Science.gov

Sample records for helium 6 target

  1. Calculation of hydrogen and helium concentrations for CSNS target

    NASA Astrophysics Data System (ADS)

    Pan, Dong-Dong; Liang, Tai-Ran; Yin, Wen; Yao, Ze-En

    2016-03-01

    The China Spallation Neutron Source (CSNS) is driven by protons whose energies are about 1.6 GeV. At such high energies, the spallation neutrons lead to the formation of large amounts of helium, hydrogen and new heavier species in the form of transmutation products. These hydrogen, helium and transmutation products have a critical effect on the mechanical properties on the one hand and exacerbate the displacement radiation damage on the other hand. In this paper, the background hydrogen/helium concentrations and the maximum hydrogen/helium concentrations near cracks in a tungsten target for CSNS have been calculated at temperatures of 100°C and 300°C by applying a theoretical model. For the CSNS tungsten target plate, we find the maximum hydrogen concentration near the tips of cracks ranges from 3.0 × 10-2-2 × 10-1, which exceeds the hydrogen background concentration by 1.2-1.8 times; the maximum helium concentration near the tips of cracks ranges from 3.0 × 10-4 -1.2 × 10-3, which exceeds the helium background concentration by 2-4 times; the maximum hydrogen/helium concentration increases with the increase of the transfer length across the surfaces of the target and it decreases with the increase of temperature. Supported by National Science Foundation of China (51371195, 11174358)

  2. Positronium formation from positron impact on hydrogen and helium targets

    NASA Astrophysics Data System (ADS)

    Naginey, T. C.; Stacy, Eric W.; Pollock, B. B.; Walters, H. R. J.; Whelan, Colm T.

    2014-06-01

    Charge-exchange cross sections are presented for collisions of positrons with hydrogen and neutral and singly ionized helium targets using a variant of the classical trajectory Monte Carlo approach. As a check on the method a comparison is made with the corresponding proton results. An extended error analysis is presented. Reasonable agreement with available experimental data is found, and the charge-exchange cross section for positrons on He+ is predicted.

  3. Active helium target: Neutron scalar polarizability extraction via Compton scattering

    SciTech Connect

    Morris, Meg Hornidge, David; Annand, John; Strandberg, Bruno

    2015-12-31

    Precise measurement of the neutron scalar polarizabilities has been a lasting challenge because of the lack of a free-neutron target. Led by the University of Glasgow and the Mount Allison University groups of the A2 collaboration in Mainz, Germany, preparations have begun to test a recent theoretical model with an active helium target with the hope of determining these elusive quantities with small statistical, systematic, and model-dependent errors. Apparatus testing and background-event simulations have been carried out, with the full experiment projected to run in 2015. Once determined, these values can be applied to help understand quantum chromodynamics in the nonperturbative region.

  4. Limiting Fragmentation Behavior of Projectile Helium (Z = 2) Fragments in Nucleus--Nucleus Interactions at 14.6 A GeV

    NASA Astrophysics Data System (ADS)

    Kumar, Ashwini; Singh, Gurmukh; Singh, Bhartendu K.

    2012-12-01

    An analysis of projectile helium (Z = 2) fragments based on 855 minimum-bias inelastic events induced by 14.6 A GeV 28Si beam in a nuclear emulsion is presented in order to test the hypothesis of limiting fragmentation. The projected angular distributions of projectile helium fragments have been fitted with Gaussian curves in individual helium reaction channels and also in different emulsion target events. Furthermore, average emission angle of projectile helium fragments has been studied in individual helium reaction channels with different emulsion target groups. On the basis of pseudo-rapidity distribution, an energy independent limiting fragmentation behavior of projectile helium fragments is also investigated in the fragmentation region.

  5. Negative ion productions in high velocity collision between small carbon clusters and Helium atom target

    NASA Astrophysics Data System (ADS)

    M, Chabot; K, Béroff; T, Pino; G, Féraud; N, Dothi; Padellec A, Le; G, Martinet; S, Bouneau; Y, Carpentier

    2012-11-01

    We measured absolute double capture cross section of Cn+ ions (n=1,5) colliding, at 2.3 and 2.6 a.u velocities, with an Helium target atom and the branching ratios of fragmentation of the so formed electronically excited anions Cn-*. We also measured absolute cross section for the electronic attachment on neutral Cn clusters colliding at same velocities with He atom. This is to our knowledge the first measurement of neutral-neutral charge exchange in high velocity collision.

