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Sample records for 2-10 ns pulse

  1. Process Performances of 2 ns Pulsed Discharge Plasma

    NASA Astrophysics Data System (ADS)

    Matsumoto, Takao; Wang, Douyan; Namihira, Takao; Akiyama, Hidenori

    2011-08-01

    Pulsed discharge plasmas have been used to treat exhaust gases. Since pulse duration and the rise time of applied voltage to the discharge electrode has a strong influence on the energy efficiency of pollutant removal, the development of a short-pulse generator is of paramount importance for practical applications. In this work, it is demonstrated that the non thermal plasma produced by the 2 ns pulsed discharge has a higher energy efficiency than the 5 ns pulsed discharge plasma for NO removal and ozone generation. Typically, the NO removal efficiency was 1.0 mol kW-1 h-1 for 70% NO removal (initial NO concentration = 200 ppm, gas flow = 10 L/min). Meanwhile, the ozone yield was 500 g kW-1 h-1 for 20 g/m3 ozone concentration in the case of oxygen feeding. These energy efficiencies are the highest in the literature.

  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

    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.

  4. Nanometer-Scale Permeabilization and Osmotic Swelling Induced by 5-ns Pulsed Electric Fields.

    PubMed

    Sözer, Esin B; Wu, Yu-Hsuan; Romeo, Stefania; Vernier, P Thomas

    2017-02-01

    High-intensity nanosecond pulsed electric fields (nsPEFs) permeabilize cell membranes. Although progress has been made toward an understanding of the mechanism of nsPEF-induced membrane poration, the dependence of pore size and distribution on pulse duration, strength, number, and repetition rate remains poorly defined experimentally. In this paper, we characterize the size of nsPEF-induced pores in living cell membranes by isosmotically replacing the solutes in pulsing media with polyethylene glycols and sugars before exposing Jurkat T lymphoblasts to 5 ns, 10 MV/m electric pulses. Pore size was evaluated by analyzing cell volume changes resulting from the permeation of osmolytes through the plasma membrane. We find that pores created by 5 ns pulses have a diameter between 0.7 and 0.9 nm at pulse counts up to 100 with a repetition rate of 1 kHz. For larger number of pulses, either the pore diameter or the number of pores created, or both, increase with increasing pulse counts. But the prevention of cell swelling by PEG 1000 even after 2000 pulses suggests that 5 ns, 10 MV/m pulses cannot produce pores with a diameter larger than 1.9 nm.

  5. 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.

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

    NASA Astrophysics Data System (ADS)

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

    2016-05-01

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

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

    PubMed Central

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

    2016-01-01

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

  8. Supression of laser breakdown by pulsed nonequilibrium ns discharge

    NASA Astrophysics Data System (ADS)

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

    2016-10-01

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

  9. Copper bromide vapour laser with an output pulse duration of up to 320 ns

    SciTech Connect

    Gubarev, F A; Fedorov, K V; Evtushenko, G S; Fedorov, V F; Shiyanov, D V

    2016-01-31

    We report the development of a copper bromide vapour laser with an output pulse duration of up to 320 ns. To lengthen the pulse, the discharge current was limited using a compound switch comprising a pulsed hydrogen thyratron and a tacitron. This technique permits limiting the excitation of the working levels at the initial stage of the discharge development to lengthen the inversion lifetime. The longest duration of a laser pulse was reached in tubes 25 and 50 mm in diameter for a pulse repetition rate of 2 – 4 kHz. (lasers and laser beams)

  10. A 0.2 ns beam pulse for the 6 MV Van de Graaff accelerator

    NASA Astrophysics Data System (ADS)

    McMurray, W. R.; Kritzinger, J. J.; Wikner, V. C.; Swart, T.; Schmitt, H.

    1984-01-01

    The 1.5 ns pulsed beam of the SUNI Van de Graaff accelerator has been used for neutron time-of-flight studies. To provide sufficient resolution for neutron scattering measurements at 22 MeV, a post-acceleration bunching system has been installed. Bunching of 2-6 MeV p, d and 3He beams is achieved in a simple quarter-wave coaxial resonator chamber designed for high Q and low power. The bunched pulse has a fwhm of less than 0.2 ns. The design and testing of the bunching system are outlined. Optimum power requirements are tabulated together with the induced beam energy spreads.

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

    NASA Astrophysics Data System (ADS)

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

    2005-03-01

    The development of a long-pulse electric-discharge XeCl laser with the 9 × 6 × 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.

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

    SciTech Connect

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

    2004-11-09

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

  13. Characterisation 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. 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. Thin film patterning techniques and deuteration parameters will be discussed.

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

    PubMed

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

    2013-09-01

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

  15. 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.

  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

    2015-10-09

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

  17. 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.

  18. 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

  19. 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.

  20. Determination of cellular injury and death thresholds following exposure to high voltage 10ns electrical pulses

    NASA Astrophysics Data System (ADS)

    Ibey, Bennett L.; Roth, Caleb C.; Bernhard, Joshua A.; Pakhomov, Andrei G.; Wilmink, Gerald J.; Pakhomova, Olga

    2011-03-01

    Intense, nanosecond-duration electric pulses (nsEP) have been introduced as a novel modality to alter cellular function, with a mechanism of action qualitatively different from micro- and millisecond duration pulses used in electroporation. In this study, we determined the thresholds for plasma membrane injury (within 15 minutes) and cell death (at 24 hours) for 4 different cell types (CHO-K1, HeLa, Jurkat and U937). Plasma membrane injury was measured by flow cytometry using two fluorescent dyes, namely Annexin V-FITC, which binds to phosphatidylserine (PS) upon its externalization (subtle membrane injury), and propidium iodide (PI), which is typically impermeable to the cell, but enters when large pores are formed in the plasma membrane. In all cell types, 10-ns pulses caused phosphatidylserine (PS) externalization at low doses (<150kV/cm and 100 pulses for each cell type) and no PI uptake. Jurkat and U937 cell lines showed substantial cell death without uptake of PI (15 minutes post exposure) suggesting either delayed permeabilization due to swelling, or damage to intracellular components. In CHO-K1 and HeLa cell lines, PI uptake occurred at low doses relative to that necessary to cause cell death suggesting a necrotic death similar to longer pulse exposures. These findings suggest that nanosecond pulses may be beneficial in applications that require selective elimination of specific cell types.

  1. Direct surface engineering of silicon nanoparticles prepared by collinear double-pulse ns laser ablation

    NASA Astrophysics Data System (ADS)

    Mahdieh, M. H.; Momeni, A.

    2017-01-01

    In this paper we study the photoluminescence properties of colloidal silicon nanoparticles (Si NPs) in distilled water, with the aim of clarifying the role of surface characteristics on the emission properties. We will show that double-pulse ns laser ablation (DPLA) of a silicon target in water with different inter-pulse delay times of i.e. 5 and 10 ns can result in production of colloidal Si NPs with different PL emission intensities at the visible spectral range of 550-650 nm. The results reveal that DPLA process at the different delay times can induce different oxide related surface characteristics on the Si NPs through the direct surface engineering of the nanoparticles. A detailed analysis of the PL emissions using the stochastic quantum confinement model explained that the different emission behaviors of the colloids are associated with the oxide-related surface states which are contributed as radiative centers in the PL process.

  2. 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.

  3. 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

  4. 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.

  5. 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.

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

    PubMed

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

    2005-05-01

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

  7. 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

  8. 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.

  9. Nanosecond Pulsed Electric Fields (nsPEFs) Regulate Phenotypes of Chondrocytes through Wnt/β-catenin Signaling Pathway

    PubMed Central

    Zhang, Kun; Guo, Jinsong; Ge, Zigang; Zhang, Jue

    2014-01-01

    Nanosecond pulsed electric fields (nsPEFs) characterized by high voltage, low energy and non-thermal effects, have been broadly investigated as a potential tumor therapy; however, little is known about their effects on somatic cells. In this current study, we evaluated effects of nsPEFs on the phenotype of chondrocytes (morphology, glycosaminoglycan (GAG) content, proliferation and gene expression) and explored the mechanisms involved. Our results demonstrated that exposing chondrocytes to nsPEFs led to enhanced proliferation and dedifferentiation, evidenced by the upregulated gene expression of collagen type I (COL I) and downregulated gene expression of Sox9, collagen type II (COL II) and aggrecan (AGG) with activation of the wnt/β-catenin signaling pathway. Inhibition of the wnt/β-catenin pathway partially blocked these effects. Thus we concluded that nsPEFs induce dedifferentiation of chondrocytes partially through transient activation of the wnt/β-catenin signaling pathway. PMID:25060711

  10. 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

  11. 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.

  12. Differential Gene Expression in Explanted Human Retinal Pigment Epithelial Cells 24-Hours Post-Exposure to 532 nm, 3.0 ns Pulsed Laser Light and 1064 nm, 170 ps Pulsed Laser Light 12-Hours Post-Exposure: Results Compendium

    DTIC Science & Technology

    2004-06-01

    Laser Light and 1064 nm, 170 ps Pulsed Laser Light 12-hours Post-Exposure: Results Compendium John W. Obringer Martin D. Johnson Laser and Optics...Explanted Human Retinal Pigment Epithelial Cells 12-hours Post-Exposure to 532 nm, 3.0 ns Pulsed Laser Light and 1064 nm, 170 ps Pulsed Laser Lightl2-hours...Explanted Human Retinal Pigment Epithelial USAFA F05611-02-P-0471 Cells 24-Hours Post-Exposure to 532 nm, 3.0 ns Pulsed Laser-Light and 1064nm, 170 ps Pulsed

  13. 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.

  14. 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.

  15. 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.

  16. Micro structuring of transparent materials with NIR ns-laser pulses

    NASA Astrophysics Data System (ADS)

    Zehnder, S.; Schwaller, P.; von Arx, U.; Bucher, G.; Neuenschwander, B.

    A current challenge in laser processing is high precision micromachining of transparent materials, e.g. to manufacture microoptical elements. This can be achieved amongst others by using laser induced backside wet etching. Research has been done by several groups in the last years. Most of the published results were obtained by using UV excimer lasers. Our approach deals with the implementation of the technique for NIR laser sources. We investigated the effects of different pulse widths and repetition rates on laser induced back side wet etching for 1064 nm wavelength and for different absorbers.

  17. Atomization and merging of two Al and W wires driven by a 1 kA, 10 ns current pulse

    NASA Astrophysics Data System (ADS)

    Wu, Jian; Li, Xingwen; Lu, Yihan; Lebedev, S. V.; Yang, Zefeng; Jia, Shenli; Qiu, Aici

    2016-11-01

    Possibility of preconditioning of wires in wire array Z-pinch loads by an auxiliary low-level current pulse was investigated in experiments with two aluminum or two polyimide-coated tungsten wires. It was found that the application of a 1 kA, 10 ns current pulse could convert all the length of the Al wires (1 cm long, 15 μm diameter) and ˜70% of length of the W wires (1 cm long, 15 μm diameter, 2 μm polyimide coating) into a gaseous state via ohmic heating. The expansion and merging of the wires, positioned at separations of 1-3 mm, were investigated with two-wavelength (532 nm and 1064 nm) laser interferometry. The gasified wire expanded freely in a vacuum and its density distribution at different times could be well described using an analytic model for the expansion of the gas into vacuum. Under an energy deposition around its atomization enthalpy of the wire material, the aluminum vapor column had an expansion velocity of 5-7 km/s, larger than the value of ˜4 km/s from tungsten wires. The dynamic atomic polarizabilities of tungsten for 532 nm and 1064 nm were also estimated.

  18. Observation of amplification of a 1ps pulse by SRS of a 1 ns pulse in a plasma with conditions relevant to pulse compression

    SciTech Connect

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

    2006-05-24

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

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

    NASA Astrophysics Data System (ADS)

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

    2002-04-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2015-06-01

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

  1. Observation of amplification of a 1ps pulse by SRS of a 1 ns pulse in a plasma with conditions relevant to pulse compression

    SciTech Connect

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

    2005-10-28

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

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. A novel Model for the Mechanism of Laser-Induced Back Side Wet Etching in Aqueous Cu Solutions using ns Pulses at 1064 nm

    NASA Astrophysics Data System (ADS)

    Schwaller, P.; Zehnder, S.; von Arx, U.; Neuenschwander, B.

    Laser induced back side wet etching has shown to be a promising tool for the micro-structuring of transparent materials. Detailed studies have been performed using UV excimer laser sources, aromatic hydrocarbon and liquid metal absorbers. Only little work is reported however using aqueous Cu solutions as absorbers and ns laser pulses at 1064 nm wavelength. We present a novel model for this specific setup. Our experiments indicate that physisorbed Cu2+ ions at the polar glass surface absorb the laser light. This leads to local thermal stresses in the glass and subsequent micro-ablation.

  7. 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).

  8. Finite element method (FEM) model of the mechanical stress on phospholipid membranes from shock waves produced in nanosecond electric pulses (nsEP)

    NASA Astrophysics Data System (ADS)

    Barnes, Ronald; Roth, Caleb C.; Shadaram, Mehdi; Beier, Hope; Ibey, Bennett L.

    2015-03-01

    The underlying mechanism(s) responsible for nanoporation of phospholipid membranes by nanosecond pulsed electric fields (nsEP) remains unknown. The passage of a high electric field through a conductive medium creates two primary contributing factors that may induce poration: the electric field interaction at the membrane and the shockwave produced from electrostriction of a polar submersion medium exposed to an electric field. Previous work has focused on the electric field interaction at the cell membrane, through such models as the transport lattice method. Our objective is to model the shock wave cell membrane interaction induced from the density perturbation formed at the rising edge of a high voltage pulse in a polar liquid resulting in a shock wave propagating away from the electrode toward the cell membrane. Utilizing previous data from cell membrane mechanical parameters, and nsEP generated shockwave parameters, an acoustic shock wave model based on the Helmholtz equation for sound pressure was developed and coupled to a cell membrane model with finite-element modeling in COMSOL. The acoustic structure interaction model was developed to illustrate the harmonic membrane displacements and stresses resulting from shockwave and membrane interaction based on Hooke's law. Poration is predicted by utilizing membrane mechanical breakdown parameters including cortical stress limits and hydrostatic pressure gradients.

  9. 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.

  10. Soft X-Ray Emission of Laser-Produced Plasmas: Comparison for 30-ps and 20-ns Laser Pulses.

    PubMed

    van Brug, H; van Dorssen, G E; van der Wiel, M J

    1989-01-01

    Soft x-ray emission spectra (250-875 eV) are presented for plasmas, produced by picosecond and nanosecond frequency-doubled Nd:YAG-glass laser pulses incident on 14 different target materials. The emitted spectra have been corrected for various apparatus functions which enables a direct comparison between plasmas produced by pico- and nanosecond laser pulses. The relative integrated emission intensity as a function of Z number, obtained from the corrected spectra, shows an oscillatory behavior, with distinct maxima for those elements exhibiting a dominant line emission in our photon energy window. We found for our two pulse lengths an approximately equal conversion efficiency from laser light into x-ray photons. General suggestions are given as to what target material should be used for different applications using the laser plasma as x-ray source in the energy range Studied.

  11. Characterization of chemical contaminants and their spectral properties from an atmospheric pressure ns-pulsed microdischarge in neon

    NASA Astrophysics Data System (ADS)

    Sillerud, Colin H.; Schwindt, Peter D. D.; Moorman, Mathew; Yee, B. T.; Anderson, John; Pfeifer, Nathaniel B.; Hedberg, E. L.; Manginell, Ronald P.

    2017-03-01

    Portable applications of microdischarges, such as the remediation of gaseous wastes or the destruction of volatile organic compounds, will mandate operation in the presence of contaminant species. This paper examines the temporal evolution of microdischarge optical and ultraviolet emissions during pulsed operation by experimental methods. By varying the pulse length of a microdischarge initiated in a 4-hole silicon microcavity array operating in a 655 Torr ambient primarily composed of Ne, we were able to measure the emission growth rates for different contaminant species native to the discharge environment as a function of pulse length. It was found that emission from hydrogen and oxygen impurities demonstrated similar rates of change, while emissions from molecular and atomic nitrogen, measured at 337.1 and 120 nm, respectively, exhibited the lowest rate of change. We conclude that it is likely that O2 undergoes the same resonant energy transfer process between rare gas excimers that has been shown for H2. Further, efficient resonant processes were found to be favored during ignition and extinction phases of the pulse, while emission at the 337.1 nm line from N2 was favored during the intermediate stage of the plasma. In addition to the experimental results, a zero-dimensional analysis is also presented to further understand the nature of the microdischarge.

  12. 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

    2012-10-08

    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.

  13. 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.

  14. 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)

  15. 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

    NASA Astrophysics Data System (ADS)

    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/LiB3O5 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 M2 parameter of the green beam was measured to be ˜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.

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

    SciTech Connect

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

    2005-06-12

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

  17. 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

    2014-10-06

    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.

  18. 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.

  19. QCL seeded, ns-pulse, multi-line, CO2 laser oscillator for laser-produced-plasma extreme-UV source

    NASA Astrophysics Data System (ADS)

    Nowak, Krzysztof Michał; Suganuma, Takashi; Kurosawa, Yoshiaki; Ohta, Takeshi; Kawasuji, Yasufumi; Nakarai, Hiroaki; Saitou, Takashi; Fujimoto, Junichi; Mizoguchi, Hakaru; Sumitani, Akira; Endo, Akira

    2017-01-01

    Successful merger of state-of-the-art, semiconductor quantum-cascade lasers (QCL), with the mature CO2 laser technology, resulted in a delivery of highly-desired qualities of CO2 laser output that were not available previously without much effort. These qualities, such as multi-line operation, excellent spectro-temporal stability and pulse waveform control, became available from a single device of moderate complexity. This paper describes the operation principle and the unique properties of the solid{state seeded CO2 laser, invented for an application in laser-produced-plasma (LPP), extreme-UV (EUV) light source.

  20. 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.

  1. 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.

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

    NASA Astrophysics Data System (ADS)

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

    2016-05-01

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

  3. Effects of a conventional photocoagulator and a 3-ns pulse laser on preconditioning responses and retinal ganglion cell survival after optic nerve crush.

    PubMed

    Shibeeb, O'Sam; Wood, John P M; Casson, Robert J; Chidlow, Glyn

    2014-10-01

    Previous research has demonstrated that laser photocoagulation treatment of the monkey retina affords protection against experimental glaucoma-induced retinal ganglion cell (RGC) loss in areas overlying laser spots. The underlying mechanism is unknown, but it is conceivable that the laser acted as a preconditioning stimulus, inducing localised, endogenous production of survival factors. The related purposes of the current study were firstly to examine whether preconditioning pathways are activated by either a conventional photocoagulator (CW) laser or a photoreceptor-sparing, short-pulse duration (2RT) laser in the rat retina, and secondly, to examine whether such preconditioning with either laser improves RGC survival after optic nerve (ON) crush. Pigmented rats were randomly assigned to one of three groups: sham, CW, 2RT. For the preconditioning study, laser spots were applied randomly to each retina in the posterior hemisphere of the eye taking care to avoid major blood vessels. Animals were killed at 6 h, 1d, and 7d after laser treatment, then analysed by qPCR, immunohistochemistry or Western immunoblotting. For the neuroprotection study, laser spots were administered to the mid-central retina of the right eye. The left eye served as a control. In two experiments, rats were lasered either 24 h or 7 days before ON crush, then killed a further 7 days later. Wholemount retinas were prepared and double labelling immunofluorescence performed. Nestin labelling allowed visualization of laser spots. Brn3a labelling identified viable RGCs. Photomicrographs of Brn3a labelling were taken in areas overlying nestin-positive laser spots. Quantification of Brn3a RGCs was then performed. Both the CW and 2RT lasers induced local glial cell activation. Moreover, both lasers induced localized upregulations of a number of well-documented (CNTF, FGF-2 Hsp27, pAKT) or putative (cFOS, ATF-3, IL-6) RGC survival factors. However, neither laser caused sustained increases in other

  4. Pulse

    MedlinePlus

    ... the underside of the opposite wrist, below the base of the thumb. Press with flat fingers until ... determine if the patient's heart is pumping. Pulse measurement has other uses as well. During or immediately ...

  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

    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.

  6. Generation in electric-discharge XeCl lasers of a high energy long pulses

    NASA Astrophysics Data System (ADS)

    Konovalov, Ivan; Losev, Valery F.; Panchenko, Yury N.

    2004-06-01

    Experimental results of long-pulse generation in X-ray preionized XeCl lasers with a 9 x 7 cm2 and 5.4 x 3 cm2 apertures are described. Lasers operate at Ne-Xe-HCl mixture with pressure up to 4 atm. Paper-oil pulse forming lines and rail-gap switch for discharge pump was used. An 2 - 10 J output with optical pulse duration of 250 - 300 ns (FWHM) have been extracted. Problems and peculiarities of long laser pulse formation are discussed.

  7. 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

  8. 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.

  9. Turbulent Mixing Layer Control using Ns-DBD Plasma Actuators

    NASA Astrophysics Data System (ADS)

    Singh, Ashish; Little, Jesse

    2016-11-01

    A low speed turbulent mixing layer (Reθo =1282, U1 /U2 = 0 . 28 and U2 = 11 . 8 m / s) is subject to nanosecond pulse driven dielectric barrier discharge (ns-DBD) plasma actuation. The forcing frequency corresponds to a Strouhal number (St) of 0.032 which is the most amplified frequency based on stability theory. Flow response is studied as a function of the pulse energy, the energy input time scale (carrier frequency) and the duration of actuation (duty cycle). It is found that successful actuation requires a combination of forcing parameters. An evaluation of the forcing efficacy is achieved by examining different flow quantities such as momentum thickness, vorticity and velocity fluctuations. In accordance with past work, a dependence is found between the initial shear layer thickness and the energy coupled to the flow. More complex relationships are also revealed such as a limitation on the maximum pulse energy which yields control. Also, the pulse energy and the carrier frequency (inverse of period between successive pulses) are interdependent whereby an optimum exists between them and extreme values of either parameter is inconsonant with the control desired. These observations establish a rich and complex process behind ns-DBD plasma actuation. Air Force Office of Scientific Research (FA9550-12-1-0044).

  10. 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.

  11. Solid-state pulse forming module with adjustable pulse duration

    NASA Astrophysics Data System (ADS)

    Wang, Langning; Liu, Jinliang; Qiu, Yongfeng; Chu, Xu; Zhang, Qingmeng

    2017-03-01

    A new solid-state pulse forming module is described in this paper. The pulse forming module is fabricated on a glass ceramic substrate, with the dimension of 250 mm × 95 mm × 4 mm. By changing the copper strips used in the pulse forming modules, the pulse duration of the obtained pulsed can range from 80 ns to 140 ns. Both the simulation and tests show that the pulse forming module has a good pulse forming ability. Under a high voltage in microsecond's time, the new pulse forming modules can hold off a voltage up to 25 kV higher than that of the previous study. In addition, future optimization for the field enhancement near the thin electrode edge has been proposed and simulated.

  12. 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.

  13. Cell electrofusion using nanosecond electric pulses

    NASA Astrophysics Data System (ADS)

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

    2013-11-01

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

  14. Pulsed Electric Fields for Biological Weapons Defense

    DTIC Science & Technology

    2002-01-01

    studies of Bacillus atrophaeus (formerly Bacillus subtilis var. niger). 15. SUBJECT TERMS nanosecond high-field electric pulse, electroperturbation...sterility monitoring kit, which utilizes spores of Bacillus atrophaeus (formerly Bacillus subtilis var. niger) deposited on paper in glassine envelopes, has...report a study of the application of ultra- short high-field electric pulses (5 MV/m, 100-ns pulse width, 4-ns rise time) to Bacillus atrophaeus spores

  15. Electron Emission from Conductors Subjected to Intense, Short-Pulse Electric Fields

    DTIC Science & Technology

    1987-06-01

    showed that for 10-ns pulse lengths, anodized alumi- num surfaces could hold off more than twice the electric field strength of bare aluminum...shorter, 3-ns pulse lengths, anodizing was less effective at improving suppression of electron emission, while surface finish became the important...pulsewidth of 10 ns. The front end of the pulser, along with a typical output pulse , is shown in Fig. 1. The vacuum coaxial line is about 6-ns long, and

  16. Mapping the Interactions between the NS4B and NS3 Proteins of Dengue Virus

    PubMed Central

    Zou, Jing; Lee, Le Tian; Wang, Qing Yin; Xie, Xuping; Lu, Siyan; Yau, Yin Hoe; Yuan, Zhiming; Geifman Shochat, Susana; Kang, Congbao

    2015-01-01

    ABSTRACT Flavivirus RNA synthesis is mediated by a multiprotein complex associated with the endoplasmic reticulum membrane, named the replication complex (RC). Within the flavivirus RC, NS4B, an integral membrane protein with a role in virulence and regulation of the innate immune response, binds to the NS3 protease-helicase. NS4B modulates the RNA helicase activity of NS3, but the molecular details of their interaction remain elusive. Here, we used dengue virus (DENV) to map the determinants for the NS3-NS4B interaction. Coimmunoprecipitation and an in situ proximity ligation assay confirmed that NS3 colocalizes with NS4B in both DENV-infected cells and cells coexpressing both proteins. Surface plasmon resonance demonstrated that subdomains 2 and 3 of the NS3 helicase region and the cytoplasmic loop of NS4B are required for binding. Using nuclear magnetic resonance (NMR), we found that the isolated cytoplasmic loop of NS4B is flexible, with a tendency to form a three-turn α-helix and two short β-strands. Upon binding to the NS3 helicase, 12 amino acids within the cytoplasmic loop of NS4B exhibited line broadening, suggesting a participation in the interaction. Sequence alignment showed that 4 of these 12 residues are strictly conserved across different flaviviruses. Mutagenesis analysis showed that three (Q134, G140, and N144) of the four evolutionarily conserved NS4B residues are essential for DENV replication. The mapping of the NS3/NS4B-interacting regions described here can assist the design of inhibitors that disrupt their interface for antiviral therapy. IMPORTANCE NS3 and NS4B are essential components of the flavivirus RC. Using DENV as a model, we mapped the interaction between the viral NS3 and NS4B proteins. The subdomains 2 and 3 of NS3 helicase as well as the cytoplasmic loop of NS4B are critical for the interaction. Functional analysis delineated residues within the NS4B cytoplasmic loop that are crucial for DENV replication. Our findings reveal

  17. Revisiting the interplay between ablation, collisional, and radiative processes during ns-laser ablation

    NASA Astrophysics Data System (ADS)

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

    2013-10-01

    A study of ns-laser ablation is presented, which focuses on the transient behavior of the physical processes that act in and above a copper sample. A dimensionless multiphase collisional radiative model describes the interplay between the ablation, collisional, and radiative mechanisms. Calculations are done for a 6 ns-Nd:YAG laser pulse operating at 532 nm and fluences up to 15 J/cm2. Temporal intensity profiles as well as transmissivities are in good agreement with experimental results. It is found that volumetric ablation mechanisms and photo-processes both play an essential role in the onset of ns-laser induced breakdown.

  18. Design and Experiment of an Ultra-wideband Dual-Pulse Radiating Antenna

    NASA Astrophysics Data System (ADS)

    Sitao, Z.; Guozhi, L.; Chaolong, Y.; Xiaoxin, S.; Yajun, F.; Lei, S.; Wenfeng, X.; Yufeng, Z.

    A method to widen the microwave spectrum by radiating two pulses of different FWHM is presented. Based on this method, a high-power ultra-wideband dual-pulse radiating antenna is developed. The antenna is made up of a half-impulse radiating antenna (IRA) over a ground plane. The diameter of the reflector is 3 m with focal length 1.2 m and the ground plane is a rectangle of metal with length of 4 m and width of 3 m. Three TEM horns are adopted to feed two pulses into the reflector. The antenna can radiate two different bipolar pulses with peak-to-peak width of 1.7 ns and 3 ns effectively. The 3 ns bipolar pulse is after 1.7 ns bipolar pulse with a delay of 12.5 ns. Simulation analysis and experiments on the antenna are performed. Good agreements between calculated and measured results are obtained. The radiated spectrum of the 1.7 ns pulse covers from 240 MHz to 400 MHz, while the radiated spectrum of the 3 ns pulse covers from 110 MHz to 210 MHz. The radiated spectrum of the combined 1.7 ns and 3 ns dual-pulse with a 12.5 ns delay covers from 100 MHz to 430 MHz. Results show that radiating the combined pulses is a more effective method to widen the microwave spectrum than radiating a single pulse.

  19. 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.

  20. 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.

  1. NS/EP Implications of Electronic Commerce

    DTIC Science & Technology

    1999-06-01

    THE PRESIDENT’S NATIONAL SECURITY TELECOMMUNICATIONS ADVISORY COMMITTEE NS/EP IMPLICATIONS OF ELECTRONIC COMMERCE JUNE 1999 Form SF298 Citation Data... Electronic Commerce Procedures Contract or Grant Number Program Element Number Authors Project Number Task Number Work Unit Number Performing Organization...99 3. REPORT TYPE AND DATES COVERED Report 4. TITLE AND SUBTITLE NS/EP Implications of Electronic Commerce 5. FUNDING NUMBERS 6. AUTHOR(S) President’s

  2. 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.

  3. 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

  4. Solution conformations of a linked construct of the Zika virus NS2B-NS3 protease.

    PubMed

    Mahawaththa, Mithun C; Pearce, Benjamin J G; Szabo, Monika; Graham, Bim; Klein, Christian D; Nitsche, Christoph; Otting, Gottfried

    2017-03-21

    The Zika virus presents a serious risk for global health. Crystal structures of different constructs of the Zika virus NS2B-NS3 protease (NS2B-NS3pro) have been determined with the aim to provide a basis for rational drug discovery. In these structures, the C-terminal β-hairpin of NS2B, NS2Bc, was observed to be either disordered (open conformation) or bound to NS3pro complementing the substrate binding site (closed conformation). Enzymatically active constructs of flaviviral NS2B-NS3 proteases commonly used for inhibitor testing contain a covalent peptide linker between NS2B and NS3pro. Using a linked construct of Zika virus NS2B-NS3pro, we studied the location of NS2Bc relative to NS3pro in solution by pseudocontact shifts generated by a paramagnetic lanthanide tag attached to NS3pro. Both closed and open conformations were observed with different inhibitors. As the NS2B co-factor is involved in substrate binding of flaviviral NS2B-NS3 proteases, the destabilization of the closed conformation in the linked construct makes it an attractive tool to search for inhibitors that interfere with the formation of the enzymatically active, closed conformation.

  5. Magnetic Piston Propagation in a 100-ns Plasma Opening Switch

    NASA Astrophysics Data System (ADS)

    Weingarten, A.; Grabowski, C.; Chakrabarti, N.; Maron, Y.; Fruchtman, A.

    1998-11-01

    The propagation of a magnetic piston through the plasma of a 90-ns, 170-kA POS is observed by studying the electron density, magnetic field, and ion velocity evolution. For the prefilled plasma n_e=(2.2± 0.5)× 10^14 cm-3, and T_e=5.5± 1 eV. The plasma composition is studied from absolute line intensities and collisional-radiative calculations. Most of the plasma ions are protons (90% near the cathode) with the rest being mainly CIV. The Hall-MHD conditions are not fulfilled for our experiment and ion motion is significant. The 3D-resolved ne evolution during the current pulse is studied from the line intensities of ions doped in the plasma using laser evaporation, and the magnetic field from Zeeman splitting. A diagonal magnetic piston propagates from the generator towards the load at about half the proton Alfven velocity. The protons are specularly reflected by the piston, while the heavy ions cross the potential hill in the piston, acquiring a lower velocity. The proton reflection causes an increase of ne ahead of the piston, followed by a sharp (10-20 ns) and substantial drop in ne (to 10-50% from the initial value). The magnetic field distribution studied using chordal observation, and theoretical analysis of ne and the magnetic field evolution are presented.

  6. The C-terminal 50 Amino Acid Residues of Dengue NS3 Protein Are Important for NS3-NS5 Interaction and Viral Replication*

    PubMed Central

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

    2015-01-01

    Dengue virus multifunctional proteins NS3 protease/helicase and NS5 methyltransferase/RNA-dependent RNA polymerase form part of the viral replication complex and are involved in viral RNA genome synthesis, methylation of the 5′-cap of viral genome, and polyprotein processing among other activities. Previous studies have shown that NS5 residue Lys-330 is required for interaction between NS3 and NS5. Here, we show by competitive NS3-NS5 interaction ELISA that the NS3 peptide spanning residues 566–585 disrupts NS3-NS5 interaction but not the null-peptide bearing the N570A mutation. Small angle x-ray scattering study on NS3(172–618) helicase and covalently linked NS3(172–618)-NS5(320–341) reveals a rigid and compact formation of the latter, indicating that peptide NS5(320–341) engages in specific and discrete interaction with NS3. Significantly, NS3:Asn-570 to alanine mutation introduced into an infectious DENV2 cDNA clone did not yield detectable virus by plaque assay even though intracellular double-stranded RNA was detected by immunofluorescence. Detection of increased negative-strand RNA synthesis by real time RT-PCR for the NS3:N570A mutant suggests that NS3-NS5 interaction plays an important role in the balanced synthesis of positive- and negative-strand RNA for robust viral replication. Dengue virus infection has become a global concern, and the lack of safe vaccines or antiviral treatments urgently needs to be addressed. NS3 and NS5 are highly conserved among the four serotypes, and the protein sequence around the pinpointed amino acids from the NS3 and NS5 regions are also conserved. The identification of the functionally essential interaction between the two proteins by biochemical and reverse genetics methods paves the way for rational drug design efforts to inhibit viral RNA synthesis. PMID:25488659

  7. 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.

  8. 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.

  9. 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...

  10. Analysis of folded pulse forming line operation.

    PubMed

    Domonkos, M T; Watrous, J; Parker, J V; Cavazos, T; Slenes, K; Heidger, S; Brown, D; Wilson, D

    2014-09-01

    A compact pulse forming line (CPFL) concept based on a folded transmission line and high-breakdown strength dielectric was explored through an effort combining proof-of-principle experiments with electromagnetic modeling. A small-scale folded CPFL was fabricated using surface-mount ceramic multilayer capacitors. The line consisted of 150 capacitors close-packed in parallel and delivered a 300 ns flat-top pulse. The concept was carried to a 10 kV class device using a polymer-ceramic nanocomposite dielectric with a permittivity of 37.6. The line was designed for a 161 ns FWHM length pulse into a matched load. The line delivered a 110 ns FWHM pulse, and the pulse peak amplitude exceeded the matched load ideal. Transient electromagnetic analysis using the particle-in-cell code ICEPIC was conducted to examine the nature of the unexpected pulse shortening and distortion. Two-dimensional analysis failed to capture the anomalous behavior. Three-dimensional analysis replicated the pulse shape and revealed that the bends were largely responsible for the pulse shortening. The bends not only create the expected reflection of the incident TEM wave but also produce a non-zero component of the Poynting vector perpendicular to the propagation direction of the dominant electromagnetic wave, resulting in power flow largely external to the PFL. This analysis explains both the pulse shortening and the amplitude of the pulse.

