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Sample records for 2-10 ns pulse

  1. Photoswitches operating upon ns pulsed laser irradiation

    NASA Astrophysics Data System (ADS)

    Athanassiou, A.; Lakiotaki, K.; Kalyva, M.; Georgiou, S.; Fotakis, C.

    2005-07-01

    We present a potential photoswitch, which undergoes reversible mechanical actuation induced exclusively by photons. The photoswitch is a polymer-based film doped with spiropyran photochromic molecules. It undergoes repeatable mechanical cycles controlled by ns laser pulses of specific wavelengths. The polymer matrix is mechanically activated due to particular photoisomerization processes of the incorporated photochromic molecules, resulting in its contraction and lengthening in a highly controllable manner. We present herein the way that the switching time of this novel photoswitch depends on different laser parameters such as the energy and the repetition rate.

  2. Autonomous Magnetoexplosive Generator of Megavolt, 100 NS Pulses

    NASA Astrophysics Data System (ADS)

    Gurin, V. Ye.; Kataev, V. N.; Korolev, P. V.; Kargin, V. I.; Makartsev, G. F.; Nudikov, V. N.; Pikar, A. S.; Popkov, N. F.; Saratov, A. F.

    2004-11-01

    Here we present the results of the work carried out at different stages aimed at the development of autonomous magnetocumulative generators having 100 ns megavolt pulses. This generator is meant to replace the PIRIT-01 stationary facility by a magnetocumulative energy source. Using a generator with permanent magnets as a source of initial energy and multiplying this energy by a cascade of magnetoexplosive generators allows 100 kJ of energy accumulation in a contour. The generator that has a permanent magnet does not need an additional energy source for its operation. It is convenient to operate and is always available for service. Shortening the MC generator current pulse up to 1 μs is implemented using a high-voltage explosive driven opening switch. In the first sharpening cascade, the voltage increases up to 500 kV. Further shortening of the current pulse duration up to 100 ns and the voltage rise up to 1 MV are performed using plasma opening switches according to the two-stage formation scheme. Such a scheme allows the decrease of electric field strength on the insulator surface and the use of magnetic insulation in the high-voltage section of the facility.

  3. 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

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

    NASA Astrophysics Data System (ADS)

    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.

  5. 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%.

  6. 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. PMID:22274245

  7. 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.

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

    PubMed

    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

  9. 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

  10. 10 ns pulsed atmospheric air plasma for uniform treatment of polymeric surfaces

    SciTech Connect

    Walsh, J. L.; Kong, M. G.

    2007-12-17

    This letter reports an experimental study of a 10 ns pulsed dielectric barrier discharge in atmospheric air, excited with a train of 65 ns voltage pulses at a repetition frequency of 5 kHz. It is shown that these ultrashort pulses produce a homogenous discharge with very high electron density in excess of 10{sup 13} cm{sup -3} and low gas temperature, which are particularly desirable for uniform treatment of thermally sensitive polymer films. Their treatment of polypropylene films is found to introduce microscale surface patterns as well as various carbon-oxygen bonds, both useful for improving the hydrophilic properties of polymeric materials.

  11. Electric-discharge XeCl laser emitting 10-J, 300-ns pulses

    SciTech Connect

    Konovalov, I N; Losev, V F; Panchenko, Yu N; Ivanov, N G; Sukhov, M Yu

    2005-03-31

    The development of a long-pulse electric-discharge XeCl laser with the 9 x 6 x 100 cm active volume is reported. Laser is excited by using a double circuit with a pulsed charged storage capacitor consisting of paper-oil capacitors forming the pulse-shaping line. The storage capacitor is switched by a multichannel extended gap. The laser mixture was preionised by X-rays. The laser generated the 10-J output pulses with the FWHM of 300 ns, and a uniform intensity distribution over the exit aperture. (lasers)

  12. 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

  13. UV-laser Ablation of Fibre Reinforced Composites with Ns-Pulses

    NASA Astrophysics Data System (ADS)

    Dittmar, H.; Gäbler, F.; Stute, U.

    Within this work the ablation behaviour of both carbon and glass fibre reinforced epoxy resin was assessed when ablated by a nanosecond-pulsed laser source emitting radiation in the ultra-violet spectrum. The investigation focussed on the influences of pulse overlap, focus spot diameter and resulting fluence on process quality and machining time.Results showed that ns-pulsed UV-lasers are capable of machining both types of fibre reinforced composites, while achieving good quality surfaces without burn marks or otherwise heat-damaged areas.

  14. 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.

  15. 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

  16. 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

    2015-01-01

    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

  17. 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.

  18. 200W average power 1mJ pulse energy from spectrally combined pulsed sub-5 ns fiber laser source

    NASA Astrophysics Data System (ADS)

    Schmidt, O.; Ortac, B.; Limpert, J.; Tünnermann, A.; Andersen, Thomas V.

    2009-02-01

    In this contribution, we report on spectral combination of four sub-5ns pulsed fiber amplifier systems with an average output power of 200W at 200kHz repetition rate resulting in 1mJ of pulse energy. A dielectric reflection grating is used to combine four individual beams to one output possessing a measured M2 value of 1.3 and 1.8, respectively, independent of power level. Extraction of higher pulse energies and peak powers will be discussed.

  19. 83 W, 3.1 MHz, square-shaped, 1 ns-pulsed all-fiber-integrated laser for micromachining.

    PubMed

    Ozgören, Kivanç; Oktem, Bülent; Yilmaz, Sinem; Ilday, F Ömer; Eken, Koray

    2011-08-29

    We demonstrate an all-fiber-integrated laser based on off-the-shelf components producing square-shaped, 1 ns-long pulses at 1.03 μm wavelength with 3.1 MHz repetition rate and 83 W of average power. The master-oscillator power-amplifier system is seeded by a fiber oscillator utilizing a nonlinear optical loop mirror and producing incompressible pulses. A simple technique is employed to demonstrate that the pulses indeed have a random chirp. We propose that the long pulse duration should result in more efficient material removal relative to picosecond pulses, while being short enough to minimize heat effects, relative to nanosecond pulses commonly used in micromachining. Micromachining of Ti surfaces using 0.1 ns, 1 ns and 100 ns pulses supports these expectations. PMID:21935132

  20. Pulsed Fiber Lasers from ns to ms range and their applications

    NASA Astrophysics Data System (ADS)

    Westphäling, Tim

    Fiber lasers are widely used in industry for various applications. For marking applications the most common types are pulsed fiber lasers with low average power (10-20 W), pulse lengths of 100 ns and pulse energy in 0,5-1 mJ range. However for applications of high speed ablations and cleaning of surfaces higher average power and pulse energy is needed to realize shorter production cycle times. For this purpose pulsed fiber lasers with morehockey 17 h than 500 W average power and 50 mJ pulse energy have been developed to realize economic processes. In the long pulse range (μs to ms pulse length) QCW fiber lasers have been introduced that fulfil the demands of high pulse energy (up to 60 J) at lower average power (few 100 W range). These lasers fulfil the requirements that so far only lamp pumped Nd:YAG-lasers have been realized: high peak power and pulse energy with low average power in order to reduce investment costs for such devices. This presentation describes the latest development of such pulsed fiber lasers and their industrial applications and focuses in more details on drilling applications.

  1. 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.

  2. 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.

  3. 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.

  4. 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

  5. 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.

  6. 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.

  7. High fluence 1.05 {mu}m performance tests using 20 ns shaped pulses on the Beamlet prototype laser

    SciTech Connect

    Van Wonterghem, B.M.; Murray, J.E.; Burkhart, S.C.; Penko, F.; Henesian, M.A.; Auerbach, J.A.; Wegner, P.J.; Caird, J.A.

    1996-12-01

    Beamlet is a single beamline, nearly full scale physics prototype of the 192 beam Nd:Glass laser driver of the National Ignition Facility. It is used to demonstrate laser performance of the NIF multipass amplifier architecture. Initial system characterization tests have all been performed at pulse durations less than 10 ns. Pinhole closure and modulation at the end of long pulses are a significant concern for the operation of NIF. We recently demonstrated the generation, amplification and propagation of high energy pulses temporally shaped to mimic 20 ns long ignition pulse shapes at fluence levels exceeding the nominal NIF design requirements for Inertial Confinement Fusion by Indirect Drive. We also demonstrated the effectiveness of a new conical pinhole design used in the transport spatial filter to mitigate plasma closure effects and increase closure time to exceed the duration of the 20 ns long pulse.

  8. 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.

  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. Dual-energy bone densitometry using a single 100 ns x-ray pulse.

    PubMed

    Seely, J F; Boyer, C N; Holland, G E

    1998-10-01

    A pulsed, portable hard x-ray source has been developed for medical imaging and flash x-ray absorptiometry. The source is powered by a Marx generator that drives a field emission x-ray tube which produces a 30-300 keV x-ray pulse of 100 ns duration. The x-ray fluence has dual-energy properties. The x-ray energy is relatively high early in the pulse and lower later in the pulse. The feasibility of using a single x-ray pulse for precision bone densitometry was analyzed. A computer simulation model was developed for the x-ray source, the filtration that enhances the dual-energy distribution, the absorption of the energy distribution by bone mineral and soft tissue, and the dual-energy detection system. It is feasible to determine the bone mineral density (BMD) of axial sites such as the lumbar spine and proximal femur with 2% precision over an area that is 15-20 mm in size, depending on the bone mineral and soft tissue thicknesses. An algorithm for determining the absolute BMD, to an accuracy of 2%, using a Plexiglas/TiO2 calibration phantom is discussed. At a distance of 50 cm from the source, the patient exposure is 3.7 mR. The average absorbed bone and tissue doses are 0.6 and 4.3 mrem, respectively. Factors that facilitate diagnostic measurements in clinical settings are the short patient observation time and the portability of the x-ray source. PMID:9800712

  11. Broadband time-domain absorption spectroscopy with a ns-pulse supercontinuum source.

    PubMed

    Sych, Yaroslav; Engelbrecht, Rainer; Schmauss, Bernhard; Kozlov, Dimitrii; Seeger, Thomas; Leipertz, Alfred

    2010-10-25

    A Q-switched laser based system for broadband absorption spectroscopy in the range of 1390-1740 nm (7200-5750 cm(-1)) has been developed and tested. In the spectrometer the 1064 nm light of a 25 kHz repetition-rate micro-chip Nd:YAG laser is directed into a photonic crystal fiber to produce a short (about 2 ns) pulse of radiation in a wide spectral range. This radiation is passed through a 25 km long dispersive single-mode fiber in order to spread the respective wavelengths over a time interval of about 140 ns at the fiber output. This fast swept-wavelength light source allows to record gas absorption spectra by temporally-resolved detection of the transmitted light power. The realized spectral resolution is about 2 cm(-1). Examples of spectra recorded in a cell with CO(2):CH(4):N(2) gas mixtures are presented. An algorithm employed for the evaluation of molar concentrations of different species from the spectra with non-overlapping absorption bands of mixture components is described. The uncertainties of the concentration values retrieved at different acquisition times due to the required averaging are evaluated. As an example, spectra with a signal-to-noise ratio large enough to provide species concentrations with a relative error of 5% can be obtained in real time at a millisecond time scale. Potentials and limitations of this technique are discussed. PMID:21164614

  12. 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

  13. Jitter characteristic of series magnetic pulse compressor employed in ns trigger generator.

    PubMed

    Lin, Jiajin; Zhang, Jiande; Yang, Jianhua; Zhang, Huibo; Qiu, Yongfeng; Yang, Xiao

    2014-05-01

    The jitter characteristic of series magnetic pulse compressor (MPC) employed in ns trigger generator was explored. The time delay of the series MPC is the sum value of the compression time in each stage. The primary voltage disturbance is the original parameter to affect the timing stability of the system. Decreasing the relative jitter of the primary voltage and the first compression time are the practical and exclusive approaches to decrease to time jitter of the series MPC. The jitter experiment was carried out on the three-stage series MPC charged with a fast step-up LC transformer. The performance data show that the delay time decreases with the increase of primary voltage. Meanwhile, the measured ratio between the time jitter and the relative jitter of the primary voltage accords with the theoretical result. PMID:24880359

  14. 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

  15. Thresholds for Phosphatidylserine Externalization in Chinese Hamster Ovarian Cells following Exposure to Nanosecond Pulsed Electrical Fields (nsPEF)

    PubMed Central

    Vincelette, Rebecca L.; Roth, Caleb C.; McConnell, Maureen P.; Payne, Jason A.; Beier, Hope T.; Ibey, Bennett L.

    2013-01-01

    High-amplitude, MV/m, nanosecond pulsed electric fields (nsPEF) have been hypothesized to cause nanoporation of the plasma membrane. Phosphatidylserine (PS) externalization has been observed on the outer leaflet of the membrane shortly after nsPEF exposure, suggesting local structural changes in the membrane. In this study, we utilized fluorescently-tagged Annexin V to observe the externalization of PS on the plasma membrane of isolated Chinese Hamster Ovary (CHO) cells following exposure to nsPEF. A series of experiments were performed to determine the dosimetric trends of PS expression caused by nsPEF as a function of pulse duration, τ, delivered field strength, ED, and pulse number, n. To accurately estimate dose thresholds for cellular response, data were reduced to a set of binary responses and ED50s were estimated using Probit analysis. Probit analysis results revealed that PS externalization followed the non-linear trend of (τ*ED2)−1 for high amplitudes, but failed to predict low amplitude responses. A second set of experiments was performed to determine the nsPEF parameters necessary to cause observable calcium uptake, using cells preloaded with calcium green (CaGr), and membrane permeability, using FM1-43 dye. Calcium influx and FM1-43 uptake were found to always be observed at lower nsPEF exposure parameters compared to PS externalization. These findings suggest that multiple, higher amplitude and longer pulse exposures may generate pores of larger diameter enabling lateral diffusion of PS; whereas, smaller pores induced by fewer, lower amplitude and short pulse width exposures may only allow extracellular calcium and FM1-43 uptake. PMID:23658665

  16. Thresholds for phosphatidylserine externalization in Chinese hamster ovarian cells following exposure to nanosecond pulsed electrical fields (nsPEF).

    PubMed

    Vincelette, Rebecca L; Roth, Caleb C; McConnell, Maureen P; Payne, Jason A; Beier, Hope T; Ibey, Bennett L

    2013-01-01

    High-amplitude, MV/m, nanosecond pulsed electric fields (nsPEF) have been hypothesized to cause nanoporation of the plasma membrane. Phosphatidylserine (PS) externalization has been observed on the outer leaflet of the membrane shortly after nsPEF exposure, suggesting local structural changes in the membrane. In this study, we utilized fluorescently-tagged Annexin V to observe the externalization of PS on the plasma membrane of isolated Chinese Hamster Ovary (CHO) cells following exposure to nsPEF. A series of experiments were performed to determine the dosimetric trends of PS expression caused by nsPEF as a function of pulse duration, τ, delivered field strength, ED, and pulse number, n. To accurately estimate dose thresholds for cellular response, data were reduced to a set of binary responses and ED50s were estimated using Probit analysis. Probit analysis results revealed that PS externalization followed the non-linear trend of (τ*ED (2))(-1) for high amplitudes, but failed to predict low amplitude responses. A second set of experiments was performed to determine the nsPEF parameters necessary to cause observable calcium uptake, using cells preloaded with calcium green (CaGr), and membrane permeability, using FM1-43 dye. Calcium influx and FM1-43 uptake were found to always be observed at lower nsPEF exposure parameters compared to PS externalization. These findings suggest that multiple, higher amplitude and longer pulse exposures may generate pores of larger diameter enabling lateral diffusion of PS; whereas, smaller pores induced by fewer, lower amplitude and short pulse width exposures may only allow extracellular calcium and FM1-43 uptake. PMID:23658665

  17. 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

  18. Investigations into sub-ns pulse generation using ferrite-loaded coaxial lines

    NASA Astrophysics Data System (ADS)

    Bolton, H. R.; Dolan, J. E.; Shapland, A. J.; Parkes, D. M.; Trafford, K.; Kerr, B.

    1995-03-01

    Systems such as Pockels Cell drivers and UWB radar require electrical pulses of less than 200 ps rise-time and amplitude of 10 kV or greater into 50 ohms. Desired p.r.f.'s may be 50 kHz or higher in burst mode. The output rise-time of high power and p.r.f. capable pulsers is generally of the order 2-20 ns, and ferrite-loaded coaxial lines are one means of reducing the leading edge 10-90% rise-time to the order of 100-200 ps. The development of the fast-rising leading edge in ferrite lines is due to the non-linearity of the magnetic medium, and the consequent formation of an 'electromagnetic shock front' at the pulse leading edge. Over the past decade, the use of magnets to bias the ferrite has been found to improve output rise-time and amplitude characteristics considerably. Steady-state analyses made by Soviet analysts in the 1960's do not explain the magnet-biased ferrite line characteristics, and a numerical approach will be presented which shows how the microwave characteristics of the ferrite may be combined with the TEM transmission line equations to model electromagnetic shock wave propagation in such ferrite-loaded lines. It now appears reasonably clear that ferrite lines may be effectively modelled and designed in terms of parameters including the ferrite saturation magnetisation, and the dimensions of the line and the ferrite beads. Second order effects such as conductor and dielectric losses may also be taken into account if required.

  19. 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. PMID:19365440

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

    PubMed

    Roth, Caleb C; 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

  1. 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

  2. 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.

  3. Improved laser triggering and guiding of meqavolt discharges with dual fs-ns pulses

    SciTech Connect

    Mejean, Guillaume; Ackermann, Roland; Kasparian, Jerome; Salmon, Estelle; Yu Jin; Wolf, Jean-Pierre; Rethmeier, Kay; Kalkner, Wilfried; Rohwetter, Philipp; Stelmaszczyk, Kamil; Woeste, Ludger

    2006-01-09

    We demonstrate that the capacity of ultrashort high-power laser pulses to trigger and guide high-voltage discharges can be significantly enhanced by a subsequent visible nanosecond laser pulse. The femtosecond pulse induces a bundle of filaments, which creates a conducting channel of low density and cold plasma connecting the electrodes. The subsequent laser pulse photodetaches electrons from O{sub 2}{sup -} ions in the electrode leader. The resulting electrons allow efficient heating by Joule effect in a retroaction loop, resulting in a 5% reduction of the breakdown voltage.

  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. 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. PMID:26866890

  6. 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.

  7. 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.

  8. A cryo-cooled high-energy DPSSL system delivering ns-pulses at 10 J and 10 Hz

    NASA Astrophysics Data System (ADS)

    Ertel, Klaus; Banerjee, Saumyabrata; Butcher, Thomas J.; De Vido, Mariastefania; Mason, Paul D.; Phillips, P. J.; Richards, David; Shaikh, Waseem; Smith, Jodie M.; Greenhalgh, R. Justin S.; Hernandez-Gomez, Cristina; Collier, John L.

    2015-02-01

    Lasers generating multi-J to kJ ns-pulses are required for many types of laser-plasma interactions. Such lasers are either used directly for compressing matter to extreme densities or they serve as pump lasers for short-pulses laser chains based on large-aperture Ti:sapphire or parametric amplifiers. The thus generated high-energy fs-pulses are most useful for laser driven secondary sources of particles (electrons, protons) or photons (from THz to gamma). While proof-of-principle experiments have been carried out with flashlamp-pumped glass lasers, lasers with much higher efficiency and repetition rate are required to make this applications practically viable. We have developed a scalable new laser concept called DiPOLE (diode pumped optical laser for experiments) based on a gas-cooled ceramic Yb:YAG multi-slab architecture operating at cryogenic temperatures. While the viability of this concept has been shown earlier [1], we have now reached our target performance of 10 J pulse energy at 10 Hz repetition rate at an optical-to-optical efficiency of 21%. To the best of our knowledge, these are record values for average power and efficiency for lasers of this type. We have also upgraded the system by adding a fibre-based front-end system with arbitrary pulse shaping capability and by installing an image-relayed multipass system enabling up to eight passes of the main amplifier. We have then used this system to demonstrate frequency doubling with 65 % conversion efficiency and a long-term shot-to-shot stability of 0.5% rms over a total of nearly 2 million shots, achieved in runs extending over 4 to 6 hours.

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

    PubMed Central

    Rassokhin, Mikhail A.; Pakhomov, Andrei G.

    2014-01-01

    Recently we described a new phenomenon of anodotropic pseudopod-like blebbing in U937 cells exposed to nanosecond pulsed electric field (nsPEF). In Ca2+-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 towards anode during nsPEF exposure. Bleb extension depends on actin polymerization and availability of actin monomers. Inhibition of intracellular Ca2+, 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 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 lifecycle of PLBs share common features with protrusions associated with amoeboid cell migration. PLB lifecycle 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. PMID:24488232

  10. 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. PMID:24488232

  11. 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

  12. Single-frequency, 500-ns laser pulses generated by a passively Q-switched Nd laser

    NASA Astrophysics Data System (ADS)

    Jones, D. C.; Rockwell, D. A.

    1993-03-01

    Accounts are given of the construction and performance of a narrowband Q-switched oscillator that addresses requirements for heavy amplifier saturation as well as a degree of temporal pulse-shaping prior to oscillator beam injection into the amplifier chain that can avoid the severe temporal distortion imposed by amplifier saturation. This oscillator encompasses a lamp-pumped Cr:Nd:GSGG laser rod, a saturable absorber Q switch, and several etalon surfaces forming the output coupler. This device can be used in large baseline holography.

  13. 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.

  14. DPSS MOPA laser system generating 300 mJ and one ns pulse

    NASA Astrophysics Data System (ADS)

    Wu, Frank F.

    2014-02-01

    This report presents a diode-pumped solid state (DPSS) high peak power laser with output energy of 300 mJ, operating frequency of 300 Hz, and pulse width of less than one nanosecond (FWHM) which corresponds to peak power of 300 MW at one micrometer emission wavelength. The laser system consists of a master oscillator power amplifier (MOPA) configuration with the output energy of one millijoule from the oscillator, the output energy of up to 15 millijoules from the pre-amplifier and the output energy of 300 mJ from the power amplifier. The transversal mode is close to the single mode with M2 less than 1.5 and the lasing wavelength is 1064 nm. The MOPA system is well packaged in a compact footprint of 2×3 square feet.

  15. 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.

  16. 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.

  17. 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.

  18. 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

  19. 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.

  20. Optical emission spectroscopy and time-of-flight investigations of plasmas generated from AlN targets in cases of pulsed laser deposition with sub-ps and ns ultraviolet laser pulses

    NASA Astrophysics Data System (ADS)

    Ristoscu, Carmen; Mihailescu, Ion N.; Velegrakis, Michalis; Massaouti, Maria; Klini, Argyro; Fotakis, Costas

    2003-02-01

    We performed a comparative study of the plasma generated from AlN targets under sub-ps vs ns UV (λ=248 nm) excimer laser pulses. Optical emission and time-of-flight spectra recorded in cases of samples irradiated with ns laser pulses showed the presence of Al lines, which became prevalent after the first laser pulse was incident on the target. These observations are congruent with the metallization of AlN targets inside each crater under multipulse ns laser action at laser fluences above the ablation threshold, observed by visual inspection and optical microscopy. Metallization was not observed when working with sub-ps laser pulses. Moreover, our studies confirmed the predominant presence of AlN positive molecular ions in the plasma generated in front of AlN targets submitted to sub-ps multipulse laser irradiation. The optical emission data are in good agreement with time-of-flight mass analysis. We emphasize that all investigations support the experimental evidence reported by György et al. [E. György et al., J. Appl. Phys. 90, 456 (2001)], according to which thin films obtained by pulsed laser deposition with ns laser pulses contain a significant amount of metallic Al, while only AlN is detected in films obtained with sub-ps laser pulses. Measurements of the velocity and kinetic energy distributions of AlN+ indicate that in the case of ns-laser ablation the ions are emitted with thermal energy, while in the case of sub-ps-laser ablation a bimodal distribution exists and has thermal (1 eV) and hyperthermal (10 eV) energy components. This points to different plasma formation mechanisms for the two cases.

  1. Robust 1550-nm single-frequency all-fiber ns-pulsed fiber amplifier for wind-turbine predictive control by wind lidar

    NASA Astrophysics Data System (ADS)

    Beier, F.; de Vries, O.; Schreiber, T.; Eberhardt, R.; Tünnermann, A.; Bollig, C.; Hofmeister, P. G.; Schmidt, J.; Reuter, R.

    2013-02-01

    Scaling of the power yield of offshore wind farms relies on the capacity of the individual wind turbines. This results in a trend to very large rotor diameters, which are difficult to control. It is crucial to monitor the inhomogeneous wind field in front of the wind turbines at different distances to ensure reliable operation and a long lifetime at high output levels. In this contribution, we demonstrate an all-fiber ns-pulsed fiber amplifier based on cost-efficient commercially available components. The amplifier is a suitable source for coherent Doppler lidar pulses making a predictive control of the turbine operation feasible.

  2. 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

  3. Use of ns and fs pulse excitation in laser-induced breakdown spectroscopy to improve its analytical performances: A case study on quaternary bronze alloys

    NASA Astrophysics Data System (ADS)

    Almaviva, Salvatore; Fantoni, Roberta; Caneve, Luisa; Colao, Francesco; Fornarini, Lucilla; Santagata, Antonio; Teghil, Roberto

    2014-09-01

    Analytical performances of Laser Induced Breakdown Spectroscopy (LIBS) resulted not fully satisfactory in some cases such as historical bronzes, therefore, efforts should be focussed on improving ablation efficiency and on better understanding the plasma parameter evolution. To this aim a set of double pulse experiments have been carried out in almost collinear geometry at about 530 nm laser excitation. The first emitting source was either a ns or a fs laser the second a ns one. Data were collected as a function of the interpulse delay, in order to determine the ablation efficiency increase, to study the kinetics of plasma parameters (temperature, electron density) and the decay of atomic and ionic intensities with respect to the optical background. In parallel a previously developed model for laser ablation, ionization and following plasma decay, was implemented, adding a second laser pulse, to analyse the double pulse excitation in the considered geometry, and the time evolution of the same variables was investigated. Model results are able to reproduce the observed experimental trends and support the possibility of improving analytical performances by using the double pulse technique with inter-pulse delays in the entire investigated range.

  4. 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.

  5. 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).

  6. 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.

  7. 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. PMID:26479792

  8. 400 µJ 79 ns amplified pulses from a Q-switched fiber laser using an Yb(3+)-doped fiber saturable absorber.

    PubMed

    Moore, Sean W; Soh, Daniel B S; Bisson, Scott E; Patterson, Brian D; Hsu, Wen L

    2012-10-01

    We report a passively Q-switched all-fiber laser using a large mode area (LMA) Yb(3+)-doped fiber cladding-pumped at 915 nm and an unpumped single-mode Yb(3+)-doped fiber as the saturable absorber (SA). The saturable absorber fiber and gain fiber were coupled with a free-space telescope to optimize the coupling efficiency between the disparate fibers, preferentially bleaching the SA fiber before gain depletion in the pumped fiber. Using this scheme we first demonstrate a Q-switched oscillator with 40 μJ 79 ns pulses at 1026 nm, and show that pulses can be generated from 1020 nm to 1040 nm. The associated peak power of the oscillator alone is more than two orders of magnitude larger than that reported in previous experimental studies using an Yb(3+)-doped fiber as a saturable absorber. We further demonstrate an amplified pulse energy of 0.4 mJ using an Yb(3+)-doped cladding pumped fiber amplifier. Experimental studies in which the saturable absorber length, pump times, and wavelengths are independently varied reveal the impact of these parameters on laser performance. PMID:23188343

  9. Amplification of an ultra short pulse laser by stimulated Raman scattering of a 1ns pulse in a low density plasma

    SciTech Connect

    Kirkwood, R K; Dewald, E; Niemann, C; Meezan, N; Wilks, S C; Price, D W; Landen, O L; Wurtele, J; Charman, A E; Lindberg, R; Fisch, N J; Malkin, V M; Valeo, E O

    2007-10-08

    Experiments are described in which a 1mJ, 1ps, 1200 nm seed laser beam is amplified by interaction with an intersecting 350 J, 1ns, 1054 nm pump beam in a low density (1 x 10{sup 19}/cm{sup 3}) plasma. The transmission of the seed beam is observed to be enhanced by > {approx} 25 x when the plasma is near the resonant density for stimulated Raman scattering (SRS), compared to measured transmissions at wavelengths just below the resonant value. The amplification is observed to increase rapidly with increases in both pump intensity and plasma density.

  10. 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.

  11. Laser damage by ns and sub-ps pulses on hafnia/silica anti-reflection coatings on fused silica double-sided polished using zirconia or ceria and washed with or without an alumina wash step.

    SciTech Connect

    Bellum, John Curtis; Rambo, Patrick K.; Schwarz, Jens; Kletecka, Damon; Atherton, Briggs W.; Kimmel, Mark W.; Smith, Ian Craig; Smith, Douglas; Hobbs, Zachary

    2010-10-01

    Sandia's Large Optics Coating Operation has extensive results of laser induced damage threshold (LIDT) testing of its anti-reflection (AR) and high reflection coatings on substrates pitch polished using ceria and washed in a process that includes an alumina wash step. The purpose of the alumina wash step is to remove residual polishing compound to minimize its role in laser damage. These LIDT tests are for multi longitudinal mode, ns class pulses at 1064 nm and 532 nm (NIF-MEL protocol) and mode locked, sub-ps class pulses at 1054 nm (Sandia measurements), and show reasonably high and adequate laser damage resistance for coatings in the beam trains of Sandia's Z-Backlighter terawatt and petawatt lasers. An AR coating in addition to coatings of our previous reports confirms this with LIDTs of 33.0 J/cm{sup 2} for 3.5 ns pulses and 1.8 J/cm{sup 2} for 350 fs pulses. In this paper, we investigate both ceria and zirconia in doublesided polishing (common for large flat Z-Backlighter laser optics) as they affect LIDTs of an AR coating on fused silica substrates washed with or without the alumina wash step. For these AR coated, double-sided polished surfaces, ceria polishing in general affords better resistance to laser damage than zirconia polishing and laser damage is less likely with the alumina wash step than without it. This is supported by specific results of laser damage tests with 3.5 ns, multi longitudinal mode, single shot pulses at 1064 nm and 532 nm, with 7.0 ns, single and multi longitudinal mode, single and multi shot pulses at 532 nm, and with 350 fs, mode-locked, single shot pulses at 1054 nm.

  12. Effect of deposition method and substrate surface quality on laser-induced damage threshold for repetitive 13-ns and 130-fs pulses

    NASA Astrophysics Data System (ADS)

    Melninkaitis, Andrius; Rakickas, Tomas; Miksys, Darius; Grigonis, Rimantas; Sirutkaitis, Valdas; Skrebutenas, Alfridas; Buzelis, Rytis; Drazdys, Ramutis; Abromavicius, Giedrius; Juskenas, Remigijus; Selskis, Algirdas

    2005-02-01

    A comparison of laser induced damage thresholds (LIDT) of ion assisted deposition (IAD) and standard electron beam deposition dielectric coatings on BK7 glass with different surface roughness was performed. Five types of high reflectance mirrors at 800 nm and two types of high reflectance mirrors at 1064 nm were tested. Mirror coatings were made of ZrO2 and SiO2. Automated LIDT measurements were performed according to the requirements of current ISO 11254-2 standard. Two lasers were used for the measurements: Nd:YAG (l = 1064 nm, t = 13 ns) and Ti:Sapphire (l = 800 nm, t = 130 fs ). All measurements were performed at 1-kHz pulse repetition rate (S-on-1 test). A fixed spot size was used for each laser. For 1064 nm it was ~ 70 um and for 800 nm ~ 500 um. The damage morphology and structure of coatings were characterized by an atomic force microscopy (AFM), Nomarski microscopy and X-ray diffraction (XRD).

  13. 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)

  14. A simple, compact, and efficient diode-side-pumped linear intracavity frequency doubled Nd:YAG rod laser with 50 ns pulse width and 124 W green output power.

    PubMed

    Sharma, Sunil K; Mukhopadhyay, Pranab K; Singh, Amarjeet; Kandasamy, Ranganathan; Oak, Shrikant M

    2010-07-01

    We have developed an efficient and high power repetitively Q-switched diode-pumped intracavity frequency doubled Nd:YAG/LiB(3)O(5) based green laser capable of generating 124 W of average green power with 50 ns pulse duration in a highly compact and robust linear cavity configuration. The pump to green beam conversion efficiency is 16.8% and the overall wall-plug efficiency is 8.3%. The long term power stability is excellent with +/-0.4 W variation at the maximum output power and +/-2% amplitude fluctuation with +/-2.9 ns timing jitter. The M(2) parameter of the green beam was measured to be approximately 27. This, combined with the short pulse duration and the high average power, makes this laser ideal for pumping ultrafast Ti:sapphire laser amplifier systems and for micromachining applications. PMID:20687702

  15. 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

  16. 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. PMID:25321974

  17. 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.