  6. Light Ion Yields from Bombardment of Thick Targets by Protons, Helium-4 and Iron-56

    NASA Astrophysics Data System (ADS)

    Castellanos, Luis A.; McGirl, Natalie A.; Srikrishna, Ashwin P.; Heilbronn, Lawrence H.; Tessa, Chiara La; Rusek, Adam; Sivertz, Michael; Blattnig, Steve; Clowdsley, Martha; Slaba, Tony; Zeitlin, Cary

    2017-09-01

    In March 2016 accelerator-based experiments colliding protons (0.4 and 0.8 GeV), helium (0.4 AGeV) and iron (0.4 and 0.8 AGeV) on thick aluminum targets with surface densities of 20, 40, and 60 g/cm2 were performed at the National Aeronautics and Space Administration Space Radiation Laboratory (NSRL) at Brookhaven National Laboratory. Two targets were utilized in each experimental configuration. Hydrogen and helium ions were detected using organic liquid scintillators in conjunction with thin plastic scintillators at 10°, 30°, 45°, 60°, 80°, and 135° from beam axis. Time-of-flight techniques and pulse shape discrimination were used to identify light ion species in order to generate double differential energy spectra of the light ion fragments. Comparisons of these measured yields were compared with Monte Carlo calculations generated by MCNP6. These yields will be used to quantify uncertainty in radiation transport codes utilized in risk assessment for spaceflight missions with prolonged exposures to galactic cosmic rays.

  7. Synthesis of Defect Perovskites (He2-x□x)(CaZr)F6 by Inserting Helium into the Negative Thermal Expansion Material CaZrF6.

    PubMed

    Hester, Brett R; Dos Santos, António M; Molaison, Jamie J; Hancock, Justin C; Wilkinson, Angus P

    2017-09-27

    Defect perovskites (He2-x□x)(CaZr)F6 can be prepared by inserting helium into CaZrF6 at high pressure. They can be recovered to ambient pressure at low temperature. There are no prior examples of perovskites with noble gases on the A-sites. The insertion of helium gas into CaZrF6 both elastically stiffens the material and reduces the magnitude of its negative thermal expansion. It also suppresses the onset of structural disorder, which is seen on compression in other media. Measurements of the gas released on warming to room temperature and Rietveld analyses of neutron diffraction data at low temperature indicate that exposure to helium gas at 500 MPa leads to a stoichiometry close to (He1□1)(CaZr)F6. Helium has a much higher solubility in CaZrF6 than silica glass or crystobalite. An analogue with composition (H2)2(CaZr)F6 would have a volumetric hydrogen storage capacity greater than current US DOE targets. We anticipate that other hybrid perovskites with small neutral molecules on the A-site can also be prepared and that they will display a rich structural chemistry.

  8. Region 6 Targeted Brownfields Assessment

    EPA Pesticide Factsheets

    A Target Brownfields Assessment (TBA) is a free service the EPA Region 6 Brownfields Team provides to communities to support their eligible brownfields projects. Region 6 consists of Arkansas, Louisiana, new Mexico, Oklahoma, and Texas.

  9. Performance characterization of a 6-K multiple JT helium adsorption cryocooler

    NASA Technical Reports Server (NTRS)

    Elliot, S.; Johnson, D. L.; Lindersmith, C. A.; Sirbi, A.

    2002-01-01

    We present the work done at the Jet Propulsion Laboratory for a Helium Adsorption Cooler to produce continuous cooling power at a temperature around 6 K. The goal of this development is to be able to propose for future space mission a long lifetime, vibration free cooler, which can cover the temperature range 18 K to 5 K.

  10. Performance characterization of a 6-K multiple JT helium adsorption cryocooler

    NASA Technical Reports Server (NTRS)

    Elliot, S.; Johnson, D. L.; Lindersmith, C. A.; Sirbi, A.