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

    PubMed

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

    2012-03-26

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

  12. 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.

  13. 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.

  14. 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.

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

    SciTech Connect

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

    2008-07-28

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

  16. Identification of the sequence on NS4A required for enhanced cleavage of the NS5A/5B site by hepatitis C virus NS3 protease.

    PubMed Central

    Shimizu, Y; Yamaji, K; Masuho, Y; Yokota, T; Inoue, H; Sudo, K; Satoh, S; Shimotohno, K

    1996-01-01

    In addition to NS3 protease, the NS4A protein is required for efficient cleavage of the nonstructural protein region of the hepatitis C virus polyprotein. To investigate the function and the sequence of NS4A required for the enhancement of NS3 protease activity, we developed an in vitro NS3 protease assay system consisting of three purified viral elements: (i) a recombinant NS3 protease which was expressed in Escherichia coli as a maltose-binding protein-NS3 fusion protein (MBP-NS3), (ii) synthetic NS4A fragments, and (iii) a synthetic peptide substrate which mimics the NS5A/5B junction. We showed that the NS3 protease activity of MBP-NS3 was enhanced in a dose-dependent manner by 4A18-40, which is a peptide composed of amino acid residues 18 to 40 of NS4A. The optimal activity was observed at a 10-fold molar excess of 4A18-40 over MBP-NS3. The coefficient for proteolytic efficiency, kcat/Km, of NS3 protease was increased by about 40 times by the addition of a 10-fold molar excess of 4A18-40. Using a series of truncations of 4A18-40, we estimated that amino acid residues 22 to 31 in NS4A (SVVIVGRIIL) constituted the core sequence for the effector activity. Single-substitution experiments with 4A21-34, a peptide composed of amino acid residues 21 to 34 of NS4A, suggested the importance of several residues (Val-23, Ile-25, Gly-27, Arg-28, Ile-29, and Leu-31) for its activity. In addition, we found that some single-amino-acid substitutions in 4A21-34 were able to inhibit the enhancement of NS3 protease activity by 4A18-40. This approach has potential as a novel strategy for inhibiting the NS3 protease activity important for hepatitis C virus proliferation. PMID:8523516

  17. 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

  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. Differential pulse-width pair BOTDA for high spatial resolution sensing.

    PubMed

    Li, Wenhai; Bao, Xiaoyi; Li, Yun; Chen, Liang

    2008-12-22

    A differential pulse-width pair Brillouin optical time domain analysis (DPP-BOTDA) for centimeter spatial resolution sensing using meter equivalent pulses is proposed. This scheme uses the time domain waveform subtraction at the same scanned Brillouin frequency obtained from pulse lights with different pulse-widths (e.g. 50ns and 49ns) to form the differential Brillouin gain spectrum (BGS) at each fiber location. The spatial resolution is defined by the average of the rise and fall time equivalent fiber length for a small stress section rather than the pulse-width difference equivalent length. The spatial resolution of 0.18m for the 50/49ns pulse pair and 0.15m for 20/19ns pulse pair over 1km sensing length with Brillouin frequency shift accuracy of 2.6MHz are demonstrated.

  20. Binary NS simulations using SpEC

    NASA Astrophysics Data System (ADS)

    Haas, Roland; Szilagyi, Bela; Kaplan, Jeffrey; Ott, Christian; Lippuner, Jonas; Scheel, Mark; Barkett, Kevin; Muhlberger, Curran; Foucart, Francois; Duez, Matthew

    2014-03-01

    NSNS binaries are expected to be one of the major sources of gravitational radiation detectable by Advanced LIGO. Together with neutrinos, gravitational waves are our only means to learn about the processes deep within a merging pair of NS, shedding light on the as yet poorly understood, equation of state governing matter at nuclear densities and beyond. We report on binary neutron star simulations using the Spectral Einstein Code (SpEC) developed by the Caltech-Cornell-CITA-WSU collaboration. We simulate the inspiral through many orbits, follow the post-merger evolution, and compute the full gravitational wave signal.

  1. A regenerative CO2 amplifier with controlled pulse duration

    NASA Astrophysics Data System (ADS)

    Apollonov, V. V.; Kazakov, K. Kh.; Sorochenko, V. R.; Shakir, Iu. A.

    1991-03-01

    The paper reports the development of a regenerative TEA CO2 amplifier with the pulse duration in a train controlled within the range from 10 to 40 ns, the interval between the pulses amounting to 110 ns and their total energy amounting to 4 J. Laser radiation screening by an optical-air-breakdown plasma in a lens telescope focus was used to form the injected pulse. Good reproduction of the temporal parameters of the injected pulse was achieved by virtue of the injection of radiation from a frequency stabilized CW CO2-laser into the master oscillator.

  2. 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.

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

    PubMed

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

    2010-03-01

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

  4. A fast leading-edge pulse generator

    NASA Astrophysics Data System (ADS)

    Wang, R.

    1986-01-01

    The pulse generator consists of ECL semiconductor integrated circuits, high speed transistors and step restorer diodes, among others; its circuitry is simple. The leading edge of the output pulse is less than 100 ps, and the output impedance is 50 ohms. An ECL four-wire receiver connected as a closed loop circut is used in the oscillator section of the set. The pulse frequency varies as low as 10 Hz and as high as 100 MHz. The control of pulse with is based on the subtraction of two pulse widths. The output pulse width may be less than 10 ns and the maximum width may be as wide as an oscillator half cycle. The pulse amplitude is continuously adjustable from + or - 35 mV to + or - 5 V. The operating principle of the oscillator stage, a simplified logic diagram, waveforms at various points, a rectifier circuit in the first stage, positive pulse channel circuit, and an adjustable power source are shown.

  5. Bulk and surface laser damage of silica by picosecond and nanosecond pulses at 1064 nm.

    PubMed

    Smith, Arlee V; Do, Binh T

    2008-09-10

    We measured bulk and surface dielectric breakdown thresholds of pure silica for 14 ps and 8 ns pulses of 1064 nm light. The thresholds are sharp and reproducible. For the 8 ns pulses the bulk threshold irradiance is 4.75 +/- 0.25 kW/microm2. The threshold is approximately three times higher for 14 ps pulses. For 8 ns pulses the input surface damage threshold can be made equal to the bulk threshold by applying an alumina or silica surface polish.

  6. Conformational flexibility of DENV NS2B/NS3pro: from the inhibitor effect to the serotype influence

    NASA Astrophysics Data System (ADS)

    Piccirillo, Erika; Merget, Benjamin; Sotriffer, Christoph A.; do Amaral, Antonia T.

    2016-03-01

    The dengue virus (DENV) has four well-known serotypes, namely DENV1 to DENV4, which together cause 50-100 million infections worldwide each year. DENV NS2B/NS3pro is a protease recognized as a valid target for DENV antiviral drug discovery. However, NS2B/NS3pro conformational flexibility, involving in particular the NS2B region, is not yet completely understood and, hence, a big challenge for any virtual screening (VS) campaign. Molecular dynamics (MD) simulations were performed in this study to explore the DENV3 NS2B/NS3pro binding-site flexibility and obtain guidelines for further VS studies. MD simulations were done with and without the Bz-nKRR-H inhibitor, showing that the NS2B region stays close to the NS3pro core even in the ligand-free structure. Binding-site conformational states obtained from the simulations were clustered and further analysed using GRID/PCA, identifying four conformations of potential importance for VS studies. A virtual screening applied to a set of 31 peptide-based DENV NS2B/NS3pro inhibitors, taken from literature, illustrated that selective alternative pharmacophore models can be constructed based on conformations derived from MD simulations. For the first time, the NS2B/NS3pro binding-site flexibility was evaluated for all DENV serotypes using homology models followed by MD simulations. Interestingly, the number of NS2B/NS3pro conformational states differed depending on the serotype. Binding-site differences could be identified that may be crucial to subsequent VS studies.

  7. 46 CFR 2.10-101 - Annual vessel inspection fee.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

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

  8. 46 CFR 2.10-101 - Annual vessel inspection fee.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

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

  9. 21 CFR 2.10 - Examination and investigation samples.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

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

  10. 21 CFR 2.10 - Examination and investigation samples.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

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

  11. 21 CFR 2.10 - Examination and investigation samples.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

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

  12. 21 CFR 2.10 - Examination and investigation samples.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 1 2010-04-01 2010-04-01 false Examination and investigation samples. 2.10 Section 2.10 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL... samples. (a)(1) When any officer or employee of the Department collects a sample of a food, drug,...

  13. 21 CFR 2.10 - Examination and investigation samples.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 1 2011-04-01 2011-04-01 false Examination and investigation samples. 2.10 Section 2.10 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL... samples. (a)(1) When any officer or employee of the Department collects a sample of a food, drug,...

  14. 28 CFR 2.10 - Date service of sentence commences.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

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

  15. 28 CFR 2.10 - Date service of sentence commences.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

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

  16. 28 CFR 2.10 - Date service of sentence commences.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

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

  17. 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 REPOSITORY Preclosure Guidelines Ease and Cost of Siting, Construction, Operation, and Closure §...

  18. 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 REPOSITORY Preclosure Guidelines Ease and Cost of Siting, Construction, Operation, and Closure §...

  19. 10 CFR 960.5-2-10 - Hydrology.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

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

  20. 10 CFR 960.5-2-10 - Hydrology.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 10 Energy 4 2011-01-01 2011-01-01 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 §...

  1. 28 CFR 2.10 - Date service of sentence commences.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

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

  2. Pulse widths dependence of programming and erasing behaviors for diamond like carbon based resistive switching memories

    NASA Astrophysics Data System (ADS)

    Xu, Jianlong; Xie, Dan; Zhang, Chenhui; Zhang, Xiaowen; Peng, Pinggang; Fu, Di; Qian, He; Ren, Tian-ling; Liu, Litian

    2014-10-01

    We report the influences of pulse widths on the programming and erasing characteristics of diamond-like carbon films based resistive random access memory. The device can be only programmed with pulses wider than 50 ns for SET operations when the pulse voltage is 1.2 V and erased with pulses narrower than 25 ns for RESET operations when the pulse voltage is 0.4 V. The formation, rupture, and re-growth of the conductive sp2-like graphitic filaments are proposed to be responsible for the resistive switching behaviors, based on which the pulse widths dependences on its programming and erasing properties can be further explained.

  3. 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

  4. Moveable wire electrode microchamber for nanosecond pulsed electric-field delivery.

    PubMed

    Wu, Yu-Hsuan; Arnaud-Cormos, Delia; Casciola, Maura; Sanders, Jason M; Leveque, Philippe; Vernier, P Thomas

    2013-02-01

    In this paper, an electromagnetic characterization of a moveable wire electrode microchamber for nanosecond pulse delivery is proposed. The characterization of the exposure system was carried out through experimental measurements and numerical simulations. The frequency and time domain analyses demonstrate the utility of the proposed assembly for delivering pulses as short as 2.5 ns. High-voltage measurements (~1.2 kV) were also performed using pulse generators based on two different technologies with applied pulse durations of 5.0 and 2.5 ns. Validation of the delivery system was accomplished with biological experiments involving cell electroporation with 2.5 and 5.0 ns, 10-MV/m pulsed electric fields. A dose-dependent area increase (osmotic swelling) of the Jurkat cells was observed with pulses as short as 2.5 ns.

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

    PubMed Central

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

    2013-01-01

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

  6. 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.

  7. Mitochondrial membrane permeabilization with nanosecond electric pulses.

    PubMed

    Vernier, P Thomas

    2011-01-01

    Ultra-short, high-field electric pulses permeabilize plasma and intracellular membranes. We report here nanosecond pulse-induced permeabilization of mitochondrial membranes in living cells. Using four independent methods based on fluorescent dyes--JC-1, rhodamine 123, tetramethyl rhodamine ethyl ester, and cobalt-quenched calcein--we show that as few as five, 4 ns, 10 MV/m pulses delivered at 1 kHz cause an increase of the inner mitochondrial membrane permeability and an associated loss of mitochondrial membrane potential. The most likely interpretation of these results is a pulse-induced permeabilization of the inner mitochondrial membrane.

  8. Binary NS simulations using SpEC

    NASA Astrophysics Data System (ADS)

    Haas, Roland; Kaplan, Jeffrey; Ott, Christian; Szilagyi, Bela; Scheel, Mark; Moesta, Philipp; Duez, Matthew; Foucart, Francois

    2012-03-01

    NSNS binaries are expected to be one of the major sources of gravitational radiation detectable by Advanced LIGO. Together with neutrinos, gravitational waves are our only means to learn about the processes deep within a merging pair of NS, shedding light on the as yet poorly understood, equation of state governing matter at nuclear densities and beyond. We report on binary neutron star simulations using the Spectral Einstein Code (SpEC) developed by the Caltech-Cornell-CITA-WSU collaboration. We simulate the inspiral through many orbits, follow the post-merger evolution, and compute the full gravitational wave signal. We provide estimates on the accuracy required for the LIGO scientific goals of constraining EOS parameters.

  9. Binary NS simulations using SpEC

    NASA Astrophysics Data System (ADS)

    Haas, Roland; Kaplan, Jeffrey; Szilagyi, Bela; Muhlberger, Curran; Foucart, Francois; Lippuner, Jonas; Scheel, Mark; Duez, Matthew; Ott, Christian

    2013-04-01

    NSNS binaries are expected to be one of the major sources of gravitational radiation detectable by Advanced LIGO. Together with neutrinos, gravitational waves are our only means to learn about the processes deep within a merging pair of NS, shedding light on the as yet poorly understood, equation of state governing matter at nuclear densities and beyond. We report on binary neutron star simulations using the Spectral Einstein Code (SpEC) developed by the Caltech-Cornell-CITA-WSU collaboration. We simulate the inspiral through many orbits, follow the post-merger evolution, and compute the full gravitational wave signal. We provide estimates on the accuracy required for the LIGO scientific goals of constraining EOS parameters.

  10. 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.

  11. A Genetic Interaction between Hepatitis C Virus NS4B and NS3 Is Important for RNA Replication▿

    PubMed Central

    Paredes, Anne M.; Blight, Keril J.

    2008-01-01

    Hepatitis C virus (HCV) nonstructural protein 4B (NS4B), a poorly characterized integral membrane protein, is thought to function as a scaffold for replication complex assembly; however, functional interactions with the other HCV nonstructural proteins within this complex have not been defined. We report that a Con1 chimeric subgenomic replicon containing the NS4B gene from the closely related H77 isolate is defective for RNA replication in a transient assay, suggesting that H77 NS4B is unable to productively interact with the Con1 replication machinery. The H77 NS4B sequences that proved detrimental for Con1 RNA replication resided in the predicted N- and C-terminal cytoplasmic domains as well as the central transmembrane region. Selection for Con1 derivatives that could utilize the entire H77 NS4B or hybrid Con1-H77 NS4B proteins yielded mutants containing single amino acid substitutions in NS3 and NS4A. The second-site mutations in NS3 partially restored the replication of Con1 chimeras containing the N-terminal or transmembrane domains of H77 NS4B. In contrast, the deleterious H77-specific sequences in the C terminus of NS4B, which mapped to a cluster of four amino acids, were completely suppressed by second-site substitutions in NS3. Collectively, these results provide the first evidence for a genetic interaction between NS4B and NS3 important for productive HCV RNA replication. PMID:18715921

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

    SciTech Connect

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

    2013-07-14

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

  13. Repetitively pulsed vacuum insulator flashover

    SciTech Connect

    Ginn, J.W.; Buttram, M.T.

    1987-01-01

    Experiments were performed to determine the flashover strength of various vacuum insulators under conditions of repetitive pulsing. The pulse duration was 30 ns, and the thickness of a typical insulator sample was 1.8 cm. Data were taken for 45 insulators from five different materials. An insulator was subjected to an extended series of pulses at a given repetition rate and field. If flashover was not detected, the field level was increased and the sequence repeated. At rates up to 50 pulses per second, there was no apparent dependence of flashover field on rate. In addition, some ''single shot'' data were taken, including various modifications of the geometries and surface textures of the insulators. Only two to the modifications increased the flashover strength significantly over that of a 45 sample: (1) annealing some plastics (roughly a 35% increase), and (2) extending the insulator to cover the surfaces of both electrodes (an increase of nearly a factor of two).

  14. Effect of Pulse Width on Ozone Yield using Inductive Energy Storage System Pulsed Power Generator

    NASA Astrophysics Data System (ADS)

    Yagi, Ippei; Mukaigawa, Seiji; Takaki, Koichi; Fujiwara, Tamiya; Go, Tomio

    Nanosecond pulse voltages of several pulse widths were applied to a cylindrical plasma reactor for ozone synthesis with high energy yield. Nanoseconds pulse voltages were produced by inductive energy storage system pulsed power generators using semiconductor opening switch (SOS) diodes. First recovery diodes were used as SOS diodes in the inductive energy storage system to produce short-pulsed high voltage with high-repetition rate. The short pulse voltage of 9.5 ns width and 33 kV peak voltage was produced at charging voltage of 15 kV and was applied to a 1 mm diameter center wire electrode in the plasma reactor. The copper cylinder of 19 mm inner diameter was used as outer electrode and was connected to a ground. The ozone yield of 271 g/kWh was obtained using the 9.5 ns width pulse voltage at synthesized 412 ppm of ozone concentration. The yield 271 g/kWh was more than twice as much as the yield 114 g/kWh at 401 ppm using a 60 ns pulse voltage.

  15. 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.

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

    SciTech Connect

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

    1997-06-01

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

  17. A Closer Look at the NS1 of Influenza Virus

    PubMed Central

    Dundon, William G.; Capua, Ilaria

    2009-01-01

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

  18. Simultaneous uncoupled expression and purification of the Dengue virus NS3 protease and NS2B co-factor domain.

    PubMed

    Shannon, A E; Chappell, K J; Stoermer, M J; Chow, S Y; Kok, W M; Fairlie, D P; Young, P R

    2016-03-01

    Dengue Virus (DENV) infection is responsible for the world's most significant insect-borne viral disease. Despite an increasing global impact, there are neither prophylactic nor therapeutic options available for the effective treatment of DENV infection. An attractive target for antiviral drugs is the virally encoded trypsin-like serine protease (NS3pro) and its associated cofactor (NS2B). The NS2B-NS3pro complex is responsible for cleaving the viral polyprotein into separate functional viral proteins, and is therefore essential for replication. Recombinant expression of an active NS2B-NS3 protease has primarily been based on constructs linking the C-terminus of the approximately 40 amino acid hydrophilic cofactor domain of NS2B to the N-terminus of NS3pro via a flexible glycine linker. The resulting complex can be expressed in high yield, is soluble and catalytically active and has been used for most in vitro screening, inhibitor, and X-ray crystallographic studies over the last 15 years. Despite extensive analysis, no inhibitor drug candidates have been identified yet. Moreover, the effect of the artificial linker introduced between the protease and its cofactor is unknown. Two alternate methods for bacterial expression of non-covalently linked, catalytically active, NS2B-NS3pro complex are described here along with a comparison of the kinetics of substrate proteolysis and binding affinities of substrate-based aldehyde inhibitors. Both expression methods produced high yields of soluble protein with improved substrate proteolysis kinetics and inhibitor binding compared to their glycine-linked equivalent. The non-covalent association between NS2B and NS3pro is predicted to be more relevant for examining inhibitors that target cofactor-protease interactions rather than the protease active site. Furthermore, these approaches offer alternative strategies for the high yield co-expression of other protein assemblies.

  19. Synergistic Activity of Combined NS5A Inhibitors

    PubMed Central

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

    2015-01-01

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

  20. The interaction between the hepatitis C proteins NS4B and NS5A is involved in viral replication.

    PubMed

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

    2015-01-15

    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.

  1. 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

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

    NASA Astrophysics Data System (ADS)

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

    2015-10-01

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

  3. 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.

  4. An improved rolled strip pulse forming line.

    PubMed

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

    2013-06-01

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

  5. An improved rolled strip pulse forming line

    NASA Astrophysics Data System (ADS)

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

    2013-06-01

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

  6. 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.

  7. 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.

  8. 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

  9. Pulse Oximetry

    MedlinePlus

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

  10. 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.

  11. Identification of novel small molecule inhibitors against NS2B/NS3 serine protease from Zika virus.

    PubMed

    Lee, Hyun; Ren, Jinhong; Nocadello, Salvatore; Rice, Amy J; Ojeda, Isabel; Light, Samuel; Minasov, George; Vargas, Jason; Nagarathnam, Dhanapalan; Anderson, Wayne F; Johnson, Michael E

    2017-03-01

    Zika flavivirus infection during pregnancy appears to produce higher risk of microcephaly, and also causes multiple neurological problems such as Guillain-Barré syndrome. The Zika virus is now widespread in Central and South America, and is anticipated to become an increasing risk in the southern United States. With continuing global travel and the spread of the mosquito vector, the exposure is expected to accelerate, but there are no currently approved treatments against the Zika virus. The Zika NS2B/NS3 protease is an attractive drug target due to its essential role in viral replication. Our studies have identified several compounds with inhibitory activity (IC50) and binding affinity (KD) of ∼5-10 μM against the Zika NS2B-NS3 protease from testing 71 HCV NS3/NS4A inhibitors that were initially discovered by high-throughput screening of 40,967 compounds. Competition surface plasmon resonance studies and mechanism of inhibition analyses by enzyme kinetics subsequently determined the best compound to be a competitive inhibitor with a Ki value of 9.5 μM. We also determined the X-ray structure of the Zika NS2B-NS3 protease in a "pre-open conformation", a conformation never observed before for any flavivirus proteases. This provides the foundation for new structure-based inhibitor design.

  12. Plasma Membrane Permeabilization by Trains of Ultrashort Electric Pulses

    DTIC Science & Technology

    2009-01-01

    ultrashort electrical pulses. Bioelectromagnetics , 2001. 22(6): p. 440-8. 4. Stacey, M., et al., Differential effects in cells exposed to ultra-short...nanosecond pulsed electric field Bioelectromagnetics , 2007. 28: p. 655-663. 13. Gowrishankar, T.R. and J.C. Weaver, Electrical behavior and pore...electric field (nsPEF). Bioelectromagnetics , 2007. 28: p. 655- 663. 19. Nuccitelli, R., et al., A new pulsed electric field therapy for melanoma disrupts

  13. 28 CFR 2.10 - Date service of sentence commences.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... Section 2.10 Judicial Administration DEPARTMENT OF JUSTICE PAROLE, RELEASE, SUPERVISION AND RECOMMITMENT... imposed. (b) The imposition of a sentence of imprisonment for civil contempt shall interrupt the running of any sentence of imprisonment being served at the time the sentence of civil contempt is...

  14. 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...

  15. 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...

  16. 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...

  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, 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...

  19. 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.

  20. Novel Dengue Virus NS2B/NS3 Protease Inhibitors

    PubMed Central

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

    2014-01-01

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

  1. 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.

  2. Vacuum transmission lines for pulse sharpening and diagnostics applications

    SciTech Connect

    Di Capua, M.S.; Goerz, D.A.; Freytag, E.K.

    1987-06-01

    We investigated the propagation of MV electrical pulses along coaxial transmission lines (TL) in vacuum with network simulations and experiments. One goal was to establish how well a 3 m-long TL would sharpen the output pulse of a relativistic electron beam accelerator. Sharpening occurs as the cathode of the TL emits electrons and the current flow forces the TL into magnetic cut-off. The other goal was to determine how well field emission must be suppressed in a TL to avoid distortion of a propagating pulse. Simulations predict a four-fold risetime improvement (8 ns to 2 ns) through magnetic insulation in a TL with an electrical length (10 ns) comparable to the risetime of the input pulse. In the laboratory we have shown a five-fold improvement (15 to 3 ns) with a velvet covered 3-m line and a 7.5 fold improvement (2 ns) when a vacuum flashover switch was incorporated between the first third and the last two thirds of the TL. Simple arguments and TL simulations suggest that even a small fraction (1 or 2%) of Child-Langmuir (CL) space charge limited emission will distort a propagating voltage pulse. This result is of particular importance when the TL is part of a voltage diagnostic system.

  3. 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)

  4. Flavivirus NS3 and NS5 proteins interaction network: a high-throughput yeast two-hybrid screen

    PubMed Central

    2011-01-01

    Background The genus Flavivirus encompasses more than 50 distinct species of arthropod-borne viruses, including several major human pathogens, such as West Nile virus, yellow fever virus, Japanese encephalitis virus and the four serotypes of dengue viruses (DENV type 1-4). Each year, flaviviruses cause more than 100 million infections worldwide, some of which lead to life-threatening conditions such as encephalitis or haemorrhagic fever. Among the viral proteins, NS3 and NS5 proteins constitute the major enzymatic components of the viral replication complex and are essential to the flavivirus life cycle. Results We report here the results of a high-throughput yeast two-hybrid screen to identify the interactions between human host proteins and the flavivirus NS3 and NS5 proteins. Using our screen results and literature curation, we performed a global analysis of the NS3 and NS5 cellular targets based on functional annotation with the Gene Ontology features. We finally created the first flavivirus NS3 and NS5 proteins interaction network and analysed the topological features of this network. Our proteome mapping screen identified 108 human proteins interacting with NS3 or NS5 proteins or both. The global analysis of the cellular targets revealed the enrichment of host proteins involved in RNA binding, transcription regulation, vesicular transport or innate immune response regulation. Conclusions We proposed that the selective disruption of these newly identified host/virus interactions could represent a novel and attractive therapeutic strategy in treating flavivirus infections. Our virus-host interaction map provides a basis to unravel fundamental processes about flavivirus subversion of the host replication machinery and/or immune defence strategy. PMID:22014111

  5. Active Control of Airfoil Boundary Layer Separation and Wake using Ns-DBD Plasma Actuators

    NASA Astrophysics Data System (ADS)

    Durasiewicz, Claudia; Castro Maldonado, Jorge; Little, Jesse

    2016-11-01

    Nanosecond pulse driven dielectric barrier discharge (ns-DBD) plasma actuators are employed to control boundary layer separation and the wake of a NACA 0012 airfoil having aspect ratio of three. Ns-DBD plasma actuators are known to operate via a thermal mechanism in contrast to ac-DBDs which are momentum-based devices. Nominally 2D forcing is applied to the airfoil leading edge with pulse energy of 0.35 mJ/cm. Experiments are conducted at a Reynolds number of 0 . 74 ×106 primarily at 18° incidence which is well within the stalled regime. Baseline and controlled flow fields are studied using surface pressure measurements, constant temperature anemometry (CTA) and PIV. Forcing at a dimensionless frequency of F+ = fc /U∞ = 1 . 14 results in reattachment of nominally separated flow to the airfoil surface. Lower frequency forcing is less optimal for separation control, but produces strong fluctuations in the wake which are intended for use in the study of vortex body interaction in the future. Actuation below F+ = 0 . 23 shows behavior consistent with an impulse-like response while forcing in the range 0 . 23

  6. LIBS using dual- and ultra-short laser pulses.

    PubMed

    Angel, S M; Stratis, D N; Eland, K L; Lai, T; Berg, M A; Gold, D M

    2001-02-01

    Pre-ablation dual-pulse LIBS enhancement data for copper, brass and steel using ns laser excitation are reported. Although large enhancements are observed for all samples, the magnitude of the enhancement is matrix dependent. Whereas all of the dual-pulse studies used ns laser excitation we see interesting effects when using ps and fs laser excitation for single-pulse LIBS. LIBS spectra of copper using 1.3 ps and 140 fs laser pulses show much lower background signals compared to ns pulse excitation. Also, the atomic emission decays much more rapidly with time. Because of relatively low backgrounds when using ps and fs pulses, non-gated detection of LIBS is shown to be very effective. The plasma dissipates quickly enough using ps and fs laser pulses, that high pulse rates, up to 1,000 Hz, are effective for increasing the LIBS signal, for a given measurement time. Finally, a simple near-collinear dual-pulse fiber-optic LIBS probe is shown to be useful for enhanced LIBS measurements.

  7. Experimental investigation on colloidal alumina nanoparticles produced by collinear nanosecond double-pulse laser ablation in liquid

    NASA Astrophysics Data System (ADS)

    Mahdieh, M. H.; Fattahi, B.; Akbari Jafarabadi, M.

    2017-01-01

    In this research, we investigated the effect of inter-pulse delay times on production of colloidal alumina nanoparticles by collinear double pulse laser ablation. In comparison to single pulse laser ablation, collinear double pulse laser ablation with inter-pulse delay times of 5, 10, 15 and 20 ns results in production of colloidal nanoparticles with smaller mean size and lower variance size distribution. In the case of 5 ns inter-pulse delay time, the highest concentration of nanoparticles was obtained due to more rapid cooling time of the plasma as a result of higher rate of nuclei generation than particle growth. The results also showed that the main pulse and the pre-pulse with 5 ns delay time have significant overlap and consequently such condition leads to maximum influence on the ablation.

  8. 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.

  9. 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.

  10. Pulse laser assist optical tweezers (PLAT) with long-duration pulse laser

    NASA Astrophysics Data System (ADS)

    Maeda, Saki; Sugiura, Tadao; Minato, Kotaro

    2011-07-01

    Optical tweezers is a technique to trap and to manipulate micron sized objects under a microscope by radiation pressure force exerted by a laser beam. Optical tweezers has been utilized for single-molecular measurements of force exerted by molecular interactions and for cell palpation. To extend applications of optical tweezers we have developed a novel optical tweezers system combined with a pulse laser. We utilize a pulse laser (Q-switched Nd: YAG laser, wavelength of 1064 nm) to assist manipulations by conventional optical tweezers with a continuous wave (CW) laser. The pulse laser beam is introduced into the same optics for conventional optical tweezers. In principle, instantaneous radiation force is proportional to instantaneous power of laser beam. As a result, pulse laser beam generates strong instantaneous force on an object to be manipulated. If the radiation force becomes strong enough to get over an obstacle structure and/or to be released from adhesion, the object will be free from these difficulties. We investigate the effect of pulse laser assistance with changing pulse duration of the laser. We report optimum pulse duration of 100 ns to 200 ns deduced from motion analysis of a particle in a beam spot. Our goal is to realize in-vivo manipulation and operation of a cell. For this purpose we need to reduce light energy of pulse laser beam and to avoid laser induced breakdown caused by strong light field. So we have developed a pulse laser with 160-ns pulse duration and have confirmed that availability on manipulation of living cells.

  11. Plastic Laminate Pulsed Power Development

    SciTech Connect

    ALEXANDER,JEFF A.; SHOPE,STEVEN L.; PATE,RONALD C.; RINEHART,LARRY F.; JOJOLA,JOHN M.; RUEBUSH,MITCHELL H.; CROWE,WAYNE; LUNDSTROM,J.; SMITH,T.; ZAGAR,D.; PRESTWICH,K.

    2000-09-01

    The desire to move high-energy Pulsed Power systems from the laboratory to practical field systems requires the development of compact lightweight drivers. This paper concerns an effort to develop such a system based on a plastic laminate strip Blumlein as the final pulseshaping stage for a 600 kV, 50ns, 5-ohm driver. A lifetime and breakdown study conducted with small-area samples identified Kapton sheet impregnated with Propylene Carbonate as the best material combination of those evaluated. The program has successfully demonstrated techniques for folding large area systems into compact geometry's and vacuum impregnating the laminate in the folded systems. The major operational challenges encountered revolve around edge grading and low inductance, low impedance switching. The design iterations and lessons learned are discussed. A multistage prototype testing program has demonstrated 600kV operation on a short 6ns line. Full-scale prototypes are currently undergoing development and testing.

  12. Subcellular Localization, Stability, and trans-Cleavage Competence of the Hepatitis C Virus NS3-NS4A Complex Expressed in Tetracycline-Regulated Cell Lines

    PubMed Central

    Wölk, Benno; Sansonno, Domenico; Kräusslich, Hans-Georg; Dammacco, Franco; Rice, Charles M.; Blum, Hubert E.; Moradpour, Darius

    2000-01-01

    A tetracycline-regulated gene expression system and a panel of novel monoclonal antibodies were used to examine the subcellular localization, stability, and trans-cleavage competence of the hepatitis C virus (HCV) NS3-NS4A complex in inducible cell lines. The NS3 serine protease domain and the full-length NS3 protein expressed in the absence of the NS4A cofactor were diffusely distributed in the cytoplasm and nucleus. Coexpression of NS4A, however, directed NS3 to the endoplasmic reticulum (ER) or an ER-like modified compartment, as demonstrated by colocalization with 3,3′-dihexyloxacarbocyanine iodide, protein disulfide isomerase, and calnexin, as well as subcellular fractionation analyses. In addition, coexpression with NS4A dramatically increased the intracellular stability of NS3 (mean protein half-life of 26 versus 3 h) and allowed for NS4A-dependent trans-cleavage at the NS4B-NS5A junction. Deletion analyses revealed that the hydrophobic amino-terminal domain of NS4A was required for ER targeting of NS3. These results demonstrate the importance of studying HCV proteins in their biological context and define a well-characterized cell culture system for further analyses of the NS3-NS4A complex and the evaluation of novel antiviral strategies against hepatitis C. PMID:10666260

  13. Tetrahydrobenzothiophene inhibitors of hepatitis C virus NS5B polymerase.

    PubMed

    Laporte, M G; Lessen, T A; Leister, L; Cebzanov, D; Amparo, E; Faust, C; Ortlip, D; Bailey, T R; Nitz, T J; Chunduru, S K; Young, D C; Burns, C J

    2006-01-01

    A novel series of selective HCV NS5B RNA dependent RNA polymerase inhibitors has been disclosed. These compounds contain an appropriately substituted tetrahydrobenzothiophene scaffold. This communication will detail the SAR and activities of this series.

  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. 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.

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

    PubMed

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

    2007-12-14

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

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

    SciTech Connect

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

    2007-12-14

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

  18. 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.

