMed Central

    Wei, Kai; Li, Wei; Gao, Shan; Ji, Bin; Zang, Yating; Su, Bo; Wang, Kaile; Yao, Maosheng; Zhang, Jue; Wang, Jinglin

    2016-01-01

    Ricin is one of the most toxic and easily produced plant protein toxin extracted from the castor oil plant, and it has been classified as a chemical warfare agent. Here, nanosecond pulsed electric fields (nsPEFs) at 30 kV/cm (pulse durations: 10 ns, 100 ns, and 300 ns) were applied to inactivating ricin up to 4.2 μg/mL. To investigate the efficacy, cells and mice were tested against the ricin treated by the nsPEFs via direct intraperitoneal injection and inhalation exposure. Results showed that nsPEFs treatments can effectively reduce the toxicity of the ricin. Without the nsPEFs treatment, 100% of mice were killed upon the 4 μg ricin injection on the first day, however 40% of the mice survived the ricin treated by the nsPEFs. Compared to injection, inhalation exposure even with higher ricin dose required longer time to observe mice fatality. Pathological observations revealed damages to heart, lung, kidney, and stomach after the ricin exposure, more pronounced for lung and kidney including severe bleeding. Sodium dodecyl sulfate polyacrylamide gel electrophoresis(SDS-PAGE) and circular dichroism (CD) analyses revealed that although the primary structure of ricin was not altered, its secondary structures (beta-sheet and beta-turn) underwent transition upon the nsPEFs treatment. PMID:26728251

  14. Inactivation of Ricin Toxin by Nanosecond Pulsed Electric Fields Including Evidences from Cell and Animal Toxicity.

    PubMed

    Wei, Kai; Li, Wei; Gao, Shan; Ji, Bin; Zang, Yating; Su, Bo; Wang, Kaile; Yao, Maosheng; Zhang, Jue; Wang, Jinglin

    2016-01-01

    Ricin is one of the most toxic and easily produced plant protein toxin extracted from the castor oil plant, and it has been classified as a chemical warfare agent. Here, nanosecond pulsed electric fields (nsPEFs) at 30 kV/cm (pulse durations: 10 ns, 100 ns, and 300 ns) were applied to inactivating ricin up to 4.2 μg/mL. To investigate the efficacy, cells and mice were tested against the ricin treated by the nsPEFs via direct intraperitoneal injection and inhalation exposure. Results showed that nsPEFs treatments can effectively reduce the toxicity of the ricin. Without the nsPEFs treatment, 100% of mice were killed upon the 4 μg ricin injection on the first day, however 40% of the mice survived the ricin treated by the nsPEFs. Compared to injection, inhalation exposure even with higher ricin dose required longer time to observe mice fatality. Pathological observations revealed damages to heart, lung, kidney, and stomach after the ricin exposure, more pronounced for lung and kidney including severe bleeding. Sodium dodecyl sulfate polyacrylamide gel electrophoresis(SDS-PAGE) and circular dichroism (CD) analyses revealed that although the primary structure of ricin was not altered, its secondary structures (beta-sheet and beta-turn) underwent transition upon the nsPEFs treatment. PMID:26728251

  15. Nanosecond pulsed electric fields modulate cell function through intracellular signal transduction mechanisms.

    PubMed

    Beebe, Stephen J; Blackmore, Peter F; White, Jody; Joshi, Ravindra P; Schoenbach, Karl H

    2004-08-01

    These studies describe the effects of nanosecond (10-300 ns) pulsed electric fields (nsPEF) on mammalian cell structure and function. As the pulse durations decrease, effects on the plasma membrane (PM) decrease and effects on intracellular signal transduction mechanisms increase. When nsPEF-induced PM electroporation effects occur, they are distinct from classical PM electroporation effects, suggesting unique, nsPEF-induced PM modulations. In HL-60 cells, nsPEF that are well below the threshold for PM electroporation and apoptosis induction induce effects that are similar to purinergic agonistmediated calcium release from intracellular stores, which secondarily initiate capacitive calcium influx through store-operated calcium channels in the PM. NsPEF with durations and electric field intensities that do or do not cause PM electroporation, induce apoptosis in mammalian cells with a well-characterized phenotype typified by externalization of phosphatidylserine on the outer PM and activation of caspase proteases. Treatment of mouse fibrosarcoma tumors with nsPEF also results in apoptosis induction. When Jurkat cells were transfected by electroporation and then treated with nsPEF, green fluorescent protein expression was enhanced compared to electroporation alone. The results indicate that nsPEF activate intracellular mechanisms that can determine cell function and fate, providing an important new tool for probing signal transduction mechanisms that modulate cell structure and function and for potential therapeutic applications for cancer and gene therapy.

  16. Wideband fluorescence-based thermometry by neural network recognition: Photothermal application with 10 ns time resolution

    NASA Astrophysics Data System (ADS)

    Liu, Liwang; Zhong, Kuo; Munro, Troy; Alvarado, Salvador; Côte, Renaud; Creten, Sebastiaan; Fron, Eduard; Ban, Heng; Van der Auweraer, Mark; Roozen, N. B.; Matsuda, Osamu; Glorieux, Christ

    2015-11-01

    Neural network recognition of features of the fluorescence spectrum of a thermosensitive probe is exploited in order to achieve fluorescence-based thermometry with an accuracy of 200 mK with 100 MHz bandwidth, and with high robustness against fluctuations of the probe laser intensity used. The concept is implemented on a rhodamine B dyed mixture of copper chloride and glycerol, and the temperature dependent fluorescence is investigated in the temperature range between 234 K and 311 K. The spatial dependence of the calibrated amplitude and phase of photothermally induced temperature oscillations along the axis of the excitation laser are determined at different modulation frequencies. The spatial and frequency dependence of the extracted temperature signals is well fitted by a 1D multi-layer thermal diffusion model. In a time domain implementation of the approach, the gradual temperature rise due to the accumulation of the DC component of the heat flux supplied by repetitive laser pulses as well the immediate transient temperature evolution after each single pulse is extracted from acquired temporal sequences of fluorescence spectra induced by a CW green laser. A stroboscopic implementation of fluorescence thermometry, using a pulsed fluorescence evoking probe laser, is shown to achieve remote detection of temperature changes with a time resolution of 10 ns.

  17. The NS1 protein: a multitasking virulence factor.

    PubMed

    Ayllon, Juan; García-Sastre, Adolfo

    2015-01-01

    The non-structural protein 1 of influenza virus (NS1) is a relatively small polypeptide with an outstanding number of ascribed functions. NS1 is the main viral antagonist of the innate immune response during influenza virus infection, chiefly by inhibiting the type I interferon system at multiple steps. As such, its role is critical to overcome the first barrier the host presents to halt the viral infection. However, the pro-viral activities of this well-studied protein go far beyond and include regulation of viral RNA and protein synthesis, and disruption of the host cell homeostasis by dramatically affecting general gene expression while tweaking the PI3K signaling network. Because of all of this, NS1 is a key virulence factor that impacts influenza pathogenesis, and adaptation to new hosts, making it an attractive target for control strategies. Here, we will overview the many roles that have been ascribed to the NS1 protein, and give insights into the sequence features and structural properties that make them possible, highlighting the need to understand how NS1 can actually perform all of these functions during viral infection. PMID:25007846

  18. The NS1 protein: a multitasking virulence factor.

    PubMed

    Ayllon, Juan; García-Sastre, Adolfo

    2015-01-01

    The non-structural protein 1 of influenza virus (NS1) is a relatively small polypeptide with an outstanding number of ascribed functions. NS1 is the main viral antagonist of the innate immune response during influenza virus infection, chiefly by inhibiting the type I interferon system at multiple steps. As such, its role is critical to overcome the first barrier the host presents to halt the viral infection. However, the pro-viral activities of this well-studied protein go far beyond and include regulation of viral RNA and protein synthesis, and disruption of the host cell homeostasis by dramatically affecting general gene expression while tweaking the PI3K signaling network. Because of all of this, NS1 is a key virulence factor that impacts influenza pathogenesis, and adaptation to new hosts, making it an attractive target for control strategies. Here, we will overview the many roles that have been ascribed to the NS1 protein, and give insights into the sequence features and structural properties that make them possible, highlighting the need to understand how NS1 can actually perform all of these functions during viral infection.

  19. Aluminum and tungsten X-pinch experiments on 100 kA, 100 ns linear transformer driver stage

    SciTech Connect

    Wu Jian; Sun Tieping; Wu Gang; Wang Liangping; Han Juanjuan; Li Mo; Cong Peitian; Qiu Aici; Lv Min

    2011-05-15

    X-pinch experiments have been carried out on a 100 kA, 100 ns linear transformer driver stage recently built up. The X-pinches exhibited a source size of about 10 {mu}m, a pulse duration of 3 ns, 3-5 keV radiation energy of 3.9 mJ, and a burst time jitter of tens of nanosecond with the 2-wire 8 {mu}m W X-pinch load. The generator output current and the X-pinch characteristics depended on the X-pinch wire materials in the tests. X-ray backlighting images from the insects showed the significant phase-contrast effect.

  20. Considering effects of nanosecond pulsed electric fields on proteins.

    PubMed

    Beebe, Stephen J

    2015-06-01

    Most, if not all, effects of intense, pulsed electric fields are analyzed in terms of electrical charging of plasma membranes and/or subcellular membranes. However, not all cell responses from nanosecond pulsed electric fields (nsPEFs) are fully explained by poration of cell membranes. Observations that nsPEFs induce a Ca2-dependent dissipation of the mitochondria membrane potential (ΔΨm), which is enhanced when high frequency components are present in fast rise-fall waveforms, are not compatible with a poration event. Ca(2+) is shown to have little or no effect on propidium iodide uptake as a measure of plasma membrane poration and consequently intracellular membranes. Since most if not all Ca(2+)-regulated events are mediated by proteins, actions of nsPEFs on a protein(s) that regulate and/or affect the mitochondria membrane potential are possible. To show that nsPEFs can directly affect proteins, nsPEFs non-thermally inactivated the catalytic (phosphotransferase) activity of the catalytic subunit of the cAMP-dependent protein kinase, which is the prototype of the protein kinase superfamily that share a common catalytic mechanism and whose functions are highly dependent on their structure. These studies present indirect and direct evidences that nsPEFs can affect proteins and their functions, at least in part, by affecting their structure.

  1. Plasma Membrane Permeabilization by Trains of Ultrashort Electric Pulses

    PubMed Central

    Ibey, Bennett L.; Mixon, Dustin G.; Payne, Jason A.; Bowman, Angela; Sickendick, Karl; Wilmink, Gerald J.; Roach, W. Patrick; Pakhomov, Andrei G.

    2010-01-01

    Ultrashort electric pulses (USEP) cause long-lasting increase of cell membrane electrical conductance, and that a single USEP increased cell membrane electrical conductance proportionally to the absorbed dose (AD) with a threshold of about 10 mJ/g. The present study extends quantification of the membrane permeabilization effect to multiple USEP and employed a more accurate protocol that identified USEP effect as the difference between post- and pre-exposure conductance values (Δg) in individual cells. We showed that Δg can be increased by either increasing the number of pulses at a constant E-field, or by increasing the E-field at a constant number of pulses. For 60-ns pulses, an E-field threshold of 6 kV/cm for a single pulse was lowered to less than 1.7 kV/cm by applying 100-pulse or longer trains. However, the reduction of the E-field threshold was only achieved at the expense of a higher AD compared to a single pulse exposure. Furthermore, the effect of multiple pulses was not fully determined by AD, suggesting that cells permeabilized by the first pulse(s) in the train become less vulnerable to subsequent pulses. This explanation was corroborated by a model that treated multiple-pulse exposures as a series of single-pulse exposures and assumed an exponential decline of cell susceptibility to USEP as Δg increased after each pulse during the course of the train. PMID:20171148

  2. Heterosandwich immunoswab assay for dengue virus Ns1 antigen detection.

    PubMed

    Ganguly, Advaita; Malabadi, Ravindra B; Loebenberg, Raimer; Suresh, Mavanur R; Sunwoo, Hoon H

    2014-01-01

    Dengue and the more severe dengue hemorrhagic fever have been a very critical public health problem globally. Millions of people especially in the tropical areas get infected with dengue. An efficient diagnostic is very important for early screening of dengue infection. In dengue-infected patients, the nonstructural protein NS1 is present on the surface of infected cells and secreted in plasma. The NS1 antigen is an important target for developing a quick diagnostic largely due to its long presence in the blood. We have developed a simple-to-use immunoswab-based diagnostic procedure employing monoclonal antibodies and the second-generation quadromas. The detection limit for NS1 has been established to be in the subnanogram range. The assay is very sensitive, has a visual end point, and also being extremely inexpensive. With this assay, screening time for a dengue-infected person would be very rapid. PMID:24211216

  3. Plasma Density and Magnetic Field Evolution in a 100-ns Plasma Opening Switch

    NASA Astrophysics Data System (ADS)

    Weingarten, A.; Maron, Y.; Krasik, Ya. E.; Weber, B. V.; Commisso, R. J.

    1997-11-01

    The electron density and magnetic field evolution in a 100-ns, 170-kA POS are investigated using emission spectroscopy. The plasma is doped by various elements using laser evaporation in order to obtain spatially resolved measurements. The prefilled plasma density, determined from Stark broadening and ionization times, is 1-2× 10^14 cm-3. The opening time was observed to depend on the prefilled plasma azimuthal uniformity. During the pulse, the plasma density drops substantially during 10-20 ns. The drop propagates mainly axially from the plasma generator side to the load side at a velocity of ≈ 2 × 10^8 cm/s. The drop is accompanied by penetration of the magnetic field, determined from the Zeeman effect. A mapping of the density and the magnetic field distributions in the r-z plane will be presented. Proton motion is probably important, but the axial velocities of heavy ions are low (≈ 10^6 cm/s << V_Alfven). These results will be compared with previous results obtained on Gamble I(B. V. Weber et. al.), Appl. Physc. Lett. 45, 1043, (1984).

  4. Pulse Data.

    ERIC Educational Resources Information Center

    Hands On!, 1998

    1998-01-01

    Presents an activity using computer software to investigate the role of the heart and blood, how the blood system responds to exercise, and how pulse rate is a good measure of physical condition. (ASK)

  5. NS1-binding protein abrogates the elevation of cell viability by the influenza A virus NS1 protein in association with CRKL

    SciTech Connect

    Miyazaki, Masaya; Nishihara, Hiroshi; Hasegawa, Hideki; Tashiro, Masato; Wang, Lei; Kimura, Taichi; Tanino, Mishie; Tsuda, Masumi; Tanaka, Shinya

    2013-11-29

    Highlights: •NS1 induced excessive phosphorylation of ERK and elevated cell viability. •NS1-BP expression and CRKL knockdown abolished survival effect of NS1. •NS1-BP and NS1 formed the complex through the interaction with CRKL-SH3(N). -- Abstract: The influenza A virus non-structural protein 1 (NS1) is a multifunctional virulence factor consisting of an RNA binding domain and several Src-homology (SH) 2 and SH3 binding motifs, which promotes virus replication in the host cell and helps to evade antiviral immunity. NS1 modulates general host cell physiology in association with various cellular molecules including NS1-binding protein (NS1-BP) and signaling adapter protein CRK-like (CRKL), while the physiological role of NS1-BP during influenza A virus infection especially in association with NS1 remains unclear. In this study, we analyzed the intracellular association of NS1-BP, NS1 and CRKL to elucidate the physiological roles of these molecules in the host cell. In HEK293T cells, enforced expression of NS1 of A/Beijing (H1N1) and A/Indonesia (H5N1) significantly induced excessive phosphorylation of ERK and elevated cell viability, while the over-expression of NS1-BP and the abrogation of CRKL using siRNA abolished such survival effect of NS1. The pull-down assay using GST-fusion CRKL revealed the formation of intracellular complexes of NS1-BP, NS1 and CRKL. In addition, we identified that the N-terminus SH3 domain of CRKL was essential for binding to NS1-BP using GST-fusion CRKL-truncate mutants. This is the first report to elucidate the novel function of NS1-BP collaborating with viral protein NS1 in modulation of host cell physiology. In addition, an alternative role of adaptor protein CRKL in association with NS1 and NS1-BP during influenza A virus infection is demonstrated.

  6. Radiographic X-Ray Pulse Jitter

    SciTech Connect

    Mitton, C. V., Good, D. E., Henderson, D. J., Hogge, K. W.

    2011-01-15

    The Dual Beam Radiographic Facility consists of two identical radiographic sources. Major components of the machines are: Marx generator, water-filled pulse-forming line (PFL), water-filled coaxial transmission line, three-cell inductive voltage adder, and rod-pinch diode. The diode pulse has the following electrical specifications: 2.25-MV, 60-kA, 60-ns. Each source has the following x-ray parameters: 1-mm-diameter spot size, 4-rad at 1 m, 50-ns full width half max. The x-ray pulse is measured with PIN diode detectors. The sources were developed to produce high resolution images on single-shot, high-value experiments. For this application it is desirable to maintain a high level of reproducibility in source output. X-ray pulse jitter is a key metric for analysis of reproducibility. We will give measurements of x-ray jitter for each machine. It is expected that x-ray pulse jitter is predominantly due to PFL switch jitter, and therefore a correlation of the two will be discussed.

  7. Fuel specificity of the hepatitis C virus NS3 helicase.

    PubMed

    Belon, Craig A; Frick, David N

    2009-05-15

    The hepatitis C virus (HCV) NS3 protein is a helicase capable of unwinding duplex RNA or DNA. This study uses a newly developed molecular-beacon-based helicase assay (MBHA) to investigate how nucleoside triphosphates (NTPs) fuel HCV helicase-catalyzed DNA unwinding. The MBHA monitors the irreversible helicase-catalyzed displacement of an oligonucleotide-bound molecular beacon so that rates of helicase translocation can be directly measured in real time. The MBHA reveals that HCV helicase unwinds DNA at different rates depending on the nature and concentration of NTPs in solution, such that the fastest reactions are observed in the presence of CTP followed by ATP, UTP, and GTP. 3'-Deoxy-NTPs generally support faster DNA unwinding, with dTTP supporting faster rates than any other canonical (d)NTP. The presence of an intact NS3 protease domain makes HCV helicase somewhat less specific than truncated NS3 bearing only its helicase region (NS3h). Various NTPs bind NS3h with similar affinities, but each NTP supports a different unwinding rate and processivity. Studies with NTP analogs reveal that specificity is determined by the nature of the Watson-Crick base-pairing region of the NTP base and the nature of the functional groups attached to the 2' and 3' carbons of the NTP sugar. The divalent metal bridging the NTP to NS3h also influences observed unwinding rates, with Mn(2+) supporting about 10 times faster unwinding than Mg(2+). Unlike Mg(2+), Mn(2+) does not support HCV helicase-catalyzed ATP hydrolysis in the absence of stimulating nucleic acids. Results are discussed in relation to models for how ATP might fuel the unwinding reaction.

  8. Comparative study of long- and short-pulsed electric fields for treating melanoma in an in vivo mouse model.

    PubMed

    Chen, Xinhua; Chen, Xinmei; Schoenbach, Karl H; Zheng, Shusen; Swanson, R James

    2011-01-01

    A mouse melanoma model was set up with green fluorescent protein (GFP) expression in vivo. With the same energy, long- (1 ms) and short- (300 ns) pulsed electric fields were delivered to two melanomas injected into the same mouse. The tumor growth and green fluorescence were followed up to compare the different treatment efficacy of long and short pulses. After two days post treatment, short pulse-treated tumors showed a significantly lower tumor volume compared with long pulse-treated tumors (n=8, p<0.05). On 8 experimental animals, a short nanosecond pulsed electric field (nsPEF) had lesser or delayed effects on GFP quenching and greater effects in reducing tumor size. Short pulses produced by nsPEFs can cause melanoma regression with less effect on the plasma membrane.

  9. Third-generation megahertz-rate pulse burst laser system.

    PubMed

    Thurow, Brian S; Satija, Aman; Lynch, Kyle

    2009-04-10

    The design and performance of a third-generation megahertz-rate pulse burst laser system is described. The third-generation system incorporates two distinct design changes that distinguish it from earlier-generation systems. The first is that pulse slicing is now achieved by using an economical acousto-optic modulator (AOM), and the second is the use of a variable pulse duration flashlamp driver that provides relatively uniform gain over a ~700 mus window. The use of an AOM for pulse slicing permits flexible operation such as pulse-on-demand operation with variable pulse durations ranging from 10 ns to DC. The laser described here is capable of producing a burst of laser pulses at repetition rates as high as 50 MHz and peak powers of 10 kW. Second-harmonic conversion efficiency using a type II KTP crystal is also demonstrated.

  10. Structures of NS5 Methyltransferase from Zika Virus.

    PubMed

    Coloma, Javier; Jain, Rinku; Rajashankar, Kanagalaghatta R; García-Sastre, Adolfo; Aggarwal, Aneel K

    2016-09-20

    The Zika virus (ZIKV) poses a major public health emergency. To aid in the development of antivirals, we present two high-resolution crystal structures of the ZIKV NS5 methyltransferase: one bound to S-adenosylmethionine (SAM) and the other bound to SAM and 7-methyl guanosine diphosphate (7-MeGpp). We identify features of ZIKV NS5 methyltransferase that lend to structure-based antiviral drug discovery. Specifically, SAM analogs with functionalities on the Cβ atom of the methionine portion of the molecules that occupy the RNA binding tunnel may provide better specificity relative to human RNA methyltransferases.

  11. Structures of NS5 Methyltransferase from Zika Virus.

    PubMed

    Coloma, Javier; Jain, Rinku; Rajashankar, Kanagalaghatta R; García-Sastre, Adolfo; Aggarwal, Aneel K

    2016-09-20

    The Zika virus (ZIKV) poses a major public health emergency. To aid in the development of antivirals, we present two high-resolution crystal structures of the ZIKV NS5 methyltransferase: one bound to S-adenosylmethionine (SAM) and the other bound to SAM and 7-methyl guanosine diphosphate (7-MeGpp). We identify features of ZIKV NS5 methyltransferase that lend to structure-based antiviral drug discovery. Specifically, SAM analogs with functionalities on the Cβ atom of the methionine portion of the molecules that occupy the RNA binding tunnel may provide better specificity relative to human RNA methyltransferases. PMID:27633330

  12. Pulse stretcher

    DOEpatents

    Horton, James A.

    1994-01-01

    Apparatus (20) for increasing the length of a laser pulse to reduce its peak power without substantial loss in the average power of the pulse. The apparatus (20) uses a White cell (10) having a plurality of optical delay paths (18a-18d) of successively increasing number of passes between the field mirror (13) and the objective mirrors (11 and 12). A pulse (26) from a laser (27) travels through a multi-leg reflective path (28) between a beam splitter (21) and a totally reflective mirror (24) to the laser output (37). The laser pulse (26) is also simultaneously injected through the beam splitter (21) to the input mirrors (14a-14d) of the optical delay paths (18a-18d). The pulses from the output mirrors (16a-16d) of the optical delay paths (18a-18d) go simultaneously to the laser output (37) and to the input mirrors ( 14b-14d) of the longer optical delay paths. The beam splitter (21) is 50% reflective and 50% transmissive to provide equal attenuation of all of the pulses at the laser output (37).

  13. hnRNP A2/B1 interacts with influenza A viral protein NS1 and inhibits virus replication potentially through suppressing NS1 RNA/protein levels and NS1 mRNA nuclear export

    SciTech Connect

    Wang, Yimeng; Zhou, Jianhong; Du, Yuchun

    2014-01-20

    The NS1 protein of influenza viruses is a major virulence factor and exerts its function through interacting with viral/cellular RNAs and proteins. In this study, we identified heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNP A2/B1) as an interacting partner of NS1 proteins by a proteomic method. Knockdown of hnRNP A2/B1 by small interfering RNA (siRNA) resulted in higher levels of NS vRNA, NS1 mRNA, and NS1 protein in the virus-infected cells. In addition, we demonstrated that hnRNP A2/B1 proteins are associated with NS1 and NS2 mRNAs and that knockdown of hnRNP A2/B1 promotes transport of NS1 mRNA from the nucleus to the cytoplasm in the infected cells. Lastly, we showed that knockdown of hnRNP A2/B1 leads to enhanced virus replication. Our results suggest that hnRNP A2/B1 plays an inhibitory role in the replication of influenza A virus in host cells potentially through suppressing NS1 RNA/protein levels and NS1 mRNA nucleocytoplasmic translocation. - Highlights: • Cellular protein hnRNP A2/B1 interacts with influenza viral protein NS1. • hnRNP A2/B1 suppresses the levels of NS1 protein, vRNA and mRNA in infected cells. • hnRNP A2/B1 protein is associated with NS1 and NS2 mRNAs. • hnRNP A2/B1 inhibits the nuclear export of NS1 mRNAs. • hnRNP A2/B1 inhibits influenza virus replication.

  14. Histopathology of normal skin and melanomas after nanosecond pulsed electric field treatment

    PubMed Central

    Chen, Xinhua; Swanson, R. James; Kolb, Juergen F.; Nuccitelli, Richard; Schoenbach, Karl H.

    2011-01-01

    Nanosecond pulsed electric fields (nsPEFs) can affect the intracellular structures of cells in vitro. This study shows the direct effects of nsPEFs on tumor growth, tumor volume, and histological characteristics of normal skin and B16-F10 melanoma in SKH-1 mice. A melanoma model was set up by injecting B16-F10 into female SKH-1 mice. After a 100-pulse treatment with an nsPEF (40-kV/cm field strength; 300-ns duration; 30-ns rise time; 2-Hz repetition rate), tumor growth and histology were studied using transillumination, light microscopy with hematoxylin and eosin stain and transmission electron microscopy. Melanin and iron within the melanoma tumor were also detected with specific stains. After nsPEF treatment, tumor development was inhibited with decreased volumes post-nsPEF treatment compared with control tumors (P< 0.05). The nsPEF-treated tumor volume was reduced significantly compared with the control group (P < 0.01). Hematoxylin and eosin stain and transmission electron microscopy showed morphological changes and nuclear shrinkage in the tumor. Fontana–Masson stain indicates that nsPEF can externalize the melanin. Iron stain suggested nsPEF caused slight hemorrhage in the treated tissue. Histology confirmed that repeated applications of nsPEF disrupted the vascular network. nsPEF treatment can significantly disrupt the vasculature, reduce subcutaneous murine melanoma development, and produce tumor cell contraction and nuclear shrinkage while concurrently, but not permanently, damaging peripheral healthy skin tissue in the treated area, which we attribute to the highly localized electric fields surrounding the needle electrodes. PMID:19730404

  15. Histopathology of normal skin and melanomas after nanosecond pulsed electric field treatment.

    PubMed

    Chen, Xinhua; James Swanson, R; Kolb, Juergen F; Nuccitelli, Richard; Schoenbach, Karl H

    2009-12-01

    Nanosecond pulsed electric fields (nsPEFs) can affect the intracellular structures of cells in vitro. This study shows the direct effects of nsPEFs on tumor growth, tumor volume, and histological characteristics of normal skin and B16-F10 melanoma in SKH-1 mice. A melanoma model was set up by injecting B16-F10 into female SKH-1 mice. After a 100-pulse treatment with an nsPEF (40-kV/cm field strength; 300-ns duration; 30-ns rise time; 2-Hz repetition rate), tumor growth and histology were studied using transillumination, light microscopy with hematoxylin and eosin stain and transmission electron microscopy. Melanin and iron within the melanoma tumor were also detected with specific stains. After nsPEF treatment, tumor development was inhibited with decreased volumes post-nsPEF treatment compared with control tumors (P<0.05). The nsPEF-treated tumor volume was reduced significantly compared with the control group (P<0.01). Hematoxylin and eosin stain and transmission electron microscopy showed morphological changes and nuclear shrinkage in the tumor. Fontana-Masson stain indicates that nsPEF can externalize the melanin. Iron stain suggested nsPEF caused slight hemorrhage in the treated tissue. Histology confirmed that repeated applications of nsPEF disrupted the vascular network. nsPEF treatment can significantly disrupt the vasculature, reduce subcutaneous murine melanoma development, and produce tumor cell contraction and nuclear shrinkage while concurrently, but not permanently, damaging peripheral healthy skin tissue in the treated area, which we attribute to the highly localized electric fields surrounding the needle electrodes.

  16. Repetitively pulsed Cr:LiSAF laser for lidar applications

    SciTech Connect

    Shimada, Tsutomu; Early, J.W.; Lester, C.S.; Cockroft, N.J.

    1994-03-01

    A Cr:LiSAF laser has been successfully operated at time averaged powers up to 11 W and at pulse repetition rates to 12 Hz. During Q-switch operation, output energy as high as 450 mJ (32 ns FWHM) was obtained. Finally, line narrowed Q-switched pulses (< 0.1 nm) from the Cr:LiSAF laser were successfully used as a tunable light source for lidar to measure atmospheric water content.

  17. Pulsed laser ablation and deposition of niobium carbide

    NASA Astrophysics Data System (ADS)

    Sansone, M.; De Bonis, A.; Santagata, A.; Rau, J. V.; Galasso, A.; Teghil, R.

    2016-06-01

    NbC crystalline films have been deposited in vacuum by ultra-short pulsed laser deposition technique. The films have been characterized by transmission and scanning electron microscopies and by X-ray diffraction. To clarify the ablation-deposition mechanism, the plasma produced by the ablation process has been characterized by optical emission spectroscopy and fast imaging. A comparison of the results with those obtained by ns pulsed deposition of the same target has been carried out.

  18. Facilitation of cell adhesion by immobilized dengue viral nonstructural protein 1 (NS1): arginine-glycine-aspartic acid structural mimicry within the dengue viral NS1 antigen.

    PubMed

    Chang, Hsin-Hou; Shyu, Huey-Fen; Wang, Yo-Ming; Sun, Der-Shan; Shyu, Rong-Hwa; Tang, Shiao-Shek; Huang, Yao-Shine

    2002-09-15

    Dengue virus infection causes life-threatening hemorrhagic fever. Increasing evidence implies that dengue viral nonstructural protein 1 (NS1) exhibits a tendency to elicit potentially hazardous autoantibodies, which show a wide spectrum of specificity against extracellular matrix and platelet antigens. How NS1 elicits autoantibodies remains unclear. To address the hypothesis that NS1 and matrix proteins may have structural and functional similarity, cell-matrix and cell-NS1 interactions were evaluated using a cell-adhesion assay. The present study showed that dengue NS1 immobilized on coverslips resulted in more cell adhesion than did the control proteins. This cell adhesion was inhibited by peptides containing arginine-glycine-aspartic acid (RGD), a motif important for integrin-mediated cell adhesion. In addition, anti-NS1 antibodies blocked RGD-mediated cell adhesion. Although there is no RGD motif in the NS1 protein sequence, these data indicate that RGD structural mimicry exists within the NS1 antigen.

  19. Advances in high-power harmonic generation: Q-switched lasers with electronically adjustable pulse width

    NASA Astrophysics Data System (ADS)

    Eyres, Loren A.; Morehead, James J.; Gregg, Jeffrey; Richard, Derek J.; Grossman, William

    2006-02-01

    We demonstrate a variable pulse width, internally-frequency-converted, near-diffraction-limited Nd:YAG laser with output power up to 40 Watts at 532 nm and pulse widths electronically adjustable over a 40-300 ns range. The variable pulse width is achieved by clipping the pulse decaying edge with the Q-switch in a laser cavity optimized for post-pulse gain insensitivity. This approach makes possible frequency converted lasers with pulse width and output power substantially independent of repetition rate.

  20. Resistance Analyses of HCV NS3/4A Protease and NS5B Polymerase from Clinical Studies of Deleobuvir and Faldaprevir

    PubMed Central

    Berger, Kristi L.; Sarrazin, Christoph; Nelson, David R.; Scherer, Joseph; Sha, Nanshi; Marquis, Martin; Côté-Martin, Alexandra; Vinisko, Richard; Stern, Jerry O.; Mensa, Federico J.; Kukolj, George

    2016-01-01

    Background & Aim The resistance profile of anti-hepatitis C virus (HCV) agents used in combination is important to guide optimal treatment regimens. We evaluated baseline and treatment-emergent NS3/4A and NS5B amino-acid variants among HCV genotype (GT)-1a and -1b-infected patients treated with faldaprevir (HCV protease inhibitor), deleobuvir (HCV polymerase non-nucleoside inhibitor), and ribavirin in multiple clinical studies. Methods HCV NS3/4A and NS5B population sequencing (Sanger method) was performed on all baseline plasma samples (n = 1425 NS3; n = 1556 NS5B) and on post-baseline plasma samples from patients with virologic failure (n = 113 GT-1a; n = 221 GT-1b). Persistence and time to loss of resistance-associated variants (RAVs) was estimated using Kaplan–Meier analysis. Results Faldaprevir RAVs (NS3 R155 and D168) and deleobuvir RAVs (NS5B 495 and 496) were rare (<1%) at baseline. Virologic response to faldaprevir/deleobuvir/ribavirin was not compromised by common baseline NS3 polymorphisms (e.g. Q80K in 17.5% of GT-1a) or by NS5B A421V, present in 20% of GT-1a. In GT-1b, alanine at NS5B codon 499 (present in 15% of baseline sequences) was associated with reduced response. Treatment-emergent RAVs consolidated previous findings: NS3 R155 and D168 were key faldaprevir RAVs; NS5B A421 and P495 were key deleobuvir RAVs. Among on-treatment virologic breakthroughs, RAVs emerged in both NS3 and NS5B (>90%). Virologic relapse was associated with RAVs in both NS3 and NS5B (53% GT-1b; 52% GT-1b); some virologic relapses had NS3 RAVs only (47% GT-1a; 17% GT-1b). Median time to loss of GT-1b NS5B P495 RAVs post-treatment (5 months) was less than that of GT-1b NS3 D168 (8.5 months) and GT-1a R155 RAVs (11.5 months). Conclusion Faldaprevir and deleobuvir RAVs are more prevalent among virologic failures than at baseline. Treatment response was not compromised by common NS3 polymorphisms; however, alanine at NS5B amino acid 499 at baseline (wild-type in GT-1a

  1. Crystal structure of Zika virus NS2B-NS3 protease in complex with a boronate inhibitor.

    PubMed

    Lei, Jian; Hansen, Guido; Nitsche, Christoph; Klein, Christian D; Zhang, Linlin; Hilgenfeld, Rolf

    2016-07-29

    The ongoing Zika virus (ZIKV) outbreak is linked to severe neurological disorders. ZIKV relies on its NS2B/NS3 protease for polyprotein processing; hence, this enzyme is an attractive drug target. The 2.7 angstrom; crystal structure of ZIKV protease in complex with a peptidomimetic boronic acid inhibitor reveals a cyclic diester between the boronic acid and glycerol. The P2 4-aminomethylphenylalanine moiety of the inhibitor forms a salt-bridge with the nonconserved Asp(83) of NS2B; ion-pairing between Asp(83) and the P2 residue of the substrate likely accounts for the enzyme's high catalytic efficiency. The unusual dimer of the ZIKV protease:inhibitor complex seen in the crystal may provide a model for assemblies formed at high local concentrations of protease at the endoplasmatic reticulum membrane, the site of polyprotein processing. PMID:27386922

  2. Further theoretical insight into the reaction mechanism of the hepatitis C NS3/NS4A serine protease

    NASA Astrophysics Data System (ADS)

    Martínez-González, José Ángel; Rodríguez, Alex; Puyuelo, María Pilar; González, Miguel; Martínez, Rodrigo

    2015-01-01

    The main reactions of the hepatitis C virus NS3/NS4A serine protease are studied using the second-order Møller-Plesset ab initio method and rather large basis sets to correct the previously reported AM1/CHARMM22 potential energy surfaces. The reaction efficiencies measured for the different substrates are explained in terms of the tetrahedral intermediate formation step (the rate-limiting process). The energies of the barrier and the corresponding intermediate are so close that the possibility of a concerted mechanism is open (especially for the NS5A/5B substrate). This is in contrast to the suggested general reaction mechanism of serine proteases, where a two-step mechanism is postulated.

  3. Crystal structure of Zika virus NS2B-NS3 protease in complex with a boronate inhibitor.

    PubMed

    Lei, Jian; Hansen, Guido; Nitsche, Christoph; Klein, Christian D; Zhang, Linlin; Hilgenfeld, Rolf

    2016-07-29

    The ongoing Zika virus (ZIKV) outbreak is linked to severe neurological disorders. ZIKV relies on its NS2B/NS3 protease for polyprotein processing; hence, this enzyme is an attractive drug target. The 2.7 angstrom; crystal structure of ZIKV protease in complex with a peptidomimetic boronic acid inhibitor reveals a cyclic diester between the boronic acid and glycerol. The P2 4-aminomethylphenylalanine moiety of the inhibitor forms a salt-bridge with the nonconserved Asp(83) of NS2B; ion-pairing between Asp(83) and the P2 residue of the substrate likely accounts for the enzyme's high catalytic efficiency. The unusual dimer of the ZIKV protease:inhibitor complex seen in the crystal may provide a model for assemblies formed at high local concentrations of protease at the endoplasmatic reticulum membrane, the site of polyprotein processing.

  4. Multiple-beam pulse shaping and preamplification

    SciTech Connect

    Wilcox, R.B.; VanWonterghem, B.W.; Burkhart, S.C.; Davin, J.M.

    1994-11-09

    Glass fusion laser systems typically use a master oscillator-power amplifier (MOPA) architecture, where control of the optical pulse temporal and spatial parameters is accomplished mainly in the master oscillator and low power optics. The pulses from this low power ``front end`` are amplified in the power amplifier, which modifies the pulse shape temporally and spatially. Nonlinear frequency conversion crystals following the amplifier further change the pulse before it reaches the target. To effectively control the optical pulse on target for different types of experiments, and compensate for nonlinearity in the preceding optics, the front end system must be versatile enough to easily control many pulse parameters over a large range. The front end pulse generation system described in this article represents a new approach to this problem. The proposed National Ignition Facility (NIF) has 192 beamlines, each of which requires an input pulse of up to 12 Joules in around 4 ns equivalent square pulse length. Considerations of laser architecture for supplying each of these beamlines from a central oscillator system were crucial in the design of the front end. Previous lasers have used bulk optics to split a single oscillator signal and report beams to multiple amplifier chains. A key idea in the current design is to replace bulk optic transport with fibers, eliminating large opto-mechanical subsystems. Another important concept is convenient pulse forming using low voltage integrated optic modulators. The integrated optic and fiber optic concepts resulted in the current pulse generation designs for NEF. An important advantage is that each of the beamlines can have an independently controlled temporal pulse shape, which provides for precise balance of instantaneous power on target.

  5. Novel fullerene derivatives as dual inhibitors of Hepatitis C virus NS5B polymerase and NS3/4A protease.

    PubMed

    Kataoka, Hiroki; Ohe, Tomoyuki; Takahashi, Kyoko; Nakamura, Shigeo; Mashino, Tadahiko

    2016-10-01

    We evaluated the Hepatitis C virus (HCV) NS5B polymerase and HCV NS3/4A protease inhibition activities of a new set of proline-type fullerene derivatives. All of the compounds had the potential to inhibit both the enzymes, indicating that the fullerene derivatives may be dual inhibitors against NS5B and NS3/4A and could be novel lead compounds for the treatment of HCV infections. PMID:27597249

  6. A straightforward experimental approach to expression, purification, refolding, and enzymatic analysis of recombinant dengue virus NS2B(H)-NS3pro protease.