  18. Fiber-solid, hybrid, single-frequency laser (100 W) with a 100 MHz repetition rate and 1 ns pulse width from a spherical aberration compensated four-stage Nd:YVO₄ amplifier.

    PubMed

    Zhang, Xiang; Wang, Yi; Liu, Bin; Wang, Chunhua; Xiang, Zhen; Liu, Chong

    2014-08-01

    A pulsed laser for laser guide stars with a 100 MHz repetition rate and 1 ns pulse width was achieved by external modulation of a continuous wave (CW) laser with a 70 kHz spectrum width. The laser is amplified first by two fiber pre-amplifiers and then by four solid-state power amplifiers. The laser achieves gains as high as 36 dB in the fiber pre-amplifiers due to the long gain medium length. The output power from the fiber amplifiers is 2.1 W. The laser receives further amplification in the solid-state amplifiers and retains good beam quality by aberration compensation. The final output average power is 102.9 W, and the beam quality factor M² is 1.46. The laser reaches high power without spectrum width and pulse width broadening at the 100 MHz repetition rate. The spectrum width of the pulsed laser is less than 0.8 GHz, which is close to the Fourier transform limit. Such a laser with single-frequency, high-repetition, and high-power features along with good beam quality will be valuable for many research areas. PMID:25090340

  19. 47 W, 6 ns constant pulse duration, high-repetition-rate cavity-dumped Q-switched TEM(00) Nd:YVO(4) oscillator.

    PubMed

    McDonagh, Louis; Wallenstein, Richard; Knappe, Ralf

    2006-11-15

    We report on a cavity-dumped Q-switched TEM(00) Nd:YVO(4) oscillator offering a unique combination of high power, constant short pulse duration, and high repetition rate, suppressing the gain dependence of pulse duration in classical Q-switched oscillators. Its performance is compared with that of the same oscillator operated in a classical Q-switched regime, demonstrating the much higher peak powers achievable with this technique, especially at high repetition rates. Up to 31 W of 532 nm green light was generated by frequency doubling in a noncritical phase matched LBO crystal, corresponding to 70% conversion efficiency. PMID:17072404

  20. 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.

  1. Extracting the distribution of laser damage precursors on fused silica surfaces for 351 nm, 3 ns laser pulses at high fluences (20-150 J/cm2).

    PubMed

    Laurence, Ted A; Bude, Jeff D; Ly, Sonny; Shen, Nan; Feit, Michael D

    2012-05-01

    Surface laser damage limits the lifetime of optics for systems guiding high fluence pulses, particularly damage in silica optics used for inertial confinement fusion-class lasers (nanosecond-scale high energy pulses at 355 nm/3.5 eV). The density of damage precursors at low fluence has been measured using large beams (1-3 cm); higher fluences cannot be measured easily since the high density of resulting damage initiation sites results in clustering. We developed automated experiments and analysis that allow us to damage test thousands of sites with small beams (10-30 µm), and automatically image the test sites to determine if laser damage occurred. We developed an analysis method that provides a rigorous connection between these small beam damage test results of damage probability versus laser pulse energy and the large beam damage results of damage precursor densities versus fluence. We find that for uncoated and coated fused silica samples, the distribution of precursors nearly flattens at very high fluences, up to 150 J/cm2, providing important constraints on the physical distribution and nature of these precursors. PMID:22565775

  2. 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.

  3. 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.

  4. Pulse

    MedlinePlus

    Heart rate; Heart beat ... The pulse can be measured at areas where an artery passes close to the skin. These areas include the: ... side of the foot Wrist To measure the pulse at the wrist, place the index and middle ...

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

    NASA Astrophysics Data System (ADS)

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

    2015-02-01

    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 (C5H12) 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 × 1014 W/cm2, 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.

  6. 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.

  7. 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.

  8. 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.

  9. Cleavage of the dengue virus polyprotein at the NS3/NS4A and NS4B/NS5 junctions is mediated by viral protease NS2B-NS3, whereas NS4A/NS4B may be processed by a cellular protease.

    PubMed Central

    Cahour, A; Falgout, B; Lai, C J

    1992-01-01

    The cleavage mechanism utilized for processing of the NS3-NS4A-NS4B-NS5 domain of the dengue virus polyprotein was studied by using the vaccinia virus expression system. Recombinant vaccinia viruses vNS2B-NS3-NS4A-NS4B-NS5, vNS3-NS4A-NS4B-NS5, vNS4A-NS4B-NS5, and vNS4B-NS5 were constructed. These recombinants were used to infect cells, and the labeled lysates were analyzed by immunoprecipitation. Recombinant vNS2B-NS3-NS4A-NS4B-NS5 expressed the authentic NS3 and NS5 proteins, but the other recombinants produced uncleaved polyproteins. These findings indicate that NS2B is required for processing of the downstream nonstructural proteins, including the NS3/NS4A and NS4B/NS5 junctions, both of which contain a dibasic amino acid sequence preceding the cleavage site. The flavivirus NS4A/NS4B cleavage site follows a long hydrophobic sequence. The polyprotein NS4A-NS4B-NS5 was cleaved at the NS4A/NS4B junction in the absence of other dengue virus functions. One interpretation for this finding is that NS4A/NS4B cleavage is mediated by a host protease, presumably a signal peptidase. Although vNS3-NS4A-NS4B-NS5 expressed only the polyprotein, earlier results demonstrated that cleavage at the NS4A/NS4B junction occurred when an analogous recombinant, vNS3-NS4A-84%NS4B, was expressed. Thus, it appears that uncleaved NS3 plus NS5 inhibit NS4A/NS4B cleavage presumably because the putative signal sequence is not accessible for recognition by the responsible protease. Finally, recombinants that expressed an uncleaved NS4B-NS5 polyprotein, such as vNS4A-NS4B-NS5 or vNS4B-NS5, produced NS5 when complemented with vNS2B-30%NS3 or with vNS2B plus v30%NS3. These results indicate that cleavage at the NS4B/NS5 junction can be mediated by NS2B and NS3 in trans. Images PMID:1531368

  10. NS-NS sector of closed superstring field theory

    NASA Astrophysics Data System (ADS)

    Erler, Theodore; Konopka, Sebastian; Sachs, Ivo

    2014-08-01

    We give a construction for a general class of vertices in superstring field theory which include integration over bosonic moduli as well as the required picture changing insertions. We apply this procedure to find a covariant action for the NS-NS sector of Type II closed superstring field theory.

  11. Bipolar pulse generator for intense pulsed ion beam accelerator

    SciTech Connect

    Ito, H.; Igawa, K.; Kitamura, I.; Masugata, K.

    2007-01-15

    A new type of pulsed ion beam accelerator named ''bipolar pulse accelerator'' (BPA) has been proposed in order to improve the purity of intense pulsed ion beams. To confirm the principle of the BPA, we developed a bipolar pulse generator for the bipolar pulse experiment, which consists of a Marx generator and a pulse forming line (PFL) with a rail gap switch on its end. In this article, we report the first experimental result of the bipolar pulse and evaluate the electrical characteristics of the bipolar pulse generator. When the bipolar pulse generator was operated at 70% of the full charge condition of the PFL, the bipolar pulse with the first (-138 kV, 72 ns) and the second pulse (+130 kV, 70 ns) was successfully obtained. The evaluation of the electrical characteristics indicates that the developed generator can produce the bipolar pulse with fast rise time and sharp reversing time.

  12. Bipolar pulse generator for intense pulsed ion beam accelerator.

    PubMed

    Ito, H; Igawa, K; Kitamura, I; Masugata, K

    2007-01-01

    A new type of pulsed ion beam accelerator named "bipolar pulse accelerator" (BPA) has been proposed in order to improve the purity of intense pulsed ion beams. To confirm the principle of the BPA, we developed a bipolar pulse generator for the bipolar pulse experiment, which consists of a Marx generator and a pulse forming line (PFL) with a rail gap switch on its end. In this article, we report the first experimental result of the bipolar pulse and evaluate the electrical characteristics of the bipolar pulse generator. When the bipolar pulse generator was operated at 70% of the full charge condition of the PFL, the bipolar pulse with the first (-138 kV, 72 ns) and the second pulse (+130 kV, 70 ns) was successfully obtained. The evaluation of the electrical characteristics indicates that the developed generator can produce the bipolar pulse with fast rise time and sharp reversing time. PMID:17503918

  13. 46 CFR 2.10-5 - Exemptions.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 1 2010-10-01 2010-10-01 false Exemptions. 2.10-5 Section 2.10-5 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY PROCEDURES APPLICABLE TO THE PUBLIC VESSEL INSPECTIONS Fees § 2.10-5 Exemptions. (a) Vessels owned or operated by a non-profit organization may be exempted from payment of...

  14. 16 CFR 2.10 - Depositions.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 16 Commercial Practices 1 2010-01-01 2010-01-01 false Depositions. 2.10 Section 2.10 Commercial Practices FEDERAL TRADE COMMISSION ORGANIZATION, PROCEDURES AND RULES OF PRACTICE NONADJUDICATIVE PROCEDURES Inquiries; Investigations; Compulsory Processes § 2.10 Depositions. In investigations other than those conducted under section 20 of...

  15. Characterization of Dengue Virus NS4A and NS4B Protein Interaction

    PubMed Central

    Zou, Jing; Xie, Xuping; Wang, Qing-Yin; Dong, Hongping; Lee, Michelle Yueqi; Kang, Congbao

    2015-01-01

    ABSTRACT Flavivirus replication is mediated by a membrane-associated replication complex where viral membrane proteins NS2A, NS2B, NS4A, and NS4B serve as the scaffold for the replication complex formation. Here, we used dengue virus serotype 2 (DENV-2) as a model to characterize viral NS4A-NS4B interaction. NS4A interacts with NS4B in virus-infected cells and in cells transiently expressing NS4A and NS4B in the absence of other viral proteins. Recombinant NS4A and NS4B proteins directly bind to each other with an estimated Kd (dissociation constant) of 50 nM. Amino acids 40 to 76 (spanning the first transmembrane domain, consisting of amino acids 50 to 73) of NS4A and amino acids 84 to 146 (also spanning the first transmembrane domain, consisting of amino acids 101 to 129) of NS4B are the determinants for NS4A-NS4B interaction. Nuclear magnetic resonance (NMR) analysis suggests that NS4A residues 17 to 80 form two amphipathic helices (helix α1, comprised of residues 17 to 32, and helix α2, comprised of residues 40 to 47) that associate with the cytosolic side of endoplasmic reticulum (ER) membrane and helix α3 (residues 52 to 75) that transverses the ER membrane. In addition, NMR analysis identified NS4A residues that may participate in the NS4A-NS4B interaction. Amino acid substitution of these NS4A residues exhibited distinct effects on viral replication. Three of the four NS4A mutations (L48A, T54A, and L60A) that affected the NS4A-NS4B interaction abolished or severely reduced viral replication; in contrast, two NS4A mutations (F71A and G75A) that did not affect NS4A-NS4B interaction had marginal effects on viral replication, demonstrating the biological relevance of the NS4A-NS4B interaction to DENV-2 replication. Taken together, the study has provided experimental evidence to argue that blocking the NS4A-NS4B interaction could be a potential antiviral approach. IMPORTANCE Flavivirus NS4A and NS4B proteins are essential components of the ER membrane

  16. Characterization of plasma formation and outflow emission from different wire-based z-pinch experiments driven at the 350kA, 1kA/ns Llampudken pulsed power driver

    NASA Astrophysics Data System (ADS)

    Veloso, Felipe; Muñoz-Cordovez, Gonzalo; Valenzuela-Villaseca, Vicente; Vescovi, Milenko; Favre, Mario; Wyndham, Edmund

    2015-11-01

    We present results on tungsten and aluminium wire-based z-pinch plasma experiments driven by the 350kA, 1kA/ns Llampudken generator at P Universidad Catolica de Chile. Our experiments are concentrated in the formation and subsequent emission of plasma from two different configurations: conical arrays and modified cylindrical arrays using different wire diameters within the load. The former produce collimated jet-like outflows by the zippering effect at the axis of the conical array, whereas the latter produce emission of an unstructured dense plasma object by the temporal variations on the global magnetic field topology of the cylindrical array. We present measurements of the ablation process in both configurations and the main features of the outflows obtained, such as plasma densities and propagation velocities. It is found that an appropriate mass per unit length in the load is particularly important for producing outflows from modified cylindrical arrays, and that high pressure background gas embedding the load hampers the emission of plasma outflows in conical arrays. In addition, the analysis of the dimensionless parameters that characterize each outflow will be presented. This work has been funded by FONDECYT 11121621. G Munoz is funded by a doctorate scholarship awarded by CONICYT.

  17. 46 CFR 2.10-5 - Exemptions.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 1 2012-10-01 2012-10-01 false Exemptions. 2.10-5 Section 2.10-5 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY PROCEDURES APPLICABLE TO THE PUBLIC VESSEL INSPECTIONS Fees § 2.10-5 Exemptions. (a) Vessels owned or operated by a non-profit organization may be exempted from payment of the fees required by this subpart, only if...

  18. 46 CFR 2.10-5 - Exemptions.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 1 2011-10-01 2011-10-01 false Exemptions. 2.10-5 Section 2.10-5 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY PROCEDURES APPLICABLE TO THE PUBLIC VESSEL INSPECTIONS Fees § 2.10-5 Exemptions. (a) Vessels owned or operated by a non-profit organization may be exempted from payment of the fees required by this subpart, only if...

  19. Investigation of laser temporal pulse duration on Rayleigh scattering

    SciTech Connect

    Nee, T.A.; Roberts, J.R.

    1982-02-01

    Relative Rayleigh-scattering cross sections from nitrogen have been measured for various pulse durations and wavelengths of incident laser radiation. No pulse-duration dependence has been observed for laser pulses as short as 5 ns, and classical theory is found to be still valid over the pulse-width range (5< or =..delta..t< or =110 ns) of our observations.

  20. [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

  1. 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.

  2. NS&T MANAGEMENT OBSERVATIONS

    SciTech Connect

    Gianotto, David

    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.

  3. 7 CFR 2.10 - Limitations.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 1 2011-01-01 2011-01-01 false Limitations. 2.10 Section 2.10 Agriculture Office of the Secretary of Agriculture DELEGATIONS OF AUTHORITY BY THE SECRETARY OF AGRICULTURE AND GENERAL... Limitations. The delegations made in this part shall not be construed to confer upon any general officer...

  4. 7 CFR 2.10 - Limitations.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 1 2010-01-01 2010-01-01 false Limitations. 2.10 Section 2.10 Agriculture Office of the Secretary of Agriculture DELEGATIONS OF AUTHORITY BY THE SECRETARY OF AGRICULTURE AND GENERAL... Limitations. The delegations made in this part shall not be construed to confer upon any general officer...

  5. Nanosecond-range multi-pulses synchronization based on magnetic switch and saturable pulse transformer.

    PubMed

    Liu, Jinliang; Fan, Xuliang; Zhang, Yu

    2012-12-01

    Magnetic switch has been widely used in the field of pulsed power system for its advantages of solid state, high repetition rate, and long lifetime. In this paper, the synchronization of ns-range multi-pulses based on magnetic switch is studied and two kinds of technical methods are proposed. One of which is based on magnetic switches on a communal magnetic core. It was proved that the synchronization accuracy of 3 pulses is about 2 ns. Another proposed method is ns-range multi-pulse synchronization based on saturable pulse transformer and the experimental result showed that the synchronization accuracy of 2 pulses could achieve 2.5 ns. In contrast to other multi-pulse synchronization methods controlled by high-voltage pulse trigger or laser trigger, the synchronization based on magnetic switch and saturable pulse transformer has the advantages of high synchronization accuracy, long lifetime, and exemption from external trigger signals. PMID:23278010

  6. Radiative Properties of High Wire Number Tungsten Arrays with Implosion Times up to 250 ns

    SciTech Connect

    Beg, F.N.; Coverdale, C.A.; Deeney, C.; Douglas, M.R.; Haines, M.G.; Peterson, D.L.; Roderick, N.F.; Ruiz-Camacho, J.; Spielman, R.B.; Struve, K.W.; Stygar, W.A.

    1999-02-02

    High wire number, 25-mm diameter tungsten wire arrays have been imploded on the 8-MA Saturn generator, operating in a long-pulse mode. By varying the mass load from 710 to 6140 ps/cm, implosion times of 130 to 250 ns have been obtained with implosion velocities of 50 to 25 cn-dys, respectively. These z-pinch implosions produced plasmas with millimeter diameters that radiated 600 to 800 kJ of x-rays, with powers of 20 to 49 TW; the corresponding pulse widths were 19 to 7.5 ns, with risetimes ranging from 6.5 to 4.0 ns. These powers and pulse widths are similar to those achieved with 50 ns implosion times on Saturn. Two-dimensional, radiation- magnetohydrodynamic calculations indicate that the imploding shells in these long implosion time experiments are comparable in width to those in the short pulse cases. This can only be due to lower initial perturbations. A heuristic wire array model suggests that the reduced perturbations, in the long pulse cases, may be due to the individual wire merger occurring well before the acceleration of the shell. The experiments and modeling suggest that 150 to 200 ns implosion time z-pinches could be employed for high-power, x-ray source applications.

  7. 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.

  8. 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.

  9. Properties of ns-laser processed polydimethylsiloxane (PDMS)

    NASA Astrophysics Data System (ADS)

    Atanasov, P. A.; Stankova, N. E.; Nedyalkov, N. N.; Stoyanchov, T. R.; Nikov, Ru G.; Fukata, N.; Gerlach, J. W.; Hirsch, D.; Rauschenbach, B.

    2016-03-01

    The medical-grade polydimethylsiloxane (PDMS) elastomer is a widely used biomaterial in medicine and for preparation of high-tech devices because of its remarkable properties. In this work, we present the experimental results on drilling holes on the PDMS surface by using ultraviolet, visible or near-infrared ns-laser pulses and on studying the changes of the chemical composition and structure inside the processed areas. The material in the zone of the holes is studied by XRD, ?-Raman analyses and 3D laser microscopy in order to obtain information on the influence of different processing laser parameters, as wavelength, fluence and number of consecutive pulses on the material transformation and its modification.

  10. 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

  11. Percussion drilling of metals using bursts of nanosecond pulses.

    PubMed

    Hendow, Sami T; Romero, Rosa; Shakir, Sami A; Guerreiro, Paulo T

    2011-05-23

    The effect of ns bursting on percussion drilling of metal is investigated experimentally and analytically, and compared with the efficiency and quality of drilling using single ns pulses. Key advantages are demonstrated, correlating well with the results from a thermal theoretical model. The 1064 nm bursts contain up to 14 pulses of various pulse widths and spacing, and at frequencies of tens of MHz within the burst. The individual pulses have pulse widths of 10 to 200 ns, and up to 12 kW peak power. Burst repetition frequency is single shot to 500 kHz. PMID:21643280

  12. Bluetongue Virus Nonstructural Protein NS3/NS3a Is Not Essential for Virus Replication

    PubMed Central

    van Gennip, René G. P.; van de Water, Sandra G. P.; van Rijn, Piet A.

    2014-01-01

    Orbiviruses form the largest genus of the family Reoviridae consisting of at least 23 different virus species. One of these is the bluetongue virus (BTV) and causes severe hemorrhagic disease in ruminants, and is transmitted by bites of Culicoides midges. BTV is a non-enveloped virus which is released from infected cells by cell lysis and/or a unique budding process induced by nonstructural protein NS3/NS3a encoded by genome segment 10 (Seg-10). Presence of both NS3 and NS3a is highly conserved in Culicoides borne orbiviruses which is suggesting an essential role in virus replication. We used reverse genetics to generate BTV mutants to study the function of NS3/NS3a in virus replication. Initially, BTV with small insertions in Seg-10 showed no CPE but after several passages these BTV mutants reverted to CPE phenotype comparable to wtBTV, and NS3/NS3a expression returned by repair of the ORF. These results show that there is a strong selection for functional NS3/NS3a. To abolish NS3 and/or NS3a expression, Seg-10 with one or two mutated start codons (mutAUG1, mutAUG2 and mutAUG1+2) were used to generate BTV mutants. Surprisingly, all three BTV mutants were generated and the respective AUGMet→GCCAla mutations were maintained. The lack of expression of NS3, NS3a, or both proteins was confirmed by westernblot analysis and immunostaining of infected cells with NS3/NS3a Mabs. Growth of mutAUG1 and mutAUG1+2 virus in BSR cells was retarded in both insect and mammalian cells, and particularly virus release from insect cells was strongly reduced. Our findings now enable research on the role of RNA sequences of Seg-10 independent of known gene products, and on the function of NS3/NS3a proteins in both types of cells as well as in the host and insect vector. PMID:24465709

  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. 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.

  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. PMID:25865663

  16. 25 ns software correlator for photon and fluorescence correlation spectroscopy

    NASA Astrophysics Data System (ADS)

    Magatti, Davide; Ferri, Fabio

    2003-02-01

    A 25 ns time resolution, multi-tau software correlator developed in LABVIEW based on the use of a standard photon counting unit, a fast timer/counter board (6602-PCI National Instrument) and a personal computer (PC) (1.5 GHz Pentium 4) is presented and quantitatively discussed. The correlator works by processing the stream of incoming data in parallel according to two different algorithms: For large lag times (τ⩾100 μs), a classical time-mode (TM) scheme, based on the measure of the number of pulses per time interval, is used; differently, for τ⩽100 μs a photon-mode (PM) scheme is adopted and the time sequence of the arrival times of the photon pulses is measured. By combining the two methods, we developed a system capable of working out correlation functions on line, in full real time for the TM correlator and partially in batch processing for the PM correlator. For the latter one, the duty cycle depends on the count rate of the incoming pulses, being ˜100% for count rates ⩽3×104 Hz, ˜15% at 105 Hz, and ˜1% at 106 Hz. For limitations imposed by the fairly small first-in, first-out (FIFO) buffer available on the counter board, the maximum count rate permissible for a proper functioning of the PM correlator is limited to ˜105 Hz. However, this limit can be removed by using a board with a deeper FIFO. Similarly, the 25 ns time resolution is only limited by maximum clock frequency available on the 6602-PCI and can be easily improved by using a faster clock. When tested on dilute solutions of calibrated latex spheres, the overall performances of the correlator appear to be comparable with those of commercial hardware correlators, but with several nontrivial advantages related to its flexibility, low cost, and easy adaptability to future developments of PC and data acquisition technology.

  17. Host cell killing by the West Nile Virus NS2B-NS3 proteolytic complex: NS3 alone is sufficient to recruit caspase-8-based apoptotic pathway

    SciTech Connect

    Ramanathan, Mathura P.; Chambers, Jerome A.; Pankhong, Panyupa; Chattergoon, Michael; Attatippaholkun, Watcharee; Dang, Kesen; Shah, Neelima; Weiner, David B. . E-mail: dbweiner@mail.med.upenn.edu

    2006-02-05

    The West Nile Virus (WNV) non-structural proteins 2B and 3 (NS2B-NS3) constitute the proteolytic complex that mediates the cleavage and processing of the viral polyprotein. NS3 recruits NS2B and NS5 proteins to direct protease and replication activities. In an effort to investigate the biology of the viral protease, we cloned cDNA encoding the NS2B-NS3 proteolytic complex from brain tissue of a WNV-infected dead crow, collected from the Lower Merion area (Merion strain). Expression of the NS2B-NS3 gene cassette induced apoptosis within 48 h of transfection. Electron microscopic analysis of NS2B-NS3-transfected cells revealed ultra-structural changes that are typical of apoptotic cells including membrane blebbing, nuclear disintegration and cytoplasmic vacuolations. The role of NS3 or NS2B in contributing to host cell apoptosis was examined. NS3 alone triggers the apoptotic pathways involving caspases-8 and -3. Experimental results from the use of caspase-specific inhibitors and caspase-8 siRNA demonstrated that the activation of caspase-8 was essential to initiate apoptotic signaling in NS3-expressing cells. Downstream of caspase-3 activation, we observed nuclear membrane ruptures and cleavage of the DNA-repair enzyme, PARP in NS3-expressing cells. Nuclear herniations due to NS3 expression were absent in the cells treated with a caspase-3 inhibitor. Expression of protease and helicase domains themselves was sufficient to trigger apoptosis generating insight into the apoptotic pathways triggered by NS3 from WNV.

  18. PVDF water-shock pressure transducer with 200-ns response

    SciTech Connect

    Johnson, D.E.; Hogeland, S.R.; Nelson, L.S.

    1992-12-01

    The design, calibration, and preliminary test results for an underwater shock gauge are presented. The active element is a 25-{mu}m thick polyvinylidene fluoride shock sensor providing rise times as short as 50 ns. Fast rise time is essential to accurate recording of shock pulses with durations of only a few microseconds. The piezoelectric polymer provides a self-generating pressure sensor requiring neither amplification nor additional active electronic circuitry. The gauge package is designed to minimize electromagnetic interference from the high-voltage fire set used to power the exploding bridge wire pressure source. The gauge package is constructed to withstand the initial water shock as well as subsequent reactions in the water that result in strong water motion and bubble generation. Thin-film diaphragm sensors are not sturdy enough to withstand this environment. Initial tests show that the gauge responds in 200 ns in water and that low-frequency response is sufficient to allow recording for at least 40 {mu}s after the initial shock arrival.

  19. 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.

  20. 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.

  1. 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

  2. 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

  3. 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...

  4. Development of high-voltage pulse-slicer unit with variable pulse duration for pulse radiolysis system

    NASA Astrophysics Data System (ADS)

    Upadhyay, J.; Sharma, M. L.; Navathe, C. P.; Toley, M. A.; Shinde, S. J.; Nadkarni, S. A.; Sarkar, S. K.

    2012-02-01

    A high-voltage pulse-slicer unit with variable pulse duration has been developed and integrated with a 7 MeV linear electron accelerator (LINAC) for pulse radiolysis investigation. The pulse-slicer unit provides switching voltage from 1 kV to 10 kV with rise time better than 5 ns. Two MOSFET based 10 kV switches were configured in differential mode to get variable duration pulses. The high-voltage pulse has been applied to the deflecting plates of the LINAC for slicing of electron beam of 2 μs duration. The duration of the electron beam has been varied from 30 ns to 2 μs with the optimized pulse amplitude of 7 kV to get corresponding radiation doses from 6 Gy to 167 Gy.

  5. 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

  6. Nonsmooth nonnegative matrix factorization (nsNMF).

    PubMed

    Pascual-Montano, Alberto; Carazo, J M; Kochi, Kieko; Lehmann, Dietrich; Pascual-Marqui, Roberto D

    2006-03-01

    We propose a novel nonnegative matrix factorization model that aims at finding localized, part-based, representations of nonnegative multivariate data items. Unlike the classical nonnegative matrix factorization (NMF) technique, this new model, denoted "nonsmooth nonnegative matrix factorization" (nsNMF), corresponds to the optimization of an unambiguous cost function designed to explicitly represent sparseness, in the form of nonsmoothness, which is controlled by a single parameter. In general, this method produces a set of basis and encoding vectors that are not only capable of representing the original data, but they also extract highly localized patterns, which generally lend themselves to improved interpretability. The properties of this new method are illustrated with several data sets. Comparisons to previously published methods show that the new nsNMF method has some advantages in keeping faithfulness to the data in the achieving a high degree of sparseness for both the estimated basis and the encoding vectors and in better interpretability of the factors. PMID:16526426

  7. Diffraction-assisted micropatterning of silicon surfaces by ns-laser irradiation

    SciTech Connect

    Haro-Poniatowski, E. Acosta-Zepeda, C.; Mecalco, G.; Hernández-Pozos, J. L.; Batina, N.; Morales-Reyes, I.; Bonse, J.

    2014-06-14

    Single-pulse (532 nm, 8 ns) micropatterning of silicon with nanometric surface modulation is demonstrated by irradiating through a diffracting pinhole. The irradiation results obtained at fluences above the melting threshold are characterized by scanning electron and scanning force microscopy and reveal a good agreement with Fresnel diffraction theory. The physical mechanism is identified and discussed on basis of both thermocapillary and chemicapillary induced material transport during the molten state of the surface.

  8. 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

  9. 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

  10. 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.

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

    NASA Astrophysics Data System (ADS)

    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.

    2009-01-01

    A necessary condition for igniting indirectly driven inertial confinement fusion 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, P. Amendt, R. L. Berger et al., Phys. Plasmas 11, 339 (2003)]. While drive symmetry during the first 2ns of the pulse can be inferred by using the re-emission pattern from a surrogate high Z sphere and symmetry during the last 5ns inferred from the shape of fully imploded capsules, the midportion (≈2-10ns ) has been shown to be amenable to detection by the in-flight shape of x-ray backlit thin-shell capsules. In this paper, we present sensitivity studies conducted on the University of Rochester's OMEGA laser [J. Soures, R. L. McCrory, C. P. Verdon et al., Phys. Plasmas 3, 2108 (1996)] 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 4.7keV radiographs of thin 1.4mm initial-diameter Ge-doped CH and Cu-doped Be shells when converged by a factor of ≈0.5 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 micrometers, meeting requirements. The promising results to date allow us to compare measured and predicted distortions and by inference drive asymmetries for the first four asymmetry modes as a function of hohlraum illumination conditions.

  12. 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.

  13. 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 §...

  14. 10 CFR 960.5-2-10 - Hydrology.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 10 Energy 4 2012-01-01 2012-01-01 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... Hydrology. (a) Qualifying condition. The site shall be located such that the geohydrologic setting of...

  15. 10 CFR 960.5-2-10 - Hydrology.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 10 Energy 4 2013-01-01 2013-01-01 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... Hydrology. (a) Qualifying condition. The site shall be located such that the geohydrologic setting of...

  16. 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... Hydrology. (a) Qualifying condition. The site shall be located such that the geohydrologic setting of...

  17. 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.

  18. 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.

  19. 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

  20. SI Engine with repetitive NS spark plug

    NASA Astrophysics Data System (ADS)

    Pancheshniy, Sergey; Nikipelov, Andrey; Anokhin, Eugeny; Starikovskiy, Andrey; Laplase Team; Mipt Team; Pu Team

    2013-09-01

    Now de-facto the only technology for fuel-air mixtures ignition in IC engines exists. It is a spark discharge of millisecond duration in a short discharge gap. The reason for such a small variety of methods of ignition initiation is very specific conditions of the engine operation. First, it is very high-pressure of fuel-air mixture - from 5-7 atmospheres in old-type engines and up to 40-50 atmospheres on the operating mode of HCCI. Second, it is a very wide range of variation of the oxidizer/fuel ratio in the mixture - from almost stoichiometric (0.8-0.9) at full load to very lean (φ = 0.3-0.5) mixtures at idle and/or economical cruising mode. Third, the high velocity of the gas in the combustion chamber (up to 30-50 m/s) resulting in a rapid compression of swirling inlet flow. The paper presents the results of tests of distributed spark ignition system powered by repetitive pulse nanosecond discharge. Dynamic pressure measurements show the increased pressure and frequency stability for nanosecond excitation in comparison with the standard spark plug. Excitation by single nanosecond high-voltage pulse and short train of pulses was examined. In all regimes the nanosecond pulsed excitation demonstrate a better performance.

  1. 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.

  2. Long pulse and high repetition rate operation of a relativistic klystron amplifier

    SciTech Connect

    Levine, J.S.; Harteneck, B.D.

    1994-12-31

    The authors are developing an L-band (1.3 GHz) high current relativistic klystron amplifier for both long pulse ({ge} 500 ns) and high repetition rate ({ge} 200 pps) capabilities. In repetitive operation, it has produced 3.3 kW of average power in 80 ns FWHM pulses of 250 MW peak power at 200 pps. They are currently transferring this same klystron to a single-shot, long-pulse driver to demonstrate its operation with a {ge} 500 ns electrical pulse.

  3. Lethality mechanisms in Escherichia coli induced by intense sub-microsecond electrical pulses

    NASA Astrophysics Data System (ADS)

    Chalise, P. R.; Perni, S.; Shama, G.; Novac, B. M.; Smith, I. R.; Kong, M. G.

    2006-10-01

    In this letter, the authors present the inactivation kinetics of cells of Escherichia coli and its mutants following treatment with high-intensity electrical pulses of 700 and 32ns durations. Their experimental results suggest that bacterial inactivation by 700ns pulses is consistent with a mechanism of reversible electroporation, whereas inactivation by 32ns pulses may occur as a result of damage to intracellular components. They believe that their results represent a first step towards elucidating the mechanism of lethality of submicrosecond pulses of different durations in prokaryotes.

  4. 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

  5. Implications of PSR J0737-3039B for the Galactic NS-NS binary merger rate

    NASA Astrophysics Data System (ADS)

    Kim, Chunglee; Perera, Benetge Bhakthi Pranama; McLaughlin, Maura A.