  19. Adherent neural stem (NS) cells from fetal and adult forebrain.

    PubMed

    Pollard, Steven M; Conti, Luciano; Sun, Yirui; Goffredo, Donato; Smith, Austin

    2006-07-01

    Stable in vitro propagation of central nervous system (CNS) stem cells would offer expanded opportunities to dissect basic molecular, cellular, and developmental processes and to model neurodegenerative disease. CNS stem cells could also provide a source of material for drug discovery assays and cell replacement therapies. We have recently reported the generation of adherent, symmetrically expandable, neural stem (NS) cell lines derived both from mouse and human embryonic stem cells and from fetal forebrain (Conti L, Pollard SM, Gorba T, Reitano E, Toselli M, Biella G, Sun Y, Sanzone S, Ying QL, Cattaneo E, Smith A. 2005. Niche-independent symmetrical self-renewal of a mammalian tissue stem cell. PLoS Biol 3(9):e283). These NS cells retain neuronal and glial differentiation potential after prolonged passaging and are transplantable. NS cells are likely to comprise the resident stem cell population within heterogeneous neurosphere cultures. Here we demonstrate that similar NS cell cultures can be established from the adult mouse brain. We also characterize the growth factor requirements for NS cell derivation and self-renewal. We discuss our current understanding of the relationship of NS cell lines to physiological progenitor cells of fetal and adult CNS.

  20. 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.

  1. Generation of high-power ultrashort optical pulses by semiconductor lasers

    NASA Astrophysics Data System (ADS)

    Dudelev, V. V.; Zazulin, S. V.; Kolykhalova, E. D.; Losev, S. N.; Deryagin, A. G.; Kuchinskii, V. I.; Efanov, M. V.; Sokolovskii, G. S.

    2016-12-01

    Fiber-coupled semiconductor lasers have been studied when pumped by high-power short electrical pulses of 5 ns width and leading front duration below 1 ns. In this pumping regime, it is possible to ensure significant sharpening of output pulses, the duration of which decreases below 80 ps for a single-mode laser and below 120 ps for a broad aperture multimode laser at an output peak optical power as high as 1.5 and 27 W, respectively.

  2. The New High Resolution Crystal Structure of NS2B-NS3 Protease of Zika Virus

    PubMed Central

    Badshah, Syed Lal; Naeem, Abdul; Mabkhot, Yahia

    2017-01-01

    Zika virus (ZIKV) is the cause of a significant viral disease affecting humans, which has spread throughout many South American countries and has also become a threat to Southeastern Asia. This commentary discusses the article “Crystal structure of unlinked NS2B-NS3 protease from Zika virus” published recently in the journal Science by Zhang et al. of Nanyang Technological University, Singapore. They resolved a 1.58 Å resolution structure of the NS2B-NS3 protease of ZIKV and demonstrated how peptide and non-peptide inhibitors interact with this structure, along with the different conformational states that were observed. This protease crystal structure offers new opportunities for the design and development of novel antiviral drugs used for the treatment and control of ZIKV. PMID:28075376

  3. Structure of the NS2B-NS3 protease from Zika virus after self-cleavage

    PubMed Central

    Phoo, Wint Wint; Li, Yan; Zhang, Zhenzhen; Lee, Michelle Yueqi; Loh, Ying Ru; Tan, Yaw Bia; Ng, Elizabeth Yihui; Lescar, Julien; Kang, CongBao; Luo, Dahai

    2016-01-01

    The recent outbreak of Zika virus (ZIKV) infections in the Americas represents a serious threat to the global public health. The viral protease that processes viral polyproteins during infection appears as an attractive drug target. Here we report a crystal structure at 1.84 Å resolution of ZIKV non-structural protein NS2B-NS3 protease with the last four amino acids of the NS2B cofactor bound at the NS3 active site. This structure represents a post-proteolysis state of the enzyme during viral polyprotein processing and provides insights into peptide substrate recognition by the protease. Nuclear magnetic resonance (NMR) studies and protease activity assays unravel the protein dynamics upon binding the protease inhibitor BPTI in solution and confirm this finding. The structural and functional insights of the ZIKV protease presented here should advance our current understanding of flavivirus replication and accelerate structure-based antiviral drug discovery against ZIKV. PMID:27845325

  4. 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.

  5. 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.

  6. 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.

  7. Point source of UV-radiation with a frequency of 1 khz and short pulse duration

    NASA Astrophysics Data System (ADS)

    Baksht, E. Kh.; Tarasenko, V. F.; Shut'ko, Yu. V.; Erofeev, M. V.

    2012-04-01

    Radiation of the discharge plasma from a nanosecond breakdown in a nonuniform electric field of short interelectrode gaps is investigated. Voltage pulses with incident wave amplitude of ~10 kV, pulse duration of ~1 ns (FWHM), and pulse front duration of ~0.2 ns are used. It is demonstrated that for pulsed-periodic breakdown of the gap 0.5 mm long in air at atmospheric pressure, the main contribution to plasma radiation give lines of the electrode material and the continuum, and the maximum radiation intensity is registered in the region of 200-300 nm, where ~40% of total radiation energy is concentrated.

  8. Q-switched Nd:glass-laser-induced acoustic pulses in lithotripsy

    NASA Astrophysics Data System (ADS)

    D'yakonov, G. I.; Mikhailov, B. A.; Pak, S. K.; Shcherbakov, Ivan A.; Andreev, Valeri G.; Rudenko, O. V.; Sapozhnikov, A. V.

    1991-07-01

    This paper describes preliminary experimental data of kidney stone fragmentation by the laser induced shock acoustic pulses. Acoustic pulses were produced in a thin layer of liquid as a result of absorption process of 1.06 micrometers radiation pulses. The phosphate Nd:glass laser operated in a pulse Q-switched regime with the pulse energy up to 10 J and pulse duration $OM 30 ns. The pressure induced by acoustic pulses on stones surface was reached up to 1-2 kbar in focal area, that was sufficient for stone destruction.

  9. 88 ns multi-millijoule LiNbO3 electro-optically Q-switched Tm:LuAG laser

    NASA Astrophysics Data System (ADS)

    Liu, C.; Yang, K.; Zhao, S.; Li, Y.; Li, G.; Li, D.; Li, T.; Qiao, W.; Feng, T.; Chen, X.

    2015-11-01

    An electro-optical modulator (EOM) made of a z-cut LiNbO3 (LN) crystal with size of 9×9×25 mm3 was designed to work in transverse-field regime. The extinction ratio of the EOM was measured to be 324:1. With the EOM operating in off Q-switching regime, a diode pumped all-solid-state actively Q-switched Tm:LuAG laser at 2 μm was realized. At repetition rate of 200 Hz, 2.5 mJ pulses with duration of 88.2 ns were generated. A maximum pulse energy of 2.51 mJ was achieved at repetition rate of 50 Hz, corresponding to a minimum pulse duration of 88 ns.

  10. 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.

  11. 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.

  12. 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.

  13. Effects of dispersion on electromagnetic parameters of tape-helix Blumlein pulse forming line of accelerator

    NASA Astrophysics Data System (ADS)

    Zhang, Y.; Liu, J. L.; Feng, J. H.

    2012-02-01

    In this paper, the tape-helix model is firstly introduced in the field of intense electron beam accelerator to analyze the dispersion effects on the electromagnetic parameters of helical Blumlein pulse forming line (PFL). Work band and dispersion relation of the PFL are analyzed, and the normalized coefficients of spatial harmonics are calculated. Dispersion effects on the important electromagnetic parameters of PFL, such as phase velocity, slow-wave coefficient, electric length and pulse duration, are analyzed as the central topic. In the PFL, electromagnetic waves with different frequencies in the work band of PFL have almost the same phase velocity. When de-ionized water, transformer oil and air are used as the PFL filling dielectric, respectively, the pulse duration of the helical Blumlein PFL is calculated as 479.6 ns, 81.1 ns and 53.1 ns in order. Electromagnetic wave simulation and experiments are carried out to demonstrate the theoretical calculations of the electric length and pulse duration which directly describe the phase velocity and dispersion of the PFL. Simulation results prove the theoretical analysis and calculation on pulse duration. Experiment is carried out based on the tape-helix Blumlein PFL and magnetic switch system. Experimental results show that the pulse durations are tested as 460 ns, 79 ns and 49 ns in order when de-ionized water, transformer oil and air are used respectively. Experimental results basically demonstrate the theoretical calculations and the analyses of dispersion.

  14. 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.

  15. Pulse oximetry

    PubMed Central

    Jubran, Amal

    1999-01-01

    Pulse oximetry is one of the most commonly employed monitoringmodalities in the critical care setting. This review describes the latesttechnological advances in the field of pulse oximetry. Accuracy of pulseoximeters and their limitations are critically examined. Finally, the existingdata regarding the clinical applications and cost-effectiveness of pulseoximeters are discussed. PMID:11094477

  16. 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.

  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. 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.

  19. Q-switched pulse laser generation from double-cladding Nd:YAG ceramics waveguides.

    PubMed

    Tan, Yang; Luan, Qingfang; Liu, Fengqin; Chen, Feng; Vázquez de Aldana, Javier Rodríguez

    2013-08-12

    This work reports on the Q-switched pulsed laser generation from double-cladding Nd:YAG ceramic waveguides. Double-cladding waveguides with different combination of diameters were inscribed into a sample of Nd:YAG ceramic. With an additional semiconductor saturable absorber, stable pulsed laser emission at the wavelength of 1064 nm was achieved with pulses of 21 ns temporal duration and ~14 μJ pulse energy at a repetition rate of 3.65 MHz.

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. High Efficient, Intense and Compact Pulsed D2O Terahertz Laser Pumped With a TEA CO2 Laser

    NASA Astrophysics Data System (ADS)

    Geng, Lijie; Qu, Yanchen; Zhao, Weijiang; Du, Jun

    2013-12-01

    A high efficient, intense and compact pulsed D2O terahertz laser is presented, which is pumped by a multi-transverse mode TEA CO2 laser. For D2O gas as the active medium, with the cavity length of 120 cm, pulse energy of the THz laser has been investigated as the variation of pump energy and gas pressure. When the pump energy was 1.41 J, the maximum single pulse energy of 6.2 mJ was achieved at the wavelength of 385 μm. Photon conversion efficiency as high as 36.5% was obtained when laser operated at the maximum output energy. As the pump energy was raised from 0.57 to 1.41 J, the optimum pressure was slightly changed from 400 to 700 Pa. The THz pulse consisted of a spike pulse with pulse width of 120 ns and a tail pulse with pulse width of about 170 ns. The peak power of the spike pulse is about 44.3 kW. Comparing with the occurring time and pulse width of pump pulse, 70 ns delay and 10ns broadening were observed in the THz spike pulse.

  6. Discovering key residues of dengue virus NS2b-NS3-protease: New binding sites for antiviral inhibitors design.

    PubMed

    Aguilera-Pesantes, D; Robayo, L E; Méndez, P E; Mollocana, D; Marrero-Ponce, Y; Torres, F J; Méndez, M A

    2017-03-23

    The NS2B-NS3 protease is essential for the Dengue Virus (DENV) replication process. This complex constitutes a target for efficient antiviral discovery because a drug could inhibit the viral polyprotein processing. Furthermore, since the protease is highly conserved between the four Dengue virus serotypes, it is probable that a drug would be equally effective against all of them. In this article, a strategy is reported that allowed us to identify influential residues on the function of the Dengue NS2b-NS3 Protease. Moreover, this is a strategy that could be applied to virtually any protein for the search of alternative influential residues, and for non-competitive inhibitor development. First, we incorporated several features derived from computational alanine scanning mutagenesis, sequence, structure conservation, and other structure-based characteristics. Second, these features were used as variables to obtain a multilayer perceptron model to identify defined groups (clusters) of key residues as possible candidate pockets for binding sites of new leads on the DENV protease. The identified residues included: i) amino acids close to the beta sheet-loop-beta sheet known to be important in its closed conformation for NS2b ii) residues close to the active site, iii) several residues evenly spread on the NS2b-NS3 contact surface, and iv) some inner residues most likely related to the overall stability of the protease. In addition, we found concordance on our list of residues with previously identified amino acids part of a highly conserved peptide studied for vaccine development.

  7. Intense Pulsed Heavy Ion Beam Technology

    NASA Astrophysics Data System (ADS)

    Masugata, Katsumi; Ito, Hiroaki

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

  8. Influence of pulse duration on mechanical effects after laser-induced breakdown in water

    NASA Astrophysics Data System (ADS)

    Noack, Joachim; Hammer, Daniel X.; Noojin, Gary D.; Rockwell, Benjamin A.; Vogel, Alfred

    1998-06-01

    The influence of the pulse duration on the mechanical effects following laser-induced breakdown in water was studied at pulse durations between 100 fs and 100 ns. Breakdown was generated by focusing laser pulses into a cuvette containing distilled water. The pulse energy corresponded to 6-times breakdown threshold energy. Plasma formation and shock wave emission were studied photographically. The plasma photographs show a strong influence of self-focusing on the plasma geometry for femtosecond pulses. Streak photographic recording of the shock propagation in the immediate vicinity of the breakdown region allowed the measurement of the near-field shock pressure. At the plasma rim, shock pressures between 3 and 9 GPa were observed for most pulse durations. The shock pressure rapidly decays proportionally to r-(2⋯3) with increasing distance r from the optical axis. At a 6 mm distance of the shock pressure has dropped to (8.5±0.6) MPa for 76 ns and to <0.1 MPa for femtosecond pulses. The radius of the cavitation bubble is reduced from 2.5 mm (76 ns pulses) to less than 50 μm for femtosecond pulses. Mechanical effects such as shock wave emission and cavitation bubble expansion are greatly reduced for shorter laser pulses, because the energy required to produce breakdown decreases with decreasing pulse duration, and because a larger fraction of energy is required to overcome the heat of vaporization with femtosecond pulses.

  9. Modified Blumlein pulse-forming networks for bioelectrical applications.

    PubMed

    Romeo, Stefania; Sarti, Maurizio; Scarfì, Maria Rosaria; Zeni, Luigi

    2010-07-01

    Intense nanosecond pulsed electric fields (nsPEFs) have been shown to induce, on intracellular structures, interesting effects dependent on electrical exposure conditions (pulse length and amplitude, repetition frequency and number of pulses), which are known in the literature as "bioelectrical effects" (Schoenbach et al., IEEE Trans Plasma Sci 30:293-300, 2002). In particular, pulses with a shorter width than the plasma membrane charging time constant (about 100 ns for mammalian cells) can penetrate the cell and trigger effects such as permeabilization of intracellular membranes, release of Ca(2+) and apoptosis induction. Moreover, the observed effects have led to exploration of medical applications, like the treatment of melanoma tumors (Nuccitelli et al., Biochem Biophys Res Commun 343:351-360, 2006). Pulsed electric fields allowing such effects usually range from several tens to a few hundred nanoseconds in duration and from a few to several tens of megavolts per meter in amplitude (Schoenbach et al., IEEE Trans Diel Elec Insul 14:1088-1109, 2007); however, the biological effects of subnanosecond pulses have been also investigated (Schoenbach et al., IEEE Trans Plasma Sci 36:414-422, 2008). The use of such a large variety of pulse parameters suggests that highly flexible pulse-generating systems, able to deliver wide ranges of pulse durations and amplitudes, are strongly required in order to explore effects and applications related to different exposure conditions. The Blumlein pulse-forming network is an often-employed circuit topology for the generation of high-voltage electric pulses with fixed pulse duration. An innovative modification to the Blumlein circuit has been recently devised which allows generation of pulses with variable amplitude, duration and polarity. Two different modified Blumlein pulse-generating systems are presented in this article, the first based on a coaxial cable configuration, matching microscopic slides as a pulse-delivery system

  10. 100 ns Z-Pinch Performance on the Inductive-Energy-Based ACE 4 Generator

    NASA Astrophysics Data System (ADS)

    Coleman, Philip; Thompson, John; Crumley, Randy; Failor, Bruce; Goodrich, Phillip; Parks, Don; Rauch, John; Song, Yuanxu; Steen, Paul; Waisman, Eduardo; Weber, Bruce; Moosman, Bryan; Qi, Niansheng; Schein, Jochen; McFarland, Mike; Campbell, Kelly; Krishnan, Mahadevan

    2000-10-01

    We report on the performance of a short implosion time ( ~100 ns) argon z-pinch using an inductive-energy-storage system. The generator, ACE 4, used a plasma opening switch (POS) to conduct for over a microsecond before driving the short implosion time 2.5 cm diameter Double Eagle gas nozzle. (Previously reported ACE 4 results used longer implosion times, 150 to over 300 ns, with z-pinch load diameters up to 14 cm.) The Double Eagle nozzle, which produces more than 20 kJ of argon K-shell radiation with a current I of almost 4 MA on Double Eagle, produced more than 6 kJ with 3 MA on ACE 4. This performance is consistent with the expected I to the 4th scaling. Pinch behavior on the two machines was quite similar in terms of zippering, pulse width and pinch diameter. As on Double Eagle, the gas flow away from the nozzle was observed to pinch best. On ACE 4, recessing the nozzle behind a wire grid cathode plane moved the high output part of the pinch down to the cathode plane. This allowed us to reduce the pinch length and load inductance, hence increasing load current and yield. Similar changes could be exploited on other gas puff loads and generators to enhance x-ray output. (Thompson, et. al., report elsewhere at this meeting on the performance of the POS and its interaction with the PRS.)

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

    PubMed

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

    2016-01-05

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

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

    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

  13. 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.

  14. 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.

  15. PBFA II, the Pulsed Power Characterization Phase

    DTIC Science & Technology

    1987-06-01

    pulsed voltages above 10 MV resulting in a compact accelerator. Thirty-six Marx generators constituting 13 MJ stored energy were repeatably fired...with less 40 ns total spread. The prefire rate of this large Marx system is very low, below .05 per charge cycle. of than The gas switch laser...oil, water, and vacuum. First the energy storage section, which consists of the Marx generators and their trigger systems, are insulated using a 33

  16. 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)

  17. 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.

  18. Configurable multipulsing of a MOPA pulsed fiber laser with applications in materials processing

    NASA Astrophysics Data System (ADS)

    Guerreiro, Paulo T.; Sousa, João. M.; Romero, Rosa; Silva, Manuel; Duarte, André; Salcedo, José R.

    2013-11-01

    The generation of configurable multipulses by advanced MOPA fiber lasers is opening new possibilities in materials processing, showing improvements in efficiency and quality while benefiting from the advantages of competitively priced fiber lasers. We show examples of the configuration capability and control of multipulses of a 20W MOPA pulsed fiber laser at 1.06μm, having and M2 of 1.3. The multipulses consist of user-defined bursts of short pulses, with burst durations ranging from 10ns up to 1000ns, frequencies up to tens of MHz within the burst, with individual pulses in the 10ns to 200ns range and with up to 12kW peak power. Multipulse repetition frequency is controlled externally from single shot up to few MHz, with the possibility of real-time switching between different multipulses.

  19. 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).

  20. Nanosecond pulse electric field (nanopulse): a novel non-ligand agonist for platelet activation.

    PubMed

    Zhang, Jue; Blackmore, Peter F; Hargrave, Barbara Y; Xiao, Shu; Beebe, Stephen J; Schoenbach, Karl H

    2008-03-15

    Nanosecond pulse stimulation of a variety of cells produces a wide range of physiological responses (e.g., apoptosis, stimulation of calcium (Ca2+) fluxes, changes in membrane potential). In this study, we investigated the effect of nanosecond pulses, which generate intense electric fields (nsPEFs), on human platelet aggregation, intracellular free Ca2+ ion concentration ([Ca2+]i) and platelet-derived growth factor release. When platelet rich plasma was pulsed with one 300ns pulse with an electric field of 30kV/cm, platelets aggregated and a platelet gel was produced. Platelet aggregation was observed with pulses as low as 7kV/cm with maximum effects seen with approximately 30kV/cm. The increases in intracellular Ca2+ release and Ca2+ influx were dose dependent on the electrical energy density and were maximally stimulated with approximately 30kV/cm. The increases in [Ca2+]i induced by nsPEF were similar to those seen with thapsigargin but not thrombin. We postulate that nsPEF caused Ca2+ to leak out of intracellular Ca2+ stores by a process involving the formation of nanopores in organelle membranes and also caused Ca2+ influx through plasma membrane nanopores. We conclude that nsPEFs dose-dependently cause platelets to rapidly aggregate, like other platelet agonists, and this is most likely initiated by the nsPEFs increasing [Ca2+]i, however by a different mechanism.

  1. 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.

  2. 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.

  3. 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.

  4. 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).

  5. 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.

  6. Pulsed Beamless High Power Microwave (HPM) Source with Integrated Antenna

    DTIC Science & Technology

    2013-06-01

    gral part of t utilized for source ope d. The peak asured to be 2 ns. SS HIGH IN kach Institu .Mironenk iv 04073, U SA; Ya. T 1 er Microwave W...Pulsed Beamless High Power Microwave (HPM) Source With Integrated Antenna 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6...NOTES See also ADM002371. 2013 IEEE Pulsed Power Conference, Digest of Technical Papers 1976-2013, and Abstracts of the 2013 IEEE International

  7. Evolution, synthesis and SAR of tripeptide alpha-ketoacid inhibitors of the hepatitis C virus NS3/NS4A serine protease.

    PubMed

    Colarusso, Stefania; Gerlach, Benjamin; Koch, Uwe; Muraglia, Ester; Conte, Immacolata; Stansfield, Ian; Matassa, Victor G; Narjes, Frank

    2002-02-25

    N-terminal truncation of the hexapeptide ketoacid 1 gave rise to potent tripeptide inhibitors of the hepatitis C virus NS3 protease/NS4A cofactor complex. Optimization of these tripeptides led to ketoacid 30 with an IC50 of 0.38 microM. The SAR of these tripeptides is discussed in the light of the recently published crystal structures of a ternary tripetide/NS3/NS4A complexes.

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

    PubMed

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

    2013-08-01

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

  9. 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.

  10. Shaped optimal control pulses for increased excitation bandwidth in EPR.

    PubMed

    Spindler, Philipp E; Zhang, Yun; Endeward, Burkhard; Gershernzon, Naum; Skinner, Thomas E; Glaser, Steffen J; Prisner, Thomas F

    2012-05-01

    A 1 ns resolution pulse shaping unit has been developed for pulsed EPR spectroscopy to enable 14-bit amplitude and phase modulation. Shaped broadband excitation pulses designed using optimal control theory (OCT) have been tested with this device at X-band frequency (9 GHz). FT-EPR experiments on organic radicals in solution have been performed with the new pulses, designed for uniform excitation over a significantly increased bandwidth compared to a classical rectangular π/2 pulse of the same B(1) amplitude. The concept of a dead-time compensated prefocused pulse has been introduced to EPR with a self-refocusing of 200 ns after the end of the pulse. Echo-like refocused signals have been recorded and compared to the performance of a classical Hahn-echo sequence. The impulse response function of the microwave setup has been measured and incorporated into the algorithm for designing OCT pulses, resulting in further significant improvements in performance. Experimental limitations and potential new applications of OCT pulses in EPR spectroscopy will be discussed.

  11. 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.

  12. A New Comptonization Model for Weakly Magnetized Accreting NS LMXBs

    NASA Astrophysics Data System (ADS)

    Paizis, A.; Farinelli, R.; Titarchuk, L.; Frontera, F.; Cocchi, M.; Ferrigno, C.

    2009-05-01

    We have developed a new Comptonization model to propose, for the first time, a self consistent physical interpretation of the complex spectral evolution seen in NS LMXBs. The model and its application to LMXBs are presented and compared to the Simbol-X expected capabilities.

  13. 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.

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

    PubMed

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

    2009-12-01

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

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

    SciTech Connect

    Yurkin, A A

    2016-03-31

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

  16. Substitutional nitrogen impurities in pulsed-laser annealed silicon

    NASA Astrophysics Data System (ADS)

    Murakami, Kouichi; Itoh, Hisayoshi; Takita, Kôki; Masuda, Kohzoh

    1984-07-01

    Single-crystal Si samples with nitrogen (N) impurities (Si:N) and with N and phosphorus (P) impurities (Si:N:P) have been investigated by electron spin resonance measurements. It was found that substitutional N impurities Ns cannot be incorporated into Si by cw laser annealing of N ion-implanted Si or by N doping during crystal growth; however, Ns is incorporated into Si by pulsed-laser annealing (PLA) of N ion-implanted Si. The spin density of Ns decreases with doping of P shallow donors into PLA Si:N and increases by introduction of slight point defects in PLA Si:N:P. These results suggest that Ns with a negative charge are formed in PLA Si: N:P system.

  17. Priming and stimulation of hepatitis C virus-specific CD4+ and CD8+ T cells against HCV antigens NS4, NS5a or NS5b from HCV-naive individuals: implications for prophylactic vaccine.

    PubMed

    Li, Wen; Krishnadas, Deepa K; Kumar, Rakesh; Tyrrell, D Lorne J; Agrawal, Babita

    2008-01-01

    Hepatitis C virus (HCV) is a devastating human pathogen, yet there is no vaccine available for this virus. From studies with acute or chronic HCV-infected humans and chimpanzees, T-cell responses against HCV-derived conserved non-structural antigens have been correlated with viral clearance. In this study, recombinant adenoviral vectors containing HCV-derived NS4, NS5a or NS5b genes were employed to endogenously express the HCV antigens in human dendritic cells (DCs). The DCs expressing these HCV antigens exhibited normal phenotype and function. Intriguingly, we found that the DCs expressing HCV NS4, NS5a or NS5b antigens were able to significantly stimulate autologous T cells obtained from uninfected healthy individuals. These T cells produced various cytokines and proliferated in an HCV antigen-dependent manner. Evidence of both CD4(+) and CD8(+) T-cell responses generated in vitro against HCV NS4, NS5a or NS5b were obtained. HCV NS4 was much less stimulatory for CD4(+) and CD8(+) T cells than NS5. Further, in secondary assays, the CD4(+) T cells primed in vitro exhibited HCV antigen-specific proliferative responses against recombinant protein antigens. In summary, we provide conclusive evidence of in vitro stimulation of CD4(+) and CD8(+) T cells from HCV-naive individuals against HCV antigens NS4, NS5a and NS5b. The studies with naive T cells represent early events in the induction of cellular immune responses, which most likely govern the outcome of HCV infection. These studies have significant implications in designing vaccines for HCV infection in both prophylactic and therapeutic settings.

  18. 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.

  19. RNA unwinding by NS3 helicase: a statistical approach.

    PubMed

    Arunajadai, Srikesh G

    2009-09-22

    The study of double-stranded RNA unwinding by helicases is a problem of basic scientific interest. One such example is provided by studies on the hepatitis C virus (HCV) NS3 helicase using single molecule mechanical experiments. HCV currently infects nearly 3% of the world population and NS3 is a protein essential for viral genome replication. The objective of this study is to model the RNA unwinding mechanism based on previously published data and study its characteristics and their dependence on force, ATP and NS3 protein concentration. In this work, RNA unwinding by NS3 helicase is hypothesized to occur in a series of discrete steps and the steps themselves occurring in accordance with an underlying point process. A point process driven change point model is employed to model the RNA unwinding mechanism. The results are in large agreement with findings in previous studies. A gamma distribution based renewal process was found to model well the point process that drives the unwinding mechanism. The analysis suggests that the periods of constant extension observed during NS3 activity can indeed be classified into pauses and subpauses and that each depend on the ATP concentration. The step size is independent of external factors and seems to have a median value of 11.37 base pairs. The steps themselves are composed of a number of substeps with an average of about 4 substeps per step and an average substep size of about 3.7 base pairs. An interesting finding pertains to the stepping velocity. Our analysis indicates that stepping velocity may be of two kinds- a low and a high velocity.

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. Serotype-specific interactions among functional domains of Dengue virus 2 non-structural proteins (NS) 5 and NS3 are crucial for viral RNA replication.

    PubMed

    Teramoto, Tadahisa; Balasubramanian, Anuradha; Choi, Kyung H; Padmanabhan, Radhakrishnan

    2017-04-10

    Four serotypes of mosquito-borne Dengue virus (DENV), evolved from a common ancestor, are human pathogens of global significance, and there is no vaccine or antiviral drug available. The N-terminal domain of DENV NS5 has guanylyltransferase and methyltransferase (MTase) and the C-terminal region has the polymerase (POL) which are important for 5'-capping and RNA replication. The crystal structure of NS5 showed it as a dimer but the functional evidence for NS5 dimer is lacking. The results of our studies show that the substitution of DENV2 NS5 MTase or POL with that of DENV4 NS5 within DENV2 RNA resulted in severe attenuation of replication in the transfected BHK-21 cells. A replication competent species evolved with acquired mutations in the DENV2 and DENV4 NS5 MTase or POL domain or in DENV2 NS3 helicase domain in the DENV2 chimera RNAs by repeated passaging of infected BHK-21 or mosquito cells. The linker region of seven residues in NS5, rich in serotype-specific residues, is important for recovery of replication fitness in the chimera RNA. Our results, taken together, provide genetic evidence for serotype-specific interaction between NS3 and NS5 as well as specific inter-domain interaction within NS5 required for RNA replication. Genome-wide RNAseq analysis revealed the distribution of adaptive mutations in RNA quasispecies. Those within NS3 and NS5 are located at the surface and/or within the NS5 dimer interface providing a functional significance to the crystal structure NS5 dimer.

  5. 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.

  6. Increased activity of unlinked Zika virus NS2B/NS3 protease compared to linked Zika virus protease.

    PubMed

    Kuiper, Benjamin D; Slater, Kristin; Spellmon, Nicholas; Holcomb, Joshua; Medapureddy, Prasanna; Muzzarelli, Kendall M; Yang, Zhe; Ovadia, Reuben; Amblard, Franck; Kovari, Iulia A; Schinazi, Raymond F; Kovari, Ladislau C

    2017-03-22

    Zika virus (ZIKV) is a flavivirus spread by daytime-active Aedes spp. mosquitoes such as A. aegypti and A. albopictus. Previously thought to be a mild infection, the latest ZIKV outbreak in the Americas is causally associated with more severe symptoms as well as severe birth defects, such as microcephaly. Currently no vaccine or antiviral exists. However, recent progress has demonstrated the viral NS2B/NS3 protease may be a suitable target for the development of small-molecule antiviral agents. To better understand the ZIKV protease, we expressed, purified, and characterized unlinked and linked NS2B/NS3 protease corresponding to an isolate from the recent outbreak in Puerto Rico. Unlinked ZIKV protease is more active and binds substrate with greater affinity than linked ZIKV protease. Therefore, we propose that unlinked ZIKV protease be used when evaluating or designing ZIKV protease inhibitors. Additionally, potent inhibitors of related viral proteases, like West Nile Virus and Dengue virus, may serve as advanced starting points to identify and develop ZIKV protease inhibitors.

  7. Novel antiviral activity and mechanism of bromocriptine as a Zika virus NS2B-NS3 protease inhibitor.

    PubMed

    Chan, Jasper Fuk-Woo; Chik, Kenn Ka-Heng; Yuan, Shuofeng; Yip, Cyril Chik-Yan; Zhu, Zheng; Tee, Kah-Meng; Tsang, Jessica Oi-Ling; Chan, Chris Chung-Sing; Poon, Vincent Kwok-Man; Lu, Gang; Zhang, Anna Jinxia; Lai, Kin-Kui; Chan, Kwok-Hung; Kao, Richard Yi-Tsun; Yuen, Kwok-Yung

    2017-02-07

    Zika virus (ZIKV) infection is associated with congenital malformations in infected fetuses and severe neurological and other systemic complications in adults. There are currently limited anti-ZIKV treatment options that are readily available and safe for use in pregnancy. In this drug repurposing study, bromocriptine was found to have inhibitory effects on ZIKV replication in cytopathic effect inhibition, virus yield reduction, and plaque reduction assays. Time-of-drug-addition assay showed that bromocriptine exerted anti-ZIKV activity between 0 and 12 h post-ZIKV inoculation, corroborating with post-entry events in the virus replication cycle prior to budding. Our docking model showed that bromocriptine interacted with several active site residues of the proteolytic cavity involving H51 and S135 in the ZIKV-NS2B-NS3 protease protein, and might occupy the active site and inhibit the protease activity of the ZIKV-NS2B-NS3 protein. A fluorescence-based protease inhibition assay confirmed that bromocriptine inhibited ZIKV protease activity. Moreover, bromocriptine exhibited synergistic effect with interferon-α2b against ZIKV replication in cytopathic effect inhibition assay. The availability of per vagina administration of bromocriptine as suppositories or vaginoadhesive discs and the synergistic anti-ZIKV activity between bromocriptine and type I interferon may make bromocriptine a potentially useful and readily available treatment option for ZIKV infection. The anti-ZIKV effects of bromocriptine should be evaluated in a suitable animal model.

  8. Dengue virus-specific CD4+ and CD8+ T lymphocytes target NS1, NS3 and NS5 in infected Indian rhesus macaques.

    PubMed

    Mladinich, Katherine M; Piaskowski, Shari M; Rudersdorf, Richard; Eernisse, Christopher M; Weisgrau, Kim L; Martins, Mauricio A; Furlott, Jessica R; Partidos, Charalambos D; Brewoo, Joseph N; Osorio, Jorge E; Wilson, Nancy A; Rakasz, Eva G; Watkins, David I

    2012-02-01

    Every year, Dengue virus (DENV) infects approximately 100 million people. There are currently several vaccines undergoing clinical studies, but most target the induction of neutralizing antibodies. Unfortunately, DENV infection can be enhanced by subneutralizing levels of antibodies that bind virions and deliver them to cells of the myeloid lineage, thereby increasing viral replication (termed antibody-dependent enhancement [ADE]). T lymphocyte-based vaccines may offer an alternative that avoids ADE. The goal of our study was to describe the cellular immune response generated after primary DENV infection in Indian rhesus macaques. We infected eight rhesus macaques with 10⁵ plaque-forming units (PFU) of DENV serotype 2 (DENV2) New Guinea C (NGC) strain, and monitored viral load and the cellular immune response to the virus. Viral replication peaked at day 4 post-infection and was resolved by day 10. DENV-specific CD4+ and CD8+ T lymphocytes targeted nonstructural (NS) 1, NS3 and NS5 proteins after resolution of peak viremia. DENV-specific CD4+ cells expressed interferon-gamma (IFN-γ) along with tumor necrosis factor-alpha (TNF-α), interleukin-2 (IL-2), and macrophage inflammatory protein-1 beta (MIP-1β). In comparison, DENV-specific CD8+ cells expressed IFN-γ in addition to MIP-1β and TNF-α and were positive for the degranulation marker CD107a. Interestingly, a fraction of the DENV-specific CD4+ cells also stained for CD107a, suggesting that they might be cytotoxic. Our results provide a more complete understanding of the cellular immune response during DENV infection in rhesus macaques and contribute to the development of rhesus macaques as an animal model for DENV vaccine and pathogenicity studies.