    PubMed

    Junaid, M; Angsuthanasombat, C; Wikberg, J E S; Ali, N; Katzenmeier, G

    2013-08-01

    Dengue virus threatens around 2.5 billion people worldwide; about 50 million become infected every year, and yet no vaccine or drug is available for prevention and/or treatment. The flaviviral NS2B-NS3pro complex is indispensable for flaviviral replication and is considered to be an important drug target. The aim of this study was to develop a simple and generally applicable experimental strategy to construct, purify, and assay a highly active recombinant NS2B(H)-NS3pro complex that would be useful for high-throughput screening of potential inhibitors. The sequence of NS2B(H)-NS3pro was generated by overlap extension PCR (SOE-PCR) and cloned into the pTrcHisA vector. Hexahistidine-tagged NS2B(H)-NS3pro complex was expressed in E. coli predominantly as insoluble protein and purified to >95% purity by single-step immobilized metal affinity chromatography. SDS-PAGE followed by immunoblotting of the purified enzyme demonstrated the presence of the NS2B(H)-NS3pro precursor and its autocleavage products, NS3pro and NS2B(H), as 37, 21, and 10 kDa bands, respectively. Kinetic parameters, Km, kcat, and kcat/Km for the fluorophore-linked protease model substrate Ac-nKRR-amc were obtained using inner-filter effect correction. The kinetic parameters Km, kcat, and kcat/Km for Ac-nKRR-amc substrate were 100 µM, 0.112 s(-1), and 1120 M(-1)·s(-1), respectively. A simplified procedure for the cloning, overexpression, and purification of the NS2B(H)-NS3pro complex was applied, and a highly active recombinant NS2B(H)-NS3pro complex was obtained that could be useful for the design of high-throughput assays aimed at flaviviral inhibitor discovery.

  7. Copper vapour laser with an efficient semiconductor pump generator having comparable pump pulse and output pulse durations

    NASA Astrophysics Data System (ADS)

    Yurkin, A. A.

    2016-03-01

    We report the results of experimental studies of a copper vapour laser with a semiconductor pump generator capable of forming virtually optimal pump pulses with a current rise steepness of about 40 A ns-1 in a KULON LT-1.5CU active element. To maintain the operating temperature of the active element's channel, an additional heating pulsed oscillator is used. High efficiency of the pump generator is demonstrated.

  8. 975nm high-peak power ns-diode laser based MOPA system suitable for water vapor DIAL applications

    NASA Astrophysics Data System (ADS)

    Sumpf, Bernd; Klehr, Andreas; Vu, Thi Nghiem; Erbert, Götz; Tränkle, Günther

    2015-03-01

    Micro-DIAL (differential absorption LIDAR) systems require light sources with peak powers in the range of several 10 W together with a spectral line width smaller than the width of absorption lines under study. For water vapor at atmospheric pressure this width should be smaller than 10 pm at 975 nm. In this paper, an all semiconductor master oscillator power amplifier system at an emission wavelength of 975 nm will be presented. This spectral range was selected with respect to a targeted absorption path length of 5000 m and H2O line strengths. A distributed feedback (DFB) ridge waveguide diode laser operated in continuous wave is used as master oscillator whereas a tapered amplifier consisting of a RW section and a flared section is implemented as power amplifier. The RW section acts as optical gate. The current pulses injected into the RW part have a length of 8 ns and the tapered part is driven with 15 ns long pulses. The delay between the pulses is adjusted for optimal pulse shape. The repetition rate is in both cases 25 kHz. A maximal pulse output power of about 16 W limited by the available current supply is achieved. The spectral line width of the system determined by the properties of the DFB laser is smaller than 10 pm. The tuning range amounts 0.9 nm and a SMSR of 40 dB is observed. From the dependence of the peak power on the power injected into the tapered amplifier, the saturation power is determined to 5.3 mW.

  9. Mosquito densonucleosis virus non-structural protein NS2 is necessary for a productive infection

    SciTech Connect

    Azarkh, Eugene; Robinson, Erin; Hirunkanokpun, Supanee; Afanasiev, Boris; Kittayapong, Pattamaporn; Carlson, Jonathan Corsini, Joe

    2008-04-25

    Mosquito densonucleosis viruses synthesize two non-structural proteins, NS1 and NS2. While NS1 has been studied relatively well, little is known about NS2. Antiserum was raised against a peptide near the N-terminus of NS2, and used to conduct Western blot analysis and immuno-fluorescence assays. Western blots revealed a prominent band near the expected size (41 kDa). Immuno-fluorescence studies of mosquito cells transfected with AeDNV indicate that NS2 has a wider distribution pattern than does NS1, and the distribution pattern appears to be a function of time post-infection. Nuclear localization of NS2 requires intact C-terminus but does not require additional viral proteins. Mutations ranging from complete NS2 knock-out to a single missense amino acid substitution in NS2 can significantly reduce viral replication and production of viable progeny.

  10. Pulse bundles and passive harmonic mode-locked pulses in Tm-doped fiber laser based on nonlinear polarization rotation.

    PubMed

    Wang, Xiong; Zhou, Pu; Wang, Xiaolin; Xiao, Hu; Liu, Zejin

    2014-03-10

    We demonstrate the nanosecond-level pulses in Tm-doped fiber laser generated by passively harmonic mode-locking. Nonlinear polarization rotation performed by two polarization controllers (PCs) is employed to induce the self-starting harmonic mode-locking. The fundamental repetition rate of the laser is 448.8 kHz, decided by the length of the cavity. Bundles of pulses with up to 17 uniform subpulses are generated due to the split of pulse when the pump power increases and the PCs are adjusted. Continuous harmonic mode-locked pulse trains are obtained with 1st to 6th and even more than 15th order when the positions of the PCs are properly fixed and the pump power is scaled up. The widths of all the uniform individual pulses are mostly 3-5 ns, and pulse with width of 304 ns at fundamental repetition rate can also be generated by adjusting the PCs. Hysteresis phenomenon of the passively harmonic mode-locked pulses' repetition frequency versus pump power is observed. The rather wide 3dB spectral bandwidth of the pulse train (25 nm) indicates that they may resemble noise-like pulses. PMID:24663948

  11. Multi-pulse extraction from Los Alamos Proton Storage Ring for radiographic applications

    SciTech Connect

    Thiessen, H.A.; Neri, F.; Rust, K.; Redd, D.B.

    1997-08-01

    In Proton Radiography, one of the goals is a motion picture of a rapidly moving object. The Los Alamos Proton Storage Ring (PSR) in its normal operating mode, delivers a single pulse approximately 120 ns wide (fwhm). In development runs at the PSR, the authors successfully demonstrated operation of a technique to deliver two pulses, each 40 nsec wide, with adjustable spacing.

  12. fs- and ns-laser processing of polydimethylsiloxane (PDMS) elastomer: Comparative study

    NASA Astrophysics Data System (ADS)

    Stankova, N. E.; Atanasov, P. A.; Nedyalkov, N. N.; Stoyanchov, T. R.; Kolev, K. N.; Valova, E. I.; Georgieva, J. S.; Armyanov, St. A.; Amoruso, S.; Wang, X.; Bruzzese, R.; Grochowska, K.; Śliwiński, G.; Baert, K.; Hubin, A.; Delplancke, M. P.; Dille, J.

    2015-05-01

    Medical grade polydimethylsiloxane (PDMS) elastomer is a widely used biomaterial as encapsulation and/or as substrate insulator carrier for long term neural implants because of its remarkable properties. Femtosecond (λ = 263 and 527 nm) and nanosecond (266 and 532 nm) laser processing of PDMS-elastomer surface, in air, is investigated. The influence of different processing parameters, including laser wavelength, pulse duration, fluence, scanning speed and overlapping of the subsequent pulses, on the surface activation and the surface morphology are studied. High definition tracks and electrodes are produced. Remarkable alterations of the chemical composition and structural morphology of the ablated traces are observed in comparison with the native material. Raman spectra illustrate well-defined dependence of the chemical composition on the laser fluence, pulse duration, number of pulses and wavelength. An extra peak about ∼512-518 cm-1, assigned to crystalline silicon, is observed after ns- or visible fs-laser processing of the surface. In all cases, the intensities of Sisbnd Osbnd Si symmetric stretching at 488 cm-1, Sisbnd CH3 symmetric rocking at 685 cm-1, Sisbnd C symmetric stretching at 709 cm-1, CH3 asymmetric rocking + Sisbnd C asymmetric stretching at 787 cm-1, and CH3 symmetric rocking at 859 cm-1, modes strongly decrease. The laser processed areas are also analyzed by SEM and optical microscopy. Selective Pt or Ni metallization of the laser processed traces is produced successfully via electroless plating. The metallization process is not sensitive with respect to the time interval after the laser treatment. DC resistance is measured to be as low as 0.5 Ω mm-1. Our results show promising prospects with respect to use such a laser-based method for micro- or nano-fabrication of PDMS devices for MEMS and NEMS.

  13. Interaction cloning of NS1-I, a human protein that binds to the nonstructural NS1 proteins of influenza A and B viruses.

    PubMed Central

    Wolff, T; O'Neill, R E; Palese, P

    1996-01-01

    The yeast interaction trap system was used to identify, NS1-I (for NS1 interactor), which is a human protein that binds to the nonstructural NS1 protein of the influenza A virus. NS1-I is a human homolog of the porcine 17beta-estradiol dehydrogenase precursor protein, to which it is 84% identical. We detected only one NS1-I mRNA species, of about 3.0 kb, in HeLa cells, and the NS1-I cDNA was found to have a coding capacity for a 79.6-kDa protein. However, immunoblot analysis detected predominantly a 55-kDa protein in human cells, suggesting that NS1-I, like the porcine 17beta-estradiol dehydrogenase, is posttranslationally processed. Using an in vitro coprecipitation assay, we showed that NS1-I interacts with NS1 proteins from extracts of cells infected with five different influenza A virus strains as well as with the NS1 of an influenza B virus. The fact that influenza A and influenza B virus NS1 proteins bind to NS1-I suggests that this cellular protein plays a role in the influenza virus life cycle. PMID:8764047

  14. Improvement in the statistical operation of a Blumlein pulse forming line in bipolar pulse mode

    SciTech Connect

    Pushkarev, A. I. Isakova, Y. I.; Khaylov, I. P.

    2014-07-15

    The paper presents the results of studies on shot-to-shot performance of a water Blumlein pulse forming line of 1–1.2 kJ of stored energy. The experiments were carried using the TEMP-4M pulsed ion beam accelerator during its operation in both unipolar pulse mode (150 ns, 250–300 kV) and bipolar-pulse mode with the first negative (300–600 ns, 100–150 kV) followed by a second positive (120 ns, 250–300 kV) pulse. The analysis was carried out for two cases when the Blumlein was terminated with a resistive load and with a self-magnetically insulated ion diode. It was found that in bipolar pulse mode the shot-to-shot variation in breakdown voltage of a preliminary spark gap is small, the standard deviation (1σ) does not exceed 2%. At the same time, the shot-to-shot variation in the breakdown voltage of the main spark gap in both bipolar-pulse and unipolar pulse mode is 3–4 times higher than that for the preliminary spark gap. To improve the statistical performance of the main spark gap we changed the regime of its operation from a self-triggered mode to an externally triggered mode. In the new arrangement the first voltage pulse at the output of Blumlein was used to trigger the main spark gap. The new trigatron-type regime of the main spark gap operation showed a good stability of breakdown voltage and thus allowed to stabilize the duration of the first pulse. The standard deviation of the breakdown voltage and duration of the first pulse did not exceed 2% for a set of 50 pulses. The externally triggered mode of the main gap operation also allowed for a decrease in the charging voltage of the Blumlein to a 0.9–0.95 of self-breakdown voltage of the main spark gap while the energy stored in Marx generator was decreased from 4 kJ to 2.5 kJ. At the same time the energy stored in Blumlein remained the same.

  15. Nociceptor activation and damage by pulsed E-fields

    NASA Astrophysics Data System (ADS)

    Nene, Deepti; Jiang, Nan; Rau, Kristofer K.; Richardson, Martin; Cooper, Brian Y.

    2006-05-01

    We assessed the capacity of ultrashort E-fields to activate rat cutaneous nociceptors. Experiments were conducted in vitro on nociceptive neurons representing hairy skin and glabrous skin. Electrical and optical recording methods were used to assess action potentials and membrane damage thresholds. Strength duration (SD) curves were formed for E-field pulses from 500 μsec to 350 ns. There were no differences in the SD time contant (taue (59 μsec) or ultrashort thresholds (129 V/cm at 350 ns) for hairy or glabrous skin nociceptors, for nociceptors with distinct geometry or for nociceptors expressing different combinations of voltage sensitive Na + channels (TTX s and TTX r Na v) or hyperpolarization activated channels (HCN; I H). Subthreshold activation was possible with high frequency pulsing at ultrashort durations (350 ns; 4,000 Hz). Relative to single pulse thresholds, activation threshold could be reduced over 50% by high frequency burst trains (4,000 Hz; 1-40 msec). Nociceptors were not damaged by E-field activation. Irreversible membrane disruption occurred at significantly higher field strength and varied by cell radius (3,266-4,240 V/cm, 350 ns, 40 Hz, 5 sec). Pulse frequency had no influence on acute membrane failure (10, 20, 40, 4,000 Hz; 5 sec).

  16. Modeling of ns and ps laser-induced soft X-ray sources using nitrogen gas puff target

    SciTech Connect

    Vrba, P.; Vrbova, M.; Zakharov, S. V.

    2014-07-15

    Gas puff laser plasma is studied as a source of water window radiation with 2.88 nm wavelength, corresponding to quantum transition 1s{sup 2} → 1s2p of helium-like nitrogen ions. Spatial development of plasma induced by Nd:YAG laser beam is simulated by 2D Radiation-Magneto-Hydro-Dynamic code Z*. The results for nitrogen gas layer (0.72 mm thickness, 1 bar pressure) and two different laser pulses (600 mJ/7 ns and 525 mJ/170 ps), corresponding to the experiments done in Laser Laboratory Gottingen are presented.

  17. Modeling of ns and ps laser-induced soft X-ray sources using nitrogen gas puff target

    NASA Astrophysics Data System (ADS)

    Vrba, P.; Vrbova, M.; Zakharov, S. V.; Zakharov, V. S.

    2014-07-01

    Gas puff laser plasma is studied as a source of water window radiation with 2.88 nm wavelength, corresponding to quantum transition 1s2 → 1s2p of helium-like nitrogen ions. Spatial development of plasma induced by Nd:YAG laser beam is simulated by 2D Radiation-Magneto-Hydro-Dynamic code Z*. The results for nitrogen gas layer (0.72 mm thickness, 1 bar pressure) and two different laser pulses (600 mJ/7 ns and 525 mJ/170 ps), corresponding to the experiments done in Laser Laboratory Gottingen are presented.

  18. High power Yb:YAG diode pumped LUCIA front-end oscillator (250 mJ, 50 ns, 2 Hz).

    NASA Astrophysics Data System (ADS)

    Bahbah, S.; Albach, D.; Assémat, F.; Bourdet, G.; Chanteloup, J.-C.; Piatti, P.; Pluvinage, M.; Vincent, B.; Touzé, G. L.

    2008-05-01

    The LULI laboratory is building a new intense laser chain with an energy goal of 100, J and at high repetition rate (10 Hz). This chain, called LUCIA, is composed of an oscillator and two diode pumped Yb:YAG amplifiers. We will show the progress of our work on the oscillator. In terms of performance in free running regime, we reach energies of about 4 J at 2 Hz with diode pumping energies of 11, J. In Q-switch regime 49ns long pulses at a repetition rate of 2 Hz were observed.

  19. Optimized Nanosecond Pulsed Electric Field Therapy Can Cause Murine Malignant Melanomas to Self-Destruct with a Single Treatment

    PubMed Central

    Nuccitelli, Richard; Tran, Kevin; Sheikh, Saleh; Athos, Brian; Kreis, Mark; Nuccitelli, Pamela

    2010-01-01

    We have identified a new, nanosecond pulsed electric field (nsPEF) therapy capable of eliminating murine melanomas located in the skin with a single treatment. When these optimized parameters are used, nsPEFs initiate apoptosis without hyperthermia. We have developed new suction electrodes that are compatible with human skin and have applied them to a xenograft nude mouse melanoma model system to identify the optimal field strength, pulse frequency and pulse number for the treatment of murine melanomas. A single treatment using the optimal pulse parameters (2000 pulses, 100 ns in duration, 30 kV/cm in amplitude at a pulse frequency of 5–7 pulses/s) eliminated all 17 melanomas treated with those parameters in 4 mice. This was the highest pulse frequency that we could use without raising the treated skin tumor temperature above 40 °C. We also demonstrate that the effects of nsPEF therapy are highly localized to only cells located between electrodes and results in very little scarring of the nsPEF-treated skin. PMID:20473857

  20. LASERS: Laser stand for irradiation of targets by laser pulses from the Iskra-5 facility at a repetition rate of 100 MHz

    NASA Astrophysics Data System (ADS)

    Annenkov, V. I.; Garanin, Sergey G.; Eroshenko, V. A.; Zhidkov, N. V.; Zubkov, A. V.; Kalipanov, S. V.; Kalmykov, N. A.; Kovalenko, V. P.; Krotov, V. A.; Lapin, S. G.; Martynenko, S. P.; Pankratov, V. I.; Faizullin, V. S.; Khrustalev, V. A.; Khudikov, N. M.; Chebotar, V. S.

    2009-08-01

    A train of a few tens of high-power subnanosecond laser pulses with a repetition period of 10 ns is generated in the Iskra-5 facility. The laser pulse train has an energy of up to 300 J and contains up to 40 pulses (by the 0.15 intensity level), the single pulse duration in the train being ~0.5 ns. The results of experiments on conversion of a train of laser pulses to a train of X-ray pulses are presented. Upon irradiation of a tungsten target, a train of X-ray pulses is generated with the shape of an envelope in the spectral band from 0.18 to 0.28 keV similar to that of the envelope of the laser pulse train. The duration of a single X-ray pulse in the train is equal to that of a single laser pulse.

  1. Investigation of Fe:ZnSe laser in pulsed and repetitively pulsed regimes

    SciTech Connect

    Velikanov, S D; Zaretskiy, N A; Zotov, E A; Maneshkin, A A; Chuvatkin, R S; Yutkin, I M; Kozlovsky, V I; Korostelin, Yu V; Krokhin, O N; Podmar'kov, Yu P; Savinova, S A; Skasyrsky, Ya K; Frolov, M P

    2015-01-31

    The characteristics of a Fe:ZnSe laser pumped by a single-pulse free-running Er : YAG laser and a repetitively pulsed HF laser are presented. An output energy of 4.9 J is achieved in the case of liquid-nitrogen cooling of the Fe{sup 2+}:ZnSe active laser element longitudinally pumped by an Er:YAG laser with a pulse duration of 1 ms and an energy up to 15 J. The laser efficiency with respect to the absorbed energy is 47%. The output pulse energy at room temperature is 53 mJ. The decrease in the output energy is explained by a strong temperature dependence of the upper laser level lifetime and by pulsed heating of the active element. The temperature dependence of the upper laser level lifetime is used to determine the pump parameters needed to achieve high pulse energies at room temperature. Stable repetitively-pulsed operation of the Fe{sup 2+}:ZnSe laser at room temperature with an average power of 2.4 W and a maximum pulse energy of 14 mJ is achieved upon pumping by a 1-s train of 100-ns HF laser pulses with a repetition rate of 200 Hz. (lasers)

  2. TFaNS-Tone Fan Noise Design/Prediction System: Users' Manual TFaNS Version 1.5

    NASA Technical Reports Server (NTRS)

    Topol, David A.; Huff, Dennis L. (Technical Monitor)

    2003-01-01

    TFaNS is the Tone Fan Noise Design/Prediction System developed by Pratt & Whitney under contract to NASA Glenn. The purpose of this system is to predict tone noise emanating from a fan stage including the effects of reflection and transmission by the rotor and stator and by the duct inlet and nozzle. The first version of this design system was developed under a previous NASA contract. Several improvements have been made to TFaNS. This users' manual shows how to run this new system. TFaNS consists of the codes that compute the acoustic properties (reflection and transmission coefficients) of the various elements and writes them to files, CUP3D Fan Noise Coupling Code that reads these files, solves the coupling problem, and outputs the desired noise predictions, and AWAKEN CFD/Measured Wake Postprocessor which reformats CFD wake predictions and/or measured wake data so they can be used by the system. This report provides information on code input and file structure essential for potential users of TFaNS.

  3. Results of Pulse-Scaling Experiments on Rapid-Growth DKDP Triplers Using the Optical Sciences Laser at 351 nm

    SciTech Connect

    Runkel, M; Burnham, A K; Milam, D; Sell, W; Feit, M; Rubenchik, A

    2000-12-11

    Results are reported from recently performed bulk-damage, pulse-scaling experiments on DKDP tripler samples taken from NIF-size, rapid-growth boule BD7. The tests were performed on LLNL's Optical Sciences Laser. A matrix of samples was exposed to single shots at 351 mn (3 {omega}) with average fluences from 4 to 8 J/cm{sup 2} for pulse durations of 1, 3 and 10 ns. The damage sites were scatter-mapped after testing to determine the damage evolution as a function of local beam fluence. The average bulk damage microcavity (pinpoint) density varied nearly linearly with fluence with peak values of approximately 16,000 pp/mm{sup 3} at 1 ns, 10,000 pp/mm{sup 3} at 3 ns and 400 pp/mm{sup 3} at 10 ns for fluences in the 8-10 J/cm{sup 2} range. The average size of a pinpoint was 10(+14,-9) {micro}m at 1 ns, 37 {+-} 20 {micro}m at 3 ns and {approx} 110 {micro}m at 10 ns, although all pulse durations produced pinpoints with a wide distribution of sizes. Analysis of the pinpoint density data yielded pulse-scaling behavior of t{sup 0.35}. Significant planar cracking around the pinpoint as was observed for the 10 ns case but not for the 1 and 3 ns pulses. Crack formation around pinpoints has also been observed frequently for Zeus ADT tests at {approx}8 ns. The high pinpoint densities also lead to significant eruption of near-surface bulk damage. Measurements of the damage site area for surface and bulk gave ratios (A{sub surf}/A{sub bulk}) of 2:1 at 1 ns, 7:1 at 3 ns and 110:1 at 10 ns. Maximum aperture averaged transmission losses on the order 15 percent have been measured by photometry for the worst damage at 1 and 3 ns for beam fluences in the 8-10 J/cm{sup 2} range. Analysis of this data yielded a pulse-scaling behavior of t{sup 0.25} for the obscured area. It was also determined that the crystals used in this test would survive unconditioned exposure to 4 J/cm{sup 2} shots on the NIF laser and still meet the obscuration requirement of 0.1%.

  4. Pulse length dependence of laser conditioning and bulk damage in KD2PO4

    SciTech Connect

    Adams, J J; Weiland, T L; Stanley, J R; Sell, W D; Luthi, R L; Vickers, J L; Carr, C W; Feit, M D; Rubenchik, A M; Spaeth, M L; Hackel, R P

    2004-11-10

    An experimental technique has been developed to measure the damage density {rho}({phi}) variation with fluence from scatter maps of bulk damage sites in plates of KD{sub 2}PO{sub 4} (DKDP) crystals combined with calibrated images of the damaging beam's spatial profile. Unconditioned bulk damage in tripler-cut DKDP crystals has been studied using 351 nm (3 {omega}) light at pulse lengths of 0.055, 0.091, 0.30, 0.86, 2.6, and 10 ns. It is found that there is less scatter due to damage at fixed fluence for longer pulse lengths. The results also show that for all the pulse lengths the scatter due to damage is a strong function of the damaging fluence. It is determined that the pulse length scaling for bulk damage scatter in unconditioned DKDP material varies as {tau}{sup 0.24 {+-} 0.05} over two orders of magnitude of pulse lengths. The effectiveness of 3 {omega} laser conditioning at pulse lengths of 0.055, 0.096, 0.30, 0.86, 3.5, and 23 ns is analyzed in term of damage density {rho}({phi}) at 3 {omega}, 2.6 ns. The 860 ps conditioning to a peak irradiance of 7 GW/cm{sup 2} had the best performance under 3 {omega}, 2.6 ns testing. It is shown that the optimal conditioning pulse length appears to lies in the range from 0.3 to 1 ns with a low sensitivity of 0.5 J/cm{sup 2}/ns to the exact pulse length.

  5. The Hepatitis C Virus NS5A Stimulates NS5B During In Vitro RNA Synthesis in a Template Specific Manner

    PubMed Central

    Quezada, Elizabeth M; Kane, Caroline M

    2009-01-01

    The hepatitis C virus (HCV) NS5B protein contains the RNA dependent RNA polymerase (RdRp) activity that catalyzes the synthesis of the viral genome with other host and viral factors. NS5A is an HCV-encoded protein previously shown to localize to the replisome and be necessary for viral replication. However, its role in replication has not been defined. Using an in vitro biochemical assay, we detected a stimulatory effect of NS5A on the NS5B replication reaction with minimal natural templates. NS5A stimulates replication by NS5B on two templates derived from the 3’ end of the RNA genome (4 fold ± 1.3 fold). A pre-incubation step with the two proteins prior to the replication reaction and substoichiometric levels of NS5A are required for detecting stimulation. With a template derived from the 3’end complementary to the RNA genome (the negative strand) no stimulation was observed. Furthermore, with a synthetic template that allows studying different phases of replication, NS5A stimulates NS5B during elongation. These findings suggest that NS5A stimulates NS5B during synthesis of the complementary (i.e., negative) strand of the RNA genome. PMID:19590581

  6. Pulsed power performance of PBFA Z

    SciTech Connect

    Spielman, R.B.; Stygar, W.A.; Seamen, J.F.

    1997-08-01

    PBFA Z is a new 60-TW/5-MJ electrical driver located at Sandia National Laboratories. The authors use PBFA Z to drive z pinches. The pulsed power design of PBFA Z is based on conventional single-pulse Marx generator, water-line pulse-forming technology used on the earlier Saturn and PBFA II accelerators. PBFA Z stores 11.4 MJ in its 36 Marx generators, couples 5 MJ in a 60-TW/105-ns pulse to the output water transmission lines, and delivers 3.0 MJ and 50 TW of electrical energy to the z-pinch load. Depending on the initial load inductance and the implosion time, the authors attain peak currents of 16-20 MA with a rise time of 105 ns. Current is fed to the z-pinch load through self magnetically-insulated transmission lines (MITLs). Peak electric fields in the MITLs exceed 2 MV/cm. The current from the four independent conical-disk MITLs is combined together in a double post-hole vacuum convolute with an efficiency greater than 95%. The authors achieved x-ray powers of 200 TW and x-ray energies of 1.9 MJ from tungsten wire-array z-pinch loads.

  7. Interspersion of fragmented fiber's splinters into tissue during pulsed alexandrite laser lithotripsy.

    PubMed

    Strunge, C; Brinkmann, R; Flemming, G; Engelhardt, R

    1991-01-01

    Laser induced shockwave lithotripsy (LISL) on artificially inserted human renal calculi was realized in explanted pig ureters. A pulse stretched Alexandrite solid state laser was used at 750nm. Pulses of 350ns and 1 microseconds duration were transmitted through a 250 microns all silica fiber onto a stone surface, keeping the fiber tip in contact with a stone close to the ureter wall. The high power density of the 350 ns pulses lead to an optical breakdown inside the distal fiber tip causing fiber fragmentation of about 28 mm/100 pulses. Deep penetration of the fiber fragments into the ureter wall was proven histologically. Fiber fragmentation was avoided by increasing the pulse duration up to 1 microseconds. Riks for patient treatment caused by short pulse lithotripsy are discussed.

  8. Single-beam Denisyuk holograms recording with pulsed 30Hz RGB laser

    NASA Astrophysics Data System (ADS)

    Zacharovas, Stanislovas; Bakanas, Ramūnas; Stankauskas, Algimantas

    2016-03-01

    It is well known fact that holograms can be recorded either by continuous wave (CW) laser, or by single pulse coming from pulsed laser. However, multi-pulse or multiple-exposure holograms were used only in interferometry as well as for information storage. We have used Geola's single longitudinal mode pulsed RGB laser to record Denisyuk type holograms. We successfully recorded objects situated at the distance of more than 30cm, employing the multi-pulse working regime of the laser. To record Denisyuk hologram we have used 50 ns duration 440, 660nm wavelength and 35ns duration 532nm wavelength laser pulses at the repetition rate of 30Hz. As photosensitive medium we have used Slavich-Geola PFG-03C glass photoplate. Radiations with different wavelengths were mixed into "white" beam, collimated and directed onto the photoplate. For further objects illumination an additional flat silver coated mirror was used.

  9. Control of boundary layer separation and the wake of an airfoil using ns-DBD plasma actuators

    NASA Astrophysics Data System (ADS)

    Ashcraft, Timothy

    The efficacy of nanosecond pulse driven dielectric barrier discharge (ns-DBD) plasma actuators for boundary layer separation and wake control is investigated experimentally. A single ns-DBD plasma actuator is placed at the leading edge of a NACA 0012 airfoil model. Both baseline and controlled flow fields are studied using static pressure measurements, Particle Image Velocimetry (PIV) and Constant Temperature Anemometry (CTA). Experiments are primarily performed at Re = 0.74 x 106 and alpha = 18°. CP, PIV and CTA data show that a forcing frequency of F+ = 1.14 is optimal for separation control. CTA surveys of the wake at x/c = 7 indicate three approximate regimes of behavior. Forcing in the range 0.92< F+ < 1.52 results in the best conditions for separation control over the airfoil, but has no dominant signature in the wake at x/c = 7. Excitation in the range of 0.23 < F+ < 0.92 produces a single dominant frequency in the wake while F+ < 0.23 shows behavior representing a possible impulse response or nonlinear effects. PIV data confirm these observations in all three regimes. Cross-correlations of CTA data are also employed to evaluate the two-dimensionality of the excited wake. The initial results presented here are part of an ongoing effort to use active flow control (AFC), in the form of ns-DBDs, as an enabling technology for the study of unsteady aerodynamics and vortex-body interactions.

  10. Ionization of sodium and rubidium nS, nP, and nD Rydberg atoms by blackbody radiation

    SciTech Connect

    Beterov, I. I.; Tretyakov, D. B.; Ryabtsev, I. I.; Ekers, A.; Bezuglov, N. N.

    2007-05-15

    Results of theoretical calculations of ionization rates of Rb and Na Rydberg atoms by blackbody radiation (BBR) are presented. Calculations have been performed for nS, nP, and nD states of Na and Rb, which are commonly used in a variety of experiments, at principal quantum numbers n=8-65 and at three ambient temperatures of 77, 300, and 600 K. A peculiarity of our calculations is that we take into account the contributions of BBR-induced redistribution of population between Rydberg states prior to photoionization and field ionization by extraction electric field pulses. The obtained results show that these phenomena affect both the magnitude of measured ionization rates and shapes of their dependences on n. The calculated ionization rates are compared with the results of our earlier measurements of BBR-induced ionization rates of Na nS and nD Rydberg states with n=8-20 at 300 K. A good agreement for all states except nS with n>15 is observed. We also present the useful analytical formulas for the quick estimation of BBR ionization rates of Rydberg atoms.

  11. PULSE COUNTER

    DOEpatents

    Trumbo, D.E.

    1959-02-10

    A transistorized pulse-counting circuit adapted for use with nuclear radiation detecting detecting devices to provide a small, light weight portable counter is reported. The small size and low power requirements of the transistor are of particular value in this instance. The circuit provides an adjustable count scale with a single transistor which is triggered by the accumulated charge on a storage capacitor.

  12. Sub 10 ns fast switching and resistance control in lateral GeTe-based phase-change memory

    NASA Astrophysics Data System (ADS)

    Yin, You; Zhang, Yulong; Takehana, Yousuke; Kobayashi, Ryota; Zhang, Hui; Hosaka, Sumio

    2016-06-01

    In this study, we investigated the fast switching and resistance control in a lateral GeTe-based phase-change memory (PCM). The resistivity of GeTe as a function of annealing temperature showed that it changed by more than 6 orders of magnitude in a very narrow temperature range. X-ray diffraction patterns of GeTe films indicated that GeTe had only one crystal structure, that is, face-centered cubic. It was demonstrated that the lateral device with a top conducting layer had a good performance. The operation characteristics of the GeTe-based lateral PCM device showed that it could be operated even when sub-10-ns voltage pulses were applied, making it much faster than a Ge2Sb2Te5-based device. The device resistance was successfully controlled by applying a staircase-like pulse, which enables the device to be used for fast multilevel storage.

  13. Use of parallel validation high-throughput screens to reduce false positives and identify novel dengue NS2B-NS3 protease inhibitors†

    PubMed Central

    Tomlinson, Suzanne M.; Watowich, Stanley J.

    2011-01-01

    Dengue virus (DENV), a mosquito-borne member of the family Flaviviridae, is a significant global pathogen affecting primarily tropical and subtropical regions of the world and placing tremendous burden on the limited medical infrastructure that exists in many of the developing countries located within these regions. Recent outbreaks in developed countries, including Australia (Hanna et al., 2009), France (Laruche et al., 2010), Taiwan (Kuan et al., 2010), and the USA (CDC, 2010), lead many researchers to believe that continued emergence into more temperate latitudes is likely. A primary concern is that there are no approved vaccines or antiviral therapies to treat DENV infections. Since the viral NS2B-NS3 protease (DENV NS2B-NS3pro) is required for virus replication, it provides a strategic target for the development of antiviral drugs. In this study, proof-of-concept high-throughput screenings (HTSs) were performed to unambiguously identify dengue 2 virus (DEN2V) NS2B-NS3pro inhibitors from a library of 2000 compounds. Validation screens were performed in parallel to concurrently eliminate insoluble, auto-fluorescing, and/or nonspecific inhibitors. Kinetic analyses of the hits revealed that parallel substrate fluorophore (AMC) interference controls and trypsin inhibition controls were able to reduce false positive rates due to solubility and fluorophore interference while the trypsin inhibition control additionally eliminated non-specific inhibitors. We identified five DEN2V NS2B-NS3pro inhibitors that also inhibited the related West Nile virus (WNV) protease (NS2B-NS3pro), but did not inhibit the trypsin protease. Biochemical analyses revealed various mechanisms of inhibition including competitive and mixed noncompetitive inhibition, with the lowest Ki values being 12 ± 1.5 μM for DEN2V NS2B-NS3pro and 2 ± 0.2 μM for WNV NS2B-NS3pro. PMID:22193283

  14. Bioelectric effects of intense ultrashort pulses.

    PubMed

    Joshi, R P; Schoenbach, K H

    2010-01-01

    Models for electric field interactions with biological cells predict that pulses with durations shorter than the charging time of the outer membrane can affect intracellular structures. Experimental studies in which human cells were exposed to pulsed electric fields of up to 300 kV/cm amplitude, with durations as short as 10 ns, have confirmed this hypothesis. The observed effects include the breaching of intracellular granule membranes without permanent damage to the cell membrane, abrupt rises in intracellular free calcium levels, enhanced expression of genes, cytochrome c release, and electroporation for gene transfer and drug delivery. At increased electric fields, the application of nanosecond pulses induces apoptosis (programmed cell death) in biological cells, an effect that has been shown to reduce the growth of tumors. Possible applications of the intracellular electroeffects are enhancing gene delivery to the nucleus, controlling cell functions that depend on calcium release (causing cell immobilization), and treating tumors. Such nanosecond electrical pulses have been shown to successfully treat melanoma tumors by using needle arrays as pulse delivery systems. Reducing the pulse duration of intense electric field pulses even further into the subnanosecond range will allow for the use of wideband antennas to deliver the electromagnetic fields into tissue with a spatial resolution in the centimeter range. This review carefully examines the above concepts, provides a theoretical basis, and modeling results based on both continuum approaches and atomistic molecular dynamics methods. Relevant experimental data are also presented, and some of the many potential bioengineering applications discussed.

  15. Pulse generation and preamplification for long pulse beamlines of Orion laser facility.

    PubMed

    Hillier, David I; Winter, David N; Hopps, Nicholas W

    2010-06-01

    We describe the pulse generation, shaping, and preamplification system for the nanosecond beamlines of the Orion laser facility. The system generates shaped laser pulses of up to approximately 1 J of 100 ps-5 ns duration with a programmable temporal profile. The laser has a 30th-power supergaussian spatial profile and is diffraction limited. The system is capable of imposing 2D smoothing by spectral dispersion upon the beam, which will produce a nonuniformity of 10% rms at the target. PMID:20517369

  16. Biophysical Studies of Nanosecond Pulsed Electric Field Induced Cell Membrane Permeabilization

    NASA Astrophysics Data System (ADS)

    Wu, Yu-Hsuan

    Nanosecond megavolts-per-meter pulsed electric field (nsPEF) offers a non-invasive manipulation of intracellular organelles and functions of biological cells. Accordingly, nsPEF is a potential technique for biophysical research and cancer therapy, and is of growing interest. Although, the application of nsPEF has shown electroperturbation on cell plasma membranes and intracellular membranes as well, the mechanisms underlying the electropermeabilization are still not clear. In this thesis, we systematically study nsPEFs (5 and 30 ns) induced membrane permeability change in biological cell in-vitro with different pulse parameters. In Chapter 3, we investigate the nsPEF-induced intracellular membrane permeabilization of mitochondria which play key roles in activating apoptosis in mammalian cells. The results show the evidences of nsPEF-induced membrane permeability increase in mitochondria, and suggest that nsPEF is a potential technology for cancer cell ablation without delivery of drug or gene into cells. In Chapter 2, 4 and 6, we study the properties of nsPEF-induced plasma membrane permeabilization. In the beginning, the change of plasma membrane permeability is studied by uptake of YO-PRO-1 and propidium iodide, fluorescent dyes specifically used as indicators of plasma membrane permeabilization. However, the detection is limited by the fluorescent emission efficiency and detector capability. To increase the detection sensitivity, we later develop a method based on cell volume change due to regulation of osmotic balance that causes water and small ions transport through plasma membrane. We find that even a single 10 MV/m pulse of 5 ns duration produces measureable cell swelling. The results demonstrate that cell swelling is susceptible to nsPEF and can detect membrane permeabilization more easily and precisely than fluorescent dyes. We compare the effects of different pulse parameters (pulse duration, pulse number, electric field amplitude and pulse repetition

  17. A high voltage nanosecond pulser with independently adjustable output voltage, pulse width, and pulse repetition frequency

    NASA Astrophysics Data System (ADS)

    Prager, James; Ziemba, Timothy; Miller, Kenneth; Carscadden, John; Slobodov, Ilia

    2014-10-01

    Eagle Harbor Technologies (EHT) is developing a high voltage nanosecond pulser capable of generating microwaves and non-equilibrium plasmas for plasma medicine, material science, enhanced combustion, drag reduction, and other research applications. The EHT nanosecond pulser technology is capable of producing high voltage (up to 60 kV) pulses (width 20-500 ns) with fast rise times (<10 ns) at high pulse repetition frequency (adjustable up to 100 kHz) for CW operation. The pulser does not require the use of saturable core magnetics, which allows for the output voltage, pulse width, and pulse repetition frequency to be fully adjustable, enabling researchers to explore non-equilibrium plasmas over a wide range of parameters. A magnetic compression stage can be added to improve the rise time and drive lower impedance loads without sacrificing high pulse repetition frequency operation. Work supported in part by the US Navy under Contract Number N00014-14-P-1055 and the US Air Force under Contract Number FA9550-14-C-0006.