    2015-03-01

    The Double Pulsar (PSR J0737-3039) is the only neutron star-neutron star (NS-NS) binary in which both NSs have been detectable as radio pulsars. The Double Pulsar has been assumed to dominate the Galactic NS-NS binary merger rate R_g among all known systems, solely based on the properties of the first-born, recycled pulsar (PSR J0737-3039A, or A) with an assumption for the beaming correction factor of 6. In this work, we carefully correct observational biases for the second-born, non-recycled pulsar (PSR J0737-0737B, or B) and estimate the contribution from the Double Pulsar on R_g using constraints available from both A and B. Observational constraints from the B pulsar favour a small beaming correction factor for A (˜2), which is consistent with a bipolar model. Considering known NS-NS binaries with the best observational constraints, including both A and B, we obtain R_g=21_{-14}^{+28} Myr-1 at 95 per cent confidence from our reference model. We expect the detection rate of gravitational waves from NS-NS inspirals for the advanced ground-based gravitational-wave detectors is to be 8^{+10}_{-5} yr-1 at 95 per cent confidence. Within several years, gravitational-wave detections relevant to NS-NS inspirals will provide us useful information to improve pulsar population models.

  6. NMR Analysis of a Novel Enzymatically Active Unlinked Dengue NS2B-NS3 Protease Complex*

    PubMed Central

    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.

    2013-01-01

    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 1H-15N 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. PMID:23511634

  7. 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.

  8. 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

  9. 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%.

  10. 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%. PMID:27250451

  11. Synergistic Activity of Combined NS5A Inhibitors.

    PubMed

    O'Boyle, Donald R; 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

  12. The interaction between the Hepatitis C proteins NS4B and NS5A is involved in viral replication

    PubMed Central

    David, Naama; Yaffe, Yakey; Hagoel, Lior; Elazar, Menashe; Glenn, Jeffrey S.; Hirschberg, Koret; Sklan, Ella H.

    2015-01-01

    Hepatitis C virus (HCV) replicates in membrane associated, highly ordered replication complexes (RCs). These complexes include viral and host proteins necessary for viral RNA genome replication. The interaction network among viral and host proteins underlying the formation of these RCs is yet to be thoroughly characterized. Here, we investigated the association between NS4B and NS5A, two critical RC components. We characterized the interaction between these proteins using fluorescence resonance energy transfer and a mammalian two-hybrid system. Specific tryptophan residues within the C-terminal domain (CTD) of NS4B were shown to mediate this interaction. Domain I of NS5A, was sufficient to mediate its interaction with NS4B. Mutations in the NS4B CTD tryptophan residues abolished viral replication. Moreover, one of these mutations also affected NS5A hyperphosphorylation. These findings provide new insights into the importance of the NS4B–NS5A interaction and serve as a starting point for studying the complex interactions between the replicase subunits. PMID:25462354

  13. Characterisation of divergent flavivirus NS3 and NS5 protein sequences detected in Rhipicephalus microplus ticks from Brazil

    PubMed Central

    Maruyama, Sandra Regina; Castro-Jorge, Luiza Antunes; Ribeiro, José Marcos Chaves; Gardinassi, Luiz Gustavo; Garcia, Gustavo Rocha; Brandão, Lucinda Giampietro; Rodrigues, Aline Rezende; Okada, Marcos Ituo; Abrão, Emiliana Pereira; Ferreira, Beatriz Rossetti; da Fonseca, Benedito Antonio Lopes; de Miranda-Santos, Isabel Kinney Ferreira

    2013-01-01

    Transcripts similar to those that encode the nonstructural (NS) proteins NS3 and NS5 from flaviviruses were found in a salivary gland (SG) complementary DNA (cDNA) library from the cattle tick Rhipicephalus microplus. Tick extracts were cultured with cells to enable the isolation of viruses capable of replicating in cultured invertebrate and vertebrate cells. Deep sequencing of the viral RNA isolated from culture supernatants provided the complete coding sequences for the NS3 and NS5 proteins and their molecular characterisation confirmed similarity with the NS3 and NS5 sequences from other flaviviruses. Despite this similarity, phylogenetic analyses revealed that this potentially novel virus may be a highly divergent member of the genus Flavivirus. Interestingly, we detected the divergent NS3 and NS5 sequences in ticks collected from several dairy farms widely distributed throughout three regions of Brazil. This is the first report of flavivirus-like transcripts in R. microplus ticks. This novel virus is a potential arbovirus because it replicated in arthropod and mammalian cells; furthermore, it was detected in a cDNA library from tick SGs and therefore may be present in tick saliva. It is important to determine whether and by what means this potential virus is transmissible and to monitor the virus as a potential emerging tick-borne zoonotic pathogen. PMID:24626302

  14. 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.

  15. 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...

  16. 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...

  17. 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...

  18. 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...

  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. 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

  1. Compact pulse forming line using barium titanate ceramic material

    NASA Astrophysics Data System (ADS)

    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 (BaTiO3) 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.

  2. 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

  3. 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

  4. Application of laser pulse stretching scheme for efficiently delivering laser energy in photoacoustic imaging

    PubMed Central

    Wang, Tianheng; Kumavor, Patrick D.

    2012-01-01

    Abstract. High-energy and short-duration laser pulses are desirable to improve the photoacoustic image quality when imaging deeply seated lesions. In many clinical applications, the high-energy pulses are coupled to tissue using optical fibers. These pulses can damage fibers if the damage threshold is exceeded. While keeping the total energy under the Food and Drug Administration limit for avoiding tissue damage, it is necessary to reduce the peak intensity and increase the pulse duration for minimizing fiber damage and delivering sufficient light for imaging. We use laser-pulse-stretching to address this problem. An initial 17-ns pulse was stretched to 27 and 37 ns by a ring-cavity laser-pulse-stretching system. The peak power of the 37-ns stretched pulse reduced to 42% of the original, while the fiber damage threshold was increased by 1.5-fold. Three ultrasound transducers centered at 1.3-, 3.5-, and 6-MHz frequencies were simulated, and the results showed that the photoacoustic signal of a 0.5-mm-diameter target obtained with 37-ns pulse was about 98, 91, and 80%, respectively, using the same energy as the 17-ns pulse. Simulations were validated using a broadband hydrophone. Quantitative comparisons of photoacoustic images obtained with three corresponding transducers showed that the image quality was not affected by stretching the pulse. PMID:22734748

  5. Application of laser pulse stretching scheme for efficiently delivering laser energy in photoacoustic imaging

    NASA Astrophysics Data System (ADS)

    Wang, Tianheng; Kumavor, Patrick D.; Zhu, Quing

    2012-06-01

    High-energy and short-duration laser pulses are desirable to improve the photoacoustic image quality when imaging deeply seated lesions. In many clinical applications, the high-energy pulses are coupled to tissue using optical fibers. These pulses can damage fibers if the damage threshold is exceeded. While keeping the total energy under the Food and Drug Administration limit for avoiding tissue damage, it is necessary to reduce the peak intensity and increase the pulse duration for minimizing fiber damage and delivering sufficient light for imaging. We use laser-pulse-stretching to address this problem. An initial 17-ns pulse was stretched to 27 and 37 ns by a ring-cavity laser-pulse-stretching system. The peak power of the 37-ns stretched pulse reduced to 42% of the original, while the fiber damage threshold was increased by 1.5-fold. Three ultrasound transducers centered at 1.3-, 3.5-, and 6-MHz frequencies were simulated, and the results showed that the photoacoustic signal of a 0.5-mm-diameter target obtained with 37-ns pulse was about 98, 91, and 80%, respectively, using the same energy as the 17-ns pulse. Simulations were validated using a broadband hydrophone. Quantitative comparisons of photoacoustic images obtained with three corresponding transducers showed that the image quality was not affected by stretching the pulse.

  6. 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

  7. Influence of pulse width and target density on pulsed laser deposition of thin YBaCuO film.

    SciTech Connect

    Vikram, S.

    1999-01-20

    We have studied the effects of temporal pulse width and target density on the deposition of thin films of YBaCuO. A 248nm excimer laser and an 825nm Ti-sapphire laser were used to conduct the experiments with pulse widths of 27 ns, 16 ns, and 150 fs, and target densities of 80% and 90%. Scanning electron microscope photomicrographs and profilometer traces show a striking difference between nanosecond and femtosecond laser irradiation. Shortening the pulse width reduced particulate formation, provided stoichiometry, and improved the film properties. Decreasing the target density raised the ablation rate, produced thicker but nonuniform films, and reduced particulate formation.

  8. Influence of pulse width on ultraviolet laser ablation of poly(methyl methacrylate)

    NASA Astrophysics Data System (ADS)

    Srinivasan, R.; Braren, Bodil

    1988-10-01

    The etching of poly(methyl methacrylate) using pulses of 248 nm laser radiation which had a full width at half maximum (FWHM) of 40-100 ns is reported. These pulses were created by combining two identical pulses, each of 40 ns FWHM, with a set time delay. The etch depth/pulse is sensitive to the pulse width and, therefore, the power density in this polymer. It can be explained by the changes in absorptivity during a pulse that have been reported by G. M. Davis and M. C. Gower [J. Appl. Phys. 61, 2090 (1987)]. The shape of the pulse was also found to influence the etch depth/pulse. The etching of polyimide by these extended pulses shows trends that are opposite to those observed in poly(methyl methacrylate). In this instance, the shielding of the latter portion of the incoming pulse by the products that are ablated by the front portion is probably a serious effect.

  9. Nanosecond electric pulses deprive zinc ions of carboxypeptidase G2.

    PubMed

    Yu, Tinghe; Fu, Xiao

    2015-02-01

    Nanosecond electric pulses (nsEP, 10kV/cm with a pulse duration of 8, 16 or 24ns) inhibited the activity of carboxypeptidase G2 (CPG2), a zinc-dependent homodimer; the relative activity was <20% when the total exposure time was >120s. No alterations were detected in electrophoresis, chromatography, mass spectroscopy and circular dichroism, thus demonstrating intactness of the apoenzyme. Inductively coupled plasma-mass spectrometry indicated that zinc levels were 3.30μg/mg protein in control CPG2, and decreased to 0.40, 0.12 or 0.38μg/mg protein after 240s of 8-, 16- or 24-ns pulses, respectively. In CPG2 exposed to 240s of 8-, 16- and 24-ns pulses, the reloading of zinc with redialysis recovered the activity to 94.7±3.4%, 84.0±5.2% and 81.7±7.0%, respectively (p=0.0853, 0.0741, 0.0668). These data demonstrated that nsEP inhibited CPG2 via removal of zinc, and that nsEP can be used to modulate CPG2. PMID:25049063

  10. 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).

  11. Mechanisms of HCV NS3 Helicase Monitored by Optical Tweezers

    PubMed Central

    Cheng, Wei

    2015-01-01

    As one of the essential enzymes for viral genome replication, the hepatitis C virus NS3 helicase is one of the best characterized RNA helicases to date in understanding the mechanistic cycles in a helicase-catalyzed strand separation reaction. Recently, single-molecule studies on NS3, in particular the use of optical tweezers with sub-base pair spatial resolution, have allowed people to examine the potential elementary steps of NS3 in unwinding the double-stranded RNA fueled by ATP binding and hydrolysis. In this chapter, I detail the essential technical elements involved in conducting a high-resolution optical tweezers study of NS3 helicase, starting from the purification of the recombinant helicase protein from E. coli to setting up a high-resolution single-molecule experiment using optical tweezers. PMID:25579590

  12. 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.

  13. Generation of nanosecond neutron pulses in vacuum accelerating tubes

    NASA Astrophysics Data System (ADS)

    Didenko, A. N.; Shikanov, A. E.; Rashchikov, V. I.; Ryzhkov, V. I.; Shatokhin, V. L.

    2014-06-01

    The generation of neutron pulses with a duration of 1-100 ns using small vacuum accelerating tubes is considered. Two physical models of acceleration of short deuteron bunches in pulse neutron generators are described. The dependences of an instantaneous neutron flux in accelerating tubes on the parameters of pulse neutron generators are obtained using computer simulation. The results of experimental investigation of short-pulse neutron generators based on the accelerating tube with a vacuum-arc deuteron source, connected in the circuit with a discharge peaker, and an accelerating tube with a laser deuteron source, connected according to the Arkad'ev-Marx circuit, are given. In the experiments, the neutron yield per pulse reached 107 for a pulse duration of 10-100 ns. The resultant experimental data are in satisfactory agreement with the results of computer simulation.

  14. Time-resolved investigation of nanosecond discharge in dense gas sustained by short and long high-voltage pulse

    NASA Astrophysics Data System (ADS)

    Yatom, S.; Gleizer, J. Z.; Levko, D.; Vekselman, V.; Gurovich, V.; Hupf, E.; Hadas, Y.; Krasik, Ya. E.

    2011-12-01

    The results of experimental and numerical studies of the generation of runaway electrons (RAE) in a pressurized air-filled diode under the application of 20 ns, 5 ns and 1 ns duration high-voltage pulses with an amplitude up to 160 kV are presented. It is shown that with a 1 ns pulse, RAE with energy >=20 keV reach the anode prior to the formation of the plasma channel between the cathode and anode. Conversely, with 20 ns or 5 ns pulses, RAE with energy >=20 keV were obtained at the anode only after the formation of the plasma channel. In addition, the high- and low-impedance stages of the development of the discharge were found. Finally, a comparison between experimental and numerical simulation results is presented.

  15. 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.

  16. 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

  17. Material micromachining using a pulsed fiber laser platform with fine temporal nanosecond pulse shaping capability

    NASA Astrophysics Data System (ADS)

    Deladurantaye, Pascal; Gay, David; Cournoyer, Alain; Roy, Vincent; Labranche, Bruno; Levesque, Marc; Taillon, Yves

    2009-02-01

    We report on recent advances in laser material processing using a novel pulsed fiber laser platform providing pulse shape agility at the nanosecond time scale and at high repetition rates. The pulse shapes can be programmed with a time resolution of 2.5 ns and with an amplitude resolution of 10 bits. Depending on the desired laser performances, the pulses are generated either by directly modulating the drive current of a seed laser diode or by modulating the output of a seed laser diode operated in CW with electro-optic modulators. The pulses are amplified in an amplifier chain in a MOPA configuration. Advanced polarization maintaining LMA fiber designs enable output energy per pulse up to 60 μJ at 1064 nm at a repetition rate of 200 kHz with excellent beam quality (M2< 1.1) and narrow line widths suitable for efficient frequency conversion. Micro-milling experiments were carried out with stainless steel, in which processing microstructures of a few tens of microns in size usually represents a challenge, and aluminum, whose thermal conductivity is about 20 times higher than stainless steel. The results obtained with two metals having very different thermal properties using different pulse shapes with durations varying between 3 ns and 80 ns demonstrate the benefits of using lasers offering flexible pulse durations and controllable pulse intensity profiles for rapidly optimizing a process in different applications while using the same laser with respect to conventional methods based on pulsed laser with fixed pulse shapes. Numerous applications are envisioned in a near future, like the micromachining of multi-layered structures, in particular when working with the harmonics of the laser.

  18. Dengue protease activity: the structural integrity and interaction of NS2B with NS3 protease and its potential as a drug target.

    PubMed

    Phong, Wai Y; Moreland, Nicole J; Lim, Siew P; Wen, Daying; Paradkar, Prasad N; Vasudevan, Subhash G

    2011-10-01

    Flaviviral NS3 serine proteases require the NS2B cofactor region (cNS2B) to be active. Recent crystal structures of WNV (West Nile virus) protease in complex with inhibitors revealed that cNS2B participates in the formation of the protease active site. No crystal structures of ternary complexes are currently available for DENV (dengue virus) to validate the role of cNS2B in active site formation. In the present study, a GST (glutathione transferase) fusion protein of DENV-2 cNS2B49-95 was used as a bait to pull down DENV-2 protease domain (NS3pro). The affinity of NS3pro for cNS2B was strong (equilibrium-binding constant <200 nM) and the heterodimeric complex displayed a catalytic efficiency similar to that of single-chain DENV-2 cNS2B/NS3pro. Various truncations and mutations in the cNS2B sequence showed that conformational integrity of the entire 47 amino acids is critical for protease activity. Furthermore, DENV-2 NS3 protease can be pulled down and transactivated by cNS2B cofactors from DENV-1, -3, -4 and WNV, suggesting that mechanisms for activation are conserved across the flavivirus genus. To validate NS2B as a potential target in allosteric inhibitor development, a cNS2B-specific human monoclonal antibody (3F10) was utilized. 3F10 disrupted the interaction between cNS2B and NS3 in vitro and reduced DENV viral replication in HEK (human embryonic kidney)-293 cells. This provides proof-of-concept for developing assays to find inhibitors that block the interaction between NS2B and NS3 during viral translation. PMID:21329491

  19. Laser generation of subnanosecond sound pulses in liquids

    NASA Astrophysics Data System (ADS)

    Vodopianov, K. L.; Kulevskii, L. A.; Mikhalevich, V. G.; Rodin, A. M.

    1986-07-01

    Laser generation of intense sound pulses of subnanosecond duration is observed for the first time. Use is made of hydroxyl-containing liquids with hydrogen bonds such as water, ethanol and glycerine which possess very high light absorption coefficients at the laser wavelength of 2.94 microns. When using ultrashort laser pulses (tau = 80 ps) with energies reaching 60 microjoules, sound pressure pulses 0.75 ns in duration with amplitudes reaching 20 kbar (in water) were obtained.

  20. Dynamic pulsing of a MOPA fiber laser for enhanced material processing

    NASA Astrophysics Data System (ADS)

    Hendow, Sami T.; Salcedo, José R.; Romero, Rosa; Guerreiro, Paulo T.

    2011-02-01

    Pulse bursting is demonstrated using a pulsed MOPA fiber laser at 1064 nm for percussion drilling of stainless steel. Bursts are configured as fast pulse sequences at tens of MHz, with a temporal envelope in the range from 10 to 420 ns. Their use rapidly enhances the efficiency of material removal by enhancing pulse energy deposition, and quality improvement. Results are shown for various pulse conditions by changing number of pulses, spacing and peak powers. Each pulse burst is collectively triggered and amplified as a single pulse group, at repetition frequencies from singleshot to hundreds of kHz.

  1. 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.

  2. 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.

  3. 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 ...

  4. Crab Nebula observations - 0.2-10 MeV

    NASA Technical Reports Server (NTRS)

    Gruber, D. E.

    1975-01-01

    Observations of the total emission from the Crab Nebula and also of the pulsed component were made over the 0.2 to 10-MeV range during three balloon flights in 1971 with an actively-collimated NaI scintillator. The total emission flux was positively observed over the entire interval. The observed spectrum to 1 MeV agrees with an extrapolation of the E to the -2.2 power law, which fits lower-energy data. The observations above 1 MeV are factors of 3 and 20 above this law and are better fit with a spectral index of 0.8. Confidence levels are 3 sigma or better for each half-decade band. The three observations are consistent with a constant flux level. The NP 0532 flux, detected during one flight only (August 8) between 0.2 and 0.38 MeV, agrees with the exponential power law spectrum already determined from other observations. The possibility of a rapidly rising pulsed emission fraction over the 0.1- to 1-MeV interval is excluded by this observation.

  5. 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)

  6. 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.

  7. 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.

  8. 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

  9. 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.

  10. 32.5 mJ and 4.6 ns 532 nm Q-switched Nd:YAG laser at 500 Hz.

    PubMed

    Zhang, Zilong; Liu, Qiang; Gong, Mali

    2013-04-20

    A laser diode side-pumped electro-optical Q-switched Nd:YAG green light laser with high repetition rates, short pulse width, and high peak power was demonstrated. We studied the performance of the oscillator at the repetition rates from 100 to 500 Hz. At 500 Hz, 61 mJ, 5 ns of 1064 nm infrared light pulses were obtained with an oscillator-amplifier system. The peak power of the pulse was 12 MW. By frequency doubling with a LiB(3)O(5)(LBO) crystal, 32.5 mJ, 4.6 ns of 532 nm green light was achieved, corresponding to a peak power of 7 MW. The frequency conversion efficiency was 53.3%. PMID:23669684

  11. Hepatitis C Virus NS3/4A Protease Inhibitors.

    PubMed

    López-Labrador, Francesc-Xavier

    2008-11-01

    Chronic hepatitis C virus infection is a global problem worldwide due to the lack of an effective therapy (the current standard of care treatment is effective in about 40-50% of the cases), and the difficulties in developing a protective vaccine. Chronic infection progresses to end-stage liver disease and liver failure in a considerable number of infected individuals. Once liver function is compromised, the only reliable therapeutic intervention is liver transplantation. Unfortunately, re-infection of the graft is unavoidable, and a new chronic hepatitis is early established in transplant recipients, that can result in graft loss. Thus, there is an urgent need for new, specifically targeted therapies for the treatment of HCV chronic infection. Among the viral proteins, the NS3/4A protease and the NS5b RNA-dependent RNA-polymerase, essential for the virus life cycle, have concentrated the efforts in the development of new antivirals, and some promising ones have already entered clinical trials. In particular, inhibitors of the HCV NS3/4A protease are the most advanced in clinical development. This review summarizes the available data for the most important HCV NS3/4A protease inhibitors in development, the most recent patents of these type of compounds, the envisioned options for future HCV therapies, and the eventual impact of HCV genetic variability on resistance to new NS3/4A protease inhibitors. PMID:18991798

  12. Dynamic pulsing of a MOPA fiber laser

    NASA Astrophysics Data System (ADS)

    Romero, Rosa; Guerreiro, Paulo T.; Hendow, Sami T.; Salcedo, José R.

    2011-05-01

    Dynamic Pulsing is demonstrated using a pulsed MOPA fiber laser at 1064nm. The output of the MOPA laser is a pulsed profile consisting of a burst of closely spaced pulses. Tests were performed under several materials with pulse bursts ranging from 10ns to 1μs and operating from 500kHz down to single shot. In particular, percussion drilling in stainless steel is demonstrated showing improvements in quality and speed of the process. These profiles allow high flexibility and optimization of the process addressing the specificity of the end application. Dynamic Pulsing allows the same MOPA fiber laser to be used in diverse materials as well as different processes such us marking, drilling, scribing and engraving. The pulsed fiber laser used in this study is a MOPA-DY by Multiwave Photonics. It is based on a modulated seed laser followed by a series of fiber amplifiers and ending with an optically isolated collimator. This pulsed laser model has an output in such a way that each trigger produces a fast burst of pulses, with a repetition frequency within the burst of the order of tens of MHz. Within the burst it is possible to change the number of pulses, the individual pulse profile, burst pulse period and even to generate non-periodic burst pulse separations. The laser allows full freedom for all these combinations. The study here reported compares the impact of pulse peak power, number of pulses within a burst and the pulse burst period, on process quality (heat affected zone, debris, hole uniformity) and drilling yield.

  13. 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.

  14. 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.

  15. High power amplification of a tailored-pulse fiber laser

    NASA Astrophysics Data System (ADS)

    Saby, Julien; Sangla, Damien; Caplette, Stéphane; Boula-Picard, Reynald; Drolet, Mathieu; Reid, Benoit; Salin, François

    2013-02-01

    We demonstrate the amplification of a 1064nm pulse-programmable fiber laser with Large Pitch Rod-Type Fibers of various Mode field diameters from 50 to 70 μm. We have developed a high power fiber amplifier at 1064nm delivering up to 100W/1mJ at 15ns pulses and 30W/300μJ at 2ns with linearly polarized and diffraction limited output beam (M²<1.2). The specific seeder from ESI - Pyrophotonics Lasers used in the experiment allowed us to obtain tailored-pulse programmable on demand at the output from 2ns to 600ns for various repetition rates from 10 to 500 kHz. We could demonstrate square pulses or any other shapes (also multi-pulses) whatever the repetition rate or the pulse duration. We also performed frequency conversion with LBO crystals leading to 50W at 532nm and 25W at 355nm with a diffraction limited output. Similar experiments performed at 1032nm are also reported.

  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. 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.

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

    NASA Astrophysics Data System (ADS)

    Wu, Jian; Sun, Tie-Ping; Wu, Gang; Wang, Liang-Ping; Han, Juan-Juan; Li, Mo; Cong, Pei-Tian; Qiu, Ai-Ci; Lv, Min

    2011-05-01

    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 μm, 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 μm 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.

  19. Deletion of the C-terminal region of dengue virus nonstructural protein 1 (NS1) abolishes anti-NS1-mediated platelet dysfunction and bleeding tendency.

    PubMed

    Chen, Mei-Chun; Lin, Chiou-Feng; Lei, Huan-Yao; Lin, Shih-Chao; Liu, Hsiao-Sheng; Yeh, Trai-Ming; Anderson, Robert; Lin, Yee-Shin

    2009-08-01

    The mechanisms underlying dengue hemorrhagic disease are incompletely understood. We previously showed that anti-dengue virus (DV) nonstructural protein 1 (NS1) Abs cross-react with human platelets and inhibit platelet aggregation. Based on sequence homology alignment, the cross-reactive epitopes reside in the C-terminal region of DV NS1. In this study, we compared the effects of Abs against full-length DV NS1 and NS1 lacking the C-terminal aa 271 to 352 (designated DeltaC NS1). Anti-DeltaC NS1 Abs exhibited lower platelet binding activity than that of anti-full-length NS1. Anti-full-length NS1 but not anti-DeltaC NS1 Abs inhibited platelet aggregation, which was shown to involve integrin alpha(IIb)beta(3) inactivation. We found that the bleeding time in full-length NS1-hyperimmunized mice was longer than that in the normal control mice. By contrast, DeltaC NS1-hyperimmunized mice showed a bleeding time similar to that of normal control mice. Passively administered anti-DV NS1, but not anti-DeltaC NS1, Ab level decreased markedly in serum and this decrease was correlated with Ab binding to platelets. A transient platelet loss in the circulation was observed after anti-DV NS1, but not anti-DeltaC NS1, Ab administration. In summary, platelet dysfunction and bleeding tendency are induced by anti-full-length DV NS1 but not by anti-DeltaC NS1 Abs. These findings may be important not only for understanding dengue hemorrhagic disease pathogenesis but also for dengue vaccine development. PMID:19592650

  20. Fine tuning of phase qubit parameters for optimization of fast single-pulse readout

    SciTech Connect

    Revin, Leonid S.; Pankratov, Andrey L.

    2011-04-18

    We analyze a two-level quantum system, describing the phase qubit, during a single-pulse readout process by a numerical solution of the time-dependent Schroedinger equation. It has been demonstrated that the readout error has a minimum for certain values of the system's basic parameters. In particular, the optimization of the qubit capacitance and the readout pulse shape leads to significant reduction in the readout error. It is shown that in an ideal case the fidelity can be increased to almost 97% for 2 ns pulse duration and to 96% for 1 ns pulse duration.

  1. 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.

  2. 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.

  3. 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. PMID:20588633

  4. 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.

  5. 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.

  6. 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.

  7. 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

  8. Efficient 13.5 nm extreme ultraviolet emission from Sn plasma irradiated by a long CO{sub 2} laser pulse

    SciTech Connect

    Tao, Y.; Tillack, M. S.; Sequoia, K. L.; Burdt, R. A.; Yuspeh, S.; Najmabadi, F.

    2008-06-23

    The effect of pulse duration on in-band (2% bandwidth) conversion efficiency (CE) from a CO{sub 2} laser to 13.5 nm extreme ultraviolet (EUV) light was investigated for Sn plasma. It was found that high in-band CE, 2.6%, is consistently obtained using a CO{sub 2} laser with pulse durations from 25 to 110 ns. Employing a long pulse, for example, 110 ns, in a CO{sub 2} laser system used in an EUV lithography source could make the system significantly more efficient, simpler, and cheaper as compared to that using a short pulse of 25 ns or shorter.

  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. PMID:27370479

  11. Pulsed power

    NASA Astrophysics Data System (ADS)

    Stone, David H.

    Pulsed power systems are critical elements for such prospective weapons technologies as high-power microwaves, electrothermal and electromagnetic projectile launchers, neutral particle beams, space-based FELs, ground-based lasers, and charged particle beams. Pulsed power will also be essential for the development of nonweapon military systems such as lidars and ultrawideband radars, and could serve as the bases for nuclear weapon effect simulators. The pulsed power generation requirements for each of these systems is considered.

  12. Construction of plasmid, bacterial expression, purification, and assay of dengue virus type 2 NS5 methyltransferase.

    PubMed

    Boonyasuppayakorn, Siwaporn; Padmanabhan, Radhakrishnan

    2014-01-01

    Dengue virus (DENV), a member of mosquito-borne flavivirus, causes self-limiting dengue fever as well as life-threatening dengue hemorrhagic fever and dengue shock syndrome. Its positive sense RNA genome has a cap at the 5'-end and no poly(A) tail at the 3'-end. The viral RNA encodes a single polyprotein, C-prM-E-NS1-NS2A-NS2B-NS3-NS4A-NS4B-NS5. The polyprotein is processed into 3 structural proteins (C, prM, and E) and 7 nonstructural (NS) proteins (NS1, NS2A, NS2B, NS3, NS4A, NS4B, NS5). NS3 and NS5 are multifunctional enzymes performing various tasks in viral life cycle. The N-terminal domain of NS5 has distinct GTP and S-adenosylmethionine (SAM) binding sites. The role of GTP binding site is implicated in guanylyltransferase (GTase) activity of NS5. The SAM binding site is involved in both N-7 and 2'-O-methyltransferase (MTase) activities involved in formation of type I cap. The C-terminal domain of NS5 catalyzes RNA-dependent RNA polymerase (RdRp) activity involved in RNA synthesis. We describe the construction of the MTase domain of NS5 in an E. coli expression vector, purification of the enzyme, and conditions for enzymatic assays of N7- and 2'O-methyltransferase activities that yield the final type I 5'-capped RNA ((7Me)GpppA2'OMe-RNA). PMID:24696348

  13. 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.

  14. 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.

  15. Tunable pulse width and multi-megawatt peak-power pulses from a nonlinearly compressed monolithic fiber MOPA system

    NASA Astrophysics Data System (ADS)

    Yamashita, Ryutarou; Maeda, Kazuo; Watanabe, Goro; Tei, Kazuyoku; Yamaguchi, Shigeru; Enokidani, Jun; Sumida, Shin

    2016-03-01

    We report on tunable pulse width and high peak power pulse generation from a nonlinearly compressed monolithic fiber MOPA system. The master seed source employs a Mach-Zehnder intensity modulator (MZIM). This seed source has operational flexibility with respect to pulse width, 90 ps to 2 ns and repetition rate, 200 kHz to 2 MHz. The seed pulses are amplified by a monolithic three-stage amplifier system based on polarization maintain Yb-doped fibers. The maximum output power was 32 W at the shortest pulse condition, the pulse width of 90 ps and the repetition rate of 750 kHz. A spectral width after amplification was broadened to 0.73 nm at RMS width. Both of ASE and SRS are not observed in the spectrum. After amplification, we also demonstrated pulse compression with a small piece of chirped volume Bragg-grating (CVBG) which has the dispersion rate of 81 ps/nm. As a result of pulse compression, the shortest pulse width was reduced from 90 ps to 3.5 ps, which brought an increase of the peak power up to 3.2 MW. The compressed pulses are clean with little structure in their wings. We can expand the operation range of the monolithic fiber MOPA system in pulse width, 3.5 ps to 2 ns.

  16. 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

  17. 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

  18. 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.

  19. 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.

  20. 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

  1. 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

  2. LABORATORY AND FIELD EVALUATION OF NS-100 REVERSE OSMOSIS MEMBRANE

    EPA Science Inventory

    Laboratory life tests were conducted with B-9 and NS-100 reverse osmosis (RO) membranes treating zinc cyanide plating solution at 10% of bath strength. The B-9 membrane was degraded by the high pH of the solution which was beyond the upper pH limit (pH 11) recommended for this me...

  3. 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.

  4. 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.

  5. 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.

  6. UV laser removal of varnish on tempera paints with nanosecond and femtosecond pulses.

    PubMed

    Oujja, Mohamed; García, Ana; Romero, Carolina; Vázquez de Aldana, Javier R; Moreno, Pablo; Castillejo, Marta

    2011-03-14

    Two laser cleaning approaches based on ablation by ultraviolet laser pulses of femtosecond (fs) and nanosecond (ns) durations for the removal of shellac varnish from egg-yolk based tempera paints are investigated. Laser irradiation effects, induced on the varnish layer and on the underlying temperas by multiple pulses in the fs domain at 398 and 265 nm and single pulses in the ns domain at 213 nm, were examined following a spectroanalytical approach. By using optical microscopy, colorimetry and laser induced fluorescence it was found that irradiation of the varnished temperas with fs pulses changes the texture of the varnish surface and results in degradation of the underlying coloured paint. In contrast, operating with pulses of 15 ns at the highly absorbed wavelength of 213 nm, controlled micrometric layer removal of the varnish is possible without noticeable modification of the coloured temperas. These results widen the choice of laser conditions for painting restoration. PMID:21264373

  7. 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.