  9. 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

  10. Pulsed Orotron - A new microwave source for submillimeter pulse high-field electron paramagnetic resonance spectroscopy

    SciTech Connect

    Grishin, Yu.A.; Fuchs, M.R.; Schnegg, A.; Dubinskii, A.A.; Dumesh, B.S.; Rusin, F.S.; Bratman, V.L.; Moebius, K.

    2004-09-01

    A vacuum-tube device for the generation of pulsed microwave radiation in the submillimeter range (up to 380 GHz) is presented, designed for use as a source in a 360 GHz high-field/high-frequency electron paramagnetic resonance (EPR) spectrometer - the pulsed Orotron. Analogous to the known continuous wave (cw) version, in the pulsed Orotron microwave radiation is generated by the interaction of a nonrelativistic electron beam with a diffraction grating (stimulated Smith-Purcell radiation) in feedback with an open Fabry-Perot resonator construction. The presented design extends the cw Orotron by a gate electrode and a high-voltage pulsing unit to control the electron beam current. The generated pulses at 360 GHz have pulse lengths from 100 ns-10 {mu}s and a pulse power of (22{+-}5) mW. The output in a broader frequency band between 320 and 380 GHz ranges from 20 up to 60 mW. Within a 10 {mu}s time slot, incoherent pulse trains of arbitrary duration can be generated. The pulsed Orotron has been incorporated in the quasioptical microwave bridge of a heterodyne induction mode EPR spectrometer. The first free induction decay measurements at a microwave frequency of 360 GHz and a magnetic field of 12.8 T on a polycrystalline perylenyl-ion sample are presented and future applications and extensions of Orotron-EPR spectroscopy are discussed.

  11. 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.

    PubMed

    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.

  12. Compact 0.7 mJ/11 ns eye-safe erbium laser

    NASA Astrophysics Data System (ADS)

    Vitkin, V. V.; Polyakov, V. M.; Kharitonov, A. A.; Buchenkov, V. A.; Rodionov, A. Yu; Zhilin, A. A.; Dymshits, O. S.; Loiko, P. A.

    2016-12-01

    We report on the development of a compact diode-end-pumped eye-safe (~1.54 µm) passively-cooled Er,Yb:glass laser. The design of this laser is facilitated by the use of a double-pass pumping scheme and a special ZrO2 diffuse reflector for a uniform pump distribution. In the free-running mode, this laser generates 8.2 mJ/3 ms pulses with a slope efficiency of 15%. Passive Q-switching is provided by saturable absorbers made of transparent glass-ceramics containing Co2+:γ-Ga2O3 or Co2+:MgAl2O4 nanocrystals with a spinel structure. In the latter case, 0.7 mJ/10.5 ns pulses are generated corresponding to  >60 kW peak power and good beam quality (M 2  =  1.4). The designed laser is suitable for portable range-finders.

  13. Lyso-myristoyl phosphatidylcholine micelles sustain the activity of Dengue non-structural (NS) protein 3 protease domain fused with the full-length NS2B.

    PubMed

    Huang, Qiwei; Li, Qingxin; Joy, Joma; Chen, Angela Shuyi; Ruiz-Carrillo, David; Hill, Jeffrey; Lescar, Julien; Kang, Congbao

    2013-12-01

    Dengue virus (DENV), a member of the flavivirus genus, affects 50-100 million people in tropical and sub-tropical regions. The DENV protease domain is located at the N-terminus of the NS3 protease and requires for its enzymatic activity a hydrophilic segment of the NS2B that acts as a cofactor. The protease is an important antiviral drug target because it plays a crucial role in virus replication by cleaving the genome-coded polypeptide into mature functional proteins. Currently, there are no drugs to inhibit DENV protease activity. Most structural and functional studies have been conducted using protein constructs containing the NS3 protease domain connected to a soluble segment of the NS2B membrane protein via a nine-residue linker. For in vitro structural and functional studies, it would be useful to produce a natural form of the DENV protease containing the NS3 protease domain and the full-length NS2B protein. Herein, we describe the expression and purification of a natural form of DENV protease (NS2BFL-NS3pro) containing the full-length NS2B protein and the protease domain of NS3 (NS3pro). The protease was expressed and purified in detergent micelles necessary for its folding. Our results show that this purified protein was active in detergent micelles such as lyso-myristoyl phosphatidylcholine (LMPC). These findings should facilitate further structural and functional studies of the protease and will facilitate drug discovery targeting DENV.

  14. 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.

  15. 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.

  16. The cytotoxic synergy of nanosecond electric pulses and low temperature leads to apoptosis

    PubMed Central

    Muratori, Claudia; Pakhomov, Andrei G.; Gianulis, Elena C.; Jensen, Sarah Damsbo; Pakhomova, Olga N.

    2016-01-01

    Electroporation by nanosecond electric pulses (nsEP) is an emerging modality for tumor ablation. Here we show the efficient induction of apoptosis even by a non-toxic nsEP exposure when it is followed by a 30-min chilling on ice. This chilling itself had no impact on the survival of U-937 or HPAF-II cells, but caused more than 75% lethality in nsEP-treated cells (300 ns, 1.8-7 kV/cm, 50-700 pulses). The cell death was largely delayed by 5-23 hr and was accompanied by a 5-fold activation of caspase 3/7 (compared to nsEP without chilling) and more than 60% cleavage of poly-ADP ribose polymerase (compared to less than 5% in controls or after nsEP or chilling applied separately). When nsEP caused a transient permeabilization of 83% of cells to propidium iodide, cells placed at 37 °C resealed in 10 min, whereas 60% of cells placed on ice remained propidium-permeable even in 30 min. The delayed membrane resealing caused cell swelling, which could be blocked by an isosmotic addition of a pore-impermeable solute (sucrose). However, the block of swelling did not prevent the delayed cell death by apoptosis. The potent enhancement of nsEP cytotoxicity by subsequent non-damaging chilling may find applications in tumor ablation therapies. PMID:27833151

  17. Human VAP-B is involved in hepatitis C virus replication through interaction with NS5A and NS5B.

    PubMed

    Hamamoto, Itsuki; Nishimura, Yorihiro; Okamoto, Toru; Aizaki, Hideki; Liu, Minyi; Mori, Yoshio; Abe, Takayuki; Suzuki, Tetsuro; Lai, Michael M C; Miyamura, Tatsuo; Moriishi, Kohji; Matsuura, Yoshiharu

    2005-11-01

    The hepatitis C virus (HCV) nonstructural protein (NS) 5A is a phosphoprotein that associates with various cellular proteins and participates in the replication of the HCV genome. Human vesicle-associated membrane protein-associated protein (VAP) subtype A (VAP-A) is known to be a host factor essential for HCV replication by binding to both NS5A and NS5B. To obtain more information on the NS5A protein in HCV replication, we screened human brain and liver libraries by a yeast two-hybrid system using NS5A as bait and identified VAP-B as an NS5A-binding protein. Immunoprecipitation and mutation analyses revealed that VAP-B binds to both NS5A and NS5B in mammalian cells and forms homo- and heterodimers with VAP-A. VAP-A interacts with VAP-B through the transmembrane domain. NS5A interacts with the coiled-coil domain of VAP-B via 70 residues in the N-terminal and 341 to 344 amino acids in the C-terminal polyproline cluster region. NS5A was colocalized with VAP-B in the endoplasmic reticulum and Golgi apparatus. The specific antibody to VAP-B suppressed HCV RNA replication in a cell-free assay. Overexpression of VAP-B, but not of a mutant lacking its transmembrane domain, enhanced the expression of NS5A and NS5B and the replication of HCV RNA in Huh-7 cells harboring a subgenomic replicon. In the HCV replicon cells, the knockdown of endogenous VAP-B by small interfering RNA decreased expression of NS5B, but not of NS5A. These results suggest that VAP-B, in addition to VAP-A, plays an important role in the replication of the HCV genome.

  18. Identification of Residues in the Dengue Virus Type 2 NS2B Cofactor That Are Critical for NS3 Protease Activation

    PubMed Central

    Niyomrattanakit, Pornwaratt; Winoyanuwattikun, Pakorn; Chanprapaph, Santad; Angsuthanasombat, Chanan; Panyim, Sakol; Katzenmeier, Gerd

    2004-01-01

    Proteolytic processing of the dengue virus polyprotein is mediated by host cell proteases and the virus-encoded NS2B-NS3 two-component protease. The NS3 protease represents an attractive target for the development of antiviral inhibitors. The three-dimensional structure of the NS3 protease domain has been determined, but the structural determinants necessary for activation of the enzyme by the NS2B cofactor have been characterized only to a limited extent. To test a possible functional role of the recently proposed Φx3Φ motif in NS3 protease activation, we targeted six residues within the NS2B cofactor by site-specific mutagenesis. Residues Trp62, Ser71, Leu75, Ile77, Thr78, and Ile79 in NS2B were replaced with alanine, and in addition, an L75A/I79A double mutant was generated. The effects of these mutations on the activity of the NS2B(H)-NS3pro protease were analyzed in vitro by sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis of autoproteolytic cleavage at the NS2B/NS3 site and by assay of the enzyme with the fluorogenic peptide substrate GRR-AMC. Compared to the wild type, the L75A, I77A, and I79A mutants demonstrated inefficient autoproteolysis, whereas in the W62A and the L75A/I79A mutants self-cleavage appeared to be almost completely abolished. With exception of the S71A mutant, which had a kcat/Km value for the GRR-AMC peptide similar to that of the wild type, all other mutants exhibited drastically reduced kcat values. These results indicate a pivotal function of conserved residues Trp62, Leu75, and Ile79 in the NS2B cofactor in the structural activation of the dengue virus NS3 serine protease. PMID:15564480

  19. 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.

  20. 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.

  1. 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.

  2. High spatial resolution BOTDA using simultaneously launched gain and loss pump pulses

    NASA Astrophysics Data System (ADS)

    Motil, A.; Danon, O.; Peled, Y.; Tur, M.

    2013-05-01

    We report a 10cm spatial resolution in a Brillouin-based distributed sensing system using two simultaneously launched gain and loss pump pulses, having slightly different durations. Post-recording subtraction of the probe signal, excited by the shorter pulse, from the corresponding one, obtained from the longer pump pulse, is no longer required, since it is done automatically by the overlapping parts of the gain and loss pump pulses. Using a 30ns gain pump pulse and a 29ns loss pump pulse we were able to improve upon previously published results, achieving a distributed strain measurement along a standard single mode optical fiber with a spatial resolution of ~10cm. This technique does not broaden the involved Brillouin gain spectra so that the strain/temperature sensitivity is not compromised.

  3. NS&T Management Observations - 3rd Quarter

    SciTech Connect

    Gianotto, David

    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.

  4. NS&T Management Observations: Quarterly Performance Analysis

    SciTech Connect

    Gianotto, David

    2014-09-01

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

  5. 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.

  6. Discovery of an irreversible HCV NS5B polymerase inhibitor.

    PubMed

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

    2013-12-15

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

  7. Coupling translocation with nucleic acid unwinding by NS3 helicase.

    PubMed

    Yu, Jin; Cheng, Wei; Bustamante, Carlos; Oster, George

    2010-12-03

    We present a semiquantitative model for translocation and unwinding activities of monomeric nonstructural protein 3 (NS3) helicase. The model is based on structural, biochemical, and single-molecule measurements. The model predicts that the NS3 helicase actively unwinds duplex by reducing more than 50% the free energy that stabilizes base pairing/stacking. The unwinding activity slows the movement of the helicase in a sequence-dependent manner, lowering the average unwinding efficiency to less than 1 bp per ATP cycle. When bound with ATP, the NS3 helicase can display significant translocational diffusion. This increases displacement fluctuations of the helicase, decreases the average unwinding efficiency, and enhances the sequence dependence. Also, interactions between the helicase and the duplex stabilize the helicase at the junction, facilitating the helicase's unwinding activity while preventing it from dissociating. In the presence of translocational diffusion during active unwinding, the dissociation rate of the helicase also exhibits sequence dependence. Based on unwinding velocity fluctuations measured from single-molecule experiments, we estimate the diffusion rate to be on the order of 10 s(-1). The generic features of coupling single-stranded nucleic acid translocation with duplex unwinding presented in this work may apply generally to a class of helicases.

  8. Membrane Interacting Regions of Dengue Virus NS2A Protein

    PubMed Central

    2015-01-01

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

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

    PubMed

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

    2006-04-01

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

  11. 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

  12. 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.

  13. 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

  14. 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.

  15. 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.

  16. Calcium-independent disruption of microtubule dynamics by nanosecond pulsed electric fields in U87 human glioblastoma cells

    PubMed Central

    Carr, Lynn; Bardet, Sylvia M.; Burke, Ryan C.; Arnaud-Cormos, Delia; Leveque, Philippe; O’Connor, Rodney P.

    2017-01-01

    High powered, nanosecond duration, pulsed electric fields (nsPEF) cause cell death by a mechanism that is not fully understood and have been proposed as a targeted cancer therapy. Numerous chemotherapeutics work by disrupting microtubules. As microtubules are affected by electrical fields, this study looks at the possibility of disrupting them electrically with nsPEF. Human glioblastoma cells (U87-MG) treated with 100, 10 ns, 44 kV/cm pulses at a frequency of 10 Hz showed a breakdown of their interphase microtubule network that was accompanied by a reduction in the number of growing microtubules. This effect is temporally linked to loss of mitochondrial membrane potential and independent of cellular swelling and calcium influx, two factors that disrupt microtubule growth dynamics. Super-resolution microscopy revealed microtubule buckling and breaking as a result of nsPEF application, suggesting that nsPEF may act directly on microtubules. PMID:28117459

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

    PubMed Central

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

    2016-01-01

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

  18. Calcium-independent disruption of microtubule dynamics by nanosecond pulsed electric fields in U87 human glioblastoma cells.

    PubMed

    Carr, Lynn; Bardet, Sylvia M; Burke, Ryan C; Arnaud-Cormos, Delia; Leveque, Philippe; O'Connor, Rodney P

    2017-01-24

    High powered, nanosecond duration, pulsed electric fields (nsPEF) cause cell death by a mechanism that is not fully understood and have been proposed as a targeted cancer therapy. Numerous chemotherapeutics work by disrupting microtubules. As microtubules are affected by electrical fields, this study looks at the possibility of disrupting them electrically with nsPEF. Human glioblastoma cells (U87-MG) treated with 100, 10 ns, 44 kV/cm pulses at a frequency of 10 Hz showed a breakdown of their interphase microtubule network that was accompanied by a reduction in the number of growing microtubules. This effect is temporally linked to loss of mitochondrial membrane potential and independent of cellular swelling and calcium influx, two factors that disrupt microtubule growth dynamics. Super-resolution microscopy revealed microtubule buckling and breaking as a result of nsPEF application, suggesting that nsPEF may act directly on microtubules.

  19. Nanosecond pulsed electric fields as a novel drug free therapy for breast cancer: an in vivo study.

    PubMed

    Wu, Shan; Wang, Yu; Guo, Jinsong; Chen, Qunzhi; Zhang, Jue; Fang, Jing

    2014-02-28

    Nanosecond pulsed electric fields (nsPEFs) is a novel non-thermal approach to induce cell apoptosis. NsPEFs has been proven effective in treating several murine tumors, but few studies focus on its efficacy in treating human tumors. To determine if nsPEFs is equally effective in treatment of human breast cancer, 30 human breast cancer tumors across 30Balb/c (nu/nu) mice were exposed to 720 pulses of 100ns duration, at 4pulsespersecond and 30kV/cm. Two weeks after treatment, the growth of treated tumors was inhibited by 79%. Morphological changes of tumors were observed via a 3.0T clinical magnetic resonance imaging (MRI) system with a self-made surface coil. Pulsed tumors exhibited apoptosis evaluated by TUNEL staining, inhibition in Bcl-2 expression and decreased blood vessel density. Notably, CD34, vascular endothelial growth factor (VEGF) and VEGF receptor (VEGFR) expression in treated tumors were strongly suppressed. To evaluate the might-be adverse effects of nsPEFs in healthy tissues, normal skin was treated exactly the same way as tumors, and pulsed skin showed no permanent damages. The results suggest nsPEFs is able to inhibit human breast cancer development and suppress tumor blood vessel growth, indicating nsPEFs may serve as a novel therapy for breast cancer in the future.

  20. RF synchronized short pulse laser ion source

    SciTech Connect

    Fuwa, Yasuhiro Iwashita, Yoshihisa; Tongu, Hiromu; Inoue, Shunsuke; Hashida, Masaki; Sakabe, Shuji; Okamura, Masahiro; Yamazaki, Atsushi

    2016-02-15

    A laser ion source that produces shortly bunched ion beam is proposed. In this ion source, ions are extracted immediately after the generation of laser plasma by an ultra-short pulse laser before its diffusion. The ions can be injected into radio frequency (RF) accelerating bucket of a subsequent accelerator. As a proof-of-principle experiment of the ion source, a RF resonator is prepared and H{sub 2} gas was ionized by a short pulse laser in the RF electric field in the resonator. As a result, bunched ions with 1.2 mA peak current and 5 ns pulse length were observed at the exit of RF resonator by a probe.

  1. Dependence of Initial Oxygen Concentration on Ozone Yield Using Inductive Energy Storage System Pulsed Power Generator

    NASA Astrophysics Data System (ADS)

    Go, Tomio; Tanaka, Yasushi; Yamazaki, Nobuyuki; Mukaigawa, Seiji; Takaki, Koichi; Fujiwara, Tamiya

    Dependence of initial oxygen concentration on ozone yield using streamer discharge reactor driven by an inductive energy storage system pulsed power generator is described in this paper. Fast recovery type diodes were employed as semiconductor opening switch to interrupt a circuit current within 100 ns. This rapid current change produced high-voltage short pulse between a secondary energy storage inductor. The repetitive high-voltage short pulse was applied to a 1 mm diameter center wire electrode placed in a cylindrical pulse corona reactor. The streamer discharge successfully occurred between the center wire electrode and an outer cylinder ground electrode of 2 cm inner diameter. The ozone was produced with the streamer discharge and increased with increasing pulse repetition rate. The ozone yield changed in proportion to initial oxygen concentration contained in the injected gas mixture at 800 ns forward pumping time of the current. However, the decrease of the ozone yield by decreasing oxygen concentration in the gas mixture at 180 ns forward pumping time of the current was lower than the decrease at 800 ns forward pumping time of the current. This dependence of the initial oxygen concentration on ozone yield at 180 ns forward pumping time is similar to that of dielectric barrier discharge reactor.

  2. Experimental study of pulsed corona discharge in air at high pressures

    NASA Astrophysics Data System (ADS)

    Lin, Yunghsu; Singleton, Dan; Sanders, Jason; Kuthi, Andras; Gundersen, Martin A.

    2012-10-01

    Understanding of the dynamics of nanosecond scale pulse discharges in air at multiatmospheric pressure is essential for the development of transient plasma enhanced combustion in internal combustion engines. Here we report the result of our experimental investigation of cathode-directed streamer discharges in synthetic air at pressures ranging from 1 to 20 bar. Two pulse generators with maximum pulse amplitudes of 50 kV and 65 kV, pulse width of approximately 12 ns and 85 ns and pulse rise times of 5 ns and 50 ns are used to generate streamers. The electrodes are coaxial with various radial gaps up to 11.75 mm. The discharge chamber is evacuated and backfilled with synthetic dry air at room temperature. Optical data is obtained from PI-MAX 3 ICCD camera with 3 ns gate width. The streamer propagation velocity variation with applied voltage, different pressures and reduced electric field, E/P, will be shown. Preliminary results indicate that the (pd) similarity law is violated at high pressures in agreement with other recent experiments [1].[4pt] [1] ``Nanosecond Scale Discharge Dynamics in High Pressure Air,'' Pierre Tardiveau, Nicolas Moreau, Francois Jorand, Christian Postel, St'ephane Pasquiers, and Pierre Vervisch, IEEE Trans. on Plasma Sci., Vol. 36, No. 4, 2008.

  3. Conformer and pharmacophore based identification of peptidomimetic inhibitors of chikungunya virus nsP2 protease.

    PubMed

    Dhindwal, Sonali; Kesari, Pooja; Singh, Harvijay; Kumar, Pravindra; Tomar, Shailly

    2016-12-02

    Chikungunya virus nsP2 replication protein is a cysteine protease, which cleaves the nonstructural nsP1234 polyprotein into functional replication components. The cleavage and processing of nsP1234 by nsP2 protease is essential for the replication and proliferation of the virus. Thus, ChikV nsP2 protease is a promising target for antiviral drug discovery. In this study, the crystal structure of the C-terminal domain of ChikV nsP2 protease (PDB ID: 4ZTB) was used for structure based identification and rational designing of peptidomimetic inhibitors against nsP2 protease. The interactions of the junction residues of nsP3/4 polyprotein in the active site of nsP2 protease have been mimicked to identify and design potential inhibitory molecules. Molecular docking of the nsP3/4 junction peptide in the active site of ChikV nsP2 protease provided the structural insight of the probable binding mode of nsP3/4 peptide and pigeonholed the molecular interactions critical for the substrate binding. Further, the shape and pharmacophoric properties of the viral nsP3/4 substrate peptide were taken into consideration and the mimetic molecules were identified and designed. The designed mimetic compounds were then analyzed by docking and their binding affinity was assessed by molecular dynamics simulations.

  4. 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.

  5. 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.

  6. 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.

  7. Ablation of steel using picosecond laser pulses in burst mode

    NASA Astrophysics Data System (ADS)

    Lickschat, Peter; Demba, Alexander; Weissmantel, Steffen

    2017-02-01

    Results obtained in picosecond laser processing of steel applying the burst mode are presented. Using the burst mode, pulse trains, i.e., bursts, consisting of a number of picosecond pulses with an inter-pulse delay of 12.5 ns and 10 ps pulse duration are applied for material processing. Small cavities with sizes in the range of the laser beam diameter made by single-burst ablation are compared to quadratic cavities of 0.5 × 0.5 mm² produced by multiburst ablation and simultaneous scanning of the laser beam across the steel sample surface. The ablated volume per pulse within the burst was calculated either from the ablated volume per burst or from the ablation depth of the quadratic cavities. With the second to fourth pulses in the bursts, a reduction of the ablated volume per pulse in comparison with the first pulse in the bursts (i.e., to the use of single pulses) was found for both single- and multiburst ablation, which is assumed to be due to plasma shielding. By contrast, the ablated volume per pulse within the bursts increases for the fifth to eighth pulses. Heat accumulation effect and the influence of the heated plasma can be assumed to be the reason for these higher ablation rates. SEM micrographs also show that there is a higher melt ejection out of the laser processed area. This is indicated by the formation of bulges about the ablated area.

  8. 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.

  9. 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.

  10. Square-wave pulse with ultra-wide tuning range in a passively mode-locked fiber laser.

    PubMed

    Zhang, Xianming; Gu, Chun; Chen, Guoliang; Sun, Biao; Xu, Lixin; Wang, Anting; Ming, Hai

    2012-04-15

    We report the generation of ultrawide tunable square-wave pulse in an erbium-doped mode-locked fiber laser. The pulse width can be tuned in an ultrawide range of more than 1700 ns by simply increasing the pump power. The pulse-width tuning is 5.1 ns/mW. To the best of our knowledge, this is the widest pulse-width tuning range of any square-wave pulse in an all-fiber passively mode-locked fiber laser. Experimental results show that the fiber nonlinearity plays an important role in the tuning range of the output pulse width. The high nonlinearity helps to increase the tuning range of the pulse width.

  11. Mutagenesis of Dengue Virus Protein NS2A Revealed a Novel Domain Responsible for Virus-Induced Cytopathic Effect and Interactions Between NS2A and NS2B Transmembrane Segments.

    PubMed

    Wu, Ren-Huang; Tsai, Ming-Han; Tsai, Kuen-Nan; Tian, Jia Ni; Wu, Jian-Sung; Wu, Su-Ying; Chern, Jyh-Haur; Chen, Chun-Hong; Yueh, Andrew

    2017-04-05

    The NS2A protein of Dengue virus (DENV) has eight predicted transmembrane segments (pTMS1-8) and participates in RNA replication, virion assembly, and host antiviral response. However, the roles of specific amino acid residues within the pTMS regions of NS2A during the viral life cycle are not clear. Here, we explored the function of DENV NS2A by introducing a series of alanine substitutions into the N-terminal half (pTMS1-4) of the protein in the context of a DENV infectious clone or subgenomic replicon. Six NS2A mutants (NM5, 7, 9, and 17-19) around pTMS1-2 displayed a novel phenotype showing a >1000-fold reduction in virus yield, an absence of plaque formation despite wild-type-like replicon activity, and infectious virus-like particle yields. The HEK293 cells infected with those six NS2A mutant viruses failed to cause a virus-induced cytopathic effect (CPE) by MitoCapture staining, cell proliferation, and lactate dehydrogenase release assays. Sequencing analyses of pseudorevertant viruses derived from lethal mutant viruses revealed two consensus reversion mutations, leucine-to-phenylalanine at codon 181 (L181F) within the pTMS7 of NS2A and isoleucine-to-threonine at codon 114 (I114T) within NS2B. The introduction of NS2A-L181F mutation into the lethal (NM15, 16, 25, and 33) and CPE-defective (NM7, 9, and 19) mutants substantially rescued virus infectivity and virus-induced CPE, respectively, whereas NS2B-L114T mutation rescued NM16, 25, and 33 mutants. In conclusion, the results revealed the essential roles of the N-terminal half of NS2A in RNA replication and virus-induced CPE. Intramolecular interactions between pTMSs of NS2A and intermolecular interactions between NS2A and NS2B protein were also implicated.Importance: The characterization of the N-terminal (current study) and C-terminal half of DENV NS2A is the most comprehensive mutagenesis study to date to investigate the function of NS2A during the flaviviral life cycle. A novel region responsible for

  12. The NS3 and NS4A genes as the targets of RNA interference inhibit replication of Japanese encephalitis virus in vitro and in vivo.

    PubMed

    Yuan, Lei; Wu, Rui; Liu, Hanyang; Wen, Xintian; Huang, Xiaobo; Wen, Yiping; Ma, Xiaoping; Yan, Qigui; Huang, Yong; Zhao, Qin; Cao, Sanjie

    2016-12-15

    Japanese encephalitis virus (JEV) is a mosquito-borne flavivirus that can cause acute encephalitis with a high fatality rate. RNA interference (RNAi) is a powerful tool to silence gene expression and a potential therapy for virus infection. In this study, the antiviral ability of eight shRNA expression plasmids targeting different sites of the NS3 and NS4A genes of JEV was determined in BHK21 cells and mice. The pGP-NS3-3 and pGP-NS4A-4 suppressed 93.9% and 82.0% of JEV mRNA in cells, respectively. The virus titer in cells was reduced approximately 950-fold by pretreating with pGP-NS3-4, and 640-fold by pretreating with pGP-NS4A-4. The results of western blot and immunofluorescence analysis showed JEV E protein and viral load in cells were remarkably inhibited by shRNA expression plasmids. The viral load in brains of mice pretreated with pGP-NS3-4 or pGP-NS4A-4 were reduced approximately 2400-fold and 800-fold, respectively, and the survival rate of mice challenged with JEV were 70% and 50%, respectively. However, the antiviral ability of shRNA expression plasmids was decreased over time. This study indicates that RNAi targeting of the NS3 and NS4A genes of JEV can sufficiently inhibit the replication of JEV in vitro and in vivo, and NS3 and NS4A genes might be potential targets of molecular therapy for JEV infection.

  13. 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

  14. Full length and protease domain activity of chikungunya virus nsP2 differ from other alphavirus nsP2 proteases in recognition of small peptide substrates.

    PubMed

    Saisawang, Chonticha; Sillapee, Pornpan; Sinsirimongkol, Kwanhathai; Ubol, Sukathida; Smith, Duncan R; Ketterman, Albert J

    2015-04-22

    Alphavirus nsP2 proteins are multifunctional and essential for viral replication. The protease role of nsP2 is critical for virus replication as only the virus protease activity is used for processing of the viral non-structural polypeptide. Chikungunya virus is an emerging disease problem that is becoming a world-wide health issue. We have generated purified recombinant chikungunya virus nsP2 proteins, both full length and a truncated protease domain from the C-terminus of the nsP2 protein. Enzyme characterization shows that the protease domain alone has different properties compared with the full length nsP2 protease. We also show chikungunya nsP2 protease possesses different substrate specificity to the canonical alphavirus nsP2 polyprotein cleavage specificity. Moreover, the chikungunya nsP2 also appears to differ from other alphavirus nsP2 in its distinctive ability to recognize small peptide substrates.

  15. Full length and protease domain activity of chikungunya virus nsP2 differ from other alphavirus nsP2 proteases in recognition of small peptide substrates

    PubMed Central

    Saisawang, Chonticha; Sillapee, Pornpan; Sinsirimongkol, Kwanhathai; Ubol, Sukathida; Smith, Duncan R.; Ketterman, Albert J.

    2015-01-01

    Alphavirus nsP2 proteins are multifunctional and essential for viral replication. The protease role of nsP2 is critical for virus replication as only the virus protease activity is used for processing of the viral non-structural polypeptide. Chikungunya virus is an emerging disease problem that is becoming a world-wide health issue. We have generated purified recombinant chikungunya virus nsP2 proteins, both full length and a truncated protease domain from the C-terminus of the nsP2 protein. Enzyme characterization shows that the protease domain alone has different properties compared with the full length nsP2 protease. We also show chikungunya nsP2 protease possesses different substrate specificity to the canonical alphavirus nsP2 polyprotein cleavage specificity. Moreover, the chikungunya nsP2 also appears to differ from other alphavirus nsP2 in its distinctive ability to recognize small peptide substrates. PMID:26182358

  16. Nanosecond pulsed electric field induced dose dependent phosphatidylinositol-4,5-bisphosphate signaling and intracellular electro-sensitization.

    PubMed

    Tolstykh, Gleb P; Tarango, Melissa; Roth, Caleb C; Ibey, Bennett L

    2017-03-01

    Previously, it was demonstrated that nanometer-sized pores (nanopores) are formed in outer cellular membranes after exposure to nanosecond electric pulses (nsEPs). We reported that plasma membrane nanoporation affects phospholipids of the cell membrane, culminating in cascading phosphoinositide phosphatidylinositol-4,5-bisphosphate (PIP2) intracellular signaling. In the current study, we show that nsEPs initiated electric field (EF) dose-dependent PIP2 hydrolysis and/or depletion from the plasma membrane. This process was confirmed using fluorescent optical probes of PIP2 hydrolysis: PLCδ-PH-EGFP and GFP-C1-PKCγ-C1a. The 50% maximum response occurs with a single 600ns pulse achieving an effective dose (ED50) of EF~8kV/cm within our model cell system. At 16.2kV/cm, the ED50 for the pulse width was 484ns. Reduction of the pulse width or EF amplitude gradually reduced the observed effect, but twenty 60ns 16.2kV/cm pulses produced an effect similar to a single 600ns pulse of the same amplitude. Propidium iodide (PI) uptake after the nsEP exposure confirmed a strong relationship between EF-induced plasma membrane impact and PIP2 depletion. These results have expanded our current knowledge of nsEPs dependent cell physiological effects, and serve as a basis for model development of new exposure standards, providing novel tools for drug independent stimulation and approaches to differential modulation of key cellular functions.

  17. Helium-Rich Bursters Reveal the NS Interiors

    NASA Astrophysics Data System (ADS)

    Misanovic, Zdenka

    Thermonuclear bursts in LMXBs accreting pure helium are sensitive to the thermal proceses in the NS interiors, as the heat for burst ignition must come entirely from the pycnonuclear reactions in the crust. But for a small number of observed He-accretors, the measured burst recurrence times are significantly shorter than predicted and cannot be reconciled with any current realistic model. We propose to do the first systematic study of He-rich bursts by observing a sample of four He-accretor candidates and measure their accretion rates and burst recurrence times. (This proposal is companion to another requesting TOO observations of one additional target.)

  18. 16th International Conference on Nuclear Structure: NS2016

    SciTech Connect

    Galindo-Uribarri, Alfredo

    2016-10-28

    Every two years the Nuclear Structure (NS) conference series brings together researchers from an international community of experimental and theoretical nuclear physicists to present and discuss their latest results in nuclear structure. This biennial conference covered the latest results on experimental and theoretical research into the structure of nuclei at the extremes of isospin, excitation energy, mass, and angular momentum. Topics included many of the most exciting areas of modern nuclear structure research such as transitional behavior, nuclear structure and its evolution across the nuclear landscape, shell structure, collectivity, nuclear structure with radioactive beams, and macroscopic and microscopic approaches to nuclear structure.

  19. 16th International Conference on Nuclear Structure: NS2016

    DOE PAGES

    Galindo-Uribarri, Alfredo

    2016-10-28

    Every two years the Nuclear Structure (NS) conference series brings together researchers from an international community of experimental and theoretical nuclear physicists to present and discuss their latest results in nuclear structure. This biennial conference covered the latest results on experimental and theoretical research into the structure of nuclei at the extremes of isospin, excitation energy, mass, and angular momentum. Topics included many of the most exciting areas of modern nuclear structure research such as transitional behavior, nuclear structure and its evolution across the nuclear landscape, shell structure, collectivity, nuclear structure with radioactive beams, and macroscopic and microscopic approaches tomore » nuclear structure.« less

  20. 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

    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

  1. Analysis of hepatitis C virus core/NS5A protein co-localization using novel cell culture systems expressing core-NS2 and NS5A of genotypes 1-7.