  18. Study of Water Purification with Pulsed Power Supply using MOSFET Switches

    NASA Astrophysics Data System (ADS)

    Shimizu, Kazuo; Blajan, Marius; Muramatsu, Shuichi

    A Marx generator using MOSFET switches was built and studied in this paper for water purification. In order to replace the spark gap type of pulse power sources, with miss fire problems and short mechanical lifetime. In case of Marx Generator which generates negative pulses, a maximum output voltage of 3.6 kV, rise time of 40 ns and pulse width of 600 ns, was obtained. Discharge energy of one pulse was about 801 μJ for negative polarity at -2.4 kV. In case of positive pulses, a maximum output voltage of 3.6 kV, rise time of 75 ns and pulse width of 750 ns, was obtained. Discharge energy of one pulse was about 1120 μJ at 2.4 kV. The discharge was generated in bubbling water using a Marx Generator with MOSFET switches. The discoloration of indigo carmine solution was carried out to investigate the feasibility of low voltage discharge in bubbling water. As a result, indigo carmine solution was decolorized, although the discharge voltage was about -2.4 kV. The treatment performance was improved when oxygen was fed in the solution. The discoloration rate was 100 % after treatment time of 15 min with oxygen used as carrier gas. Emission of OH was confirmed and considered to play a role for water purification.

  19. Transient Features in Nanosecond Pulsed Electric Fields Differentially Modulate Mitochondria and Viability

    PubMed Central

    Beebe, Stephen J.; Chen, Yeong-Jer; Sain, Nova M.; Schoenbach, Karl H.; Xiao, Shu

    2012-01-01

    It is hypothesized that high frequency components of nanosecond pulsed electric fields (nsPEFs), determined by transient pulse features, are important for maximizing electric field interactions with intracellular structures. For monopolar square wave pulses, these transient features are determined by the rapid rise and fall of the pulsed electric fields. To determine effects on mitochondria membranes and plasma membranes, N1-S1 hepatocellular carcinoma cells were exposed to single 600 ns pulses with varying electric fields (0–80 kV/cm) and short (15 ns) or long (150 ns) rise and fall times. Plasma membrane effects were evaluated using Fluo-4 to determine calcium influx, the only measurable source of increases in intracellular calcium. Mitochondria membrane effects were evaluated using tetramethylrhodamine ethyl ester (TMRE) to determine mitochondria membrane potentials (ΔΨm). Single pulses with short rise and fall times caused electric field-dependent increases in calcium influx, dissipation of ΔΨm and cell death. Pulses with long rise and fall times exhibited electric field-dependent increases in calcium influx, but diminished effects on dissipation of ΔΨm and viability. Results indicate that high frequency components have significant differential impact on mitochondria membranes, which determines cell death, but lesser variances on plasma membranes, which allows calcium influxes, a primary determinant for dissipation of ΔΨm and cell death. PMID:23284682

  20. Nanosecond pulsed electric field generators for the study of subcellular effects.

    PubMed

    Kolb, Juergen F; Kono, Susumu; Schoenbach, Karl H

    2006-04-01

    Modeling and experimental studies have shown that pulsed electric fields of nanosecond duration and megavolt per meter amplitude affect subcellular structures but do not lead to the formation of large pores in the outer membrane. This "intracellular electromanipulation" requires the use of pulse generators which provide extremely high power but low energy pulses. In this study, we describe the concept of the required pulsed power sources, their design, operation, and the necessary diagnostics. Two types of pulse generators based on the Blumlein line principle have been developed and are described here. One system is designed to treat a large number of cells in cuvettes holding volumes from 0.1 to 0.8 ml. Pulses of up to 40 kV amplitude, with a duration of 10 ns and a rise time close to 1 ns can be applied to the cuvette. For an electrode gap of 1 mm this voltage corresponds to an average electric field of 40 MV/m. The second system allows for real time observation of individual cells under a microscope. It generates pulses of 10-300 ns duration with a rise time of 3.5 ns and voltage amplitudes up to 1 kV. Connected to a microreactor with an electrode gap of 100 microm, electric fields up to 10 MV/m are applied.

  1. Transient features in nanosecond pulsed electric fields differentially modulate mitochondria and viability.

    PubMed

    Beebe, Stephen J; Chen, Yeong-Jer; Sain, Nova M; Schoenbach, Karl H; Xiao, Shu

    2012-01-01

    It is hypothesized that high frequency components of nanosecond pulsed electric fields (nsPEFs), determined by transient pulse features, are important for maximizing electric field interactions with intracellular structures. For monopolar square wave pulses, these transient features are determined by the rapid rise and fall of the pulsed electric fields. To determine effects on mitochondria membranes and plasma membranes, N1-S1 hepatocellular carcinoma cells were exposed to single 600 ns pulses with varying electric fields (0-80 kV/cm) and short (15 ns) or long (150 ns) rise and fall times. Plasma membrane effects were evaluated using Fluo-4 to determine calcium influx, the only measurable source of increases in intracellular calcium. Mitochondria membrane effects were evaluated using tetramethylrhodamine ethyl ester (TMRE) to determine mitochondria membrane potentials (ΔΨm). Single pulses with short rise and fall times caused electric field-dependent increases in calcium influx, dissipation of ΔΨm and cell death. Pulses with long rise and fall times exhibited electric field-dependent increases in calcium influx, but diminished effects on dissipation of ΔΨm and viability. Results indicate that high frequency components have significant differential impact on mitochondria membranes, which determines cell death, but lesser variances on plasma membranes, which allows calcium influxes, a primary determinant for dissipation of ΔΨm and cell death.

  2. Multiphoton imaging reveals that nanosecond pulsed electric fields collapse tumor and normal vascular perfusion in human glioblastoma xenografts

    PubMed Central

    Bardet, Sylvia M.; Carr, Lynn; Soueid, Malak; Arnaud-Cormos, Delia; Leveque, Philippe; O’Connor, Rodney P.

    2016-01-01

    Despite the biomedical advances of the last century, many cancers including glioblastoma are still resistant to existing therapies leaving patients with poor prognoses. Nanosecond pulsed electric fields (nsPEF) are a promising technology for the treatment of cancer that have thus far been evaluated in vitro and in superficial malignancies. In this paper, we develop a tumor organoid model of glioblastoma and apply intravital multiphoton microscopy to assess their response to nsPEFs. We demonstrate for the first time that a single 10 ns, high voltage electric pulse (35–45 kV/cm), collapses the perfusion of neovasculature, and also alters the diameter of capillaries and larger vessels in normal tissue. These results contribute to the fundamental understanding of nsPEF effects in complex tissue environments, and confirm the potential of nsPEFs to disrupt the microenvironment of solid tumors such as glioblastoma. PMID:27698479

  3. Application of a single-board computer as a low-cost pulse generator

    NASA Astrophysics Data System (ADS)

    Fedrizzi, Marcus; Soria, Julio

    2015-09-01

    A BeagleBone Black (BBB) single-board open-source computer was implemented as a low-cost fully programmable pulse generator. The pulse generator makes use of the BBB Programmable Real-Time Unit (PRU) subsystem to achieve a deterministic temporal resolution of 5 ns, an RMS jitter of 290 ps and a timebase stability on the order of 10 ppm. A Python-based software framework has also been developed to simplify the usage of the pulse generator.

  4. Phylogenetic analysis of the NS5 gene of Zika virus.

    PubMed

    Adiga, Rama

    2016-10-01

    ZIKV infection has become a global threat spreading across 31 countries in Central America, South America, and the Caribbean. However, little information is available about the molecular epidemiology of ZIKV. Shared mutation of a threonine residue to alanine at the same position in the C terminal of NS5 sequences was observed in sequences from Colombia, Mexico, Panama, and Martinique. The sequences in the phylogenetic tree fell within the same cluster. Based on shared mutation the presence of a Latin American genotype was proposed. Comparison of African and Asian lineages yielded R29N, N273S, H383Q, and P391S mutation. The study highlights that mutation of amino acids at NS5 may contribute to neutropism of ZIKV. J. Med. Virol. 88:1821-1826, 2016. © 2016 Wiley Periodicals, Inc.

  5. Phylogenetic analysis of the NS5 gene of Zika virus.

    PubMed

    Adiga, Rama

    2016-10-01

    ZIKV infection has become a global threat spreading across 31 countries in Central America, South America, and the Caribbean. However, little information is available about the molecular epidemiology of ZIKV. Shared mutation of a threonine residue to alanine at the same position in the C terminal of NS5 sequences was observed in sequences from Colombia, Mexico, Panama, and Martinique. The sequences in the phylogenetic tree fell within the same cluster. Based on shared mutation the presence of a Latin American genotype was proposed. Comparison of African and Asian lineages yielded R29N, N273S, H383Q, and P391S mutation. The study highlights that mutation of amino acids at NS5 may contribute to neutropism of ZIKV. J. Med. Virol. 88:1821-1826, 2016. © 2016 Wiley Periodicals, Inc. PMID:27335310

  6. NS&T Managment Observations - 1st Quarter

    SciTech Connect

    David Gianotto

    2014-06-01

    The INL Management Observation Program (MOP) is designed to improve managers and supervisors understanding of work being performed by employees and the barriers impacting their success. The MOP also increases workers understanding of managements’ expectations as they relate to safety, security, quality, and work performance. Management observations (observations) are designed to improve the relationship and trust between employees and managers through increased engagement and interactions between managers and researchers in the field. As part of continuous improvement, NS&T management took initiative to focus on the participation and quality of observations in FY 14. This quarterly report is intended to (a) summarize the participation and quality of management’s observations, (b) assess observations for commonalities or trends related to facility or process barriers impacting research, and (c) provide feedback and make recommendations for improvements NS&T’s MOP.

  7. NS&T Management Observations: Quarterly Performance Analysis

    SciTech Connect

    Gianotto, David

    2014-09-01

    The INL Management Observation Program (MOP) is designed to improve managers and supervisors understanding of work being performed by employees and the barriers impacting their success. The MOP also increases workers understanding of managements’ expectations as they relate to safety, security, quality, and work performance. Management observations (observations) are designed to improve the relationship and trust between employees and managers through increased engagement and interactions between managers and researchers in the field. As part of continuous improvement, NS&T management took initiative to focus on the participation and quality of observations in FY-14. This quarterly report is intended to (a) summarize the participation and quality of management’s observations, (b) assess observations for commonalities or trends related to facility or process barriers impacting research, and (c) provide feedback and make recommendations for improvements NS&T’s MOP.

  8. NS&T Management Observations - 3rd Quarter

    SciTech Connect

    David Gianotto

    2014-07-01

    The INL Management Observation Program (MOP) is designed to improve managers and supervisors understanding of work being performed by employees and the barriers impacting their success. The MOP also increases workers understanding of managements’ expectations as they relate to safety, security, quality, and work performance. Management observations are designed to improve the relationship and trust between employees and managers through increased engagement and interactions between managers and researchers in the field. As part of continuous improvement, NS&T management took initiative to focus on the participation and quality of observations in FY 14. This quarterly report is intended to (a) summarize the participation and quality of management’s observations, (b) assess observations for commonalities or trends related to facility or process barriers impacting research, and (c) provide feedback and make recommendations for improvements NS&T’s MOP.

  9. SAT: a Late NS Protein of Porcine Parvovirus

    PubMed Central

    Zádori, Zoltán; Szelei, József; Tijssen, Peter

    2005-01-01

    The genomes of all members of the Parvovirus genus were found to contain a small open reading frame (ORF), designated SAT, with a start codon four or seven nucleotides downstream of the VP2 initiation codon. Green fluorescent protein or FLAG fusion constructs of SAT demonstrated that these ORFs were expressed. Although the SAT proteins of the different parvoviruses are not particularly conserved, they were all predicted to contain a membrane-spanning helix, and mutations in this hydrophobic stretch affected the localization of the SAT protein. SAT colocalized with calreticulin in the membranes of the endoplasmic reticulum and the nucleus. A knockout mutant (SAT−), with an unmodified VP sequence, showed a “slow-spreading” phenotype. These knockout mutants could be complemented with VP2− SAT+ mutant. The SAT protein is a late nonstructural (NS) protein, in contrast to previously identified NS proteins, since it is expressed from the same mRNA as VP2. PMID:16189014

  10. [Isolation of Achromobacter xylosoxidans NS12 and degradation of nitrophenols].

    PubMed

    Wan, Nian-Sheng; Gu, Ji-Dong; Huang, Jin-Hui; Gao, Chuan-De

    2007-02-01

    A nitrophenols-degrading bacterium, strain NS12, was isolated from a mangrove sediment by enrichment culture under aerobic conditions. Based on the analysis of 16S rDNA gene sequence the isolate was identified as Achromobacter xylosoxidans Strain NS12 was able to metabolize both o-nitrophenol (ONP) and p-nitrophenol (PNP) as the sole source of carbon, energy and nitrogen. However, this strain was not able to use 3-nitrophenol (MNP) as the only source of carbon energy and nitrogen for growth. The study demonstrated that when PNP and ONP occurred as a mixed substrate PNP degradation restrained the degradation of ONP and caused the major carbon source shift from ONP to PNP. Moreover, the results showed nitrophenols could be degraded by the indigenous bacteria in mangrove sediment.

  11. Plasma Membrane Voltage Changes during Nanosecond Pulsed Electric Field Exposure

    PubMed Central

    Frey, W.; White, J. A.; Price, R. O.; Blackmore, P. F.; Joshi, R. P.; Nuccitelli, R.; Beebe, S. J.; Schoenbach, K. H.; Kolb, J. F.

    2006-01-01

    The change in the membrane potential of Jurkat cells in response to nanosecond pulsed electric fields was studied for pulses with a duration of 60 ns and maximum field strengths of ∼100 kV/cm (100 V/cell diameter). Membranes of Jurkat cells were stained with a fast voltage-sensitive dye, ANNINE-6, which has a subnanosecond voltage response time. A temporal resolution of 5 ns was achieved by the excitation of this dye with a tunable laser pulse. The laser pulse was synchronized with the applied electric field to record images at times before, during, and after exposure. When exposing the Jurkat cells to a pulse, the voltage across the membrane at the anodic pole of the cell reached values of 1.6 V after 15 ns, almost twice the voltage level generally required for electroporation. Voltages across the membrane on the side facing the cathode reached values of only 0.6 V in the same time period, indicating a strong asymmetry in conduction mechanisms in the membranes of the two opposite cell hemispheres. This small voltage drop of 0.6–1.6 V across the plasma membrane demonstrates that nearly the entire imposed electric field of 10 V/μm penetrates into the interior of the cell and every organelle. PMID:16513782

  12. Plasma membrane voltage changes during nanosecond pulsed electric field exposure.

    PubMed

    Frey, W; White, J A; Price, R O; Blackmore, P F; Joshi, R P; Nuccitelli, R; Beebe, S J; Schoenbach, K H; Kolb, J F

    2006-05-15

    The change in the membrane potential of Jurkat cells in response to nanosecond pulsed electric fields was studied for pulses with a duration of 60 ns and maximum field strengths of approximately 100 kV/cm (100 V/cell diameter). Membranes of Jurkat cells were stained with a fast voltage-sensitive dye, ANNINE-6, which has a subnanosecond voltage response time. A temporal resolution of 5 ns was achieved by the excitation of this dye with a tunable laser pulse. The laser pulse was synchronized with the applied electric field to record images at times before, during, and after exposure. When exposing the Jurkat cells to a pulse, the voltage across the membrane at the anodic pole of the cell reached values of 1.6 V after 15 ns, almost twice the voltage level generally required for electroporation. Voltages across the membrane on the side facing the cathode reached values of only 0.6 V in the same time period, indicating a strong asymmetry in conduction mechanisms in the membranes of the two opposite cell hemispheres. This small voltage drop of 0.6-1.6 V across the plasma membrane demonstrates that nearly the entire imposed electric field of 10 V/mum penetrates into the interior of the cell and every organelle.

  13. Heating and ablation of tokamak graphite by pulsed nanosecond Nd-YAG lasers

    SciTech Connect

    Semerok, A.; Fomichev, S. V.; Weulersse, J.-M.; Brygo, F.; Thro, P.-Y.; Grisolia, C.

    2007-04-15

    The results on laser heating and ablation of graphite tiles of thermonuclear tokamaks are presented. Two pulsed Nd-YAG lasers (20 Hz repetition rate, 5 ns pulse duration and 10 kHz repetition rate, 100 ns pulse duration) were applied for ablation measurements. The ablation thresholds (1.0{+-}0.5 J/cm{sup 2} for 5 ns and 2.5{+-}0.5 J/cm{sup 2} for 100 ns laser pulses) were determined for the Tore Supra tokamak graphite tiles (backside) nonexposed to plasma. The high repetition rate Nd-YAG laser (10 kHz, 100 ns pulse duration) and the developed pyrometer system were applied for graphite heating measurements. Some unexpected features of laser heating of the graphite surface were observed. They were explained by the presence of a thin surface layer with the properties different from those of the bulk graphite. The theoretical models of laser heating and near-threshold ablation of graphite with imperfectly adhered layer were developed to interpret the experimental results.

  14. Photoconductive Semiconductor Switches for pulsed power applications

    SciTech Connect

    Loubriel, G.M.; Zutavern, F.J.; Denison, G.J.; Helgeson, W.D.; McLaughlin, D.L.; O`Malley, M.W.; Buttram, M.T.

    1993-08-01

    Photoconductive Semiconductor Switches (PCSS) are being used in, or tested for, many different pulsed power applications as diverse as ultrawideband (UWB) transmitters and high current pulsers. Some aspects of the switches that are relevant to most of the applications are: switch lifetime (longevity), switch opening time (related to the lifetime of carriers in the semiconductor), switching jitter, and the required laser energy. This paper will emphasize the results that we have obtained with Si switches for UWB applications. These include: measurement of switch longevity (a total of 80 Coulombs or 40 C/cm for a 2 cm wide switch and 18.4 Coulombs or 73 Coulombs/cm for a 0.25 cm wide switch), switching at high repetition rates (up to 540 Hz), measurement of carrier lifetime decay rates (a fast one of a few {mu}s, and a slow one of about 330 {mu}s), and measurements on the effect of neutron irradiation on carrier lifetimes. The total charge switched seems to be the highest ever reported for a PCSS. We have used these Si switches in a variety of circuits to produce: a monocycle with a period of about 10 ns corresponding to a center frequency of about 84 MHz, and ringing (many pulse) waveforms with periods of about 1 ns and 7.5 ns corresponding to center frequencies of 770 MHz and 133 MHz. We will also discuss recent studies on the switching properties of GaP.

  15. Discovery of an irreversible HCV NS5B polymerase inhibitor.

    PubMed

    Zeng, Qingbei; Nair, Anilkumar G; Rosenblum, Stuart B; Huang, Hsueh-Cheng; Lesburg, Charles A; Jiang, Yueheng; Selyutin, Oleg; Chan, Tin-Yau; Bennett, Frank; Chen, Kevin X; Venkatraman, Srikanth; Sannigrahi, Mousumi; Velazquez, Francisco; Duca, Jose S; Gavalas, Stephen; Huang, Yuhua; Pu, Haiyan; Wang, Li; Pinto, Patrick; Vibulbhan, Bancha; Agrawal, Sony; Ferrari, Eric; Jiang, Chuan-kui; Li, Cheng; Hesk, David; Gesell, Jennifer; Sorota, Steve; Shih, Neng-Yang; Njoroge, F George; Kozlowski, Joseph A

    2013-12-15

    The discovery of lead compound 2e was described. Its covalent binding to HCV NS5B polymerase enzyme was investigated by X-ray analysis. The results of distribution, metabolism and pharmacokinetics were reported. Compound 2e was demonstrated to be potent (replicon GT-1b EC50 = 0.003 μM), highly selective, and safe in in vitro and in vivo assays.

  16. Nanosecond pulsed electric fields cause melanomas to self-destruct

    PubMed Central

    Nuccitelli, Richard; Pliquett, Uwe; Chen, Xinhua; Ford, Wentia; Swanson, R. James; Beebe, Stephen J.; Kolb, Juergen F.; Schoenbach, Karl H.

    2006-01-01

    We have discovered a new, drug-free therapy for treating solid skin tumors. Pulsed electric fields greater than 20 kV/cm with rise times of 30 ns and durations of 300 ns penetrate into the interior of tumor cells and cause tumor cell nuclei to rapidly shrink and tumor blood flow to stop. Melanomas shrink by 90% within two weeks following a cumulative field exposure time of 120 μs. A second treatment at this time can result in complete remission. This new technique provides a highly localized targeting of tumor cells with only minor effects on overlying skin. Each pulse deposits 0.2 J and 100 pulses increase the temperature of the treated region by only 3 °C, ten degrees lower than the minimum temperature for hyperthermia effects. PMID:16545779

  17. Nanosecond pulsed electric fields cause melanomas to self-destruct.

    PubMed

    Nuccitelli, Richard; Pliquett, Uwe; Chen, Xinhua; Ford, Wentia; James Swanson, R; Beebe, Stephen J; Kolb, Juergen F; Schoenbach, Karl H

    2006-05-01

    We have discovered a new, drug-free therapy for treating solid skin tumors. Pulsed electric fields greater than 20 kV/cm with rise times of 30 ns and durations of 300 ns penetrate into the interior of tumor cells and cause tumor cell nuclei to rapidly shrink and tumor blood flow to stop. Melanomas shrink by 90% within two weeks following a cumulative field exposure time of 120 micros. A second treatment at this time can result in complete remission. This new technique provides a highly localized targeting of tumor cells with only minor effects on overlying skin. Each pulse deposits 0.2 J and 100 pulses increase the temperature of the treated region by only 3 degrees C, ten degrees lower than the minimum temperature for hyperthermia effects.

  18. Membrane interacting regions of Dengue virus NS2A protein.

    PubMed

    Nemésio, Henrique; Villalaín, José

    2014-08-28

    The Dengue virus (DENV) NS2A protein, essential for viral replication, is a poorly characterized membrane protein. NS2A displays both protein/protein and membrane/protein interactions, yet neither its functions in the viral cycle nor its active regions are known with certainty. To highlight the different membrane-active regions of NS2A, we characterized the effects of peptides derived from a peptide library encompassing this protein's full length on different membranes by measuring their membrane leakage induction and modulation of lipid phase behavior. Following this initial screening, one region, peptide dens25, had interesting effects on membranes; therefore, we sought to thoroughly characterize this region's interaction with membranes. This peptide presents an interfacial/hydrophobic pattern characteristic of a membrane-proximal segment. We show that dens25 strongly interacts with membranes that contain a large proportion of lipid molecules with a formal negative charge, and that this effect has a major electrostatic contribution. Considering its membrane modulating capabilities, this region might be involved in membrane rearrangements and thus be important for the viral cycle.

  19. Membrane Interacting Regions of Dengue Virus NS2A Protein

    PubMed Central

    2015-01-01

    The Dengue virus (DENV) NS2A protein, essential for viral replication, is a poorly characterized membrane protein. NS2A displays both protein/protein and membrane/protein interactions, yet neither its functions in the viral cycle nor its active regions are known with certainty. To highlight the different membrane-active regions of NS2A, we characterized the effects of peptides derived from a peptide library encompassing this protein’s full length on different membranes by measuring their membrane leakage induction and modulation of lipid phase behavior. Following this initial screening, one region, peptide dens25, had interesting effects on membranes; therefore, we sought to thoroughly characterize this region’s interaction with membranes. This peptide presents an interfacial/hydrophobic pattern characteristic of a membrane-proximal segment. We show that dens25 strongly interacts with membranes that contain a large proportion of lipid molecules with a formal negative charge, and that this effect has a major electrostatic contribution. Considering its membrane modulating capabilities, this region might be involved in membrane rearrangements and thus be important for the viral cycle. PMID:25119664

  20. Pulsed power systems for the DARHT accelerators

    SciTech Connect

    Downing, J.N.; Parsons, W.M.; Earley, L.M.; Melton, J.G.; Moir, D.C.; Carlson, R.L.; Barnes, G.A.; Builta, L.A.; Eversole, S.A.; Keel, G.I.; Rader, D.C.; Romero, J.A.; Shurter, R.P.

    1991-01-01

    The Dual-Axis Radiographic Hydro Test (DARHT) Facility is being designed to produce high-resolution flash radiographs of hydrodynamics experiments. Two 16- to 20-MeV linear induction accelerators (LIA), with an included angle of 90{degree}, are used to produce intense bremsstrahlung x-ray pulses of short duration (60-ns flat-top). Each accelerator has a 4-MeV electron source that injects an electron beam into a series of 250-kV induction cells. The three major pulsed-power systems are the injectors, the induction-cell pulsed-power (ICPP) units, and the ICPP trigger systems, and are discussed in this paper. 11 refs., 5 figs, 3 tabs.

  1. 41 CFR 60-2.10 - General purpose and contents of affirmative action programs.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... contents of affirmative action programs. 60-2.10 Section 60-2.10 Public Contracts and Property Management... EMPLOYMENT OPPORTUNITY, DEPARTMENT OF LABOR 2-AFFIRMATIVE ACTION PROGRAMS Purpose and Contents of Affirmative Action Programs § 60-2.10 General purpose and contents of affirmative action programs. (a) Purpose....

  2. 9 CFR 2.10 - Licensees whose licenses have been suspended or revoked.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 false Licensees whose licenses have been suspended or revoked. 2.10 Section 2.10 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE ANIMAL WELFARE REGULATIONS Licensing § 2.10 Licensees whose...

  3. 9 CFR 2.10 - Licensees whose licenses have been suspended or revoked.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 9 Animals and Animal Products 1 2012-01-01 2012-01-01 false Licensees whose licenses have been suspended or revoked. 2.10 Section 2.10 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE ANIMAL WELFARE REGULATIONS Licensing § 2.10 Licensees whose...

  4. 9 CFR 2.10 - Licensees whose licenses have been suspended or revoked.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 9 Animals and Animal Products 1 2013-01-01 2013-01-01 false Licensees whose licenses have been suspended or revoked. 2.10 Section 2.10 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE ANIMAL WELFARE REGULATIONS Licensing § 2.10 Licensees whose...

  5. 9 CFR 2.10 - Licensees whose licenses have been suspended or revoked.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Licensees whose licenses have been suspended or revoked. 2.10 Section 2.10 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE ANIMAL WELFARE REGULATIONS Licensing § 2.10 Licensees whose...

  6. 9 CFR 2.10 - Licensees whose licenses have been suspended or revoked.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 9 Animals and Animal Products 1 2014-01-01 2014-01-01 false Licensees whose licenses have been suspended or revoked. 2.10 Section 2.10 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE ANIMAL WELFARE REGULATIONS Licensing § 2.10 Licensees whose...

  7. Effects of influenza A virus NS1 protein on protein expression: the NS1 protein enhances translation and is not required for shutoff of host protein synthesis.

    PubMed

    Salvatore, Mirella; Basler, Christopher F; Parisien, Jean-Patrick; Horvath, Curt M; Bourmakina, Svetlana; Zheng, Hongyong; Muster, Thomas; Palese, Peter; García-Sastre, Adolfo

    2002-02-01

    The influenza A virus NS1 protein, a virus-encoded alpha/beta interferon (IFN-alpha/beta) antagonist, appears to be a key regulator of protein expression in infected cells. We now show that NS1 protein expression results in enhancement of reporter gene activity from transfected plasmids. This effect appears to be mediated at the translational level, and it is reminiscent of the activity of the adenoviral virus-associated I (VAI) RNA, a known inhibitor of the antiviral, IFN-induced, PKR protein. To study the effects of the NS1 protein on viral and cellular protein synthesis during influenza A virus infection, we used recombinant influenza viruses lacking the NS1 gene (delNS1) or expressing truncated NS1 proteins. Our results demonstrate that the NS1 protein is required for efficient viral protein synthesis in COS-7 cells. This activity maps to the amino-terminal domain of the NS1 protein, since cells infected with wild-type virus or with a mutant virus expressing a truncated NS1 protein-lacking approximately half of its carboxy-terminal end-showed similar kinetics of viral and cellular protein expression. Interestingly, no major differences in host cell protein synthesis shutoff or in viral protein expression were found among NS1 mutant viruses in Vero cells. Thus, another viral component(s) different from the NS1 protein is responsible for the inhibition of host protein synthesis during viral infection. In contrast to the earlier proposal suggesting that the NS1 protein regulates the levels of spliced M2 mRNA, no effects on M2 protein accumulation were seen in Vero cells infected with delNS1 virus.

  8. Pulsed response of a TWT

    NASA Technical Reports Server (NTRS)

    May, Brian D.

    1991-01-01

    The consequence of frequency domain multiple access channelization in a satellite communications system is that the ground- and space-based components often are required to operate in a linear region to prevent the generation of distortion signals. Components of a time division multiple access (TDMA) satellite system, such as a traveling-wave tube (TWT), can operate in the highest output power state because the channelization technique is relatively insensitive to the distortions resulting from saturated operation. A 30 GHz TWT was tested to determine the suitability of such a device in a TDMA system. Testing was focused on the ability of the TWT's output signal to rise up to full power at the leading edge of TDMA bursts, simulated by a pulse train. A peak power meter was used to display and measure the pulsed signal waveform. Measurements on the TWT output pulse rise time indicate that the TWT lengthened the rise time by 10 to 20 ns. Imposing modulator turn on timing that precedes the data burst by the TWT rise time is a logical approach to coordination of the two subsystem specification.

  9. Two regimes of widely tuneable noise-like pulses from a figure-eight fibre laser

    NASA Astrophysics Data System (ADS)

    Pottiez, O.; Ibarra-Escamilla, B.; Kuzin, E. A.; Hernández-García, J. C.; González-García, A.; Durán-Sánchez, M.

    2014-10-01

    In this paper we study a dispersion-managed figure-eight fibre laser generating noise-like pulses with adjustable characteristics. Non-self-starting mode locking leads to the formation of a single noise-like pulse circulating in the cavity. Both the duration of the pulse and its spectral width can be adjusted by tuning the angle of wave retarders, in particular a half-wave retarder that controls the switching power of the polarization-imbalanced nonlinear optical loop mirror that is used as mode locker. Wave retarder tuning also allows observing an abrupt transition between two clearly distinct noise-like pulse regimes, one characterized by a long (> 1 ns) rectangular pulse envelope with a narrow spectrum and the other characterized by shorter sub-ns bell-shaped pulses whose Raman-enhanced spectrum extends far beyond the doped fibre gain spectrum. The existence of two distinct noise-like pulsing modes can be understood in terms of the periodic variation of the pulse spectrum along the cavity, which is able to shift the effective dispersion regime of the laser. By joining the tuning ranges of each regime, the noise-like pulse duration can be adjusted between 57 ps and 6.3 ns, and its bandwidth between 3.5 and 59 nm.

  10. Generation of 7W nanosecond pulses with 670nm ridge-waveguide lasers

    NASA Astrophysics Data System (ADS)

    Klehr, A.; Prziwarka, T.; Liero, A.; Hoffmann, Th.; Pohl, J.; Fricke, J.; Wünsche, H.-J.; Wenzel, H.; Heinrich, W.; Erbert, G.

    2016-03-01

    The aim of this paper is to present detailed experimental and theoretical investigations of the behavior of ridge-waveguide (RW) lasers emitting at 670 nm under injection of sub-ns current pulses with high amplitudes. The RW lasers are based on strained GaInP double quantum wells embedded in an asymmetric AlGaInP/AlInP waveguide structure. The width of the ridge is 15 μm and the cavity length 3 mm. The laser diode is mounted on an in-house developed laser driver with a final stage based on GaN transistors, which generates nearly rectangular shaped current pulses with amplitudes up to 30 A and widths down to 300 ps. The pulse width can be varied electronically between 300 ps and 1.2 ns with a repetition frequency up to 1 MHz, which results in a variation of the pulse width of the emitted optical pulses between 200 ps and 1.2 ns. The maximum pulse power depends on the electrical pulse width and reaches 7.2 W for a ridge width of 15 μm. At high pulse current amplitudes the pulse power saturates. Time-dependent simulations with the drift-diffusion simulator WIAS-TeSCA reveal that accumulation of excess electrons under the ridge is the root cause for the power saturation, limiting the maximum achievable output power.

  11. Intense microwave pulse propagation through gas breakdown plasmas in a waveguide

    SciTech Connect

    Byrne, D.P.

    1986-10-08

    High-power microwave pulse-compression techniques are used to generate 2.856 GHz pulses which are propagated in a TE/sub 10/ mode through a gas filled section of waveguide, where the pulses interact with self-generated gas-breakdown plasmas. Pulse envelopes transmitted through the plasmas, with duration varying from 2 ns to greater than 1 ..mu..s, and peak powers of a few kW to nearly 100 MW, are measured as a function of incident pulse and gas pressure for air, nitrogen, and helium. In addition, the spatial and temporal development of the optical radiation emitted by the breakdown plasmas are measured. For transmitted pulse durations greater than or equal to 100 ns, good agreement is found with both theory and existing measurements. For transmitted pulse duration as short as 2 ns (less than 10 rf cycles), a two-dimensional model is used in which the electrons in the plasma are treated as a fluid whose interactions with the microwave pulse are governed by a self-consistent set of fluid equations and Maxwell's equations for the electromagnetic field. The predictions of this model for air are compared with the experimental results over a pressure range of 0.8 torr to 300 torr. Good agreement is obtained above about 1 torr pressure, demonstrating that microwave pulse propagation above the breakdown threshold can be accurately modeled on this time scale. 63 refs., 44 figs., 2 tabs.

  12. Time-Domain X-ray Diffraction in the Pulsed Laser Heated Diamond Anvil Cell

    NASA Astrophysics Data System (ADS)

    Prakapenka, V.; Goncharov, A. F.; Struzhkin, V.; Kantor, I.; Rivers, M. L.; Dalton, D. A.

    2011-12-01

    We have developed in situ x-ray synchrotron diffraction measurements of samples heated by a pulsed laser in the diamond anvil cell (DAC) at pressure up to 100 GPa and 3500 K. We used an electronically modulated 2-10 kHz repetition rate, 1064-1075 nm fiber laser with 1-100 microseconds pulse width synchronized with a gated x-ray detector (Pilatus) and time resolved radiometric temperature measurements. For the special APS hybrid mode, the measurements were also synchronized with a 500 ns long bunch carrying 88% of the ring current. This setup enables time domain measurements as a function of temperature in a micrometers time scale (averaged over many events, typically more than 10,000). X-ray diffraction data, temperature measurements, and finite element calculations with realistic geometric and thermochemical parameters show that in the present experimental configuration samples 4 micrometers thick can be continuously temperature monitored (up to 3000 K in our experiments) with the same level of axial and radial temperature uniformity as with continuous heating. We find that this novel technique offers a new and convenient way of fine tuning the maximum sample temperature by changing the pulse width of the laser. We will show examples of studies of the melting, thermal equation of state, and chemical reactivity. We acknowledge support from NSF EAR-0842057, DOE/ NNSA (CDAC), and EFree, an Energy Frontier Research Center funded by the U.S. Department of Energy, Office of Science, Office of Basic Energy Sciences under Award No. DESC0001057. X-ray diffraction measurements were performed at GSECARS (APS) supported by DOE Contract No.W-31-109- Eng-38.

  13. Retinal threshold studies for nanosecond and picosecond visible laser pulses

    NASA Astrophysics Data System (ADS)

    Roach, William P.; DiCarlo, Cheryl D.; Noojin, Gary D.; Stolarski, David J.; Amnotte, Rodney E.; Smith, Audrey B.; Rogers, Mark E.; Cain, Clarence P.

    1995-05-01

    Threshold measurements for Minimum Visible Lesions (MVL) at the retina are reported for 60 picoseconds (ps) and 4 nanoseconds (ns), single laser pulses in rhesus monkey eyes using a visible wavelength of 532 nanometers (nm) from a doubled Nd:YAG laser. The 50% probability for damage (ED50) dosages are calculated for 1 hour and 24 hour post exposures using 95% fiducial limits. For both pulsewidths, the threshold values calculated by probit analysis decrease between the 1 hour and 24 hour ophthalmoscopic evaluations. The ED50 value determined for the 60 ps pulsewidth was less than half the value at 4 ns (0.43 (mu) J/60 ps vs. 0.90 (mu) J/4 ns at 24 hours) for both readings. Of the 136 exposures for pulse energies ranging from 0.03 to 5.0 (mu) J no hemorrhagic lesions were produced for either pulsewidth studied. However, at 6.6 (mu) J one intraretinal hemorrhagic lesion was observed for 60 ps. The slope of the probit curve was higher for 60 ps when compared with the 4 ns value (3.03 at 60 ps vs. 2.68 at 4 ns). MVL threshold doses calculated are comparable with those reported in the literature. However, the 4 ns MVL values is less than one order of magnitude (a factor 4.7) above the Maximum Permissible Exposure (MPE) level as defined by the 'American National Standard For The Safe Use Of Lasers', ANSI Z136.1-19932. We present the current MVL data as it compares with previous data obtained for picosecond and femtosecond laser pulse thresholds and provide a preliminary assessment of how the ANSI MPE standard might be amended.

  14. Pulsed hydrojet

    DOEpatents

    Bohachevsky, I.O.; Torrey, M.D.

    1986-06-10

    An underwater pulsed hydrojet propulsion system is provided for accelerating and propelling a projectile or other vessel. A reactant, such as lithium, is fluidized and injected into a water volume. The resulting reaction produces an energy density in a time effective to form a steam pocket. Thrust flaps or baffles direct the pressure from the steam pocket toward an exit nozzle for accelerating a water volume to create thrust. A control system regulates the dispersion of reactant to control thrust characteristics.

  15. Generation of optical pulse packet using a fiber stacker for time fiducial applications

    NASA Astrophysics Data System (ADS)

    Lin, Honghuan; Wang, Jianjun; Huang, Zhihua; Li, Qi; Xu, Lixin; Tang, Xuan; Li, Chengyu; Guo, Chao; Zhao, Pengfei; Jing, Feng

    2016-08-01

    We present the concept of multicolor optical pulse packet generation based on modified fiber stackers featured with reflection geometries. Infrared radiation, visible and ultraviolet time fiducials were obtained by the amplification and frequency-conversion of the pulse packet generated in this fiber stacker. Application for the inertial confinement fusion (ICF) experiment diagnosis with time fiducials was demonstrated. With featured reflection geometries, the shaped packet pulses with uniform sub-pulse polarization states in a temporal window of ns range were generated in the fiber stacker. The design greatly simplifies the packet pulse generation for time fiducial and could be used for laser-driven ICF experimental diagnosis.

  16. Detection of dengue NS1 and NS3 proteins in placenta and umbilical cord in fetal and maternal death.

    PubMed

    Nunes, Priscila Conrado Guerra; Paes, Marciano Viana; de Oliveira, Carlos Alberto Basilio; Soares, Ana Carla Gomes; de Filippis, Ana Maria Bispo; Lima, Monique da Rocha Queiroz; de Barcelos Alves, Ada Maria; da Silva, Juliana Fernandes Amorim; de Oliveira Coelho, Janice Mery Chicarino; de Carvalho Rodrigues, Francisco das Chagas; Nogueira, Rita Maria Ribeiro; Dos Santos, Flávia Barreto

    2016-08-01

    In Brazil, dengue is a public health problem with the occurrence of explosive epidemics. This study reports maternal and fetal deaths due to dengue and which tissues of placenta and umbilical cord were analyzed by molecular methods and immunohistochemistry. The dengue NS3 and NS1 detection revealed the viral presence in different cells from placenta and umbilical cord. In the latter, DENV-2 was detected at a viral titer of 1,02 × 10(4) amounts of viral RNA. It was shown that the DENV markers analyzed here may be an alternative approach for dengue fatal cases investigation, especially involving maternal and fetal death. J. Med. Virol. 88:1448-1452, 2016. © 2016 Wiley Periodicals, Inc.