    2002-01-01

    We present the work done at the Jet Propulsion Laboratory for a Helium Adsorption Cooler to produce continuous cooling power at a temperature around 6 K. The goal of this development is to be able to propose for future space mission a long lifetime, vibration free cooler, which can cover the temperature range 18 K to 5 K.

  11. Photoionization and photofragmentation of SF6 in helium nanodroplets.

    PubMed

    Peterka, Darcy S; Kim, Jeong Hyun; Wang, Chia C; Neumark, Daniel M

    2006-10-12

    The photoionization of He droplets doped with SF6 was investigated using tunable vacuum ultraviolet (VUV) synchrotron radiation from the Advanced Light Source (ALS). The resulting ionization and photofragmentation dynamics were characterized using time-of-flight mass spectrometry combined with photofragment and photoelectron imaging. Results are compared to those of gas-phase SF6 molecules. We find dissociative photoionization to SF5+ to be the dominant channel, in agreement with previous results. Key new findings are that (a) the photoelectron spectrum of the SF6 in the droplet is similar but not identical to that of the gas-phase species, (b) the SF5+ photofragment velocity distribution is considerably slower upon droplet photoionization, and (c) fragmentation to SF4+ and SF3+ is much less than in the photoionization of bare SF6. From these measurements we obtain new insights into the mechanism of SF6 photoionization within the droplet and the cooling of the hot photofragment ions produced by dissociative photoionization.

  12. Mixing studies of helium in air at Mach 6

    NASA Technical Reports Server (NTRS)

    Thomas, R. H.; Schetz, J. A.; Fuller, E. J.; Mays, R. B.

    1991-01-01

    Concentration and mean flow measurements with nanoshadowgraphs and surface flow visualization have been obtained by a study of mixing phenomena during gas injection into hypersonic flow. At Mach 6, a comparison of the matched-pressure injection case with the underexpanded case indicated a greater injectant core penetration rate and a greater concentration-decay rate, leading to a shorter distance for the injectant core to reach an H2-air stoichiometric ratio. The entire injectant plume remained supersonic, and only moderate pressure losses were found. While injector yaw did not increase the mixing rates, it led to an increase in overall injectant plume cross-section, with consequent increase in the size of the mixing region.

  13. Polarization of the light from the 3P(1)-2S(1) transition in proton beam excited helium. Ph.D. Thesis; [target gas pressure effects

    NASA Technical Reports Server (NTRS)

    Weinhous, M. S.

    1973-01-01

    Measurements of the polarization of the light from the 3 1p-2 1s transition in proton beam excited Helium have shown both a proton beam energy and Helium target gas pressure dependence. Results for the linear polarization fraction range from +2.6% at 100 keV proton energy to -5.5% at 450 keV. The zero crossover occurs at approximately 225 keV. This is in good agreement with other experimental work in the field, but in poor agreement with theoretical predictions. Measurements at He target gas pressures as low as .01 mtorr show that the linear polarization fraction is still pressure dependent at .01 mtorr.

  14. Analysis of conductive target influence in plasma jet experiments through helium metastable and electric field measurements

    NASA Astrophysics Data System (ADS)

    Darny, T.; Pouvesle, J.-M.; Puech, V.; Douat, C.; Dozias, S.; Robert, Eric

    2017-04-01

    The use of cold atmospheric pressure plasma jets for in vivo treatments implies most of the time plasma interaction with conductive targets. The effect of conductive target contact on the discharge behavior is studied here for a grounded metallic target and compared to the free jet configuration. In this work, realized with a plasma gun, we measured helium metastable HeM (23S1) concentration (by laser absorption spectroscopy) and electric field (EF) longitudinal and radial components (by electro-optic probe). Both diagnostics were temporally and spatially resolved. Mechanisms after ionization front impact on the target surface have been identified. The remnant conductive ionized channel behind the ionization front electrically transiently connects the inner high voltage electrode to the target. Due to impedance mismatching between the ionized channel and the target, a secondary ionization front is initiated and rapidly propagates from the target surface to the inner electrode through this ionized channel. This leads to a greatly enhanced HeM production inside the plasma plume and the capillary. Forward and reverse dynamics occur with further multi reflections of more or less damped ionization fronts between the inner electrode and the target as long as the ionized channel is persisting. This phenomenon is very sensitive to parameters such as target distance and ionized channel conductivity affecting electrical coupling between these two and evidenced using positive or negative voltage polarity and nitrogen admixture. In typical operating conditions for the plasma gun used in this work, it has been found that after the secondary ionization front propagation, when the ionized channel is conductive enough, a glow like discharge occurs with strong conduction current. HeM production and all species excitation, especially reactive ones, are then driven by high voltage pulse evolution. The control of forward and reverse dynamics, impacting on the production of the glow