    PubMed

    Galli, Andrea; Scheel, Troels K H; Prentoe, Jannick C; Mikkelsen, Lotte S; Gottwein, Judith M; Bukh, Jens

    2013-10-01

    Hepatitis C virus (HCV) is an important human pathogen infecting hepatocytes. With the advent of infectious cell culture systems, the HCV particle assembly and release processes are finally being uncovered. The HCV core and NS5A proteins co-localize on cytoplasmic lipid droplets (cLDs) or on the endoplasmic reticulum (ER) at different stages of particle assembly. Current knowledge on assembly and release is primarily based on studies in genotype 2a cell culture systems; however, given the high genetic heterogeneity of HCV, variations might exist among genotypes. Here, we developed novel HCV strain JFH1-based recombinants expressing core-NS2 and NS5A from genotypes 1-7, and analysed core and NS5A co-localization in infected cells. Huh7.5 cells were transfected with RNA of core-NS2/NS5A recombinants and putative adaptive mutations were analysed by reverse genetics. Adapted core-NS2/NS5A recombinants produced infectivity titres of 10(2.5)-10(4.5) f.f.u. ml(-1). Co-localization analysis demonstrated that the core and NS5A proteins from all genotypes co-localized extensively, and there was no significant difference in protein co-localization among genotypes. In addition, we found that the core and NS5A proteins were highly associated with cLDs at 12 h post-infection but became mostly ER associated at later stages. Finally, we found that different genotypes showed varying levels of core/cLD co-localization, with a possible effect on viral assembly/release. In summary, we developed a panel of HCV genotype 1-7 core-NS2/NS5A recombinants producing infectious virus, and an immunostaining protocol detecting the core and NS5A proteins from seven different genotypes. These systems will allow, for the first time, investigation of core/NS5A interactions during assembly and release of HCV particles of all major genotypes.

  2. Terahertz field enhancement via coherent superposition of the pulse sequences after a single optical-rectification crystal

    SciTech Connect

    Sajadi, Mohsen Wolf, Martin; Kampfrath, Tobias

    2014-03-03

    Terahertz electromagnetic pulses are frequently generated by optical rectification of femtosecond laser pulses. In many cases, the efficiency of this process is known to saturate with increasing intensity of the generation beam because of two-photon absorption. Here, we demonstrate two routes to reduce this effect in ZnTe(110) crystals and enhance efficiency, namely, by (i) recycling the generation pulses and by (ii) splitting each generation pulse into two pulses before pumping the crystal. In both methods, the second pulse arrives ∼1 ns after the first one, sufficiently long for optically generated carriers to relax. Enhancement is achieved by coherently superimposing the two resulting terahertz fields.

  3. 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.

  4. Investigation of the phase stability of an X-band long pulse multibeam relativistic klystron amplifier

    NASA Astrophysics Data System (ADS)

    Liu, Zhenbang; Huang, Hua; Jin, Xiao; Lei, Lurong; Zhu, Lei; Li, Lele; Li, Shifeng; Yan, Wenkang; He, Hu

    2016-09-01

    To realize coherent high power microwave combining, an X-band long pulse multibeam relativistic klystron amplifier is designed, and the relative phase stability is investigated by three dimensions particle in cell simulation and high power microwave experiment. The simulation shows that the relative phase difference can be stabilized at gigawatt level radiation power. But the relative phase jitter increases in the experiment, then some measures are proposed to improve the stability of relative phase difference and avoid pulse shortening. A 0.98 GW radiation power with pulse duration of 160 ns is obtained in the experiment, the pulse shortening is avoided. The relative phase difference fluctuation between output microwave and input RF signal is less than ±25° in a single shot with duration of 100 ns. Then, the experiment of pulse repetition is carried out, and an output microwave with 0.98 GW radiation power at 25 Hz repetition rate is obtained. The power conversion efficiency is about 35% with pulse duration of 160 ns. The relative phase difference is less than ±30° at 25 Hz repetition rate in 100 ns.

  5. 75 FR 66734 - Proposed Voluntary Product Standard PS 2-10, Structural Plywood

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-10-29

    ... National Institute of Standards and Technology Proposed Voluntary Product Standard PS 2-10, Structural... Structural-Use Panels. This revised standard, PS 2-10, was prepared by the Standing Committee for PS 2 and... Acrobat File) of the proposed standard, PS 2-10, can be obtained at the following Web site:...

  6. 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.

  7. 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.

  8. Calcium influx affects intracellular transport and membrane repair following nanosecond pulsed electric field exposure.

    PubMed

    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.

  9. Silicon carbide synthesis with energy pulses

    NASA Astrophysics Data System (ADS)

    Majni, G.; Mengucci, P.; D'Anna, E.; Leggieri, G.; Luches, A.; Nassisi, V.

    1989-08-01

    Polycrystalline SiC layers were synthesized through nanosecond pulse heating of thin carbon films deposited on single-crystalline silicon wafers. The samples were submitted to electron beam irradiation (25 keV, 50 ns) at various current densities in vacuum (˜10-4mbar) and to XeCl excimer laser pulses (308 nm, 15ns) in air. Rutherford backscattering spectrometry (RBS) showed that in the e-beam annealed samples mixing of the elements at the interface starts at current densities of about 1200 A/cm2. The mixed layer thickness increases almost linearly with current density. From the RBS spectra a composition of the intermixed layers close to the SiC compound was deduced. Transmission electron microscopy (TEM) and electron diffraction studies clearly evidenced the formation of SiC polycrystals. Using the XeCl excimer laser, intermixing of the deposited C film with the Si substrate was observed after a single 0.3 J/cm2 pulse. Further analysis evidenced the formation of SiC nanocrystals, embedded in a diamond film.

  10. Activity of purified hepatitis C virus protease NS3 on peptide substrates.

    PubMed Central

    Steinkühler, C; Urbani, A; Tomei, L; Biasiol, G; Sardana, M; Bianchi, E; Pessi, A; De Francesco, R

    1996-01-01

    The protease domain of the hepatitis C virus (HCV) protein NS3 was expressed in Escherichia coli, purified to homogeneity, and shown to be active on peptides derived from the sequence of the NS4A-NS4B junction. Experiments were carried out to optimize protease activity. Buffer requirements included the presence of detergent, glycerol, and dithiothreitol, pH between 7.5 and 8.5, and low ionic strength. C- and N-terminal deletion experiments defined a peptide spanning from the P6 to the P4' residue as a suitable substrate. Cleavage kinetics were subsequently measured by using decamer P6-P4' peptides corresponding to all intermolecular cleavage sites of the HCV polyprotein. The following order of cleavage efficiency, in terms of kcat/Km, was determined: NS5A-NS5B > NS4A-NS4B >> NS4B-NS5A. A 14-mer peptide containing residues 21 to 34 of the protease cofactor NS4A (Pep4A 21-34), when added in stoichiometric amounts, was shown to increase cleavage rates of all peptides, the largest effect (100-fold) being observed on the hydrolysis of the NS4B-NS5A decamer. From the kinetic analysis of cleavage data, we conclude that (i) primary structure is an important determinant of the efficiency with which each site is cleaved during polyprotein processing, (ii) slow cleavage of the NS4B-NS5A site in the absence of NS4A is due to low binding affinity of the enzyme for this site, and (iii) formation of a 1:1 complex between the protease and Pep4A 21-34 is sufficient and required for maximum activation. PMID:8794305

  11. Disassembly of actin structures by nanosecond pulsed electric field is a downstream effect of cell swelling.

    PubMed

    Pakhomov, Andrei G; Xiao, Shu; Pakhomova, Olga N; Semenov, Iurii; Kuipers, Marjorie A; Ibey, Bennett L

    2014-12-01

    Disruption of the actin cytoskeleton structures was reported as one of the characteristic effects of nanosecond-duration pulsed electric field (nsPEF) in both mammalian and plant cells. We utilized CHO cells that expressed the monomeric fluorescent protein (mApple) tagged to actin to test if nsPEF modifies the cell actin directly or as a consequence of cell membrane permeabilization. A train of four 600-ns pulses at 19.2 kV/cm (2 Hz) caused immediate cell membrane poration manifested by YO-PRO-1 dye uptake, gradual cell rounding and swelling. Concurrently, bright actin features were replaced by dimmer and uniform fluorescence of diffuse actin. To block the nsPEF-induced swelling, the bath buffer was isoosmotically supplemented with an electropore-impermeable solute (sucrose). A similar addition of a smaller, electropore-permeable solute (adonitol) served as a control. We demonstrated that sucrose efficiently blocked disassembly of actin features by nsPEF, whereas adonitol did not. Sucrose also attenuated bleaching of mApple-tagged actin in nsPEF-treated cells (as integrated over the cell volume), although did not fully prevent it. We conclude that disintegration of the actin cytoskeleton was a result of cell swelling, which, in turn, was caused by cell permeabilization by nsPEF and transmembrane diffusion of solutes which led to the osmotic imbalance.

  12. Generation of microseconds-duration square pulses in a passively mode-locked fiber laser

    NASA Astrophysics Data System (ADS)

    Liu, Tonghui; Jia, Dongfang; Liu, Ying; Wang, Zhaoying; Yang, Tianxin

    2015-12-01

    An ultra-wide tunable square pulse operating in dissipative soliton resonance (DSR) region has been experimentally investigated in a passively mode-locked figure-of-eight fiber laser. In our experiment, by simply increasing the pump power, the pulse width can be tuned in an ultra-wide range from 135 ns to 2272 ns without wave-breaking while the peak power remains almost constant. The maximum output single pulse energy is 236.8 nJ at the pump power of 508 mW. A 960 m highly nonlinear fiber (HNLF) is employed to realize widely tunable square pulse in the DSR region. To the best of our knowledge, this is the widest tunable range of pulse width in any all-fiber passively mode-locked fiber laser.

  13. 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

  14. 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.

  15. Multiple determinants influence complex formation of the hepatitis C virus NS3 protease domain with its NS4A cofactor peptide.

    PubMed

    Urbani, A; Biasiol, G; Brunetti, M; Volpari, C; Di Marco, S; Sollazzo, M; Orrú, S; Piaz, F D; Casbarra, A; Pucci, P; Nardi, C; Gallinari, P; De Francesco, R; Steinkühler, C

    1999-04-20

    The interaction of the hepatitis C virus (HCV) NS3 protease domain with its NS4A cofactor peptide (Pep4AK) was investigated at equilibrium and at pre-steady state under different physicochemical conditions. Equilibrium dissociation constants of the NS3-Pep4AK complex varied by several orders of magnitude depending on buffer additives. Glycerol, NaCl, detergents, and peptide substrates were found to stabilize this interaction. The extent of glycerol-induced stabilization varied in an HCV strain-dependent way with at least one determinant mapping to an NS3-NS4A interaction site. Conformational transitions affecting at least the first 18 amino acids of NS3 were the main energy barriers for both the association and the dissociation reactions of the complex. However, deletion of this N-terminal portion of the protease molecule only slightly influenced equilibrium dissociation constants determined under different physicochemical conditions. Limited proteolysis experiments coupled with mass spectrometric identification of cleavage fragments suggested a high degree of conformational flexibility affecting at least the first 21 residues of NS3. The accessibility of this region of the protease to limited chymotryptic digestion did not significantly change in any condition tested, whereas a significant reduction of chymotryptic cleavages within the NS3 core was detected under conditions of high NS3-Pep4AK complex affinity. We conclude the following: (1) The N-terminus of the NS3 protease that, according to the X-ray crystal structure, makes extensive contacts with the cofactor peptide is highly flexible in solution and contributes only marginally to the thermodynamic stability of the complex. (2) Affinity enhancement is accomplished by several factors through a general stabilization of the fold of the NS3 molecule.

  16. 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.

  17. Assessing ubiquitination of viral proteins: lessons from flavivirus NS5

    PubMed Central

    Taylor, R. Travis; Best, Sonja M.

    2011-01-01

    Ubiquitin (Ub) conjugation to a substrate protein is a widely used cellular mechanism for control of protein stability and function, modulation of signal transduction pathways and antiviral responses. Identification and characterization of ubiquitinated viral proteins is an important step in understanding novel mechanisms of viral protein regulation as well as elucidating cellular antiviral strategies. Here we describe a protocol to easily detect and characterize the ubiquitination status of a viral substrate protein expressed either during infection or ectopically expressed as a fusion with a biotinylatable epitope tag. This tag provides advantages over current immunoprecipitation techniques by making use of the extremely tight biotin-streptavidin interaction. We provide an example of this protocol using the nonstructural protein 5 (NS5) from Langat virus (LGTV), a member of the tick-borne encephalitis virus (TBEV) serocomplex within the Flavivirus genus. Using the protocols outlined here, we describe some of the pitfalls inherent in determination of Ub linkage and demonstrate that NS5 is modified by at least two distinct ubiquitination types, multiubiquitination and K48-linked polyubiquitin chains. PMID:21855635

  18. Assessing ubiquitination of viral proteins: Lessons from flavivirus NS5.

    PubMed

    Taylor, R Travis; Best, Sonja M

    2011-10-01

    Ubiquitin (Ub) conjugation to a substrate protein is a widely used cellular mechanism for control of protein stability and function, modulation of signal transduction pathways and antiviral responses. Identification and characterization of ubiquitinated viral proteins is an important step in understanding novel mechanisms of viral protein regulation as well as elucidating cellular antiviral strategies. Here we describe a protocol to easily detect and characterize the ubiquitination status of a viral substrate protein expressed either during infection or ectopically expressed as a fusion with a biotinylatable epitope tag. This tag provides advantages over current immunoprecipitation techniques by making use of the extremely tight biotin-streptavidin interaction. We provide an example of this protocol using the nonstructural protein 5 (NS5) from Langat virus (LGTV), a member of the tick-borne encephalitis virus (TBEV) serocomplex within the Flavivirus genus. Using the protocols outlined here, we describe some of the pitfalls inherent in determination of Ub linkage and demonstrate that NS5 is modified by at least two distinct ubiquitination types, multiubiquitination and K48-linked polyubiquitin chains.

  19. Investigation of phase explosion in aluminum induced by nanosecond double pulse technique

    NASA Astrophysics Data System (ADS)

    Jafarabadi, Marzieh Akbari; Mahdieh, Mohammad Hossein

    2015-08-01

    In this paper, the influence of double pulse technique on phase explosion threshold in laser ablation of an aluminum target is investigated. Single and double pulse laser ablation of aluminum target was performed by a high power Nd:YAG laser beam in ambient air. In the double pulse excitation, the two pulses were from a single laser source which separated by a delay time in the range of 5-20 ns. Measuring ablation depth and rate, the phase explosion threshold was estimated in double pulse configuration as well as in the single pulse regime. The results show that in comparison between single and double pulse regimes, the phase explosion threshold fluence is decreased in double pulse configuration. The lowest phase explosion threshold fluence of 0.9 J/cm2 was obtained at 5 ns delay time. The results also show that plasma shielding effect reduced crater depth at a laser fluence which depended on the laser ablation configuration (single pulse or double pulse). The reduction of crater depth occurs at lower laser fluences for double pulse regime.

  20. A fast pulsed power source applied to treatment of conducting liquids and air

    SciTech Connect

    Heesch, E.J.M. van; Pemen, A.J.M.; Huijbrechts, P.A.H.J.; Laan, P.C.T. van der; Ptasinski, K.J.; Zanstra, G.J.; Jong, P. de

    2000-02-01

    Two pilot pulsed power sources were developed for fundamental investigations and industrial demonstrations of treatment of conducting liquids. The developed heavy-duty power sources have an output voltage of 100 kV (rise time 10 ns, pulse duration 150 ns, pulse repetition rate maximum 1,000 pps). A pulse energy of 0.5--3 J/pulse and an average pulse power of 1.5 kW have been achieved with an efficiency of about 80%. In addition, adequate electromagnetic compatibility is achieved between the high-voltage pulse sources and the surrounding equipment. Various applications, such as the use of pulsed electric fields (PEF's) or pulsed corona discharges for inactivation of microorganisms in liquids or air, have been tested in the laboratory. For PEF treatment, homogeneous electric fields in the liquid of up to 70 kV/cm at a pulse repetition rate of 10--400 pps could be achieved. The inactivation is found to be 85 kJ/L per log reduction for Pseudomonas fluorescens and 500 kJ/L per log reduction for spores of Bacillus cereus. Corona directly applied to the liquid is found to be more efficient than PEF. With direct corona they achieve 25 kJ/L per log reduction for both Gram positive and Gram negative bacteria. For air disinfection using their corona pulse source, the measured efficiencies are excellent: 2 J/L per log reduction.

  1. 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.

  2. Hepatitis C virus NS5A inhibitors and drug resistance mutations.

    PubMed

    Nakamoto, Shingo; Kanda, Tatsuo; Wu, Shuang; Shirasawa, Hiroshi; Yokosuka, Osamu

    2014-03-21

    Some direct-acting antiviral agents for hepatitis C virus (HCV), such as telaprevir and boceprevir have been available since 2011. It was reported that HCV NS5A is associated with interferon signaling related to HCV replication and hepatocarcinogenesis. HCV NS5A inhibitors efficiently inhibited HCV replication in vitro. Human studies showed that dual, triple and quad regimens with HCV NS5A inhibitors, such as daclatasvir and ledipasvir, in combination with other direct-acting antiviral agents against other regions of HCV with or without peginterferon/ribavirin, could efficiently inhibit HCV replication according to HCV genotypes. These combinations might be a powerful tool for "difficult-to-treat" HCV-infected patients. "First generation" HCV NS5A inhibitors such as daclatasvir, ledipasvir and ABT-267, which are now in phase III clinical trials, could result in resistance mutations. "Second generation" NS5A inhibitors such as GS-5816, ACH-3102, and MK-8742, have displayed improvements in the genetic barrier while maintaining potency. HCV NS5A inhibitors are safe at low concentrations, which make them attractive for use despite low genetic barriers, although, in fact, HCV NS5A inhibitors should be used with HCV NS3/4A inhibitors, HCV NS5B inhibitors or peginterferon plus ribavirin. This review article describes HCV NS5A inhibitor resistance mutations and recommends that HCV NS5A inhibitors be used in combination regimens potent enough to prevent the emergence of resistant variants.

  3. The 2NS Translocation from Aegilops ventricosa Confers Resistance to the Triticum Pathotype of Magnaporthe oryzae

    PubMed Central

    Cruz, C.D.; Peterson, G.L.; Bockus, W.W.; Kankanala, P.; Dubcovsky, J.; Jordan, K.W.; Akhunov, E.; Chumley, F.; Baldelomar, F.D.; Valent, B.

    2016-01-01

    Wheat blast is a serious disease caused by the fungus Magnaporthe oryzae (Triticum pathotype) (MoT). The objective of this study was to determine the effect of the 2NS translocation from Aegilops ventricosa (Zhuk.) Chennav on wheat head and leaf blast resistance. Disease phenotyping experiments were conducted in growth chamber, greenhouse, and field environments. Among 418 cultivars of wheat (Triticum aestivum L.), those with 2NS had 50.4 to 72.3% less head blast than those without 2NS when inoculated with an older MoT isolate under growth chamber conditions. When inoculated with recently collected isolates, cultivars with 2NS had 64.0 to 80.5% less head blast. Under greenhouse conditions when lines were inoculated with an older MoT isolate, those with 2NS had a significant head blast reduction. With newer isolates, not all lines with 2NS showed a significant reduction in head blast, suggesting that the genetic background and/or environment may influence the expression of any resistance conferred by 2NS. However, when near-isogenic lines (NILs) with and without 2NS were planted in the field, there was strong evidence that 2NS conferred resistance to head blast. Results from foliar inoculations suggest that the resistance to head infection that is imparted by the 2NS translocation does not confer resistance to foliar disease. In conclusion, the 2NS translocation was associated with significant reductions in head blast in both spring and winter wheat. PMID:27814405

  4. Oxacilin-resistant Coagulase-negative staphylococci (CoNS) bacteremia in a general hospital at São Paulo city, Brasil.

    PubMed

    d'Azevedo, P A; Secchi, C; Antunes, A L S; Sales, T; Silva, F M; Tranchesi, R; Pignatari, A C C

    2008-10-01

    In the last decades, coagulase-negative staphylococci (CoNS), especially Staphylococcus epidermidis have become an important cause of bloodstream infections. In addition, rates of methicillin-resistance among CoNS have increased substantially, leading to the use of glicopeptides for therapy. The objective of this study was to evaluate eleven consecutives clinically relevant cases of oxacillin-resistant CoNS bacteremia in a general hospital localized in São Paulo city, Brazil. Five different species were identified by different phenotypic methods, including S. epidermidis (5), S. haemolyticus (3), S. hominis (1), S. warneri (1) and S. cohnii subsp urealyticus (1). A variety of Pulsed Field Gel Electrophoresis profiles was observed by macrorestriction DNA analysis in S. epidermidis isolates, but two of three S. haemolyticus isolates presented the same profile. These data indicated the heterogeneity of the CoNS isolates, suggesting that horizontal dissemination of these microorganisms in the investigated hospital was not frequent. One S. epidermidis and one S. haemolyticus isolates were resistant to teicoplanin and susceptible to vancomycin. The selective pressure due to the use of teicoplanin in this hospital is relevant.

  5. HTS identifies novel and specific uncompetitive inhibitors of the two-component NS2B-NS3 proteinase of West Nile virus.

    PubMed

    Johnston, Paul A; Phillips, Jennifer; Shun, Tong Ying; Shinde, Sunita; Lazo, John S; Huryn, Donna M; Myers, Michael C; Ratnikov, Boris I; Smith, Jeffrey W; Su, Ying; Dahl, Russell; Cosford, Nicholas D P; Shiryaev, Sergey A; Strongin, Alex Y

    2007-12-01

    West Nile virus (WNV), a member of the Flavividae family, is a mosquito-borne, emerging pathogen. In addition to WNV, the family includes dengue, yellow fever, and Japanese encephalitis viruses, which affect millions of individuals worldwide. Because countermeasures are currently unavailable, flaviviral therapy is urgently required. The flaviviral two-component nonstructural NS2B-NS3 proteinase (protease [pro]) is essential for viral life cycle and, consequently, is a promising drug target. We report here the results of the miniaturization of an NS2B-NS3pro activity assay, followed by high-throughput screening of the National Institutes of Health's 65,000 compound library and identification of novel, uncompetitive inhibitors of WNV NS2B-NS3pro that appear to interfere with the productive interactions of the NS2B cofactor with the NS3pro domain. We anticipate that following structure optimization, the identified probes could form the foundation for the design of novel and specific therapeutics for WNV infection. We also provide the structural basis for additional species-selective allosteric inhibitors of flaviviruses.

  6. Simple Short-Pulse CO2 Laser Excited by Longitudinal Discharge without High-Voltage Switch

    NASA Astrophysics Data System (ADS)

    Uno, Kazuyuki; Jitsuno, Takahisa; Akitsu, Tetsuya

    2012-05-01

    We have developed a longitudinally excited CO2 laser without a high-voltage switch. The laser produces a short laser pulse similar to those from TEA and Q-switched CO2 lasers. This system, which is the simplest short-pulse CO2 laser yet constructed, includes a pulsed power supply, a high-speed step-up transformer, a storage capacitor, and a laser tube. At high pressure (4.2 kPa and above), a rapid discharge produces a short laser pulse with a sharp spike pulse. In mixed gas (CO2: N2: He = 1: 1: 2) at a pressure of 9.0 kPa, the laser pulse contains a spike pulse of 218 ns and has a pulse tail length of 16.7 μs.

  7. 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.

  8. 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

    2015-03-09

    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.

  9. 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

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. Fast pulsed radar reflectometry for the Textor Tokamak

    NASA Astrophysics Data System (ADS)

    Hugenholtz, C. A. J.; Donné, A. J. H.; Elzendoorn, B. S. Q.; van Gorkom, J. C.; Kooijman, W.; van der Laan, H. A.; van de Pol, M. J.; Putter, A. J.; van Ramele, H. J. F.; Smit, D.; de Vries, P. C.; Wijnoltz, F.; Pysik, W.; Waidmann, G.; Ermak, G. P.

    1999-01-01

    Progress in fusion research shows an increasing demand for diagnostics with high temporal and spatial resolution in order to study small and fast phenomena in fusion plasmas. Therefore, a new ten-channel pulsed radar reflectometer is under development for the TEXTOR Tokamak, to measure electron density profiles in the range of 0.4-4×1019m-3 at a high repetition rate of 2 MHz. An additional feature of this diagnostic is the possibility to perform correlation measurements at 10 MHz repetition rate to investigate density fluctuations. The reflectometer will scan the plasma with 1-ns-long radar pulses in the 18-57 GHz range. In spite of the long flight time of the pulses of about 100 ns, the above mentioned high repetition rates could be achieved by time multiplexing the generation and reception of the radar pulses. Temporal selection of the received pulses is performed by fast switching of the local oscillators inputs of the heterodyne receiver, to generate time windows in which the reception of the reflected pulses is expected. An embedded VME controller will manage the system and store the data with a speed of 20 Msamples/s, up to a maximum of 64 Mbyte data per plasma shot. In order to facilitate the handling of such a huge amount of data, an advanced data reduction scheme is being developed. Remote operation with a fast data link from FZ Jülich (Germany) to FOM Nieuwegein (The Netherlands) will be possible.

  15. 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.

  16. Nanosecond pulsed electric fields have differential effects on cells in the S-phase.

    PubMed

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

    2007-03-01

    Nanosecond pulsed electric fields (nsPEFs) are a type of nonthermal, nonionizing radiation that exhibit intense electric fields with high power, but low energy. NsPEFs extend conventional electroporation (EP) to affect intracellular structures and functions and depending on the intensity, can induce lethal and nonlethal cell signaling. In this study, HCT116 human colon carcinoma cells were synchronized to the S-phase or remained unsynchronized, exposed to electric fields of 60 kV/cm with either 60-ns or 300-ns durations, and analyzed for apoptosis and proliferative markers. Several nsPEF structural and functional targets were identified. Unlike unsynchronized cells, S-phase cells under limiting conditions exhibited greater membrane integrity and caspase activation and maintained cytoskeletal structure. Regardless of synchronization, cells exposed to nsPEFs under these conditions primarily survived, but exhibited some turnover and delayed proliferation in cell populations, as well as reversible increases in phosphatidylserine externalization, membrane integrity, and nuclei size. These results show that nsPEFs can act as a nonligand agonist to modulate plasma membrane (PM) and intracellular structures and functions, as well as differentially affect cells in the S-phase, but without effect on cell survival. Furthermore, nsPEF effects on the nucleus and cytoskeleton may provide synergistic therapeutic actions with other agents, such as ionizing radiation or chemotherapeutics that affect these same structures.

  17. 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.

  18. N-->S phosphoryl migration in phosphoryl glutathion.

    PubMed

    Yang, H J; Liu, J; Zhao, Y F

    1993-07-01

    It was found that in the case of N-(diisopropylphosphoryl) glutathion (reduced form), 2, N-->S phosphoryl migration took place, but not for N,N-bis(diisopropylphosphoryl) glutathion (oxidized form) or N-diisopropylphosphoryl cysteine. These results were deduced by 31P-NMR tracing experiments. It was shown that phosphoryl migration was catalyzed by an intramolecular carboxyl group, and a mechanism involving a mixed carboxyl-phosphoric anhydride was proposed. A competitive reaction between the amino and thiol group toward diisopropyl phosphite indicated that the phospho-thiol derived from N-(diisopropylphosphoryl) glutathion (reduced form), 2, did not result from direct phosphorylation of the thiol group. N,S-Bis(diisopropylphosphoryl) glutathion provides an authentic sample to confirm the migrated phosphoryl thiol product.

  19. 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 %.

  20. 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

  1. 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.

  2. 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.

  3. 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.

  4. 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

  5. X-ray emission from a nanosecond-pulse discharge in an inhomogeneous electric field at atmospheric pressure

    NASA Astrophysics Data System (ADS)

    Zhang, Cheng; Shao, Tao; Tarasenko, Victor; Ma, Hao; Ren, Chengyan; Kostyrya, Igor D.; Zhang, Dongdong; Yan, Ping

    2012-12-01

    This paper describes experimental studies of the dependence of the X-ray intensity on the anode material in nanosecond high-voltage discharges. The discharges were generated by two nanosecond-pulse generators in atmospheric air with a highly inhomogeneous electric field by a tube-plate gap. The output pulse of the first generator (repetitive pulse generator) has a rise time of about 15 ns and a full width at half maximum of 30-40 ns. The output of the second generator (single pulse generator) has a rise time of about 0.3 ns and a full width at half maximum of 1 ns. The electrical characteristics and the X-ray emission of nanosecond-pulse discharge in atmospheric air are studied by the measurement of voltage-current waveforms, discharge images, X-ray count and dose. Our experimental results showed that the anode material rarely affects electrical characteristics, but it can significantly affect the X-ray density. Comparing the density of X-rays, it was shown that the highest x-rays density occurred in the diffuse discharge in repetitive pulse mode, then the spark discharge with a small air gap, and then the corona discharge with a large air gap, in which the X-ray density was the lowest. Therefore, it could be confirmed that the bremsstrahlung at the anode contributes to the X-ray emission from nanosecond-pulse discharges.

  6. X-ray emission from a nanosecond-pulse discharge in an inhomogeneous electric field at atmospheric pressure

    SciTech Connect

    Zhang Cheng; Shao Tao; Ren Chengyan; Zhang Dongdong; Tarasenko, Victor; Kostyrya, Igor D.; Ma Hao; Yan Ping

    2012-12-15

    This paper describes experimental studies of the dependence of the X-ray intensity on the anode material in nanosecond high-voltage discharges. The discharges were generated by two nanosecond-pulse generators in atmospheric air with a highly inhomogeneous electric field by a tube-plate gap. The output pulse of the first generator (repetitive pulse generator) has a rise time of about 15 ns and a full width at half maximum of 30-40 ns. The output of the second generator (single pulse generator) has a rise time of about 0.3 ns and a full width at half maximum of 1 ns. The electrical characteristics and the X-ray emission of nanosecond-pulse discharge in atmospheric air are studied by the measurement of voltage-current waveforms, discharge images, X-ray count and dose. Our experimental results showed that the anode material rarely affects electrical characteristics, but it can significantly affect the X-ray density. Comparing the density of X-rays, it was shown that the highest x-rays density occurred in the diffuse discharge in repetitive pulse mode, then the spark discharge with a small air gap, and then the corona discharge with a large air gap, in which the X-ray density was the lowest. Therefore, it could be confirmed that the bremsstrahlung at the anode contributes to the X-ray emission from nanosecond-pulse discharges.

  7. 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.

  8. 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.

  9. CONTROL OF LASER RADIATION PARAMETERS: Generation of diffraction-limited nanosecond and subnanosecond pulses in a XeCl laser

    NASA Astrophysics Data System (ADS)

    Panchenko, Yu N.; Losev, V. F.; Dudarev, V. V.

    2008-04-01

    The generation of nanosecond and subnanosecond pulses in a XeCl laser is studied. The short radiation pulses are generated in a resonator with a SBS mirror. By focusing laser radiation inside and on the surface of a nonlinear medium, it is possible to generate pulses of duration 3 ns and 150 ps, respectively. The laser beams obtained in this way contain more than 70% of energy within the diffraction angle and have the signal-to-noise ration exceeding 104.

  10. 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.

  11. Pulsed Optics

    NASA Astrophysics Data System (ADS)

    Hirlimann, C.

    Optics is the field of physics which comprises knowledge on the interaction between light and matter. When the superposition principle can be applied to electromagnetic waves or when the properties of matter do not depend on the intensity of light, one speaks of linear optics. This situation occurs with regular light sources such as light bulbs, low-intensity light-emitting diodes and the sun. With such low-intensity sources the reaction of matter to light can be characterized by a set of parameters such as the index of refraction, the absorption and reflection coefficients and the orientation of the medium with respect to the polarization of the light. These parameters depend only on the nature of the medium. The situation changed dramatically after the development of lasers in the early sixties, which allowed the generation of light intensities larger than a kilowatt per square centimeter. Actual large-scale short-pulse lasers can generate peak powers in the petawatt regime. In that large-intensity regime the optical parameters of a material become functions of the intensity of the impinging light. In 1818 Fresnel wrote a letter to the French Academy of Sciences in which he noted that the proportionality between the vibration of the light and the subsequent vibration of matter was only true because no high intensities were available. The intensity dependence of the material response is what usually defines nonlinear optics.

  12. 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.

  13. 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.

  14. 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.

  15. Suppressing spectral diffusion of emitted photons with optical pulses

    SciTech Connect

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

    2016-01-22

    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. As a result, 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.

  16. Pulsed blue laser source based on frequency quadrupling of a thulium fiber laser

    NASA Astrophysics Data System (ADS)

    Honea, Eric; Savage-Leuchs, Matthias; Bowers, Mark S.; Yilmaz, Tolga; Mead, Roy

    2013-03-01

    We describe a pulsed blue (485 nm) laser source based on frequency quadrupling a pulsed Tm fiber laser. Up to 1.2 W at 485 nm was generated with an M2 of 1.3. At 10 kHz pulse repetition frequency, the output pulse at 485 nm was 65 ns FWHM resulting in an estimated peak power of 1.8 kW. We anticipate further improvements in power scaling with higher power Tm fiber lasers and improved conversion efficiency to the blue with optimized AR coatings and nonlinear optical crystals.

  17. 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.

  18. Optimisation of thulium fibre laser parameters with generation of pulses by pump modulation

    SciTech Connect

    Obronov, I V; Larin, S V; Sypin, V E

    2015-07-31

    The formation of relaxation pulses of a thulium fibre laser (λ = 1.9 μm) by modulating the power of a pump erbium fibre laser (λ = 1.55 μm) is studied. A theoretical model is developed to find the dependences of pulse duration and peak power on different cavity parameters. The optimal cavity parameters for achieving the minimal pulse duration are determined. The results are confirmed by experimental development of a laser emitting pulses with a duration shorter than 10 ns, a peak power of 1.8 kW and a repetition rate of 50 kHz. (control of radiation parameters)

  19. Sub-10 ns single-shot dynamic recording in holographic polymeric medium by nonlinear absorption using excited state absorption process

    NASA Astrophysics Data System (ADS)

    Kamada, Kenji; Satoh, Kazuyuki; Tanaka, Yoshito

    2016-09-01

    Optical recording by a single shot of an 8 ns laser pulse in a dye-doped holographic polymeric medium was demonstrated with a peak power as low as 71 W at a wavelength of 402 nm. Nonlinear absorption triggered by two-photon absorption and enhanced by the succeeding process allows high-speed recording corresponding to 125 Mbps (3.4 times the recording speed of a Blu-ray Disc). The preformed holographic grating in the medium enhanced the readout signal through diffraction, resulting in a signal-to-noise ratio of about 15 dB. The recording capacity was estimated at ca. 80 GB/side for 100 µm/side by recording 20 layers, but that of over TB/side class would be possible for optical optimization. Theoretically, it can be improved to 10 TB/side for 800 µm/side by recording 400 layers.