  8. 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

  9. 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

  10. 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.

  11. 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.

  12. 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.

  13. 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. PMID:24985810

  14. 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. PMID:24289423

  15. 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.

  16. 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.

  17. 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.

  18. RNA-protein interactions: involvement of NS3, NS5, and 3' noncoding regions of Japanese encephalitis virus genomic RNA.

    PubMed Central

    Chen, C J; Kuo, M D; Chien, L J; Hsu, S L; Wang, Y M; Lin, J H

    1997-01-01

    The mechanism of replication of the flavivirus Japanese encephalitis virus (JEV) is not well known. The structures at the 3' end of the viral genome are highly conserved among divergent flaviviruses, suggesting that they may function as cis-acting signals for RNA replication and, as such, might specifically bind to cellular or viral proteins. UV cross-linking experiments were performed to identify the proteins that bind with the JEV plus-strand 3' noncoding region (NCR). Two proteins, p71 and p110, from JEV-infected but not from uninfected cell extracts were shown to bind specifically to the plus-strand 3' NCR. The quantities of these binding proteins increased during the course of JEV infection and correlated with the levels of JEV RNA synthesis in cell extracts. UV cross-linking coupled with Western blot and immunoprecipitation analysis showed that the p110 and p71 proteins were JEV NS5 and NS3, respectively, which are proposed as components of the RNA replicase. The putative stem-loop structure present within the plus-strand 3' NCR was required for the binding of these proteins. Furthermore, both proteins could interact with each other and form a protein-protein complex in vivo. These findings suggest that the 3' NCR of JEV genomic RNA may form a replication complex together with NS3 and NS5; this complex may be involved in JEV minus-strand RNA synthesis. PMID:9094618

  19. 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.

  20. Generating Microwave Radiation Pulses with MCG

    NASA Astrophysics Data System (ADS)

    Zherlitsyn, A. G.; Kanaev, G. G.; Melnikov, G. V.; Tsvetkov, V. I.; Ushnurtsev, A. E.; Dudin, S. V.; Mintsev, V. B.; Fortov, V. E.

    2004-11-01

    Transformer schemes matching magnetocumulative generators (MCG) with high impedance loads, like vircator, look promising for achieving long pulse duration of 1 μs. An analysis of expected parameters is made here. The necessary MCG and transformer parameters are discussed and the experimental set-up is described. The shots with the MCG simulator were carried out first. At simulator voltage 40 kV and reserved energy 12 kJ, the voltage pulse with amplitude to 600 kV and 320 ns duration is generated on a triode with a virtual cathode. Microwave radiation of 300-400 MW and 200-300 ns duration is generated within a 10 cm wavelength range.

  1. 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.

  2. 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.

  3. 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.

  4. Performance of commercial dengue NS1 ELISA and molecular analysis of NS1 gene of dengue viruses obtained during surveillance in Indonesia

    PubMed Central

    2013-01-01

    Background Early diagnosis of dengue infection is crucial for better management of the disease. Diagnostic tests based on the detection of dengue virus (DENV) Non Structural Protein 1 (NS1) antigen are commercially available with different sensitivities and specificities observed in various settings. Dengue is endemic in Indonesia and clinicians are increasingly using the NS1 detection for dengue confirmation. This study described the performance of Panbio Dengue Early NS1 and IgM Capture ELISA assays for dengue detection during our surveillance in eight cities in Indonesia as well as the genetic diversity of DENV NS1 genes and its relationship with the NS1 detection. Methods The NS1 and IgM/IgG ELISA assays were used for screening and confirmation of dengue infection during surveillance in 2010–2012. Collected serum samples (n = 440) were subjected to RT-PCR and virus isolation, in which 188 samples were confirmed for dengue infection. The positivity of the ELISA assays were correlated with the RT-PCR results to obtain the sensitivity of the assays. The NS1 genes of 48 Indonesian virus isolates were sequenced and their genetic characteristics were studied. Results Using molecular data as gold standard, the sensitivity of NS1 ELISA assay for samples from Indonesia was 56.4% while IgM ELISA was 73.7%. When both NS1 and IgM results were combined, the sensitivity increased to 89.4%. The NS1 sensitivity varied when correlated with city/geographical origins and DENV serotype, in which the lowest sensitivity was observed for DENV-4 (19.0%). NS1 sensitivity was higher in primary (67.6%) compared to secondary infection (48.2%). The specificity of NS1 assay for non-dengue samples were 100%. The NS1 gene sequence analysis of 48 isolates revealed the presence of polymorphisms of the NS1 genes which apparently did not influence the NS1 sensitivity. Conclusions We observed a relatively low sensitivity of NS1 ELISA for dengue detection on RT-PCR-positive dengue samples

  5. Inhibition of hepatitis C virus infection by DNA aptamer against NS2 protein.

    PubMed

    Gao, Yimin; Yu, Xiaoyan; Xue, Binbin; Zhou, Fei; Wang, Xiaohong; Yang, Darong; Liu, Nianli; Xu, Li; Fang, Xiaohong; Zhu, Haizhen

    2014-01-01

    NS2 protein is essential for hepatitis C virus (HCV) replication. NS2 protein was expressed and purified. Aptamers against NS2 protein were raised and antiviral effects of the aptamers were examined. The molecular mechanism through which the aptamers exert their anti-HCV activity was investigated. The data showed that aptamer NS2-3 inhibited HCV RNA replication in replicon cell line and infectious HCV cell culture system. NS2-3 and another aptamer NS2-2 were demonstrated to inhibit infectious virus production without cytotoxicity in vitro. They did not affect hepatitis B virus replication. Interferon beta (IFN-β) and interferon-stimulated genes (ISGs) were not induced by the aptamers in HCV-infected hepatocytes. Furthermore, our study showed that N-terminal region of NS2 protein is involved in the inhibition of HCV infection by NS2-2. I861T within NS2 is the major resistance mutation identified. Aptamer NS2-2 disrupts the interaction of NS2 with NS5A protein. The data suggest that NS2-2 aptamer against NS2 protein exerts its antiviral effects through binding to the N-terminal of NS2 and disrupting the interaction of NS2 with NS5A protein. NS2-specific aptamer is the first NS2 inhibitor and can be used to understand the mechanisms of virus replication and assembly. It may be served as attractive candidates for inclusion in the future HCV direct-acting antiviral combination therapies. PMID:24587329

  6. Japanese encephalitis virus NS2B-NS3 protease induces caspase 3 activation and mitochondria-mediated apoptosis in human medulloblastoma cells.

    PubMed

    Yang, Tsuey-Ching; Shiu, Su-Lian; Chuang, Pei-Hsin; Lin, Ying-Ju; Wan, Lei; Lan, Yu-Ching; Lin, Cheng-Wen

    2009-07-01

    Japanese encephalitis virus (JEV) causes severe neurological diseases with a high fatality rate. Clinical, neurophysiological and radiological features of Japanese encephalitis JE patients showed that JEV infection resulted in widespread involvement of the nervous system, including thalamus, basal ganglia, brainstem, cerebellum, cerebral cortex and spinal cord. In this study, we characterized the apoptotic effect of JEV infection and its viral proteins on the TE671 human medulloblastoma cells. JEV replicated in TE671 cells, inducing caspase 3-mediated apoptosis in MOI- and time-dependent manners. Of viral proteins, co-expression of JEV NS3 protease with NS2B cofactor significantly induced higher degrees of apoptosis and triggered higher caspase 3 activities than single expression of E, NS1, NS2B or NS3 protease in human medulloblastoma cells. Moreover, JEV NS2B-NS3 protease induced reduction of mitochondrial membrane potential and release of mitochondrial cytochrome C, which were responsible for the mitochondria-mediated apoptosis. In addition, the production of reactive oxygen species production and activation of ASK1-p38 MAPK signaling pathway might be associated with JEV NS2B-NS3 protease-induced mitochondria-mediated apoptosis. The results demonstrated that the JEV infection and the co-expression of JEV NS3 protease with NS2B cofactor induced caspase 3 activation and mitochondria-mediated apoptosis in human medulloblastoma cells, being valuable insight for cellular and molecular levels of JEV pathogenesis. PMID:19463724

  7. 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. PMID:25218277

  8. NF90 is a novel influenza A virus NS1-interacting protein that antagonizes the inhibitory role of NS1 on PKR phosphorylation.

    PubMed

    Li, Ting; Li, Xi; Zhu, WenFei; Wang, HuiYu; Mei, Lin; Wu, ShaoQiang; Lin, XiangMei; Han, XueQing

    2016-08-01

    NF90 is a novel host antiviral factor that regulates PKR activation and stress granule formation in influenza A virus (IAV)-infected cells, but the precise mechanisms by which it operates remain unclear. We identified NF90 as a novel interacting protein of IAV nonstructural protein 1 (NS1). The interaction was dependent on the RNA-binding properties of NS1. NS1 associated with NF90 and PKR simultaneously; however, the interaction between NF90 and PKR was restricted by NS1. Knockdown of NF90 promoted inhibition of PKR phosphorylation induced by NS1, while coexpression of NF90 impeded reduction of PKR phosphorylation and stress granule formation triggered by NS1. In summary, NF90 exerts its antiviral activity by antagonizing the inhibitory role of NS1 on PKR phosphorylation. PMID:27423063

  9. Structure of a murine norovirus NS6 protease-product complex revealed by adventitious crystallisation.

    PubMed

    Leen, Eoin N; Baeza, Gabriela; Curry, Stephen

    2012-01-01

    Murine noroviruses have emerged as a valuable tool for investigating the molecular basis of infection and pathogenesis of the closely related human noroviruses, which are the major cause of non-bacterial gastroenteritis. The replication of noroviruses relies on the proteolytic processing of a large polyprotein precursor into six non-structural proteins (NS1-2, NS3, NS4, NS5, NS6(pro), NS7(pol)) by the virally-encoded NS6 protease. We report here the crystal structure of MNV NS6(pro), which has been determined to a resolution of 1.6 Å. Adventitiously, the crystal contacts are mediated in part by the binding of the C-terminus of NS6(pro) within the peptide-binding cleft of a neighbouring molecule. This insertion occurs for both molecules in the asymmetric unit of the crystal in a manner that is consistent with physiologically-relevant binding, thereby providing two independent views of a protease-peptide complex. Since the NS6(pro) C-terminus is formed in vivo by NS6(pro) processing, these crystal contacts replicate the protease-product complex that is formed immediately following cleavage of the peptide bond at the NS6-NS7 junction. The observed mode of binding of the C-terminal product peptide yields new insights into the structural basis of NS6(pro) specificity. PMID:22685603

  10. 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

  11. 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.

  12. 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

  13. 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

  14. Heterotic NS5-branes from closed string tachyon condensation

    NASA Astrophysics Data System (ADS)

    Garcia-Etxebarria, Iñaki; Montero, Miguel; Uranga, Angel

    2014-12-01

    We show how to construct the familiar heterotic NS5 brane as a topological soliton in a supercritical version of heterotic string theory. Closed string tachyon condensation removes the extra dimensions, leaving the NS5 in ten dimensions, in a process highly reminiscent of the K-theoretical description of type II D-branes, but linking nontrivial gauge bundles and geometry. This establishes a new kind of equivalence between gravitational and gauge configurations, reminiscent of the gauge/geometry correspondence. We also use the K-theory description to build other heterotic branes as solitons of closed string tachyons. The construction requires a modification of the anomalous Bianchi identity for H3 in supercritical heterotic string theory. We give various proofs for the existence of this modification.

  15. 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.

  16. 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.

  17. Correlation between NS5A Dimerization and Hepatitis C Virus Replication*

    PubMed Central

    Lim, Precious J.; Chatterji, Udayan; Cordek, Daniel; Sharma, Suresh D.; Garcia-Rivera, Jose A.; Cameron, Craig E.; Lin, Kai; Targett-Adams, Paul; Gallay, Philippe A.

    2012-01-01

    Hepatitis C virus (HCV) is the main agent of acute and chronic liver diseases leading to cirrhosis and hepatocellular carcinoma. The current standard therapy has limited efficacy and serious side effects. Thus, the development of alternate therapies is of tremendous importance. HCV NS5A (nonstructural 5A protein) is a pleiotropic protein with key roles in HCV replication and cellular signaling pathways. Here we demonstrate that NS5A dimerization occurs through Domain I (amino acids 1–240). This interaction is not mediated by nucleic acids because benzonase, RNase, and DNase treatments do not prevent NS5A-NS5A interactions. Importantly, DTT abrogates NS5A-NS5A interactions but does not affect NS5A-cyclophilin A interactions. Other reducing agents such as tris(2-carboxyethyl)phosphine and 2-mercaptoethanol also abrogate NS5A-NS5A interactions, implying that disulfide bridges may play a role in this interaction. Cyclophilin inhibitors, cyclosporine A, and alisporivir and NS5A inhibitor BMS-790052 do not block NS5A dimerization, suggesting that their antiviral effects do not involve the disruption of NS5A-NS5A interactions. Four cysteines, Cys-39, Cys-57, Cys-59, and Cys-80, are critical for dimerization. Interestingly, the four cysteines have been proposed to form a zinc-binding motif. Supporting this notion, NS5A dimerization is greatly facilitated by Zn2+ but not by Mg2+ or Mn2+. Importantly, the four cysteines are vital not only for viral replication but also critical for NS5A binding to RNA, revealing a correlation between NS5A dimerization, RNA binding, and HCV replication. Altogether our data suggest that NS5A-NS5A dimerization and/or multimerization could represent a novel target for the development of HCV therapies. PMID:22801423

  18. 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.

  19. A very high sensitivity RF pulse profile measurement system.

    SciTech Connect

    Christodoulou, Christos George; Lai, Jesse B.

    2009-06-01

    A technique for characterizing the pulse profile of a radio-frequency (RF) amplifier over a very wide power range under fast-pulsing conditions is presented. A pulse-modulated transmitter is used to drive a device under test (DUT) with a phase-coded signal that allows for an increased measurement range beyond standard techniques. A measurement receiver that samples points on the output pulse power profile and performs the necessary signal processing and coherent pulse integration, improving the detectability of low-power signals, is described. The measurement technique is applied to two sample amplifiers under fast-pulsing conditions with a pulsewidth of 250 ns at 3-GHz carrier frequency. A full measurement range of greater than 160 dB is achieved, extending the current state of the art in pulse-profiling techniques.

  20. Development of diagnostics for high-energy petawatt pulses

    SciTech Connect

    Jovanovic, I; Hernandez, J; Appel, G; Barker, D; Betts, S; Brewer, W; Brown, C; Chang, J; Chrisp, M; Crane, J; Haefner, C; Lucianetti, A; Rushford, M; Semenov, V; Seppala, L; Shverdin, M; Siders, C; Taranowski, M; Tietbohl, G; Barty, C J

    2006-06-15

    Applications accessed by high energy petawatt (HEPW) lasers require complete, single-shot characterization of pulse spatial, temporal, and energy characteristics. We describe techniques that enable single-shot characterization of the temporal shape and pulse contrast of HEPW pulses with >10{sup 8} dynamic range over a ns-temporal window. Approaches to measure pulse durations that span two orders of magnitude will be discussed. Finally, we describe a novel implementation of spectrally dispersed two-beam interferometry for measurement of the phase difference between two HEPW pulses. This technique can be applied to dispersion and B-integral measurements in a HEPW system, as well as to achieve precise timing of nanosecond pulses. Lastly, spectrally dispersed interferometry represents an ideal technique to enable coherent addition of HEPW pulses for production of ultrahigh intensities.

  1. Short Pulse Experimental Capability at the Nike Laser Facility

    NASA Astrophysics Data System (ADS)

    Weaver, J. L.; Chan, Y.; Gardner, J.; Giuliani, J.; Karasik, M.; Kehne, D.; Mostovych, A.; Obenschain, S.; Velikovich, A.; Schmitt, A.; Serlin, V.; Aglitskiy, Y.; Metzler, N.; Smyth, Z.; Terrell, S.

    2004-11-01

    Recent simulations demonstrated high gain for direct drive pellets compressed by a laser pulse incorporating a short pulse prior to the main pulse. Theoretical work has also shown that a short prepulse can create a tailored density profile that reduces the initial instability growth due to laser imprinting. A new short pulse (0.35-0.75 ns FWHM)is being added to the Nike KrF laser system to facilitate hydrodynamic experiments with short prepulses. This capability has been incorporated into the initial stages of the laser system and the propagation of these pulses through the angularly multiplexed amplifiers is being studied. Measurements of pulse shape and energy will be compared to simulations using the KrF physics code Orestes for the next to last amplifier of the laser system, the 20 cm x 20 cm e-beam pumped laser cell. The effects of amplified spontaneous emission (ASE) upon individual output pulses will be also discussed.

  2. Pulse Voltammetry.

    ERIC Educational Resources Information Center

    Osteryoung, Janet

    1983-01-01

    Discusses the nature of pulse voltammetry, indicating that its widespread use arises from good sensitivity and detection limits and from ease of application and low cost. Provides analytical and mechanistic applications of the procedure. (JN)

  3. Pestivirus NS3 (p80) protein possesses RNA helicase activity.

    PubMed Central

    Warrener, P; Collett, M S

    1995-01-01

    The pestivirus bovine viral diarrhea virus (BVDV) p80 protein (referred to here as the NS3 protein) contains amino acid sequence motifs predictive of three enzymatic activities: serine proteinase, nucleoside triphosphatase, and RNA helicase. We have previously demonstrated that the former two enzymatic activities are associated with this protein. Here, we show that a purified recombinant BVDV NS3 protein derived from baculovirus-infected insect cells possesses RNA helicase activity. BVDV NS3 RNA helicase activity was specifically inhibited by monoclonal antibodies to the p80 protein. The activity was dependent on the presence of nucleoside triphosphate and divalent cation, with a preference for ATP and Mn2+. Hydrolysis of the nucleoside triphosphate was necessary for strand displacement. The helicase activity required substrates with an un-base-paired region on the template strand 3' of the duplex region. As few as three un-base-paired nucleotides were sufficient for efficient oligonucleotide displacement. However, the enzyme did not act on substrates having a single-stranded region only to the 5' end of the duplex or on substrates lacking single-stranded regions altogether (blunt-ended duplex substrates), suggesting that the directionality of the BVDV RNA helicase was 3' to 5' with respect to the template strand. The BVDV helicase activity was able to displace both RNA and DNA oligonucleotides from RNA template strands but was unable to release oligonucleotides from DNA templates. The possible role of this activity in pestivirus replication is discussed. PMID:7853509

  4. 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.

  5. 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.

  6. 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.

  7. 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).

  8. Recovery Time Measurements of Silicon Photomultipliers Using a Pulsed Laser

    NASA Astrophysics Data System (ADS)

    Gruber, L.; Brunner, S. E.; Curceanu, C.; Marton, J.; Romero Vidal, A.; Scordo, A.; Suzuki, K.; Vazquez, O. D.

    We performed an experimental study to determine the pixel recovery time of various Multi Pixel Photon Counters (MPPCs) in order to characterize their rate capability and double-hit resolution. The recovery time constant and its dependence on the operating voltage has been evaluated by measuring the photosensor response to two consecutive laser pulses with varying relative time differences of a few ns (2-3 ns) up to some 100 ns using a waveform analysis technique. A Monte Carlo simulation tool is being developed to model the MPPC recovery process and interpret experimental data. In this context, the influence of after-pulsing, cross-talk and dark-noise on the recovery process can be studied.

  9. Discovery of Dengue Virus NS4B Inhibitors

    PubMed Central

    Wang, Qing-Yin; Dong, Hongping; Zou, Bin; Karuna, Ratna; Wan, Kah Fei; Zou, Jing; Susila, Agatha; Yip, Andy; Shan, Chao; Yeo, Kim Long; Xu, Haoying; Ding, Mei; Chan, Wai Ling; Gu, Feng; Seah, Peck Gee; Liu, Wei; Lakshminarayana, Suresh B.; Kang, CongBao; Lescar, Julien; Blasco, Francesca; Smith, Paul W.

    2015-01-01

    ABSTRACT The four serotypes of dengue virus (DENV-1 to -4) represent the most prevalent mosquito-borne viral pathogens in humans. No clinically approved vaccine or antiviral is currently available for DENV. Here we report a spiropyrazolopyridone compound that potently inhibits DENV both in vitro and in vivo. The inhibitor was identified through screening of a 1.8-million-compound library by using a DENV-2 replicon assay. The compound selectively inhibits DENV-2 and -3 (50% effective concentration [EC50], 10 to 80 nM) but not DENV-1 and -4 (EC50, >20 μM). Resistance analysis showed that a mutation at amino acid 63 of DENV-2 NS4B (a nonenzymatic transmembrane protein and a component of the viral replication complex) could confer resistance to compound inhibition. Genetic studies demonstrate that variations at amino acid 63 of viral NS4B are responsible for the selective inhibition of DENV-2 and -3. Medicinal chemistry improved the physicochemical properties of the initial “hit” (compound 1), leading to compound 14a, which has good in vivo pharmacokinetics. Treatment of DENV-2-infected AG129 mice with compound 14a suppressed viremia, even when the treatment started after viral infection. The results have proven the concept that inhibitors of NS4B could potentially be developed for clinical treatment of DENV infection. Compound 14a represents a potential preclinical candidate for treatment of DENV-2- and -3-infected patients. IMPORTANCE Dengue virus (DENV) threatens up to 2.5 billion people and is now spreading in many regions in the world where it was not previously endemic. While there are several promising vaccine candidates in clinical trials, approved vaccines or antivirals are not yet available. Here we describe the identification and characterization of a spiropyrazolopyridone as a novel inhibitor of DENV by targeting the viral NS4B protein. The compound potently inhibits two of the four serotypes of DENV (DENV-2 and -3) both in vitro and in vivo. Our

  10. The Herschel Planetary Nebula Survey (HerPlaNS)

    NASA Astrophysics Data System (ADS)

    Ueta, T.; Ladjal, D.; HerPlaNS Team

    2012-12-01

    The Herschel Planetary Nebula Survey (HerPlaNS, PI: T. Ueta) is one of the largest Herschel Open Time 1 program in which we explore the far-infrared aspects of 11 planetary nebulae (PNs) with the Herschel Space Observatory, exploiting its unprecedented capabilities in broadband photometry mapping, spectral mapping, and integral-field spectroscopy. We perform (1) deep PACS/SPIRE broadband mapping to account for the coldest dust component of the nebulae and determine the spatial distribution of the dusty haloes in the target PNs, (2) exhaustive PACS/SPIRE line mapping in far-IR atomic and molecular lines in two representative PNs to diagnose the energetics of the nebulae as a function of location in the nebulae, and (3) PACS/SPIRE spectral-energy-distribution spectroscopy at several positions in the target PNs to understand variations in the physical conditions as a function of location in the nebulae, to build a more complete picture of the interplay between the dust and gas components as a function of location in the nebulae. The HerPlaNS survey is distinguished from the existing guaranteed-time Key Program (KPGT), "Mass Loss of Evolved StarS" (MESS, PI: M. Groenewegen, including 10 PNs) by the extra dimension added by spectral mapping and integral-field spatio-spectroscopy that permit simultaneous probing of the gas and dust component in the target PNs. Through these investigations, we will consider the energetics of the entire gas-dust system as a function of location in the nebulae, which is a novel approach that has rarely been taken previously. HerPlaNS is conducted in collaboration with the Chandra Planetary Survey (ChanPlaNS, PI: J.H. Kastner) to furnish substantial PN data resources that would allow us—a community of PN astronomers—to tackle a multitude of unanswered issues in PN physics, from the shaping mechanisms of the nebulae to the energetics of the multi-phased gas-dust system surrounding the central white dwarf. These PN surveys, combined with

  11. 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. PMID:26792253

  12. Fast magneto-optic switch based on nanosecond pulses

    NASA Astrophysics Data System (ADS)

    Weng, Zi-Hua; Ruan, Jian-Jian; Lin, Shao-Han; Chen, Zhi-Min

    2011-09-01

    The paper studies an all fiber high-speed magneto-optic switch which includes an optical route, a nanosecond pulse generator, and a magnetic field module in order to reduce the switching time of the optical switch in the all optical network. A compact nanosecond pulse generator can be designed based on the special character of the avalanche transistor. The output current pulse of the nanosecond pulse generator is less than 5 ns, while the pulse amplitude is more than 100 V and the pulse width is about 10 to 20 ns, which is able to drive a high-speed magnetic field. A solenoid is used as the magnetic field module, and a bismuth-substituted rare-earth iron garnet single crystal is chosen as the Faraday rotator. By changing the direction of current in the solenoid quickly, the magnetization of the magneto-optic material is reversed, and the optical beam can be rapidly switched. The experimental results indicate that the switching time of the device is about 100 to 400 ns, which can partially meet the demand of the rapid development of the all optical network.

  13. 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.

  14. 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.

  15. 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

  16. 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).

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

    NASA Astrophysics Data System (ADS)

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

    2014-07-01

    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.

  18. 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.

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

    PubMed

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

    2014-07-01

    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. PMID:25085130

  20. 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

  1. The effect of pulse duration on laser-induced damage by 1053-nm light in potassium dihydrogen phosphate crystals

    NASA Astrophysics Data System (ADS)

    Cross, D. A.; Braunstein, M. R.; Carr, C. W.

    2007-01-01

    Laser induced damage in potassium dihydogen phosphate (KDP) has previously been shown to depend significantly on pulse duration for 351-nm Gaussian pulses. In this work we studied the properties of damage initiated by 1053-nm temporally Gaussian pulses with 10ns and 3ns FWHM durations. Our results indicate that the number of damage sites induced by 1053-nm light scales with pulse duration (τ) as τ I/τ II) 0.17 in contrast to the previously reported results for 351-nm light as (τ I/τ II) 0.35. This indicates that damage site formation is significantly less probable at longer wavelengths for a given fluence.

  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. 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....

  4. 41 CFR 60-2.10 - General purpose and contents of affirmative action programs.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 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....

  5. 41 CFR 60-2.10 - General purpose and contents of affirmative action programs.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 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....

  6. 41 CFR 60-2.10 - General purpose and contents of affirmative action programs.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 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....

  7. 46 CFR 2.10-105 - Prepayment of annual vessel inspection fees.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 1 2010-10-01 2010-10-01 false Prepayment of annual vessel inspection fees. 2.10-105 Section 2.10-105 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY PROCEDURES APPLICABLE TO THE PUBLIC VESSEL INSPECTIONS Fees § 2.10-105 Prepayment of annual vessel inspection fees. (a) Vessel owners...

  8. 46 CFR 2.10-105 - Prepayment of annual vessel inspection fees.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 1 2011-10-01 2011-10-01 false Prepayment of annual vessel inspection fees. 2.10-105 Section 2.10-105 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY PROCEDURES APPLICABLE TO THE PUBLIC VESSEL INSPECTIONS Fees § 2.10-105 Prepayment of annual vessel inspection fees. (a) Vessel owners...

  9. A Combined Genetic-Proteomic Approach Identifies Residues within Dengue Virus NS4B Critical for Interaction with NS3 and Viral Replication

    PubMed Central

    Chatel-Chaix, Laurent; Fischl, Wolfgang; Scaturro, Pietro; Cortese, Mirko; Kallis, Stephanie; Bartenschlager, Marie; Fischer, Bernd

    2015-01-01

    ABSTRACT Dengue virus (DENV) infection causes the most prevalent arthropod-borne viral disease worldwide. Approved vaccines are not available, and targets suitable for the development of antiviral drugs are lacking. One possible drug target is nonstructural protein 4B (NS4B), because it is absolutely required for virus replication; however, its exact role in the DENV replication cycle is largely unknown. With the aim of mapping NS4B determinants critical for DENV replication, we performed a reverse genetic screening of 33 NS4B mutants in the context of an infectious DENV genome. While the majority of these mutations were lethal, for several of them, we were able to select for second-site pseudoreversions, most often residing in NS4B and restoring replication competence. To identify all viral NS4B interaction partners, we engineered a fully viable DENV genome encoding an affinity-tagged NS4B. Mass spectrometry-based analysis of the NS4B complex isolated from infected cells identified the NS3 protease/helicase as a major interaction partner of NS4B. By combining the genetic complementation map of NS4B with a replication-independent expression system, we identified the NS4B cytosolic loop—more precisely, amino acid residue Q134—as a critical determinant for NS4B-NS3 interaction. An alanine substitution at this site completely abrogated the interaction and DENV RNA replication, and both were restored by pseudoreversions A69S and A137V. This strict correlation between the degree of NS4B-NS3 interaction and DENV replication provides strong evidence that this viral protein complex plays a pivotal role during the DENV replication cycle, hence representing a promising target for novel antiviral strategies. IMPORTANCE With no approved therapy or vaccine against dengue virus infection, the viral nonstructural protein 4B (NS4B) represents a possible drug target, because it is indispensable for virus replication. However, little is known about its precise structure and

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

    SciTech Connect

    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

    2009-08-31

    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 {approx}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. (lasers)

  11. 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

  12. Human Bocavirus NS1 and NS1-70 Proteins Inhibit TNF-α-Mediated Activation of NF-κB by targeting p65.

    PubMed

    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

  13. Nanosecond pulsed electric field thresholds for nanopore formation in neural cells

    NASA Astrophysics Data System (ADS)

    Roth, Caleb C.; Tolstykh, Gleb P.; Payne, Jason A.; Kuipers, Marjorie A.; Thompson, Gary L.; DeSilva, Mauris N.; Ibey, Bennett L.

    2013-03-01

    The persistent influx of ions through nanopores created upon cellular exposure to nanosecond pulse electric fields (nsPEF) could be used to modulate neuronal function. One ion, calcium (Ca), is important to action potential firing and regulates many ion channels. However, uncontrolled hyper-excitability of neurons leads to Ca overload and neurodegeneration. Thus, to prevent unintended consequences of nsPEF-induced neural stimulation, knowledge of optimum exposure parameters is required. We determined the relationship between nsPEF exposure parameters (pulse width and amplitude) and nanopore formation in two cell types: rodent neuroblastoma (NG108) and mouse primary hippocampal neurons (PHN). We identified thresholds for nanoporation using Annexin V and FM1-43, to detect changes in membrane asymmetry, and through Ca influx using Calcium Green. The ED50 for a single 600 ns pulse, necessary to cause uptake of extracellular Ca, was 1.76 kV/cm for NG108 and 0.84 kV/cm for PHN. At 16.2 kV/cm, the ED50 for pulse width was 95 ns for both cell lines. Cadmium, a nonspecific Ca channel blocker, failed to prevent Ca uptake suggesting that observed influx is likely due to nanoporation. These data demonstrate that moderate amplitude single nsPEF exposures result in rapid Ca influx that may be capable of controllably modulating neurological function.

  14. 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)

  15. 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.