  15. The Effects of Helium Bubble Microstructure on Ductility in Annealed and HERF 21Cr-6Ni-9Mn Stainless Steel

    SciTech Connect

    Tosten, M.H.; Morgan, M.J.

    1998-01-01

    This study examined the effects of microstructure on the ambient temperature embrittlement from hydrogen isotopes and decay helium in 21Cr-6Ni-9Mn stainless steel. Hydrogen and tritium-exposed 21Cr-6Ni-9Mn stainless steel tensile samples were pulled to failure and then characterized by transmission electron microscopy (TEM) and optical microscopy. This study determined that ductility differences between annealed and high-energy-rate-forged (HERF) stainless steel containing tritium and its decay product, helium, could be related to differences in the helium bubble microstructures. The HERF microstructures were more resistant to tritium-induced embrittlement than annealed microstructures because the high number density of helium bubbles on dislocations trap tritium within the matrix and away from the grain boundaries.

  16. Properties of V-(8-9)Cr-(5-6)Ti alloys irradiated in the dynamic helium charging experiment

    SciTech Connect

    Chung, H.M.; Nowicki, L.; Smith, D.L.

    1996-10-01

    In the Dynamic Helium Charging Experiment (DHCE), helium was produced uniformly in vanadium alloy specimens by the decay of tritium during irradiation to 18-31 dpa at 425-600{degrees}C in lithium-filled capsules in the Fast Flux Test Facility. This report presents results of postirradiation tests of tensile properties and density change in V-8Cr-6Ti and V-9Cr-5Ti. Compared to tensile properties of the alloys irradiated in the non-DHCE (helium generation negligible), the effect of helium on tensile strength and ductility of V-8Cr-6Ti and V-9Cr-5Ti was insignificant after irradiation and testing at 420, 500, and 600{degrees}C. Both alloys retained a total elongation of >11 % at these temperatures. Density change was <0.48% for both alloys.

  17. Study of Rayleigh scattering for visualization of helium-air mixing at Mach 6

    NASA Technical Reports Server (NTRS)

    Shirinzadeh, B.; Balla, R. J.; Hillard, M. E.; Anders, J. B.; Exton, R. J.; Waitz, I. A.

    1991-01-01

    Using an ArF excimer laser, planar Rayleigh scattering measurements were performed to investigate helium mixing into air at supersonic speeds. These experiments were conducted in the Mach 6, high-Reynolds-number facility at NASA Langley Research Center. The capability of the Rayleigh scattering technique for flow visualization of a turbulent environment was demonstrated. The qualitative agreement between the averaged Rayleigh results and the reduced mean-mass-densities obtained from probe measurements substantiate that careful application of the technique, even in the presence of clusters, can give very useful results. It was also demonstrated that planar, quantitative measurements can be made in the absence of clusters.

  18. Planar Rayleigh scattering results in helium-air mixing experiments in a Mach-6 wind tunnel

    NASA Technical Reports Server (NTRS)

    Shirinzadeh, B.; Hillard, M. E.; Balla, R. J.; Waitz, I. A.; Anders, J. B.; Exton, R. J.

    1992-01-01

    Planar Rayleigh scattering measurements with an argon-fluoride excimer laser are performed to investigate helium mixing into air at supersonic speeds. The capability of the Rayleigh scattering technique for flow visualization of a turbulent environment is demonstrated in a large-scale, Mach-6 facility. The detection limit obtained with the present setup indicates that planar, quantitative measurements of density can be made over a large cross-sectional area (5 cm x 10 cm) of the flow field in the absence of clusters.