  17. Narrow-linewidth megahertz-rate pulse-burst laser for high-speed flow diagnostics.

    PubMed

    Thurow, Brian; Jiang, Naibo; Samimy, Mo; Lempert, Walter

    2004-09-10

    A second-generation pulse-burst laser system for high-speed flow diagnostics is described in detail. The laser can produce a burst of high-energy pulses (of the order of hundreds of millijoules per pulse) with individual pulse durations of less than 10 ns and pulse separations as short as 1 micros. A key improvement is the addition of a phase-conjugate mirror, which effectively isolates the high-intensity, short-duration pulses from the low-intensity, long-duration background illumination. It allows for more-efficient amplification and harmonic generation, with efficiencies exceeding 50% for second-harmonic and 40% for third-harmonic generation. Characteristics of the laser system, including gain narrowing, pulse-burst energy distribution, pulse narrowing, and overall pulse-burst energy, are described. In addition, the applicability of the laser for spectroscopic-based flow diagnostics is demonstrated through the presentation of megahertz-rate planar Doppler velocimetry results.

  18. High-energy square pulses and burst-mode pulses in an all-normal dispersion double-clad mode-locked fiber laser

    NASA Astrophysics Data System (ADS)

    Qiao, Zhi; Wang, Xiaochao; Wang, Chao; Jing, Yuanyuan; Fan, Wei; Lin, Zunqi

    2016-05-01

    A double-clad Yb-doped mode-locked fiber laser that can operate in burst-mode and square-pulse states is experimentally investigated. In the burst-mode state, a burst train with 55 pulses of 500 ps duration is obtained. In the square-pulse state, which is similar to noiselike pulses, the maximum pulse energy is 820 nJ and the duration can be tuned from 15.8 to 546 ns. The square pulses have a narrow and multipeak spectrum, which is quite different from that of normal noiselike pulses. The fiber laser promises an alternative formation mechanism for burst-mode and square-pulse mode-locked fiber lasers.

  19. Influence of the Pulse Duration onto the Material Removal Rate and Machining Quality for Different Types of Steel

    NASA Astrophysics Data System (ADS)

    Lauer, Benjamin; Jäggi, Beat; Neuenschwander, Beat

    When high requirements concerning machining quality are demanded, ultra short pulsed lasers with pulse durations from a few 100fs to 10ps may be the tool of choice. For these pulses it is known that the removal rate and machining quality slightly increases with shorter pulse duration. But as cost-effectiveness is also a key factor for a successful transfer of a technology to industrial applications, these systems compete against more cost effective systems with pulse durations from several 10ps to a few ns. It was found in previous work that the removal rate for metals strongly depends on the pulse duration. For steel also the composition and microstructure will influence the ablation processes. A systematic study of the removal rate and the machining quality for different types of steel and for pulse durations of several 100 fs to few ns will be presented.

  20. Pulsed hologram recording by nanosecond and subnanosecond small-dimensioned laser system

    NASA Astrophysics Data System (ADS)

    Bespalov, Victor G.; Dikasov, A. B.

    1991-02-01

    The results of the investigation of small-sized laser system on crystals KGd(W04)2 coherence are presented. This laser system generates pulses with durat i on of 3 ns or 0 . 2 ns . The i nvest i gat ion of the rec i pros i ty 1 aw and hologram diffraction efficiency of silver halide holographic materials on these durations are reported. With the help of this hololaser hologram recordings of diffuse objects are produced. 1 .

  1. Human Bocavirus NS1 and NS1-70 Proteins Inhibit TNF-α-Mediated Activation of NF-κB by targeting p65

    PubMed Central

    Liu, Qingshi; Zhang, Zhenfeng; Zheng, Zhenhua; Zheng, Caishang; Liu, Yan; Hu, Qinxue; Ke, Xianliang; Wang, Hanzhong

    2016-01-01

    Human bocavirus (HBoV), a parvovirus, is a single-stranded DNA etiologic agent causing lower respiratory tract infections in young children worldwide. Nuclear factor kappa B (NF-κB) transcription factors play crucial roles in clearance of invading viruses through activation of many physiological processes. Previous investigation showed that HBoV infection could significantly upregulate the level of TNF-α which is a strong NF-κB stimulator. Here we investigated whether HBoV proteins modulate TNF-α–mediated activation of the NF-κB signaling pathway. We showed that HBoV NS1 and NS1-70 proteins blocked NF-κB activation in response to TNF-α. Overexpression of TNF receptor-associated factor 2 (TRAF2)-, IκB kinase alpha (IKKα)-, IκB kinase beta (IKKβ)-, constitutively active mutant of IKKβ (IKKβ SS/EE)-, or p65-induced NF-κB activation was inhibited by NS1 and NS1-70. Furthermore, NS1 and NS1-70 didn’t interfere with TNF-α-mediated IκBα phosphorylation and degradation, nor p65 nuclear translocation. Coimmunoprecipitation assays confirmed the interaction of both NS1 and NS1-70 with p65. Of note, NS1 but not NS1-70 inhibited TNF-α-mediated p65 phosphorylation at ser536. Our findings together indicate that HBoV NS1 and NS1-70 inhibit NF-κB activation. This is the first time that HBoV has been shown to inhibit NF-κB activation, revealing a potential immune-evasion mechanism that is likely important for HBoV pathogenesis. PMID:27329558

  2. Terahertz field enhancement via coherent superposition of the pulse sequences after a single optical-rectification crystal

    SciTech Connect

    Sajadi, Mohsen Wolf, Martin; Kampfrath, Tobias

    2014-03-03

    Terahertz electromagnetic pulses are frequently generated by optical rectification of femtosecond laser pulses. In many cases, the efficiency of this process is known to saturate with increasing intensity of the generation beam because of two-photon absorption. Here, we demonstrate two routes to reduce this effect in ZnTe(110) crystals and enhance efficiency, namely, by (i) recycling the generation pulses and by (ii) splitting each generation pulse into two pulses before pumping the crystal. In both methods, the second pulse arrives ∼1 ns after the first one, sufficiently long for optically generated carriers to relax. Enhancement is achieved by coherently superimposing the two resulting terahertz fields.

  3. Calcium influx affects intracellular transport and membrane repair following nanosecond pulsed electric field exposure

    NASA Astrophysics Data System (ADS)

    Thompson, Gary Lee; Roth, Caleb C.; Dalzell, Danielle R.; Kuipers, Marjorie; Ibey, Bennett L.

    2014-05-01

    The cellular response to subtle membrane damage following exposure to nanosecond pulsed electric fields (nsPEF) is not well understood. Recent work has shown that when cells are exposed to nsPEF, ion permeable nanopores (<2 nm) are created in the plasma membrane in contrast to larger diameter pores (>2 nm) created by longer micro- and millisecond duration pulses. Nanoporation of the plasma membrane by nsPEF has been shown to cause a transient increase in intracellular calcium concentration within milliseconds after exposure. Our research objective is to determine the impact of nsPEF on calcium-dependent structural and repair systems in mammalian cells. Chinese hamster ovary (CHO-K1) cells were exposed in the presence and absence of calcium ions in the outside buffer to either 1 or 20, 600-ns duration electrical pulses at 16.2 kV/cm, and pore size was determined using propidium iodide and calcium green. Membrane organization was observed with morphological changes and increases in FM1-43 fluorescence. Migration of lysosomes, implicated in membrane repair, was followed using confocal microscopy of red fluorescent protein-tagged LAMP1. Microtubule structure was imaged using mEmerald-tubulin. We found that at high 600-ns PEF dosage, calcium-induced membrane restructuring and microtubule depolymerization coincide with interruption of membrane repair via lysosomal exocytosis.

  4. Disassembly of actin structures by nanosecond pulsed electric field is a downstream effect of cell swelling.

    PubMed

    Pakhomov, Andrei G; Xiao, Shu; Pakhomova, Olga N; Semenov, Iurii; Kuipers, Marjorie A; Ibey, Bennett L

    2014-12-01

    Disruption of the actin cytoskeleton structures was reported as one of the characteristic effects of nanosecond-duration pulsed electric field (nsPEF) in both mammalian and plant cells. We utilized CHO cells that expressed the monomeric fluorescent protein (mApple) tagged to actin to test if nsPEF modifies the cell actin directly or as a consequence of cell membrane permeabilization. A train of four 600-ns pulses at 19.2 kV/cm (2 Hz) caused immediate cell membrane poration manifested by YO-PRO-1 dye uptake, gradual cell rounding and swelling. Concurrently, bright actin features were replaced by dimmer and uniform fluorescence of diffuse actin. To block the nsPEF-induced swelling, the bath buffer was isoosmotically supplemented with an electropore-impermeable solute (sucrose). A similar addition of a smaller, electropore-permeable solute (adonitol) served as a control. We demonstrated that sucrose efficiently blocked disassembly of actin features by nsPEF, whereas adonitol did not. Sucrose also attenuated bleaching of mApple-tagged actin in nsPEF-treated cells (as integrated over the cell volume), although did not fully prevent it. We conclude that disintegration of the actin cytoskeleton was a result of cell swelling, which, in turn, was caused by cell permeabilization by nsPEF and transmembrane diffusion of solutes which led to the osmotic imbalance. PMID:24507565

  5. Generation and characterization of mouse monoclonal antibodies against NS4B protein of dengue virus.

    PubMed

    Xie, Xuping; Zou, Jing; Wang, Qing-Yin; Noble, Christian G; Lescar, Julien; Shi, Pei-Yong

    2014-02-01

    Dengue virus (DENV) non-structural protein 4B (NS4B) has been demonstrated to be an attractive antiviral target. Due to its nature as an integral membrane protein, NS4B remains poorly characterized. In this study, we generated and characterized two monoclonal antibodies (mAb) that selectively bind to DENV NS4B protein. One mAb, 10-3-7, is specific for DENV-2 NS4B, and its epitope was mapped to residues 5-15 of NS4B. The other mAb, 44-4-7, cross-reacts with all the four serotypes of DENV NS4B, and its epitope was mapped to residues 141-147 of NS4B. Using the mAbs, we probed the intracellular orientation of the epitopes of NS4B by an epitope accessibility assay. The results showed that the N-terminus of NS4B is located in the ER lumen, whereas amino acids 130-148 of NS4B are located in the cytosol. The study demonstrates that the two anti-NS4B mAbs will be useful for future structural and functional analyses of DENV NS4B. PMID:24503088

  6. A comparative biochemical analysis of the NS2B(H)-NS3pro protease complex from four dengue virus serotypes.

    PubMed

    Iempridee, Tawin; Thongphung, Ratchanu; Angsuthanasombat, Chanan; Katzenmeier, Gerd

    2008-01-01

    The two-component protease NS2B-NS3 of dengue virus mediates proteolytic processing of the polyprotein precursor and therefore represents a target for the development of antiviral drugs. The amino acid sequences of the NS3 serine protease and the NS2B cofactor exhibit relatively low degrees of conservation among the 4 serotypes thus suggesting that differences in enzyme activity exist which could modulate their susceptibility to future protease inhibitors. In this study we have addressed the question of functional similarity among the NS2B(H)-NS3pro proteases from 4 dengue virus serotypes by employing a uniform approach to clone, purify and assay proteolytic activity of these enzymes. Significant differences were observed for patterns of protein formation and expression levels in the E. coli host. Renaturation of the NS2B(H)-NS3pro precursors from dengue virus serotypes 2, 3 and 4 mediated by artificial chaperone-assisted refolding yielded enzymatically active proteases, whereas the enzyme from serotype 1 was obtained as soluble protein. Kinetic experiments using the GRR-amc substrate revealed comparable K(m) values while k(cat) values as obtained by active-site titration experiments displayed minor variations. Denaturation experiments demonstrated significant differences in half-life of the NS3 proteases from serotypes 2, 3 and 4 at 50 degrees C, whereas pH optima for all 4 enzymes were comparable.

  7. Investigation of the phase stability of an X-band long pulse multibeam relativistic klystron amplifier

    NASA Astrophysics Data System (ADS)

    Liu, Zhenbang; Huang, Hua; Jin, Xiao; Lei, Lurong; Zhu, Lei; Li, Lele; Li, Shifeng; Yan, Wenkang; He, Hu

    2016-09-01

    To realize coherent high power microwave combining, an X-band long pulse multibeam relativistic klystron amplifier is designed, and the relative phase stability is investigated by three dimensions particle in cell simulation and high power microwave experiment. The simulation shows that the relative phase difference can be stabilized at gigawatt level radiation power. But the relative phase jitter increases in the experiment, then some measures are proposed to improve the stability of relative phase difference and avoid pulse shortening. A 0.98 GW radiation power with pulse duration of 160 ns is obtained in the experiment, the pulse shortening is avoided. The relative phase difference fluctuation between output microwave and input RF signal is less than ±25° in a single shot with duration of 100 ns. Then, the experiment of pulse repetition is carried out, and an output microwave with 0.98 GW radiation power at 25 Hz repetition rate is obtained. The power conversion efficiency is about 35% with pulse duration of 160 ns. The relative phase difference is less than ±30° at 25 Hz repetition rate in 100 ns.

  8. Nanosecond pulsed electric fields and the cell cycle

    NASA Astrophysics Data System (ADS)

    Mahlke, Megan A.

    Exposure to nanosecond pulsed electrical fields (nsPEFs) can cause poration of external and internal cell membranes, DNA damage, and disassociation of cytoskeletal components, all of which are capable of disrupting a cell's ability to replicate. The phase of the cell cycle at the time of exposure is linked to differential sensitivities to nsPEFs across cell lines, as DNA structure, membrane elasticity, and cytoskeletal structure change dramatically during the cell cycle. Additionally, nsPEFs are capable of activating cell cycle checkpoints, which could lead to apoptosis or slow population growth. NsPEFs are emerging as a method for treating tumors via apoptotic induction; therefore, investigating the relevance of nsPEFs and the cell cycle could translate into improved efficacy in tumor treatment. Populations of Jurkat and Chinese Hamster Ovary (CHO) cells were examined post-exposure (10 ns pulse trains at 150kV/cm) by analysis of DNA content via propidium iodide staining and flow cytometric analysis at various time points (1, 6, and 12h post-exposure) to determine population distribution in cell cycle phases. Additionally, CHO and Jurkat cells were synchronized in G1/S and G2/M phases, pulsed, and analyzed to evaluate the role of cell cycle phase in survival of nsPEFs. CHO populations appeared similar to sham populations post-nsPEFs but exhibited arrest in the G1 phase at 6h after exposure. Jurkat cells exhibited increased cell death after nsPEFs compared to CHO cells but did not exhibit checkpoint arrest at any observed time point. The G1/S phase checkpoint is partially controlled by the action of p53; the lack of an active p53 response in Jurkat cells could contribute to their ability to pass this checkpoint and resist cell cycle arrest. Both cell lines exhibited increased sensitivity to nsPEFs in G2/M phase. Live imaging of CHO cells after nsPEF exposure supports the theory of G1/S phase arrest, as a reduced number of cells undergo mitosis within 24 h when

  9. PULSE COLUMN

    DOEpatents

    Grimmett, E.S.

    1964-01-01

    This patent covers a continuous countercurrent liquidsolids contactor column having a number of contactor states each comprising a perforated plate, a layer of balls, and a downcomer tube; a liquid-pulsing piston; and a solids discharger formed of a conical section at the bottom of the column, and a tubular extension on the lowest downcomer terminating in the conical section. Between the conical section and the downcomer extension is formed a small annular opening, through which solids fall coming through the perforated plate of the lowest contactor stage. This annular opening is small enough that the pressure drop thereacross is greater than the pressure drop upward through the lowest contactor stage. (AEC)

  10. Precision timing measurement of phototube pulses using a flash analog-to-digital converter

    SciTech Connect

    J.V. Bennett, M. Kornicer, M.R. Shepherd, M.M. Ito

    2010-10-01

    We present the timing characteristics of the flash ADC readout of the GlueX forward calorimeter, which depends on precise measurement of arrival time of pulses from FEU 84-3 photomultiplier tubes to suppress backgrounds. The tests presented were performed using two different 250 MHz prototype flash ADC devices, one with eight-bit and one with 12-bit sampling depth. All measured time resolutions were better than 1 ns, independent of signal size, which is the design goal for the GlueX forward calorimeter. For pulses with an amplitude of 100 mV the timing resolution is 0.57±0.18 ns, while for 500 mV pulses it is 0.24±0.08 ns.

  11. A XeCl laser with a controlled radiation pulse shape

    SciTech Connect

    Fedorov, A I

    2009-04-30

    The pump parameters of a three-contour excitation system are studied in a gas-discharge excimer XeCl laser using a Ne-Xe-HCl mixture. A computation model is developed for finding the parameters of multi-contour excitation systems. A setup incorporating a three-contour system for excitation and automatic UV preionisation is designed, which provides multipulse generation of 65-ns, 26-mJ laser pulses at the laser efficiency of 1%. It is shown that generation of short radiation pulses of duration 7 ns and relatively long pulses of duration 65 ns in the multipulse generation regime is possible in the excitation system under study in Xe:HCl = 20:1 mixtures containing neon as buffer gas. (lasers)

  12. Note: A novel method for generating multichannel quasi-square-wave pulses

    NASA Astrophysics Data System (ADS)

    Mao, C.; Zou, X.; Wang, X.

    2015-08-01

    A 21-channel quasi-square-wave nanosecond pulse generator was constructed. The generator consists of a high-voltage square-wave pulser and a channel divider. Using an electromagnetic relay as a switch and a 50-Ω polyethylene cable as a pulse forming line, the high-voltage pulser produces a 10-ns square-wave pulse of 1070 V. With a specially designed resistor-cable network, the channel divider divides the high-voltage square-wave pulse into 21 identical 10-ns quasi-square-wave pulses of 51 V, exactly equal to 1070 V/21. The generator can operate not only in a simultaneous mode but also in a delay mode if the cables in the channel divider are different in length.

  13. Nanosecond repetitively pulsed discharge control of premixed lean methane-air combustion

    NASA Astrophysics Data System (ADS)

    Bak, Moon Soo; Cappelli, Mark A.

    2012-10-01

    Two-dimensional kinetic simulations are carried out to investigate the effects of the discharge repetition rate and pulse width of nanosecond repetitively pulsed discharges on stabilizing premixed lean methane-air combustion. The repetition rate and pulse widths are varied from 10 kHz to 50 kHz and from 9 ns to 2 ns respectively, while the total power is held constant. The lower repetition rates, because of their higher pulse energies, produce a larger fraction of radicals such as O, H, and OH. Surprisingly, however, the effect on flame stabilization is found to be essentially the same for all of the tested repetition rates. The shorter pulse width is found to favor the production of species in higher electronic states, but the varying effects on stabilization is also found to be small. Our results indicate that the total deposited power is the critical element that determines the extent of stabilization over this range of discharge properties studied.

  14. Note: A novel method for generating multichannel quasi-square-wave pulses.

    PubMed

    Mao, C; Zou, X; Wang, X

    2015-08-01

    A 21-channel quasi-square-wave nanosecond pulse generator was constructed. The generator consists of a high-voltage square-wave pulser and a channel divider. Using an electromagnetic relay as a switch and a 50-Ω polyethylene cable as a pulse forming line, the high-voltage pulser produces a 10-ns square-wave pulse of 1070 V. With a specially designed resistor-cable network, the channel divider divides the high-voltage square-wave pulse into 21 identical 10-ns quasi-square-wave pulses of 51 V, exactly equal to 1070 V/21. The generator can operate not only in a simultaneous mode but also in a delay mode if the cables in the channel divider are different in length. PMID:26329250

  15. The 150 ns detector project: Prototype preamplifier results

    NASA Astrophysics Data System (ADS)

    Warburton, W. K.; Russell, S. R.; Kleinfelder, Stuart A.

    1994-08-01

    The long-term goal of the 150 ns detector project is to develop a pixel area detector capable of 6 MHz frame rates (150 ns/frame). Our milestones toward this goal are: a single pixel, 1×256 1D and 8×8 2D detectors, 256×256 2D detectors and, finally, 1024 × 1024 2D detectors. The design strategy is to supply a complete electronics chain (resetting preamp, selectable gain amplifier, analog-to-digital converter (ADC), and memory) for each pixel. In the final detectors these will all be custom integrated circuits. The front-end preamplifiers are integrated first, since their design and performance are the most unusual and also critical to the project's success. Similarly, our early work is concentrated on devising and perfecting detector structures. In this paper we demonstrate the performance of prototypes of our integrated preamplifiers. While the final design will have 64 preamps to a chip, including a switchable gain stage, the prototypes were integrated 8 channels to a "Tiny Chip" and tested in 4 configurations (feedback capacitor Cf equal 2.5 or 4.0 pF, output directly or through a source follower). These devices have been tested thoroughly for reset settling times, gain, linearity, and electronic noise. They generally work as designed, being fast enough to easily integrate detector charge, settle, and reset in 150 ns. Gain and linearity appear to be acceptable. Current values of electronic noise, in double-sampling mode, are about twice the design goal of {2}/{3} of a single photon at 6 keV. We expect this figure to improve with the addition of the onboard amplifier stage and improved packaging. Our next test chip will include these improvements and allow testing with our first detector samples, which will be 1×256 (50 μm wide pixels) and 8×8 (1 mm 2 pixels) element detector on 1 mm thick silicon.

  16. VM version of INTERLAN's NS4240 Xerox ITP Network Software

    SciTech Connect

    Frese, H.; Cottrell, R.L.; Downey, T.

    1986-04-01

    This manual describes Stanford Linear Accelerator Center's VM adaptation of INTERLAN's NS4240 ITP Network Software. The ITP Network Software is an implementation of the Xerox Network Systems Internet Transport Protocols. The ITP Network Software runs under the VM/SP operating system. This manual assumes familiarity with the use of the VM operating system. The user is also expected to have experience in assembling, linking, and running application programs on a system. The user should be familiar with the concepts of computer networking and have an understanding of the more specific concepts of Ethernet-based networks. 10 refs.

  17. Tapered pulse tube for pulse tube refrigerators

    DOEpatents

    Swift, Gregory W.; Olson, Jeffrey R.

    1999-01-01

    Thermal insulation of the pulse tube in a pulse-tube refrigerator is maintained by optimally varying the radius of the pulse tube to suppress convective heat loss from mass flux streaming in the pulse tube. A simple cone with an optimum taper angle will often provide sufficient improvement. Alternatively, the pulse tube radius r as a function of axial position x can be shaped with r(x) such that streaming is optimally suppressed at each x.

  18. Controlling output pulse and prepulse in a resonant microwave pulse compressor

    SciTech Connect

    Shlapakovski, A.; Artemenko, S.; Chumerin, P.; Yushkov, Yu.

    2013-02-07

    A resonant microwave pulse compressor with a waveguide H-plane-tee-based energy extraction unit was studied in terms of its capability to produce output pulses that comprise a low-power long-duration (prepulse) and a high-power short-duration part. The application of such combined pulses with widely variable prepulse and high-power pulse power and energy ratios is of interest in the research area of electronic hardware vulnerability. The characteristics of output radiation pulses are controlled by the variation of the H-plane tee transition attenuation at the stage of microwave energy storage in the compressor cavity. Results of theoretical estimations of the parameters tuning range and experimental investigations of the prototype S-band compressor (1.5 MW, 12 ns output pulse; {approx}13.2 dB gain) are presented. The achievable maximum in the prepulse power is found to be about half the power of the primary microwave source. It has been shown that the energy of the prepulse becomes comparable with that of the short-duration (nanosecond) pulse, while the power of the latter decreases insignificantly. The possible range of variation of the prepulse power and energy can be as wide as 40 dB. In the experiments, the prepulse level control within the range of {approx}10 dB was demonstrated.

  19. Cyclosporine Inhibits a Direct Interaction between Cyclophilins and Hepatitis C NS5A

    PubMed Central

    Striker, Rob

    2010-01-01

    Background Hepatitis C Virus (HCV) infection is a leading indication for liver transplantation. HCV infection reoccurs almost universally post transplant, decreasing both graft longevity and patient survival. The immunosuppressant, cyclosporine A (CsA) has potent anti-HCV activity towards both HCV replicons and the genotype 2a cell culture infectious virus. Previously, we isolated mutations in the 1bN replicon with less sensitivity to CsA that mapped to both NS5A and NS5B regions of the virus. Mutations in NS5A alone conferred decreased CsA susceptibility regardless of NS5B mutations. Methodology/Principal Findings We examined the mechanisms by which NS5A mutations contribute to CsA resistance and if they are strain dependent. Using in vitro mutagenesis, the amino acid position 321 mutation of NS5A was restored to the wild-type tyrosine residue conferring partial CsA susceptibility on the mutant replicon. The 321 mutation also alters CsA susceptibility of the JFH cell culture virus. Additionally, we demonstrated a novel CsA-sensitive interaction between NS5A and both cyclophilin A and B. Both the mutant NS5A and wild type NS5A bind cyclophilin in vitro. The NS5A: cyclophilin interaction requires both the NS5A region identified by the resistance mutants and cyclophilin catalytic residues. In cell culture, NS5A from CsA resistant mutant has an enhanced interaction with cyclophilin B. Additionally; NS5B facilitates a stronger binding of mutant NS5A to endogenous cyclophilin B than wild-type in cell culture. Conclusions/Significance Collectively, this data suggests direct interactions between cyclophilins and NS5A are critical to understand for optimal use of cyclophilin inhibitors in anti-HCV therapy. PMID:20352119

  20. Compact field programmable gate array-based pulse-sequencer and radio-frequency generator for experiments with trapped atoms

    SciTech Connect

    Pruttivarasin, Thaned; Katori, Hidetoshi

    2015-11-15

    We present a compact field-programmable gate array (FPGA) based pulse sequencer and radio-frequency (RF) generator suitable for experiments with cold trapped ions and atoms. The unit is capable of outputting a pulse sequence with at least 32 transistor-transistor logic (TTL) channels with a timing resolution of 40 ns and contains a built-in 100 MHz frequency counter for counting electrical pulses from a photo-multiplier tube. There are 16 independent direct-digital-synthesizers RF sources with fast (rise-time of ∼60 ns) amplitude switching and sub-mHz frequency tuning from 0 to 800 MHz.

  1. Compact field programmable gate array-based pulse-sequencer and radio-frequency generator for experiments with trapped atoms.

    PubMed

    Pruttivarasin, Thaned; Katori, Hidetoshi

    2015-11-01

    We present a compact field-programmable gate array (FPGA) based pulse sequencer and radio-frequency (RF) generator suitable for experiments with cold trapped ions and atoms. The unit is capable of outputting a pulse sequence with at least 32 transistor-transistor logic (TTL) channels with a timing resolution of 40 ns and contains a built-in 100 MHz frequency counter for counting electrical pulses from a photo-multiplier tube. There are 16 independent direct-digital-synthesizers RF sources with fast (rise-time of ∼60 ns) amplitude switching and sub-mHz frequency tuning from 0 to 800 MHz. PMID:26628171

  2. Effects of Pulse Duration on Bulk Laser Damage in 350-nm Raster-Scanned DKDP

    SciTech Connect

    Runkel, M; Bruere, J; Sell, W; Weiland, T; Milam, D; Hahn, D E; Nostrand, M C

    2002-10-30

    In this paper we present the results of bulk damage experiments done on Type-I1 DKDP triple harmonic generator crystals that were raster conditioned with 351-355 nm wavelengths and pulse durations of 4 and 23.2 ns. In the first phase of experiments 20 different scan protocols were rastered into a sample of rapid growth DKDP. The sample was then rastered at damage-causing fluences to determine the three most effective protocols. These three protocols were scanned into a 15-cm sample of conventional-growth DKDP and then exposed to single shots of a I-cm beam from LLNL's Optical Sciences Laser at fluences ranging from 0.5 - 1.5X of the 10% damage probability fluence and nominal pulse durations of 0.1,0.3,0.8,3.2,7.0 and 20 ns. The experiment showed that pulse durations in the 1-3 ns range were much more effective at conditioning than pulses in the 16.3 ns range and that the multiple pass 'peak fluence' scan was more effective than the single pass 'leading edge' scan for 23.2 ns XeF scans.

  3. Nanosecond pulse shaping at 780 nm with fiber-based electro-optical modulators and a double-pass tapered amplifier

    NASA Astrophysics Data System (ADS)

    Rogers, C. E.; Gould, P. L.

    2016-02-01

    We describe a system for generating frequency-chirped and amplitude-shaped pulses on time scales from sub-nanosecond to ten nanoseconds. The system starts with cw diode-laser light at 780 nm and utilizes fiber-based electro-optical phase and intensity modulators, driven by an arbitrary waveform generator, to generate the shaped pulses. These pulses are subsequently amplified to several hundred mW with a tapered amplifier in a delayed double-pass configuration. Frequency chirps up to 5 GHz in 2 ns and pulse widths as short as 0.15 ns have been realized.

  4. Multiple current peaks in room-temperature atmospheric pressure homogenous dielectric barrier discharge plasma excited by high-voltage tunable nanosecond pulse in air

    SciTech Connect

    Yang, De-Zheng; Wang, Wen-Chun; Zhang, Shuai; Tang, Kai; Liu, Zhi-jie; Wang, Sen

    2013-05-13

    Room temperature homogenous dielectric barrier discharge plasma with high instantaneous energy efficiency is acquired by using nanosecond pulse voltage with 20-200 ns tunable pulse width. Increasing the voltage pulse width can lead to the generation of regular and stable multiple current peaks in each discharge sequence. When the voltage pulse width is 200 ns, more than 5 organized current peaks can be observed under 26 kV peak voltage. Investigation also shows that the organized multiple current peaks only appear in homogenous discharge mode. When the discharge is filament mode, organized multiple current peaks are replaced by chaotic filament current peaks.

  5. Nanosecond pulse shaping at 780 nm with fiber-based electro-optical modulators and a double-pass tapered amplifier.

    PubMed

    Rogers, C E; Gould, P L

    2016-02-01

    We describe a system for generating frequency-chirped and amplitude-shaped pulses on time scales from sub-nanosecond to ten nanoseconds. The system starts with cw diode-laser light at 780 nm and utilizes fiber-based electro-optical phase and intensity modulators, driven by an arbitrary waveform generator, to generate the shaped pulses. These pulses are subsequently amplified to several hundred mW with a tapered amplifier in a delayed double-pass configuration. Frequency chirps up to 5 GHz in 2 ns and pulse widths as short as 0.15 ns have been realized. PMID:26906832

  6. A fast pulsed power source applied to treatment of conducting liquids and air

    SciTech Connect

    Heesch, E.J.M. van; Pemen, A.J.M.; Huijbrechts, P.A.H.J.; Laan, P.C.T. van der; Ptasinski, K.J.; Zanstra, G.J.; Jong, P. de

    2000-02-01

    Two pilot pulsed power sources were developed for fundamental investigations and industrial demonstrations of treatment of conducting liquids. The developed heavy-duty power sources have an output voltage of 100 kV (rise time 10 ns, pulse duration 150 ns, pulse repetition rate maximum 1,000 pps). A pulse energy of 0.5--3 J/pulse and an average pulse power of 1.5 kW have been achieved with an efficiency of about 80%. In addition, adequate electromagnetic compatibility is achieved between the high-voltage pulse sources and the surrounding equipment. Various applications, such as the use of pulsed electric fields (PEF's) or pulsed corona discharges for inactivation of microorganisms in liquids or air, have been tested in the laboratory. For PEF treatment, homogeneous electric fields in the liquid of up to 70 kV/cm at a pulse repetition rate of 10--400 pps could be achieved. The inactivation is found to be 85 kJ/L per log reduction for Pseudomonas fluorescens and 500 kJ/L per log reduction for spores of Bacillus cereus. Corona directly applied to the liquid is found to be more efficient than PEF. With direct corona they achieve 25 kJ/L per log reduction for both Gram positive and Gram negative bacteria. For air disinfection using their corona pulse source, the measured efficiencies are excellent: 2 J/L per log reduction.

  7. In vitro Splicing of Influenza Viral NS1 mRNA and NS1-β -globin Chimeras: Possible Mechanisms for the Control of Viral mRNA Splicing

    NASA Astrophysics Data System (ADS)

    Plotch, Stephen J.; Krug, Robert M.

    1986-08-01

    In influenza virus-infected cells, the splicing of the viral NS1 mRNA catalyzed by host nuclear enzymes is controlled so that the steady-state amount of the spliced NS2 mRNA is only 5-10% of that of the unspliced NS1 mRNA. Here we examine the splicing of NS1 mRNA in vitro, using nuclear extracts from HeLa cells. We show that in addition to its consensus 5' and 3' splice sites, NS1 mRNA has an intron branch-point adenosine residue that was functional in lariat formation. Nonetheless, this RNA was not detectably spliced in vitro under conditions in which a human β -globin precursor was efficiently spliced. Using chimeric RNA precursors containing both NS1 and β -globin sequences, we show that the NS1 5' splice site was effectively utilized by the β -globin branch-point sequence and 3' splice site to form a spliced RNA, whereas the NS1 3' splice site did not function in detectable splicing in vitro, even in the presence of the β -globin branch-point sequence or in the presence of both the branch-point sequence and 5' exon and splice site from β -globin With the chimeric precursors that were not detectably spliced, as with NS1 mRNA itself, a low level of a lariat structure containing only intron and not 3' exon sequences was formed. The inability of the consensus 3' splice site of NS1 mRNA to function effectively in in vitro splicing suggests that this site is structurally inaccessible to components of the splicing machinery. Based on these results, we propose two mechanisms whereby NS1 mRNA splicing in infected cells is controlled via the accessibility of its 3' splice site.

  8. Antiviral potential of 4-hydroxypanduratin A, secondary metabolite of Fingerroot, Boesenbergia pandurata (Schult.), towards Japanese Encephalitis virus NS2B/NS3 protease.

    PubMed

    Seniya, Chandrabhan; Mishra, Harshal; Yadav, Ajay; Sagar, Nitin; Chaturvedi, Babita; Uchadia, Kuldeep; Wadhwa, Gulshan

    2013-01-01

    4-hydroxypanduratin A is a secondary metabolite of Boesenbergia pandurata Schult. (Fingerroot) plant with various pharmacological activities such as neuroprotective, potent antioxidant, antibacterial and antifungal. Flaviviral NS2B/NS3 protease activity is essential for polyprotein processing and viral replication for Japanese Encephalitis Virus (JEV), a major cause of Acute Encephaltis in Asia. Inhibition of formation of this complex by arresting the binding of NS2B with NS3 would reduce the enzyme's activity to meager proportions and hence would prevent further viral proliferation. The automated 3D structure of NS2B protein of the JEV GP78 was predicted based on the sequence-to-structure-to-function paradigm using I-TASSER and the function of NS2B protein was inferred by matching to other known proteins. The stereochemical quality of predicted structure was checked by PROCHECK. The antiviral activity of 4-hydroxypanduratin A against NS2B protein as a potential drug has been elucidated in this paper. Docking simulation analysis showed 4-hydroxypanduratin A as potential inhibitor of NS2B protein/cofactor which is necessary for NS3 protease activity. 220 derivatives of 4-hydroxypanduratin A were virtually screened with rigid criteria of Lipinski's rule of 5 using Autodock4.2. 4-hydroxypanduratin A was found interacting with target hydrophilic domain in NS2B protein by two Hbonds (Gly80 and Asp81) with active residues, several hydrophobic interactions, Log P value of 5.6, inhibition constant (Ki) of 51.07nM and lowest binding energy of -9.95Kcal/Mol. Hence, 4-hydroxypanduratin A targeted to Site 2 will have sufficient profound effect to inhibit protease activity to abrogate viral replication. It could be a promising potential drug candidate for JEV infections using NS2B Site 2 as a Drug target.

  9. Appearance of chromosomal aberrations in females heterozygous for deletion MS2-10: Maternal effect

    SciTech Connect

    Artemova, E.V.; Chadov, B.F.

    1995-01-01

    The mutagenic effect of the paracentromeric heterochromatin deletion MS2-10 was studied in direct and reciprocal crosses of laboratory and wild-type lines of Drosophila melanogaster. The effect of deletion MS2-10 depended on the opposite chromosome. This was shown for the combination of autosome MS2-10 with autosome 2 from the Berlin wild line, but when MS2-10 was combined with an autosome 2 from lines Canton S and pr pk cn, the effect was absent. When deletion MS2-10 was inherited from the female parent and the opposite chromosome from the male parent, the effect of the deletion was present, but it was absent in males heterozygous for MS2-10, obtained in reciprocal crosses. In maternal effect, this case of mutagenesis is similar to hybrid dysgenesis. However, the pattern of P-M dysgenesis was shown to differ from the type of mutagenesis described in the present work.

  10. Influenza C virus NS1 protein upregulates the splicing of viral mRNAs.

    PubMed

    Muraki, Yasushi; Furukawa, Takatoshi; Kohno, Yoshihiko; Matsuzaki, Yoko; Takashita, Emi; Sugawara, Kanetsu; Hongo, Seiji

    2010-02-01

    Pre-mRNAs of the influenza A virus M and NS genes are poorly spliced in virus-infected cells. By contrast, in influenza C virus-infected cells, the predominant transcript from the M gene is spliced mRNA. The present study was performed to investigate the mechanism by which influenza C virus M gene-specific mRNA (M mRNA) is readily spliced. The ratio of M1 encoded by a spliced M mRNA to CM2 encoded by an unspliced M mRNA in influenza C virus-infected cells was about 10 times larger than that in M gene-transfected cells, suggesting that a viral protein(s) other than M gene translational products facilitates viral mRNA splicing. RNase protection assays showed that the splicing of M mRNA in infected cells was much higher than that in M gene-transfected cells. The unspliced and spliced mRNAs of the influenza C virus NS gene encode two nonstructural (NS) proteins, NS1(C/NS1) and NS2(C/NS2), respectively. The introduction of premature translational termination into the NS gene, which blocked the synthesis of the C/NS1 and C/NS2 proteins, drastically reduced the splicing of NS mRNA, raising the possibility that C/NS1 or C/NS2 enhances viral mRNA splicing. The splicing of influenza C virus M mRNA was increased by coexpression of C/NS1, whereas it was reduced by coexpression of the influenza A virus NS1 protein (A/NS1). The splicing of influenza A virus M mRNA was also increased by coexpression of C/NS1, though it was inhibited by that of A/NS1. These results suggest that influenza C virus NS1, but not A/NS1, can upregulate viral mRNA splicing.

  11. Laser pulse duration dependence of blister formation on back-radiated Ti thin films for BB-LIFT

    NASA Astrophysics Data System (ADS)

    Goodfriend, N. T.; Starinskiy, S. V.; Nerushev, O. A.; Bulgakova, N. M.; Bulgakov, A. V.; Campbell, E. E. B.

    2016-03-01

    The influence of the laser pulse duration on the mechanism of blister formation in the particle transfer technique, blister-based laser-induced forward transfer, was investigated. Pulses from a fs Ti:Sapphire laser (120 fs, 800 nm) and from a ns Nd:YAG laser (7 ns, 532 nm) were used to directly compare blister formation on thin titanium films of ca. 300 nm thickness, deposited on glass. The different blister morphologies were compared and contrasted by using optical microscopy and atomic force microscopy. The results provide evidence for different blister formation mechanisms: for fs pulses the mechanism is predominantly ablation at the metal-glass interface accompanied by confined plasma expansion and deformation of the remaining metal film; for ns pulses it is heating accompanied by thermal expansion of the metal film.