  16. Inhibition of hepatitis C virus infection by NS5A-specific aptamer.

    PubMed

    Yu, Xiaoyan; Gao, Yimin; Xue, Binbin; Wang, Xiaohong; Yang, Darong; Qin, Yuwen; Yu, Rong; Liu, Nianli; Xu, Li; Fang, Xiaohong; Zhu, Haizhen

    2014-06-01

    To increase efficacy of hepatitis C treatment, future regiments will incorporate multiple direct-acting antiviral drugs. HCV NS5A protein was expressed and purified. Aptamers against NS5A were screened and obtained by the selective evolution of ligands by exponential enrichment approach and the antiviral actions of the aptamers were tested. The mechanisms through which the aptamers exert their antiviral activity were explored. The aptamers NS5A-4 and NS5A-5 inhibit HCV RNA replication and infectious virus production without causing cytotoxicity in human hepatocytes. The aptamers do not affect hepatitis B virus replication in HepG2.2.15 cells. Interferon beta (IFN-β) and interferon-stimulated genes (ISGs) are not induced by the aptamers in HCV-infected hepatocytes. Further study shows that domain I and domain III of NS5A protein are involved in the suppression of HCV RNA replication and infectious virus production by NS5A-4. Y2105H within NS5A is the major resistance mutation identified. NS5A aptamer disrupts the interaction of NS5A with core protein. The data suggest that the aptamers against NS5A protein may exert antiviral effects through inhibiting viral RNA replication, preventing the interaction of NS5A with core protein. Aptamers for NS5A may be used to understand the mechanisms of virus replication and assembly and served as potential therapeutic agents for hepatitis C. PMID:24713119

  17. Strong HCV NS3/4a, NS4b, NS5a, NS5b-specific cellular immune responses induced in Rhesus macaques by a novel HCV genotype 1a/1b consensus DNA vaccine

    PubMed Central

    Latimer, Brian; Toporovski, Roberta; Yan, Jian; Pankhong, Panyupa; Morrow, Matthew P; Khan, Amir S; Sardesai, Niranjan Y; Welles, Seth L; Jacobson, Jeffrey M; Weiner, David B; Kutzler, Michele A

    2014-01-01

    Chronic HCV is a surreptitious disease currently affecting approximately 3% of the world's population that can lead to liver failure and cancer decades following initial infection. However, there are currently no vaccines available for the prevention of chronic HCV. From patients who acutely resolve HCV infection, it is apparent that a strong and broad cytotoxic T lymphocyte (CTL) response is important in HCV clearance. DNA vaccines are naked plasmid DNA molecules that encode pathogen antigens to induce a pathogen-specific immune response. They are inexpensive to produce and have an excellent safety profile in animals and humans. Additionally, DNA vaccines are able to induce strong CTL responses, making them well-suited for an HCV vaccine. We aimed to maximize vaccine recipients' opportunity to induce a broad T cell response with a novel antigenic sequence, multi-antigen vaccine strategy. We have generated DNA plasmids encoding consensus sequences of HCV genotypes 1a and 1b non-structural proteins NS3/4a, NS4b, NS5a, and NS5b. Rhesus macaques were used to study the immunogenicity of these constructs. Four animals were immunized 3 times, 6 weeks apart, at a dose of 1.0mg per antigen construct, as an intramuscular injection followed by in vivo electroporation, which greatly increases DNA uptake by local cells. Immune responses were measured 2 weeks post-immunization regimen (PIR) in immunized rhesus macaques and showed a broad response to multiple HCV nonstructural antigens, with up to 4680 spot-forming units per million peripheral blood mononuclear cells (PBMCs) as measured by Interferon-γ ELISpot. In addition, multiparametric flow cytometry detected HCV-specific CD4+ and CD8+ T cell responses by intracellular cytokine staining and detected HCV-specific CD107a+/GrzB+ CD8+ T cells indicating an antigen specific cytolytic response 2 weeks PIR compared with baseline measurements. At the final study time point, 6 weeks PIR, HCV-specific CD45RA- memory-like T cells

  18. ChanPlaNS: The Chandra Planetary Nebula Survey

    NASA Astrophysics Data System (ADS)

    Kastner, Joel; Montez, Rodolfo; Freeman, Marcus; ChanPlaNS Team

    2015-01-01

    The physical mechanisms responsible for the morphological diversity among planetary nebulae (PNe) have been the subject of intense interest and hot debate among PN researchers over the past two decades. The PN shaping problem is multifaceted, with connections to (and implications for) a wide variety of astrophysical systems. Two areas of particular importance are (1) binary star astrophysics and (2) wind interactions and their implications for nebular shaping. X-ray observations play a pivotal role in the study of both of these fundamental aspects of PNe, by revealing (1) point-like X-ray sources at PN central stars that may be indicative of binary companions, and (2) diffuse X-ray emission generated by energetic, PN-shaping shocks. To assess the frequency of appearance and characteristics of these respective PN X-ray sources, we have undertaken the Chandra Planetary Nebula Survey (ChanPlaNS), the first comprehensive X-ray survey of planetary nebulae (PNe) in the solar neighborhood. ChanPlaNS began with a combined Cycle 12 Large Program and archival survey of 35 PNe, with emphasis on high-excitation nebulae, and continued via a Cycle 14 Large Program targeting an additional 24 known compact (R_neb <~ 0.4 pc) PNe. For the latter category of relatively young nebulae, we estimate that the ChanPlaNS survey is ~90% complete within ~1.5 kpc from the Sun. For the ~60 nebulae within this distance observed by Chandra, the point source detection rate is ~36%, and the diffuse X-ray source detection rate is ~27%. However, the point-like and diffuse X-ray detection rates, respectively, are significantly higher for PNe known to harbor binary central stars (~60%) and for the compact (young) PN subsample (~50%). These results demonstrate the potential for insight into PN shaping processes provided by ChanPlaNS. In companion presentations at this meeting (Montez et al.; Freeman et al.), we present highlights of the astrophysics gleaned to date from these Chandra detections (and

  19. 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.

  20. MOSFET-based high voltage double square-wave pulse generator with an inductive adder configuration

    NASA Astrophysics Data System (ADS)

    Zhao, Xin; Zhang, Qiaogen; Long, Jinghua; Lei, Yunfei; Liu, Jinyuan

    2015-09-01

    This paper presents a fast MOSFET-based solid-state pulse generator for high voltage double square-wave pulses. The generator consists mainly of an inductive adder system stacked of 20 solid-state modules. Each of the modules has 18 power MOSFETs in parallel, which are triggered by individual drive circuits; these drive circuits themselves are synchronously triggered by a signal from avalanche transistors. Our experiments demonstrate that the output pulses with amplitude of 8.1 kV and peak current of about 405 A are available at a load impedance of 20 Ω. The pulse has a double square-wave form with a rise and fall time of 40 ns and 26 ns, respectively and bottom flatness better than 12%. The interval time of the double square-wave pulses can be adjustable by varying the interval time of the trigger pulses.

  1. 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.

  2. 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.

  3. 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

  4. 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

  5. Ultrashort Pulse Propagation in Nonlinear Dispersive Fibers

    NASA Astrophysics Data System (ADS)

    Agrawal, Govind P.

    Ultrashort optical pulses are often propagated through optical waveguides for a variety of applications including telecommunications and supercontinuum generation [1]. Typically the waveguide is in the form of an optical fiber but it can also be a planar waveguide. The material used to make the waveguide is often silica glass, but other materials such as silicon or chalcogenides have also been used in recent years. What is common to all such materials is they exhibit chromatic dispersion as well as the Kerr nonlinearity. The former makes the refractive index frequency dependent, whereas the latter makes it to depend on the intensity of light propagating through the medium [2]. Both of these effects become more important as optical pulses become shorter and more intense. For pulses not too short (pulse widths > 1 ns) and not too intense (peak powers < 10 mW), the waveguide plays a passive role (except for small optical losses) and acts as a transporter of optical pulses from one place to another, without significantly affecting their shape or spectrum. However, as pulses become shorter and more intense, both the dispersion and the Kerr nonlinearity start to affect the shape and spectrum of an optical pulse during its propagation inside the waveguide. This chapter focuses on silica fibers but similar results are expected for other waveguides made of different materials

  6. 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. PMID:23284682

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. Binding specificity of polypeptide substrates in NS2B/NS3pro serine protease of dengue virus type 2: A molecular dynamics Study.

    PubMed

    Yotmanee, Pathumwadee; Rungrotmongkol, Thanyada; Wichapong, Kanin; Choi, Sy Bing; Wahab, Habibah A; Kungwan, Nawee; Hannongbua, Supot

    2015-07-01

    The pathogenic dengue virus (DV) is a growing global threat, particularly in South East Asia, for which there is no specific treatment available. The virus possesses a two-component (NS2B/NS3) serine protease that cleaves the viral precursor proteins. Here, we performed molecular dynamics simulations of the NS2B/NS3 protease complexes with six peptide substrates (capsid, intNS3, 2A/2B, 4B/5, 3/4A and 2B/3 containing the proteolytic site between P(1) and P(1)' subsites) of DV type 2 to compare the specificity of the protein-substrate binding recognition. Although all substrates were in the active conformation for cleavage reaction by NS2B/NS3 protease, their binding strength was somewhat different. The simulated results of intermolecular hydrogen bonds and decomposition energies suggested that among the ten substrate residues (P(5)-P(5)') the P(1) and P(2) subsites play a major role in the binding with the focused protease. The arginine residue at these two subsites was found to be specific preferential binding at the active site with a stabilization energy of <-10 kcal mol(-1). Besides, the P(3), P(1)', P(2)' and P(4)' subsites showed a less contribution in binding interaction (<-2 kcal mol(-1)). The catalytic water was detected nearby the carbonyl oxygen of the P(1) reacting center of the capsid, intNS3, 2A/2B and 4B/5 peptides. These results led to the order of absolute binding free energy (ΔGbind) between these substrates and the NS2B/NS3 protease ranked as capsid>intNS3>2A/2B>4B/5>3/4A>2B/3 in a relative correspondence with previous experimentally derived values. PMID:26086900

  12. Processing of the yellow fever virus nonstructural polyprotein: a catalytically active NS3 proteinase domain and NS2B are required for cleavages at dibasic sites.

    PubMed Central

    Chambers, T J; Grakoui, A; Rice, C M

    1991-01-01

    The vaccinia virus-T7 transient expression system was used to further examine the role of the NS3 proteinase in processing of the yellow fever (YF) virus nonstructural polyprotein in BHK cells. YF virus-specific polyproteins and cleavage products were identified by immunoprecipitation with region-specific antisera, by size, and by comparison with authentic YF virus polypeptides. A YF virus polyprotein initiating with a signal sequence derived from the E protein fused to the N terminus of NS2A and extending through the N-terminal 356 amino acids of NS5 exhibited processing at the 2A-2B, 2B-3, 3-4A, 4A-4B, and 4B-5 cleavage sites. Similar results were obtained with polyproteins whose N termini began within NS2A (position 110) or with NS2B. When the NS3 proteinase domain was inactivated by replacing the proposed catalytic Ser-138 with Ala, processing at all sites was abolished. The results suggest that an active NS3 proteinase domain is necessary for cleavage at the diabasic nonstructural cleavage sites and that cleavage at the proposed 4A-4B signalase site requires prior cleavage at the 4B-5 site. Cleavages were not observed with a polyprotein whose N terminus began with NS3, but cleavage at the 4B-5 site could be restored by supplying the the NS2B protein in trans. Several experimental results suggested that trans cleavage at the 4B-5 site requires association of NS2B and the NS3 proteinase domain. Coexpression of different proteinases and catalytically inactive polyprotein substrates revealed that trans cleavage at the 2B-3 and 4B-5 sites was relatively efficient when compared with trans cleavage at the 2A-2B and 3-4A sites. Images PMID:1833562

  13. 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.

  14. 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.

  15. Laser-induced damage measurements with 266-nm pulses

    NASA Astrophysics Data System (ADS)

    Deaton, T. F.; Smith, W. L.

    1980-07-01

    Results of a survey of laser-induced damage thresholds for optical components at 266-nm are reported. The thresholds were measured at two pulse durations; 0.150 ns and 1.0 ns. The 30 samples tested include four commercial dielectric reflectors, three metallic reflectors, two anti-reflection films, a series of eight half-wave oxide and fluoride films, and twelve bare surfaces (fluoride crystals, silica, sapphire, BK-7 glass, cesium dideuterium arsenate and potassium dihydrogen phosphate). The 266-nm pulses were obtained by frequency-quadrupling a Nd:YAG, glass laser. Equivalent plane imagery and calorimetry were used to measure the peak fluence of each of the UV pulses with an accuracy of + or - of 15%; the uncertainty in the threshold determinations is typically + or - 30%.

  16. 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.

  17. Highly efficient pulse-periodic XeCl lasers

    SciTech Connect

    Dudarev, V V; Ivanov, N G; Konovalov, I N; Losev, V F; Pavlinskii, A V; Panchenko, Yu N

    2011-08-31

    The parameters of electric-discharge pulse-periodic XeCl lasers with a pulse duration of 25 - 40 ns, an energy of 0.2 - 0.7 J, and a pulse repetition rate up to 100 Hz have been investigated. It is shown that the total laser efficiency of 2.6 % and the maximum efficiency with respect to the stored energy of 3.8 % are obtained at a specific pump power of 2.8 - 3.3 MW cm{sup -3} and a discharge circuit inductance of 3.5 - 4 nH. (lasers)

  18. Note: external multipass optical trap for counterpropagating pulsed laser applications.

    PubMed

    Graul, J S; Ketsdever, A D; Andersen, G P; Lilly, T C

    2013-07-01

    Pulses from a 12 mJ, frequency doubled, 5 ns FWHM, pulsed Nd:YAG laser were split and injected into opposing sides of a symmetric 2.44 m (96 in.) optical ring trap. Using a Pockels cell, the counterpropagating pulses were "locked" into the trap for ≥50 round trips. This optical trap has potential applications ranging from established cavity processes, e.g., laser-based absorption spectroscopy and x-ray production, to new processes such as non-resonant optical lattice gas heating and time-resolved coherent Rayleigh-Brillouin scattering diagnostic studies. PMID:23902119

  19. Wide-range monitor for pulsed x-ray sources

    SciTech Connect

    Kaifer, R.C.; Jenkins, T.E.; Straume, T.

    1981-10-12

    A monitoring instrument based on a high-pressure ionization chamber has been developed that measures average dose rates as low as 0.1 mR/h and responds linearly to short pulses at dose rates up to 1.2 x 10/sup 10/ R/h. Its sensitivity can be remotely changed by a factor of 10/sup 4/, to enable accurate measurement of both background radiation and very high intensities such as can be expected from accelerator beam-spills. The instrument's detector-electrometer pulse response was measured using a dose-calibrated field-emission accelerator having a 30-ns pulse width.

  20. Note: External multipass optical trap for counterpropagating pulsed laser applications

    NASA Astrophysics Data System (ADS)

    Graul, J. S.; Ketsdever, A. D.; Andersen, G. P.; Lilly, T. C.

    2013-07-01

    Pulses from a 12 mJ, frequency doubled, 5 ns FWHM, pulsed Nd:YAG laser were split and injected into opposing sides of a symmetric 2.44 m (96 in.) optical ring trap. Using a Pockels cell, the counterpropagating pulses were "locked" into the trap for ≥50 round trips. This optical trap has potential applications ranging from established cavity processes, e.g., laser-based absorption spectroscopy and x-ray production, to new processes such as non-resonant optical lattice gas heating and time-resolved coherent Rayleigh-Brillouin scattering diagnostic studies.

  1. 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.

  2. 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

  3. 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

  4. 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. PMID:12198607

  5. 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.

  6. SLAC pulsed x-ray facility

    SciTech Connect

    Ipe, N.E.; McCall, R.C.; Baker, E.D.

    1986-05-01

    The Stanford Linear Accelerator Center (SLAC) operates a high energy (up to 33 GeV) linear accelerator delivering pulses up to a few microseconds wide. The pulsed nature of the electron beam creates problems in the detection and measurement of radiation both from the accelerator beam and the klystrons that provide the rf power for the accelerator. Hence, a pulsed x-ray facility has been built at SLAC mainly for the purpose of testing the response of different radiation detection instruments to pulsed radiation fields. The x-ray tube consists of an electron gun with a control grid. This provides a stream of pulsed electrons that can be accelerated towards a confined target-window. The window is made up of aluminium 0.051 cm (20 mils) thick, plated on the vacuum side with a layer of gold 0.0006 cm (1/4 mil) thick. The frequency of electron pulses can be varied by an internal pulser from 60 to 360 pulses per second with pulse widths of 360 ns to 5 ..mu..s. The pulse amplitude can be varied over a wide range of currents. An external pulser can be used to obtain other frequencies or special pulse shapes. The voltage across the gun can be varied from 0 to 100 kV. The major part of the x-ray tube is enclosed in a large walk-in-cabinet made of 1.9 cm (3/4 in) plywood and lined with 0.32 cm (1/8 in) lead to make a very versatile facility. 3 refs., 5 figs.

  7. SLAC pulsed X-ray facility

    NASA Astrophysics Data System (ADS)

    Ipe, N. E.; McCall, R. C.; Baker, E. D.

    1986-05-01

    The Stanford Linear Accelerator Center (SLAC) operates a high energy (up to 33 GeV) linear accelerator delivering pulses up to a few microseconds wide. The pulsed nature of the electron beam creates problems in the detection and measurement of radiation both from the accelerator beam and the klystrons that provide the RF power for the accelerator. Hence, a pulsed X-ray facility has been built at SLAC mainly for the purpose of testing the response of different radiation detection instruments to pulsed radiation fields. The X-ray tube consists of an electron gun with a control grid. This provides a stream of pulsed electrons that can be accelerated towards a confined target-window. The window is made up of aluminum 0.051 cm (20 mils) thick, plated on the vacuum side with a layer of gold 0.0006 cm (1/4 mil) thick. The frequency of electron pulses can be varied by an internal pulser from 60 to 360 pulses per second with pulse widths of 360 ns to 5 ms. The pulse amplitude can be varied over a wide range of currents. An external pulser can be used to obtain other frequencies or special pulse shapes. The voltage across the gun can be varied from 0 to 100 kV. The major part of the X-ray tube is enclosed in a large walk-in-cabinet made of 1.9 cm (3/4 in) plywood and lined with 0.32 cm (1/8 in) lead to make a very versatile facility.

  8. 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.

  9. 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.

  10. Recombinant dengue virus type 1 NS3 protein exhibits specific viral RNA binding and NTPase activity regulated by the NS5 protein.

    PubMed

    Cui, T; Sugrue, R J; Xu, Q; Lee, A K; Chan, Y C; Fu, J

    1998-07-01

    The full-length dengue virus NS3 protein has been successfully expressed as a 94-kDa GST fusion protein in Escherichia coli. Treatment of the purified fusion protein with thrombin released a 68-kDa protein which is the expected molecular mass for the DEN1 NS3 protein. The identity of this protein was confirmed by Western blotting using dengue virus antisera. Two related activities of the recombinant NS3 protein were characterized, which were the binding of the protein to the 3'-noncoding region of the dengue virus RNA genome and NTPase activity. We demonstrated using a band shift assay that the DEN1 NS3 protein could form a complex with the stem-loop structure in the 3'-noncoding region (3'-NCR), although sites outside the stem-loop may also participate in binding. Using various unlabeled homopolymeric and heteropolymeric RNAs as competitors for binding, it was further shown that the DEN1 NS3 protein exhibits preferential binding to a 94-nt RNA transcript from the 3'-NCR of the dengue virus. The NTPase activity of the recombinant DEN1 NS3 protein was characterized using a thin-layer chromatography assay. We found that the DEN1 NS3 protein possesses some aspects of NTPase activity, which are distinct from those found in other flaviviruses. Although the NS3 protein was able to utilize all four ribonucleoside triphosphates as its substrates, the NS3 protein showed a distinct preference for purine triphosphates (i.e., ATP and GTP). The addition of poly(U) did not stimulate NTPase activity in DEN1 NS3 protein, which contrasts with the reports for other flaviviral NS3 proteins. However, NTPase activity was specifically stimulated by the viral NS5 protein, which was manifested by a more than twofold increase in the rate of ATP hydrolysis and a 25% increase in the yield of ADP at the end of a 120-min reaction. These data suggest that the NTPase activity of the NS3 protein may be regulated by the viral NS5 protein during virus replication. PMID:9657959

  11. 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.

  12. Note: compact helical pulse forming line for the generation of longer duration rectangular pulse.

    PubMed

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

    2012-06-01

    The helical pulsed forming line (PFL) can generate longer duration rectangular pulse in a smaller length. A compact PFL using helical water line is designed and experimentally investigated. The impedance of the helical PFL is 22 [ohm sign]. The compactness is achieved in terms of reduction in length of the PFL by a factor of 5.5 using helical water PFL as compared to coaxial water PFL of same length. The helical PFL was pulsed charged to 200 kV using a high voltage pulse transformer in 4.5 μs and discharged into the matched 22 Ω resistive load through a self-breakdown pressurized spark gap switch. The rectangular voltage pulse of 100 kV, 260 ns (FWHM) is measured across the load. The effect of reduction in water temperature on the pulse width is also studied experimentally. The increase in pulse width up to 7% more is observed by reducing the temperature of the deionized water to 5 °C. It will further reduce the length of the PFL and make the system small for compact pulsed power drivers. PMID:22755669

  13. 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

  14. 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

  15. 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.

  16. 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.

  17. Preclinical Characterization of BI 201335, a C-Terminal Carboxylic Acid Inhibitor of the Hepatitis C Virus NS3-NS4A Protease ▿ †

    PubMed Central

    White, Peter W.; Llinàs-Brunet, Montse; Amad, Ma'an; Bethell, Richard C.; Bolger, Gordon; Cordingley, Michael G.; Duan, Jianmin; Garneau, Michel; Lagacé, Lisette; Thibeault, Diane; Kukolj, George

    2010-01-01

    BI 201335 is a hepatitis C virus (HCV) NS3-NS4A (NS3 coexpressed with NS4A) protease inhibitor that has been shown to have potent clinical antiviral activity. It is a highly optimized noncovalent competitive inhibitor of full-length NS3-NS4A proteases of HCV genotypes 1a and 1b with Ki values of 2.6 and 2.0 nM, respectively. Ki values of 2 to 230 nM were measured against the NS3-NS4A proteases of HCV genotypes 2 to 6, whereas it was a very weak inhibitor of cathepsin B and showed no measurable inhibition of human leukocyte elastase. BI 201335 was also shown to be a potent inhibitor of HCV RNA replication in vitro with 50% effective concentrations (EC50s) of 6.5 and 3.1 nM obtained in genotype 1a and 1b replicon assays. Combinations of BI 201335 with either interferon or ribavirin had additive effects in replicon assays. BI 201335 had good permeability in Caco-2 cell assays and high metabolic stability after incubation with human, rat, monkey, and dog liver microsomes. Its good absorption, distribution, metabolism, and excretion (ADME) profile in vitro, as well as in rat, monkey, and dog, predicted good pharmacokinetics (PK) in humans. Furthermore, drug levels were significantly higher in rat liver than in plasma, suggesting that distribution to the target organ may be especially favorable. BI 201335 is a highly potent and selective NS3-NS4A protease inhibitor with good in vitro and animal ADME properties, consistent with its good human PK profile, and shows great promise as a treatment for HCV infection. PMID:20823284

  18. Preclinical characterization of BI 201335, a C-terminal carboxylic acid inhibitor of the hepatitis C virus NS3-NS4A protease.

    PubMed

    White, Peter W; Llinàs-Brunet, Montse; Amad, Ma'an; Bethell, Richard C; Bolger, Gordon; Cordingley, Michael G; Duan, Jianmin; Garneau, Michel; Lagacé, Lisette; Thibeault, Diane; Kukolj, George

    2010-11-01

    BI 201335 is a hepatitis C virus (HCV) NS3-NS4A (NS3 coexpressed with NS4A) protease inhibitor that has been shown to have potent clinical antiviral activity. It is a highly optimized noncovalent competitive inhibitor of full-length NS3-NS4A proteases of HCV genotypes 1a and 1b with K(i) values of 2.6 and 2.0 nM, respectively. K(i) values of 2 to 230 nM were measured against the NS3-NS4A proteases of HCV genotypes 2 to 6, whereas it was a very weak inhibitor of cathepsin B and showed no measurable inhibition of human leukocyte elastase. BI 201335 was also shown to be a potent inhibitor of HCV RNA replication in vitro with 50% effective concentrations (EC(50)s) of 6.5 and 3.1 nM obtained in genotype 1a and 1b replicon assays. Combinations of BI 201335 with either interferon or ribavirin had additive effects in replicon assays. BI 201335 had good permeability in Caco-2 cell assays and high metabolic stability after incubation with human, rat, monkey, and dog liver microsomes. Its good absorption, distribution, metabolism, and excretion (ADME) profile in vitro, as well as in rat, monkey, and dog, predicted good pharmacokinetics (PK) in humans. Furthermore, drug levels were significantly higher in rat liver than in plasma, suggesting that distribution to the target organ may be especially favorable. BI 201335 is a highly potent and selective NS3-NS4A protease inhibitor with good in vitro and animal ADME properties, consistent with its good human PK profile, and shows great promise as a treatment for HCV infection. PMID:20823284

  19. 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.

  20. 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.

  1. NS/EPp Enhancement Of Fiber Optic Long-Haul Links

    NASA Astrophysics Data System (ADS)

    Peach, David F.; Hull, Joseph A.

    1990-01-01

    The National Communications System (NCS) is responsible for defining reasonable enhancements that could be applied to commercial common carrier (or carriers'-carrier) fiber optic systems that will be leased or owned by Government agencies and that may be used for National Security and Emergency Preparedness (NS/EP) purposes. This paper describes enhancements recommended by the authors for making fiber optic long-haul systems more survivable against both man-made and natural disasters. For a limited nuclear environment, outside of the blast region where buildings and personnel would be expected to survive, involving surface and in-atmosphere nuclear bursts, the vulnerability of optical fiber waveguides to fallout radiation is a primary concern. An assessment of fiber darkening from gamma radiation, based on a review of unclassified literature, is presented. For exoatmospheric nuclear bursts, the fiber optic system is exposed to high altitude electromagnetic pulse (HEMP) radiation. Other man-made disasters include sabotage, fires, accidents, and unintentional dig-ups. Natural disasters considered were floods, earthquakes, lightning, temperature extremes, rodents, etc.

  2. Nonstructural protein 3 of the hepatitis C virus encodes a serine-type proteinase required for cleavage at the NS3/4 and NS4/5 junctions.

    PubMed Central

    Bartenschlager, R; Ahlborn-Laake, L; Mous, J; Jacobsen, H

    1993-01-01

    We have studied processing of the nonstructural (NS) polyprotein of the hepatitis C virus. A series of cDNAs corresponding to predicted NS2/3/4 or NS3/4 regions were constructed, and processing of the polyproteins was studied in an in vitro transcription-translation system. We report that a catalytically active serine-type proteinase is encoded by the NS3 region. Substitution of the serine residue of the putative catalytic triad (H, D, and S) by alanine blocked cleavage at the NS3/4 junction, while processing between NS2 and NS3 was not affected. Thus, cleavage at the NS2/3 junction is mediated either by cellular enzymes or by an NS-2 inherent proteinase activity. Deletion analysis of an NS3/4 cDNA construct mapped the amino terminus of the enzymatically active proteinase between amino acids 1049 and 1065 of the polyprotein. As internal deletions of variable segments of the presumed helicase domain prevented processing at the NS314 junction, a continuous NS3 region appears to be required for processing at this site. To analyze hepatitis C virus polyprotein cleavage in vivo, recombinant vaccinia viruses expressing NS2/3/4 or NS3/4/5 proteins were generated. In agreement with the in vitro data, cleavage between NS2 and NS3 was independent of a catalytically active NS3 proteinase, whereas substitution of the active-site serine residue by the amino acid alanine completely blocked processing at the NS3/4 and NS4/5 junctions. These results demonstrate that NS3 encodes the viral proteinase essential for generating the amino termini of NS4 and NS5. Images PMID:8389908

  3. 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

  4. 850 J, 150 ns narrow-band krypton fluoride laser

    SciTech Connect

    Goldhar, J.; Jancaitis, K.S.; Murray, J.R.; Schlitt, L.G.

    1983-12-16

    We report laser experiments on a 248 nm KrF laser with a 30x40x120 cm gain volume and an injection locked unstable resonator cavity. The volume is pumped by six 450 kV, 90 kA electron beam generators using water pulse forming lines.

  5. Upregulation of signalase processing and induction of prM-E secretion by the flavivirus NS2B-NS3 protease: roles of protease components.

    PubMed Central

    Yamshchikov, V F; Trent, D W; Compans, R W

    1997-01-01

    Recently, we have shown that the ability of the flavivirus NS2B-NS3 protease complex to promote efficient signalase processing of the C-prM precursor, as well as secretion of prM and E, does not appear to depend strictly on cleavage of the precursor at its Lys-Arg-Gly dibasic site by the protease. We suggested that the association of the protease with the precursor via NS2B may be sufficient by itself for the above effects. To study the proposed association in more detail, we have developed an assay in which processing at the C-prM dibasic cleavage site is abolished by Lys-->Gly conversion. We constructed deletion mutants and chimeras of the West Nile (WN) flavivirus NS2B protein and expressed them in the context of [5'-C-->NS3(243)] containing either wild-type C-prM or its cleavage site mutant. All NS2B variants were able to form active protease complexes. Deletion of the carboxy-terminal cluster of hydrophobic amino acids in NS2B had no apparent effect on the formation of prM and prM-E secretion for the cassettes containing either wild-type or mutated C-prM precursor. Deletion of the amino-terminal hydrophobic cluster in NS2B did not affect prM-E secretion for the cassettes with wild-type C-prM but abrogated prM-E secretion for the cassettes with the mutated dibasic cleavage site in C-prM. Similarly, the NS2B-NS3(178) protease of Japanese encephalitis (JE) virus, when substituted for the WN virus NS2B-NS3(243) protease, was able to promote prM-E secretion for the cassette with the wild-type C-prM precursor but not with the mutated one. Replacement of the deleted amino-terminal hydrophobic cluster in the WN virus NS2B protein with an analogous JE virus sequence restored the ability of the protease to promote prM-E secretion. On the basis of these observations, roles of individual protease components in upregulation of C-prM signalase processing are discussed. PMID:9151825

  6. Role of cytoskeleton and elastic moduli in cellular response to nanosecond pulsed electric fields

    NASA Astrophysics Data System (ADS)

    Thompson, Gary L.; Roth, Caleb; Tolstykh, Gleb; Kuipers, Marjorie; Ibey, Bennett L.

    2013-02-01

    Nanosecond pulsed electric fields (nsPEFs) are known to increase cell membrane permeability to small molecules in accordance with dosages. As previous work has focused on nsPEF exposures in whole cells, electrodeformation may contribute to this induced-permeabilization in addition to other biological mechanisms. Here, we hypothesize that cellular elasticity, based upon the cytoskeleton, affects nsPEF-induced decrease in cellular viability. Young's moduli of various types of cells have been calculated from atomic force microscopy (AFM) force curve data, showing that CHO cells are stiffer than non-adherent U937 and Jurkat cells, which are more susceptible to nsPEF exposure. To distinguish any cytoskeletal foundation for these observations, various cytoskeletal reagents were applied. Inhibiting actin polymerization significantly decreased membrane integrity, as determined by relative propidium uptake and phosphatidylserine externalization, upon exposure at 150 kV/cm with 100 pulses of 10 ns pulse width. Exposure in the presence of other drugs resulted in insignificant changes in membrane integrity and 24-hour viability. However, Jurkat cells showed greater lethality than latrunculin-treated CHO cells of comparable elasticity. From these results, it is postulated that cellular elasticity rooted in actin-membrane interaction is only a minor contributor to the differing responses of adherent and non-adherent cells to nsPEF insults.

  7. 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.

  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. 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. PMID:26621477

  10. 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

  11. 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. PMID:25915516

  12. 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.

  13. Dependence of light pulse propagation on its temporal width: Transition from group velocity to c-propagation

    NASA Astrophysics Data System (ADS)

    Ignesti, Emilio; Tommasi, Federico; Fini, Lorenzo; Cavalieri, Stefano

    2016-07-01

    We show how the velocity of an optical pulse propagating through a dispersive medium depends on the pulse duration. A transition from the group velocity for long pulses to the in-vacuum velocity for short pulses is shown both in experimental results and in theoretical predictions. The temporal duration of the experimental pulses are 150 ps and 3.5 ns. A description of the pulse propagation in terms of the time "center of mass" of the energy flow allows an intuitive overview of the results.

  14. Precision timing measurement of phototube pulses using a flash analog-to-digital converter

    NASA Astrophysics Data System (ADS)

    Bennett, J. V.; Kornicer, M.; Shepherd, M. R.; Ito, M. M.

    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.

  15. Sintering of solution-based nano-particles by a UV laser pulse train

    NASA Astrophysics Data System (ADS)

    Zhang, Jie; Li, Ming; Morimoto, Kiyoshi

    2011-03-01

    Sintering of palladium (Pd) and silicon (Si) nano-particles (NPs) by a 266nm laser pulse train on ink-printed films was investigated. Organic Pd-ink, and organic Si-ink were used as precursors. A high repetition rate DPSS laser (up to 300 kHz, 25ns, 266nm, Coherent AVIA series), which produces a ns pulse train with 3.3 μs -33.3 μs interval of pulse-topulse, was used as the heating source. Highly electrically conductive Pd (Resistivity=~150μΩ.cm) thin film on PET substrate and semi-conductive Si (Resistivity=~23kΩ.cm) thin film on glass substrate were successfully obtained with this laser pulse train sintering process. The sintered films were characterized by AFM, SEM, TEM and Raman spectroscopy, respectively. The pulse train heating process was also numerically simulated.

  16. 9 CFR 2.10 - Licensees whose licenses have been suspended or revoked.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... suspended or revoked. 2.10 Section 2.10 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION... have been suspended or revoked. (a) Any person whose license has been suspended for any reason shall....12. (b) Any person whose license has been revoked shall not be licensed in his or her own name or...

  17. A simple highly stable and temporally synchronizable Nd:glass laser oscillator delivering laser pulses of variable pulse duration from sub-nanosecond to few nanoseconds

    NASA Astrophysics Data System (ADS)

    Sharma, A. K.; Joshi, R. A.; Patidar, R. K.; Naik, P. A.; Gupta, P. D.

    2007-04-01

    A simple flash lamp pumped Nd:phosphate glass laser oscillator has been designed and set up delivering laser pulses of variable duration from ˜800 ps to 6 ns. It is based on Q-switching and full-wavelength cavity dumping and provides single laser pulse energy of 5 mJ and 11 mJ corresponding to pulse duration of ˜800 ps and 6 ns respectively at an electrical pump energy of 50 J. While the maximum pulse duration is governed by the cavity round trip time, the lower limit is decided by the switching speed of the high voltage pulse to the Pockels cell of the cavity dumper. Output laser pulses have shown enhanced pulse energy stability by dumping the cavity four round trips after the peak buildup. The laser pulses were synchronized with 250 ps positively chirped laser pulse train derived from an independent commercial cw mode locked Nd:fluorophosphate glass laser oscillator. The temporal jitter between these two pulses was measured to be ˜200 ps, limited by the speed of the electronics used.