  19. Planar Rayleigh scattering results in helium-air mixing experiments in a Mach-6 wind tunnel.

    PubMed

    Shirinzadeh, B; Hillard, M E; Balla, R J; Waitz, I A; Anders, J B; Exton, R J

    1992-10-20

    Planar Rayleigh scattering measurements with an argon-fluoride excimer laser are performed to investigate helium mixing into air at supersonic speeds. The capability of the Rayleigh scattering technique for flow visualization of a turbulent environment is demonstrated in a large-scale, Mach-6 facility. The detection limit obtained with the present setup indicates that planar, quantitative measurements of density can be made over a large cross-sectional area (5 cm x 10 cm) of the flow field in the absence of clusters.

  20. Planar Rayleigh Scattering Results in Helium/Air Mixing Experiments in a Mach 6 Wind Tunnel

    NASA Technical Reports Server (NTRS)

    Shirinzadeh, B.; Balla, R. Jeffrey; Hillard, M. E.; Anders, J. B.; Exton, R. J.; Waitz, I. A.

    1991-01-01

    Planar Rayleigh scattering measurements using an ArF-excimer laser have been performed to investigate helium mixing into air at supersonic speeds. The capability of the Rayleigh scattering technique for flow visualization of a turbulent environment is demonstrated in a large-scale, Mach 6facility. The detection limit obtained with the present setup indicates that planar, quantitative measurements of density can be made over a large cross sectional area (5 cm by 10 cm) of the flow field in the absence of clusters.

  1. Effect of helium nanoclusters on the spectroscopic properties of embedded SF6: Ionization, excitation and vibration

    NASA Astrophysics Data System (ADS)

    Dehdashti-Jahromi, M.; Farrokhpour, H.

    2017-02-01

    Ionization and excitation energies, IR and Raman spectra of sulfur hexafluoride (SF6), located inside helium (He) nanoclusters with different sizes (SF6@Hen; n = 20, 40, 60), were calculated. The effect of the cluster size on the spectroscopic properties of the SF6 was investigated and found that the Hen-SF6 interaction in the He clusters with large number of atoms is small so that the ionization and absorption energies of SF6 are not affected while for small He nanoclusters the Hen-SF6 interaction is more important. The effect of Hen-SF6 interaction and deformation of the fragments on the photoelectron and absorption spectra of SF6@Hen were separated theoretically and discussed in details. It was deduced that the effect of the cluster size on the IR and Raman vibrational frequencies of the SF6 is negligible for the cluster size range considered in this work. Density functional theory (DFT) employing M06-2X functional and 6-31 + G(df) basis set were used for optimizing the structures of SF6@Hen. Symmetry adapted cluster-configuration interaction (SAC-CI) methodology, with the same basis set, were used to calculate the ionization and excitation energies of the SF6@Hen structures. Using the calculated ionization and absorption energies and their intensities, the photoelectron and absorption spectra of the considered SF6@Hen structures were simulated and compared with the experiment.

  2. Effect of helium nanoclusters on the spectroscopic properties of embedded SF6: Ionization, excitation and vibration.

    PubMed

    Dehdashti-Jahromi, M; Farrokhpour, H

    2017-02-15

    Ionization and excitation energies, IR and Raman spectra of sulfur hexafluoride (SF6), located inside helium (He) nanoclusters with different sizes (SF6@Hen; n=20, 40, 60), were calculated. The effect of the cluster size on the spectroscopic properties of the SF6 was investigated and found that the Hen-SF6 interaction in the He clusters with large number of atoms is small so that the ionization and absorption energies of SF6 are not affected while for small He nanoclusters the Hen-SF6 interaction is more important. The effect of Hen-SF6 interaction and deformation of the fragments on the photoelectron and absorption spectra of SF6@Hen were separated theoretically and discussed in details. It was deduced that the effect of the cluster size on the IR and Raman vibrational frequencies of the SF6 is negligible for the cluster size range considered in this work. Density functional theory (DFT) employing M06-2X functional and 6-31+G(df) basis set were used for optimizing the structures of SF6@Hen. Symmetry adapted cluster-configuration interaction (SAC-CI) methodology, with the same basis set, were used to calculate the ionization and excitation energies of the SF6@Hen structures. Using the calculated ionization and absorption energies and their intensities, the photoelectron and absorption spectra of the considered SF6@Hen structures were simulated and compared with the experiment. Copyright © 2016 Elsevier B.V. All rights reserved.