  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. 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

  2. Effect of pulse duration on the acoustic frequency emissions during the laser-induced breakdown of atmospheric air.

    PubMed

    Manikanta, E; Vinoth Kumar, L; Venkateshwarlu, P; Leela, Ch; Kiran, P Prem

    2016-01-20

    Acoustic shock waves (ASWs) in the frequency range of 30-120 kHz generated during laser-induced breakdown (LIB) of ambient air using 7 ns and 30 ps pulse durations are studied. The specific frequency range and peak amplitudes are observed to be different for nanosecond (ns) and picosecond (ps) LIB. The ASW frequencies for ps-LIB lie between 90 and 120 kHz with one dominant peak, whereas for ns-LIB, two dominant peaks with frequencies in the 30-70 kHz and 80-120 kHz range are observed. These frequencies are observed to be laser pulse intensity dependent. With increasing energy of ns laser pulses, acoustic frequencies move toward the audible frequency range. The variation in the acoustic parameters, such as peak-to-peak pressures, signal energy, frequency and acoustic pulse widths as a function of laser energy, for two different pulse durations are presented in detail and compared. The acoustic emissions are observed to be higher for ns-LIB than ps-LIB, indicating higher conversion efficiency of optical energy into mechanical energy.

  3. 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

  4. 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.

  5. 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

  6. A novel miniaturized passively Q-switched pulse-burst laser for engine ignition.

    PubMed

    Ma, Yufei; Li, Xudong; Yu, Xin; Fan, Rongwei; Yan, Renpeng; Peng, Jiangbo; Xu, Xinrui; Sun, Rui; Chen, Deying

    2014-10-06

    A novel miniaturized Cr⁴⁺:YAG passively Q-switched Nd:YAG pulse-burst laser under 808 nm diode-laser pulse-pumping was demonstrated for the purpose of laser-induced plasma ignition, in which pulse-burst mode can realize both high repetition rate and high pulse energy simultaneously in a short period. Side-pumping configuration and two different types of laser cavities were employed. The pumping pulse width was constant at 250 μs. For the plane-plane cavity, the output beam profile was flat-top Gaussian and the measured M² value was 4.1 at the maximum incident pump energy of 600 mJ. The pulse-burst laser contained a maximum of 8 pulses, 7 pulses and 6 pulses for pulse-burst repetition rate of 10 Hz, 50 Hz and 100 Hz, respectively. The energy obtained was 15.5 mJ, 14.9 mJ and 13.9 mJ per pulse for pulse-burst repetition rate of 10 Hz, 50 Hz and 100 Hz, respectively. The maximum repetition rate of laser pulses in pulse-burst was 34.6 kHz for 8 pulses at the incident pump energy of 600 mJ and the single pulse width was 13.3 ns. The thermal lensing effect of Nd:YAG rod was investigated, and an plane-convex cavity was adopted to compensate the thermal lensing effect of Nd:YAG rod and improve the mode matching. For the plane-convex cavity, the output beam profile was quasi-Gaussian and the measured M2 value was 2.2 at the incident pump energy of 600 mJ. The output energy was 10.6 mJ per pulse for pulse-burst repetition rate of 100 Hz. The maximum repetition rate of laser pulses in pulse-burst was 27.4 kHz for 6 pulses at the incident pump energy of 600 mJ and the single pulse width was 14.2 ns. The experimental results showed that this pulse-burst laser can produce high repetition rate (>20 kHz) and high pulse energy (>10 mJ) simultaneously in a short period for both two different cavities.

  7. 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

  8. 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.

  9. Characterization of Bombyx mori parvo-like virus non-structural protein NS1.

    PubMed

    Li, Guohui; Sun, Chen; Zhang, Junhong; He, Yuanqing; Chen, Huiqing; Kong, Jie; Huang, Guoping; Chen, Keping; Yao, Qin

    2009-12-01

    NS1 gene of Bombyx mori parvo-like virus (China Zhenjiang isolate, BmDNV-Z) codes a predicted 316-amino acid protein, but its function remains unknown. Results of the current study showed that purified recombinant 6 x His-NS1 protein possesses ATP binding, ATPase, DNA binding, and helicase activities. Only one protein was captured in infected Bombyx mori midgut cells against NS1 target protein by employing co-immunoprecipitation, which was identified to be a viral protein by mass spectrometry. The NS1-interacting protein is encoded by BmDNV-Z ORF4 and its molecular is about 100 kD. Analysis of His pull-down confirmed that binding of identified viral protein to purified recombinant 6 x His-NS1 protein in vitro. Taken together, our results indicated that BmDNV-Z NS1 was a multifunctional protein, which may be involved with virus replication.

  10. Inhibition of Hepatitis C Virus NS5B Polymerase by S-Trityl-L-Cysteine Derivatives

    PubMed Central

    Nichols, Daniel B.; Fournet, Guy; Gurukumar, K. R.; Basu, Amartya; Lee, Jin-Ching; Sakamoto, Naoya; Kozielski, Frank; Musmuca, Ira; Joseph, Benoît; Ragno, Rino; Kaushik-Basu, Neerja

    2012-01-01

    Structure-based studies led to the identification of a constrained derivative of S-trityl-L-cysteine (STLC) scaffold as a candidate inhibitor of hepatitis C virus (HCV) NS5B polymerase. A panel of STLC derivatives were synthesized and investigated for their activity against HCV NS5B. Three STLC derivatives, 9, F-3070, and F-3065, were identified as modest HCV NS5B inhibitors with IC50 values between 22.3 to 39.7 μM. F-3070 and F-3065 displayed potent inhibition of intracellular NS5B activity in the BHK-NS5B-FRLuc reporter and also inhibited HCV RNA replication in the Huh7/Rep-Feo1b reporter system. Binding mode investigations suggested that the STLC scaffold can be used to develop new NS5B inhibitors by further chemical modification at one of the trityl phenyl group. PMID:22280819

  11. Intracellular degradation and localization of NS1 of TBEV affects its protective properties.

    PubMed

    Kuzmenko, Yulia; Starodubova, Elizaveta; Shevtsova, Anastasia; Chernokhaeva, Lubov; Latanova, Anastasia; Preobrazhenskaia, Olga; Timofeev, Andrey; Karganova, Galina; Karpov, Vadim

    2016-12-30

    Currently many DNA vaccines against infectious diseases are in clinical trials however their efficacy is needed to be improved. Potency of DNA immunogen can be optimized by targeting technologies. In a current study to increase the efficacy of NS1encoded by plasmid the proteasome targeting was applied. NS1 variants with or without translocation sequence and with signal of proteasomal degradation of ornithine decarboxylase were tested for expression, localization, protein turnover, proteasomal degradation and protection properties. Deletion of translocation signal abrogated presentation of NS1 on the cell surface and increased proteasomal processing of NS1. Fusion with ODC signal led to increase of protein turnover and proteasome degradation rate of NS1. Immunization with NS1 variants with increased proteasome processing protected mice from viral challenge only partially, however, the survival time of infected mice was prolonged in these groups. This data can give a presupposition for formulation of specific immune therapy for infected individuals.

  12. Nanosecond Pulsed Electric Fields Enhance the Anti-tumour Effects of the mTOR Inhibitor Everolimus against Melanoma

    NASA Astrophysics Data System (ADS)

    Dai, Jie; Wu, Shan; Kong, Yan; Chi, Zhihong; Si, Lu; Sheng, Xinan; Cui, Chuanliang; Fang, Jing; Zhang, Jue; Guo, Jun

    2017-01-01

    The PI3K/mTOR/AKT pathway is activated in most melanomas, but mTOR inhibitors used singly have limited activity against advanced melanomas. The application of nanosecond pulsed electric fields (nsPEFs) is a promising cancer therapy approach. In this study, we evaluated the synergistic anti-tumour efficacy of the mTOR inhibitor everolimus in conjunction with nsPEFs against melanoma. The combined treatment of nsPEFs and everolimus gradually decreased cell growth concurrent with nsPEF intensity. nsPEFs alone or combined with everolimus could promote melanoma cell apoptosis, accompanied with a loss in cellular mitochondrial membrane potential and an increase in Ca2+ levels. In vivo experiments showed that a combination of the mTOR inhibitor everolimus and nsPEFs improved the inhibitory effect, and all skin lesions caused by nsPEFs healed in 1 week without any observed adverse effect. Combination treatment induced caspase-dependent apoptosis through the upregulation of the pro-apoptotic factor Bax and downregulation of the anti-apoptotic factor Bcl-2. Everolimus and nsPEFs synergistically inhibited angiogenesis by decreasing the expression of vascular endothelial growth factor (VEGF), VEGF receptor (VEGFR), and CD34. Our findings indicate that nsPEFs in combination with an mTOR inhibitor can be used as a potential treatment approach for advanced melanoma.

  13. Nanosecond Pulsed Electric Fields Enhance the Anti-tumour Effects of the mTOR Inhibitor Everolimus against Melanoma

    PubMed Central

    Dai, Jie; Wu, Shan; Kong, Yan; Chi, Zhihong; Si, Lu; Sheng, Xinan; Cui, Chuanliang; Fang, Jing; Zhang, Jue; Guo, Jun

    2017-01-01

    The PI3K/mTOR/AKT pathway is activated in most melanomas, but mTOR inhibitors used singly have limited activity against advanced melanomas. The application of nanosecond pulsed electric fields (nsPEFs) is a promising cancer therapy approach. In this study, we evaluated the synergistic anti-tumour efficacy of the mTOR inhibitor everolimus in conjunction with nsPEFs against melanoma. The combined treatment of nsPEFs and everolimus gradually decreased cell growth concurrent with nsPEF intensity. nsPEFs alone or combined with everolimus could promote melanoma cell apoptosis, accompanied with a loss in cellular mitochondrial membrane potential and an increase in Ca2+ levels. In vivo experiments showed that a combination of the mTOR inhibitor everolimus and nsPEFs improved the inhibitory effect, and all skin lesions caused by nsPEFs healed in 1 week without any observed adverse effect. Combination treatment induced caspase-dependent apoptosis through the upregulation of the pro-apoptotic factor Bax and downregulation of the anti-apoptotic factor Bcl-2. Everolimus and nsPEFs synergistically inhibited angiogenesis by decreasing the expression of vascular endothelial growth factor (VEGF), VEGF receptor (VEGFR), and CD34. Our findings indicate that nsPEFs in combination with an mTOR inhibitor can be used as a potential treatment approach for advanced melanoma. PMID:28054548

  14. 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.

  15. Using an active temporal compensating system to achieve the super-Gaussian pulses in high-power lasers

    NASA Astrophysics Data System (ADS)

    Wang, Yulei; Liu, Rui; Yuan, Hang; Li, Sensen; Liu, Zhaohong; Zhu, Xuehua; He, Weiming; Lv, Zhiwei

    2015-08-01

    In high-power solid-state laser, initiative pulse shaping can help improve the output laser's performance. The evaluation for output laser pulse is also incomplete. In this paper, we propose a method of initiative pulse shaping by using arbitrary waveform generator (AWG), and establish a relatively complete evaluation system for the output pulses shape simultaneously. It achieves the super-Gaussian pulse output with high SNR (signal-to-noise ratio). As a consequence, a square laser pulse with pulse adjustable width ~5ns, rising time 197ps is obtained. The power imbalance of the output square pulse is 3.72%. The similarity between the eight-order super-Gaussian pulse and the one we get from experiment reached 99%.

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

    PubMed Central

    Higashi, Koichi; Tobe, Toru; Kanai, Akinori; Uyar, Ebru; Ishikawa, Shu; Suzuki, Yutaka; Ogasawara, Naotake; Kurokawa, Ken; Oshima, Taku

    2016-01-01

    Bacteria can acquire new traits through horizontal gene transfer. Inappropriate expression of transferred genes, however, can disrupt the physiology of the host bacteria. To reduce this risk, Escherichia coli expresses the nucleoid-associated protein, H-NS, which preferentially binds to horizontally transferred genes to control their expression. Once expression is optimized, the horizontally transferred genes may actually contribute to E. coli survival in new habitats. Therefore, we investigated whether and how H-NS contributes to this optimization process. A comparison of H-NS binding profiles on common chromosomal segments of three E. coli strains belonging to different phylogenetic groups indicated that the positions of H-NS-bound regions have been conserved in E. coli strains. The sequences of the H-NS-bound regions appear to have diverged more so than H-NS-unbound regions only when H-NS-bound regions are located upstream or in coding regions of genes. Because these regions generally contain regulatory elements for gene expression, sequence divergence in these regions may be associated with alteration of gene expression. Indeed, nucleotide substitutions in H-NS-bound regions of the ybdO promoter and coding regions have diversified the potential for H-NS-independent negative regulation among E. coli strains. The ybdO expression in these strains was still negatively regulated by H-NS, which reduced the effect of H-NS-independent regulation under normal growth conditions. Hence, we propose that, during E. coli evolution, the conservation of H-NS binding sites resulted in the diversification of the regulation of horizontally transferred genes, which may have facilitated E. coli adaptation to new ecological niches. PMID:26789284

  18. Molecular dynamics simulations of Zika virus NS3 helicase: Insights into RNA binding site activity.

    PubMed

    Mottin, Melina; Braga, Rodolpho C; da Silva, Roosevelt A; Silva, Joao H Martins da; Perryman, Alexander L; Ekins, Sean; Andrade, Carolina Horta

    2017-03-21

    America is still suffering with the outbreak of Zika virus (ZIKV) infection. Congenital ZIKV syndrome has already caused a public health emergency of international concern. However, there are still no vaccines to prevent or drugs to treat the infection caused by ZIKV. The ZIKV NS3 helicase (NS3h) protein is a promising target for drug discovery due to its essential role in viral genome replication. NS3h unwinds the viral RNA to enable the replication of the viral genome by the NS5 protein. NS3h contains two important binding sites: the NTPase binding site and the RNA binding site. Here, we used molecular dynamics (MD) simulations to study the molecular behavior of ZIKV NS3h in the presence and absence of ssRNA and the potential implications for NS3h activity and inhibition. Although there is conformational variability and poor electron densities of the RNA binding loop in various apo flaviviruses NS3h crystallographic structures, the MD trajectories of NS3h-ssRNA demonstrated that the RNA binding loop becomes more stable when NS3h is occupied by RNA. Our results suggest that the presence of RNA generates important interactions with the RNA binding loop, and these interactions stabilize the loop sufficiently that it remains in a closed conformation. This closed conformation likely keeps the ssRNA bound to the protein for a sufficient duration to enable the unwinding/replication activities of NS3h to occur. In addition, conformational changes of this RNA binding loop can change the nature and location of the optimal ligand binding site, according to ligand binding site prediction results. These are important findings to help guide the design and discovery of new inhibitors of NS3h as promising compounds to treat the ZIKV infection.

  19. 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

  20. 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.

  1. Long pulse production from short pulses

    DOEpatents

    Toeppen, John S.

    1994-01-01

    A method of producing a long output pulse (SA) from a short pump pulse (P), using an elongated amplified fiber (11) having a doped core (12) that provides an amplifying medium for light of one color when driven into an excited state by light of a shorter wavelength and a surrounding cladding 13. A seed beam (S) of the longer wavelength is injected into the core (12) at one end of the fiber (11) and a pump pulse (P) of the shorter wavelength is injected into the cladding (13) at the other end of the fiber (11). The counter-propagating seed beam (S) and pump pulse (P) will produce an amplified output pulse (SA) having a time duration equal to twice the transit time of the pump pulse (P) through the fiber (11) plus the length of the pump pulse (P).

  2. Pulse-modulated light source for psychometric and vision experiments.

    PubMed

    Scholfield, C N; Murdock, M

    1987-03-01

    Light-emitting diodes (LED) of various colours were used to produce accurately controllable light sources. Variable light intensity was obtained by applying 800-ns current pulses to the LEDs at frequencies 1-1000 kHz using a single potentiometer. These current pulses were generated from an oscillator which was voltage-controlled from a potentiometer and an antilogarithmic amplifier. Its output was gated to produce an optional flicker of 1-100 Hz. The light intensity was indicated by a frequency meter connected to the oscillator. The reading of this was found to linearly indicate light intensity.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. Microsecond-scale electric field pulses in cloud lightning discharges

    NASA Technical Reports Server (NTRS)

    Villanueva, Y.; Rakov, V. A.; Uman, M. A.; Brook, M.

    1994-01-01

    From wideband electric field records acquired using a 12-bit digitizing system with a 500-ns sampling interval, microsecond-scale pulses in different stages of cloud flashes in Florida and New Mexico are analyzed. Pulse occurrence statistics and waveshape characteristics are presented. The larger pulses tend to occur early in the flash, confirming the results of Bils et al. (1988) and in contrast with the three-stage representation of cloud-discharge electric fields suggested by Kitagawa and Brook (1960). Possible explanations for the discrepancy are discussed. The tendency for the larger pulses to occur early in the cloud flash suggests that they are related to the initial in-cloud channel formation processes and contradicts the common view found in the atmospheric radio-noise literature that the main sources of VLF/LF electromagnetic radiation in cloud flashes are the K processes which occur in the final, or J type, part of the cloud discharge.

  10. 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.

  11. 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.

  12. 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.

  13. Broadband electrically detected magnetic resonance using adiabatic pulses

    NASA Astrophysics Data System (ADS)

    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).

  14. 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).

  15. Analysis on the characteristics of pulsed laser proximity fuze's echo

    NASA Astrophysics Data System (ADS)

    Wang, Kun; Chen, Huimin

    2011-06-01

    With the rapid development of semiconductor technology and laser technology, a kind of proximity fuze named pulsed laser proximity fuze has been applied. Compared with other fuzes, pulsed laser proximity fuze has high ranging precision and strong resistance to artificial active interference. It is an important development tendency of proximity fuze. The paper analyze the characteristic of target echo of laser signal, and then make theoretical analysis and calculation on the laser signal transmission in the smog. Firstly, use the pulse width of 10ns semiconductor laser fuze to do typical targets experiment, to get the echo information of target distance is 5m; then to do smog interference experiment, by comparing the pulse width amplitude and backscattering signal amplitude of laser fuze in simulation and experiment, analyzing the effect of anti-clutter, providing the evidence for the subsequent of circuit of signal amplification and processing.

  16. Effect of actin cytoskeleton disruption on electric pulse-induced apoptosis and electroporation in tumour cells.

    PubMed

    Xiao, Deyou; Tang, Liling; Zeng, Chao; Wang, Jianfei; Luo, Xiao; Yao, Chenguo; Sun, Caixin

    2011-02-01

    Electric pulses are known to affect the outer membrane and intracellular structures of tumour cells. By applying electrical pulses of 450 ns duration with electric field intensity of 8 kV/cm to HepG2 cells for 30 s, electric pulse-induced changes in the integrity of the plasma membrane, apoptosis, viability and mitochondrial transmembrane potential were investigated. Results demonstrated that electric pulses induced cell apoptosis and necrosis accompanied with the decrease of mitochondrial transmembrane potential and the formation of pores in the membrane. The role of cytoskeleton in cellular response to electric pulses was investigated. We found that the apoptotic and necrosis percentages of cells in response to electric pulses decreased after cytoskeletal disruption. The electroporation of cell was not affected by cytoskeletal disruption. The results suggest that the disruption of actin skeleton is positive in protecting cells from killing by electric pulses, and the skeleton is not involved in the electroporation directly.

  17. 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.

  18. Giant pulses of the Crab Nebula pulsar as an indicator of a strong electromagnetic wave

    NASA Astrophysics Data System (ADS)

    Popov, M. V.; Rudnitskii, A. G.; Soglasnov, V. A.

    2017-03-01

    The spectra and visibility functions of giant pulses of the Crab Nebula pulsar derived from VLBI observations carried out through the "RadioAstron" project in 2015 are analyzed. Parameters of the scattering of the pulses in the interstellar medium are measured, namely, the scattering time and decorrelation bandwidth. A comparative analysis of the shapes of the spectra and visibility functions of giant pulses obtained in real observations and via modeling of their scattering is carried out. The results suggest the presence of short bursts ( dt < 30 ns) in the structure of the giant pulses at 1668 MHz, whose brightness temperatures exceed 1038 K. These pulses propagate in the pulsar magnetosphere in a strong electromagneticwave regime, leading to the generation of additional radiation perpendicular to the direction of propagation of the giant pulses. This radiation may be associated with anomalous components of the mean pulse profile observed at frequencies above 4 GHz.

  19. 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.

  20. Expression of dengue virus NS3 protein in Drosophila alters its susceptibility to infection

    PubMed Central

    Querenet, Matthieu; Danjoy, Marie-Laure; Mollereau, Bertrand; Davoust, Nathalie

    2015-01-01

    We developed a Drosophila model in which the dengue virus NS3 protein is expressed in a tissue specific and inducible manner. Dengue virus NS3 is a multifunctional protein playing a major role during viral replication. Both protease and helicase domains of NS3 are interacting with human and insect host proteins including innate immune components of the host machinery. We characterized the NS3 transgenic flies showing that NS3 expression did not affect fly development. To further study the links between NS3 and the innate immune response, we challenge the flies with gram-positive and gram-negative bacteria. Interestingly, the Drosophila transgenic flies expressing NS3 were more susceptible to bacterial infections than control flies. However ubiquitous or immune-specific NS3 expression affected neither the life span nor the response to a non-infectious stress of the flies. In conclusion, we generated a new in vivo system to study the functional impact of DENV NS3 protein on the innate immune response. PMID:26267447

  1. Attenuation of equine influenza viruses through truncations of the NS1 protein.

    PubMed

    Quinlivan, Michelle; Zamarin, Dmitriy; García-Sastre, Adolfo; Cullinane, Ann; Chambers, Thomas; Palese, Peter

    2005-07-01

    Equine influenza is a common disease of the horse, causing significant morbidity worldwide. Here we describe the establishment of a plasmid-based reverse genetics system for equine influenza virus. Utilizing this system, we generated three mutant viruses encoding carboxy-terminally truncated NS1 proteins. We have previously shown that a recombinant human influenza virus lacking the NS1 gene (delNS1) could only replicate in interferon (IFN)-incompetent systems, suggesting that the NS1 protein is responsible for IFN antagonist activity. Contrary to previous findings with human influenza virus, we found that in the case of equine influenza virus, the length of the NS1 protein did not correlate with the level of attenuation of that virus. With equine influenza virus, the mutant virus with the shortest NS1 protein turned out to be the least attenuated. We speculate that the basis for attenuation of the equine NS1 mutant viruses generated is related to their level of NS1 protein expression. Our findings show that the recombinant mutant viruses are impaired in their ability to inhibit IFN production in vitro and they do not replicate as efficiently as the parental recombinant strain in embryonated hen eggs, in MDCK cells, or in vivo in a mouse model. Therefore, these attenuated mutant NS1 viruses may have potential as candidates for a live equine influenza vaccine.

  2. 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.

  3. 41 CFR 60-2.10 - General purpose and contents of affirmative action programs.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 41 Public Contracts and Property Management 1 2010-07-01 2010-07-01 true General purpose and 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...

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

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 41 Public Contracts and Property Management 1 2012-07-01 2009-07-01 true General purpose and 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...

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

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 41 Public Contracts and Property Management 1 2014-07-01 2014-07-01 false General purpose and contents of affirmative action programs. 60-2.10 Section 60-2.10 Public Contracts and Property Management... EMPLOYMENT OPPORTUNITY, DEPARTMENT OF LABOR 2-AFFIRMATIVE ACTION PROGRAMS Purpose and Contents of...

  6. 9 CFR 2.10 - Licensees whose licenses have been suspended or revoked.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Licensees whose licenses have been suspended or revoked. 2.10 Section 2.10 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION... have been suspended or revoked. (a) Any person whose license has been suspended for any reason...

  7. 41 CFR 102-2.10 - What is the FMR's purpose?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 41 Public Contracts and Property Management 3 2010-07-01 2010-07-01 false What is the FMR's purpose? 102-2.10 Section 102-2.10 Public Contracts and Property Management Federal Property Management Regulations System (Continued) FEDERAL MANAGEMENT REGULATION GENERAL 2-FEDERAL MANAGEMENT REGULATION...

  8. 41 CFR 102-2.10 - What is the FMR's purpose?

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 41 Public Contracts and Property Management 3 2011-01-01 2011-01-01 false What is the FMR's purpose? 102-2.10 Section 102-2.10 Public Contracts and Property Management Federal Property Management Regulations System (Continued) FEDERAL MANAGEMENT REGULATION GENERAL 2-FEDERAL MANAGEMENT REGULATION...

  9. 41 CFR 102-2.10 - What is the FMR's purpose?

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 41 Public Contracts and Property Management 3 2012-01-01 2012-01-01 false What is the FMR's purpose? 102-2.10 Section 102-2.10 Public Contracts and Property Management Federal Property Management Regulations System (Continued) FEDERAL MANAGEMENT REGULATION GENERAL 2-FEDERAL MANAGEMENT REGULATION...

  10. 41 CFR 102-2.10 - What is the FMR's purpose?

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 41 Public Contracts and Property Management 3 2013-07-01 2013-07-01 false What is the FMR's purpose? 102-2.10 Section 102-2.10 Public Contracts and Property Management Federal Property Management Regulations System (Continued) FEDERAL MANAGEMENT REGULATION GENERAL 2-FEDERAL MANAGEMENT REGULATION...

  11. Progress Towards Plasma Pulse Compression of High Energy, Long Pulse Laser Beams

    SciTech Connect

    Kirkwood, R K; Ping, Y; Rygg, R; Wilks, S; Meezan, N; Niemann, C; Landen, O; Fisch, N; Malkin, V; Valeo, E; Wurtele, J

    2008-06-19

    Compression of laser pulses to < {approx} 1-10 ps duration using stimulated Raman scattering (SRS) in a plasma promises to provide unprecedented power and intensity for a variety of applications, by avoiding the limits to fluence and intensity that are needed to avoid damage to the solid state optics that are used in conventional approaches. In particular, the ability to compress pump beam pulses of {approx} ns duration will allow present facilities with 10's kJ to over a MJ of energy to produce ultra short pulses efficiently, advancing applications in; fusion by fast ignition, x-ray production of high energy density experiments, as well as laser driven particle accelerators. We will discuss a series of experiments to demonstrate the needed beam amplification rate, and focal spot quality in a < 3mm plasma with the properties needed for compression of these pulses (n{sub e} {approx} 10{sup 19}/cm{sup 3}, T{sub e} 200 to 300 eV) when the plasma is extended. The experiments use He plasmas produced with a 300 J, 1 ns, beam at the Jupiter Laser facility to amplify a counter-propagating, ultra-short pulse (USP) seed by a factor of 10x to 37x and study the dependence of the amplification, the associated non-linear wave response, and the resulting beam quality and energy, on the intensity of both seed and pump beam. In particular, a regime in which amplification of USP beams is achieved while maintaining a low angular divergence of the beam consistent with good focal spot quality will be discussed.

  12. 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.

  13. The Putative Metal Coordination Motif in the Endonuclease Domain of Human Parvovirus B19 NS1 Is Critical for NS1 Induced S Phase Arrest and DNA Damage

    PubMed Central

    Kivovich, Violetta; Gilbert, Leona; Vuento, Matti; Naides, Stanley J.

    2012-01-01

    The non-structural proteins (NS) of the parvovirus family are highly conserved multi-functional molecules that have been extensively characterized and shown to be integral to viral replication. Along with NTP-dependent helicase activity, these proteins carry within their sequences domains that allow them to bind DNA and act as nucleases in order to resolve the concatameric intermediates developed during viral replication. The parvovirus B19 NS1 protein contains sequence domains highly similar to those previously implicated in the above-described functions of NS proteins from adeno-associated virus (AAV), minute virus of mice (MVM) and other non-human parvoviruses. Previous studies have shown that transient transfection of B19 NS1 into human liver carcinoma (HepG2) cells initiates the intrinsic apoptotic cascade, ultimately resulting in cell death. In an effort to elucidate the mechanism of mammalian cell demise in the presence of B19 NS1, we undertook a mutagenesis analysis of the protein's endonuclease domain. Our studies have shown that, unlike wild-type NS1, which induces an accumulation of DNA damage, S phase arrest and apoptosis in HepG2 cells, disruptions in the metal coordination motif of the B19 NS1 protein reduce its ability to induce DNA damage and to trigger S phase arrest and subsequent apoptosis. These studies support our hypothesis that, in the absence of replicating B19 genomes, NS1-induced host cell DNA damage is responsible for apoptotic cell death observed in parvoviral infection of non-permissive mammalian cells. PMID:22211107

  14. The putative metal coordination motif in the endonuclease domain of human Parvovirus B19 NS1 is critical for NS1 induced S phase arrest and DNA damage.

    PubMed

    Kivovich, Violetta; Gilbert, Leona; Vuento, Matti; Naides, Stanley J

    2012-01-01

    The non-structural proteins (NS) of the parvovirus family are highly conserved multi-functional molecules that have been extensively characterized and shown to be integral to viral replication. Along with NTP-dependent helicase activity, these proteins carry within their sequences domains that allow them to bind DNA and act as nucleases in order to resolve the concatameric intermediates developed during viral replication. The parvovirus B19 NS1 protein contains sequence domains highly similar to those previously implicated in the above-described functions of NS proteins from adeno-associated virus (AAV), minute virus of mice (MVM) and other non-human parvoviruses. Previous studies have shown that transient transfection of B19 NS1 into human liver carcinoma (HepG2) cells initiates the intrinsic apoptotic cascade, ultimately resulting in cell death. In an effort to elucidate the mechanism of mammalian cell demise in the presence of B19 NS1, we undertook a mutagenesis analysis of the protein's endonuclease domain. Our studies have shown that, unlike wild-type NS1, which induces an accumulation of DNA damage, S phase arrest and apoptosis in HepG2 cells, disruptions in the metal coordination motif of the B19 NS1 protein reduce its ability to induce DNA damage and to trigger S phase arrest and subsequent apoptosis. These studies support our hypothesis that, in the absence of replicating B19 genomes, NS1-induced host cell DNA damage is responsible for apoptotic cell death observed in parvoviral infection of non-permissive mammalian cells.

  15. Design, structure-based focusing and in silico screening of combinatorial library of peptidomimetic inhibitors of Dengue virus NS2B-NS3 protease

    NASA Astrophysics Data System (ADS)

    Frecer, Vladimir; Miertus, Stanislav

    2010-03-01

    Serine protease activity of the NS3 protein of Dengue virus is an important target of antiviral agents that interfere with the viral polyprotein precursor processing catalyzed by the NS3 protease (NS3pro), which is important for the viral replication and maturation. Recent studies showed that substrate-based peptidomimetics carrying an electrophilic warhead inhibit the NS2B-NS3pro cofactor-protease complex with inhibition constants in the low micromolar concentration range when basic amino acid residues occupy P1 and P2 positions of the inhibitor, and an aldehyde warhead is attached to the P1. We have used computer-assisted combinatorial techniques to design, focus using the NS2B-NS3pro receptor 3D structure, and in silico screen a virtual library of more than 9,200 peptidomimetic analogs targeted around the template inhibitor Bz-Nle-Lys-Arg-Arg- H (Bz—benzoyl) that are composed mainly of unusual amino acid residues in all positions P1-P4. The most promising virtual hits were analyzed in terms of computed enzyme-inhibitor interactions and Adsorption, Distribution, Metabolism and Excretion (ADME) related physico-chemical properties. Our study can direct the interest of medicinal chemists working on a next generation of antiviral chemotherapeutics against the Dengue Fever towards the explored subset of the chemical space that is predicted to contain peptide aldehydes with NS3pro inhibition potencies in nanomolar range which display ADME-related properties comparable to the training set inhibitors.

  16. Design, structure-based focusing and in silico screening of combinatorial library of peptidomimetic inhibitors of Dengue virus NS2B-NS3 protease.

    PubMed

    Frecer, Vladimir; Miertus, Stanislav

    2010-03-01

    Serine protease activity of the NS3 protein of Dengue virus is an important target of antiviral agents that interfere with the viral polyprotein precursor processing catalyzed by the NS3 protease (NS3pro), which is important for the viral replication and maturation. Recent studies showed that substrate-based peptidomimetics carrying an electrophilic warhead inhibit the NS2B-NS3pro cofactor-protease complex with inhibition constants in the low micromolar concentration range when basic amino acid residues occupy P(1) and P(2) positions of the inhibitor, and an aldehyde warhead is attached to the P(1). We have used computer-assisted combinatorial techniques to design, focus using the NS2B-NS3pro receptor 3D structure, and in silico screen a virtual library of more than 9,200 peptidomimetic analogs targeted around the template inhibitor Bz-Nle-Lys-Arg-Arg-H (Bz-benzoyl) that are composed mainly of unusual amino acid residues in all positions P(1)-P(4). The most promising virtual hits were analyzed in terms of computed enzyme-inhibitor interactions and Adsorption, Distribution, Metabolism and Excretion (ADME) related physico-chemical properties. Our study can direct the interest of medicinal chemists working on a next generation of antiviral chemotherapeutics against the Dengue Fever towards the explored subset of the chemical space that is predicted to contain peptide aldehydes with NS3pro inhibition potencies in nanomolar range which display ADME-related properties comparable to the training set inhibitors.

  17. 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.

  18. 10-J long-pulse electric-discharge XeCl laser

    NASA Astrophysics Data System (ADS)

    Losev, Valery F.; Konovalov, Ivan; Liu, Jingru; Panchenko, Yury

    2003-11-01

    An X-ray preionized XeCl laser with a large aperture (9x7 cm) is described. Laser operates at Ne-Xe-HCl mixture with pressure up to 4 atm. Paper-oil pulse forming lines and rail-gap switch for discharge pump was used. 10 J output with optical pulse duration up to 300 ns (FWHM) have been extracted from active volume 5.4 l with an electric efficiency 1.2%.

  19. Optical gain in Si/SiO2 lattice: Experimental evidence with nanosecond pulses

    NASA Astrophysics Data System (ADS)

    Khriachtchev, Leonid; Räsänen, Markku; Novikov, Sergei; Sinkkonen, Juha

    2001-08-01

    Experimental evidence of population inversion and amplified spontaneous emission was found for Si nanocrystallites embedded in SiO2 surrounding under pumping with 5 ns light pulses at 380, 400, and 500 nm. As an important property, our experiments show a short lifetime of the population inversion allowing a generation of short (a few nanosecond) amplified light pulses in the Si/SiO2 lattice. The estimate for optical gain in the present samples is 6 cm-1 at 720 nm.