  12. Generation and evolution of mode-locked noise-like square-wave pulses in a large-anomalous-dispersion Er-doped ring fiber laser.

    PubMed

    Liu, Jun; Chen, Yu; Tang, Pinghua; Xu, Changwen; Zhao, Chujun; Zhang, Han; Wen, Shuangchun

    2015-03-01

    In a passively mode-locked Erbium-doped fiber laser with large anomalous-dispersion, we experimentally demonstrate the formation of noise-like square-wave pulse, which shows quite different features from conventional dissipative soliton resonance (DSR). The corresponding temporal and spectral characteristics of a variety of operation states, including Q-switched mode-locking, continuous-wave mode-locking and Raman-induced noise-like pulse near the lasing threshold, are also investigated. Stable noise-like square-wave mode-locked pulses can be obtained at a fundamental repetition frequency of 195 kHz, with pulse packet duration tunable from 15 ns to 306 ns and per-pulse energy up to 200 nJ. By reducing the linear cavity loss, stable higher-order harmonic mode-locking had also been observed, with pulse duration ranging from 37 ns at the 21st order harmonic wave to 320 ns at the fundamental order. After propagating along a piece of long telecom fiber, the generated square-wave pulses do not show any obvious change, indicating that the generated noise-like square-wave pulse can be considered as high-energy pulse packet for some promising applications. These experimental results should shed some light on the further understanding of the mechanism and characteristics of noise-like square-wave pulses. PMID:25836862

  13. Oxacilin-resistant Coagulase-negative staphylococci (CoNS) bacteremia in a general hospital at São Paulo city, Brasil

    PubMed Central

    d’Azevedo, P.A.; Secchi, C.; Antunes, A.L.S.; Sales, T.; Silva, F.M.; Tranchesi, R.; Pignatari, A.C.C.

    2008-01-01

    In the last decades, coagulase-negative staphylococci (CoNS), especially Staphylococcus epidermidis have become an important cause of bloodstream infections. In addition, rates of methicillin-resistance among CoNS have increased substantially, leading to the use of glicopeptides for therapy. The objective of this study was to evaluate eleven consecutives clinically relevant cases of oxacillin-resistant CoNS bacteremia in a general hospital localized in São Paulo city, Brazil. Five different species were identified by different phenotypic methods, including S. epidermidis (5), S. haemolyticus (3), S. hominis (1), S. warneri (1) and S. cohnii subsp urealyticus (1). A variety of Pulsed Field Gel Electrophoresis profiles was observed by macrorestriction DNA analysis in S. epidermidis isolates, but two of three S. haemolyticus isolates presented the same profile. These data indicated the heterogeneity of the CoNS isolates, suggesting that horizontal dissemination of these microorganisms in the investigated hospital was not frequent. One S. epidermidis and one S. haemolyticus isolates were resistant to teicoplanin and susceptible to vancomycin. The selective pressure due to the use of teicoplanin in this hospital is relevant. PMID:24031279

  14. Folding Proteins at 500 ns/hour with Work Queue

    PubMed Central

    Abdul-Wahid, Badi’; Yu, Li; Rajan, Dinesh; Feng, Haoyun; Darve, Eric; Thain, Douglas; Izaguirre, Jesús A.

    2014-01-01

    Molecular modeling is a field that traditionally has large computational costs. Until recently, most simulation techniques relied on long trajectories, which inherently have poor scalability. A new class of methods is proposed that requires only a large number of short calculations, and for which minimal communication between computer nodes is required. We considered one of the more accurate variants called Accelerated Weighted Ensemble Dynamics (AWE) and for which distributed computing can be made efficient. We implemented AWE using the Work Queue framework for task management and applied it to an all atom protein model (Fip35 WW domain). We can run with excellent scalability by simultaneously utilizing heterogeneous resources from multiple computing platforms such as clouds (Amazon EC2, Microsoft Azure), dedicated clusters, grids, on multiple architectures (CPU/GPU, 32/64bit), and in a dynamic environment in which processes are regularly added or removed from the pool. This has allowed us to achieve an aggregate sampling rate of over 500 ns/hour. As a comparison, a single process typically achieves 0.1 ns/hour. PMID:25540799

  15. X-ray structures of NS1 effector domain mutants.

    PubMed

    Xia, Shuangluo; Robertus, Jon D

    2010-02-15

    The influenza A virus nonstructural protein NS1 is a multifunctional dimeric protein that acts as a potent inhibitor of the host cellular antiviral state. The C-terminal effector domain of NS1 binds host proteins, including CPSF30, and is a target for the development of new antiviral drugs. Here we present crystallographic structures of two mutant effector domains, W187Y and W187A, of influenza A/Udorn/72 virus. Unlike wild-type, the mutants behave exclusively as monomers in solution based on gel filtration data and light scattering. The W187Y mutant is able to bind CPSF30 with a binding affinity close to the wild-type protein; that is, it retains a receptor site for aromatic ligands nearly identical to the wild-type. Therefore, this monomeric mutant protein could serve as a drug target for a high throughput inhibitor screening assays, since its binding pocket is unoccupied in solution and potentially more accessible to small molecule ligands.

  16. Dengue virus RNA polymerase NS5: a potential therapeutic target?

    PubMed

    Rawlinson, Stephen M; Pryor, Melinda J; Wright, Peter J; Jans, David A

    2006-12-01

    Dengue fever (DF)/dengue haemorrhagic fever (DHF) is the most common arthropod-borne viral infection, where it is now estimated that 2.5-3 billion people world-wide are at risk of infection. Currently there is no available treatment, in the form of vaccine or drug, making eradication of the mosquito vector the only viable control measure, which has proved costly and of limited success. There are a number of different vaccines undergoing testing, but whilst a dengue vaccine is clearly desirable, there are several issues which make live-attenuated vaccines problematic. These include the phenomenon of antibody-dependent enhancement (ADE) and the possibility of recombination of attenuated vaccine strains with wild-type flavivirus members reverting vaccines to a virulent form. Until we gain a better understanding of these issues and their associated risks, the safety of any live dengue vaccine cannot be assured. It therefore may be safer and more feasible for therapeutic-based approaches to be developed as an alternative to live vaccines. As our understanding of dengue molecular biology expands, new potential targets for drugs are emerging. One of the most promising is the dengue non-structural protein 5 (NS5), the largest and most highly conserved of the dengue proteins. This review examines the unique properties of NS5, including its functions, interactions, subcellular localisation and regulation, and looks at ways in which some of these may be exploited in our quest for effective drugs.

  17. The 2NS Translocation from Aegilops ventricosa Confers Resistance to the Triticum Pathotype of Magnaporthe oryzae

    PubMed Central

    Cruz, C.D.; Peterson, G.L.; Bockus, W.W.; Kankanala, P.; Dubcovsky, J.; Jordan, K.W.; Akhunov, E.; Chumley, F.; Baldelomar, F.D.; Valent, B.

    2016-01-01

    Wheat blast is a serious disease caused by the fungus Magnaporthe oryzae (Triticum pathotype) (MoT). The objective of this study was to determine the effect of the 2NS translocation from Aegilops ventricosa (Zhuk.) Chennav on wheat head and leaf blast resistance. Disease phenotyping experiments were conducted in growth chamber, greenhouse, and field environments. Among 418 cultivars of wheat (Triticum aestivum L.), those with 2NS had 50.4 to 72.3% less head blast than those without 2NS when inoculated with an older MoT isolate under growth chamber conditions. When inoculated with recently collected isolates, cultivars with 2NS had 64.0 to 80.5% less head blast. Under greenhouse conditions when lines were inoculated with an older MoT isolate, those with 2NS had a significant head blast reduction. With newer isolates, not all lines with 2NS showed a significant reduction in head blast, suggesting that the genetic background and/or environment may influence the expression of any resistance conferred by 2NS. However, when near-isogenic lines (NILs) with and without 2NS were planted in the field, there was strong evidence that 2NS conferred resistance to head blast. Results from foliar inoculations suggest that the resistance to head infection that is imparted by the 2NS translocation does not confer resistance to foliar disease. In conclusion, the 2NS translocation was associated with significant reductions in head blast in both spring and winter wheat. PMID:27814405

  18. Nanosecond pulsed electric fields have differential effects on cells in the S-phase.

    PubMed

    Hall, Emily H; Schoenbach, Karl H; Beebe, Stephen J

    2007-03-01

    Nanosecond pulsed electric fields (nsPEFs) are a type of nonthermal, nonionizing radiation that exhibit intense electric fields with high power, but low energy. NsPEFs extend conventional electroporation (EP) to affect intracellular structures and functions and depending on the intensity, can induce lethal and nonlethal cell signaling. In this study, HCT116 human colon carcinoma cells were synchronized to the S-phase or remained unsynchronized, exposed to electric fields of 60 kV/cm with either 60-ns or 300-ns durations, and analyzed for apoptosis and proliferative markers. Several nsPEF structural and functional targets were identified. Unlike unsynchronized cells, S-phase cells under limiting conditions exhibited greater membrane integrity and caspase activation and maintained cytoskeletal structure. Regardless of synchronization, cells exposed to nsPEFs under these conditions primarily survived, but exhibited some turnover and delayed proliferation in cell populations, as well as reversible increases in phosphatidylserine externalization, membrane integrity, and nuclei size. These results show that nsPEFs can act as a nonligand agonist to modulate plasma membrane (PM) and intracellular structures and functions, as well as differentially affect cells in the S-phase, but without effect on cell survival. Furthermore, nsPEF effects on the nucleus and cytoskeleton may provide synergistic therapeutic actions with other agents, such as ionizing radiation or chemotherapeutics that affect these same structures.

  19. Enhancement of Virus Replication in An Influenza A Virus NS1-Expresssing 293 Cell Line.

    PubMed

    Zhu, Wu Yang; Tao, Xiao Yan; Lyu, Xin Jun; Yu, Peng Cheng; Lu, Zhuo Zhuang

    2016-03-01

    The nonstructural protein 1 (NS1) of influenza A virus, which is absent from the viral particle, but highly expressed in infected cells, strongly antagonizes the interferon (IFN)-mediated antiviral response. We engineered an NS1-expressing 293 (293-NS1) cell line with no response to IFN stimulation. Compared with the parental 293 cells, the IFN-nonresponsive 293-NS1 cells improved the growth capacity of various viruses, but the introduction of NS1 barely enhanced the propagation of Tahyna virus, a negative-strand RNA virus. In particular, fastidious enteric adenovirus that replicates poorly in 293 cells may grow more efficiently in 293-NS1 cells; thus, IFN-nonresponsive 293-NS1 cells might be of great value in diagnostic laboratories for the cultivation and isolation of human enteric adenoviruses.

  20. Enhancement of Virus Replication in An Influenza A Virus NS1-Expresssing 293 Cell Line.

    PubMed

    Zhu, Wu Yang; Tao, Xiao Yan; Lyu, Xin Jun; Yu, Peng Cheng; Lu, Zhuo Zhuang

    2016-03-01

    The nonstructural protein 1 (NS1) of influenza A virus, which is absent from the viral particle, but highly expressed in infected cells, strongly antagonizes the interferon (IFN)-mediated antiviral response. We engineered an NS1-expressing 293 (293-NS1) cell line with no response to IFN stimulation. Compared with the parental 293 cells, the IFN-nonresponsive 293-NS1 cells improved the growth capacity of various viruses, but the introduction of NS1 barely enhanced the propagation of Tahyna virus, a negative-strand RNA virus. In particular, fastidious enteric adenovirus that replicates poorly in 293 cells may grow more efficiently in 293-NS1 cells; thus, IFN-nonresponsive 293-NS1 cells might be of great value in diagnostic laboratories for the cultivation and isolation of human enteric adenoviruses. PMID:27109134

  1. Design of compact Marx module with square pulse output

    NASA Astrophysics Data System (ADS)

    Liu, Hongwei; Xie, Weiping; Yuan, Jianqiang; Wang, Lingyun; Ma, Xun; Jiang, Ping

    2016-07-01

    Compact pulsed power system based on compact Marx generator is widely used in terms of drive resistance and capacitive loads. This system usually adopts high performance components such as high energy density capacitors, compact switches, and integrated structure. Traditional compact Marx generator can only output double-exponential pulse profile. In this paper a compact, low-impedance Marx module which can output rectangular pulse profile is design and tested. This module has multiple circuits of different discharge frequencies in parallel to generate quasi-rectangular pulse. Discharge characteristic of an ideal module with infinite branches is calculated theoretically. A module with two branches has been designed and tested. Test results show that the impedance of the module is 1.2 Ω. When charging voltage is 100.6 kV and load resistance is 1 Ω, the peak output pulse is 45.2 kV voltage, the peak power is about 2 GW, the pulse width is about 130 ns, and the rise time is about 35 ns. The energy density and power density of the module are 15 kJ/m3 and 140 GW/m3, respectively.

  2. Optimized pulse shapes for a resonator-induced phase gate

    NASA Astrophysics Data System (ADS)

    Cross, Andrew W.; Gambetta, Jay M.

    2015-03-01

    The resonator-induced phase gate is a multiqubit controlled-phase gate for fixed-frequency superconducting qubits. Through off-resonant driving of a bus resonator, statically coupled qubits acquire a state-dependent phase. However, photon loss leads to dephasing during the gate, and any residual entanglement between the resonator and qubits after the gate leads to decoherence. Here we consider how to shape the drive pulse to minimize these unwanted effects. First, we review how the gate's entangling and dephasing rates depend on the system parameters and validate closed-form solutions against direct numerical solution of a master equation. Next, we propose spline pulse shapes that reduce residual qubit-bus entanglement, are robust to imprecise knowledge of the resonator shift, and can be shortened by using higher-degree polynomials. Finally, we present a procedure that optimizes over the subspace of pulses that leave the resonator unpopulated. This finds shaped drive pulses that further reduce the gate duration. Assuming realistic parameters, we exhibit shaped pulses that have the potential to realize ˜212 ns spline pulse gates and ˜120 ns optimized gates with ˜6 ×10-4 average gate infidelity. These examples do not represent fundamental limits of the gate and, in principle, even shorter gates may be achievable.

  3. Simulation of Pulse Shortening in a Relativistic Klystron Oscillator

    NASA Astrophysics Data System (ADS)

    Verboncoeur, J. P.; Cartwright, K. L.

    1996-11-01

    The relativistic klystron is a strong candidate for a high power microwave source for a number of applications; one of the impediments to higher power and longer pulses is shortening of the RF pulse compared to the current pulse. In this work, we simulate a high power, high perveance relativistic klystron oscillator(K. J. Hendricks, P. D. Coleman, R. W. Lemke, M. J. Arman and L. Bowers, Phys. Rev. Lett.) 76, 154 (1996). using a 2d PIC-MCC code(J. P. Verboncoeur, A. B. Langdon and N. T. Gladd, Comp. Phys. Comm.) 87, 199 (1995).. The experimental klystron was operated as an injection-locked oscillator at 1.25-1.35 GHz, with up to 1.2 GW rms output power for a 100 ns pulse. The beam voltage was 500 kV, with current of 10 kA, and a beam pulse length of 300 ns. Simulations indicate formation of a plasma due to ionization of gases from the porous graphite collector reduces the output power, but is insufficient to fully explain the pulse shortening. In addition, mode conversion from the 3 λ / 4 mode to the λ / 4 fundamental cavity mode also occurs. Loss in the walls may attenuate the fundamental mode in the experiment. The effects of charged particle formation in the output gap, due to ionization, field emission and multipactor, are also studied. This work supported in part by AFOSR/MURI grant F49620-95-1-0253.

  4. Design of compact Marx module with square pulse output.

    PubMed

    Liu, Hongwei; Xie, Weiping; Yuan, Jianqiang; Wang, Lingyun; Ma, Xun; Jiang, Ping

    2016-07-01

    Compact pulsed power system based on compact Marx generator is widely used in terms of drive resistance and capacitive loads. This system usually adopts high performance components such as high energy density capacitors, compact switches, and integrated structure. Traditional compact Marx generator can only output double-exponential pulse profile. In this paper a compact, low-impedance Marx module which can output rectangular pulse profile is design and tested. This module has multiple circuits of different discharge frequencies in parallel to generate quasi-rectangular pulse. Discharge characteristic of an ideal module with infinite branches is calculated theoretically. A module with two branches has been designed and tested. Test results show that the impedance of the module is 1.2 Ω. When charging voltage is 100.6 kV and load resistance is 1 Ω, the peak output pulse is 45.2 kV voltage, the peak power is about 2 GW, the pulse width is about 130 ns, and the rise time is about 35 ns. The energy density and power density of the module are 15 kJ/m(3) and 140 GW/m(3), respectively. PMID:27475580

  5. A Single Pulse Sub-Nanosecond Proton RFQ

    SciTech Connect

    Hamm, R W; Pearce-Percy, H; Pearson, D; Rougieri, M; Weir, J; Zografos, A; Guethlein, G; Hawkins, S; Falabella, S; Poole, B; Blackfield, D

    2011-03-29

    A Radio Frequency Quadrupole (RFQ) linac system has been developed to provide a single pulse of 2 MeV protons with a beam pulse width of {approx}300 ps and a charge of 30 pC, either for injection into a pulsed Dielectric Wall Accelerator or for bombardment of a target to produce a fast neutron pulse. The 1.2 m long RFQ structure operates at 425 MHz and bunches and accelerates a single 2.35 ns beam pulse injected into it at 35 keV using a parallel plate deflector placed directly in front of the RFQ entrance. The input acceptance properties of the RFQ allow a simple dc bias voltage on the plates to block acceleration of the unwanted beam, with a short rf voltage pulse applied to null the deflection field for the ions within the 8 mm 'kicker' plate length. The use of the RFQ as the accelerating structure allows one to efficiently produce a large charge in a single sub-ns bunch. In addition, the kicker can also be used without the dc bias voltage to produce a 'notch' in the normal RFQ output beam for synchrotron injection.

  6. Experimental study of the hydrodynamic expansion following a nanosecond repetitively pulsed discharge in air

    NASA Astrophysics Data System (ADS)

    Xu, Da A.; Lacoste, Deanna A.; Rusterholtz, Diane L.; Elias, Paul-Quentin; Stancu, Gabi D.; Laux, Christophe O.

    2011-09-01

    We report on an experimental study of the hydrodynamic expansion following a nanosecond repetitively pulsed (NRP) discharge in atmospheric pressure air preheated up to 1000 K. Single-shot schlieren images starting from 50 ns after the discharge were recorded to show the shock-wave propagation and the expansion of the heated gas channel. The temporal evolution of the gas temperature behind the shock-front is estimated from the measured shock-wave velocity by using the Rankine-Hugoniot relationships. The results show that a gas temperature increase of up to 1100 K can be observed 50 ns after the nanosecond pulse.

  7. A conserved predicted pseudoknot in the NS2A-encoding sequence of West Nile and Japanese encephalitis flaviviruses suggests NS1' may derive from ribosomal frameshifting

    PubMed Central

    Firth, Andrew E; Atkins, John F

    2009-01-01

    Japanese encephalitis, West Nile, Usutu and Murray Valley encephalitis viruses form a tight subgroup within the larger Flavivirus genus. These viruses utilize a single-polyprotein expression strategy, resulting in ~10 mature proteins. Plotting the conservation at synonymous sites along the polyprotein coding sequence reveals strong conservation peaks at the very 5' end of the coding sequence, and also at the 5' end of the sequence encoding the NS2A protein. Such peaks are generally indicative of functionally important non-coding sequence elements. The second peak corresponds to a predicted stable pseudoknot structure whose biological importance is supported by compensatory mutations that preserve the structure. The pseudoknot is preceded by a conserved slippery heptanucleotide (Y CCU UUU), thus forming a classical stimulatory motif for -1 ribosomal frameshifting. We hypothesize, therefore, that the functional importance of the pseudoknot is to stimulate a portion of ribosomes to shift -1 nt into a short (45 codon), conserved, overlapping open reading frame, termed foo. Since cleavage at the NS1-NS2A boundary is known to require synthesis of NS2A in cis, the resulting transframe fusion protein is predicted to be NS1-NS2AN-term-FOO. We hypothesize that this may explain the origin of the previously identified NS1 'extension' protein in JEV-group flaviviruses, known as NS1'. PMID:19196463

  8. Association of hepatitis C virus replication complexes with microtubules and actin filaments is dependent on the interaction of NS3 and NS5A.

    PubMed

    Lai, Chao-Kuen; Jeng, King-Song; Machida, Keigo; Lai, Michael M C

    2008-09-01

    The hepatitis C virus (HCV) RNA replication complex (RC), which is composed of viral nonstructural (NS) proteins and host cellular proteins, replicates the viral RNA genome in association with intracellular membranes. Two viral NS proteins, NS3 and NS5A, are essential elements of the RC. Here, by using immunoprecipitation and fluorescence resonance energy transfer assays, we demonstrated that NS3 and NS5A interact with tubulin and actin. Furthermore, immunofluorescence microscopy and electron microscopy revealed that HCV RCs were aligned along microtubules and actin filaments in both HCV replicon cells and HCV-infected cells. In addition, the movement of RCs was inhibited when microtubules or actin filaments were depolymerized by colchicine and cytochalasin B, respectively. Based on our observations, we propose that microtubules and actin filaments provide the tracks for the movement of HCV RCs to other regions in the cell, and the molecular interactions between RCs and microtubules, or RCs and actin filaments, are mediated by NS3 and NS5A. PMID:18562541

  9. Development of novel antibodies against non-structural proteins nsP1, nsP3 and nsP4 of chikungunya virus: potential use in basic research.

    PubMed

    Kumar, Sameer; Mamidi, Prabhudutta; Kumar, Abhishek; Basantray, Itishree; Bramha, Umarani; Dixit, Anshuman; Maiti, Prasanta Kumar; Singh, Sujay; Suryawanshi, Amol Ratnakar; Chattopadhyay, Subhasis; Chattopadhyay, Soma

    2015-11-01

    Chikungunya virus (CHIKV) has reemerged recently as an important pathogen, causing several large epidemics worldwide. This necessitates the development of better reagents to understand its biology and to establish effective and safe control measures. The present study describes the development and characterization of polyclonal antibodies (pAbs) against synthetic peptides of CHIKV non-structural proteins (nsPs; nsP1, nsP3 and nsP4). The reactivity of these pAbs was demonstrated by ELISA and Western blot. Additionally, in vitro infection studies in a mammalian system confirmed that these pAbs are highly sensitive and specific for CHIKV nsPs, as these proteins were detected very early during viral replication. Homology analysis of the selected epitope sequences revealed that they are conserved among all of the CHIKV strains of different genotypes, while comparison with other alphavirus sequences showed that none of them are 100% identical to the epitope sequences (except Onyong-nyong and Igbo Ora viruses, which show 100% identity to the nsP4 epitope). Interestingly, two different forms of CHIKV nsP1 and three different forms of nsP3 were detected in Western blot analysis during infection; however, further experimental investigations are required to confirm their identity. Also, the use of these antibodies demonstrated faster and enhanced expression profiles of all CHIKV nsPs in 2006 Indian outbreak strains when compared to the CHIKV prototype strain, suggesting the epidemic potential of the 2006 isolate. Accordingly, it can be suggested that the pAbs reported in this study can be used as sensitive and specific tools for experimental investigations of CHIKV replication and infection. PMID:26280524

  10. Development of novel antibodies against non-structural proteins nsP1, nsP3 and nsP4 of chikungunya virus: potential use in basic research.

    PubMed

    Kumar, Sameer; Mamidi, Prabhudutta; Kumar, Abhishek; Basantray, Itishree; Bramha, Umarani; Dixit, Anshuman; Maiti, Prasanta Kumar; Singh, Sujay; Suryawanshi, Amol Ratnakar; Chattopadhyay, Subhasis; Chattopadhyay, Soma

    2015-11-01

    Chikungunya virus (CHIKV) has reemerged recently as an important pathogen, causing several large epidemics worldwide. This necessitates the development of better reagents to understand its biology and to establish effective and safe control measures. The present study describes the development and characterization of polyclonal antibodies (pAbs) against synthetic peptides of CHIKV non-structural proteins (nsPs; nsP1, nsP3 and nsP4). The reactivity of these pAbs was demonstrated by ELISA and Western blot. Additionally, in vitro infection studies in a mammalian system confirmed that these pAbs are highly sensitive and specific for CHIKV nsPs, as these proteins were detected very early during viral replication. Homology analysis of the selected epitope sequences revealed that they are conserved among all of the CHIKV strains of different genotypes, while comparison with other alphavirus sequences showed that none of them are 100% identical to the epitope sequences (except Onyong-nyong and Igbo Ora viruses, which show 100% identity to the nsP4 epitope). Interestingly, two different forms of CHIKV nsP1 and three different forms of nsP3 were detected in Western blot analysis during infection; however, further experimental investigations are required to confirm their identity. Also, the use of these antibodies demonstrated faster and enhanced expression profiles of all CHIKV nsPs in 2006 Indian outbreak strains when compared to the CHIKV prototype strain, suggesting the epidemic potential of the 2006 isolate. Accordingly, it can be suggested that the pAbs reported in this study can be used as sensitive and specific tools for experimental investigations of CHIKV replication and infection.

  11. REVIEWS OF TOPICAL PROBLEMS: Laser excitation of ultrashort acoustic pulses: New possibilities in solid-state spectroscopy, diagnostics of fast processes, and nonlinear acoustics

    NASA Astrophysics Data System (ADS)

    Akhmanov, S. A.; Gusev, V. É.

    1992-03-01

    The experimental results in the field of laser generation of acoustic pulses of duration less than 1 ns are reviewed. The various physical mechanisms of optoacoustic conversion are analyzed theoretically. Possibilities are shown for shortening the duration of optoacoustic pulses by increasing the intensity of the laser exposure. The prospects of initiating ultrashort, strong shock pulses with high-power femtosecond light pulses, are discussed.

  12. Glass drilling by longitudinally excited CO2 laser with short laser pulse

    NASA Astrophysics Data System (ADS)

    Uno, Kazuyuki; Yamamoto, Takuya; Akitsu, Tetsuya; Jitsuno, Takahisa

    2015-03-01

    We developed a longitudinally excited CO2 laser that produces a short laser pulse. The laser was very simple and consisted of a 45-cm-long alumina ceramic pipe with an inner diameter of 9 mm, a pulse power supply, a step-up transformer, a storage capacitance, and a spark-gap switch. The laser pulse had a spike pulse and a pulse tail. The energy of the pulse tail was controlled by adjusting medium gas. Using three types of CO2 laser pulse with the same spike-pulse energy and the different pulse-tail energy, the characteristics of the hole drilling of synthetic silica glass was investigated. Higher pulse-tail energy gave deeper ablation depth. In the short laser pulse with the spike-pulse energy of 1.2 mJ, the spike pulse width of 162 ns, the pulse-tail energy of 24.6 mJ, and the pulse-tail length of 29.6 μs, 1000 shots irradiation produced the ablation depth of 988 μm. In the hole drilling of synthetic silica glass by the CO2 laser, a crack-free process was realized.

  13. Suitable technological conditions for enzymatic hydrolysis of waste paper by Novozymes® enzymes NS50013 and NS50010.

    PubMed

    Brummer, Vladimir; Skryja, Pavel; Jurena, Tomas; Hlavacek, Viliam; Stehlik, Petr

    2014-10-01

    Waste paper belongs to a group of quantitatively the most produced waste types. Enzymatic hydrolysis is becoming a suitable way to treat this type of waste and at the same time, to produce a valuable liquid biofuel, because reducing sugars solutions that are formed during the process of saccharification can be a precursor for following or simultaneous fermentation. If it will be possible to make the enzymatic hydrolysis of the waste paper economically viable, it could serve as one of the new ways to lower the dependence of the transport sector on oil in the future. Only several studies comparing the enzymatic hydrolysis of different waste papers were performed in the past; they are summarized in this manuscript. In our experimental trials, suitable technological conditions for waste paper enzymatic hydrolysis using enzymes from Novozymes® biomass kit: enzymes NS50013 and NS50010 were investigated. The following enzymatic hydrolysis parameters in laboratory scale trials were verified on high cellulose content substrates-filter paper and cellulose pulp: type of buffer, pH, temperature, concentration of the substrate, loading of the enzyme and rate of stirring.

  14. In Silico Screening, Alanine Mutation, and DFT Approaches for Identification of NS2B/NS3 Protease Inhibitors

    PubMed Central

    Balajee, R.; Srinivasadesikan, V.; Sakthivadivel, M.; Gunasekaran, P.

    2016-01-01

    To identify the ligand that binds to a target protein with high affinity is a nontrivial task in computer-assisted approaches. Antiviral drugs have been identified for NS2B/NS3 protease enzyme on the mechanism to cleave the viral protein using the computational tools. The consequence of the molecular docking, free energy calculations, and simulation protocols explores the better ligand. It provides in-depth structural insights with the catalytic triad of His51, Asp75, Ser135, and Gly133. The MD simulation was employed here to predict the stability of the complex. The alanine mutation has been performed and its stability was monitored by using the molecular dynamics simulation. The minimal RMSD value suggests that the derived complexes are close to equilibrium. The DFT outcome reveals that the HOMO-LUMO gap of Ligand19 is 2.86 kcal/mol. Among the considered ligands, Ligand19 shows the lowest gap and it is suggested that the HOMO of Ligand19 may transfer the electrons to the LUMO in the active regions. The calculated binding energy of Ligand19 using the DFT method is in good agreement with the docking studies. The pharmacological activity of ligand was performed and satisfies Lipinski rule of 5. Moreover, the computational results are compared with the available IC50 values of experimental results. PMID:27057355

  15. Digital pulse processing for NaI(Tl) detectors

    NASA Astrophysics Data System (ADS)

    Di Fulvio, A.; Shin, T. H.; Hamel, M. C.; Pozzi, S. A.

    2016-01-01

    We apply two different post-processing techniques to digital pulses induced by photons in a NaI(Tl) detector and compare the obtained energy resolution to the standard analog approach. Our digital acquisition approach is performed using a single-stage acquisition with a fast digitizer. Both the post-processing techniques we propose rely on signal integration. In the first, the pulse integral is calculated by directly numerically integrating the pulse digital samples, while in the second the pulse integral is estimated by a model-based fitting of the pulse. Our study used a 7.62 cm×7.62 cm cylindrical NaI(Tl) detector that gave a 7.60% energy resolution (at 662 keV), using the standard analog acquisition approach, based on a pulse shaping amplifier. The new direct numerical integration yielded a 6.52% energy resolution. The fitting approach yielded a 6.55% energy resolution, and, although computationally heavier than numerical integration, is preferable when only the early samples of the pulse are available. We also evaluated the timing performance of a fast-slow detection system, encompassing an EJ-309 and a NaI(Tl) scintillator. We use two techniques to determine the pulse start time: constant fraction discrimination (CFD) and adaptive noise threshold timing (ANT), for both the analog and digital acquisition approach. With the analog acquisition approach, we found a system time resolution of 5.8 ns and 7.3 ns, using the constant fraction discrimination and adaptive noise threshold timing, respectively. With the digital acquisition approach, a time resolution of 1.2 ns was achieved using the ANT method and 3.3 ns using CFD at 50% of the maximum, to select the pulse start time. The proposed direct digital readout and post-processing techniques can improve the application of NaI(Tl) detectors, traditionally considered 'slow', for fast counting and correlation measurements, while maintaining a good measurement of the energy resolution.

  16. Ablation of Myocardial Tissue With Nanosecond Pulsed Electric Fields

    PubMed Central

    Xie, Fei; Varghese, Frency; Pakhomov, Andrei G.; Semenov, Iurii; Xiao, Shu; Philpott, Jonathan; Zemlin, Christian

    2015-01-01

    Background Ablation of cardiac tissue is an essential tool for the treatment of arrhythmias, particularly of atrial fibrillation, atrial flutter, and ventricular tachycardia. Current ablation technologies suffer from substantial recurrence rates, thermal side effects, and long procedure times. We demonstrate that ablation with nanosecond pulsed electric fields (nsPEFs) can potentially overcome these limitations. Methods We used optical mapping to monitor electrical activity in Langendorff-perfused New Zealand rabbit hearts (n = 12). We repeatedly inserted two shock electrodes, spaced 2–4 mm apart, into the ventricles (through the entire wall) and applied nanosecond pulsed electric fields (nsPEF) (5–20 kV/cm, 350 ns duration, at varying pulse numbers and frequencies) to create linear lesions of 12–18 mm length. Hearts were stained either with tetrazolium chloride (TTC) or propidium iodide (PI) to determine the extent of ablation. Some stained lesions were sectioned to obtain the three-dimensional geometry of the ablated volume. Results In all animals (12/12), we were able to create nonconducting lesions with less than 2 seconds of nsPEF application per site and minimal heating (< 0.2°C) of the tissue. The geometry of the ablated volume was smoother and more uniform throughout the wall than typical for RF ablation. The width of the lesions could be controlled up to 6 mm via the electrode spacing and the shock parameters. Conclusions Ablation with nsPEFs is a promising alternative to radiofrequency (RF) ablation of AF. It may dramatically reduce procedure times and produce more consistent lesion thickness than RF ablation. PMID:26658139

  17. Pulsed UV and VUV excilamps

    NASA Astrophysics Data System (ADS)

    Tarasenko, Victor F.; Erofeev, Mikhail V.; Kostyrja, Igor D.; Lomaev, Mikhail I.; Rybka, Dmitri V.

    2008-05-01

    Emission characteristics of a nanosecond discharge in nitrogen, inert gases and its halogenides without preionization of the gap from an auxiliary source have been investigated. A volume discharge, initiated by an avalanche electron beam (VDIAEB) was realized at pressures up to 12 atm. It has been shown that at VDIAEB excitation no less than 90% energy in the 120-850 nm range is emitted by Xe, Kr, Ar dimers. Xenon spectra in the range 120-850 nm and time-amplitude characteristics have been recorded and analyzed for various excitation regimes. In xenon at pressure of 1.2 atm, the energy of spontaneous radiation in the full solid angle was ~ 45 mJ/cm3, and the FWHM of a radiation pulse was ~ 110 ns. The spontaneous radiation power rise in xenon was observed at pressures up to 12 atm. Pulsed power densities of radiation of inert gases halogenides excited by VDIAEB was ~ 4.5 kW/cm2 at efficiency up to 5.5 %.

  18. On the chemistry of CS and NS in cometary comae

    NASA Astrophysics Data System (ADS)

    Canaves, M.; de Almeida, A.; Boice, D.; Sanzovo, G.

    The most fundamental scientific reason for studying comets is to retrieve information on their origin, relationship to interstellar and interplanetary material and implication for the formation of the Solar System or Cosmogony. The determination of the basic parameters of the nucleus and its activity and comp osition is desirable in order to establish a consistent database for comparative studies of comets and, as such, is vital for the safety and success of space missions. The objective of the present work is to contribute to the establishment of a unique description of the physical-chemical nature of the nucleus. We study carbon monosulfide (CS) - which is the only sulfur compound that persistently appears in cometary ultraviolet spectra and, therefore, seems to play a key role in sulfur photochemistry in cometary comae - and nitrogen monosulfide (NS) - the first cometary molecular species to contain both nitrogen and sulfur atoms which was recently observed by Irvine et al. (2000) in comet Hale -Bopp. The determination of the abundance of each such species helps to constrain the chemistry and physics of comets and hence their place and mode of origin of the nucleus. With this purpose in mind we have developed a multifluid chemical model of cometary comae (Boice 1990) with gas-phase chemical kinetics and gas dynamics to predict molecular abundance variations in a sensitive manner with cometocentric distance. We apply the model to the recent bright comets Hyakutake and Hale-Bopp at a heliocentric distance of 1 AU to study the abundances of CS and NS in their comae using a detailed photo and chemical reaction network with more than 100 species and over 1000 reactions. We conclude that the CS abundance in comets does not seem to vary much with the cometocentric distance. In particular, if NS is the daughter of an unknown long-lived parent molecular species, its production rate and abundance should be much larger than the obtained values. These results should be

  19. 41 CFR 60-2.10 - General purpose and contents of affirmative action programs.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 41 Public Contracts and Property Management 1 2014-07-01 2014-07-01 false General purpose and contents of affirmative action programs. 60-2.10 Section 60-2.10 Public Contracts and Property Management...) An affirmative action program is a management tool designed to ensure equal employment opportunity....

  20. 41 CFR 60-2.10 - General purpose and contents of affirmative action programs.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...) Identification of problem areas; (iii) Action-oriented programs; and (iv) Periodic internal audits. (c... programs also include internal auditing and reporting systems as a means of measuring the contractor's... contents of affirmative action programs. 60-2.10 Section 60-2.10 Public Contracts and Property...

  1. Investigation of a direct effect of nanosecond pulse electric fields on mitochondria

    NASA Astrophysics Data System (ADS)

    Estlack, Larry E.; Roth, Caleb C.; Cerna, Cesario Z.; Wilmink, Gerald J.; Ibey, Bennett L.

    2014-03-01

    The unique cellular response to nanosecond pulsed electric field (nsPEF) exposure, as compared to longer pulse exposure, has been theorized to be due to permeabilization of intracellular organelles including the mitochondria. In this investigation, we utilized a high-throughput oxygen and pH sensing system (Seahorse® XF24 extracellular flux analyzer) to assess the mitochondrial activity of Jurkat and U937 cells after nsPEF. The XF Analyzer uses a transient micro-chamber of only a few μL in specialized cell culture micro-plates to enable oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) to be monitored in real-time. We found that for nsPEF exposures of 10 pulses at 10-ns pulse width and at 50 kV/cm e-field, we were able to cause an increase in OCR in both U937 and Jurkat cells. We also found that high pulse numbers (>100) caused a significant decrease in OCR. Higher amplitude 150 kV/cm exposures had no effect on U937 cells and yet they had a deleterious effect on Jurkat cells, matching previously published 24 hour survival data. These results suggest that the exposures were modulating metabolic activity in cells possibly due to direct effects on the mitochondria themselves. To validate this hypothesis, we isolated mitochondria from U937 cells and exposed them similarly and found no significant change in metabolic activity for any pulse number. In a final experiment, we removed calcium from the buffer solution that the cells were exposed in and found that no significant enhancement in metabolic activity was observed. These results suggest that direct permeabilization of the mitochondria is unlikely a primary effect of nsPEF exposure and calcium-mediated intracellular pathway activation is likely responsible for observed pulse-induced mitochondrial effects.

  2. The Influence of Electrode Surface Mercury Film Deformation on the Breakdown Voltage of a Sub-Nanosecond Pulse Discharge Tube

    NASA Astrophysics Data System (ADS)

    Weng, Ming; Xu, Weijun; Wang, Rui

    2012-11-01

    A sub-nanosecond pulse discharge tube is a gas discharge tube which can generate a rapid high-voltage pulse of kilo-volts in amplitude and sub-nanoseconds in width. In this paper, the sub-nanosecond pulse discharge tube and its working principles are described. Because of the phenomenon that the deformation process of the mercury film on the electrode surface lags behind the charging process, the mercury film deformation process affects the dynamic breakdown voltage of the tube directly. The deformation of the mercury film is observed microscopically, and the dynamic breakdown voltage of the tube is measured using an oscillograph. The results show that all the parameters in the charging process, such as charging resistance, charging capacitance and DC power supply, affect the dynamic breakdown voltage of the tube. Based on these studies, the output pulse amplitude can be controlled continuously and individually by adjusting the power supply voltage. When the DC power supply is adjusted from 7 kV to 10 kV, the dynamic breakdown voltage ranges from 6.5 kV to 10 kV. According to our research, a kind of sub-nanosecond pulse generator is made, with a pulse width ranging from 0.5 ns to 2.5 ns, a rise time from 0.32 ns to 0.58 ns, and a pulse amplitude that is adjustable from 1.5 kV to 5 kV.