  18. 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

  19. 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

  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. 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)

  2. Response of silicon solar cell to pulsed laser illumination

    NASA Technical Reports Server (NTRS)

    Willowby, D.; Alexander, D.; Edge, T.; Herren, K.

    1993-01-01

    The response of silicon solar cell(s) to pulsed laser illumination is discussed. The motivation was due to the interest of Earth to space/Moon power beaming applications. When this work began, it was not known if solar cells would respond to laser light with pulse lengths in the nanosecond range and a repetition frequency in the kHz range. This is because the laser pulse would be shorter than the minority carrier lifetime of silicon. A 20-nanosecond (ns) full width half max (FWHM) pulse from an aluminum-gallium/arsenide (Al-Ga-As) diode laser was used to illuminate silicon solar cells at a wavelength of 885 nanometers (nm). Using a high-speed digital oscilloscope, the response of the solar cells to individual pulses across various resistive loads was observed and recorded.

  3. 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

  4. 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

  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. 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.

  7. Impact of ns-DBD plasma actuation on the boundary layer transition using convective heat transfer measurements

    NASA Astrophysics Data System (ADS)

    Ullmer, Dirk; Peschke, Philip; Terzis, Alexandros; Ott, Peter; Weigand, Bernhard

    2015-09-01

    This paper demonstrates that the impact of nanosecond pulsed dielectric barrier discharge (ns-DBD) actuators on the structure of the boundary layer can be investigated using quantitative convective heat transfer measurements. For the experiments, the flow over a flat plate with a C4 leading edge thickness distribution was examined at low speed incompressible flow (6.6-11.5 m s-1). An ns-DBD plasma actuator was mounted 5 mm downstream of the leading edge and several experiments were conducted giving particular emphasis on the effect of actuation frequency and the freestream velocity. Local heat transfer distributions were measured using the transient liquid crystal technique with and without plasma activated. As a result, any effect of plasma on the structure of the boundary layer is interpreted by local heat transfer coefficient distributions which are compared with laminar and turbulent boundary layer correlations. The heat transfer results, which are also confirmed by hot-wire measurements, show the considerable effect of the actuation frequency on the location of the transition point elucidating that liquid crystal thermography is a promising method for investigating plasma-flow interactions very close to the wall. Additionally, the hot-wire measurements indicate possible velocity oscillations in the near wall flow due to plasma activation.

  8. H-NS and RNA polymerase: a love-hate relationship?

    PubMed

    Landick, Robert; Wade, Joseph T; Grainger, David C

    2015-04-01

    Histone-like nucleoid structuring (H-NS) protein is a component of bacterial chromatin and influences gene expression both locally and on a global scale. Although H-NS is broadly considered a silencer of transcription, the mechanisms by which H-NS inhibits gene expression remain poorly understood. Here we discuss recent advances in the context of a 'love-hate' relationship between H-NS and RNA polymerase, in which these factors recognise similar DNA sequences but interfere with each other's activity. Understanding the complex relationship between H-NS and RNA polymerase may unite the multiple models that have been proposed to describe gene silencing by H-NS. PMID:25638302

  9. 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.

  10. The effect of glycosylation on cytotoxicity of Ibaraki virus nonstructural protein NS3

    PubMed Central

    URATA, Maho; WATANABE, Rie; IWATA, Hiroyuki

    2015-01-01

    The cytotoxicity of Ibaraki virus nonstructural protein NS3 was confirmed, and the contribution of glycosylation to this activity was examined by using glycosylation mutants of NS3 generated by site-directed mutagenesis. The expression of NS3 resulted in leakage of lactate dehydrogenase to the culture supernatant, suggesting the cytotoxicity of this protein. The lack of glycosylation impaired the transport of NS3 to the plasma membrane and resulted in reduced cytotoxicity. Combined with the previous observation that NS3 glycosylation was specifically observed in mammalian cells (Urata et al., Virus Research 2014), it was suggested that the alteration of NS3 cytotoxicity through modulating glycosylation is one of the strategies to achieve host specific pathogenisity of Ibaraki virus between mammals and vector arthropods. PMID:26178820

  11. 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.

  12. 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.

  13. 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.

  14. 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

  15. H-NS Facilitates Sequence Diversification of Horizontally Transferred DNAs during Their Integration in Host Chromosomes.

    PubMed

    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

  16. 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

  17. 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

  18. 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

  19. Nanosecond pulsed laser blackening of copper

    NASA Astrophysics Data System (ADS)

    Tang, Guang; Hourd, Andrew C.; Abdolvand, Amin

    2012-12-01

    Nanosecond (12 ns) pulsed laser processing of copper at 532 nm resulted in the formation of homogenously distributed, highly organized microstructures. This led to the fabrication of large area black copper substrates with absorbance of over 97% in the spectral range from 250 nm to 750 nm, and a broadband absorbance of over 80% between 750 nm and 2500 nm. Optical and chemical analyses of the fabricated black metal are presented and discussed. The employed laser is an industrially adaptable source and the presented technique for fabrication of black copper could find applications in broadband thermal radiation sources, solar energy absorbers, irradiative heat transfer devices, and thermophotovoltaics.

  20. Investigation of Optimum Applied Voltage for Water Treatment by Pulsed Streamer Discharge in Air Spraying Water Droplets

    NASA Astrophysics Data System (ADS)

    Sugai, Taichi; Suzuki, Tomoya; Minamitani, Yasushi; Nose, Taisuke

    In this study, we investigated a water treatment method spraying the droplets of wastewater into pulse discharge space. The water treatment was carried out by applying voltage with different pulse widths to determine the optimum pulse width, and the optimum pulse voltage determined on the basis of the results of the study was analyzed. The rise time of the voltages with pulse widths of 40, 60, and 80 ns was about 12, 19, and 32 ns, respectively, and the discharge current in the case of the faster rise time was higher. The number of streamer discharges is believed to increase with a decrease in the rise time. The energy efficiency in the case of the pulse width of 40 ns is higher than that in the case of the other pulse widths. This is because almost all of active species are generated by early streamer discharge, and longer discharging time by longer pulse width makes more ineffectual energy by thermal loss. These results show that the pulsed voltage of faster rise time and shorter pulse width is optimum for the treatment.

  1. 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.

  2. Intense Pulsed Neutron Emission from a Compact Pyroelectric Driven Accelerator

    SciTech Connect

    Tang, V; Meyer, G; Falabella, S; Guethlein, G; Sampayan, S; Kerr, P; Rusnak, B; Morse, J

    2008-10-08

    Intense pulsed D-D neutron emission with rates >10{sup 10} n/s during the pulse, pulse widths of {approx}100's ns, and neutron yields >10 k per pulse are demonstrated in a compact pyroelectric accelerator. The accelerator consists of a small pyroelectric LiTaO{sub 3} crystal which provides the accelerating voltage and an independent compact spark plasma ion source. The crystal voltage versus temperature is characterized and compare well with theory. Results show neutron output per pulse that scales with voltage as V{approx}1.7. These neutron yields match a simple model of the system at low voltages but are lower than predicted at higher voltages due to charge losses not accounted for in the model. Interpretation of the data against modeling provides understanding of the accelerator and in general pyroelectric LiTaO{sub 3} crystals operated as charge limited negative high voltage targets. The findings overall serve as the proof-of-principle and basis for pyroelectric neutron generators that can be pulsed, giving peak neutron rates orders of magnitude greater than previous work, and notably increase the potential applications of pyroelectric based neutron generators.

  3. 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.

  4. 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.

  5. 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

  6. 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.

  7. Cellular tolerance to pulsed heating

    NASA Astrophysics Data System (ADS)

    Simanovski, Dimitrii; Sarkar, M.; Irani, A.; O'Connell-Rodwell, C.; Contag, C.; Schwettman, H. Alan; Palanker, D.

    2005-04-01

    Many laser therapies involve significant heating of tissue with pulses varying from picoseconds to minutes in duration. In some of the applications heating is a primary goal, while in others it is an undesirable side effect. In both cases, if a hyperthermia is involved, the knowledge about the threshold temperature leading to irreversible cellular damage is critically important. We study the dependence of the threshold temperature on duration of the heat exposure in the range of 0.3 ms to 5 seconds. Thin layer of cells cultured in a Petri dish was exposed to a pulsed CO2 laser radiation. Laser beam was focused onto sample providing Gaussian intensity distribution in the focal plane with a beam diameter (2w) 2-10 mm. Surface temperature in the central part of the focal spot (1mm in diameter) was measured by thermal infrared (IR) emission from the sample, recorded with a fast IR detector. For pulses shorter than 1 s the temperature profile across the focal spot was found to closely correspond to the radial distribution of the laser beam intensity, thus allowing for accurate determination of temperature at any given distance from the center of the spot. Immediate cellular damage was assessed using vital staining with the live/dead fluorescent assay. Threshold temperatures were found to vary from 65 °C at 5 s of heating to 160 °C at pulses of 0.3 ms in duration. The shorter end of this range was limited by vaporization, which occurs during the laser pulse and results in mechanical damage to cells. Dependence of the maximal temperature on pulse duration could be approximated by Arrhenius law with activation energy being about 1 eV.

  8. 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.

  9. Multiple nanosecond electric pulses increase the number but not the size of long-lived nanopores in the cell membrane.

    PubMed

    Pakhomov, Andrei G; Gianulis, Elena; Vernier, P Thomas; Semenov, Iurii; Xiao, Shu; Pakhomova, Olga N

    2015-04-01

    Exposure to intense, nanosecond-duration electric pulses (nsEP) opens small but long-lived pores in the plasma membrane. We quantified the cell uptake of two membrane integrity marker dyes, YO-PRO-1 (YP) and propidium (Pr) in order to test whether the pore size is affected by the number of nsEP. The fluorescence of the dyes was calibrated against their concentrations by confocal imaging of stained homogenates of the cells. The calibrations revealed a two-phase dependence of Pr emission on the concentration (with a slower rise at<4μM) and a linear dependence for YP. CHO cells were exposed to nsEP trains (1 to 100 pulses, 60ns, 13.2kV/cm, 10Hz) with Pr and YP in the medium, and the uptake of the dyes was monitored by time-lapse imaging for 3min. Even a single nsEP triggered a modest but detectable entry of both dyes, which increased linearly when more pulses were applied. The influx of Pr per pulse was constant and independent of the pulse number. The influx of YP per pulse was highest with 1- and 2-pulse exposures, decreasing to about twice the Pr level for trains from 5 to 100 pulses. The constant YP/Pr influx ratio for trains of 5 to 100 pulses suggests that increasing the number of pulses permeabilizes cells to a greater extent by increasing the pore number and not the pore diameter. PMID:25585279

  10. Expression of NS3/NS4A Proteins of Hepatitis C Virus in Huh7 Cells Following Engineering Its Eukaryotic Expression Vector

    PubMed Central

    Behzadi, Mohammad Amin; Alborzi, Abdolvahab; Pouladfar, Gholamreza; Dianatpour, Mehdi; Ziyaeyan, Mazyar

    2015-01-01

    Background: Although the development of novel therapeutic regimens to combat hepatitis C virus (HCV) infection have been speeded up with successful results, no efficient vaccines exist yet. Objectives: This study aimed to construct a eukaryotic expression vector encoding nonstructural proteins, NS3/NS4A, of HCV genotype 3a, and evaluate its expression on Huh7 cell surface. Materials and Methods: The NS3/NS4A sequence was isolated from a patient with HCV-3a chronic infection, cloned into intermediate vector pTZ57R/T, and then used for engineering a mammalian expression vector, pDisplay, to direct the respective protein to the secretory pathway and anchor it to the plasma membrane. The expression of the protein in Huh7 cell, which was transiently transfected with the vector using Lipofectamine, was determined by immunocytochemical staining assay with fluorescein isothiocyanate (FITC)-conjugated antibodies to the HA/myc tags located besides the fusion fragment. Results: The results showed that the fragment was successfully amplified and cloned into a eukaryotic expression vector. Sequencing and enzyme digestion analysis confirmed the cloned gene completion and its correct position in the pDisply-NS3/NS4A plasmid. Immunocytochemical staining revealed that the target protein was expressed as a membrane-anchored protein in the Huh7 cells. Conclusions: This study can serve as a fundamental experiment for the construction of a NS3/NS4A eukaryotic expression vector and its expression in mammalian cells. Further research is underway to evaluate the fragment immunogenicity in lab animal models. PMID:26862385

  11. 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

  12. 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.

  13. 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.

  14. Discovery of new scaffolds for rational design of HCV NS5B polymerase inhibitors.

    PubMed

    Golub, Andriy G; Gurukumar, K R; Basu, Amartya; Bdzhola, Volodymyr G; Bilokin, Yaroslav; Yarmoluk, Sergiy M; Lee, Jin-Ching; Talele, Tanaji T; Nichols, Daniel B; Kaushik-Basu, Neerja

    2012-12-01

    Hepatitis C virus (HCV) NS5B polymerase is a key target for the development of anti-HCV drugs. Here we report on the identification of novel allosteric inhibitors of HCV NS5B through a combination of structure-based virtual screening and in vitro NS5B inhibition assays. One hundred and sixty thousand compounds from the Otava database were virtually screened against the thiazolone inhibitor binding site on NS5B (thumb pocket-2, TP-2), resulting in a sequential down-sizing of the library by 2.7 orders of magnitude to yield 59 NS5B non-nucleoside inhibitor (NNI) candidates. In vitro evaluation of the NS5B inhibitory activity of the 59 selected compounds resulted in a 14% hit rate, yielding 8 novel structural scaffolds. Of these, compound 1 bearing a 4-hydrazinoquinazoline scaffold was the most active (IC(50) = 16.0 μM). The binding site of all 8 NNIs was mapped to TP-2 of NS5B as inferred by a decrease in their inhibition potency against the M423T NS5B mutant, employed as a screen for TP-2 site binders. At 100 μM concentration, none of the eight compounds exhibited any cytotoxicity, and all except compound 8 exhibited between 40 and 60% inhibition of intracellular NS5B polymerase activity in BHK-NS5B-FRLuc reporter cells. These inhibitor scaffolds will form the basis for future optimization and development of more potent NS5B inhibitors. PMID:23127989

  15. 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.

  16. 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 %.

  17. Impact of nanosecond pulsed electric fields on primary hippocampal neurons

    NASA Astrophysics Data System (ADS)

    Roth, Caleb C.; Payne, Jason A.; Kuipers, Marjorie A.; Thompson, Gary L.; Wilmink, Gerald J.; Ibey, Bennett L.

    2012-02-01

    Cellular exposure to nanosecond pulsed electric fields (nsPEF) are believed to cause immediate creation of nanopores in the plasma membrane. These nanopores enable passage of small ions, but remain impermeable to larger molecules like propidium iodide. Previous work has shown that nanopores are stable for minutes after exposure, suggesting that formation of nanopores in excitable cells could lead to prolonged action potential inhibition. Previously, we measured the formation of nanopores in neuroblastoma cells by measuring the influx of extracellular calcium by preloading cells with Calcium Green-AM. In this work, we explored the impact of changing the width of a single nsPEF, at constant amplitude, on uptake of extracellular calcium ions by primary hippocampal neurons (PHN). Calcium Green was again used to measure the influx of extracellular calcium and FM1-43 was used to monitor changes in membrane conformation. The observed thresholds for nanopore formation in PHN by nsPEF were comparable to those measured in neuroblastoma. This work is the first study of nsPEF effects on PHN and strongly suggests that neurological inhibition by nanosecond electrical pulses is highly likely at doses well below irreversible damage.

  18. 43 CFR 2.10 - Where do I send my request?

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... INFORMATION ACT Requests for Records under the FOIA § 2.10 Where do I send my request? (a) DOI does not have a... of documents in its possession. DOI's files are decentralized and are maintained by various...

  19. DNA Electrophoretic Migration Patterns Change after Exposure of Jurkat Cells to a Single Intense Nanosecond Electric Pulse

    PubMed Central

    Romeo, Stefania; Zeni, Luigi; Sarti, Maurizio; Sannino, Anna; Scarfì, Maria Rosaria; Vernier, P. Thomas; Zeni, Olga

    2011-01-01

    Intense nanosecond pulsed electric fields (nsPEFs) interact with cellular membranes and intracellular structures. Investigating how cells respond to nanosecond pulses is essential for a) development of biomedical applications of nsPEFs, including cancer therapy, and b) better understanding of the mechanisms underlying such bioelectrical effects. In this work, we explored relatively mild exposure conditions to provide insight into weak, reversible effects, laying a foundation for a better understanding of the interaction mechanisms and kinetics underlying nsPEF bio-effects. In particular, we report changes in the nucleus of Jurkat cells (human lymphoblastoid T cells) exposed to single pulses of 60 ns duration and 1.0, 1.5 and 2.5 MV/m amplitudes, which do not affect cell growth and viability. A dose-dependent reduction in alkaline comet-assayed DNA migration is observed immediately after nsPEF exposure, accompanied by permeabilization of the plasma membrane (YO-PRO-1 uptake). Comet assay profiles return to normal within 60 minutes after pulse delivery at the highest pulse amplitude tested, indicating that our exposure protocol affects the nucleus, modifying DNA electrophoretic migration patterns. PMID:22164287

  20. All-solid-state repetitive semiconductor opening switch-based short pulse generator

    NASA Astrophysics Data System (ADS)

    Ding, Zhenjie; Hao, Qingsong; Hu, Long; Su, Jiancang; Liu, Guozhi

    2009-09-01

    The operating characteristics of a semiconductor opening switch (SOS) are determined by its pumping circuit parameters. SOS is still able to cut off the current when pumping current duration falls to the order of tens of nanoseconds and a short pulse forms simultaneously in the output load. An all-solid-state repetitive SOS-based short pulse generator (SPG100) with a three-level magnetic pulse compression unit was successfully constructed. The generator adopts magnetic pulse compression unit with metallic glass and ferrite cores, which compresses a 600 V, 10 μs primary pulse into short pulse with forward pumping current of 825 A, 60 ns and reverse pumping current of 1.3 kA, 30 ns. The current is sent to SOS in which the reverse pumping current is interrupted. The generator is capable of providing a pulse with the voltage of 120 kV and duration of 5-6 ns while output load being 125 Ω. The highest repetition rate is up to 1 kHz.

  1. All-solid-state repetitive semiconductor opening switch-based short pulse generator.

    PubMed

    Ding, Zhenjie; Hao, Qingsong; Hu, Long; Su, Jiancang; Liu, Guozhi

    2009-09-01

    The operating characteristics of a semiconductor opening switch (SOS) are determined by its pumping circuit parameters. SOS is still able to cut off the current when pumping current duration falls to the order of tens of nanoseconds and a short pulse forms simultaneously in the output load. An all-solid-state repetitive SOS-based short pulse generator (SPG100) with a three-level magnetic pulse compression unit was successfully constructed. The generator adopts magnetic pulse compression unit with metallic glass and ferrite cores, which compresses a 600 V, 10 mus primary pulse into short pulse with forward pumping current of 825 A, 60 ns and reverse pumping current of 1.3 kA, 30 ns. The current is sent to SOS in which the reverse pumping current is interrupted. The generator is capable of providing a pulse with the voltage of 120 kV and duration of 5-6 ns while output load being 125 Omega. The highest repetition rate is up to 1 kHz. PMID:19791935

  2. Suppressing Spectral Diffusion of Emitted Photons with Optical Pulses

    NASA Astrophysics Data System (ADS)

    Fotso, H. F.; Feiguin, A. E.; Awschalom, D. D.; Dobrovitski, V. V.

    2016-01-01

    In many quantum architectures the solid-state qubits, such as quantum dots or color centers, are interfaced via emitted photons. However, the frequency of photons emitted by solid-state systems exhibits slow uncontrollable fluctuations over time (spectral diffusion), creating a serious problem for implementation of the photon-mediated protocols. Here we show that a sequence of optical pulses applied to the solid-state emitter can stabilize the emission line at the desired frequency. We demonstrate efficiency, robustness, and feasibility of the method analytically and numerically. Taking nitrogen-vacancy center in diamond as an example, we show that only several pulses, with the width of 1 ns, separated by few ns (which is not difficult to achieve) can suppress spectral diffusion. Our method provides a simple and robust way to greatly improve the efficiency of photon-mediated entanglement and/or coupling to photonic cavities for solid-state qubits.

  3. 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. PMID:21529005

  4. A compact repetitive high-voltage nanosecond pulse generator for the application of gas discharge

    NASA Astrophysics Data System (ADS)

    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.

  5. 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.

  6. 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

  7. 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

  8. 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.

  9. Structure and Function of Flavivirus NS5 Methyltransferase

    SciTech Connect

    Zhou,Y.; Ray, D.; Zhao, Y.; Dong, H.; Ren, S.; Li, Z.; Guo, Y.; Bernard, K.; Shi, P.; Li, H.

    2007-01-01

    The plus-strand RNA genome of flavivirus contains a 5' terminal cap 1 structure (m{sup 7}GpppAmG). The flaviviruses encode one methyltransferase, located at the N-terminal portion of the NS5 protein, to catalyze both guanine N-7 and ribose 2'-OH methylations during viral cap formation. Representative flavivirus methyltransferases from dengue, yellow fever, and West Nile virus (WNV) sequentially generate GpppA {yields} m{sup 7}GpppA {yields} m{sup 7}GpppAm. The 2'-O methylation can be uncoupled from the N-7 methylation, since m{sup 7}GpppA-RNA can be readily methylated to m{sup 7}GpppAm-RNA. Despite exhibiting two distinct methylation activities, the crystal structure of WNV methyltransferase at 2.8 {angstrom} resolution showed a single binding site for S-adenosyl-L-methionine (SAM), the methyl donor. Therefore, substrate GpppA-RNA should be repositioned to accept the N-7 and 2'-O methyl groups from SAM during the sequential reactions. Electrostatic analysis of the WNV methyltransferase structure showed that, adjacent to the SAM-binding pocket, is a highly positively charged surface that could serve as an RNA binding site during cap methylations. Biochemical and mutagenesis analyses show that the N-7 and 2'-O cap methylations require distinct buffer conditions and different side chains within the K{sub 61}-D{sub 146}-K{sub 182}-E{sub 218} motif, suggesting that the two reactions use different mechanisms. In the context of complete virus, defects in both methylations are lethal to WNV; however, viruses defective solely in 2'-O methylation are attenuated and can protect mice from later wild-type WNV challenge. The results demonstrate that the N-7 methylation activity is essential for the WNV life cycle and, thus, methyltransferase represents a novel target for flavivirus therapy.

  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. 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.

  12. Active Microwave Pulse Compressor Using an Electron-Beam Triggered Switch

    NASA Astrophysics Data System (ADS)

    Ivanov, O. A.; Lobaev, M. A.; Vikharev, A. L.; Gorbachev, A. M.; Isaev, V. A.; Hirshfield, J. L.; Gold, S. H.; Kinkead, A. K.

    2013-03-01

    A high-power active microwave pulse compressor is described that operates by modulating the quality factor of an energy storage cavity by means of mode conversion controlled by a triggered electron-beam discharge across a switch cavity. This Letter describes the principle of operation, the design of the switch cavity, the configuration used for the tests, and the experimental results. The pulse compressor produced output pulses with 140-165 MW peak power, record peak power gains of 16∶1-20∶1, and FWHM pulse duration of 16-20 ns at a frequency of 11.43 GHz.

  13. Active microwave pulse compressor using an electron-beam triggered switch.

    PubMed

    Ivanov, O A; Lobaev, M A; Vikharev, A L; Gorbachev, A M; Isaev, V A; Hirshfield, J L; Gold, S H; Kinkead, A K

    2013-03-15

    A high-power active microwave pulse compressor is described that operates by modulating the quality factor of an energy storage cavity by means of mode conversion controlled by a triggered electron-beam discharge across a switch cavity. This Letter describes the principle of operation, the design of the switch cavity, the configuration used for the tests, and the experimental results. The pulse compressor produced output pulses with 140-165 MW peak power, record peak power gains of 16∶1-20∶1, and FWHM pulse duration of 16-20 ns at a frequency of 11.43 GHz. PMID:25166547

  14. 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...

  15. Phosphoproteomics Identified an NS5A Phosphorylation Site Involved in Hepatitis C Virus Replication.

    PubMed

    Chong, Weng Man; Hsu, Shih-Chin; Kao, Wei-Ting; Lo, Chieh-Wen; Lee, Kuan-Ying; Shao, Jheng-Syuan; Chen, Yi-Hung; Chang, Justin; Chen, Steve S-L; Yu, Ming-Jiun

    2016-02-19

    The non-structural protein 5A (NS5A) is a hepatitis C virus (HCV) protein indispensable for the viral life cycle. Many prior papers have pinpointed several serine residues in the low complexity sequence I region of NS5A responsible for NS5A phosphorylation; however, the functions of specific phosphorylation sites remained obscure. Using phosphoproteomics, we identified three phosphorylation sites (serines 222, 235, and 238) in the NS5A low complexity sequence I region. Reporter virus and replicon assays using phosphorylation-ablated alanine mutants of these sites showed that Ser-235 dominated over Ser-222 and Ser-238 in HCV replication. Immunoblotting using an Ser-235 phosphorylation-specific antibody showed a time-dependent increase in Ser-235 phosphorylation that correlated with the viral replication activity. Ser-235 phosphorylated NS5A co-localized with double-stranded RNA, consistent with its role in HCV replication. Mechanistically, Ser-235 phosphorylation probably promotes the replication complex formation via increasing NS5A interaction with the human homologue of the 33-kDa vesicle-associated membrane protein-associated protein. Casein kinase Iα (CKIα) directly phosphorylated Ser-235 in vitro. Inhibition of CKIα reduced Ser-235 phosphorylation and the HCV RNA levels in the infected cells. We concluded that NS5A Ser-235 phosphorylated by CKIα probably promotes HCV replication via increasing NS5A interaction with the 33-kDa vesicle-associated membrane protein-associated protein. PMID:26702051

  16. Mutations in classical swine fever virus NS4B affect virulence in swine

    Technology Transfer Automated Retrieval System (TEKTRAN)

    NS4B is one of the non-structural proteins of Classical Swine Fever Virus (CSFV), a virus causing a severe disease in swine. Protein domain analysis of the predicted amino acid sequence of NS4B in highly pathogenic CSFV strain Brescia (BICv) identified a Toll/Interleukin-1 receptor like domain (TIR...

  17. 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. PMID:26739427

  18. 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

  19. 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...

  20. 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 %.

  1. Polyethylene welding by pulsed visible laser irradiation

    NASA Astrophysics Data System (ADS)

    Torrisi, L.; Caridi, F.; Visco, A. M.; Campo, N.

    2011-01-01

    Laser welding of plastics is a relatively new process that induces locally a fast polymer heating. For most applications, the process involves directing a pulsed beam of visible light at the weld joint by going through one of the two parts. This is commonly referred to as “through transmission visible laser welding”. In this technique, the monochromatic visible light source uses a power ns pulsed laser in order to irradiate the joint through one part and the light is absorbed in the vicinity of the other part. In order to evaluate the mechanical resistance of the welded joint, mass quadrupole spectrometry, surface profilometry, microscopy techniques and mechanical shear tests were employed. The welding effect was investigated as a function of the laser irradiation time, nature of the polyethylene materials and temperature.

  2. 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. PMID:21034107

  3. A Tesla-pulse forming line-plasma opening switch pulsed power generator

    NASA Astrophysics Data System (ADS)

    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 (SF6), 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.

  4. 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.

  5. Phosphorylation of influenza A virus NS1 protein at threonine 49 suppresses its interferon antagonistic activity.

    PubMed

    Kathum, Omer Abid; Schräder, Tobias; Anhlan, Darisuren; Nordhoff, Carolin; Liedmann, Swantje; Pande, Amit; Mellmann, Alexander; Ehrhardt, Christina; Wixler, Viktor; Ludwig, Stephan

    2016-06-01

    Phosphorylation and dephosphorylation acts as a fundamental molecular switch that alters protein function and thereby regulates many cellular processes. The non-structural protein 1 (NS1) of influenza A virus is an important factor regulating virulence by counteracting cellular immune responses against viral infection. NS1 was shown to be phosphorylated at several sites; however, so far, no function has been conclusively assigned to these post-translational events yet. Here, we show that the newly identified phospho-site threonine 49 of NS1 is differentially phosphorylated in the viral replication cycle. Phosphorylation impairs binding of NS1 to double-stranded RNA and TRIM25 as well as complex formation with RIG-I, thereby switching off its interferon antagonistic activity. Because phosphorylation was shown to occur at later stages of infection, we hypothesize that at this stage other functions of the multifunctional NS1 beyond its interferon-antagonistic activity are needed. PMID:26687707

  6. BOREAS Level-2 NS001 TMS Imagery: Reflectance and Temperature in BSQ Format

    NASA Technical Reports Server (NTRS)

    Lobitz, Brad; Spanner, Michael; Hall, Forrest G. (Editor); Newcomer, Jeffrey A. (Editor); Strub, Richard

    2000-01-01

    For BOREAS, the NS001 TMS images, along with the other remotely sensed data, were collected to provide spatially extensive information over the primary study areas. This information includes detailed land cover and biophysical parameter maps such as fPAR and LAI. Collection of the NS001 images occurred over the study areas during the 1994 field campaigns. The level-2 NS001 data are atmospherically corrected versions of some of the best original NS001 imagery and cover the dates of 19-Apr-1994, 07-Jun-1994, 21-Jul-1994, 08-Aug-1994, and 16-Sep-1994. The data are not geographically/geometrically corrected; however, files of relative X and Y coordinates for each image pixel were derived by using the C130 INS data in an NS001 scan model. The data are provided in binary image format files.

  7. Potent hepatitis C inhibitors bind directly to NS5A and reduce its affinity for RNA.

    PubMed

    Ascher, David B; Wielens, Jerome; Nero, Tracy L; Doughty, Larissa; Morton, Craig J; Parker, Michael W

    2014-01-01

    Hepatitis C virus (HCV) infection affects more than 170 million people. The high genetic variability of HCV and the rapid development of drug-resistant strains are driving the urgent search for new direct-acting antiviral agents. A new class of agents has recently been developed that are believed to target the HCV protein NS5A although precisely where they interact and how they affect function is unknown. Here we describe an in vitro assay based on microscale thermophoresis and demonstrate that two clinically relevant inhibitors bind tightly to NS5A domain 1 and inhibit RNA binding. Conversely, RNA binding inhibits compound binding. The compounds bind more weakly to known resistance mutants L31V and Y93H. The compounds do not affect NS5A dimerisation. We propose that current NS5A inhibitors act by favouring a dimeric structure of NS5A that does not bind RNA. PMID:24755925

  8. Potent hepatitis C inhibitors bind directly to NS5A and reduce its affinity for RNA

    PubMed Central

    Ascher, David B.; Wielens, Jerome; Nero, Tracy L.; Doughty, Larissa; Morton, Craig J.; Parker, Michael W.