  20. 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.

  1. 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.

  2. Effect of CO2 pulsed laser irradiation on improving the biocompatibility of a polyethersulfone film

    NASA Astrophysics Data System (ADS)

    Jelvani, S.; Pazokian, H.; Moradi Farisar, S.

    2013-02-01

    In this paper a 200 ns pulsed TEA CO2 laser is used for treatment of polyethersulfone (PES) films surface. The laser induced structures and chemical compositions on the surface upon irradiation are studied. The hydrophilicity and biocompatibility of the irradiated surfaces are examined by contact angle and platelet adhesion measurements, respectively. The optimum number of pulses and fluence for improving the surface biocompatibility are found.

  3. 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.

  4. Compression of pulses during their amplification in the field of a focused counterpropagating pump pulse of the same frequency and width in media with electrostriction nonlinearity

    SciTech Connect

    Dement'ev, Aleksandr S; Demin, I; Murauskas, E; Slavinskis, S

    2011-02-28

    Efficient compression of focused {approx}0.9-ns pulses of a miniature Nd:YAG laser to less than 60 ps is experimentally obtained at their interaction with counterpropagating pulses of the same carrier frequency and width in CCl{sub 4}. In this case, electrostriction interaction (amplification) begins not from the level of spontaneous-scattering noise; therefore, the counterpropagating pulses can be compressed at pump pulse energies below the stimulated Brillouin scattering (SBS) threshold energies. When counterpropagating seed pulses are used, the energy and temporal stability of compressed pulses are several times higher, and their time jitter is smaller than that for SBS compression from the level of spontaneous-scattering noise. (nonlinear optical phenomena)

  5. 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.

  6. 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.

  7. Extended substrate specificity and first potent irreversible inhibitor/activity-based probe design for Zika virus NS2B-NS3 protease.

    PubMed

    Rut, Wioletta; Zhang, Linlin; Kasperkiewicz, Paulina; Poreba, Marcin; Hilgenfeld, Rolf; Drąg, Marcin

    2017-03-01

    Zika virus is spread by Aedes mosquitoes and is linked to acute neurological disorders, especially to microcephaly in newborn children and Guillan-Barré Syndrome. The NS2B-NS3 protease of this virus is responsible for polyprotein processing and therefore considered an attractive drug target. In this study, we have used the Hybrid Combinatorial Substrate Library (HyCoSuL) approach to determine the substrate specificity of ZIKV NS2B-NS3 protease in the P4-P1 positions using natural and a large spectrum of unnatural amino acids. Obtained data demonstrate a high level of specificity of the S3-S1 subsites, especially for basic amino acids. However, the S4 site exhibits a very broad preference toward natural and unnatural amino acids with selected D-amino acids being favored over L enantiomers. This information was used for the design of a very potent phosphonate inhibitor/activity-based probe of ZIKV NS2B-NS3 protease.

  8. Laser-induced retinal damage threshold for repetitive-pulse exposure to 100-microsecs pulses

    DTIC Science & Technology

    2014-10-07

    exposure duration.1 The primary retinal damage mechanism for exposure to a single pulse in the range of 10 ns to 10 μs duration is micro cavitation , or...thermal denaturation injury mechanism dominates for PRF > ∼1000 Hz. At 1000 Hz, thermal denaturation occurs at near the same level that micro cavitation ...with the observation of micro cavitation for exposure durations < ∼50 μs, while for expo sures >100 to 200 μs, cell death occurs at radiant exposures

  9. Development of a pulse height analyzer

    NASA Astrophysics Data System (ADS)

    Moreira, E. S.

    The development of a Pulse Height Analyzer is described. This equipment is essential to analize data coming from detectors producing information codified in pulse amplitudes. The system developed consists of a Signal Input Module connected to a Controller Module based on a 8085A microprocessor capable of memorizing pulses up to 1 uS in 256 channels with a resolution better than 20 mV. A Communication Module with a serial interface is used for data transfer to a host computer using RS232c protocol. The Monitoring and Operation Module consists of a hexadecimal Keybord, a 6 digit 7-segment display and a XY analog output enabling real time visualization of data on a XY monitor. The hardware and the software designed for this low cost system were optimized to obtain a typical dead time of approximately 100 uS. This device was used to acquire curves at the Small Angle X-ray Scattering Laboratory in this department. The appraratus performance was tested by comparing its data with a Northern Pulse Height Analizer model NS633 output, with favorable results.

  10. Discovery of New Scaffolds for Rational Design of HCV NS5B Polymerase Inhibitors

    PubMed Central

    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

    2012-01-01

    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 (IC50 = 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 40–60% 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

  11. Novel ATP-Independent RNA Annealing Activity of the Dengue Virus NS3 Helicase

    PubMed Central

    Gebhard, Leopoldo G.; Kaufman, Sergio B.; Gamarnik, Andrea V.

    2012-01-01

    The flavivirus nonstructural protein 3 (NS3) bears multiple enzymatic activities and represents an attractive target for antiviral intervention. NS3 contains the viral serine protease at the N-terminus and ATPase, RTPase, and helicase activities at the C-terminus. These activities are essential for viral replication; however, the biological role of RNA remodeling by NS3 helicase during the viral life cycle is still unclear. Secondary and tertiary RNA structures present in the viral genome are crucial for viral replication. Here, we used the NS3 protein from dengue virus to investigate functions of NS3 associated to changes in RNA structures. Using different NS3 variants, we characterized a domain spanning residues 171 to 618 that displays ATPase and RNA unwinding activities similar to those observed for the full-length protein. Interestingly, we found that, besides the RNA unwinding activity, dengue virus NS3 greatly accelerates annealing of complementary RNA strands with viral or non-viral sequences. This new activity was found to be ATP-independent. It was determined that a mutated NS3 lacking ATPase activity retained full-RNA annealing activity. Using an ATP regeneration system and different ATP concentrations, we observed that NS3 establishes an ATP-dependent steady state between RNA unwinding and annealing, allowing modulation of the two opposing activities of this enzyme through ATP concentration. In addition, we observed that NS3 enhanced RNA-RNA interactions between molecules representing the ends of the viral genome that are known to be necessary for viral RNA synthesis. We propose that, according to the ATP availability, NS3 could function regulating the folding or unfolding of viral RNA structures. PMID:22558403

  12. Fiber laser pumped high power mid-infrared laser with picosecond pulse bunch output.

    PubMed

    Wei, Kaihua; Chen, Tao; Jiang, Peipei; Yang, Dingzhong; Wu, Bo; Shen, Yonghang

    2013-10-21

    We report a novel quasi-synchronously pumped PPMgLN-based high power mid-infrared (MIR) laser with picosecond pulse bunch output. The pump laser is a linearly polarized MOPA structured all fiberized Yb fiber laser with picosecond pulse bunch output. The output from a mode-locked seed fiber laser was directed to pass through a FBG reflector via a circulator to narrow the pulse duration from 800 ps to less than 50 ps and the spectral FWHM from 9 nm to 0.15 nm. The narrowed pulses were further directed to pass through a novel pulse multiplier through which each pulse was made to become a pulse bunch composing of 13 sub-pulses with pulse to pulse time interval of 1.26 ns. The pulses were then amplified via two stage Yb fiber amplifiers to obtain a linearly polarized high average power output up to 85 W, which were then directed to pass through an isolator and to pump a PPMgLN-based optical parametric oscillator via quasi-synchronization pump scheme for ps pulse bunch MIR output. High MIR output with average power up to 4 W was obtained at 3.45 micron showing the feasibility of such pump scheme for ps pulse bunch MIR output.

  13. Adrenal chromaffin cells do not swell when exposed to nanosecond electric pulses.

    PubMed

    Craviso, Gale L; Fisher, Christa; Chatterjee, Indira; Vernier, P Thomas

    2015-06-01

    High intensity, nanosecond duration electric pulses (NEPs) permeabilize plasma membranes causing osmotic cell swelling that can elicit a wide variety of cellular effects. This study examined the possibility that cell swelling is the mechanism by which 5 ns NEPs trigger the release of catecholamines from neuroendocrine adrenal chromaffin cells. Swelling was assessed by comparing measurements of cell area obtained from bright field images of the cells before and at 10s intervals following exposure of the cells to 5 ns pulses at a field intensity of 5-6 MV/m. The results indicated that chromaffin cells do not swell in response to a single pulse or a train of ten pulses delivered at repetition frequencies of 10 Hz and 1 kHz. Swelling was also not observed in response to a train of 50 pulses whereas Jurkat T lymphoblast cell area increased 15% on average under the same NEP exposure conditions. These results demonstrating that chromaffin cells do not undergo swelling when exposed to 5 ns NEPs have important implications regarding the mechanism by which these pulses stimulate the release of catecholamines from these cells, namely that catecholamine secretion is most likely not caused by cell swelling.

  14. Commercial counterboard for 10 ns software correlator for photon and fluorescence correlation spectroscopy

    NASA Astrophysics Data System (ADS)

    Molteni, Matteo; Ferri, Fabio

    2016-11-01

    A 10 ns time resolution, multi-tau software correlator, capable of computing simultaneous autocorrelation (A-A, B-B) and cross (A-B) correlation functions at count rates up to ˜10 MHz, with no data loss, has been developed in LabVIEW and C++ by using the National Instrument timer/counterboard (NI PCIe-6612) and a fast Personal Computer (PC) (Intel Core i7-4790 Processor 3.60 GHz ). The correlator works by using two algorithms: for large lag times (τ ≳ 1 μs), a classical time-mode scheme, based on the measure of the number of pulses per time interval, is used; differently, for τ ≲ 1 μs a photon-mode (PM) scheme is adopted and the correlation function is retrieved from the sequence of the photon arrival times. Single auto- and cross-correlation functions can be processed online in full real time up to count rates of ˜1.8 MHz and ˜1.2 MHz, respectively. Two autocorrelation (A-A, B-B) and a cross correlation (A-B) functions can be simultaneously processed in full real time only up to count rates of ˜750 kHz. At higher count rates, the online processing takes place in a delayed modality, but with no data loss. When tested with simulated correlation data and latex spheres solutions, 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.

  15. Commercial counterboard for 10 ns software correlator for photon and fluorescence correlation spectroscopy.

    PubMed

    Molteni, Matteo; Ferri, Fabio

    2016-11-01

    A 10 ns time resolution, multi-tau software correlator, capable of computing simultaneous autocorrelation (A-A, B-B) and cross (A-B) correlation functions at count rates up to ∼10 MHz, with no data loss, has been developed in LabVIEW and C++ by using the National Instrument timer/counterboard (NI PCIe-6612) and a fast Personal Computer (PC) (Intel Core i7-4790 Processor 3.60 GHz ). The correlator works by using two algorithms: for large lag times (τ ≳ 1 μs), a classical time-mode scheme, based on the measure of the number of pulses per time interval, is used; differently, for τ ≲ 1 μs a photon-mode (PM) scheme is adopted and the correlation function is retrieved from the sequence of the photon arrival times. Single auto- and cross-correlation functions can be processed online in full real time up to count rates of ∼1.8 MHz and ∼1.2 MHz, respectively. Two autocorrelation (A-A, B-B) and a cross correlation (A-B) functions can be simultaneously processed in full real time only up to count rates of ∼750 kHz. At higher count rates, the online processing takes place in a delayed modality, but with no data loss. When tested with simulated correlation data and latex spheres solutions, 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.

  16. Phase-locked MHz pulse selector for x-ray sources.

    PubMed

    Förster, Daniel F; Lindenau, Bernd; Leyendecker, Marko; Janssen, Franz; Winkler, Carsten; Schumann, Frank O; Kirschner, Jürgen; Holldack, Karsten; Föhlisch, Alexander

    2015-05-15

    Picosecond x-ray pulses are extracted with a phase-locked x-ray pulse selector at 1.25 MHz repetition rate from the pulse trains of the accelerator-driven multiuser x-ray source BESSY II preserving the peak brilliance at high pulse purity. The system consists of a specially designed in-vacuum chopper wheel rotating with ≈1  kHz angular frequency. The wheel is driven in an ultrahigh vacuum and is levitated on magnetic bearings being capable of withstanding high centrifugal forces. Pulses are picked by 1252 high-precision slits of 70 μm width on the outer rim of the wheel corresponding to a temporal opening window of the chopper of 70 ns. We demonstrate how the electronic phase stabilization of ±2  ns together with an arrival time jitter of the individual slits of the same order of magnitude allows us to pick short single bunch x-ray pulses out of a 200 ns ion clearing gap in a multibunch pulse train as emitted from a synchrotron facility at 1.25 MHz repetition rate with a pulse purity below the shot noise detection limit. The approach is applicable to any high-repetition pulsed radiation source, in particular in the x-ray spectral range up to 10 keV. The opening window in a real x-ray beamline, its stability, as well as the limits of mechanical pulse picking techniques in the MHz range are discussed.

  17. Emission spectra of YAG:Er3+ under pulse laser-thermal excitation

    NASA Astrophysics Data System (ADS)

    Marchenko, V. M.; Shakir, Yu. A.

    2016-12-01

    Spectra and kinetics of emission of YAG:0.5% Er3+ monocrystal in visible and NIR ranges were investigated under laser-thermal excitation by the pulses of CO2 laser of 100 ns duration at wavelength λ = 10,6 μμm. Kinetics of integral emission was interpreted.

  18. Synergistic hemolysins of coagulase-negative staphylococci (CoNS).

    PubMed

    Różalska, Małgorzata; Derczyńska, Anna; Maszewska, Agnieszka

    2015-01-01

    A total of 104 coagulase negative staphylococci, belonging to S. capitis, S. hominis, S. haemolyticus and S. warneri, originating from the collection of the Department of Pharmaceutical Microbiology (ZMF), Medical University of Lodz, Poland, were tested for their synergistic hemolytic activity. 83% of strains produced δ-hemolysin, however, the percentage of positive strains of S. haemolyticus, S. warneri, S. capitis and S. hominis was different - 98%, 78%, 75% and 68%, respectively. Highly pure hemolysins were obtained from culture supernatants by protein precipitation with ammonium sulphate (0-70% of saturation) and extraction by using a mixture of organic solvents. The purity and molecular mass of hemolysins was determined by TRIS/Tricine PAGE. All CoNS hemolysins were small peptides with a molar mass of about 3.5 kDa; they possessed cytotoxic activity against the line of human foreskin fibroblasts ATCC Hs27 and lysed red cells from different mammalian species, however, the highest activity was observed when guinea pig, dog and human red blood cells were used. The cytotoxic effect on fibroblasts occurred within 30 minutes. The S. cohnii ssp. urealyticus strain was used as a control. The antimicrobial activity was examined using hemolysins of S. capitis, S. hominis, S. cohnii ssp. cohnii and S. cohnii ssp. urealyticus. Hemolysins of the two S. cohnii subspecies did not demonstrate antimicrobial activity. Cytolysins of S. capitis and S. hominis had a very narrow spectrum of action; out of 37 examined strains, the growth of only Micrococcus luteus, Corynebacterium diphtheriae and Pasteurella multocida was inhibited.

  19. 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.

  20. Modulation of cell growth by the hepatitis C virus nonstructural protein NS5A.

    PubMed

    Arima, N; Kao, C Y; Licht, T; Padmanabhan, R; Sasaguri, Y; Padmanabhan, R

    2001-04-20

    Hepatitis C virus nonstructural protein, NS5A, is a phosphoprotein produced from the processing of the viral polyprotein precursor. NS5A associates with several cellular proteins in mammalian cells, and the biological consequences of this interaction are currently unknown. To this end, five stable NS5A-expressing murine and human cell lines were established. Tetracycline-regulated NIH3T3 cells and rat liver epithelial cells as well as the constitutive, NS5A-expressing, human Chang liver, HeLa, and NIH3T3 cells all exhibited cell growth retardation compared with the control cells. Cell cycle analysis by flow cytometry indicated that the NS5A-expressing human epitheloid tumor cells had a reduced S phase and an increase in the G(2)/M phase, which could be explained by a p53-dependent induction of p21(Waf1/Cip1) protein and mRNA levels. NS5A interacts with Cdk1 in vivo and in vitro, and a significant portion of the p21(Waf1/Cip1) was found to be in a complex with Cdk2 in the NS5A-expressing human hepatic cell line. Cdk1 and cyclin B1 proteins were also reduced in human Chang liver cells consistent with the increase in G(2)/M phase. Our results suggest that the NS5A protein causes growth inhibition and cell cycle perturbations by targeting the Cdk1/2-cyclin complexes.

  1. 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...

  2. Introduction to Cognitive and Affective Skills (NS 127): Competency-Based Course Syllabus.

    ERIC Educational Resources Information Center

    Brady, Marilyn H.; Wells, Tanya G.

    "Introduction to Cognitive and Affective Skills" (NS 127) is an associate degree nursing course offered at Chattanooga State Technical Community College to help students develop competencies in decision making, communication, teaching-learning, and management. The course syllabus for NS 127 begins with information on class, laboratory, and credit…

  3. 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...

  4. 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...

  5. 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

    2016-02-02

    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.

  6. Experimental evidence and molecular modeling of the interaction between hRSV-NS1 and quercetin.

    PubMed

    Gomes, Deriane Elias; Caruso, Ícaro Putinhon; de Araujo, Gabriela Campos; de Lourenço, Isabella Otenio; de Melo, Fernando Alves; Cornélio, Marinônio Lopes; Fossey, Marcelo Andrés; de Souza, Fátima Pereira

    2016-04-01

    Human Respiratory Syncytial Virus is one of the major causes of acute respiratory infections in children, causing bronchiolitis and pneumonia. Non-Structural Protein 1 (NS1) is involved in immune system evasion, a process that contributes to the success of hRSV replication. This protein can act by inhibiting or neutralizing several steps of interferon pathway, as well as by silencing the hRSV ribonucleoproteic complex. There is evidence that quercetin can reduce the infection and/or replication of several viruses, including RSV. The aims of this study include the expression and purification of the NS1 protein besides experimental and computational assays of the NS1-quercetin interaction. CD analysis showed that NS1 secondary structure composition is 30% alpha-helix, 21% beta-sheet, 23% turn and 26% random coils. The melting temperature obtained through DSC analysis was around 56°C. FRET analysis showed a distance of approximately 19Å between the NS1 and quercetin. Fluorescence titration results showed that the dissociation constant of the NS1-quercetin interaction was around 10(-6)M. In thermodynamic analysis, the enthalpy and entropy balanced forces indicated that the NS1-quercetin interaction presented both hydrophobic and electrostatic contributions. The computational results from the molecular modeling for NS1 structure and molecular docking regarding its interaction with quercetin corroborate the experimental data.

  7. Structural analysis and insight into Zika virus NS5 mediated interferon inhibition.

    PubMed

    Dar, Hamza Arshad; Zaheer, Tahreem; Paracha, Rehan Zafar; Ali, Amjad

    2017-03-30

    The Zika virus outbreak in 2015-2016 is the largest of its kind for which WHO declared a Public Health Emergency of International Concerns. No FDA approved drug is available for the treatment of the viral infection. The interaction of flavivirus NS5 protein with SIAH2 ubiquitin ligase has been previously known. NS5 of Zika virus has been implicated in the degradation of STAT2 protein, which activates interferon-stimulated antiviral activity. Based on our proposition that NS5 utilizes SIAH2-mediated proteasomal degradation of STAT2, an in-silico study was carried out to characterize the protein-protein interactions between NS5, SIAH2 and STAT2 proteins. The aim of our study was to identify the amino acid residues of NS5 involved in IFN antagonism as well as to find the association between NS5, SIAH2 and STAT2 to predict the interaction pattern of these proteins. Analysis proposed that NS5 recruits SIAH2 for the ubiquitination-dependent degradation of STAT2. NS5 residues involved in interaction with SIAH2 and/or STAT2 were found to be mostly conserved across related flaviviruses. These are novel findings regarding the Zika virus and require confirmation through experimental approaches.

  8. Identification and characterization of coumestans as novel HCV NS5B polymerase inhibitors

    PubMed Central

    Kaushik-Basu, Neerja; Bopda-Waffo, Alain; Talele, Tanaji T.; Basu, Amartya; Costa, Paulo R. R.; da Silva, Alcides J. M.; Sarafianos, Stefan G.; Noël, François

    2008-01-01

    The hepatitis C virus (HCV) NS5B is essential for viral RNA replication and is therefore a prime target for development of HCV replication inhibitors. Here, we report the identification of a new class of HCV NS5B inhibitors belonging to the coumestan family of phytoestrogens. Based on the in vitro NS5B RNA-dependent RNA polymerase (RdRp) inhibition in the low micromolar range by wedelolactone, a naturally occurring coumestan, we evaluated the anti-NS5B activity of four synthetic coumestan analogues bearing different patterns of substitutions in their A and D rings, and observed a good structure-activity correlation. Kinetic characterization of coumestans revealed a noncompetitive mode of inhibition with respect to nucleoside triphosphate (rNTP) substrate and a mixed mode of inhibition towards the nucleic acid template, with a major competitive component. The modified order of addition experiments with coumestans and nucleic acid substrates affected the potencies of the coumestan inhibitors. Coumestan interference at the step of NS5B–RNA binary complex formation was confirmed by cross-linking experiments. Molecular docking of coumestans within the allosteric site of NS5B yielded significant correlation between their calculated binding energies and IC50 values. Coumestans thus add to the diversifying pool of anti-NS5B agents and provide a novel scaffold for structural refinement and development of potent NS5B inhibitors. PMID:18203743

  9. NS1-mediated delay of type I interferon induction contributes to influenza A virulence in ferrets.

    PubMed

    Meunier, Isabelle; von Messling, Veronika

    2011-07-01

    Interference of the influenza A virus non-structural protein NS1 with type I interferon (IFN) signalling has been characterized extensively in vitro. To assess the contribution of NS1 to the virulence of a specific strain, we generated recombinant USSR/90/77 viruses bearing the NS1 proteins of the attenuated strain PR/8/34 or the highly pathogenic strain 1918 'Spanish flu', all belonging to the H1N1 subtype. In vitro, the extent of interference with type I IFN production exerted by the different NS1 proteins correlated with the reported virulence of the respective strain. Infection of ferrets with the recombinant viruses revealed that the presence of the 1918 NS1 resulted in a slightly more severe disease with generally higher clinical scores and increased lung pathology. Analysis of mRNA from nasal wash cells revealed that viruses carrying the 1918 and, to a lesser extent, USSR/90/77 NS1 proteins caused a delay in upregulation of type I IFNs compared with the NS1 PR/8/34-expressing virus, demonstrating the importance of NS1 for early host-response control and virulence.

  10. Structure and sequence based functional annotation of Zika virus NS2b protein: Computational insights.

    PubMed

    Aguilera-Pesantes, Daniel; Méndez, Miguel A

    2017-02-08

    While Zika virus (ZIKV) outbreaks are a growing concern for global health, a deep understanding about the virus is lacking. Here we report a contribution to the basic science on the virus- a detailed computational analysis of the non structural protein NS2b. This protein acts as a cofactor for the NS3 protease (NS3Pro) domain that is important on the viral life cycle, and is an interesting target for drug development. We found that ZIKV NS2b cofactor is highly similar to other virus within the Flavivirus genus, especially to West Nile Virus, suggesting that it is completely necessary for the protease complex activity. Furthermore, the ZIKV NS2b has an important role to the function and stability of the ZIKV NS3 protease domain even when presents a low conservation score. In addition, ZIKV NS2b is mostly rigid, which could imply a non dynamic nature in substrate recognition. Finally, by performing a computational alanine scanning mutagenesis, we found that residues Gly 52 and Asp 83 in the NS2b could be important in substrate recognition.

  11. Structural basis for substrate specificity of alphavirus nsP2 proteases.

    PubMed

    Russo, Andrew T; Malmstrom, Robert D; White, Mark A; Watowich, Stanley J

    2010-08-24

    The alphavirus nsP2 protease is essential for correct processing of the alphavirus nonstructural polyprotein (nsP1234) and replication of the viral genome. We have combined molecular dynamics simulations with our structural studies to reveal features of the nsP2 protease catalytic site and S1'-S4 subsites that regulate the specificity of the protease. The catalytic mechanism of the nsP2 protease appears similar to the papain-like cysteine proteases, with the conserved catalytic dyad forming a thiolate-imidazolium ion pair in the nsP2-activated state. Substrate binding likely stabilizes this ion pair. Analysis of bimolecular complexes of Venezuelan equine encephalitis virus (VEEV) nsP2 protease with each of the nsP1234 cleavage sites identified protease residues His(510), Ser(511), His(546) and Lys(706) as critical for cleavage site recognition. Homology modelling and molecular dynamics simulations of diverse alphaviruses and their cognate cleavage site sequences revealed general features of substrate recognition that operate across alphavirus strains as well as strain specific covariance between binding site and cleavage site residues. For instance, compensatory changes occurred in the P3 and S3 subsite residues to maintain energetically favourable complementary binding surfaces. These results help explain how alphavirus nsP2 proteases recognize different cleavage sites within the nonstructural polyprotein and discriminate between closely related cleavage targets.

  12. Double-pulse laser-induced breakdown spectroscopy for trace element analysis in sintered iron oxide ceramics

    NASA Astrophysics Data System (ADS)

    Heilbrunner, H.; Huber, N.; Wolfmeir, H.; Arenholz, E.; Pedarnig, J. D.; Heitz, J.

    2012-01-01

    Double-pulse laser-induced breakdown spectroscopy (LIBS) is an emerging technique for accurate compositional analysis of many different materials. We present a systematic study of collinear double-pulse LIBS for analysis of the trace and side elements boron, manganese, copper, aluminum, titanium, silicon, chromium, nickel, potassium, and calcium in sintered iron oxide targets. The samples were ablated in air by single-pulse and double-pulse Nd:YAG laser radiation (6 ns pulse duration, laser wavelength of 532 nm) and spectra were recorded with an Echelle spectrometer equipped with an ICCD camera. We investigated the evolution of atomic and ionic line emission intensities for different interpulse delay times between the laser pulses (from 100 ns to 50 μs) and gate delays after the second laser pulse. We also varied the energy partition between the first and second laser pulse and the size of the irradiated spot at the sample surface. For the trace and side elements, we observed double-pulse LIBS signals that were enhanced as compared to single-pulse measurements depending on the interpulse delay time, the energy partition between the pulses, and the spot size. For the elements boron, copper, aluminum, titanium, chromium, potassium, and calcium limits of detection below 10 ppm were achieved.

  13. 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.

  14. High energy, single-polarized, single-transverse-mode, nanosecond pulses generated by a multi-stage Yb-doped photonic crystal fiber amplifier

    NASA Astrophysics Data System (ADS)

    Shen, Xinglai; Zhang, Haitao; Hao, He; Li, Dan; Li, Qinghua; Yan, Ping; Gong, Mali

    2015-06-01

    We report the construction of a cascaded fiber amplifier where a 40-μm-core-diameter photonic crystal fiber is utilized in the main amplifier stage. Single-transverse-mode, linearly-polarized, 7.5 ns pulses with 1.5 mJ energy, 123 kW peak power and 10 nm spectral bandwidth centered at 1062 nm are generated. To our knowledge, the pulse energy we obtain is the highest from 40-μm-core-diameter photonic crystal fibers, and also the highest for long pulses (>1 ns) with linear polarization and single transverse mode.

  15. 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.

  16. H-NS, Its Family Members and Their Regulation of Virulence Genes in Shigella Species

    PubMed Central

    Picker, Michael A.; Wing, Helen J.

    2016-01-01

    The histone-like nucleoid structuring protein (H-NS) has played a key role in shaping the evolution of Shigella spp., and provides the backdrop to the regulatory cascade that controls virulence by silencing many genes found on the large virulence plasmid. H-NS and its paralogue StpA are present in all four Shigella spp., but a second H-NS paralogue, Sfh, is found in the Shigella flexneri type strain 2457T, which is routinely used in studies of Shigella pathogenesis. While StpA and Sfh have been proposed to serve as “molecular backups” for H-NS, the apparent redundancy of these proteins is questioned by in vitro studies and work done in Escherichia coli. In this review, we describe the current understanding of the regulatory activities of the H-NS family members, the challenges associated with studying these proteins and their role in the regulation of virulence genes in Shigella. PMID:27916940

  17. 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

    2005-10-05

    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.

  18. Sensitivity, stability, and precision of quantitative Ns-LIBS-based fuel-air-ratio measurements for methane-air flames at 1-11 bar.

    PubMed

    Hsu, Paul S; Gragston, Mark; Wu, Yue; Zhang, Zhili; Patnaik, Anil K; Kiefer, Johannes; Roy, Sukesh; Gord, James R

    2016-10-01

    Nanosecond laser-induced breakdown spectroscopy (ns-LIBS) is employed for quantitative local fuel-air (F/A) ratio (i.e., ratio of actual fuel-to-oxidizer mass over ratio of fuel-to-oxidizer mass at stoichiometry, measurements in well-characterized methane-air flames at pressures of 1-11 bar). We selected nitrogen and hydrogen atomic-emission lines at 568 nm and 656 nm, respectively, to establish a correlation between the line intensities and the F/A ratio. We have investigated the effects of laser-pulse energy, camera gate delay, and pressure on the sensitivity, stability, and precision of the quantitative ns-LIBS F/A ratio measurements. We determined the optimal laser energy and camera gate delay for each pressure condition and found that measurement stability and precision are degraded with an increase in pressure. We have identified primary limitations of the F/A ratio measurement employing ns-LIBS at elevated pressures as instabilities caused by the higher density laser-induced plasma and the presence of the higher level of soot. Potential improvements are suggested.

  19. CONTROL OF LASER RADIATION PARAMETER: Temporal evolution of a coherent stimulated radiation pulse in the three-level system in a Pr3+ : LaF3 crystal

    NASA Astrophysics Data System (ADS)

    Agafonov, Aleksandr I.; Grigoryan, Grigorii G.; Znamenskiy, Nikolay V.; Manykin, Eduard A.; Orlov, Yurii V.; Petrenko, Evgenii A.; Shashkov, Andrei Yu

    2004-09-01

    The temporal characteristics of coherent stimulated radiation at the 3P0— 3H6 transition in the Pr3+ ion in a LaF3 matrix are studied by tuning the pump frequency in the vicinity of the 3H4— 3P0 transition. It is found that in the case of the exact tuning to the resonance, a laser pulse, consisting of a train of picosecond spikes of total duration about 10 ns, was delayed by 3-4 ns with respect to the pump pulse onset. As the pump pulse detuning was increased, the shape of the coherent laser pulse changes and its delay increased up to 10 ns. The experimental results are interpreted theoretically.

  20. 9 CFR 2.10 - Licensees whose licenses have been suspended or revoked.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

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  1. 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.

  2. 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

  3. NS5ATP13 Promotes Liver Fibrogenesis via Activation of Hepatic Stellate Cells.

    PubMed

    Li, Yaru; Liu, Shunai; Han, Ming; Lu, Hongping; Wang, Qi; Zhang, Yu; Tursun, Kelbinur; Li, Zhongshu; Feng, Shenghu; Cheng, Jun

    2017-01-29

    Liver fibrosis is a reversible wound-healing response to any etiology of chronic hepatic injuries. Activation of hepatic stellate cells (HSCs) is the key event in liver fibrogenesis. Generally, persistent activation and proliferation of HSCs results in liver fibrosis progression, while primary mechanisms of liver fibrosis resolution are apoptosis and reversion to a quiescent phenotype of activated HSCs. NS5ATP13 (HCV NS5A-transactivated protein 13) is involved in nucleologenesis and tumorigenesis, but its role in liver fibrosis and HSC activation remains unclear. This study found that NS5ATP13 was upregulated in both fibrotic liver tissues and activated human HSCs induced by TGF-β1. Moreover, NS5ATP13 enhanced extracellular matrix (ECM) production and HSC activation, with or without TGF-β1 treatment, likely involving the TGF-β1/Smad3 signaling pathway. Additionally, NS5ATP13 boosted HSC proliferation by inhibiting cell apoptosis. Furthermore, HCV NS5A promoted the profibrogenic effect of NS5ATP13 partly through TGF-β1 and NF-κB p65 (RelA) upregulation. Meanwhile, NS5ATP13 was required for the pro-fibrogenic effect of NF-κB. Moreover, NS5ATP13 and NF-κB phosphorylation as well as HSC activation were reduced by CX-4945, a CK2 specific inhibitor. These findings indicated that NS5ATP13 acts as a profibrogenic factor, providing a potential target for antifibrotic therapies. This article is protected by copyright. All rights reserved.

  4. Laser pulse stacking method

    DOEpatents

    Moses, Edward I.

    1992-01-01

    A laser pulse stacking method is disclosed. A problem with the prior art has been the generation of a series of laser beam pulses where the outer and inner regions of the beams are generated so as to form radially non-synchronous pulses. Such pulses thus have a non-uniform cross-sectional area with respect to the outer and inner edges of the pulses. The present invention provides a solution by combining the temporally non-uniform pulses in a stacking effect to thus provide a more uniform temporal synchronism over the beam diameter.

  5. Laser pulse stacking method

    DOEpatents

    Moses, E.I.

    1992-12-01

    A laser pulse stacking method is disclosed. A problem with the prior art has been the generation of a series of laser beam pulses where the outer and inner regions of the beams are generated so as to form radially non-synchronous pulses. Such pulses thus have a non-uniform cross-sectional area with respect to the outer and inner edges of the pulses. The present invention provides a solution by combining the temporally non-uniform pulses in a stacking effect to thus provide a more uniform temporal synchronism over the beam diameter. 2 figs.