  3. Real-time imaging of membrane potentials during exposure to nanosecond pulsed electric fields

    NASA Astrophysics Data System (ADS)

    Kolb, Juergen F.; Frey, Wolfgang; White, Jody A.; Price, R. O.; Blackmore, Peter F.; Beebe, Stephen J.; Joshi, Ravindra P.; Schoenbach, Karl H.

    2005-04-01

    The charging of mammalian cell plasma membranes in response to ultrashort pulsed electric fields of 60 ns and field strengths up to 100 kV/cm was investigated. Membranes of Jurkat cells were stained with a potential-sensitive dye, Annine-6 and placed in a microreactor mounted on an inverted fluorescence microscope. Images of changes in the fluorescence intensity during the exposure were recorded with a high-sensitivity CCD-camera. A temporal resolution of 5 ns was achieved by illuminating the cells with a 5 ns laser pulse from a dye-laser. The laser pulse was synchronized with the high voltage pulse to record images at specific times before, during and after exposure to the electric field. When exposing Jurkat cells to a 60 ns, 100 kV/cm pulse, each hemisphere of the plasma membrane (as oriented with respect to the electrodes) responded uniquely to the applied field. From these observations it is possible to draw conclusions on the charging time of the membrane, maximum transmembrane voltages and the onset of poration.

  4. Characterization of the Determinants of NS2-3-Independent Virion Morphogenesis of Pestiviruses

    PubMed Central

    Klemens, O.; Dubrau, D.

    2015-01-01

    ABSTRACT A peculiarity of the Flaviviridae is the critical function of nonstructural (NS) proteins for virus particle formation. For pestiviruses, like bovine viral diarrhea virus (BVDV), uncleaved NS2-3 represents an essential factor for virion morphogenesis, while NS3 is an essential component of the viral replicase. Accordingly, in natural pestivirus isolates, processing at the NS2-3 cleavage site is not complete, to allow for virion morphogenesis. Virion morphogenesis of the related hepatitis C virus (HCV) shows a major deviation from that of pestiviruses: while RNA replication also requires free NS3, virion formation does not depend on uncleaved NS2-NS3. Recently, we described a BVDV-1 chimera based on strain NCP7 encompassing the NS2-4B*-coding region of strain Osloss (E. Lattwein, O. Klemens, S. Schwindt, P. Becher, and N. Tautz, J Virol 86:427–437, 2012, doi:10.1128/JVI.06133-11). This chimera allowed for the production of infectious virus particles in the absence of uncleaved NS2-3. The Osloss sequence deviates in the NS2-4B* part from NCP7 in 48 amino acids and also has a ubiquitin insertion between NS2 and NS3. The present study demonstrates that in the NCP7 backbone, only two amino acid exchanges in NS2 (E1576V) and NS3 (V1721A) are sufficient and necessary to allow for efficient NS2-3-independent virion morphogenesis. The adaptation of a bicistronic virus encompassing an internal ribosomal entry site element between the NS2 and NS3 coding sequences to efficient virion morphogenesis led to the identification of additional amino acids in E2, NS2, and NS5B that are critically involved in this process. The surprisingly small requirements for approximating the packaging schemes of pestiviruses and HCV with respect to the NS2-3 region is in favor of a common mechanism in an ancestral virus. IMPORTANCE For positive-strand RNA viruses, the processing products of the viral polyprotein serve in RNA replication as well as virion morphogenesis. For bovine viral

  5. A compact repetitive high-voltage nanosecond pulse generator for the application of gas discharge.

    PubMed

    Pang, Lei; Zhang, Qiaogen; Ren, Baozhong; He, Kun

    2011-04-01

    Uniform and stable discharge plasma requires very short duration pulses with fast rise times. A repetitive high-voltage nanosecond pulse generator for the application of gas discharge is presented in this paper. It is constructed with all solid-state components. Two-stage magnetic compression is used to generate a short duration pulse. Unlike in some reported studies, common commercial fast recovery diodes instead of a semiconductor opening switch (SOS) are used in our experiment that plays the role of SOS. The SOS-like effects of four different kinds of diodes are studied experimentally to optimize the output performance. It is found that the output pulse voltage is higher with a shorter reverse recovery time, and the rise time of pulse becomes faster when the falling time of reverse recovery current is shorter. The SOS-like effect of the diodes can be adjusted by changing the external circuit parameters. Through optimization the pulse generator can provide a pulsed voltage of 40 kV with a 40 ns duration, 10 ns rise time, and pulse repetition frequency of up to 5 kHz. Diffuse plasma can be formed in air at standard atmospheric pressure using the developed pulse generator. With a light weight and small packaging the pulse generator is suitable for gas discharge application.

  6. Influence of laser pulse duration on extreme ultraviolet and ion emission features from tin plasmas

    SciTech Connect

    Roy, A. E-mail: aroy@barc.gov.in; Harilal, S. S.; Polek, M. P.; Hassan, S. M.; Hassanein, A.; Endo, A.

    2014-03-15

    We investigated the role of laser pulse duration and intensity on extreme ultraviolet (EUV) generation and ion emission from a laser produced Sn plasma. For producing plasmas, planar slabs of pure Sn were irradiated with 1064 nm Nd:YAG laser pulses with varying pulse duration (5–20 ns) and intensity. Experimental results performed at CMUXE indicate that the conversion efficiency (CE) of the EUV radiation strongly depend on laser pulse width and intensity, with a maximum CE of ∼2.0% measured for the shortest laser pulse width used (5 ns). Faraday Cup ion analysis of Sn plasma showed that the ion flux kinetic profiles are shifted to higher energy side with the reduction in laser pulse duration and narrower ion kinetic profiles are obtained for the longest pulse width used. However, our initial results showed that at a constant laser energy, the ion flux is more or less constant regardless of the excitation laser pulse width. The enhanced EUV emission obtained at shortest laser pulse duration studied is related to efficient laser-plasma reheating supported by presence of higher energy ions at these pulse durations.

  7. Diversified pulse generation from frequency shifted feedback Tm-doped fibre lasers

    NASA Astrophysics Data System (ADS)

    Chen, He; Chen, Sheng-Ping; Jiang, Zong-Fu; Hou, Jing

    2016-05-01

    Pulsed fibre lasers operating in the eye-safe 2 μm spectral region have numerous potential applications in areas such as remote sensing, medicine, mid-infrared frequency conversion, and free-space communication. Here, for the first time, we demonstrate versatile 2 μm ps-ns pulses generation from Tm-based fibre lasers based on frequency shifted feedback and provide a comprehensive report of their special behaviors. The lasers are featured with elegant construction and the unparalleled capacity of generating versatile pulses. The self-starting mode-locking is initiated by an intra-cavity acousto-optical frequency shifter. Diversified mode-locked pulse dynamics were observed by altering the pump power, intra-cavity polarization state and cavity structure, including as short as 8 ps single pulse sequence, pulse bundle state and up to 12 nJ, 3 ns nanosecond rectangular pulse. A reflective nonlinear optical loop mirror was introduced to successfully shorten the pulses from 24 ps to 8 ps. Beside the mode-locking operation, flexible Q-switching and Q-switched mode-locking operation can also be readily achieved in the same cavity. Up to 78 μJ high energy nanosecond pulse can be generated in this regime. Several intriguing pulse dynamics are characterized and discussed.

  8. Diversified pulse generation from frequency shifted feedback Tm-doped fibre lasers

    PubMed Central

    Chen, He; Chen, Sheng-Ping; Jiang, Zong-Fu; Hou, Jing

    2016-01-01

    Pulsed fibre lasers operating in the eye-safe 2 μm spectral region have numerous potential applications in areas such as remote sensing, medicine, mid-infrared frequency conversion, and free-space communication. Here, for the first time, we demonstrate versatile 2 μm ps-ns pulses generation from Tm-based fibre lasers based on frequency shifted feedback and provide a comprehensive report of their special behaviors. The lasers are featured with elegant construction and the unparalleled capacity of generating versatile pulses. The self-starting mode-locking is initiated by an intra-cavity acousto-optical frequency shifter. Diversified mode-locked pulse dynamics were observed by altering the pump power, intra-cavity polarization state and cavity structure, including as short as 8 ps single pulse sequence, pulse bundle state and up to 12 nJ, 3 ns nanosecond rectangular pulse. A reflective nonlinear optical loop mirror was introduced to successfully shorten the pulses from 24 ps to 8 ps. Beside the mode-locking operation, flexible Q-switching and Q-switched mode-locking operation can also be readily achieved in the same cavity. Up to 78 μJ high energy nanosecond pulse can be generated in this regime. Several intriguing pulse dynamics are characterized and discussed. PMID:27193213

  9. Diversified pulse generation from frequency shifted feedback Tm-doped fibre lasers.

    PubMed

    Chen, He; Chen, Sheng-Ping; Jiang, Zong-Fu; Hou, Jing

    2016-01-01

    Pulsed fibre lasers operating in the eye-safe 2 μm spectral region have numerous potential applications in areas such as remote sensing, medicine, mid-infrared frequency conversion, and free-space communication. Here, for the first time, we demonstrate versatile 2 μm ps-ns pulses generation from Tm-based fibre lasers based on frequency shifted feedback and provide a comprehensive report of their special behaviors. The lasers are featured with elegant construction and the unparalleled capacity of generating versatile pulses. The self-starting mode-locking is initiated by an intra-cavity acousto-optical frequency shifter. Diversified mode-locked pulse dynamics were observed by altering the pump power, intra-cavity polarization state and cavity structure, including as short as 8 ps single pulse sequence, pulse bundle state and up to 12 nJ, 3 ns nanosecond rectangular pulse. A reflective nonlinear optical loop mirror was introduced to successfully shorten the pulses from 24 ps to 8 ps. Beside the mode-locking operation, flexible Q-switching and Q-switched mode-locking operation can also be readily achieved in the same cavity. Up to 78 μJ high energy nanosecond pulse can be generated in this regime. Several intriguing pulse dynamics are characterized and discussed. PMID:27193213

  10. STATISTICAL STUDIES OF GIANT PULSE EMISSION FROM THE CRAB PULSAR

    SciTech Connect

    Majid, Walid A.; Naudet, Charles J.; Lowe, Stephen T.; Kuiper, Thomas B. H.

    2011-11-01

    We have observed the Crab pulsar with the Deep Space Network Goldstone 70 m antenna at 1664 MHz during three observing epochs for a total of 4 hr. Our data analysis has detected more than 2500 giant pulses, with flux densities ranging from 0.1 kJy to 150 kJy and pulse widths from 125 ns (limited by our bandwidth) to as long as 100 {mu}s, with median power amplitudes and widths of 1 kJy and 2 {mu}s, respectively. The most energetic pulses in our sample have energy fluxes of approximately 100 kJy {mu}s. We have used this large sample to investigate a number of giant pulse emission properties in the Crab pulsar, including correlations among pulse flux density, width, energy flux, phase, and time of arrival. We present a consistent accounting of the probability distributions and threshold cuts in order to reduce pulse-width biases. The excellent sensitivity obtained has allowed us to probe further into the population of giant pulses. We find that a significant portion, no less than 50%, of the overall pulsed energy flux at our observing frequency is emitted in the form of giant pulses.

  11. Free-electron laser-based pulsed electron paramagnetic resonance

    NASA Astrophysics Data System (ADS)

    Takahashi, Susumu; Sherwin, Mark S.; Ramian, Gerald; Brunel, Louis-Claude; van Tol, Johan

    2008-03-01

    High-power pulsed electron paramagnetic resonance (EPR) is extremely useful to study the ultrafast dynamics of spins. At present, most high-power pulsed EPR spectrometers operate near the X-band frequency of 9.5 GHz with kW-level power. A trend in the evolution of next generation pulsed EPR is for higher magnetic field and frequency, both for finer spectral and time resolution and because motional averaging becomes negligible. Since the linewidth of resonances studied by pulsed EPR tends to be extremely narrow, the source radiation also has to be stable and have narrow bandwidth. High-power pulsed EPR, using few-ns pulses to rapidly manipulate spins for spin-echo and related experiments, has been demonstrated at 95 GHz using kW- power Klystron-based sources. A bottleneck for higher frequency pulsed EPR spectroscopy is a lack of sources with high power and narrow bandwidth. The University of California Santa Barbara (UCSB) free-electron lasers (FEL) are potential sources for high-power pulsed EPR because they generate kW of power tunable from 120 GHz to 4.7 THz. We present the current status of the UCSB FEL-based 240 GHz pulsed EPR spectrometer.

  12. Dengue NS1 antigen contributes to disease severity by inducing interleukin (IL)-10 by monocytes.

    PubMed

    Adikari, T N; Gomes, L; Wickramasinghe, N; Salimi, M; Wijesiriwardana, N; Kamaladasa, A; Shyamali, N L A; Ogg, G S; Malavige, G N

    2016-04-01

    Both dengue NS1 antigen and serum interleukin (IL)-10 levels have been shown to associate with severe clinical disease in acute dengue infection, and IL-10 has also been shown to suppress dengue-specific T cell responses. Therefore, we proceeded to investigate the mechanisms by which dengue NS1 contributes to disease pathogenesis and if it is associated with altered IL-10 production. Serum IL-10 and dengue NS1 antigen levels were assessed serially in 36 adult Sri Lankan individuals with acute dengue infection. We found that the serum IL-10 levels correlated positively with dengue NS1 antigen levels (Spearman's r = 0·47, P < 0·0001), and NS1 also correlated with annexin V expression by T cells in acute dengue (Spearman's r = 0·63, P = 0·001). However, NS1 levels did not associate with the functionality of T cell responses or with expression of co-stimulatory molecules. Therefore, we further assessed the effect of dengue NS1 on monocytes and T cells by co-culturing primary monocytes and peripheral blood mononuclear cells (PBMC), with varying concentrations of NS1 for up to 96 h. Monocytes co-cultured with NS1 produced high levels of IL-10, with the highest levels seen at 24 h, and then declined gradually. Therefore, our data show that dengue NS1 appears to contribute to pathogenesis of dengue infection by inducing IL-10 production by monocytes.

  13. Characterising Non-Structural Protein NS4 of African Horse Sickness Virus

    PubMed Central

    Zwart, Lizahn; Potgieter, Christiaan A.; Clift, Sarah J.; van Staden, Vida

    2015-01-01

    African horse sickness is a serious equid disease caused by the orbivirus African horse sickness virus (AHSV). The virus has ten double-stranded RNA genome segments encoding seven structural and three non-structural proteins. Recently, an additional protein was predicted to be encoded by genome segment 9 (Seg-9), which also encodes VP6, of most orbiviruses. This has since been confirmed in bluetongue virus and Great Island virus, and the non-structural protein was named NS4. In this study, in silico analysis of AHSV Seg-9 sequences revealed the existence of two main types of AHSV NS4, designated NS4-I and NS4-II, with different lengths and amino acid sequences. The AHSV NS4 coding sequences were in the +1 reading frame relative to that of VP6. Both types of AHSV NS4 were expressed in cultured mammalian cells, with sizes close to the predicted 17–20 kDa. Fluorescence microscopy of these cells revealed a dual cytoplasmic and nuclear, but not nucleolar, distribution that was very similar for NS4-I and NS4-II. Immunohistochemistry on heart, spleen, and lung tissues from AHSV-infected horses showed that NS4 occurs in microvascular endothelial cells and mononuclear phagocytes in all of these tissues, localising to the both the cytoplasm and the nucleus. Interestingly, NS4 was also detected in stellate-shaped dendritic macrophage-like cells with long cytoplasmic processes in the red pulp of the spleen. Finally, nucleic acid protection assays using bacterially expressed recombinant AHSV NS4 showed that both types of AHSV NS4 bind dsDNA, but not dsRNA. Further studies will be required to determine the exact function of AHSV NS4 during viral replication. PMID:25915516

  14. Characterising Non-Structural Protein NS4 of African Horse Sickness Virus.

    PubMed

    Zwart, Lizahn; Potgieter, Christiaan A; Clift, Sarah J; van Staden, Vida

    2015-01-01

    African horse sickness is a serious equid disease caused by the orbivirus African horse sickness virus (AHSV). The virus has ten double-stranded RNA genome segments encoding seven structural and three non-structural proteins. Recently, an additional protein was predicted to be encoded by genome segment 9 (Seg-9), which also encodes VP6, of most orbiviruses. This has since been confirmed in bluetongue virus and Great Island virus, and the non-structural protein was named NS4. In this study, in silico analysis of AHSV Seg-9 sequences revealed the existence of two main types of AHSV NS4, designated NS4-I and NS4-II, with different lengths and amino acid sequences. The AHSV NS4 coding sequences were in the +1 reading frame relative to that of VP6. Both types of AHSV NS4 were expressed in cultured mammalian cells, with sizes close to the predicted 17-20 kDa. Fluorescence microscopy of these cells revealed a dual cytoplasmic and nuclear, but not nucleolar, distribution that was very similar for NS4-I and NS4-II. Immunohistochemistry on heart, spleen, and lung tissues from AHSV-infected horses showed that NS4 occurs in microvascular endothelial cells and mononuclear phagocytes in all of these tissues, localising to the both the cytoplasm and the nucleus. Interestingly, NS4 was also detected in stellate-shaped dendritic macrophage-like cells with long cytoplasmic processes in the red pulp of the spleen. Finally, nucleic acid protection assays using bacterially expressed recombinant AHSV NS4 showed that both types of AHSV NS4 bind dsDNA, but not dsRNA. Further studies will be required to determine the exact function of AHSV NS4 during viral replication.

  15. The 150 ns detector project: Progress with small detectors

    NASA Astrophysics Data System (ADS)

    Warburton, W. K.; Russell, S. R.; Kleinfelder, Stuart A.; Segal, Julie

    1994-09-01

    This project's long term goal is to develop a pixel area detector capable of 6 MHz frame rates (150 ns/frame). Our milestones toward this goal are: a single pixel, 1 × 256 1D and 8 × 8 2D detectors, 256 × 256 2D detectors and, finally, 1024 × 1024 2D detectors. The design strategy is to supply a complete electronics chain (resetting preamp, selectable gain amplifier, analog-to-digital converter (ADC), and memory) for each pixel. In the final detectors these will all be custom integrated circuits. The front end preamplifiers are being integrated first, since their design and performance are both the most unusual and also critical to the project's success. Similarly, our early work is also concentrating on devising and perfecting detector structures which are thick enough (1 mm) to absorb over 99% of the incident X-rays in the energy range of interest. In this paper we discuss our progress toward the 1 × 256 1D and 8 × 8 2D detectors. We have fabricated sample detectors at Stanford's Center for Integrated Systems and are preparing both to test them individually and to wirebond them to the preamplifier samples to produce our first working small 1D and 2D detectors. We will describe our solutions to the design problems associated with collecting charge in less than 30 ns from 1 mm thick pixels in high resistivity silicon. We have constructed and tested the front end of our preamplifier design using a commercial 1.2 μm CMOS technology and are moving on to produce a few channels of the complete preamplifier, including a switchable gain stage and output stage. We will discuss both the preamplifier design and our initial test results.

  16. High-power pulsed thulium fiber oscillator modulated by stimulated Brillouin scattering

    SciTech Connect

    Tang, Yulong Xu, Jianqiu

    2014-01-06

    A pulsed ∼2-μm thulium-doped fiber laser passively modulated by distributed stimulated Brillouin scattering achieves 10.2 W average power and >100 kHz repetition rate with a very simple all-fiber configuration. The maximum pulse energy and peak power surpass 100 μJ and 6 kW, respectively. Another distinct property is that the pulse width is clamped around 17 ns at all power levels. All the average-power, pulse energy, and peak power show the highest values from passively modulated fiber lasers in all wavelength regions.

  17. A Tesla-pulse forming line-plasma opening switch pulsed power generator.

    PubMed

    Novac, B M; Kumar, R; Smith, I R

    2010-10-01

    A pulsed power generator based on a high-voltage Tesla transformer which charges a 3.85 Ω/55 ns water-filled pulse forming line to 300 kV has been developed at Loughborough University as a training tool for pulsed power students. The generator uses all forms of insulation specific to pulsed power technology, liquid (oil and water), gas (SF(6)), and magnetic insulation in vacuum, and a number of fast voltage and current sensors are implemented for diagnostic purposes. A miniature (centimeter-size) plasma opening switch has recently been coupled to the output of the pulse forming line, with the overall system comprising the first phase of a program aimed at the development of a novel repetitive, table-top generator capable of producing 15 GW pulses for high power microwave loads. Technical details of all the generator components and the main experimental results obtained during the program and demonstrations of their performance are presented in the paper, together with a description of the various diagnostic tools involved. In particular, it is shown that the miniature plasma opening switch is capable of reducing the rise time of the input current while significantly increasing the load power. Future plans are outlined in the conclusions.

  18. Long Pulse Vacuum Hohlraum Performance on NIF

    NASA Astrophysics Data System (ADS)

    Landen, O. L.; Suter, L. J.; Dewald, E.; Turner, R. E.; Campbell, K. M.; McDonald, J. W.; Holder, J.; Schein, J.; Glenzer, S. H.; MacKinnon, A. J.; Froula, D.; Niemann, C.; Schneider, M. S.; Wallace, R. J.; Manes, K.; Kauffman, R. L.; Kalantar, D. H.; Stevenson, M.; Foster, J.; Monteil, M. C.

    2004-11-01

    We report on the design and performance of the first hohlraums on NIF. Gold vacuum hohlraums will be irradiated with the first four beams of NIF with up to 7 TW / 16 kJ in pulse lengths ranging from 2-9 ns, the longest pulses representing a new regime for single beam irradiation of hohlraums. The hohlraums will be diagnosed by multiple, newly activated optical, soft and hard x-ray diagnostics, including a soft x-ray power diagnostic, hard x-ray spectrometer for hot electron inference, coronal plasma imager and energy, time, and spectrally-resolved laser backscatter and near-backscatter detectors. We will compare the radiation temperature, hot electron flux and imaging results with various radiation-hydrodynamic simulations.

  19. High power UV and VUV pulsed excilamps

    NASA Astrophysics Data System (ADS)

    Tarasenko, V.; Erofeev, M.; Lomaev, M.; Rybka, D.

    2008-07-01

    Emission characteristics of a nanosecond discharge in inert gases and its halogenides without preionization of the gap from an auxiliary source have been investigated. A volume discharge, initiated by an avalanche electron beam (VDIAEB) was realized at pressures up to 12 atm. In xenon at pressure of 1.2 atm, the energy of spontaneous radiation in the full solid angle was sim 45 mJ/cm^3, and the FWHM of a radiation pulse was sim 110 ns. The spontaneous radiation power rise in xenon was observed at pressures up to 12 atm. Pulsed radiant exitance of inert gases halogenides excited by VDIAEB was sim 4.5 kW/cm^2 at efficiency up to 5.5 %.

  20. ADJUSTABLE DOUBLE PULSE GENERATOR

    DOEpatents

    Gratian, J.W.; Gratian, A.C.

    1961-08-01

    >A modulator pulse source having adjustable pulse width and adjustable pulse spacing is described. The generator consists of a cross coupled multivibrator having adjustable time constant circuitry in each leg, an adjustable differentiating circuit in the output of each leg, a mixing and rectifying circuit for combining the differentiated pulses and generating in its output a resultant sequence of negative pulses, and a final amplifying circuit for inverting and square-topping the pulses. (AEC)

  1. Study of laser-plasma interaction using a physics-based model for understanding the physical mechanism of double-pulse effect in nanosecond laser ablation

    SciTech Connect

    Wu Benxin; Zhou Yun; Forsman, Andrew

    2009-12-21

    This paper studies the double-pulse effect in high-intensity ({>=}{approx}GW/cm{sup 2}) nanosecond (ns) laser ablation, which refers to the significant material removal rate enhancement for ablation by two ns laser pulses (often separated by a delay time of {approx}10 to 100 ns). The early-stage interaction of the second laser pulse with the plasma plume created by the first pulse is very important for understanding the physical mechanism of the double pulse effect. However, the plasma properties in the early stage (during a laser pulse or within 20 to 30 ns after the completion of the pulse) are very difficult to measure experimentally. In this letter, a physics-based predictive model is used as the investigation tool, which was previously verified based on experiments on plasma properties in the late stage, which are relatively easy to measure. The study shows that the second laser pulse does not directly strike the target condensed phase. Instead, it mainly interacts with the plasma plume created by the first laser pulse, heats and accelerates the ablated material in the plume lingering above the target surface.

  2. Design and implementation of an FPGA-based timing pulse programmer for pulsed-electron paramagnetic resonance applications.

    PubMed

    Sun, Li; Savory, Joshua J; Warncke, Kurt

    2013-08-01

    The design, construction and implementation of a field-programmable gate array (FPGA) -based pulse programmer for pulsed-electron paramagnetic resonance (EPR) experiments is described. The FPGA pulse programmer offers advantages in design flexibility and cost over previous pulse programmers, that are based on commercial digital delay generators, logic pattern generators, and application-specific integrated circuit (ASIC) designs. The FPGA pulse progammer features a novel transition-based algorithm and command protocol, that is optimized for the timing structure required for most pulsed magnetic resonance experiments. The algorithm was implemented by using a Spartan-6 FPGA (Xilinx), which provides an easily accessible and cost effective solution for FPGA interfacing. An auxiliary board was designed for the FPGA-instrument interface, which buffers the FPGA outputs for increased power consumption and capacitive load requirements. Device specifications include: Nanosecond pulse formation (transition edge rise/fall times, ≤3 ns), low jitter (≤150 ps), large number of channels (16 implemented; 48 available), and long pulse duration (no limit). The hardware and software for the device were designed for facile reconfiguration to match user experimental requirements and constraints. Operation of the device is demonstrated and benchmarked by applications to 1-D electron spin echo envelope modulation (ESEEM) and 2-D hyperfine sublevel correlation (HYSCORE) experiments. The FPGA approach is transferrable to applications in nuclear magnetic resonance (NMR; magnetic resonance imaging, MRI), and to pulse perturbation and detection bandwidths in spectroscopies up through the optical range.

  3. Design and implementation of an FPGA-based timing pulse programmer for pulsed-electron paramagnetic resonance applications

    PubMed Central

    Sun, Li; Savory, Joshua J.; Warncke, Kurt

    2014-01-01

    The design, construction and implementation of a field-programmable gate array (FPGA) -based pulse programmer for pulsed-electron paramagnetic resonance (EPR) experiments is described. The FPGA pulse programmer offers advantages in design flexibility and cost over previous pulse programmers, that are based on commercial digital delay generators, logic pattern generators, and application-specific integrated circuit (ASIC) designs. The FPGA pulse progammer features a novel transition-based algorithm and command protocol, that is optimized for the timing structure required for most pulsed magnetic resonance experiments. The algorithm was implemented by using a Spartan-6 FPGA (Xilinx), which provides an easily accessible and cost effective solution for FPGA interfacing. An auxiliary board was designed for the FPGA-instrument interface, which buffers the FPGA outputs for increased power consumption and capacitive load requirements. Device specifications include: Nanosecond pulse formation (transition edge rise/fall times, ≤3 ns), low jitter (≤150 ps), large number of channels (16 implemented; 48 available), and long pulse duration (no limit). The hardware and software for the device were designed for facile reconfiguration to match user experimental requirements and constraints. Operation of the device is demonstrated and benchmarked by applications to 1-D electron spin echo envelope modulation (ESEEM) and 2-D hyperfine sublevel correlation (HYSCORE) experiments. The FPGA approach is transferrable to applications in nuclear magnetic resonance (NMR; magnetic resonance imaging, MRI), and to pulse perturbation and detection bandwidths in spectroscopies up through the optical range. PMID:25076864

  4. A novel miniaturized passively Q-switched pulse-burst laser for engine ignition.

    PubMed

    Ma, Yufei; Li, Xudong; Yu, Xin; Fan, Rongwei; Yan, Renpeng; Peng, Jiangbo; Xu, Xinrui; Sun, Rui; Chen, Deying

    2014-10-01

    A novel miniaturized Cr⁴⁺:YAG passively Q-switched Nd:YAG pulse-burst laser under 808 nm diode-laser pulse-pumping was demonstrated for the purpose of laser-induced plasma ignition, in which pulse-burst mode can realize both high repetition rate and high pulse energy simultaneously in a short period. Side-pumping configuration and two different types of laser cavities were employed. The pumping pulse width was constant at 250 μs. For the plane-plane cavity, the output beam profile was flat-top Gaussian and the measured M² value was 4.1 at the maximum incident pump energy of 600 mJ. The pulse-burst laser contained a maximum of 8 pulses, 7 pulses and 6 pulses for pulse-burst repetition rate of 10 Hz, 50 Hz and 100 Hz, respectively. The energy obtained was 15.5 mJ, 14.9 mJ and 13.9 mJ per pulse for pulse-burst repetition rate of 10 Hz, 50 Hz and 100 Hz, respectively. The maximum repetition rate of laser pulses in pulse-burst was 34.6 kHz for 8 pulses at the incident pump energy of 600 mJ and the single pulse width was 13.3 ns. The thermal lensing effect of Nd:YAG rod was investigated, and an plane-convex cavity was adopted to compensate the thermal lensing effect of Nd:YAG rod and improve the mode matching. For the plane-convex cavity, the output beam profile was quasi-Gaussian and the measured M2 value was 2.2 at the incident pump energy of 600 mJ. The output energy was 10.6 mJ per pulse for pulse-burst repetition rate of 100 Hz. The maximum repetition rate of laser pulses in pulse-burst was 27.4 kHz for 6 pulses at the incident pump energy of 600 mJ and the single pulse width was 14.2 ns. The experimental results showed that this pulse-burst laser can produce high repetition rate (>20 kHz) and high pulse energy (>10 mJ) simultaneously in a short period for both two different cavities. PMID:25322040

  5. Response of surge protection devices to fast rising pulses

    NASA Technical Reports Server (NTRS)

    Mindel, I. N.

    1980-01-01

    Two types of lightning protection modules incorporating leadless (pill type) Zener like devices were evaluated with regard to their ability to suppress EMP induced transients. Two series of tests were performed to evaluate the ability of these modules to react to fast rate of rise ( 1Kv/ns) transients, and the attenuation introduced and the ability to limit damped sinusoid pulses which may be induced due to an EMP resulting from a nuclear detonation.

  6. Sub-10 ns single-shot dynamic recording in holographic polymeric medium by nonlinear absorption using excited state absorption process

    NASA Astrophysics Data System (ADS)

    Kamada, Kenji; Satoh, Kazuyuki; Tanaka, Yoshito

    2016-09-01

    Optical recording by a single shot of an 8 ns laser pulse in a dye-doped holographic polymeric medium was demonstrated with a peak power as low as 71 W at a wavelength of 402 nm. Nonlinear absorption triggered by two-photon absorption and enhanced by the succeeding process allows high-speed recording corresponding to 125 Mbps (3.4 times the recording speed of a Blu-ray Disc). The preformed holographic grating in the medium enhanced the readout signal through diffraction, resulting in a signal-to-noise ratio of about 15 dB. The recording capacity was estimated at ca. 80 GB/side for 100 µm/side by recording 20 layers, but that of over TB/side class would be possible for optical optimization. Theoretically, it can be improved to 10 TB/side for 800 µm/side by recording 400 layers.

  7. Dengue Virus NS1 Protein Modulates Cellular Energy Metabolism by Increasing Glyceraldehyde-3-Phosphate Dehydrogenase Activity

    PubMed Central

    Allonso, Diego; Andrade, Iamara S.; Conde, Jonas N.; Coelho, Diego R.; Rocha, Daniele C. P.; da Silva, Manuela L.; Ventura, Gustavo T.

    2015-01-01

    ABSTRACT Dengue is one of the main public health concerns worldwide. Recent estimates indicate that over 390 million people are infected annually with the dengue virus (DENV), resulting in thousands of deaths. Among the DENV nonstructural proteins, the NS1 protein is the only one whose function during replication is still unknown. NS1 is a 46- to 55-kDa glycoprotein commonly found as both a membrane-associated homodimer and a soluble hexameric barrel-shaped lipoprotein. Despite its role in the pathogenic process, NS1 is essential for proper RNA accumulation and virus production. In the present study, we identified that glyceraldehyde-3-phosphate dehydrogenase (GAPDH) interacts with intracellular NS1. Molecular docking revealed that this interaction occurs through the hydrophobic protrusion of NS1 and the hydrophobic residues located at the opposite side of the catalytic site. Moreover, addition of purified recombinant NS1 enhanced the glycolytic activity of GAPDH in vitro. Interestingly, we observed that DENV infection promoted the relocalization of GAPDH to the perinuclear region, where NS1 is commonly found. Both DENV infection and expression of NS1 itself resulted in increased GAPDH activity. Our findings indicate that the NS1 protein acts to increase glycolytic flux and, consequently, energy production, which is consistent with the recent finding that DENV induces and requires glycolysis for proper replication. This is the first report to propose that NS1 is an important modulator of cellular energy metabolism. The data presented here provide new insights that may be useful for further drug design and the development of alternative antiviral therapies against DENV. IMPORTANCE Dengue represents a serious public health problem worldwide and is caused by infection with dengue virus (DENV). Estimates indicate that half of the global population is at risk of infection, with almost 400 million cases occurring per year. The NS1 glycoprotein is found in both the

  8. Augmentation of cognitive function by NS9283, a stoichiometry-dependent positive allosteric modulator of α2- and α4-containing nicotinic acetylcholine receptors

    PubMed Central

    Timmermann, DB; Sandager-Nielsen, K; Dyhring, T; Smith, M; Jacobsen, A-M; Nielsen, EØ; Grunnet, M; Christensen, JK; Peters, D; Kohlhaas, K; Olsen, GM; Ahring, PK

    2012-01-01

    BACKGROUND AND PURPOSE Positive allosteric modulation of α4β2 nicotinic acetylcholine (nACh) receptors could add a new dimension to the pharmacology and therapeutic approach to these receptors. The novel modulator NS9283 was therefore tested extensively. EXPERIMENTAL APPROACH Effects of NS9283 were evaluated in vitro using fluorescence-based Ca2+ imaging and electrophysiological voltage clamp experiments in Xenopus oocytes, mammalian cells and thalamocortical neurons. In vivo the compound was tested in models covering a range of cognitive domains in mice and rats. KEY RESULTS NS9283 was shown to increase agonist-evoked response amplitude of (α4)3(β2)2 nACh receptors in electrophysiology paradigms. (α2)3(β2)2, (α2)3(β4)2 and (α4)3(β4)2 were modulated to comparable extents, but no effects were detected at α3-containing or any 2α : 3β stoichiometry nACh receptors. Native nACh receptors in thalamocortical neurons similarly displayed DHβE-sensitive currents that were receptive to modulation. NS9283 had favourable effects on sensory information processing, as shown by reversal of PCP-disrupted pre-pulse inhibition. NS9283 further improved performance in a rat model of episodic memory (social recognition), a rat model of sustained attention (five-choice serial reaction time task) and a rat model of reference memory (Morris water maze). Importantly, the effects in the Morris water maze could be fully reversed with mecamylamine, a blocker of nACh receptors. CONCLUSIONS AND IMPLICATIONS These results provide compelling evidence that positive allosteric modulators acting at the (α4)3(β2)2 nACh receptors can augment activity across a broad range of cognitive domains, and that α4β2 nACh receptor allosteric modulation therefore constitutes a promising therapeutic approach to symptomatic treatment of cognitive impairment. PMID:22506660

  9. Using an active temporal compensating system to achieve the super-Gaussian pulses in high-power lasers

    NASA Astrophysics Data System (ADS)

    Wang, Yulei; Liu, Rui; Yuan, Hang; Li, Sensen; Liu, Zhaohong; Zhu, Xuehua; He, Weiming; Lv, Zhiwei

    2015-08-01

    In high-power solid-state laser, initiative pulse shaping can help improve the output laser's performance. The evaluation for output laser pulse is also incomplete. In this paper, we propose a method of initiative pulse shaping by using arbitrary waveform generator (AWG), and establish a relatively complete evaluation system for the output pulses shape simultaneously. It achieves the super-Gaussian pulse output with high SNR (signal-to-noise ratio). As a consequence, a square laser pulse with pulse adjustable width ~5ns, rising time 197ps is obtained. The power imbalance of the output square pulse is 3.72%. The similarity between the eight-order super-Gaussian pulse and the one we get from experiment reached 99%.

  10. 973 nm wavelength stabilized hybrid ns-MOPA diode laser system with 15.5 W peak power and a spectral line width below 10 pm

    NASA Astrophysics Data System (ADS)

    Vu, Thi N.; Klehr, Andreas; Sumpf, Bernd; Wenzel, Hans; Erbert, Götz; Tränkle, Günther

    2014-05-01

    A master oscillator power amplifier (MOPA) system for the generation of ns-pulses with high peak power, narrow spectral line width, and stabilized emission wavelength will be presented. The master oscillator is a distributed feedback (DFB) ridge waveguide (RW) laser. The tapered amplifier consists of one RW section and one flared gain-guided section. The DFB laser is operated in continuous wave mode and emits at 973.5 nm with a spectral line width below 10 pm. The RW section of the amplifier acts as an optical gate. The tapered section amplifies the generated optical pulse. An optical peak power of 15.5 W for a pulse width of 8 ns is obtained. The emission wavelength remains constant at all output power levels of the MOPA system for a fixed current into the DFB laser. The spectral power density of the ASE is 37 dB smaller than the lasing spectral power density. The spectral line width is smaller than 10 pm, limited by the resolution of the optical spectrum analyzer.

  11. Pulsed electron beam propagation in argon and nitrogen gas mixture

    NASA Astrophysics Data System (ADS)

    Kholodnaya, G. E.; Sazonov, R. V.; Ponomarev, D. V.; Remnev, G. E.; Zhirkov, I. S.

    2015-10-01

    The paper presents the results of current measurements for the electron beam, propagating inside a drift tube filled in with a gas mixture (Ar and N2). The experiments were performed using the TEA-500 pulsed electron accelerator. The main characteristics of electron beam were as follows: 60 ns pulse duration, up to 200 J energy, and 5 cm diameter. The electron beam propagated inside the drift tube assembled of three sections. Gas pressures inside the drift tube were 760 ± 3, 300 ± 3, and 50 ± 1 Torr. The studies were performed in argon, nitrogen, and their mixtures of 33%, 50%, and 66% volume concentrations, respectively.

  12. Rectangular waveguide calorimeter for single intense microwave pulses

    SciTech Connect

    Earley, L.M.; Ballard, W.P.; Roose, L.D.

    1986-09-01

    A new calorimeter for single intense microwave pulses has been designed and tested. The device was constructed in WR284 rectangular waveguide and was operated at frequencies from 2.5 to 4.3 GHz with a tunable instantaneous bandwidth of approximately 500 MHz. The calorimeter used a single thermistor to measure the energy deposited on a carbon absorber having a microwave power absorbance of 90%. The calorimeter was tested at power levels from 100 to 1000 MW for pulse lengths of 12--6 ns, respectively. The sensitivity of the device was 200--300 mV/J.