    2014-01-01

    Hepatitis C virus (HCV) infection affects more than 170 million people. The high genetic variability of HCV and the rapid development of drug-resistant strains are driving the urgent search for new direct-acting antiviral agents. A new class of agents has recently been developed that are believed to target the HCV protein NS5A although precisely where they interact and how they affect function is unknown. Here we describe an in vitro assay based on microscale thermophoresis and demonstrate that two clinically relevant inhibitors bind tightly to NS5A domain 1 and inhibit RNA binding. Conversely, RNA binding inhibits compound binding. The compounds bind more weakly to known resistance mutants L31V and Y93H. The compounds do not affect NS5A dimerisation. We propose that current NS5A inhibitors act by favouring a dimeric structure of NS5A that does not bind RNA. PMID:24755925

  9. NsLTP1 and NsLTP2 isoforms in soft wheat (Triticum aestivum Cv. Centauro) and farro (Triticum dicoccon Schrank) bran.

    PubMed

    Capocchi, Antonella; Fontanini, Debora; Muccilli, Vera; Cunsolo, Vincenzo; Saviozzi, Franco; Saletti, Rosaria; Lorenzi, Roberto; Foti, Salvatore; Galleschi, Luciano

    2005-10-01

    Isoforms of nonspecific lipid-transfer protein 1 (nsLTP1) and nonspecific lipid-transfer protein 2 (nsLTP2) were investigated in bran tissues isolated from caryopses of two cereal crops quite relevant for the Italian market, the cultivar Centauro of soft wheat (Triticum aestivum) and Italian emmer or farro (Triticum dicoccon Schrank). By sequential separation of the bran extracts on cation-exchange and gel filtration chromatographies, fractions containing only proteins belonging to the nsLTP1 and nsLTP2 classes were obtained. The proteins were roughly identified by SDS-PAGE and by immunoreactions in Western blotting experiments. By MALDI-MS and RP-HPLC/ESI-MS analyses we were able to show the presence of several LTP1 and LTP2 isoforms in the investigated species. Bioinformatic searches based on the determined Mr indicated that (i) two nsLTP1s already identified in T. aestivum have Mr and number of Cys residues identical to that of a 9.6 kDa protein present both in soft wheat cv. Centauro and in farro; (ii) two isoforms of nsLTP2 detected in T. aestivum have the same Mr and number of Cys residues of two 7 kDa proteins found in Centauro; and (iii) a nsLTP1 detected in Ambrosia artemisiifolia has Mr and number of Cys residues coincident to that of a 9.9 kDa protein found both in soft wheat cv. Centauro and in farro. PMID:16190659

  10. Design and docking studies of peptide inhibitors as potential antiviral drugs for dengue virus ns2b/ns3 protease.

    PubMed

    Velmurugan, Devadasan; Mythily, Udhayakumar; Rao, Kutumba

    2014-01-01

    Dengue virus (DENV), one of the members of genus Flavivirus is emerging as a global threat to human health. It had led to the emergence of dengue fever (flu-like illness), dengue shock syndrome, and the most severe dengue hemorrhagic fever (severe dengue with bleeding abnormalities). As Dengue hemorrhage diseases are the life-threatening ones, attempts are being made worldwide to design inhibitors for DENV-2 NS2B-NS3 protease. NS2B/NS3 protease plays a vital role in the replication of dengue virus. The trypsin-like serine protease domain of NS3 contains the functional catalytic triad His-51, Asp-75, and Ser-135 in the N-terminal region. Inhibition of the NS3 protease activity is expected to prevent the propagation of dengue virus. Current drug discovery methods are largely inefficient and thus relatively ineffective in tackling the growing threat to public health presented by emerging and remerging viral pathogens. Recently, there has been a need of interest in peptides and their mimetics as potential antagonists for dengue protease because these small peptides are unlikely to invoke an immune response since they fall below the immunogenic threshold. They are often potent and display fewer toxicity issues than small-molecule compounds as a result of high specificity. This study was conducted to design peptides as enzyme inhibitors of dengue virus NS3 protease through computational approach. Crystallographic structure of dengue protease was retrieved from Protein Data Bank (PDBID: 2FOM) and docked with the peptides and the results are analyzed. From the docking studies reported in this paper, tetrapeptide (Lys-Gly-Pro-Glu), pentapeptide (Ser-Ile-Lys-Phe-Ala) and hexapeptide (Ala-Ile-Lys-Lys-Phe-Ser) with glide energy -70.0 kcal/mol, -72.2 kcal/mol and - 80.4 kcal/mol respectively show promising results which can be considered for further optimization and in vitro studies. PMID:23855663

  11. External stimulation by nanosecond pulsed electric fields to enhance cellular uptake of nanoparticles

    NASA Astrophysics Data System (ADS)

    Franklin, Samantha; Beier, Hope T.; Ibey, Bennett L.; Nash, Kelly

    2015-03-01

    As an increasing number of studies use gold nanoparticles (AuNPs) for potential medicinal, biosensing and therapeutic applications, the synthesis and use of readily functional, bio-compatible nanoparticles is receiving much interest. For these efforts, the particles are often taken up by the cells to allow for optimum sensing or therapeutic measures. This process typically requires incubation of the particles with the cells for an extended period. In an attempt to shorten and control this incubation, we investigated whether nanosecond pulsed electric field (nsPEF) exposure of cells will cause a controlled uptake of the particles. NsPEF are known to induce the formation of nanopores in the plasma membrane, so we hypothesized that by controlling the number, amplitude or duration of the nsPEF exposure, we could control the size of the nanopores, and thus control the particle uptake. Chinese hamster ovary (CHO-K1) cells were incubated sub-10 nm AuNPs with and without exposure to 600-ns electrical pulses. Contrary to our hypothesis, the nsPEF exposure was found to actually decrease the particle uptake in the exposed cells. This result suggests that the nsPEF exposure may be affecting the endocytotic pathway and processes due to membrane disruption.

  12. 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)

  13. 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

  14. 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. PMID:25076864

  15. Dengue Virus NS1 Disrupts the Endothelial Glycocalyx, Leading to Hyperpermeability.

    PubMed

    Puerta-Guardo, Henry; Glasner, Dustin R; Harris, Eva

    2016-07-01

    Dengue is the most prevalent arboviral disease in humans and a major public health problem worldwide. Systemic plasma leakage, leading to hypovolemic shock and potentially fatal complications, is a critical determinant of dengue severity. Recently, we and others described a novel pathogenic effect of secreted dengue virus (DENV) non-structural protein 1 (NS1) in triggering hyperpermeability of human endothelial cells in vitro and systemic vascular leakage in vivo. NS1 was shown to activate toll-like receptor 4 signaling in primary human myeloid cells, leading to secretion of pro-inflammatory cytokines and vascular leakage. However, distinct endothelial cell-intrinsic mechanisms of NS1-induced hyperpermeability remained to be defined. The endothelial glycocalyx layer (EGL) is a network of membrane-bound proteoglycans and glycoproteins lining the vascular endothelium that plays a key role in regulating endothelial barrier function. Here, we demonstrate that DENV NS1 disrupts the EGL on human pulmonary microvascular endothelial cells, inducing degradation of sialic acid and shedding of heparan sulfate proteoglycans. This effect is mediated by NS1-induced expression of sialidases and heparanase, respectively. NS1 also activates cathepsin L, a lysosomal cysteine proteinase, in endothelial cells, which activates heparanase via enzymatic cleavage. Specific inhibitors of sialidases, heparanase, and cathepsin L prevent DENV NS1-induced EGL disruption and endothelial hyperpermeability. All of these effects are specific to NS1 from DENV1-4 and are not induced by NS1 from West Nile virus, a related flavivirus. Together, our data suggest an important role for EGL disruption in DENV NS1-mediated endothelial dysfunction during severe dengue disease. PMID:27416066

  16. Raman spectroscopy based discrimination of NS1 positive and negative dengue virus infected serum

    NASA Astrophysics Data System (ADS)

    Bilal, M.; Saleem, M.; Bilal, Maria; Khurram, M.; Khan, Saranjam; Ullah, Rahat; Ali, Hina; Ahmed, M.

    2016-09-01

    This study is intended to develop a multivariate statistical model for the prediction of nonstructural protein 1 (NS1) in dengue virus (DENV) infected blood serum in humans. The model has been developed on the basis of partial least squares regression using the Raman spectra of NS1 positive and NS1 negative samples. Human blood sera of 218 subjects is included in this study, of which 95 were NS1 positive and 123 were NS1 negative, which was confirmed with the enzyme linked immunosorbent assay method. For model development, 80 NS1 positive and 98 NS1 negative samples were used, while 40 DENV suspected samples were used for double blind testing of the model. This selection of samples was performed by the code in an automatic manner to avoid biasing. A laser at 785 nm was used as the excitation source to acquire Raman spectra of samples with an integration time of 15 s. The multivariate model yields coefficients of regression at corresponding Raman shifts. These coefficients represent changes in the molecular structures associated with NS1 positive and negative samples. The analysis of the regression coefficients which differentiate NS1 positive and NS1 negative groups shows an increasing trend for phosphatidylinositol, ceramide, and amide-III, and a decreasing trend for thiocyanate in the DENV infected serum. The R-squared value of the model was found to be 0.91, which is clinically acceptable. The blind testing of 40 suspected samples yields an accuracy, sensitivity, and specificity of about 100% each.

  17. Dengue Virus NS1 Disrupts the Endothelial Glycocalyx, Leading to Hyperpermeability

    PubMed Central

    Puerta-Guardo, Henry; Glasner, Dustin R.; Harris, Eva

    2016-01-01

    Dengue is the most prevalent arboviral disease in humans and a major public health problem worldwide. Systemic plasma leakage, leading to hypovolemic shock and potentially fatal complications, is a critical determinant of dengue severity. Recently, we and others described a novel pathogenic effect of secreted dengue virus (DENV) non-structural protein 1 (NS1) in triggering hyperpermeability of human endothelial cells in vitro and systemic vascular leakage in vivo. NS1 was shown to activate toll-like receptor 4 signaling in primary human myeloid cells, leading to secretion of pro-inflammatory cytokines and vascular leakage. However, distinct endothelial cell-intrinsic mechanisms of NS1-induced hyperpermeability remained to be defined. The endothelial glycocalyx layer (EGL) is a network of membrane-bound proteoglycans and glycoproteins lining the vascular endothelium that plays a key role in regulating endothelial barrier function. Here, we demonstrate that DENV NS1 disrupts the EGL on human pulmonary microvascular endothelial cells, inducing degradation of sialic acid and shedding of heparan sulfate proteoglycans. This effect is mediated by NS1-induced expression of sialidases and heparanase, respectively. NS1 also activates cathepsin L, a lysosomal cysteine proteinase, in endothelial cells, which activates heparanase via enzymatic cleavage. Specific inhibitors of sialidases, heparanase, and cathepsin L prevent DENV NS1-induced EGL disruption and endothelial hyperpermeability. All of these effects are specific to NS1 from DENV1-4 and are not induced by NS1 from West Nile virus, a related flavivirus. Together, our data suggest an important role for EGL disruption in DENV NS1-mediated endothelial dysfunction during severe dengue disease. PMID:27416066

  18. A design approach for systems based on magnetic pulse compression.

    PubMed

    Kumar, D Durga Praveen; Mitra, S; Senthil, K; Sharma, D K; Rajan, Rehim N; Sharma, Archana; Nagesh, K V; Chakravarthy, D P

    2008-04-01

    A design approach giving the optimum number of stages in a magnetic pulse compression circuit and gain per stage is given. The limitation on the maximum gain per stage is discussed. The total system volume minimization is done by considering the energy storage capacitor volume and magnetic core volume at each stage. At the end of this paper, the design of a magnetic pulse compression based linear induction accelerator of 200 kV, 5 kA, and 100 ns with a repetition rate of 100 Hz is discussed with its experimental results. PMID:18447549

  19. 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.

  20. Permeabilization of yeast Saccharomyces cerevisiae cell walls using nanosecond high power electrical pulses

    NASA Astrophysics Data System (ADS)

    Stirke, A.; Zimkus, A.; Balevicius, S.; Stankevic, V.; Ramanaviciene, A.; Ramanavicius, A.; Zurauskiene, N.

    2014-12-01

    The electrical field-induced changes of the yeast Saccharomyces cerevisiae cells permeabilization to tetraphenylphosphonium (TPP+) ions were studied using square-shaped, nanosecond duration high power electrical pulses. It was obtained that pulses having durations ranging from 10 ns to 60 ns, and generating electric field strengths up to 190 kV/cm significantly (up to 65 times) increase the absorption rate of TPP+ ions without any detectible influence on the yeast cell viability. The modelling of the TPP+ absorption process using a second order rate equation demonstrates that depending on the duration of the pulses, yeast cell clusters of different sizes are homogeniously permeabilized. It was concluded, that nanosecond pulse-induced permeabilization can be applied to increase the operational speed of whole cell biosensors.

  1. 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

  2. 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.

  3. 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.

  4. Generation of high-voltage pulses with subnanosecond front rise times in open discharge

    SciTech Connect

    Bokhan, P. A.; Gugin, P. P.; Lavrukhin, M. A.; Zakrevsky, Dm. E.

    2013-03-15

    The investigation results for plasma switching devices of high-voltage pulses with pulse rise times less than 1 ns are presented. The approach is based on using conditions suitable for bringing a gas discharge chamber in a state with high conductivity due to generation of an electron beam owing to photoelectron emission from the device cathode. It is shown that in co-axial geometry pulses, switching time 0.45 ns on an active load R{sub L} = 50 {Omega} at voltage U = 20 kV can be achieved. It is shown with the method of doubled impulses that such a device can regenerate the acceptable electric strength during 10 {mu}s. It is indicated of the principle possibility of working in the pulse-periodical regime to the repetition rate of 100 kHz.

  5. Permeabilization of the nuclear envelope following nanosecond pulsed electric field exposure.

    PubMed

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

    2016-01-29

    Permeabilization of cell membranes occurs upon exposure to a threshold absorbed dose (AD) of nanosecond pulsed electric fields (nsPEF). The ultimate, physiological bioeffect of this exposure depends on the type of cultured cell and environment, indicating that cell-specific pathways and structures are stimulated. Here we investigate 10 and 600 ns duration PEF effects on Chinese hamster ovary (CHO) cell nuclei, where our hypothesis is that pulse disruption of the nuclear envelope membrane leads to observed cell death and decreased viability 24 h post-exposure. To observe short-term responses to nsPEF exposure, CHO cells have been stably transfected with two fluorescently-labeled proteins known to be sequestered for cellular chromosomal function within the nucleus - histone-2b (H2B) and proliferating cell nuclear antigen (PCNA). H2B remains associated with chromatin after nsPEF exposure, whereas PCNA leaks out of nuclei permeabilized by a threshold AD of 10 and 600 ns PEF. A downturn in 24 h viability, measured by MTT assay, is observed at the number of pulses required to induce permeabilization of the nucleus. PMID:26721436

  6. In-vitro bipolar nano- and microsecond electro-pulse bursts for irreversible electroporation therapies.

    PubMed

    Sano, Michael B; Arena, Christopher B; DeWitt, Matthew R; Saur, Dieter; Davalos, Rafael V

    2014-12-01

    Under the influence of external electric fields, cells experience a rapid potential buildup across the cell membrane. Above a critical threshold of electric field strength, permanent cell damage can occur, resulting in cell death. Typical investigations of electroporation effects focus on two distinct regimes. The first uses sub-microsecond duration, high field strength pulses while the second uses longer (50 μs+) duration, but lower field strength pulses. Here we investigate the effects of pulses between these two extremes. The charging behavior of the cell membrane and nuclear envelope is evaluated numerically in response to bipolar pulses between 250 ns and 50 μs. Typical irreversible electroporation protocols expose cells to 90 monopolar pulses, each 100 μs in duration with a 1 second inter-pulse delay. Here, we replace each monopolar waveform with a burst of alternating polarity pulses, while keeping the total energized time (100 μs), burst number (80), and inter-burst delay (1s) the same. We show that these bursts result in instantaneous and delayed cell death mechanisms and that there exists an inverse relationship between pulse-width and toxicity despite the delivery of equal quantities of energy. At 1500 V/cm only treatments with bursts containing 50 μs pulses (2×) resulted in viability below 10%. At 4000 V/cm, bursts with 1 μs (100×), 2 μs (50×), 5 μs (20×), 10 μs (10×), and 50 μs (2×) duration pulses reduced viability below 10% while bursts with 500 ns (200×) and 250 ns (400×) pulses resulted in viabilities of 31% and 92%, respectively. PMID:25131187

  7. 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.

  8. Conductive versus capacitive coupling for cell electroporation with nanosecond pulses

    NASA Astrophysics Data System (ADS)

    French, David M.; Uhler, Michael D.; Gilgenbach, Ronald M.; Lau, Y. Y.

    2009-10-01

    Experiments and simulations were performed to determine the difference between capacitive coupling and conductive connection for the electroporation of cells. The pulses used in the experiments have a peak voltage of 24 kV, 0.6 ns rise time, and 1.6 ns full width at half maximum. Experiments performed compare the conductive connection of the cell suspension versus a capacitively coupled cell suspension. The magnitude of the electric field was 16 kV/cm in both cases; however, the pulse shape is different. For the conductively connected case the cells located between the electrodes experienced an electric field in one direction only, whereas cells located between the electrodes in the capacitive coupling case were subject to an electric field that reverses direction. For the capacitively coupled case the bipolar pulse leads to no net cell charging. The conductive connection case is different, in that cells are left with a net polarization after the pulse is applied. Experimentally, only cells subject to the pulse with conductive connection demonstrated electroporation with the drug Bleomycin.

  9. Fast pulsed electroluminescence from polymer light-emitting diodes

    NASA Astrophysics Data System (ADS)

    Wang, J.; Sun, R. G.; Yu, G.; Heeger, A. J.

    2002-02-01

    Transient electroluminescence (EL) from polymer light emitting diodes is investigated by measurements of the response to short voltage pulses. The carrier mobility is derived from the delay time between the electrical pulse and the onset of EL, μ≈3×10-4 cm2/V s. Bilayer devices with a polyethylene-dioxythiophene (PEDOT), hole injection layer are also studied. The delay time between the electrical pulse and the onset of EL is independent of the thickness of the injection layer, implying that the conducting PEDOT functions as a part of the electrode. When a dc forward bias is applied to the device, the delay time decreases, probably as a result of the shift of the emission zone towards the anode. The EL turn-on depends on the amplitude of the voltage pulse. The data are modeled by an equivalent circuit with a fixed capacitance connected in parallel with a nonlinear resistance. The solution of the differential equation depends on the exact form of the device's I-V curve. Two analytical solutions are provided, and an analysis based on space-charge-limited current is presented. By applying a dc forward bias in advance to precharge the space-charge capacitance, the turn-on response time is reduced to 12 ns. The EL decay consists of two components with time constants of 15 ns and 1 μs. The decay does not depend on either the amplitude of the voltage pulse or the prebias.

  10. Broadband electrically detected magnetic resonance using adiabatic pulses.

    PubMed

    Hrubesch, F M; Braunbeck, G; Voss, A; Stutzmann, M; Brandt, M S

    2015-05-01

    We present a broadband microwave setup for electrically detected magnetic resonance (EDMR) based on microwave antennae with the ability to apply arbitrarily shaped pulses for the excitation of electron spin resonance (ESR) and nuclear magnetic resonance (NMR) of spin ensembles. This setup uses non-resonant stripline structures for on-chip microwave delivery and is demonstrated to work in the frequency range from 4 MHz to 18 GHz. π pulse times of 50 ns and 70 μs for ESR and NMR transitions, respectively, are achieved with as little as 100 mW of microwave or radiofrequency power. The use of adiabatic pulses fully compensates for the microwave magnetic field inhomogeneity of the stripline antennae, as demonstrated with the help of BIR4 unitary rotation pulses driving the ESR transition of neutral phosphorus donors in silicon and the NMR transitions of ionized phosphorus donors as detected by electron nuclear double resonance (ENDOR). PMID:25828243

  11. 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.

  12. 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.

  13. 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.

  14. Pulse and hold strategy for switching current measurements

    NASA Astrophysics Data System (ADS)

    Walter, Jochen; Tholén, Erik; Haviland, David B.; Sjöstrand, Joachim

    2007-03-01

    We investigate by theory and experiment, the Josephson junction switching current detector in an environment with frequency-dependent damping. Analysis of the circuit’s phase space shows that a favorable topology for switching can be obtained with overdamped dynamics at high frequencies. A pulse-and-hold method is described, where a fast switch pulse brings the circuit close to an unstable point in the phase space when biased at the hold level. Experiments are performed on Cooper pair transistors and quantronium circuits, which are overdamped at high frequencies with an on-chip RC shunt. For 20μs switch pulses the switching process is well described by thermal equilibrium escape, based on a generalization of the Kramers formula to the case of frequency-dependent damping. A capacitor bias method is used to create very rapid, 25ns switch pulses, where it is observed that the switching process is not governed by thermal equilibrium noise.

  15. Magnetic Field Sampling using a Pulsed Hysteretic SQUID

    NASA Astrophysics Data System (ADS)

    Kwon, S. P.; Vlahacos, C. P.; Berkley, A. J.; Gubrud, M. A.; Wellstood, F. C.; Cawthorne, A.

    2004-03-01

    Weak magnetic field detection using a non-hysteretic DC SQUID with Flux-Locked-Loop electronics is typically limited to 1MHz bandwidth or less. However, there is demand for larger bandwidth magnetic field detection for use in the semiconductor industry. We have studied the possibility of using a 4.2K hysteretic trilayer Nb DC SQUID, fabricated by Hypres Inc., with pulsed bias current to increase the bandwidth by an order of magnitude or more. The technique is based on the fast switching of a hysteretic SQUID from the superconducting state to the normal conducting state. By observing the switching of the SQUID, the applied magnetic field at the time of a pulse can be followed. Experimental results show that the technique can be used to follow magnetic fields of up to 60MHz with 5ns pulses. With shorter pulses and better electronics, the technique could further increase the bandwidth by another order of magnitude.

  16. Electroporation visualized under a multishot pulsed laser fluorescence microscope system

    NASA Astrophysics Data System (ADS)

    Itoh, Hiroyasu; Yu, Irene I. K.; Hibino, Masahiro; Hayakawa, Tsuyoshi; Kinosita, Kazuhiko, Jr.

    1993-10-01

    We describe a new fluorescence microscope system, which is the third generation of our pulsed-laser microscope systems developed for the purpose of capturing rapid cellular phenomena. Time resolution of this latest version is supported by the combination of a Q- switched Nd:YAG laser producing a burst of 4 pulses and a large format framing camera. We obtain series images at intervals on the order of 10 microsecond(s) with exposure times of 30 ns. With this multi-shot pulsed laser fluorescence microscope system, we examined the behavior of the transmembrane potential in a sea urchin egg under an intense electric field. Irreversible process of cell electroporation was revealed in serial images taken under a single electric pulse of microsecond duration.

  17. 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.

  18. 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.

  19. High efficiency, high pulse energy fiber laser system

    NASA Astrophysics Data System (ADS)

    Bowers, Mark S.; Henrie, Jason; Garske, Megan; Templeman, Dan; Afzal, Robert

    2013-05-01

    We report a master-oscillator/power-amplifier laser system featuring a polarizing and coilable 40-micron-core Yb-doped photonic crystal fiber as the final-stage amplifier. The laser source generates 3.4 ns pulses at a repetition rate 19 kHz, with maximum pulse energy 1.2 mJ, maximum average power 22.8 W, near diffraction-limited (M2 < 1.1) beam quality, and 20% electrical to optical efficiency in a compact package. This pulsed-fiber laser flight system provides high pulse energy, average power, peak power, diffraction limited beam quality, and high efficiency all in a thermally and mechanically stable compact package.

  20. 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.

  1. 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).

  2. Nucleolin Interacts with the Feline Calicivirus 3′ Untranslated Region and the Protease-Polymerase NS6 and NS7 Proteins, Playing a Role in Virus Replication ▿

    PubMed Central

    Cancio-Lonches, Clotilde; Yocupicio-Monroy, Martha; Sandoval-Jaime, Carlos; Galvan-Mendoza, Iván; Ureña, Luis; Vashist, Surender; Goodfellow, Ian; Salas-Benito, Juan; Gutiérrez-Escolano, Ana Lorena

    2011-01-01

    Cellular proteins play many important roles during the life cycle of all viruses. Specifically, host cell nucleic acid-binding proteins interact with viral components of positive-stranded RNA viruses and regulate viral translation, as well as RNA replication. Here, we report that nucleolin, a ubiquitous multifunctional nucleolar shuttling phosphoprotein, interacts with the Norwalk virus and feline calicivirus (FCV) genomic 3′ untranslated regions (UTRs). Nucleolin can also form a complex in vitro with recombinant Norwalk virus NS6 and -7 (NS6/7) and can be copurified with the analogous protein from feline calicivirus (p76 or NS6/7) from infected feline kidney cells. Nucleolin RNA levels or protein were not modified during FCV infection; however, as a consequence of the infection, nucleolin was seen to relocalize from the nucleoli to the nucleoplasm, as well as to the perinuclear area where it colocalizes with the feline calicivirus NS6/7 protein. In addition, antibodies to nucleolin were able to precipitate viral RNA from feline calicivirus-infected cells, indicating a direct or indirect association of nucleolin with the viral RNA during virus replication. Small interfering RNA (siRNA)-mediated knockdown of nucleolin resulted in a reduction of the cytopathic effect and virus yield in CrFK cells. Taken together, these results demonstrate that nucleolin is a nucleolar component that interacts with viral RNA and NS6/7 and is required for feline calicivirus replication. PMID:21680514

  3. Nucleolin interacts with the feline calicivirus 3' untranslated region and the protease-polymerase NS6 and NS7 proteins, playing a role in virus replication.

    PubMed

    Cancio-Lonches, Clotilde; Yocupicio-Monroy, Martha; Sandoval-Jaime, Carlos; Galvan-Mendoza, Iván; Ureña, Luis; Vashist, Surender; Goodfellow, Ian; Salas-Benito, Juan; Gutiérrez-Escolano, Ana Lorena

    2011-08-01

    Cellular proteins play many important roles during the life cycle of all viruses. Specifically, host cell nucleic acid-binding proteins interact with viral components of positive-stranded RNA viruses and regulate viral translation, as well as RNA replication. Here, we report that nucleolin, a ubiquitous multifunctional nucleolar shuttling phosphoprotein, interacts with the Norwalk virus and feline calicivirus (FCV) genomic 3' untranslated regions (UTRs). Nucleolin can also form a complex in vitro with recombinant Norwalk virus NS6 and -7 (NS6/7) and can be copurified with the analogous protein from feline calicivirus (p76 or NS6/7) from infected feline kidney cells. Nucleolin RNA levels or protein were not modified during FCV infection; however, as a consequence of the infection, nucleolin was seen to relocalize from the nucleoli to the nucleoplasm, as well as to the perinuclear area where it colocalizes with the feline calicivirus NS6/7 protein. In addition, antibodies to nucleolin were able to precipitate viral RNA from feline calicivirus-infected cells, indicating a direct or indirect association of nucleolin with the viral RNA during virus replication. Small interfering RNA (siRNA)-mediated knockdown of nucleolin resulted in a reduction of the cytopathic effect and virus yield in CrFK cells. Taken together, these results demonstrate that nucleolin is a nucleolar component that interacts with viral RNA and NS6/7 and is required for feline calicivirus replication. PMID:21680514

  4. A 6.4 kV pulse generator with transformers

    NASA Astrophysics Data System (ADS)

    Bastein, W. L.

    The possibility of producing a 6.4 kV voltage pulse using transformers was investigated. The pulse has to have a rise and fall time of 100 ns, a pulse duration of 2 to 50 microns, a repetition frequency of 2500 Hz, and a ripple of less than 10 V. It is shown that it is in principle possible, using transformers for the low frequency and high frequency parts of the pulse, to produce a pulse which fulfills the slope requirements. However, it is difficult to make and tune the circuits to flatten the pulse sufficiently. The losses are so high that it is recommended to investigate the possibility of producing the pulse with a number of MOSFET's in series.

  5. A semiconductor opening switch based generator with pulse repetitive frequency of 4 MHz.

    PubMed

    Wang, Gang; Su, Jiancang; Ding, Zhenjie; Yuan, Xuelin; Pan, Yafeng

    2013-12-01

    A MHz repetitive and nanosecond pulsed power generator based on the semiconductor opening switch (SOS) is developed, in which the pulse compression unit utilizes several Radio Frequency (RF) MOSFETs and a saturable Linear Transformer Driver (LTD). The RF MOSFETs are employed to obtain the forward pumping current pulses with the duration of tens of nanoseconds; the saturable LTD is used to raise the pulse voltage, to compress the pulse width and to pump SOS reversely. The SOS assembly cuts off the reverse current in a few nanoseconds, leading to a narrow output pulse on an external load. The experimental results show that the amplitude of the output pulse on a 106 Ω resistive load is about 3.8 kV and the width is 2 ns. Due to the repetitive ability of the RF MOSFETs, the generator can operate at a repetitive frequency of higher than 4 MHz in burst mode. PMID:24387463

  6. 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.

  7. Epitope mapping and functional analysis of sigma A and sigma NS proteins of avian reovirus

    SciTech Connect

    Huang, Pi H.; Li, Ying J.; Su, Yu P.; Lee, Long H.; Liu, Hung J. . E-mail: hjliu@mail.npust.edu.tw

    2005-02-20

    We have previously shown that avian reovirus (ARV) {sigma}A and {sigma}NS proteins possess dsRNA and ssRNA binding activity and suggested that there are two epitopes on {sigma}A (I and II) and three epitopes (A, B, and C) on {sigma}NS. To further define the location of epitopes on {sigma}A and {sigma}NS proteins and to further elucidate the biological functions of these epitopes by using monoclonal antibodies (MAbs) 62, 1F9, H1E1, and 4A123 against the ARV S1133 strain, the full-length and deletion fragments of S2 and S4 genes of ARV generated by polymerase chain reaction (PCR) were cloned into pET32 expression vectors and the fusion proteins were overexpressed in Escherichia coli BL21 strain. Epitope mapping using MAbs and E. coli-expressed deletion fragments of {sigma}A and {sigma}NS of the ARV S1133 strain, synthetic peptides, and the cross reactivity of MAbs to heterologous ARV strains demonstrated that epitope II on {sigma}A was located at amino acid residues {sup 340}QWVMAGLVSAA{sup 350} and epitope B on {sigma}NS at amino acid residues {sup 180}MLDMVDGRP{sup 188}. The MAbs (62, 1F9, and H1E1) directed against epitopes II and B did not require the native conformation of {sigma}A and {sigma}NS, suggesting that their binding activities were conformation-independent. On the other hand, MAb 4A123 only reacted with complete {sigma}NS but not with truncated {sigma}NS fusion proteins in Western blot, suggesting that the binding activity of MAb to epitope A on {sigma}NS was conformation-dependent. Amino acid sequence analysis and the binding assays of MAb 62 to heterologous ARV strains suggested that epitope II on {sigma}A was highly conserved among ARV strains and that this epitope is suitable as a serological marker for the detection of ARV antibodies following natural infection in chickens. On the contrary, an amino acid substitution at position 183 (M to V) in epitope B of ARV could hinder the reactivity of the {sigma}NS with MAb 1F9. The {sigma}NS of ARV with ss

  8. X-Ray Structure of the Pestivirus NS3 Helicase and Its Conformation in Solution

    PubMed Central

    Duquerroy, Stéphane; Kwok, Jane; Vonrhein, Clemens; Perez, Javier; Lamp, Benjamin; Bricogne, Gerard; Rümenapf, Till; Vachette, Patrice

    2015-01-01

    ABSTRACT Pestiviruses form a genus in the Flaviviridae family of small enveloped viruses with a positive-sense single-stranded RNA genome. Viral replication in this family requires the activity of a superfamily 2 RNA helicase contained in the C-terminal domain of nonstructural protein 3 (NS3). NS3 features two conserved RecA-like domains (D1 and D2) with ATPase activity, plus a third domain (D3) that is important for unwinding nucleic acid duplexes. We report here the X-ray structure of the pestivirus NS3 helicase domain (pNS3h) at a 2.5-Å resolution. The structure deviates significantly from that of NS3 of other genera in the Flaviviridae family in D3, as it contains two important insertions that result in a narrower nucleic acid binding groove. We also show that mutations in pNS3h that rescue viruses from which the core protein is deleted map to D3, suggesting that this domain may be involved in interactions that facilitate particle assembly. Finally, structural comparisons of the enzyme in different crystalline environments, together with the findings of small-angle X-ray-scattering studies in solution, show that D2 is mobile with respect to the rest of the enzyme, oscillating between closed and open conformations. Binding of a nonhydrolyzable ATP analog locks pNS3h in a conformation that is more compact than the closest apo-form in our crystals. Together, our results provide new insight and bring up new questions about pNS3h function during pestivirus replication. IMPORTANCE Although pestivirus infections impose an important toll on the livestock industry worldwide, little information is available about the nonstructural proteins essential for viral replication, such as the NS3 helicase. We provide here a comparative structural and functional analysis of pNS3h with respect to its orthologs in other viruses of the same family, the flaviviruses and hepatitis C virus. Our studies reveal differences in the nucleic acid binding groove that could have implications

  9. NMR and MD Studies Reveal That the Isolated Dengue NS3 Protease Is an Intrinsically Disordered Chymotrypsin Fold Which Absolutely Requests NS2B for Correct Folding and Functional Dynamics

    PubMed Central

    Gupta, Garvita; Lim, Liangzhong; Song, Jianxing

    2015-01-01

    Dengue genome encodes a two component protease complex (NS2B-NS3pro) essential for the viral maturation/infectivity, thus representing a key drug target. Previously, due to its “complete insolubility”, the isolated NS3pro could not be experimentally studied and it remains elusive what structure it adopts without NS2B and why NS2B is indispensable. Here as facilitated by our previous discovery, the isolated NS3pro has been surprisingly deciphered by NMR to be the first intrinsically-disordered chymotrypsin-like fold, which exists in a loosely-packed state with non-native long-range interactions as revealed by paramagnetic relaxation enhancement (PRE). The disordered NS3pro appears to be needed for binding a human host factor to trigger the membrane remodeling. Moreover, we have in vitro refolded the NS3pro in complex with either NS2B (48–100) or the full-length NS2B (1–130) anchored into the LMPC micelle, and the two complexes have similar activities but different dynamics. We also performed molecular dynamics (MD) simulations and the results revealed that NS2B shows the highest structural fluctuations in the complex, thus providing the dynamic basis for the observation on its conformational exchange between open and closed states. Remarkably, the NS2B cofactor plays a central role in maintaining the correlated motion network required for the catalysis as we previously decoded for the SARS 3CL protease. Indeed, a truncated NS2B (48–100;Δ77–84) with the flexible loop deleted is able to trap the NS2B-NS3pro complex in a highly dynamic and catalytically-impotent state. Taken together, our study implies potential strategies to perturb the NS2B-NS3pro interface for design of inhibitors for treating dengue infection. PMID:26258523

  10. Lysosomal exocytosis in response to subtle membrane damage following nanosecond pulse exposure

    NASA Astrophysics Data System (ADS)

    Dalzell, Danielle R.; Roth, Caleb C.; Bernhard, Joshua A.; Payne, Jason A.; Wilmink, Gerald J.; Ibey, Bennett L.