  6. Dominant recognition by human CD8+ cytotoxic T lymphocytes of dengue virus nonstructural proteins NS3 and NS1.2a.

    PubMed Central

    Mathew, A; Kurane, I; Rothman, A L; Zeng, L L; Brinton, M A; Ennis, F A

    1996-01-01

    A severe complication of dengue virus infection, dengue hemorrhagic fever (DHF), is hypothesized to be immunologically mediated and virus-specific cytotoxic T lymphocytes (CTLs) may trigger DHF. It is also likely that dengue virus-specific CTLs are important for recovery from dengue virus infections. There is little available information on the human CD8+ T cell responses to dengue viruses. Memory CD8+CTL responses were analyzed to determine the diversity of the T cell response to dengue virus and to identify immunodominant proteins using PBMC from eight healthy adult volunteers who had received monovalent, live-attenuated candidate vaccines of the four dengue serotypes. All the donors had specific T cell proliferation to dengue and to other flaviviruses that we tested. CTLs were generated from the stimulated PBMC of all donors, and in the seven donors tested, dengue virus-specific CD8+CTL activity was demonstrated. The nonstructural (NS3 and NS1.2a) and envelope (E) proteins were recognized by CD8+CTLs from six, five, and three donors, respectively. All donors recognized either NS3 or NS1.2a. In one donor who received a dengue 4 vaccine, CTL killing was seen in bulk culture against the premembrane protein (prM). This is the first demonstration of a CTL response against the prM protein. The CTL responses using the PBMC of two donors were serotype specific, whereas all other donors had serotype-cross-reactive responses. For one donor, CTLs specific for E, NS1.2a, and NS3 proteins were all HLA-B44 restricted. For three other donors tested, the potential restricting alleles for recognition of NS3 were B38, A24, and/or B62 and B35.These results indicate that the CD8+CTL responses of humans after immunization with one serotype of dengue virus are diverse and directed against a variety of proteins. The NS3 and NS1.2a proteins should be considered when designing subunit vaccines for dengue. PMID:8833919

  7. Quasi-steady-state air plasma channel produced by a femtosecond laser pulse sequence

    PubMed Central

    Lu, Xin; Chen, Shi-You; Ma, Jing-Long; Hou, Lei; Liao, Guo-Qian; Wang, Jin-Guang; Han, Yu-Jing; Liu, Xiao-Long; Teng, Hao; Han, Hai-Nian; Li, Yu-Tong; Chen, Li-Ming; Wei, Zhi-Yi; Zhang, Jie

    2015-01-01

    A long air plasma channel can be formed by filamentation of intense femtosecond laser pulses. However, the lifetime of the plasma channel produced by a single femtosecond laser pulse is too short (only a few nanoseconds) for many potential applications based on the conductivity of the plasma channel. Therefore, prolonging the lifetime of the plasma channel is one of the key challenges in the research of femtosecond laser filamentation. In this study, a unique femtosecond laser source was developed to produce a high-quality femtosecond laser pulse sequence with an interval of 2.9 ns and a uniformly distributed single-pulse energy. The metre scale quasi-steady-state plasma channel with a 60–80 ns lifetime was formed by such pulse sequences in air. The simulation study for filamentation of dual femtosecond pulses indicated that the plasma channel left by the previous pulse was weakly affected the filamentation of the next pulse in sequence under our experimental conditions. PMID:26493279

  8. Generation of an ultra-short electrical pulse with width shorter than the excitation laser

    PubMed Central

    Shi, Wei; Wang, Shaoqiang; Ma, Cheng; Xu, Ming

    2016-01-01

    We demonstrate experimentally a rare phenomenon that the width of an electrical response is shorter than that of the excitation laser. In this work, generation of an ultrashort electrical pulse is by a semi-insulating GaAs photoconductive semiconductor switch (PCSS) and the generated electrical pulse width is shorter than that of the excitation laser from diode laser. When the pulse width and energy of the excitation laser are fixed at 25.7 ns and 1.6 μJ respectively, the width of the generated electrical pulse width by 3-mm-gap GaAs PCSS at the bias voltage of 9 kV is only 7.3 ns. The model of photon-activated charge domain (PACD) is used to explain the peculiar phenomenon in our experiment. The ultrashort electrical pulse width is mainly relevant to the time interval of PACD from occurrence to disappearance in the mode. The shorter the time interval is, the narrower the electrical pulse width will become. In more general terms, our result suggests that in nonlinear regime a response signal can have a much short width than the excitation pulses. The result clearly indicates that generating ultrashort electrical pulses can be achieved without the need of ultrashort lasers. PMID:27273512

  9. High-Power Multimode X-Band RF Pulse Compression System for Future Linear Colliders

    SciTech Connect

    Tantawi, S.G.; Nantista, C.D.; Dolgashev, V.A.; Pearson, C.; Nelson, J.; Jobe, K.; Chan, J.; Fant, K.; Frisch, J.; Atkinson, D.; /LLNL, Livermore

    2005-08-10

    We present a multimode X-band rf pulse compression system suitable for a TeV-scale electron-positron linear collider such as the Next Linear Collider (NLC). The NLC main linac operating frequency is 11.424 GHz. A single NLC rf unit is required to produce 400 ns pulses with 475 MW of peak power. Each rf unit should power approximately 5 m of accelerator structures. The rf unit design consists of two 75 MW klystrons and a dual-moded resonant-delay-line pulse compression system that produces a flat output pulse. The pulse compression system components are all overmoded, and most components are designed to operate with two modes. This approach allows high-power-handling capability while maintaining a compact, inexpensive system. We detail the design of this system and present experimental cold test results. We describe the design and performance of various components. The high-power testing of the system is verified using four 50 MW solenoid-focused klystrons run off a common 400 kV solid-state modulator. The system has produced 400 ns rf pulses of greater than 500 MW. We present the layout of our system, which includes a dual-moded transmission waveguide system and a dual-moded resonant line (SLED-II) pulse compression system. We also present data on the processing and operation of this system, which has set high-power records in coherent and phase controlled pulsed rf.

  10. Antibiotic susceptibility of coagulase-negative staphylococci (CoNS): emergence of teicoplanin-non-susceptible CoNS strains with inducible resistance to vancomycin.

    PubMed

    Ma, Xiao Xue; Wang, En Hua; Liu, Yong; Luo, En Jie

    2011-11-01

    Coagulase-negative staphylococci (CoNS) have become increasingly recognized as important agents of nosocomial infection. One of the characteristics of CoNS is their resistance to multiple antimicrobial agents commonly used for the treatment of staphylococcal infections. CoNS strains (n = 745) isolated from a university teaching hospital in China between 2004 and 2009 were tested for antibiotic resistance. The antibiotics were placed into three categories based on resistance levels of the CoNS strains to these antibiotics: high resistance (resistance rate >70 %), including penicillin G, oxacillin and erythromycin; medium resistance (resistance rate between 30 and 70 %), including tetracycline, clindamycin, ciprofloxacin, trimethoprim/sulfamethoxazole and chloramphenicol; and low resistance (resistance rate <30 %), including rifampicin, ceftizoxime and gentamicin. We also found that the prevalence of strains non-susceptible to teicoplanin increased from 4.5 to 6.7 % between 2008 and 2009. A one-step vancomycin agar selection experiment and subsequent population analysis revealed potentially vancomycin-resistant subpopulations that have been selected from the teicoplanin-non-susceptible strains. Vigilant surveillance of nosocomial isolates of CoNS is needed to determine their resistance to glycopeptides.

  11. The NS4A Cofactor Dependent Enhancement of HCV NS3 Protease Activity Correlates with a 4D Geometrical Measure of the Catalytic Triad Region

    PubMed Central

    Hamad, Hamzah A.; Thurston, Jeremy; Teague, Thomas; Ackad, Edward; Yousef, Mohammad S.

    2016-01-01

    We are developing a 4D computational methodology, based on 3D structure modeling and molecular dynamics simulation, to analyze the active site of HCV NS3 proteases, in relation to their catalytic activity. In our previous work, the 4D analyses of the interactions between the catalytic triad residues (His57, Asp81, and Ser139) yielded divergent, gradual and genotype-dependent, 4D conformational instability measures, which strongly correlate with the known disparate catalytic activities among genotypes. Here, the correlation of our 4D geometrical measure is extended to intra-genotypic alterations in NS3 protease activity, due to sequence variations in the NS4A activating cofactor. The correlation between the 4D measure and the enzymatic activity is qualitatively evident, which further validates our methodology, leading to the development of an accurate quantitative metric to predict protease activity in silico. The results suggest plausible “communication” pathways for conformational propagation from the activation subunit (the NS4A cofactor binding site) to the catalytic subunit (the catalytic triad). The results also strongly suggest that the well-sampled (via convergence quantification) structural dynamics are more connected to the divergent catalytic activity observed in HCV NS3 proteases than to rigid structures. The method could also be applicable to predict patients’ responses to interferon therapy and better understand the innate interferon activation pathway. PMID:27936126

  12. Detergent-Resistant Membrane Association of NS2 and E2 during Hepatitis C Virus Replication

    PubMed Central

    Shanmugam, Saravanabalaji; Saravanabalaji, Dhanaranjani

    2015-01-01

    ABSTRACT Previously, we demonstrated that the efficiency of hepatitis C virus (HCV) E2-p7 processing regulates p7-dependent NS2 localization to putative virus assembly sites near lipid droplets (LD). In this study, we have employed subcellular fractionations and membrane flotation assays to demonstrate that NS2 associates with detergent-resistant membranes (DRM) in a p7-dependent manner. However, p7 likely plays an indirect role in this process, since only the background level of p7 was detectable in the DRM fractions. Our data also suggest that the p7-NS2 precursor is not involved in NS2 recruitment to the DRM, despite its apparent targeting to this location. Deletion of NS2 specifically inhibited E2 localization to the DRM, indicating that NS2 regulates this process. Treatment of cells with methyl-β-cyclodextrin (MβCD) significantly reduced the DRM association of Core, NS2, and E2 and reduced infectious HCV production. Since disruption of the DRM localization of NS2 and E2, either due to p7 and NS2 defects, respectively, or by MβCD treatment, inhibited infectious HCV production, these proteins' associations with the DRM likely play an important role during HCV assembly. Interestingly, we detected the HCV replication-dependent accumulation of ApoE in the DRM fractions. Taking into consideration the facts that ApoE was shown to be a major determinant for infectious HCV particle production at the postenvelopment step and that the HCV Core protein strongly associates with the DRM, recruitment of E2 and ApoE to the DRM may allow the efficient coordination of Core particle envelopment and postenvelopment events at the DRM to generate infectious HCV production. IMPORTANCE The biochemical nature of HCV assembly sites is currently unknown. In this study, we investigated the correlation between NS2 and E2 localization to the detergent-resistant membranes (DRM) and HCV particle assembly. We determined that although NS2's DRM localization is dependent on p7, p7 was not

  13. 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

  14. All-fiber high-average power nanosecond-pulsed master-oscillator power amplifier at 2  μm with mJ-level pulse energy.

    PubMed

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

    2016-03-10

    We present a high-power nanosecond-pulsed Tm-doped fiber amplifier at 1.971 μm based on a master-oscillator power amplifier (MOPA) configuration. When the repetition rate is 500 kHz and the pulse width is 63.3 ns, the average power reaches 238 W, the peak power reaches 7.06 kW, and the pulse energy is 0.477 mJ. When the pulse train's repetition rate is 300 kHz with a pulse width of 63.7 ns, the average power reaches 197 W, the peak power reaches 9.73 kW, and the pulse energy is 0.66 mJ. When the pulse train's repetition rate is 200 kHz with a pulse width of 58.2 ns, the average power reaches 150 W, the peak power reaches 12.1 kW, and the pulse energy is 0.749 mJ. The spectral linewidths of the pulse trains are 0.15, 0.14, and 0.10 nm for 500 kHz repetition rate, 300 kHz repetition rate, and 200 kHz repetition rate, respectively. To the best of our knowledge, this is the first demonstration of high-power nanosecond-pulsed MOPA at 2 μm with the maximum average power reaching 238 W, the maximum peak power reaching 12.1 kW, and the maximum pulse energy reaching 0.749 mJ.

  15. Ultrawide-band electromagnetic pulses induced hypotension in rats.

    PubMed

    Lu, S T; Mathur, S P; Akyel, Y; Lee, J C

    The ultrawide-band (UWB) electromagnetic pulses are used as a new modality in radar technology. Biological effects of extremely high peak E-field, fast rise time, ultrashort pulse width, and ultrawide band have not been investigated heretofore due to the lack of animal exposure facilities. A new biological effects database is needed to establish personnel protection guidelines for these new type of radiofrequency radiation. Functional indices of the cardiovascular system (heart rate, systolic, mean, and diastolic pressures) were selected to represent biological end points that may be susceptible to the UWB radiation. A noninvasive tail-cuff photoelectric sensor sphygmomanometer was used. Male Wistar-Kyoto rats were subjected to sham exposure, 0.5-kHz (93 kV/m, 180 ps rise time, 1.00 ns pulse width, whole-body averaged specific absorption rate, SAR = 70 mW/kg) or a 1-kHz (85 kV/m, 200 ps rise time, 1.03 ns pulse width, SAR = 121 mW/kg) UWB fields in a tapered parallel plate GTEM cell for 6 min. Cardiovascular functions were evaluated from 45 min to 4 weeks after exposures. Significant decrease in arterial blood pressures (hypotension) was found. In contrast, heart rate was not altered by these exposures. The UWB radiation-induced hypotension was a robust, consistent, and persistent effect.

  16. Ultrawide-band electromagnetic pulses induced hypotension in rats.

    PubMed

    Lu, S T; Mathur, S P; Akyel, Y; Lee, J C

    1999-09-01

    The ultrawide-band (UWB) electromagnetic pulses are used as a new modality in radar technology. Biological effects of extremely high peak E-field, fast rise time, ultrashort pulse width, and ultrawide band have not been investigated heretofore due to the lack of animal exposure facilities. A new biological effects database is needed to establish personnel protection guidelines for these new type of radiofrequency radiation. Functional indices of the cardiovascular system (heart rate, systolic, mean, and diastolic pressures) were selected to represent biological end points that may be susceptible to the UWB radiation. A noninvasive tail-cuff photoelectric sensor sphygmomanometer was used. Male Wistar-Kyoto rats were subjected to sham exposure, 0.5-kHz (93 kV/m, 180 ps rise time, 1.00 ns pulse width, whole-body averaged specific absorption rate, SAR = 70 mW/kg) or a 1-kHz (85 kV/m, 200 ps rise time, 1.03 ns pulse width, SAR = 121 mW/kg) UWB fields in a tapered parallel plate GTEM cell for 6 min. Cardiovascular functions were evaluated from 45 min to 4 weeks after exposures. Significant decrease in arterial blood pressures (hypotension) was found. In contrast, heart rate was not altered by these exposures. The UWB radiation-induced hypotension was a robust, consistent, and persistent effect.

  17. 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

  18. 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.

  19. Characteristics of pulsed power generator by versatile inductive voltage adder

    NASA Astrophysics Data System (ADS)

    Yatsui, Kiyoshi; Shimiya, Kouichi; Masugata, Katsumi; Shigeta, Masao; Shibata, Kazuhiko

    2005-10-01

    A pulsed power generator by inductive voltage adder, versatile inductive voltage adder (VIVA-I), which features a high average potential gradient (2.5 MV/m), was designed and is currently in operation,. It was designed to produce an output pulse of 4 MV/60 ns by adding 2 MV pulses in two-stages of induction cells, where amorphous cores are installed. As a pulse forming line, we used a Blumlein line with the switching reversed, where cores are automatically biased due to the presence of prepulse. Good reproducibility was obtained even in the absence of the reset pulse. Within [similar]40% of full charge voltage, pulsed power characteristics of Marx generator, pulse forming line (PFL), transmission line (TL), and induction cells were tested for three types of loads; open-circuit, dummy load of liquid (CuSO4) resistor, and electron beam diode. In the open-circuit test, [similar]2.0 MV of output voltage was obtained with good reproducibility. Dependences of output voltage on diode impedances were evaluated by using various dummy loads, and the results were found as expected. An electron-beam diode was operated successfully, and [similar]18 kA of beam current was obtained at the diode voltage of [similar]1 MV.

  20. Clutter discrimination algorithm simulation in pulse laser radar imaging

    NASA Astrophysics Data System (ADS)

    Zhang, Yan-mei; Li, Huan; Guo, Hai-chao; Su, Xuan; Zhu, Fule

    2015-10-01

    Pulse laser radar imaging performance is greatly influenced by different kinds of clutter. Various algorithms are developed to mitigate clutter. However, estimating performance of a new algorithm is difficult. Here, a simulation model for estimating clutter discrimination algorithms is presented. This model consists of laser pulse emission, clutter jamming, laser pulse reception and target image producing. Additionally, a hardware platform is set up gathering clutter data reflected by ground and trees. The data logging is as clutter jamming input in the simulation model. The hardware platform includes a laser diode, a laser detector and a high sample rate data logging circuit. The laser diode transmits short laser pulses (40ns FWHM) at 12.5 kilohertz pulse rate and at 905nm wavelength. An analog-to-digital converter chip integrated in the sample circuit works at 250 mega samples per second. The simulation model and the hardware platform contribute to a clutter discrimination algorithm simulation system. Using this system, after analyzing clutter data logging, a new compound pulse detection algorithm is developed. This new algorithm combines matched filter algorithm and constant fraction discrimination (CFD) algorithm. Firstly, laser echo pulse signal is processed by matched filter algorithm. After the first step, CFD algorithm comes next. Finally, clutter jamming from ground and trees is discriminated and target image is produced. Laser radar images are simulated using CFD algorithm, matched filter algorithm and the new algorithm respectively. Simulation result demonstrates that the new algorithm achieves the best target imaging effect of mitigating clutter reflected by ground and trees.

  1. Evolution of hole shape and size during short and ultrashort pulse laser deep drilling.

    PubMed

    Döring, Sven; Szilagyi, John; Richter, Sören; Zimmermann, Felix; Richardson, Martin; Tünnermann, Andreas; Nolte, Stefan

    2012-11-19

    A detailed study of the influence of the pulse duration, from the femtosecond to the nanosecond regime, on the evolution of the hole shape and depth during percussion drilling in silicon is presented. Real-time backlight imaging of the hole development is obtained for holes up to 2 mm deep with aspect ratios extending to 25:1. For low pulse energies, the hole-shape and drilling characteristics are similar for femtosecond, picoseconds and nanosecond regimes. At higher pulse energies, ns-pulses exhibit slower average drilling rates but eventually reach greater final depths. The shape of these holes is however dominated by branching and large internal cavities. For ps-pulses, a cylindrical shape is maintained with frequent small bulges on the side-walls. In contrast, fs-pulses cause only a limited number of imperfections on a tapered hole shape.

  2. Characteristics of micro air plasma produced by double femtosecond laser pulses.

    PubMed

    Zhang, Nan; Wu, Zehua; Xu, Kuanhong; Zhu, Xiaonong

    2012-01-30

    Dynamic characteristics of air plasma generated by focused double collinear femtosecond laser pulses with a time interval of 10 ns are experimentally investigated. The air plasma emission changes significantly when altering the energy ratio between the two laser pulses. Time-resolved shadowgraphic measurements reveal that a small volume of transient vacuum is formed inside the air shock wave produced by the first laser pulse, which causes the second laser pulse induced ionization zone to present as two separate sections in space. Also recorded is strong scattering of the second laser pulse by the ionized air just behind the ionization front of the first laser pulse produced shock wave. Due to the high intensity of the scattered light, coherent Thomson scattering enhanced by plasma instabilities is believed to be the main scattering mechanism in this case.

  3. Solitary pulse generation by backward Raman scattering in H2-filled photonic crystal fibers.

    PubMed

    Abdolvand, A; Nazarkin, A; Chugreev, A V; Kaminski, C F; Russell, P St J

    2009-10-30

    Using a hydrogen-filled hollow-core photonic crystal fiber as a nonlinear optical gas cell, we study amplification of ns-laser pulses by backward rotational Raman scattering. We find that the amplification process has two characteristic stages. Initially, the pulse energy grows and its duration shortens due to gain saturation at the trailing edge of the pulse. This phase is followed by formation of a symmetric pulse with a duration significantly shorter than the phase relaxation time of the Raman transition. Stabilization of the Stokes pulse profile to a solitonlike hyperbolic secant shape occurs as a result of nonlinear amplification at its front edge and nonlinear absorption at its trailing edge (caused by energy conversion back to the pump field), leading to a reshaped pulse envelope that travels at superluminal velocity.

  4. Plasma chemical conversion of sulphur hexafluoride initiated by a pulsed electron beam

    NASA Astrophysics Data System (ADS)

    Kholodnaya, Galina; Sazonov, Roman; Ponomarev, Denis; Guzeeva, Tatiana

    2017-01-01

    This paper presents the results of the experimental investigation of plasma chemical conversion of sulphur hexafluoride initiated by a pulsed electron beam (TEA-500 pulsed electron accelerator) with the following characteristics: 400-450 keV electron energy, 60 ns pulse duration, up to 200 J pulse energy, and 5 cm beam diameter. Experiments were conducted on the effect of the pulsed electron beam on SF6 and on mixtures of SF6 with O2, Ar, or N2. For the mixture of SF6 and oxygen, the results indicated chemical reactions involving the formation of a number of products of which one is sulphur, confirming the Wray - Fluorescence Analysis. The plasma chemical conversion of SF6 initiated by the pulsed electron beam was not detected when SF6 was mixed with Ar or N2, suggesting a possible mechanism for the reaction of SF6 in the presence of O2.

  5. [The antioxidant enzyme activity in mouse liver mitochondria after nanosecond pulsed periodic X-ray exposure].

    PubMed

    Kniazeva, I R; Ivanov, V V; Bol'shakov, M A; Zharkova, L P; Kereia, A V; Kutenkov, O P; Rostov, V V

    2013-01-01

    The effect of repetitive pulsed X-ray (4 ns pulse duration, 300 kV accelerating voltage; 2.5 kA electron beam current) on the antioxidant enzyme activity in mouse liver mitochondria has been investigated. The mitochondrial suspension was exposed to single 4000 pulse X-ray radiation with repetition rates ranging between 10 and 22 pps (pulsed dose was 0.3-1.8 x 10(-6) Gy/pulse, the total absorbed dose following a single exposure was 7.2 x 10(-3) Gy). It was shown that a short-time exposure to X-ray radiation changes the antioxidant enzyme activity in mouse liver mitochondria. The greatest effect was observed in the changes of the activity of the metal-containing enzymes: superoxide dismutase and glutathione peroxidase. The effect depends on the pulse repetition frequency and radiation dose.

  6. Intense Nanosecond-Pulsed Cavity-Dumped Laser Radiation at 1.04 THz

    NASA Astrophysics Data System (ADS)

    Wilson, Thomas

    2013-03-01

    We report first results of intense far-infrared (FIR) nanosecond-pulsed laser radiation at 1.04 THz from a previously described[2] cavity-dumped, optically-pumped molecular gas laser. The gain medium, methyl fluoride, is pumped by the 9R20 line of a TEA CO2 laser[3] with a pulse energy of 200 mJ. The THz laser pulses contain of 30 kW peak power in 5 nanosecond pulse widths at a pulse repetition rate of 10 Hz. The line width, measured by a scanning metal-mesh FIR Fabry-Perot interferometer, is 100 MHz. The novel THz laser is being used in experiments to resonantly excite coherent ns-pulsed 1.04 THz longitudinal acoustic phonons in silicon doping-superlattices. The research is supported by NASA EPSCoR NNX11AM04A and AFOSR FA9550-12-1-0100 awards.

  7. Nanosecond pulse pumped, narrow linewidth all-fiber Raman amplifier with stimulated Brillouin scattering suppression

    NASA Astrophysics Data System (ADS)

    Su, Rongtao; Zhou, Pu; Wang, Xiaolin; Lü, Haibin; Xu, Xiaojun

    2014-01-01

    We report on a narrow linewidth nanosecond all-fiber Raman amplifier core pumped by a pulsed laser at approximately 1030 nm. The Raman amplifier was based on a standard single-mode fiber with a length of ∼1 km, and stimulated Brillouin scattering (SBS) was suppressed by employing pulses with a short pulse width. 1083 nm pulses with an average power of 32.6 mW, a repetition rate of 2 MHz, and pulse widths of ∼7.2 ns were achieved. A maximum slope efficiency of 46.1% and a gain of 31 dB were obtained. The output Raman power can be scaled further by using fiber with shorter lengths and pump pulses with a higher power.

  8. Electric field in an AC dielectric barrier discharge overlapped with a nanosecond pulse discharge

    NASA Astrophysics Data System (ADS)

    Goldberg, Benjamin M.; Shkurenkov, Ivan; Adamovich, Igor V.; Lempert, Walter R.

    2016-08-01

    The effect of ns discharge pulses on the AC barrier discharge in hydrogen in plane-to-plane geometry is studied using time-resolved measurements of the electric field in the plasma. The AC discharge was operated at a pressure of 300 Torr at frequencies of 500 and 1750 Hz, with ns pulses generated when the AC voltage was near zero. The electric field vector is measured by ps four-wave mixing technique, which generates coherent IR signal proportional to the square of electric field. Absolute calibration was done using an electrostatic (sub-breakdown) field applied to the discharge electrodes, when no plasma was generated. The results are compared with one-dimensional kinetic modeling of the AC discharge and the nanosecond pulse discharge, predicting behavior of both individual micro-discharges and their cumulative effect on the electric field distribution in the electrode gap, using stochastic averaging based on the experimental micro-discharge temporal probability distribution during the AC period. Time evolution of the electric field in the AC discharge without ns pulses, controlled by a superposition of random micro-discharges, exhibits a nearly ‘flat top’ distribution with the maximum near breakdown threshold, reproduced quite well by kinetic modeling. Adding ns pulse discharges on top of the AC voltage waveform changes the AC discharge behavior in a dramatic way, inducing transition from random micro-discharges to a more regular, near-1D discharge. In this case, reproducible volumetric AC breakdown is produced at a well-defined moment after each ns pulse discharge. During the reproducible AC breakdown, the electric field in the plasma exhibits a sudden drop, which coincides in time with a well-defined current pulse. This trend is also predicted by the kinetic model. Analysis of kinetic modeling predictions shows that this effect is caused by large-volume ionization and neutralization of surface charges on the dielectrics by ns discharge pulses. The present

  9. Optically pulsed electron accelerator

    DOEpatents

    Fraser, J.S.; Sheffield, R.L.

    1985-05-20

    An optically pulsed electron accelerator can be used as an injector for a free electron laser and comprises a pulsed light source, such as a laser, for providing discrete incident light pulses. A photoemissive electron source emits electron bursts having the same duration as the incident light pulses when impinged upon by same. The photoemissive electron source is located on an inside wall of a radiofrequency-powered accelerator cell which accelerates the electron burst emitted by the photoemissive electron source.

  10. Optically pulsed electron accelerator

    DOEpatents

    Fraser, John S.; Sheffield, Richard L.

    1987-01-01

    An optically pulsed electron accelerator can be used as an injector for a free electron laser and comprises a pulsed light source, such as a laser, for providing discrete incident light pulses. A photoemissive electron source emits electron bursts having the same duration as the incident light pulses when impinged upon by same. The photoemissive electron source is located on an inside wall of a radio frequency powered accelerator cell which accelerates the electron burst emitted by the photoemissive electron source.

  11. Current Drug Discovery for Anti-hepatitis C Virus Targeting NS4B.

    PubMed

    Wang, Zhenya; Chen, Xinli; Wu, Chunli; Xu, Haiwei; Liu, Hongmin

    2016-01-01

    Hepatitis C virus (HCV) infection is a major worldwide epidemic disease. It is estimated that more than 170 million individuals are infected with HCV and with three to four million new cases each year. Many new direct-acting antiviral (DAA) agents that specifically target HCV NS3 protease or NS5B polymerase inhibitors are therefore in development, with a significant effect for the patient and for the market recently. The non-structural 4B (NS4B) protein, is among the least characterized of the HCV proteins. A variety of functions have been recognized for NS4B, such as the ability to induce the membranous web replication platform, RNA binding and NTPase activity. In order to maximize antiviral efficacy and prevent the emergence of resistance, novel NS4B inhibitors have been subjected to pharmacological studies. In this review, we discussed current understanding of the structure and function of NS4B, and novel drug discoveries targeting NS4B as anti-hepatitis C virus such as sulfonamide, piperidine, carboxamide, piperazinone and quinoline derivatives within the last three years.

  12. Purification and characterization of the major nonstructural protein (NS-1) of Aleutian mink disease parvovirus.

    PubMed Central

    Christensen, J; Pedersen, M; Aasted, B; Alexandersen, S

    1995-01-01

    We have previously described the expression of the major nonstructural protein (NS-1) of Aleutian mink disease parvovirus (ADV) in insect cells by using a baculovirus vector (J. Christensen, T. Storgaard, B. Bloch, S. Alexandersen, and B. Aasted, J. Virol. 67:229-238, 1993). To study its biochemical properties, ADV NS-1 was expressed in Sf9 insect cells and purified to apparent homogeneity with a combination of nuclear extraction, Zn2+ ion chromatography, and immunoaffinity chromatography on monoclonal antibodies. The purified protein showed ATP binding and ATPase- and ATP- or dATP-dependent helicase activity requiring either Mg2+ or Mn2+ as a cofactor. The ATPase activity of NS-1 was efficiently stimulated by single-stranded DNA and, to a lesser extent, double-stranded DNA. We also describe the expression, purification, and characterization of a mutant NS-1 protein, in which a lysine in the putative nucleotide binding consensus sequence of the molecule was replaced with serine. The mutated NS-1 was expressed at 10-fold higher levels than wild-type NS-1, but it exhibited no ATP binding. ATPase, or helicase activity. The availability of large amounts of purified functional NS-1 protein will facilitate studies of the biochemistry of ADV replication and gene regulation leading to disease in mink. PMID:7853520

  13. Efficacy of NS-718, a novel lipid nanosphere-encapsulated amphotericin B, against Cryptococcus neoformans.

    PubMed

    Hossain, M A; Maesaki, S; Kakeya, H; Noda, T; Yanagihara, K; Sasaki, E; Hirakata, Y; Tomono, K; Tashiro, T; Kohno, S

    1998-07-01

    In vitro and in vivo efficacies of NS-718, a lipid nanosphere-encapsulated amphotericin B (AMPH-B), have been studied. Of the tested AMPH-B formulations, NS-718 had the lowest MIC for Cryptococcus neoformans. In a murine model, low-dose therapy (0.8 mg/kg of body weight) with NS-718 showed higher efficacy than that with AmBisome. High-dose therapy (2.0 mg/kg) with NS-718 was much more effective than those with Fungizone and AmBisome. In mice treated with a high dose of NS-718, only a few yeast cells had grown in lung by 7 days after inoculation. A pharmacokinetic study showed higher concentrations of AMPH-B in lung following administration of NS-718 than after administration of AmBisome. Our results indicated that NS-718, a new AMPH-B formulation, is a promising antifungal agent for treatment of pulmonary cryptococcosis and could be the most effective antifungal agent against C. neoformans infections.

  14. 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

  15. 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.

  16. 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

  17. Molecular Modeling and Docking Study to Elucidate Novel Chikungunya Virus nsP2 Protease Inhibitors.

    PubMed

    Agarwal, T; Asthana, Somya; Bissoyi, A

    2015-01-01

    Chikungunya is one of the tropical viral infections that severely affect the Asian and African countries. Absence of any suitable drugs or vaccines against Chikungunya virus till date makes it essential to identify and develop novel leads for the same. Recently, nsP2 cysteine protease has been classified as a crucial drug target to combat infections caused by Alphaviruses including Chikungunya virus due to its involvement viral replication. Here in, we investigated the structural aspects of the nsP2 protease through homology modeling based on nsP2 protease from Venezuelan equine encephalitis virus. Further, the ligands were virtually screened based on various pharmacological, ADME/Tox filters and subjected to docking with the modeled Chikungunya nsP2 protease using AutoDock4.2. The interaction profiling of ligand with the protein was carried out using LigPlot(+). The results demonstrated that the ligand with PubChem Id (CID_5808891) possessed highest binding affinity towards Chikungunya nsP2 protease with a good interaction profile with the active site residues. We hereby propose that these compounds could inhibit the nsP2 protease by binding to its active site. Moreover, they may provide structural scaffold for the design of novel leads with better efficacy and specificity for the nsP2 protease.

  18. Molecular Modeling and Docking Study to Elucidate Novel Chikungunya Virus nsP2 Protease Inhibitors

    PubMed Central

    Agarwal, T.; Asthana, Somya; Bissoyi, A.

    2015-01-01

    Chikungunya is one of the tropical viral infections that severely affect the Asian and African countries. Absence of any suitable drugs or vaccines against Chikungunya virus till date makes it essential to identify and develop novel leads for the same. Recently, nsP2 cysteine protease has been classified as a crucial drug target to combat infections caused by Alphaviruses including Chikungunya virus due to its involvement viral replication. Here in, we investigated the structural aspects of the nsP2 protease through homology modeling based on nsP2 protease from Venezuelan equine encephalitis virus. Further, the ligands were virtually screened based on various pharmacological, ADME/Tox filters and subjected to docking with the modeled Chikungunya nsP2 protease using AutoDock4.2. The interaction profiling of ligand with the protein was carried out using LigPlot+. The results demonstrated that the ligand with PubChem Id (CID_5808891) possessed highest binding affinity towards Chikungunya nsP2 protease with a good interaction profile with the active site residues. We hereby propose that these compounds could inhibit the nsP2 protease by binding to its active site. Moreover, they may provide structural scaffold for the design of novel leads with better efficacy and specificity for the nsP2 protease. PMID:26664062

  19. Pulse compression in plasma: Generation of femtosecond pulses without CPA

    SciTech Connect

    G. Shvets; N. J. Fisch; A. Pukhov; J. Meyer-ter-Vehn

    2000-07-20

    Laser pulses can be efficiently compressed to femtosecond duration when a smaller-frequency short pulse collides with high frequency long pulse in rare plasma, absorbing most of its energy. The mechanism of short pulse amplification is nonlinear superradiance.

  20. Crystal structure of full-length Zika virus NS5 protein reveals a conformation similar to Japanese encephalitis virus NS5.

    PubMed

    Upadhyay, Anup K; Cyr, Matthew; Longenecker, Kenton; Tripathi, Rakesh; Sun, Chaohong; Kempf, Dale J

    2017-03-01

    The rapid spread of the recent Zika virus (ZIKV) epidemic across various countries in the American continent poses a major health hazard for the unborn fetuses of pregnant women. To date, there is no effective medical intervention. The nonstructural protein 5 of Zika virus (ZIKV-NS5) is critical for ZIKV replication through the 5'-RNA capping and RNA polymerase activities present in its N-terminal methyltransferase (MTase) and C-terminal RNA-dependent RNA polymerase (RdRp) domains, respectively. The crystal structure of the full-length ZIKV-NS5 protein has been determined at 3.05 Å resolution from a crystal belonging to space group P21212 and containing two protein molecules in the asymmetric unit. The structure is similar to that reported for the NS5 protein from Japanese encephalitis virus and suggests opportunities for structure-based drug design targeting either its MTase or RdRp domain.