  13. Policresulen, a novel NS2B/NS3 protease inhibitor, effectively inhibits the replication of DENV2 virus in BHK-21 cells

    PubMed Central

    Wu, Deng-wei; Mao, Fei; Ye, Yan; Li, Jian; Xu, Chuan-lian; Luo, Xiao-min; Chen, Jing; Shen, Xu

    2015-01-01

    Aim: Dengue is a severe epidemic disease caused by dengue virus (DENV) infection, for which no effective treatment is available. The protease complex, consisting of nonstructural protein 3 (NS3) and its cofactor NS2B, plays a pivotal role in the replication of DENV, thus may be a potential target for anti-DENV drugs. Here, we report a novel inhibitor of DENV2 NS2B/NS3 protease and its antiviral action. Methods: An enzymatic inhibition assay was used for screening DENV2 NS2B/NS3 inhibitors. Cytotoxicity to BHK-21 cells was assessed with MTT assay. Antiviral activity was evaluated in BHK-21 cells transfected with Rlu-DENV-Rep. The molecular mechanisms of the antiviral action was analyzed using surface plasmon resonance, ultraviolet-visible spectral analysis and differential scanning calorimetry assays, as well as molecular docking analysis combined with site-directed mutagenesis. Results: In our in-house library of old drugs (∼1000 compounds), a topical hemostatic and antiseptic 2-hydroxy-3,5-bis[(4-hydroxy-2-methyl-5-sulfophenyl)methyl]-4-methyl-benzene-sulfonic acid (policresulen) was found to be a potent inhibitor of DENV2 NS2B/NS3 protease with IC50 of 0.48 μg/mL. Furthermore, policresulen inhibited DENV2 replication in BHK-21 cells with IC50 of 4.99 μg/mL, whereas its IC50 for cytotoxicity to BHK-21 cells was 459.45 μg/mL. Policresulen acted as a competitive inhibitor of the protease, and slightly affected the protease stability. Using biophysical technology-based assays and molecular docking analysis combined with site-directed mutagenesis, we demonstrated that the residues Gln106 and Arg133 of DENV2 NS2B/NS3 protease directly interacted with policresulen via hydrogen bonding. Conclusion: Policresulen is a potent inhibitor of DENV2 NS2B/NS3 protease that inhibits DENV2 replication in BHK-21 cells. The binding mode of the protease and policresulen provides useful hints for designing new type of inhibitors against the protease. PMID:26279156

  14. VP2 Exchange and NS3/NS3a Deletion in African Horse Sickness Virus (AHSV) in Development of Disabled Infectious Single Animal Vaccine Candidates for AHSV

    PubMed Central

    van de Water, Sandra G. P.; van Gennip, René G. P.; Potgieter, Christiaan A.; Wright, Isabel M.

    2015-01-01

    ABSTRACT African horse sickness virus (AHSV) is a virus species in the genus Orbivirus of the family Reoviridae. There are nine serotypes of AHSV showing different levels of cross neutralization. AHSV is transmitted by species of Culicoides biting midges and causes African horse sickness (AHS) in equids, with a mortality rate of up to 95% in naive horses. AHS has become a serious threat for countries outside Africa, since endemic Culicoides species in moderate climates appear to be competent vectors for the related bluetongue virus (BTV). To control AHS, live-attenuated vaccines (LAVs) are used in Africa. We used reverse genetics to generate “synthetic” reassortants of AHSV for all nine serotypes by exchange of genome segment 2 (Seg-2). This segment encodes VP2, which is the serotype-determining protein and the dominant target for neutralizing antibodies. Single Seg-2 AHSV reassortants showed similar cytopathogenic effects in mammalian cells but displayed different growth kinetics. Reverse genetics for AHSV was also used to study Seg-10 expressing NS3/NS3a proteins. We demonstrated that NS3/NS3a proteins are not essential for AHSV replication in vitro. NS3/NS3a of AHSV is, however, involved in the cytopathogenic effect in mammalian cells and is very important for virus release from cultured insect cells in particular. Similar to the concept of the bluetongue disabled infectious single animal (BT DISA) vaccine platform, an AHS DISA vaccine platform lacking NS3/NS3a expression was developed. Using exchange of genome segment 2 encoding VP2 protein (Seg-2[VP2]), we will be able to develop AHS DISA vaccine candidates for all current AHSV serotypes. IMPORTANCE African horse sickness virus is transmitted by species of Culicoides biting midges and causes African horse sickness in equids, with a mortality rate of up to 95% in naive horses. African horse sickness has become a serious threat for countries outside Africa, since endemic Culicoides species in moderate

  15. [Grouping of the NS1 nonstructural proteins of influenza A viruses].

    PubMed

    Sokolov, B P; Rudneva, I A; Zhdanov, V M

    1981-01-01

    Peptide mapping was used for comparative analysis of nonstructural proteins (NS1) of 21 strains of human and animal influenza A viruses. At least 4 groups of NS1 proteins could be distinguished by the analysis of the peptide maps; we designated these groups as 0, 1, 2, and 3. Group O includes NS1 proteins of human influenza virus serotype HON1, group 1 - NS1 proteins of viruses of serotypes H1N1 and H2N2, group 2 - NS1 proteins of viruses of serotype H3N2. NS1 proteins of avian influenza viruses A/duck Czechoslovakia/63, A/turkey Massachusetts/65, A/petrel Australia/1/71, A/duck Ukraine/63, and A/turkey Ontario/68 have been included into group 3. PMID:7336689

  16. Functions of the influenza A virus NS1 protein in antiviral defense.

    PubMed

    Krug, Robert M

    2015-06-01

    Influenza A viruses counteract host antiviral activities, especially the production of interferons (IFNs) and the activities of IFN-induced proteins that inhibit virus replication. The viral NS1 protein is largely responsible for countering these IFN antiviral responses, but there are functional differences between the NS1 proteins of different virus strains. The NS1 protein inhibits IFN production by two mechanisms: inhibition of the activation of IRF3 and IFN transcription; and inhibition of the processing of IFN pre-mRNAs. The NS1 proteins of several virus strains do not inhibit IRF3 activation, and the NS1 protein of one virus strain does not inhibit the processing of IFN pre-mRNAs. Many issues remain concerning the mechanisms of action of the various NS1 proteins in countering the IFN response.

  17. Functions of the Influenza A Virus NS1 Protein In Antiviral Defense

    PubMed Central

    Krug, Robert M.

    2015-01-01

    Influenza A viruses counteract host antiviral activities, especially the production of interferons (IFNs) and the activities of IFN-induced proteins that inhibit virus replication. The viral NS1 protein is largely responsible for countering these IFN antiviral responses, but there are functional differences between the NS1 proteins of different virus strains. The NS1 protein inhibits IFN production by two mechanisms: inhibition of the activation of IRF3 and IFN transcription; and inhibition of the processing of IFN pre-mRNAs. The NS1 proteins of several virus strains do not inhibit IRF3 activation, and the NS1 protein of one virus strain does not inhibit the processing of IFN pre-mRNAs. Many issues remain concerning the mechanisms of action of the various NS1 proteins in countering the IFN response. PMID:25638592

  18. Structure of NS1A effector domain from the influenza A/Udorn/72 virus

    SciTech Connect

    Xia, Shuangluo; Monzingo, Arthur F.; Robertus, Jon D.

    2009-01-01

    The structure of the effector domain of the influenza protein NS1, a validated antiviral drug target, has been solved in two space groups. The nonstructural protein NS1A from influenza virus is a multifunctional virulence factor and a potent inhibitor of host immunity. It has two functional domains: an N-terminal 73-amino-acid RNA-binding domain and a C-terminal effector domain. Here, the crystallographic structure of the NS1A effector domain of influenza A/Udorn/72 virus is presented. Structure comparison with the NS1 effector domain from mouse-adapted influenza A/Puerto Rico/8/34 (PR8) virus strain reveals a similar monomer conformation but a different dimer interface. Further analysis and evaluation shows that the dimer interface observed in the structure of the PR8 NS1 effector domain is likely to be a crystallographic packing effect. A hypothetical model of the intact NS1 dimer is presented.

  19. Electron-Beam Switches For A High Peak Power Sled-II Pulse Compressor

    SciTech Connect

    Hirshfield, Jay, L.

    2015-12-02

    Omega-P demonstrated triggered electron-beam switches on the L=2 m dual-delay-line X-band pulse compressor at Naval Research Laboratory (NRL). In those experiments, with input pulses of up to 9 MW from the Omega-P/NRL X-band magnicon, output pulses having peak powers of 140-165 MW and durations of 16-20 ns were produced, with record peak power gains M of 18-20. Switch designs are described based on the successful results that should be suitable for use with the existing SLAC SLED-II delay line system, to demonstrate C=9, M=7, and n>>78%, yielding 173ns compressed pulses with peak powers up to 350MW with input of a single 50-MW.

  20. A high voltage pulsed power supply for capillary discharge waveguide applications

    SciTech Connect

    Abuazoum, S.; Wiggins, S. M.; Issac, R. C.; Welsh, G. H.; Vieux, G.; Jaroszynski, D. A.; Ganciu, M.

    2011-06-15

    We present an all solid-state, high voltage pulsed power supply for inducing stable plasma formation (density {approx}10{sup 18} cm{sup -3}) in gas-filled capillary discharge waveguides. The pulser (pulse duration of 1 {mu}s) is based on transistor switching and wound transmission line transformer technology. For a capillary of length 40 mm and diameter 265 {mu}m and gas backing pressure of 100 mbar, a fast voltage pulse risetime of 95 ns initiates breakdown at 13 kV along the capillary. A peak current of {approx}280 A indicates near complete ionization, and the r.m.s. temporal jitter in the current pulse is only 4 ns. Temporally stable plasma formation is crucial for deploying capillary waveguides as plasma channels in laser-plasma interaction experiments, such as the laser wakefield accelerator.

  1. The effects of pulse duration on ablation pressure driven by laser radiation

    SciTech Connect

    Zhou, Lei; Li, Xiao-Ya Zhu, Wen-Jun; Wang, Jia-Xiang; Tang, Chang-Jian

    2015-03-28

    The effects of laser pulse duration on the ablation pressure induced by laser radiation are investigated using Al target. Numerical simulation results using one dimensional radiation hydro code for laser intensities from 5×10{sup 12}W/cm{sup 2} to 5×10{sup 13}W/cm{sup 2} and pulse durations from 0.5 ns to 20 ns are presented. These results suggest that the laser intensity scaling law of ablation pressure differs for different pulse durations. And the theoretical analysis shows that the effects of laser pulse duration on ablation pressure are mainly caused by two regimes: the unsteady-state flow and the radiative energy loss to vacuum.

  2. Transform-limited pulses generated by an actively Q-switched distributed fiber laser.

    PubMed

    Cuadrado-Laborde, C; Pérez-Millán, P; Andrés, M V; Díez, A; Cruz, J L; Barmenkov, Yu O

    2008-11-15

    A single-mode, transform-limited, actively Q-switched distributed-feedback fiber laser is presented, based on a new in-line acoustic pulse generator. Our technique permits a continuous adjustment of the repetition rate that modulates the Q factor of the cavity. Optical pulses of 800 mW peak power, 32 ns temporal width, and up to 20 kHz repetition rates were obtained. The measured linewidth demonstrates that these pulses are transform limited: 6 MHz for a train of pulses of 10 kHz repetition rate, 80 ns temporal width, and 60 mW peak power. Efficient excitation of spontaneous Brillouin scattering is demonstrated. PMID:19015677

  3. Functional differences in hepatitis C virus nonstructural (NS) 3/4A- and 5A-specific T cell responses

    PubMed Central

    Holmström, Fredrik; Chen, Margaret; Balasiddaiah, Anangi; Sällberg, Matti; Ahlén, Gustaf; Frelin, Lars

    2016-01-01

    The hepatitis C virus nonstructural (NS) 3/4A and NS5A proteins are major targets for the new direct-acting antiviral compounds. Both viral proteins have been suggested as modulators of the response to the host cell. We have shown that NS3/4A- and NS5A-specific T cell receptors confer different effector functions, and that killing of NS3/4A-expressing hepatocytes is highly dependent on IFN-γ. We here characterize the functional differences in the T cell responses to NS3/4A and NS5A. NS3/4A- and NS5A-specific T cells could be induced at various frequencies in wild-type-, NS3/4A-, and NS5A-transgenic mice. Priming of NS5A-specific T cells required a high DNA dose, and was unlike NS3/4A dependent on both CD4+ and CD8+ T cells, but less influenced by CD25+/GITR+ regulatory T cells. The presence of IL-12 greatly improved specific CD8+ T cell priming by NS3/4A but not by NS5A, suggesting a less dependence of IFN-γ for NS5A. This notion was supported by the observation that NS5A-specific T cells could eliminate NS5A-expressing hepatocytes also in the absence of IFN-γ-receptor-2. This supports that NS3/4A- and NS5A-specific T cells become activated and eliminate antigen expressing, or infected hepatocytes, by distinct mechanisms, and that NS5A-specific T cells show an overall less dependence of IFN-γ. PMID:27141891

  4. Long-pulse-width narrow-bandwidth solid state laser

    DOEpatents

    Dane, C.B.; Hackel, L.A.

    1997-11-18

    A long pulse laser system emits 500-1000 ns quasi-rectangular pulses at 527 nm with near diffraction-limited divergence and near transform-limited bandwidth. The system consists of one or more flashlamp-pumped Nd:glass zig-zag amplifiers, a very low threshold stimulated-Brillouin-scattering (SBS) phase conjugator system, and a free-running single frequency Nd:YLF master oscillator. Completely passive polarization switching provides eight amplifier gain passes. Multiple frequency output can be generated by using SBS cells having different pressures of a gaseous SBS medium or different SBS materials. This long pulse, low divergence, narrow-bandwidth, multi-frequency output laser system is ideally suited for use as an illuminator for long range speckle imaging applications. Because of its high average power and high beam quality, this system has application in any process which would benefit from a long pulse format, including material processing and medical applications. 5 figs.

  5. Long-pulse-width narrow-bandwidth solid state laser

    DOEpatents

    Dane, C. Brent; Hackel, Lloyd A.

    1997-01-01

    A long pulse laser system emits 500-1000 ns quasi-rectangular pulses at 527 nm with near diffraction-limited divergence and near transform-limited bandwidth. The system consists of one or more flashlamp-pumped Nd:glass zig-zag amplifiers, a very low threshold stimulated-Brillouin-scattering (SBS) phase conjugator system, and a free-running single frequency Nd:YLF master oscillator. Completely passive polarization switching provides eight amplifier gain passes. Multiple frequency output can be generated by using SBS cells having different pressures of a gaseous SBS medium or different SBS materials. This long pulse, low divergence, narrow-bandwidth, multi-frequency output laser system is ideally suited for use as an illuminator for long range speckle imaging applications. Because of its high average power and high beam quality, this system has application in any process which would benefit from a long pulse format, including material processing and medical applications.

  6. PCF based high power narrow line width pulsed fiber laser

    NASA Astrophysics Data System (ADS)

    Chen, H.; Yan, P.; Xiao, Q.; Wang, Y.; Gong, M.

    2012-09-01

    Based on semiconductor diode seeded multi-stage cascaded fiber amplifiers, we have obtained 88-W average power of a 1063-nm laser with high repetition rate of up to 1.5 MHz and a constant 2-ns pulse duration. No stimulated Brillouin scattering pulse or optical damage occurred although the maximum pulse peak power has exceeded 112 kW. The output laser exhibits excellent beam quality (M2x = 1.24 and M2y = 1.18), associated with a spectral line width as narrow as 0.065 nm (FWHM). Additionally, we demonstrate high polarization extinction ratio of 18.4 dB and good pulse stabilities superior to 1.6 % (RMS).

  7. Optodynamic aspect of a pulsed laser ablation process

    NASA Astrophysics Data System (ADS)

    Hrovatin, Rok; Možina, Janez

    1995-02-01

    A study of a pulsed laser ablation process is presented from a novel, optodynamic aspect. By quantitative analysis of laser-induced bulk ultrasonic and blast waves in the air the ablation dynamics is characterized. In this way the influence of the laser pulse parameters and of the interacting material on the ablation process was assessed. By the analysis of the laser drilling process of thin layered samples the material influence was demonstrated. Besides the ultrasonic evaluation of the laser pulse power density the plasma shielding for 10 ns laser pulses was analyzed by the same method. All measurements were noncontact. Bulk waves in the solid and blast waves in the air were measured simultaneously, an interferometric and a probe beam deflection method were used, respectively.

  8. Recycle Rate in a Pulsed, Optically Pumped Rubidium Laser

    SciTech Connect

    Miller, Wooddy S.; Sulham, Clifford V.; Holtgrave, Jeremy C.; Perram, Glen P.

    2010-10-08

    A pulsed, optically pumped rubidium laser operating in analogy to the diode pumped alkali laser (DPAL) system at pump intensities as high as 750 kW/cm{sup 2} has been demonstrated with output energies of up to 13 {mu}J/pulse. Output energy is dramatically limited by spin-orbit relaxation rates under these high intensity pump conditions. More than 250 photons are available for every rubidium atom in the pumped volume, requiring a high number of cycles per atom during the 2-8 ns duration of the pump pulse. At 550 Torr of ethane, the spin-orbit relaxation rate is too slow to effectively utilize all the incident pump photons. Indeed, a linear dependence of output energy on pump pulse duration for fixed pump energy is demonstrated.

  9. Microsecond-scale electric field pulses in cloud lightning discharges

    NASA Technical Reports Server (NTRS)

    Villanueva, Y.; Rakov, V. A.; Uman, M. A.; Brook, M.

    1994-01-01

    From wideband electric field records acquired using a 12-bit digitizing system with a 500-ns sampling interval, microsecond-scale pulses in different stages of cloud flashes in Florida and New Mexico are analyzed. Pulse occurrence statistics and waveshape characteristics are presented. The larger pulses tend to occur early in the flash, confirming the results of Bils et al. (1988) and in contrast with the three-stage representation of cloud-discharge electric fields suggested by Kitagawa and Brook (1960). Possible explanations for the discrepancy are discussed. The tendency for the larger pulses to occur early in the cloud flash suggests that they are related to the initial in-cloud channel formation processes and contradicts the common view found in the atmospheric radio-noise literature that the main sources of VLF/LF electromagnetic radiation in cloud flashes are the K processes which occur in the final, or J type, part of the cloud discharge.

  10. Analysis on the characteristics of pulsed laser proximity fuze's echo

    NASA Astrophysics Data System (ADS)

    Wang, Kun; Chen, Huimin

    2011-06-01

    With the rapid development of semiconductor technology and laser technology, a kind of proximity fuze named pulsed laser proximity fuze has been applied. Compared with other fuzes, pulsed laser proximity fuze has high ranging precision and strong resistance to artificial active interference. It is an important development tendency of proximity fuze. The paper analyze the characteristic of target echo of laser signal, and then make theoretical analysis and calculation on the laser signal transmission in the smog. Firstly, use the pulse width of 10ns semiconductor laser fuze to do typical targets experiment, to get the echo information of target distance is 5m; then to do smog interference experiment, by comparing the pulse width amplitude and backscattering signal amplitude of laser fuze in simulation and experiment, analyzing the effect of anti-clutter, providing the evidence for the subsequent of circuit of signal amplification and processing.

  11. Diode laser based water vapor DIAL using modulated pulse technique

    NASA Astrophysics Data System (ADS)

    Pham, Phong Le Hoai; Abo, Makoto

    2014-11-01

    In this paper, we propose a diode laser based differential absorption lidar (DIAL) for measuring lower-tropospheric water vapor profile using the modulated pulse technique. The transmitter is based on single-mode diode laser and tapered semiconductor optical amplifier with a peak power of 10W around 800nm absorption band, and the receiver telescope diameter is 35cm. The selected wavelengths are compared to referenced wavelengths in terms of random error and systematic errors. The key component of modulated pulse technique, a macropulse, is generated with a repetition rate of 10 kHz, and the modulation within the macropulse is coded according to a pseudorandom sequence with 100ns chip width. As a result, we evaluate both single pulse modulation and pseudorandom coded pulse modulation technique. The water vapor profiles conducted from these modulation techniques are compared to the real observation data in summer in Japan.

  12. Xenon excimer emission from pulsed microhollow cathode discharges

    NASA Astrophysics Data System (ADS)

    Moselhy, M.; Shi, W.; Stark, R. H.; Schoenbach, K. H.

    2001-08-01

    By applying electrical pulses of 20 ns duration to xenon microplasmas, generated by direct current microhollow cathode discharges, we were able to increase the xenon excimer emission by more than an order of magnitude over direct current discharge excimer emission. For pulsed voltages in excess of 500 V, the optical power at 172 nm was found to increase exponentially with voltage. Largest values obtained were 2.75 W of vacuum-ultraviolet optical power emitted from a single microhollow cathode discharge in 400 Torr xenon with a 750 V pulse applied to a discharge. Highest radiative emittance was 15.2 W/cm2. The efficiency for excimer emission was found to increase linearly with pulsed voltages above 500 V reaching values of 20% at 750 V.

  13. Pulsed Power for a Dynamic Transmission Electron Microscope

    SciTech Connect

    dehope, w j; browning, n; campbell, g; cook, e; king, w; lagrange, t; reed, b; stuart, b; Shuttlesworth, R; Pyke, B

    2009-06-25

    Lawrence Livermore National Laboratory (LLNL) has converted a commercial 200kV transmission electron microscope (TEM) into an ultrafast, nanoscale diagnostic tool for material science studies. The resulting Dynamic Transmission Electron Microscope (DTEM) has provided a unique tool for the study of material phase transitions, reaction front analyses, and other studies in the fields of chemistry, materials science, and biology. The TEM's thermionic electron emission source was replaced with a fast photocathode and a laser beam path was provided for ultraviolet surface illumination. The resulting photoelectron beam gives downstream images of 2 and 20 ns exposure times at 100 and 10 nm spatial resolution. A separate laser, used as a pump pulse, is used to heat, ignite, or shock samples while the photocathode electron pulses, carefully time-synchronized with the pump, function as probe in fast transient studies. The device functions in both imaging and diffraction modes. A laser upgrade is underway to make arbitrary cathode pulse trains of variable pulse width of 10-1000 ns. Along with a fast e-beam deflection scheme, a 'movie mode' capability will be added to this unique diagnostic tool. This talk will review conventional electron microscopy and its limitations, discuss the development and capabilities of DTEM, in particularly addressing the prime and pulsed power considerations in the design and fabrication of the DTEM, and conclude with the presentation of a deflector and solid-state pulser design for Movie-Mode DTEM.

  14. Analytical calculations of wake field generated by microwave pulses in a plasma filled waveguide for electron acceleration

    SciTech Connect

    Malik, Hitendra K.

    2008-09-01

    Analytical expressions are obtained for the longitudinal field (wake field), density perturbation, and the potential behind microwave pulse propagating in a plasma filled rectangular waveguide with the pulse duration half of the electron plasma period. A feasibility study on wake field is carried out with rectangular pulse and its combination with Gaussian and triangular pulses under the effects of microwave pulse parameters and waveguide dimensions. It is inferred that the wake field in the waveguide cannot be attained when the length of rectangular microwave pulse is exactly equal to the plasma wavelength. A 1 ns short rectangular pulse with intensity of 250 kW/cm{sup 2} at the frequency of 5.03 GHz can excite the wake field of 1.0 MV/m in a waveguide with width of 6 cm and height of 4 cm. However, enhanced field is obtained when rectangular-triangular pulse (combination of rectangular and triangular pulses) is used. The field of wake gets weakened at higher microwave frequency and larger dimensions of the waveguide for other fixed parameters. However, a larger field is achieved when the pulse length of the microwave pulses is made shorter and/or intensity of the pulses is increased. A comparative study of the pulses shows that better results can be obtained with rectangular pulse (rectangular-Gaussian pulse: combination of rectangular and Gaussian pulses) if the microwave of shorter pulse duration (higher intensity) is available.

  15. The NS5A protein of hepatitis C virus is a zinc metalloprotein.

    PubMed

    Tellinghuisen, Timothy L; Marcotrigiano, Joseph; Gorbalenya, Alexander E; Rice, Charles M

    2004-11-19

    The NS5A protein of hepatitis C virus is believed to be an integral part of the viral replicase. Despite extensive investigation, the role of this protein remains elusive. Only limited biochemical characterization of NS5A has been performed, with most research to date involving the myriad of host proteins and signaling cascades that interact with NS5A. The need for better characterization of NS5A is paramount for elucidating the role of this protein in the virus life cycle. Examination of NS5A using bioinformatics tools suggested the protein consisted of three domains and contained an unconventional zinc binding motif within the N-terminal domain. We have developed a method to produce NS5A and performed limited proteolysis to confirm the domain organization model. The zinc content of purified NS5A and the N-terminal domain of NS5A was determined, and each of these proteins was found to coordinate one zinc atom per protein. The predicted zinc binding motif consists of four cysteine residues, conserved among the Hepacivirus and Pestivirus genera, fitting the formula of CX17CXCX20C. Mutation of any of the four cysteine components of this motif reduced NS5A zinc coordination and led to a lethal phenotype for HCV RNA replication, whereas mutation of other potential metal coordination residues in the N-terminal domain of NS5A, but outside the zinc binding motif, had little effect on zinc binding and, aside from one exception, were tolerated for replication. Collectively, these results indicate that NS5A is a zinc metalloprotein and that zinc coordination is likely required for NS5A function in the hepatitis C replicase.

  16. Daclatasvir inhibits hepatitis C virus NS5A motility and hyper-accumulation of phosphoinositides

    PubMed Central

    Chukkapalli, Vineela; Berger, Kristi L.; Kelly, Sean M.; Thomas, Meryl; Deiters, Alexander; Randall, Glenn

    2014-01-01

    Combinations of direct-acting antivirals (DAAs) against the hepatitis C virus (HCV) have the potential to revolutionize the HCV therapeutic regime. An integral component of DAA combination therapies are HCV NS5A inhibitors. It has previously been proposed that NS5A DAAs inhibit two functions of NS5A: RNA replication and virion assembly. In this study, we characterize the impact of a prototype NS5A DAA, daclatasvir (DCV), on HCV replication compartment formation. DCV impaired HCV replicase localization and NS5A motility. In order to characterize the mechanism behind altered HCV replicase localization, we examined the impact of DCV on the interaction of NS5A with its essential cellular cofactor, phosphatidylinositol-4-kinase III α (PI4KA). We observed that DCV does not inhibit PI4KA directly, nor does it impair early events of the NS5A-PI4KA interaction that can occur when NS5A is expressed alone. NS5A functions that are unaffected by DCV include PI4KA binding, as determined by co-immunoprecipitation, and a basal accumulation of the PI4KA product, PI4P. However, DCV impairs late steps in PI4KA activation that requires NS5A expressed in the context of the HCV polyprotein. These NS5A functions include hyper-stimulation of PI4P levels and appropriate replication compartment formation. The data are most consistent with a model wherein DCV inhibits conformational changes in the NS5A protein or protein complex formations that occur in the context of HCV polyprotein expression and stimulate PI4P hyper-accumulation and replication compartment formation. PMID:25546252

  17. Multifunctional adaptive NS1 mutations are selected upon human influenza virus evolution in the mouse.

    PubMed

    Forbes, Nicole E; Ping, Jihui; Dankar, Samar K; Jia, Jian-Jun; Selman, Mohammed; Keleta, Liya; Zhou, Yan; Brown, Earl G

    2012-01-01

    The role of the NS1 protein in modulating influenza A virulence and host range was assessed by adapting A/Hong Kong/1/1968 (H3N2) (HK-wt) to increased virulence in the mouse. Sequencing the NS genome segment of mouse-adapted variants revealed 11 mutations in the NS1 gene and 4 in the overlapping NEP gene. Using the HK-wt virus and reverse genetics to incorporate mutant NS gene segments, we demonstrated that all NS1 mutations were adaptive and enhanced virus replication (up to 100 fold) in mouse cells and/or lungs. All but one NS1 mutant was associated with increased virulence measured by survival and weight loss in the mouse. Ten of twelve NS1 mutants significantly enhanced IFN-β antagonism to reduce the level of IFN β production relative to HK-wt in infected mouse lungs at 1 day post infection, where 9 mutants induced viral yields in the lung that were equivalent to or significantly greater than HK-wt (up to 16 fold increase). Eight of 12 NS1 mutants had reduced or lost the ability to bind the 30 kDa cleavage and polyadenylation specificity factor (CPSF30) thus demonstrating a lack of correlation with reduced IFN β production. Mutant NS1 genes resulted in increased viral mRNA transcription (10 of 12 mutants), and protein production (6 of 12 mutants) in mouse cells. Increased transcription activity was demonstrated in the influenza mini-genome assay for 7 of 11 NS1 mutants. Although we have shown gain-of-function properties for all mutant NS genes, the contribution of the NEP mutations to phenotypic changes remains to be assessed. This study demonstrates that NS1 is a multifunctional virulence factor subject to adaptive evolution.

  18. H-NS Facilitates Sequence Diversification of Horizontally Transferred DNAs during Their Integration in Host Chromosomes

    PubMed Central

    Higashi, Koichi; Tobe, Toru; Kanai, Akinori; Uyar, Ebru; Ishikawa, Shu; Suzuki, Yutaka; Ogasawara, Naotake; Kurokawa, Ken; Oshima, Taku

    2016-01-01

    Bacteria can acquire new traits through horizontal gene transfer. Inappropriate expression of transferred genes, however, can disrupt the physiology of the host bacteria. To reduce this risk, Escherichia coli expresses the nucleoid-associated protein, H-NS, which preferentially binds to horizontally transferred genes to control their expression. Once expression is optimized, the horizontally transferred genes may actually contribute to E. coli survival in new habitats. Therefore, we investigated whether and how H-NS contributes to this optimization process. A comparison of H-NS binding profiles on common chromosomal segments of three E. coli strains belonging to different phylogenetic groups indicated that the positions of H-NS-bound regions have been conserved in E. coli strains. The sequences of the H-NS-bound regions appear to have diverged more so than H-NS-unbound regions only when H-NS-bound regions are located upstream or in coding regions of genes. Because these regions generally contain regulatory elements for gene expression, sequence divergence in these regions may be associated with alteration of gene expression. Indeed, nucleotide substitutions in H-NS-bound regions of the ybdO promoter and coding regions have diversified the potential for H-NS-independent negative regulation among E. coli strains. The ybdO expression in these strains was still negatively regulated by H-NS, which reduced the effect of H-NS-independent regulation under normal growth conditions. Hence, we propose that, during E. coli evolution, the conservation of H-NS binding sites resulted in the diversification of the regulation of horizontally transferred genes, which may have facilitated E. coli adaptation to new ecological niches. PMID:26789284

  19. Short pulse, high power microwave radiation source with a laser-induced sheet plasma mirror

    SciTech Connect

    Higashiguchi, Takeshi; Yugami, Noboru

    2009-05-01

    We have demonstrated the short pulse, high power microwave radiation source using an ultraviolet laser-induced sheet plasma mirror in a gas-filled x-band rectangular waveguide from the conventional microwave sources and components. A laser-induced sheet plasma with an overdense plasma acts as a plasma mirror. The long pulse propagating in the gas-filled waveguide was sliced by the sheet plasma mirror at two different points along the waveguide. We observed about twice the power of the pulse by adding the two sliced microwave pulses produced by this scheme. A maximum peak power of 200 kW with a pulse duration of 10 ns (full width at half maximum) from the long microwave pulse source with a pulse duration of 0.8 mus was observed.

  20. High Energy, Short Pulse Fiber Injection Lasers at Lawrence Livermore National Laboratory

    SciTech Connect

    Dawson, J W; Messerly, M J; Phan, H H; Crane, J K; Beach, R J; Siders, C W; Barty, C J

    2008-09-10

    A short pulse fiber injection laser for the Advanced Radiographic Capability (ARC) on the National Ignition Facility (NIF) has been developed at Lawrence Livermore National Laboratory (LLNL). This system produces 100 {micro}J pulses with 5 nm of bandwidth centered at 1053 nm. The pulses are stretched to 2.5 ns and have been recompressed to sub-ps pulse widths. A key feature of the system is that the pre-pulse power contrast ratio exceeds 80 dB. The system can also precisely adjust the final recompressed pulse width and timing and has been designed for reliable, hands free operation. The key challenges in constructing this system were control of the signal to noise ratio, dispersion management and managing the impact of self phase modulation on the chirped pulse.

  1. Long pulse production from short pulses

    DOEpatents

    Toeppen, John S.

    1994-01-01

    A method of producing a long output pulse (SA) from a short pump pulse (P), using an elongated amplified fiber (11) having a doped core (12) that provides an amplifying medium for light of one color when driven into an excited state by light of a shorter wavelength and a surrounding cladding 13. A seed beam (S) of the longer wavelength is injected into the core (12) at one end of the fiber (11) and a pump pulse (P) of the shorter wavelength is injected into the cladding (13) at the other end of the fiber (11). The counter-propagating seed beam (S) and pump pulse (P) will produce an amplified output pulse (SA) having a time duration equal to twice the transit time of the pump pulse (P) through the fiber (11) plus the length of the pump pulse (P).

  2. Long pulse production from short pulses

    DOEpatents

    Toeppen, J.S.

    1994-08-02

    A method of producing a long output pulse from a short pump pulse is disclosed, using an elongated amplified fiber having a doped core that provides an amplifying medium for light of one color when driven into an excited state by light of a shorter wavelength and a surrounding cladding. A seed beam of the longer wavelength is injected into the core at one end of the fiber and a pump pulse of the shorter wavelength is injected into the cladding at the other end of the fiber. The counter-propagating seed beam and pump pulse will produce an amplified output pulse having a time duration equal to twice the transit time of the pump pulse through the fiber plus the length of the pump pulse. 3 figs.

  3. Study on the influence of laser pulse duration in the long nanosecond regime on the laser induced plasma spectroscopy

    NASA Astrophysics Data System (ADS)

    Elnasharty, I. Y.

    2016-10-01

    By using a high power pulsed fiber laser, this study reports the experimental investigation of the laser-induced plasma characteristics for the laser pulse duration range extended from 40 ns to 200 ns. The experiments were performed with keeping the laser fluence constant at 64 J/cm2. The measurements show that, for the early phase of plasma formation, the spectral line intensities and the continuum emissions as well as the plasma characteristics decay to a certain extent with the increase of the pulse duration. On the other hand, as the plasma evolves in post laser pulse regime, the electron density and the degree of ionization increase slightly for the longer pulses, while the plume temperature is more or less independent from the pulse duration. Furthermore, the ablation characteristics, such as the ablation rate, coincide with the results of plasma characteristics for the different pulse durations. Eventually, with keeping the laser fluence constant at 64 J/cm2, the analytical performance of Laser-Induced Plasma Spectroscopy (LIPS) for the corresponding pulse duration range is examined by using a temporal gating and non-gating analyses. The measurements show that, in the case of gating analysis, all pulse durations yield almost the same range of limits of detections LODs. On the other hand, for non-gating analysis, the longer pulse durations provide lower LODs (better) than the shorter ones by orders of magnitude. Moreover, the calculated absolute limit of detection (LODAbs) for the longest pulse duration (i.e. 200 ns) is lower by approximately factor 2 than that of the shortest one (i.e. 40 ns).

  4. A Hepatitis C Virus NS5A Phosphorylation Site That Regulates RNA Replication

    PubMed Central

    LeMay, K. L.; Treadaway, J.; Angulo, I.

    2013-01-01

    The hepatitis C virus NS5A protein is essential for RNA replication and virion assembly. NS5A is phosphorylated on multiple residues during infections, but these sites remain uncharacterized. Here we identify serine 222 of genotype 2a NS5A as a phosphorylation site that functions as a negative regulator of RNA replication. This site is a component of the hyperphosphorylated form of NS5A, which is in good agreement with previous observations that hyperphosphorylation negatively affects replication. PMID:23115292

  5. Laser photoionization of triacetone triperoxide (TATP) by femtosecond and nanosecond laser pulses

    NASA Astrophysics Data System (ADS)

    Mullen, Christopher; Huestis, David; Coggiola, Michael; Oser, Harald

    2006-05-01

    Laser ionization time-of-flight mass spectrometry has been applied to the study of triacetone triperoxide (TATP), an improvised explosive. Wavelength dependent mass spectra in two time regimes were acquired using nanosecond (5 ns) and femtosecond (130 fs) laser pulses. We find the major difference between the two time regimes to be the detection of the parent molecular ion when femtosecond laser pulses are employed.

  6. A long-pulse repetitive operation magnetically insulated transmission line oscillator

    SciTech Connect

    Fan, Yu-Wei; Zhong, Hui-Huang; Zhang, Jian-De; Shu, Ting; Liu, Jin Liang

    2014-05-15

    The improved magnetically insulated transmission line oscillator (MILO) is a gigawatt-class L-band high power microwave tube. It has allowed us to generate 3.1 GW pulse of 40 ns duration in the single-pulse operation and 500 MW pulse of 25 ns duration in the repetition rate operation. However, because of the severe impedance mismatch, the power conversion efficiency is only about 4% in the repetition rate operation. In order to eliminate the impedance mismatch and obtain repetitive long-pulse high-power microwave (HPM), a series of experiments are carried out and the recent progress is presented in this paper. In the single-pulse operation, when the diode voltage is 466 kV and current is 41.6 kA, the radiated microwave power is above 2.2 GW, the pulse duration is above 102 ns, the microwave frequency is about 1.74 GHz, and the power conversion efficiency is about 11.5%. In the repetition rate operation, under the condition of the diode voltage about 400 kV, beam current about 38 kA, the radiated microwave power is about 1.0 GW, the pulse duration is about 85 ns. Moreover, the radiated microwave power and the pulse duration decline little by little when the shot numbers increase gradually. The experimental results show that the impedance matching is a vital factor for HPM systems and one of the major technical challenges is to improve the cathode for the repetition rate operation MILO.

  7. A long-pulse repetitive operation magnetically insulated transmission line oscillator.

    PubMed

    Fan, Yu-Wei; Zhong, Hui-Huang; Zhang, Jian-De; Shu, Ting; Liu, Jin Liang

    2014-05-01

    The improved magnetically insulated transmission line oscillator (MILO) is a gigawatt-class L-band high power microwave tube. It has allowed us to generate 3.1 GW pulse of 40 ns duration in the single-pulse operation and 500 MW pulse of 25 ns duration in the repetition rate operation. However, because of the severe impedance mismatch, the power conversion efficiency is only about 4% in the repetition rate operation. In order to eliminate the impedance mismatch and obtain repetitive long-pulse high-power microwave (HPM), a series of experiments are carried out and the recent progress is presented in this paper. In the single-pulse operation, when the diode voltage is 466 kV and current is 41.6 kA, the radiated microwave power is above 2.2 GW, the pulse duration is above 102 ns, the microwave frequency is about 1.74 GHz, and the power conversion efficiency is about 11.5%. In the repetition rate operation, under the condition of the diode voltage about 400 kV, beam current about 38 kA, the radiated microwave power is about 1.0 GW, the pulse duration is about 85 ns. Moreover, the radiated microwave power and the pulse duration decline little by little when the shot numbers increase gradually. The experimental results show that the impedance matching is a vital factor for HPM systems and one of the major technical challenges is to improve the cathode for the repetition rate operation MILO.

  8. 188 W nanosecond pulsed fiber amplifier at 1064 nm

    NASA Astrophysics Data System (ADS)

    Li, Zebiao; Guo, Chao; Li, Qi; Zhao, Pengfei; Li, Chengyu; Huang, Zhihua; Tang, Xuan; Lin, Honghuan; Xu, Shanhui; Yang, Zhongmin; Wang, Jianjun; Jing, Feng

    2016-07-01

    We report an all-fiber high power nanosecond pulsed laser at a center wavelength of 1064 nm. Optimizing the coiling diameter of the active fiber, 188 W average power is achieved at a repetition rate of 40 kHz. The pulse width is measured as 101 ns, while the peak power can be estimated to 46.5 kW.