    2011-03-01

    The cellular response to subtle membrane damage following exposure to nanosecond electric pulses (nsEP) is not well understood. Recent work has shown that when cells are exposed to nsEP, ion permeable nanopores (< 2nm) are created in the plasma membrane in contrast to larger diameter pores (> 2nm) created by longer micro and millisecond duration pulses. Macroscopic damage to a plasma membrane by a micropipette has been shown to cause internal vesicles (lysosomes) to undergo exocytosis to repair membrane damage, a calcium mediated process called lysosomal exocytosis. Formation of large pores in the plasma membrane by electrical pulses has been shown to elicit lysosomal exocytosis in a variety of cell types. Our research objective is to determine whether lysosomal exocytosis will occur in response to nanopores formed by exposure to nsEP. In this paper we used propidium iodide (PI) and Calcium Green-1 AM ester (CaGr) to differentiate between large and small pores formed in CHO-K1 cells following exposure to either 1 or 20, 600-ns duration electrical pulses at 16.2 kV/cm. This information was compared to changes in membrane organization observed by increases in FM1-43 fluorescence, both in the presence and absence of calcium ions in the outside buffer. In addition, we monitored the real time migration of lysosomes within the cell using Cellular Lights assay to tag LAMP-1, a lysosomal membrane protein. Both 1 and 20 pulses elicited a large influx of extracellular calcium, while little PI uptake was observed following a single pulse exposure. Statistically significant increases in FM1-43 fluorescence were seen in samples containing calcium suggesting that calcium-triggered membrane repair may be occurring. Lastly, density of lysosomes within cells, specifically around the nucleus, appeared to change rapidly upon nsEP stimulation suggesting lysosomal migration.

  11. X-ray framing camera for pulsed, high current, electron beam x-ray sources

    NASA Astrophysics Data System (ADS)

    Failor, B. H.; Rodriguez, J. C.; Riordan, J. C.; Lojewski, D. Y.

    2007-07-01

    High power x-ray sources built for nuclear weapons effects testing are evolving toward larger overall diameters and smaller anode cathode gaps. We describe a framing camera developed to measure the time-evolution of these 20-50 ns pulsed x-ray sources produced by currents in the 1.5-2.5 MA range and endpoint voltages between 0.2 and 1.5 MV. The camera has up to 4 frames with 5 ns gate widths; the frames are separated by 5 ns. The image data are recorded electronically with a gated intensified CCD camera and the data are available immediately following a shot. A fast plastic scintillator (2.1 ns decay time) converts the x-rays to visible light and, for high sensitivity, a fiber optic imaging bundle carries the light to the CCD input. Examples of image data are shown.

  12. Absolute wavelength calibration of pulsed lasers by use of machine vision.

    PubMed

    Nayuki, T; Fujii, T; Nemoto, K

    2001-04-01

    We developed a new absolute wavelength calibration system that uses machine vision for measurement of low-repetition-rate, short-pulse-duration (10-Hz, 5-ns) tunable lasers. Weak fluorescence from an iodine cell was measured by use of machine vision as a spatially gated integrator, and a pulsed dye-laser wavelength was calibrated with an accuracy of +/-0.005 nm , which is precise enough for differential absorption lidar application. PMID:18040341

  13. Characterization of partial discharge pulses in artificial voids in polypropylene films used in capacitors

    SciTech Connect

    Ramachandra, B.; Nema, R.S.

    1996-12-31

    Partial discharges in voids may cause deterioration of solid insulating materials. They often start in voids enclosed in insulation and or at the interface defects. A method of measuring fast discharge pulses with rise times below 1 ns is reported. Characterization of partial discharge pulses in artificial voids in polypropylene films at atmospheric pressure is analyzed that incorporates inception voltage, apparent and real charge, drift velocity and mobility of electrons.

  14. Single-mode operation of a long-pulse flashlamp pumped dye laser

    SciTech Connect

    Mandl, A.; Klimek, D.E.; Chou, H.P.; Litzenberger, L.; Wang, Y.

    1995-02-01

    The authors describe the achievement of single-mode operation of a flashlamp pumped long-pulse, {approximately} 700 ns dye laser, with output energy of about 350 mJ using a linear optical cavity with a ``twisted mode`` configuration. Measurements indicate that the laser frequency chirps by about 40 MHz over the entire pulse. Homodyne measurements indicate that the instantaneous bandwidth is close to the transform limit. This represents a significant advance in dye laser performance.

  15. 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. PMID:24880374

  16. 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.

  17. 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.

  18. 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

  19. Characterization of nanosecond pulse electrical field shock waves using imaging techniques

    NASA Astrophysics Data System (ADS)

    Mimun, L. Chris; Ibey, Bennett L.; Roth, Caleb C.; Barnes, Ronald A.; Sardar, Dhiraj K.; Beier, Hope T.

    2015-03-01

    Nanosecond pulsed electric fields (nsPEF) cause the formation of small pores, termed nanopores, in the membrane of cells. Current nanoporation models treat nsPEF exposure as a purely electromagnetic phenomenon, but recent publications showing pressure transients, ROS production, temperature gradients, and pH waves suggest the stimulus may be physically and chemically multifactorial causing elicitation of diverse biological conditions and stressors. Our research group's goal is to quantify the breadth and participation of these stressors generated during nsPEF exposure and determine their relative importance to the observed cellular response. In this paper, we used advanced imaging techniques to identify a possible source of nsPEF-induced acoustic shock waves. nsPEFs were delivered in an aqueous media via a pair of 125 μm tungsten electrodes separated by 100 μm, mirroring our previously published cellular exposure experiments. To visualize any pressure transients emanating from the electrodes or surrounding medium, we used the Schlieren imaging technique. Resulting images and measurements confirmed that mechanical pressure waves and electrode-based stresses are formed during nsPEF, resulting in a clearer understanding of the whole exposure dosimetry. This information will be used to better quantify the impact of nsPEF-induced acoustic shock waves on cells, and has provided further evidence of non-electrical-field induced exposures for elicitation of bioieffects.

  20. 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.

  1. 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.

  2. 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).

  3. Current pulse shaping of the load current on PTS

    NASA Astrophysics Data System (ADS)

    Xia, Minghe; Li, Fengping; Ji, Ce; Wei, Bing; Feng, Shuping; Wang, Meng; Xie, Weiping

    2016-02-01

    The typical rise time of PTS machine is ˜110 ns with about 10 MA peak current under short pulse mode when all 24 modules discharge simultaneously. By distributing the trigger times of 12 laser beams logically and adjusting the statues of the pulse output switches, longer rise-time pulse can be obtained on the PTS facility. Based on the required pulse shape, whole circuit simulations will be used to calculate the trigger times of each laser triggering gas switch and the status of the pulse output switches. The rise time of the current is determined by the time difference between the first and last trigged laser triggering gas switches. In order to trigger the laser triggering gas switch, sufficient laser power is needed to be sent into the gap of the gas switches. The gas pressure and voltage difference on the two electrodes of the gas switches also affect the triggering of the gas switches, and the voltage added on the gas switch is determined by its transition time. Traditionally the trigger time difference should be less than the transition time of the two neighboring modules. A new simulation model of PTS shows one can break this transition time limits. Series of current pulse shaping experiments have been investigated on the PTS (Primary Test Stand). As results, more than 5 MA peak current were successfully achieved on the load with a rise time of 600 ns. This study and experiments of the pulse shaping on PTS demonstrate the adaptable ability of the PTS for offering different waveform of mega ampere current pulse for different research purpose.

  4. Characterization and mechanism of glass microwelding by double-pulse ultrafast laser irradiation.

    PubMed

    Wu, Sizhu; Wu, Dong; Xu, Jian; Hanada, Yasutaka; Suganuma, Ryo; Wang, Haiyu; Makimura, Testuya; Sugioka, Koji; Midorikawa, Katsumi

    2012-12-17

    We investigated the physical mechanism of high-efficiency glass microwelding by double-pulse ultrafast laser irradiation by measuring the dependences of the size of the heat-affected zone and the bonding strength on the delay time between the two pulses for delay time up to 80 ns. The size of the heat-affected zone increases rapidly when the delay time is increased from 0 to 12.5 ps. It then decreases dramatically when the delay time is further increased to 30 ps. It has a small peak around 100 ps. For delay time up to 40 ns, the size of the heat-affected zone exceeds that for a delay time of 0 ps, whereas for delay time over 60 ps, it becomes smaller than that for a delay time of 0 ps. The bonding strength exhibits the same tendency. The underlying physical mechanism is discussed in terms of initial electron excitation by the first pulse and subsequent excitation by the second pulse: specifically, the first pulse induces multiphoton ionization or tunneling ionization, while the second pulse induces electron heating or avalanche ionization or the second pulse is absorbed by the localized state. Transient absorption of glass induced by the ultrafast laser pulse was analyzed by an ultrafast pump-probe technique. We found that the optimum pulse energy ratio is unity. These results provide new insights into high-efficiency ultrafast laser microwelding of glass and suggest new possibilities for further development of other ultrafast laser processing techniques. PMID:23263129

  5. System parameters germane to relativistic klystron amplifiers: how the utility of pulse energy depends on pulse duration, the target, and the atmosphere

    NASA Astrophysics Data System (ADS)

    Myers, John M.

    1994-05-01

    Relativistic klystron amplifiers (RKAs) at a variety of carrier wavelengths and pulse durations appear feasible to supply microwave pulses to an array of antennas acting as a beam weapon against targets at or above 100 km in altitude. In order to avoid voltage breakdown in the atmosphere, the array area must be large enough to converge the beam, producing a higher energy flux on target than at intermediate altitudes susceptible to breakdown. The area required depends on the physics of atmospheric ionization and on the pulse duration and the carrier wavelength of the RKA. A quantitative statement of the dependence of array area on relevant parameters is presented. The energy per RKA pulse that is usable without delay lines is determined here as a function of RKA pulse duration and wavelength. Changing the pulse length from 160 ns to 1 microsecond(s) and shortening the wavelength raise the energy usable without delay lines by a factor of 1000.

  6. The NS3 proteinase domain of hepatitis C virus is a zinc-containing enzyme.

    PubMed Central

    Stempniak, M; Hostomska, Z; Nodes, B R; Hostomsky, Z

    1997-01-01

    NS3 proteinase of hepatitis C virus (HCV), contained within the N-terminal domain of the NS3 protein, is a chymotrypsin-like serine proteinase responsible for processing of the nonstructural region of the HCV polyprotein. In this study, we examined the sensitivity of the NS3 proteinase to divalent metal ions, which is unusual behavior for this proteinase class. By using a cell-free coupled transcription-translation system, we found that HCV polyprotein processing can be activated by Zn2+ (and, to a lesser degree, by Cd2+, Pb2+, and Co2+) and inhibited by Cu2+ and Hg2+ ions. Elemental analysis of the purified NS3 proteinase domain revealed the presence of zinc in an equimolar ratio. The zinc content was unchanged in a mutated NS3 proteinase in which active-site residues His-57 and Ser-139 were replaced with Ala, suggesting that the zinc atom is not directly involved in catalysis but rather may have a structural role. Based on data from site-directed mutagenesis combined with zinc content determination, we propose that Cys-97, Cys-99, Cys-145, and His-149 coordinate the structural zinc in the HCV NS3 proteinase. A similar metal binding motif is found in 2A proteinases of enteroviruses and rhinoviruses, suggesting that these 2A proteinases and HCV NS3 proteinase are structurally related. PMID:9060645

  7. The Dengue Virus NS5 Protein Intrudes in the Cellular Spliceosome and Modulates Splicing.

    PubMed

    De Maio, Federico A; Risso, Guillermo; Iglesias, Nestor G; Shah, Priya; Pozzi, Berta; Gebhard, Leopoldo G; Mammi, Pablo; Mancini, Estefania; Yanovsky, Marcelo J; Andino, Raul; Krogan, Nevan; Srebrow, Anabella; Gamarnik, Andrea V

    2016-08-01

    Dengue virus NS5 protein plays multiple functions in the cytoplasm of infected cells, enabling viral RNA replication and counteracting host antiviral responses. Here, we demonstrate a novel function of NS5 in the nucleus where it interferes with cellular splicing. Using global proteomic analysis of infected cells together with functional studies, we found that NS5 binds spliceosome complexes and modulates endogenous splicing as well as minigene-derived alternative splicing patterns. In particular, we show that NS5 alone, or in the context of viral infection, interacts with core components of the U5 snRNP particle, CD2BP2 and DDX23, alters the inclusion/exclusion ratio of alternative splicing events, and changes mRNA isoform abundance of known antiviral factors. Interestingly, a genome wide transcriptome analysis, using recently developed bioinformatics tools, revealed an increase of intron retention upon dengue virus infection, and viral replication was improved by silencing specific U5 components. Different mechanistic studies indicate that binding of NS5 to the spliceosome reduces the efficiency of pre-mRNA processing, independently of NS5 enzymatic activities. We propose that NS5 binding to U5 snRNP proteins hijacks the splicing machinery resulting in a less restrictive environment for viral replication. PMID:27575636

  8. The Dengue Virus NS5 Protein Intrudes in the Cellular Spliceosome and Modulates Splicing

    PubMed Central

    Shah, Priya; Pozzi, Berta; Gebhard, Leopoldo G.; Mammi, Pablo; Yanovsky, Marcelo J.; Andino, Raul; Krogan, Nevan; Srebrow, Anabella; Gamarnik, Andrea V.

    2016-01-01

    Dengue virus NS5 protein plays multiple functions in the cytoplasm of infected cells, enabling viral RNA replication and counteracting host antiviral responses. Here, we demonstrate a novel function of NS5 in the nucleus where it interferes with cellular splicing. Using global proteomic analysis of infected cells together with functional studies, we found that NS5 binds spliceosome complexes and modulates endogenous splicing as well as minigene-derived alternative splicing patterns. In particular, we show that NS5 alone, or in the context of viral infection, interacts with core components of the U5 snRNP particle, CD2BP2 and DDX23, alters the inclusion/exclusion ratio of alternative splicing events, and changes mRNA isoform abundance of known antiviral factors. Interestingly, a genome wide transcriptome analysis, using recently developed bioinformatics tools, revealed an increase of intron retention upon dengue virus infection, and viral replication was improved by silencing specific U5 components. Different mechanistic studies indicate that binding of NS5 to the spliceosome reduces the efficiency of pre-mRNA processing, independently of NS5 enzymatic activities. We propose that NS5 binding to U5 snRNP proteins hijacks the splicing machinery resulting in a less restrictive environment for viral replication. PMID:27575636

  9. Identification of Hydroxyanthraquinones as Novel Inhibitors of Hepatitis C Virus NS3 Helicase

    PubMed Central

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

    2015-01-01

    Hepatitis C virus (HCV) is an important etiological agent of severe liver diseases, including cirrhosis and hepatocellular carcinoma. The HCV genome encodes nonstructural protein 3 (NS3) helicase, which is a potential anti-HCV drug target because its enzymatic activity is essential for viral replication. Some anthracyclines are known to be NS3 helicase inhibitors and have a hydroxyanthraquinone moiety in their structures; mitoxantrone, a hydroxyanthraquinone analogue, is also known to inhibit NS3 helicase. Therefore, we hypothesized that the hydroxyanthraquinone moiety alone could also inhibit NS3 helicase. Here, we performed a structure–activity relationship study on a series of hydroxyanthraquinones by using a fluorescence-based helicase assay. Hydroxyanthraquinones inhibited NS3 helicase with IC50 values in the micromolar range. The inhibitory activity varied depending on the number and position of the phenolic hydroxyl groups, and among different hydroxyanthraquinones examined, 1,4,5,8-tetrahydroxyanthraquinone strongly inhibited NS3 helicase with an IC50 value of 6 µM. Furthermore, hypericin and sennidin A, which both have two hydroxyanthraquinone-like moieties, were found to exert even stronger inhibition with IC50 values of 3 and 0.8 µM, respectively. These results indicate that the hydroxyanthraquinone moiety can inhibit NS3 helicase and suggest that several key chemical structures are important for the inhibition. PMID:26262613

  10. Antagonism of the complement component C4 by flavivirus nonstructural protein NS1

    PubMed Central

    Avirutnan, Panisadee; Fuchs, Anja; Hauhart, Richard E.; Somnuke, Pawit; Youn, Soonjeon

    2010-01-01

    The complement system plays an essential protective role in the initial defense against many microorganisms. Flavivirus NS1 is a secreted nonstructural glycoprotein that accumulates in blood, is displayed on the surface of infected cells, and has been hypothesized to have immune evasion functions. Herein, we demonstrate that dengue virus (DENV), West Nile virus (WNV), and yellow fever virus (YFV) NS1 attenuate classical and lectin pathway activation by directly interacting with C4. Binding of NS1 to C4 reduced C4b deposition and C3 convertase (C4b2a) activity. Although NS1 bound C4b, it lacked intrinsic cofactor activity to degrade C4b, and did not block C3 convertase formation or accelerate decay of the C3 and C5 convertases. Instead, NS1 enhanced C4 cleavage by recruiting and activating the complement-specific protease C1s. By binding C1s and C4 in a complex, NS1 promotes efficient degradation of C4 to C4b. Through this mechanism, NS1 protects DENV from complement-dependent neutralization in solution. These studies define a novel immune evasion mechanism for restricting complement control of microbial infection. PMID:20308361

  11. Structure of the catalytic domain of the hepatitis C virus NS2-3 protease

    SciTech Connect

    Lorenz,I.; Marcotrigiano, J.; Dentzer, T.; Rice, C.

    2006-01-01

    Hepatitis C virus is a major global health problem affecting an estimated 170 million people worldwide. Chronic infection is common and can lead to cirrhosis and liver cancer. There is no vaccine available and current therapies have met with limited success. The viral RNA genome encodes a polyprotein that includes two proteases essential for virus replication. The NS2-3 protease mediates a single cleavage at the NS2/NS3 junction, whereas the NS3-4A protease cleaves at four downstream sites in the polyprotein. NS3-4A is characterized as a serine protease with a chymotrypsin-like fold, but the enzymatic mechanism of the NS2-3 protease remains unresolved. Here we report the crystal structure of the catalytic domain of the NS2-3 protease at 2.3 Angstroms resolution. The structure reveals 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 carboxy-terminal residues remain coordinated in the two active sites, predicting an inactive post-cleavage form. Proteolysis through formation of a composite active site occurs in the context of the viral polyprotein expressed in mammalian cells. These features offer unexpected insights into polyprotein processing by hepatitis C virus and new opportunities for antiviral drug design.

  12. Influenza virus NS1 protein inhibits pre-mRNA splicing and blocks mRNA nucleocytoplasmic transport.

    PubMed Central

    Fortes, P; Beloso, A; Ortín, J

    1994-01-01

    The influenza virus RNA segment 8 encodes two proteins, NS1 and NS2, by differential splicing. The collinear transcript acts as mRNA for NS1 protein, while the spliced mRNA encodes NS2 protein. The splicing of NS1 mRNA was studied in cells transfected with a recombinant plasmid that has the cDNA of RNA segment 8 cloned under the SV40 late promoter and polyadenylation signals. As described for influenza virus-infected cells, NS1 mRNA was poorly spliced to yield NS2 mRNA. However, inactivation of the NS1 gene, but not the NS2 gene, led to a substantial increase in the splicing efficiency, as shown by the relative accumulations of NS1 and NS2 mRNAs. This effect was not specific for NS1 mRNA, since the splicing of the endogenous SV40 early transcript was altered in such a way that t-Ag mRNA was almost eliminated. These changes in the splicing pattern coincided with a strong inhibition of the mRNA nucleocytoplasmic transport. Both NS1 and NS2 mRNAs were retained in the nucleus of cells expressing NS1 protein, but no effect was observed when only NS2 protein was expressed. Furthermore, other mRNAs tested, such as T-Ag mRNA and the non-spliceable nucleoprotein transcript, were also retained in the nucleus upon expression of NS1 protein, suggesting that it induced a generalized block of mRNA export from the nucleus. Images PMID:8313914

  13. High-level expression of recombinant dengue viral NS-1 protein and its potential use as a diagnostic antigen.

    PubMed

    Huang, J L; Huang, J H; Shyu, R H; Teng, C W; Lin, Y L; Kuo, M D; Yao, C W; Shaio, M F

    2001-11-01

    The prevalence of NS1 Ab response in patients with dengue viral infection and the potential of using recombinant NS1 protein as a diagnostic antigen for dengue viral infection were investigated. In this study, the full-length and C-terminal half of NS1 proteins (rNS1, rNS1-C) were highly expressed (10-30 mg/l) and further purified and refolded. The good antigenicity of the full-length rNS1 protein was confirmed by interaction with 19 dengue NS1-specific monoclonal antibodies (MAbs) in ELISA; however, the antigenicity of rNS1-C was relatively lower. The full-length rNS1 antigen also differentiated reliably between sera from dengue virus-infected patients and sera from normal controls. When rNS1 was used as an antigen to detect human anti-NS1 IgM and IgG Ab, the anti-NS1 Ab response was found in 15 of 17 patients (88%) with primary dengue infection and all 16 patients (100%) with secondary dengue infection. These results indicated that using the full-length rNS1 whose antigenicity is restored as ELISA antigen, a high anti-NS1 antibody prevalence could be detected in patients with either primary or secondary dengue infection. This finding suggested that the anti-NS1 antibody appeared not only in secondary and severe dengue virus infection and might not correlate the pathogenesis of dengue hemorrhagic fever. The study also verified that our purified rNS1 protein showed similar immunological properties as native dengue viral proteins. Genetic engineering production of recombinant NS1 antigen could provide a safe and valuable resource for dengue virus serodiagnosis. PMID:11596093

  14. The N-Terminal of Aquareovirus NS80 Is Required for Interacting with Viral Proteins and Viral Replication

    PubMed Central

    Zhang, Jie; Guo, Hong; Chen, Qingxiu; Zhang, Fuxian; Fang, Qin

    2016-01-01

    Reovirus replication and assembly occurs within viral inclusion bodies that formed in specific intracellular compartments of cytoplasm in infected cells. Previous study indicated that aquareovirus NS80 is able to form inclusion bodies, and also can retain viral proteins within its inclusions. To better understand how NS80 performed in viral replication and assembly, the functional regions of NS80 associated with other viral proteins in aquareovirus replication were investigated in this study. Deletion mutational analysis and rotavirus NSP5-based protein association platform were used to detect association regions. Immunofluorescence images indicated that different N-terminal regions of NS80 could associate with viral proteins VP1, VP4, VP6 and NS38. Further co-immunoprecipitation analysis confirmed the interaction between VP1, VP4, VP6 or NS38 with different regions covering the N-terminal amino acid (aa, 1–471) of NS80, respectively. Moreover, removal of NS80 N-terminal sequences required for interaction with proteins VP1, VP4, VP6 or NS38 not only prevented the capacity of NS80 to support viral replication in NS80 shRNA-based replication complementation assays, but also inhibited the expression of aquareovirus proteins, suggesting that N-terminal regions of NS80 are necessary for viral replication. These results provided a foundational basis for further understanding the role of NS80 in viral replication and assembly during aquareovirus infection. PMID:26871941

  15. Comprehensive Mapping Antigenic Epitopes of NS1 Protein of Japanese Encephalitis Virus with Monoclonal Antibodies.

    PubMed

    Hua, Rong-Hong; Liu, Li-Ke; Chen, Zhen-Shi; Li, Ye-Nan; Bu, Zhi-Gao

    2013-01-01

    Japanese encephalitis virus (JEV) non-structural protein 1 (NS1) contributes to virus replication and elicits protective immune responses during infection. JEV NS1-specific antibody responses could be a target in the differential diagnosis of different flavivirus infections. However, the epitopes on JEV NS1 are poorly characterized. The present study describes the full mapping of linear B-cell epitopes in JEV NS1. We generated eleven NS1-specific monoclonal antibodies from mice immunized with recombinant NS1. For epitope mapping of monoclonal antibodies, a set of 51 partially-overlapping peptides covering the entire NS1 protein were expressed with a GST-tag and then screened using monoclonal antibodies. Through enzyme-linked immunosorbent assay (ELISA), five linear epitope-containing peptides were identified. By sequentially removing amino acid residues from the carboxy and amino terminal of peptides, the minimal units of the five linear epitopes were identified and confirmed using monoclonal antibodies. Five linear epitopes are located in amino acids residues (5)AIDITRK(11), (72)RDELNVL(78), (251)KSKHNRREGY(260), (269)DENGIVLD(276), and (341)DETTLVRS(348). Furthermore, it was found that the epitopes are highly conserved among JEV strains through sequence alignment. Notably, none of the homologous regions on NS1 proteins from other flaviviruses reacted with the MAbs when they were tested for cross-reactivity, and all five epitope peptides were not recognized by sera against West Nile virus or Dengue virus. These novel virus-specific linear B-cell epitopes of JEV NS1 would benefit the development of new vaccines and diagnostic assays. PMID:23825668

  16. Resensitizing daclatasvir-resistant hepatitis C variants by allosteric modulation of NS5A.

    PubMed

    Sun, Jin-Hua; O'Boyle, Donald R; Fridell, Robert A; Langley, David R; Wang, Chunfu; Roberts, Susan B; Nower, Peter; Johnson, Benjamin M; Moulin, Frederic; Nophsker, Michelle J; Wang, Ying-Kai; Liu, Mengping; Rigat, Karen; Tu, Yong; Hewawasam, Piyasena; Kadow, John; Meanwell, Nicholas A; Cockett, Mark; Lemm, Julie A; Kramer, Melissa; Belema, Makonen; Gao, Min

    2015-11-12

    It is estimated that more than 170 million people are infected with hepatitis C virus (HCV) worldwide. Clinical trials have demonstrated that, for the first time in human history, the potential exists to eradicate a chronic viral disease using combination therapies that contain only direct-acting antiviral agents. HCV non-structural protein 5A (NS5A) is a multifunctional protein required for several stages of the virus replication cycle. NS5A replication complex inhibitors, exemplified by daclatasvir (DCV; also known as BMS-790052 and Daklinza), belong to the most potent class of direct-acting anti-HCV agents described so far, with in vitro activity in the picomolar (pM) to low nanomolar (nM) range. The potency observed in vitro has translated into clinical efficacy, with HCV RNA declining by ~3-4 log10 in infected patients after administration of single oral doses of DCV. Understanding the exceptional potency of DCV was a key objective of this study. Here we show that although DCV and an NS5A inhibitor analogue (Syn-395) are inactive against certain NS5A resistance variants, combinations of the pair enhance DCV potency by >1,000-fold, restoring activity to the pM range. This synergistic effect was validated in vivo using an HCV-infected chimaeric mouse model. The cooperative interaction of a pair of compounds suggests that NS5A protein molecules communicate with each other: one inhibitor binds to resistant NS5A, causing a conformational change that is transmitted to adjacent NS5As, resensitizing resistant NS5A so that the second inhibitor can act to restore inhibition. This unprecedented synergistic anti-HCV activity also enhances the resistance barrier of DCV, providing additional options for HCV combination therapy and new insight into the role of NS5A in the HCV replication cycle. PMID:26536115

  17. Identification and characterization of two cleavage fragments from the Aquareovirus nonstructural protein NS80.

    PubMed

    Chen, Qingxiu; Zhang, Jie; Zhang, Fuxian; Guo, Hong; Fang, Qin

    2016-08-01

    Aquareovirus species vary with respect to pathogenicity, and the nonstructural protein NS80 of aquareoviruses has been implicated in the regulation of viral replication and assembly, which can form viral inclusion bodies (VIBs) and recruit viral proteins to its VIBs in infected cells. NS80 consists of 742 amino acids with a molecular weight of approximately 80 kDa. Interestingly, a short specific fragment of NS80 has also been detected in infected cells. In this study, an approximately 58-kDa product of NS80 was confirmed in various infected and transfected cells by immunoblotting analyses using α-NS80C. Mutational analysis and time course expression assays indicated that the accumulation of the 58-kDa fragment was related to time and infection dose, suggesting that the fragment is not a transient intermediate of protein degradation. Moreover, another smaller fragment with a molecular mass of approximately 22 kDa was observed in transfected and infected cells by immunoblotting with a specific anti-FLAG monoclonal antibody or α-NS80N, indicating that the 58- kDa polypeptide is derived from a specific cleavage site near the amino terminus of NS80. Additionally, different subcellular localization patterns were observed for the 22-kDa and 58-kDa fragments in an immunofluorescence analysis, implying that the two cleavage fragments of NS80 function differently in the viral life cycle. These results provide a basis for additional studies of the role of NS80 played in replication and particle assembly of the Aquareovirus. PMID:27279144

  18. Diffuse, non-polar electropermeabilization and reduced propidium uptake distinguish the effect of nanosecond electric pulses.

    PubMed

    Semenov, Iurii; Zemlin, Christian; Pakhomova, Olga N; Xiao, Shu; Pakhomov, Andrei G

    2015-10-01

    Ca2+ activation and membrane electroporation by 10-ns and 4-ms electric pulses (nsEP and msEP) were compared in rat embryonic cardiomyocytes. The lowest electric field which triggered Ca2+ transients was expectedly higher for nsEP (36 kV/cm) than for msEP (0.09 kV/cm) but the respective doses were similar (190 and 460 mJ/g). At higher intensities, both stimuli triggered prolonged firing in quiescent cells. An increase of basal Ca2+ level by >10 nM in cells with blocked voltage-gated Ca2+ channels and depleted Ca2+ depot occurred at 63 kV/cm (nsEP) or 0.14 kV/cm (msEP) and was regarded as electroporation threshold. These electric field values were at 150-230% of stimulation thresholds for both msEP and nsEP, notwithstanding a 400,000-fold difference in pulse duration. For comparable levels of electroporative Ca2+ uptake, msEP caused at least 10-fold greater uptake of propidium than nsEP, suggesting increased yield of larger pores. Electroporation by msEP started Ca2+ entry abruptly and locally at the electrode-facing poles of cell, followed by a slow diffusion to the center. In a stark contrast, nsEP evoked a "supra-electroporation" pattern of slower but spatially uniform Ca2+ entry. Thus nsEP and msEP had comparable dose efficiency, but differed profoundly in the size and localization of electropores. PMID:26112464

  19. 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.

  20. Design of a 5-MA 100-ns linear-transformer-driver accelerator for wire array Z-pinch experiments

    NASA Astrophysics Data System (ADS)

    Zhou, Lin; Li, Zhenghong; Wang, Zhen; Liang, Chuan; Li, Mingjia; Qi, Jianmin; Chu, Yanyun

    2016-03-01

    The linear-transformer-driver (LTD) is a recently developed pulsed-power technology that shows great promise for a number of applications. These include a Z -pinch-driven fission-fusion-hybrid reactor that is being developed by the Chinese Academy of Engineering Physics. In support of the reactor development effort, we are planning to build an LTD-based accelerator that is optimized for driving wire-array Z -pinch loads. The accelerator comprises six modules in parallel, each of which has eight series 0.8-MA LTD cavities in a voltage-adder configuration. Vacuum transmission lines are used from the interior of the adder to the central vacuum chamber where the load is placed. Thus the traditional stack-flashover problem is eliminated. The machine is 3.2 m tall and 12 m in outer diameter including supports. A prototype cavity was built and tested for more than 6000 shots intermittently at a repetition rate of 0.1 Hz. A novel trigger, in which only one input trigger pulse is needed by utilizing an internal trigger brick, was developed and successfully verified in these shots. A full circuit modeling was conducted for the accelerator. The simulation result shows that a current pulse rising to 5.2 MA in 91 ns (10%-90%) can be delivered to the wire-array load, which is 1.5 cm in height, 1.2 cm in initial radius, and 1 mg in mass. The maximum implosion velocity of the load is 32 cm /μ s when compressed to 0.1 of the initial radius. The maximum kinetic energy is 78 kJ, which is 11.7% of the electric energy stored in the capacitors. This accelerator is supposed to enable a radiation energy efficiency of 20%-30%, providing a high efficient facility for research on the fast Z pinch and technologies for repetition-rate-operated accelerators.