  9. Improvement of deoxidization efficiency of nitric monoxide by shortening pulse width of semiconductor opening switch pulse power generator

    NASA Astrophysics Data System (ADS)

    Kakuta, Takatoshi; Yagi, Ippei; Takaki, Koichi

    2015-01-01

    The deoxidization efficiency of nitric monoxide (NO) was improved by shortening the pulse width of the voltage applied to a corona reactor. The deoxidization efficiency of NO was evaluated as the NO removal efficiency in nitrogen (N2) gas containing 200 ppm NO. The corona reactor had a coaxial geometry and consisted of center high-voltage wire and outer grounded cylinder electrodes. A nanosecond high-voltage pulse was generated using an inductive energy storage pulse power circuit with a semiconductor opening switch and was applied to the center wire electrode in the corona reactor. Fast recovery diodes were utilized as a semiconductor opening switch. The pulse width of the applied voltage was reduced from 21 to 14 ns with the arrester connected in parallel to the reactor. The energy efficiency for NO removal was improved from 8.2 to 35.7 g kW-1 h-1 with the arrester connected. The pulse width was also reduced to 8 ns by optimizing the circuit parameters. It was confirmed from observation with an intensified charge-coupled device (ICCD) camera that the streamer corona discharge transited to a glowlike discharge after the streamer propagated from the center wire electrode to the outer cylinder electrode. The duration of the glowlike phase was reduced with the arrester connected. The energy consumed in the glowlike phase was also reduced from 15.7 to 4.6 mJ with the arrester connected.

  10. A compact, low jitter, nanosecond rise time, high voltage pulse generator with variable amplitude.

    PubMed

    Mao, Jiubing; Wang, Xin; Tang, Dan; Lv, Huayi; Li, Chengxin; Shao, Yanhua; Qin, Lan

    2012-07-01

    In this paper, a compact, low jitter, nanosecond rise time, command triggered, high peak power, gas-switch pulse generator system is developed for high energy physics experiment. The main components of the system are a high voltage capacitor, the spark gap switch and R = 50 Ω load resistance built into a structure to obtain a fast high power pulse. The pulse drive unit, comprised of a vacuum planar triode and a stack of avalanche transistors, is command triggered by a single or multiple TTL (transistor-transistor logic) level pulses generated by a trigger pulse control unit implemented using the 555 timer circuit. The control unit also accepts user input TTL trigger signal. The vacuum planar triode in the pulse driving unit that close the first stage switches is applied to drive the spark gap reducing jitter. By adjusting the charge voltage of a high voltage capacitor charging power supply, the pulse amplitude varies from 5 kV to 10 kV, with a rise time of <3 ns and the maximum peak current up to 200 A (into 50 Ω). The jitter of the pulse generator system is less than 1 ns. The maximum pulse repetition rate is set at 10 Hz that limited only by the gas-switch and available capacitor recovery time.

  11. A compact, low jitter, nanosecond rise time, high voltage pulse generator with variable amplitude

    NASA Astrophysics Data System (ADS)

    Mao, Jiubing; Wang, Xin; Tang, Dan; Lv, Huayi; Li, Chengxin; Shao, Yanhua; Qin, Lan

    2012-07-01

    In this paper, a compact, low jitter, nanosecond rise time, command triggered, high peak power, gas-switch pulse generator system is developed for high energy physics experiment. The main components of the system are a high voltage capacitor, the spark gap switch and R = 50 Ω load resistance built into a structure to obtain a fast high power pulse. The pulse drive unit, comprised of a vacuum planar triode and a stack of avalanche transistors, is command triggered by a single or multiple TTL (transistor-transistor logic) level pulses generated by a trigger pulse control unit implemented using the 555 timer circuit. The control unit also accepts user input TTL trigger signal. The vacuum planar triode in the pulse driving unit that close the first stage switches is applied to drive the spark gap reducing jitter. By adjusting the charge voltage of a high voltage capacitor charging power supply, the pulse amplitude varies from 5 kV to 10 kV, with a rise time of <3 ns and the maximum peak current up to 200 A (into 50 Ω). The jitter of the pulse generator system is less than 1 ns. The maximum pulse repetition rate is set at 10 Hz that limited only by the gas-switch and available capacitor recovery time.

  12. A compact, low jitter, nanosecond rise time, high voltage pulse generator with variable amplitude.

    PubMed

    Mao, Jiubing; Wang, Xin; Tang, Dan; Lv, Huayi; Li, Chengxin; Shao, Yanhua; Qin, Lan

    2012-07-01

    In this paper, a compact, low jitter, nanosecond rise time, command triggered, high peak power, gas-switch pulse generator system is developed for high energy physics experiment. The main components of the system are a high voltage capacitor, the spark gap switch and R = 50 Ω load resistance built into a structure to obtain a fast high power pulse. The pulse drive unit, comprised of a vacuum planar triode and a stack of avalanche transistors, is command triggered by a single or multiple TTL (transistor-transistor logic) level pulses generated by a trigger pulse control unit implemented using the 555 timer circuit. The control unit also accepts user input TTL trigger signal. The vacuum planar triode in the pulse driving unit that close the first stage switches is applied to drive the spark gap reducing jitter. By adjusting the charge voltage of a high voltage capacitor charging power supply, the pulse amplitude varies from 5 kV to 10 kV, with a rise time of <3 ns and the maximum peak current up to 200 A (into 50 Ω). The jitter of the pulse generator system is less than 1 ns. The maximum pulse repetition rate is set at 10 Hz that limited only by the gas-switch and available capacitor recovery time. PMID:22852729

  13. Plasma-focus-based tabletop hard x-ray source for 50 ns resolution introspective imaging of metallic objects through metallic walls

    SciTech Connect

    Moreno, C.; Raspa, V.; Sigaut, L.; Vieytes, R.; Clausse, A.

    2006-08-28

    A tabletop 4.7 kJ, 30 kV plasma focus device was used as a pulsed hard x-ray source for fast radiography (50 ns exposure time) of metallic pieces even through several millimeter thick metallic walls. An experimental estimation of the effective average energy of the x-ray beam (found to be around 100 keV) and a numerical estimation of the induced voltage on the focus during the compressional stage of a plasma focus are briefly discussed.

  14. Activation of autophagy in response to nanosecond pulsed electric field exposure.

    PubMed

    Ullery, Jody C; Tarango, Melissa; Roth, Caleb C; Ibey, Bennett L

    2015-03-01

    Previous work demonstrated significant changes in cellular membranes following exposure of cells to nanosecond pulsed electric fields (nsPEF), including nanoporation and increases in intracellular calcium concentration. While it is known that nsPEF exposure can cause cell death, how cells repair and survive nsPEF-induced cellular damage is not well understood. In this paper, we investigated whether autophagy is stimulated following nsPEF exposure to repair damaged membranes, proteins, and/or organelles in a pro-survival response. We hypothesized that autophagy is activated to repair nsPEF-induced plasma membrane damage and overwhelming this compensatory mechanism results in cell death. Activation of autophagy and subsequent cell death pathways were assessed measuring toxicity, gene and protein expression of autophagy markers, and by monitoring autophagosome formation and maturation using fluorescent microscopy. Results show that autophagy is activated at subtoxic nsPEF doses, as a compensatory mechanism to repair membrane damage. However, prolonged exposure results in increased cell death and a concomitant decrease in autophagic markers. These results suggest that cells take an active role in membrane repair, through autophagy, following exposure to nsPEF. PMID:25660455

  15. Silver-lined proportional counter for detection of pulsed neutrons

    NASA Astrophysics Data System (ADS)

    Dighe, P. M.; Prasad, K. R.; Kataria, S. K.

    2004-05-01

    A silver-lined proportional counter is developed for pulsed neutron monitoring near the electron accelerator INDUS-I at CAT, Indore. The device was developed since neutron flux meters with boron counters showed poor response to pulsed neutron background. The detector has 110 mm length and its inner diameter (26 mm) is lined with silver foil of 0.025 cm thickness. Tests in a thermal neutron flux of 150 nv show that it has 0.2 cps/nv neutron sensitivity. Tests at Plasma Focus Device facility with single neutron pulse (pulse width 50 ns) showed that the counter has 1.2×10 6 neutron/pulse counts sensitivity. Tests at INDUS-I electron accelerator facility in multiple neutron pulses (pulse width 1 μs and 1 Hz repetition rate) showed that the neutron flux estimated by the counter is comparable to the flux measured by passive CR-39 foils. The counter has potential application to detect neutron pulses of high intensity that occur within the shielded areas of electron accelerators during partial or total beam loss.

  16. Pulsed lasers in dentistry: sense or nonsense?

    NASA Astrophysics Data System (ADS)

    Koort, Hans J.; Frentzen, Matthias

    1991-05-01

    The great interest in the field of laser applications in dentistry provokes the question, if all these new techniques may really fulfill advantages, which are expected after initial in-vitro studies. Whereas laser surgery of soft oral tissues has been developed to a standard method, laser treatment of dental hard tissues and the bone are attended with many unsolved problems. Different laser types, especially pulsed lasers in a wide spectrum of wavelengths have been proofed for dental use. Today neither the excimer lasers, emitting in the far uv-range from 193 to 351 nm, nor the mid-infrared lasers like Nd:YAG (1,064 μm), Ho:YAG (2,1 μm) and Er:YAG (2,96 μm) or the C02-laser (10,6 μm) show mechanism of interaction more carefully and faster than a preparation of teeth with diamond drillers. The laser type with the most precise and considerate treatment effects in the moment is the short pulsed (15 ns) ArF-excimer laser with a wavelength of 193 nm. However this laser type has not yet the effectivity of mechanical instruments and it needs a mirror system to deliver the radiation. Histological results point out, that this laser shows no significant pathological alterations in the adjacent tissues. Another interesting excimer laser, filled with XeCI and emitting at a wavelength of 308 nm has the advantage to be good to deliver through quartz fibers. A little more thermal influence is to be seen according to the longer wavelength. Yet the energy density, necessary to cut dental hard tissues will not be reached with the laser systems available now. Both the pulsed Er:YAG- (2,94 μm, pulse duration 250 s) and the Ho:YAG -laser (2,1 μm, pulse duration 250 μs) have an effective coupling of the laser energy to hydrogeneous tissues, but they do not work sufficient on healthy enamel and dentine. The influence to adjacent healthy tissue is not tolerable, especially in regard of the thermal damage dentine and pulp tissues. Moreover, like the 193 nm ArF-excimer laser

  17. Development and clinical evaluation of a highly accurate dengue NS1 rapid test: from the preparation of a soluble NS1 antigen to the construction of an RDT.

    PubMed

    Lee, Jihoo; Kim, Hak-Yong; Chong, Chom-Kyu; Song, Hyun-Ok

    2015-06-01

    Early diagnosis of dengue virus (DENV) is important. There are numerous products on the market claiming to detect DENV NS1, but these are not always reliable. In this study, a highly sensitive and accurate rapid diagnostic test (RDT) was developed using anti-dengue NS1 monoclonal antibodies. A recombinant NS1 protein was produced with high antigenicity and purity. Monoclonal antibodies were raised against this purified NS1 antigen. The RDT was constructed using a capturing (4A6A10, Kd=7.512±0.419×10(-9)) and a conjugating antibody (3E12E6, Kd=7.032±0.322×10(-9)). The diagnostic performance was evaluated with NS1-positive clinical samples collected from various dengue endemic countries and compared to SD BioLine Dengue NS1 Ag kit. The constructed RDT exhibited higher sensitivity (92.9%) with more obvious diagnostic performance than the commercial kit (83.3%). The specificity of constructed RDT was 100%. The constructed RDT could offer a reliable point-of-care testing tool for the early detection of dengue infections in remote areas and contribute to the control of dengue-related diseases. PMID:25824725

  18. Development and clinical evaluation of a highly accurate dengue NS1 rapid test: from the preparation of a soluble NS1 antigen to the construction of an RDT.

    PubMed

    Lee, Jihoo; Kim, Hak-Yong; Chong, Chom-Kyu; Song, Hyun-Ok

    2015-06-01

    Early diagnosis of dengue virus (DENV) is important. There are numerous products on the market claiming to detect DENV NS1, but these are not always reliable. In this study, a highly sensitive and accurate rapid diagnostic test (RDT) was developed using anti-dengue NS1 monoclonal antibodies. A recombinant NS1 protein was produced with high antigenicity and purity. Monoclonal antibodies were raised against this purified NS1 antigen. The RDT was constructed using a capturing (4A6A10, Kd=7.512±0.419×10(-9)) and a conjugating antibody (3E12E6, Kd=7.032±0.322×10(-9)). The diagnostic performance was evaluated with NS1-positive clinical samples collected from various dengue endemic countries and compared to SD BioLine Dengue NS1 Ag kit. The constructed RDT exhibited higher sensitivity (92.9%) with more obvious diagnostic performance than the commercial kit (83.3%). The specificity of constructed RDT was 100%. The constructed RDT could offer a reliable point-of-care testing tool for the early detection of dengue infections in remote areas and contribute to the control of dengue-related diseases.

  19. Antiviral activities of 15 dengue NS2B-NS3 protease inhibitors using a human cell-based viral quantification assay.

    PubMed

    Chu, Justin Jang Hann; Lee, Regina Ching Hua; Ang, Melgious Jin Yan; Wang, Wei-Ling; Lim, Huichang Annie; Wee, John Liang Kuan; Joy, Joma; Hill, Jeffrey; Brian Chia, C S

    2015-06-01

    The dengue virus is a mosquito-borne pathogen responsible for an estimated 50-100 million human dengue infections annually. There are currently no approved drugs against this disease, resulting in a major unmet clinical need. The dengue viral NS2B-NS3 protease has been identified as a plausible drug target due to its involvement in viral replication in mammalian host cells. In the past decade, at least 20 dengue NS2B-NS3 protease inhibitors have been reported in the literature with a range of inhibitory activities in protease assays. However, such assays do not shed light on an inhibitor's ability to penetrate human cell membranes where the viral protease resides. In this study, we investigated the antiviral activities of 15 small-molecule and peptide-based NS2B-NS3 inhibitors on dengue serotype 2-infected HuH-7 human hepatocarcinoma cells. Experimental results revealed anthraquinone ARDP0006 (compound 5) to be the most potent inhibitor which reduced dengue viral titer by more than 1 log PFU/mL at 1 μM in our cell-based assays involving HuH-7 and K562 cell lines, suggesting that its scaffold could serve as a lead for further medicinal chemistry studies. Compound 5 was also found to be non-cytotoxic at 1 μM over 3 days incubation on HuH-7 cells using the Alamar Blue cellular toxicity assay.

  20. Development of parallel incompressible NS solver on stretched grids

    NASA Astrophysics Data System (ADS)

    Jothiprasad, G.; Caughey, D.; Pope, S. B.

    2003-11-01

    Development of a parallel NS solver for studying DNS and LES of temporal mixing layers is discussed. The equations are cast in strong conservation form on a uniform computational mesh, transformed from a stretched mesh in the physical domain. Variables are defined on a collocated grid, and the transformed equations are solved using a fractional step method. Convective and dissipative terms are treated using explicit Adams-Bashforth and implicit Crank-Nicolson, respectively. Fourth order spatial accuracy is maintained except for hyperviscous subgrid model terms, which are only 2nd order accurate. The block LU analysis of J. B. Perot, extended to fractional step methods on collocated grids, shows that an O(Δ t^2) term involving the pressure gradient must be added to the momentum equations to maintain 2nd order accuracy in time. Using a smaller stencil for the pressure gradients largely simplifies the pressure Poisson equation while still ensuring that discrete continuity is satisfied to appropriate order. Implementation on distributed-memory multiprocessors is achieved using MPI, with care taken to minimize communication overhead.

  1. Comments on D-brane dynamics near NS5-branes

    NASA Astrophysics Data System (ADS)

    Sahakyan, David A.

    2004-10-01

    We study the properties of a D-brane in the presence of k NS5 branes. The Dirac-Born-Infeld action describing the dynamics of this D-brane is very similar to that of a non-BPS D-brane in ten dimensions. As the D-brane approaches the fivebranes, its equation of state approaches that of a pressureless fluid. In non-BPS D-brane case this is considered as an evidence for the decay of the D-brane into ``tachyon matter''. We show that in our case similar behavior is the consequence of the motion of the D-brane. In particular in the rest frame of the moving D-brane the equation of state is that of a usual D-brane, for which the pressure is equal to the energy density. We also compute the total cross-section for the decay of the D-brane into closed string modes and show that the emitted energy has a power like divergence for D0, D1 and D2 branes, while converges for higher dimensional D-branes. We also speculate on the possibility that the infalling D-brane describes a decaying defect in six dimensional Little String Theory.

  2. Dynamic effects and applications for nanosecond pulsed electric fields in cells and tissues

    NASA Astrophysics Data System (ADS)

    Beebe, Stephen J.; Blackmore, Peter F.; Hall, Emily; White, Jody A.; Willis, Lauren K.; Fauntleroy, Laura; Kolb, Juergen F.; Schoenbach, Karl H.

    2005-04-01

    Nanosecond, high intensity pulsed electric fields [nsPEFs] that are below the plasma membrane [PM] charging time constant have decreasing effects on the PM and increasing effects on intracellular structures and functions as the pulse duration decreases. When human cell suspensions were exposed to nsPEFs where the electric fields were sufficiently intense [10-300ns, <=300 kV/cm.], apoptosis signaling pathways could be activated in several cell models. Multiple apoptosis markers were observed in Jurkat, HL-60, 3T3L1-preadipocytes, and isolated rat adipocytes including decreased cell size and number, caspase activation, DNA fragmentation, and/or cytochrome c release into the cytoplasm. Phosphatidylserine externalization was observed as a biological response to nsPEFs in 3T3-L1 preadipocytes and p53-wildtype and -null human colon carcinoma cells. B10.2 mouse fibrosarcoma tumors that were exposed to nsPEFs ex vivo and in vivo exhibited DNA fragmentation, elevated caspase activity, and reduced size and weight compared to contralateral sham-treated control tumors. When nsPEF conditions were below thresholds for apoptosis and classical PM electroporation, non-apoptotic responses were observed similar to those initiated through PM purinergic receptors in HL-60 cells and thrombin in human platelets. These included Ca2+ mobilization from intracellular stores [endoplasmic reticulum] and subsequently through store-operated Ca2+ channels in the PM. In addition, platelet activation measured as aggregation responses were observed in human platelets. Finally, when nsPEF conditions followed classical electroporation-mediated transfection, the expression intensity and number of GFP-expressing cells were enhanced above cells exposed to electroporation conditions alone. These studies demonstrate that application of nsPEFs to cells or tissues can modulate cell-signaling mechanisms with possible applications as a new basic science tool, cancer treatment, wound healing, and gene therapy.

  3. A new panel of NS1 antibodies for easy detection and titration of influenza A virus.

    PubMed

    Tan, Zhihao; Akerstrom, Sara; Wee, Boon Yu; Lal, Sunil K; Mirazimi, Ali; Tan, Yee-Joo

    2010-03-01

    The non-structural protein NS1 of the influenza A virus is a good target for the development of diagnostic assays. In this study, three NS1 monoclonal antibodies (mAbs) were generated by using recombinant NS1 protein of H5N1 virus and found to bind both the native and denatured forms of NS1. Two of the mAbs, 6A4 and 2H6, bind NS1 of three different strains of influenza A virus, namely H1N1, H3N2, and H5N1. Epitope mapping revealed that residues 42-53 of H5N1 NS1 are essential for the interaction with both mAbs. Between the three strains, there is only one amino acid difference in this domain, which is consistent with the observed cross-reactivities. On the other hand, mAb 1G1 binds to residues 206-215 of H5N1 NS1 and does not bind NS1 of H1N1 or H3N2. Furthermore, all three mAbs detected NS1 proteins expressed in virus infected MDCK cells and indirect immunofluorescence staining with mAbs 6A4 and 2H6 provided an alternative method for viral titer determination. Quantifying the numbers of fluorescent foci units yielded viral titers for three different isolates of H5N1 virus that are highly comparable to that obtained by observing cytopathic effect induced by virus infection. Importantly, this alternative method yields results at 1 day post-infection while the conventional method using cytopathic effect yields results at 3 days post-infection. The results showed that this new panel of NS1 antibodies can detect NS1 protein expressed during viral infection and can be used for fast and easy titration of influenza A virus. J. Med. Virol. 82:467-475, 2010. (c) 2010 Wiley-Liss, Inc.

  4. Influence of pulse duration on the doping quality in laser chemical processing (LCP)—a simulative approach

    NASA Astrophysics Data System (ADS)

    Fell, Andreas; Granek, Filip

    2013-03-01

    The laser chemical processing (LCP) technique for the local doping of crystalline silicon solar cells is investigated. Here, a liquid jet containing a dopant source acts as a waveguide for pulsed laser light, which results in the melting and subsequent doping of the silicon surface. Typical LCP pulse durations are in the 15 ns range, giving satisfactory results for specific parameter settings. While great potential is assumed to exist, optimization of the pulse duration has until now not been deeply investigated, because it is hard to change this parameter in laser systems. Therefore, this paper accesses the influence of the pulse duration by a simulative approach. The model includes optics, thermodynamics, and melt dynamics induced by the liquid jet and dopant diffusion into the silicon melt. It is solved by coupling our existing finite differences Matlab-code LCPSim with the commercial fluid flow solver Ansys Fluent. Simulations of axial symmetric single pulses were performed for pulse durations ranging from 15 ns to 500 ns. Detailed results are given, which show that for longer pulse durations lateral heat conduction significantly homogenizes the inhomogeneous dopant distribution caused by the speckled intensity profile within the liquid jet cross section. The melt expulsion by the liquid jet is low enough that a sufficiently doped layer remains after full resolidification for all pulse durations. Last, temperature gradients are evaluated to give an indication on the amount of laser damage induced by thermal stress.

  5. Phase-locked MHz pulse selector for x-ray sources.

    PubMed

    Förster, Daniel F; Lindenau, Bernd; Leyendecker, Marko; Janssen, Franz; Winkler, Carsten; Schumann, Frank O; Kirschner, Jürgen; Holldack, Karsten; Föhlisch, Alexander

    2015-05-15

    Picosecond x-ray pulses are extracted with a phase-locked x-ray pulse selector at 1.25 MHz repetition rate from the pulse trains of the accelerator-driven multiuser x-ray source BESSY II preserving the peak brilliance at high pulse purity. The system consists of a specially designed in-vacuum chopper wheel rotating with ≈1  kHz angular frequency. The wheel is driven in an ultrahigh vacuum and is levitated on magnetic bearings being capable of withstanding high centrifugal forces. Pulses are picked by 1252 high-precision slits of 70 μm width on the outer rim of the wheel corresponding to a temporal opening window of the chopper of 70 ns. We demonstrate how the electronic phase stabilization of ±2  ns together with an arrival time jitter of the individual slits of the same order of magnitude allows us to pick short single bunch x-ray pulses out of a 200 ns ion clearing gap in a multibunch pulse train as emitted from a synchrotron facility at 1.25 MHz repetition rate with a pulse purity below the shot noise detection limit. The approach is applicable to any high-repetition pulsed radiation source, in particular in the x-ray spectral range up to 10 keV. The opening window in a real x-ray beamline, its stability, as well as the limits of mechanical pulse picking techniques in the MHz range are discussed. PMID:26393715

  6. High energy, single-polarized, single-transverse-mode, nanosecond pulses generated by a multi-stage Yb-doped photonic crystal fiber amplifier

    NASA Astrophysics Data System (ADS)

    Shen, Xinglai; Zhang, Haitao; Hao, He; Li, Dan; Li, Qinghua; Yan, Ping; Gong, Mali

    2015-06-01

    We report the construction of a cascaded fiber amplifier where a 40-μm-core-diameter photonic crystal fiber is utilized in the main amplifier stage. Single-transverse-mode, linearly-polarized, 7.5 ns pulses with 1.5 mJ energy, 123 kW peak power and 10 nm spectral bandwidth centered at 1062 nm are generated. To our knowledge, the pulse energy we obtain is the highest from 40-μm-core-diameter photonic crystal fibers, and also the highest for long pulses (>1 ns) with linear polarization and single transverse mode.

  7. Double-pulse laser-induced breakdown spectroscopy for trace element analysis in sintered iron oxide ceramics

    NASA Astrophysics Data System (ADS)

    Heilbrunner, H.; Huber, N.; Wolfmeir, H.; Arenholz, E.; Pedarnig, J. D.; Heitz, J.

    2012-01-01

    Double-pulse laser-induced breakdown spectroscopy (LIBS) is an emerging technique for accurate compositional analysis of many different materials. We present a systematic study of collinear double-pulse LIBS for analysis of the trace and side elements boron, manganese, copper, aluminum, titanium, silicon, chromium, nickel, potassium, and calcium in sintered iron oxide targets. The samples were ablated in air by single-pulse and double-pulse Nd:YAG laser radiation (6 ns pulse duration, laser wavelength of 532 nm) and spectra were recorded with an Echelle spectrometer equipped with an ICCD camera. We investigated the evolution of atomic and ionic line emission intensities for different interpulse delay times between the laser pulses (from 100 ns to 50 μs) and gate delays after the second laser pulse. We also varied the energy partition between the first and second laser pulse and the size of the irradiated spot at the sample surface. For the trace and side elements, we observed double-pulse LIBS signals that were enhanced as compared to single-pulse measurements depending on the interpulse delay time, the energy partition between the pulses, and the spot size. For the elements boron, copper, aluminum, titanium, chromium, potassium, and calcium limits of detection below 10 ppm were achieved.

  8. Chirped-pulse amplification with narrowband pulses.

    PubMed

    Shverdin, M Y; Albert, F; Anderson, S G; Betts, S M; Gibson, D J; Messerly, M J; Hartemann, F V; Siders, C W; Barty, C P J

    2010-07-15

    We demonstrate a compact hyperdispersion stretcher and compressor pair that permit chirped-pulse amplification in Nd:YAG. We generate 750 mJ, 0.2 nm FWHM, 10 Hz pulses recompressed to an 8 ps near-transform-limited duration. The dispersion-matched pulse compressor and stretcher impart a chirp of 7300 ps/nm, in a 3 m x 1 m footprint.

  9. Chirped-pulse amplification with narrowband pulses.

    PubMed

    Shverdin, M Y; Albert, F; Anderson, S G; Betts, S M; Gibson, D J; Messerly, M J; Hartemann, F V; Siders, C W; Barty, C P J

    2010-07-15

    We demonstrate a compact hyperdispersion stretcher and compressor pair that permit chirped-pulse amplification in Nd:YAG. We generate 750 mJ, 0.2 nm FWHM, 10 Hz pulses recompressed to an 8 ps near-transform-limited duration. The dispersion-matched pulse compressor and stretcher impart a chirp of 7300 ps/nm, in a 3 m x 1 m footprint. PMID:20634869

  10. High-efficiency and compact semiconductor lasers with monolithically integrated switches for generation of high-power nanosecond pulses in time-of-flight (TOF) systems

    NASA Astrophysics Data System (ADS)

    Slipchenko, Sergey; Podoskin, Aleksandr; Soboleva, Olga; Zakharov, Maxim S.; Bakhvalov, Kirill; Romanovich, Dmitrii; Pikhtin, Nikita; Tarasov, Il`ya; Bagaev, Timur; Ladugin, Maxim; Marmalyuk, Aleksandr; Simakov, Vladimir

    2016-03-01

    We present a new approach based on the integration of the functions of a high-efficiency current switch and a laser emitter into a single heterostructure as elements of time-of-flight (TOF) systems. The approach being developed employs the effect of an electrical bistability, which occurs in the general case in thyristor structures. We report recent results obtained in a study of the dynamic electrical and optical characteristics of the pulsed sources we developed. An effective generation of 2- to 100-ns laser pulses at a wavelength of 905 nm is demonstrated. The possibility of generating laser pulses shorter than 1 ns is considered. The maximum peak power reached values of 7 and 50 W for 10- and 100-ns pulses, respectively.

  11. Experimental evidence and molecular modeling of the interaction between hRSV-NS1 and quercetin.

    PubMed

    Gomes, Deriane Elias; Caruso, Ícaro Putinhon; de Araujo, Gabriela Campos; de Lourenço, Isabella Otenio; de Melo, Fernando Alves; Cornélio, Marinônio Lopes; Fossey, Marcelo Andrés; de Souza, Fátima Pereira

    2016-04-01

    Human Respiratory Syncytial Virus is one of the major causes of acute respiratory infections in children, causing bronchiolitis and pneumonia. Non-Structural Protein 1 (NS1) is involved in immune system evasion, a process that contributes to the success of hRSV replication. This protein can act by inhibiting or neutralizing several steps of interferon pathway, as well as by silencing the hRSV ribonucleoproteic complex. There is evidence that quercetin can reduce the infection and/or replication of several viruses, including RSV. The aims of this study include the expression and purification of the NS1 protein besides experimental and computational assays of the NS1-quercetin interaction. CD analysis showed that NS1 secondary structure composition is 30% alpha-helix, 21% beta-sheet, 23% turn and 26% random coils. The melting temperature obtained through DSC analysis was around 56°C. FRET analysis showed a distance of approximately 19Å between the NS1 and quercetin. Fluorescence titration results showed that the dissociation constant of the NS1-quercetin interaction was around 10(-6)M. In thermodynamic analysis, the enthalpy and entropy balanced forces indicated that the NS1-quercetin interaction presented both hydrophobic and electrostatic contributions. The computational results from the molecular modeling for NS1 structure and molecular docking regarding its interaction with quercetin corroborate the experimental data.

  12. Identification and characterization of coumestans as novel HCV NS5B polymerase inhibitors

    PubMed Central

    Kaushik-Basu, Neerja; Bopda-Waffo, Alain; Talele, Tanaji T.; Basu, Amartya; Costa, Paulo R. R.; da Silva, Alcides J. M.; Sarafianos, Stefan G.; Noël, François

    2008-01-01

    The hepatitis C virus (HCV) NS5B is essential for viral RNA replication and is therefore a prime target for development of HCV replication inhibitors. Here, we report the identification of a new class of HCV NS5B inhibitors belonging to the coumestan family of phytoestrogens. Based on the in vitro NS5B RNA-dependent RNA polymerase (RdRp) inhibition in the low micromolar range by wedelolactone, a naturally occurring coumestan, we evaluated the anti-NS5B activity of four synthetic coumestan analogues bearing different patterns of substitutions in their A and D rings, and observed a good structure-activity correlation. Kinetic characterization of coumestans revealed a noncompetitive mode of inhibition with respect to nucleoside triphosphate (rNTP) substrate and a mixed mode of inhibition towards the nucleic acid template, with a major competitive component. The modified order of addition experiments with coumestans and nucleic acid substrates affected the potencies of the coumestan inhibitors. Coumestan interference at the step of NS5B–RNA binary complex formation was confirmed by cross-linking experiments. Molecular docking of coumestans within the allosteric site of NS5B yielded significant correlation between their calculated binding energies and IC50 values. Coumestans thus add to the diversifying pool of anti-NS5B agents and provide a novel scaffold for structural refinement and development of potent NS5B inhibitors. PMID:18203743

  13. Canine parvovirus NS1 protein exhibits anti-tumor activity in a mouse mammary tumor model.

    PubMed

    Gupta, Shishir Kumar; Yadav, Pavan Kumar; Gandham, Ravi Kumar; Sahoo, A P; Harish, D R; Singh, Arvind Kumar; Tiwari, A K

    2016-02-01

    Many viral proteins have the ability to kill tumor cells specifically without harming the normal cells. These proteins, on ectopic expression, cause lysis or induction of apoptosis in the target tumor cells. Parvovirus NS1 is one of such proteins, which is known to kill high proliferating tumor cells. In the present study, we assessed the apoptosis inducing ability of canine parvovirus type 2 NS1 protein (CPV2.NS1) in vitro in 4T1 cells, and found it to cause significant cell death due to induction of apoptosis through intrinsic or mitochondrial pathway. Further, we also evaluated the oncolytic activity of CPV2.NS1 protein in a mouse mammary tumor model. The results suggested that CPV2.NS1 was able to inhibit the growth of 4T1 induced mouse mammary tumor as indicated by significantly reduced tumor volume, mitotic, AgNOR and PCNA indices. Further, inhibition of tumor growth was found to be because of induction of apoptosis in the tumor cells, which was evident by a significant increase in the number of TUNEL positive cells. Further, CPV2.NS1 was also able to stimulate the immune cells against the tumor antigens as indicated by the increased CD4+ and CD8+ counts in the blood of CVP2.NS1 treated mice. Further optimization of the delivery of NS1 protein and use of an adjuvant may further enhance its anti-tumor activity.

  14. NS1-mediated delay of type I interferon induction contributes to influenza A virulence in ferrets.

    PubMed

    Meunier, Isabelle; von Messling, Veronika

    2011-07-01

    Interference of the influenza A virus non-structural protein NS1 with type I interferon (IFN) signalling has been characterized extensively in vitro. To assess the contribution of NS1 to the virulence of a specific strain, we generated recombinant USSR/90/77 viruses bearing the NS1 proteins of the attenuated strain PR/8/34 or the highly pathogenic strain 1918 'Spanish flu', all belonging to the H1N1 subtype. In vitro, the extent of interference with type I IFN production exerted by the different NS1 proteins correlated with the reported virulence of the respective strain. Infection of ferrets with the recombinant viruses revealed that the presence of the 1918 NS1 resulted in a slightly more severe disease with generally higher clinical scores and increased lung pathology. Analysis of mRNA from nasal wash cells revealed that viruses carrying the 1918 and, to a lesser extent, USSR/90/77 NS1 proteins caused a delay in upregulation of type I IFNs compared with the NS1 PR/8/34-expressing virus, demonstrating the importance of NS1 for early host-response control and virulence.

  15. Influenza virus non-structural protein NS1: interferon antagonism and beyond.

    PubMed

    Marc, Daniel

    2014-12-01

    Most viruses express one or several proteins that counter the antiviral defences of the host cell. This is the task of non-structural protein NS1 in influenza viruses. Absent in the viral particle, but highly expressed in the infected cell, NS1 dramatically inhibits cellular gene expression and prevents the activation of key players in the IFN system. In addition, NS1 selectively enhances the translation of viral mRNAs and may regulate the synthesis of viral RNAs. Our knowledge of the virus and of NS1 has increased dramatically during the last 15 years. The atomic structure of NS1 has been determined, many cellular partners have been identified and its multiple activities have been studied in depth. This review presents our current knowledge, and attempts to establish relationships between the RNA sequence, the structure of the protein, its ligands, its activities and the pathogenicity of the virus. A better understanding of NS1 could help in elaborating novel antiviral strategies, based on either live vaccines with altered NS1 or on small-compound inhibitors of NS1.

  16. A Second RNA-Binding Site in the NS1 Protein of Influenza B Virus.

    PubMed

    Ma, Li-Chung; Guan, Rongjin; Hamilton, Keith; Aramini, James M; Mao, Lei; Wang, Shanshan; Krug, Robert M; Montelione, Gaetano T

    2016-09-01

    Influenza viruses cause a highly contagious respiratory disease in humans. The NS1 proteins of influenza A and B viruses (NS1A and NS1B proteins, respectively) are composed of two domains, a dimeric N-terminal domain and a C-terminal domain, connected by a flexible polypeptide linker. Here we report the 2.0-Å X-ray crystal structure and nuclear magnetic resonance studies of the NS1B C-terminal domain, which reveal a novel and unexpected basic RNA-binding site that is not present in the NS1A protein. We demonstrate that single-site alanine replacements of basic residues in this site lead to reduced RNA-binding activity, and that recombinant influenza B viruses expressing these mutant NS1B proteins are severely attenuated in replication. This novel RNA-binding site of NS1B is required for optimal influenza B virus replication. Most importantly, this study reveals an unexpected RNA-binding function in the C-terminal domain of NS1B, a novel function that distinguishes influenza B viruses from influenza A viruses.

  17. A Second RNA-Binding Site in the NS1 Protein of Influenza B Virus.

    PubMed

    Ma, Li-Chung; Guan, Rongjin; Hamilton, Keith; Aramini, James M; Mao, Lei; Wang, Shanshan; Krug, Robert M; Montelione, Gaetano T

    2016-09-01

    Influenza viruses cause a highly contagious respiratory disease in humans. The NS1 proteins of influenza A and B viruses (NS1A and NS1B proteins, respectively) are composed of two domains, a dimeric N-terminal domain and a C-terminal domain, connected by a flexible polypeptide linker. Here we report the 2.0-Å X-ray crystal structure and nuclear magnetic resonance studies of the NS1B C-terminal domain, which reveal a novel and unexpected basic RNA-binding site that is not present in the NS1A protein. We demonstrate that single-site alanine replacements of basic residues in this site lead to reduced RNA-binding activity, and that recombinant influenza B viruses expressing these mutant NS1B proteins are severely attenuated in replication. This novel RNA-binding site of NS1B is required for optimal influenza B virus replication. Most importantly, this study reveals an unexpected RNA-binding function in the C-terminal domain of NS1B, a novel function that distinguishes influenza B viruses from influenza A viruses. PMID:27545620

  18. Reverting cholesterol auxotrophy of NS0 cells by altering epigenetic gene silencing.

    PubMed

    Seth, Gargi; Ozturk, Mustafa; Hu, Wei-Shou

    2006-03-01

    NS0 is a cholesterol-requiring mouse myeloma cell line widely used in the production of recombinant antibodies. We have previously reported that the deficiency of 17beta-hydroxysteroid dehydrogenase type7 (Hsd17b7) is responsible for the cholesterol auxotrophy of NS0 cells. Here we demonstrate DNA methylation to be the mechanism underlying transcriptional suppression of Hsd17b7 in cholesterol dependent NS0 cells. Analysis of the DNA methylation pattern revealed methylation of the CpG-rich region upstream of the Hsd17b7 transcription start site in NS0 cells. This is in contrast to the unmethylated status of this sequence in a naturally isolated cholesterol independent revertant cell population (NS0_r). This transcriptional repression was relieved after treating cells with the demethylating drug, 5-azacytidine. Drug treatment also gave rise to high frequency cholesterol-independent variants. Characterization of revertants revealed substantially elevated transcript level of 17beta-hydroxysteroid dehydrogenase type7 (Hsd17b7) gene along with hypomethylation of the CpG-rich region. These results affirm that deficiency of Hsd17b7 causes cholesterol dependence of NS0 cells. Furthermore, induction of cholesterol independence by altering DNA methylation pattern alludes to the role of epigenetics in the metabolic adaptation of NS0 cells. With the widespread use of NS0 cells, this finding will have a significant impact on the optimization of recombinant antibody production processes. PMID:16189819

  19. Identification of an NTPase motif in classical swine fever virus NS4B protein

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Classical swine fever (CSF) is a highly contagious and often fatal disease of swine caused by CSF virus (CSFV), a positive sense single-stranded RNA virus in the genus Pestivirus of the Flaviviridae family. Here, we have identified, within CSFV non-structural (NS) protein NS4B, conserved sequence el...

  20. Mutations in the classical swine fever virus NS4B protein affects virulence in swine

    Technology Transfer Automated Retrieval System (TEKTRAN)

    NS4B is one of the non-structural proteins of Classical Swine Fever Virus (CSFV), the etiological agent of a severe, highly lethal disease of swine. Protein domain analysis of the predicted amino acid sequence of the NS4B protein of highly pathogenic CSFV strain Brescia (BICv) identified a Toll/Inte...