  3. Targets Involved in Cardioprotection by the Non-Anesthetic Noble Gas Helium.

    PubMed

    Weber, Nina C; Smit, Kirsten F; Hollmann, Markus W; Preckel, Benedikt

    2015-01-01

    Research data from the past decade indicate that noble gases like xenon and helium exert profound cardioprotection when applied before, during or after organ ischemia. Of all noble gases, especially helium, has gained interest in the past years because it does not have an anesthetic "side effect" like xenon, allowing application of this specific gas in numerous clinical ischemia/reperfusion situations. Because helium has several unique characteristics and no hemodynamic side effects, helium could be administered in severely ill patients. Investigations in animals as well as in humans have proven that this noble gas is not completely inert and can induce several biological effects. Though the underlying molecular mechanisms of helium-induced cardiac protection are still not yet fully understood, recently different signaling pathways have been elucidated.

  4. The effect of hydrogen isotopes and helium on the tensile properties of 21-6-9 stainless steel

    SciTech Connect

    Morgan, M.J.; Lohmeier, D.

    1990-01-01

    High-energy-rate-forged (HERF) stainless steels are used as the materials of construction for pressure vessels designed for the containment of hydrogen and its isotopes. Hydrogen and helium, the decay product of tritium, are known to embrittle these materials. HERF stainless steels have a relatively good resistance to hydrogen-and-helium-induced embrittlement when compared to annealed stainless steels due to their high number density of dislocations, which act as traps for hydrogen and helium. However, the degree of embrittlement in these materials can vary considerably because of microstructure and yield strength variations introduced during the forging process. In this study the effect of hydrogen and tritium on the tensile properties of 21-6-9 stainless steel was measured as a function of HERF yield strength in the range of 660 to 930 MPa. The effect of microstructure was studied also be conducting tensile tests with HERF and annealed samples.

  5. Targeting interleukin-6 for noninfectious uveitis.

    PubMed

    Lin, Phoebe

    2015-01-01

    Interleukin-6 (IL-6) is a pleiotropic cytokine implicated in the pathogenesis of many immune-mediated disorders including several types of non-infectious uveitis. These uveitic conditions include Vogt-Koyanagi-Harada syndrome, uveitis associated with Behçet disease, and sarcoidosis. This review summarizes the role of IL-6 in immunity, highlighting its effect on Th17, Th1, and plasmablast differentiation. It reviews the downstream mediators activated in the process of IL-6 binding to its receptor complex. This review also summarizes the biologics targeting either IL-6 or the IL-6 receptor, including tocilizumab, sarilumab, sirukumab, olokizumab, clazakizumab, and siltuximab. The target, dosage, potential side effects, and potential uses of these biologics are summarized in this article based on the existing literature. In summary, anti-IL-6 therapy for non-infectious uveitis shows promise in terms of efficacy and side effect profile.

  6. Spent Nuclear Fuel (SNF) Project Cask and MCO Helium Purge System Design Review Completion Report Project A.5 and A.6

    SciTech Connect

    ARD, K.E.

    2000-04-19

    This report documents the results of the design verification performed on the Cask and Multiple Canister Over-pack (MCO) Helium Purge System. The helium purge system is part of the Spent Nuclear Fuel (SNF) Project Cask Loadout System (CLS) at 100K area. The design verification employed the ''Independent Review Method'' in accordance with Administrative Procedure (AP) EN-6-027-01.

  7. Characterization of deuterium clusters mixed with helium gas for an application in beam-target-fusion experiments

    SciTech Connect

    Bang, W.; Quevedo, H. J.; Bernstein, A. C.; Dyer, G.; Ihn, Y. S.; Cortez, J.; Aymond, F.; Gaul, E.; Donovan, M. E.; Barbui, M.; Bonasera, A.; Natowitz, J. B.; Albright, B. J.; Fernández, J. C.; Ditmire, T.

    2014-12-10

    We measured the average deuterium cluster size within a mixture of deuterium clusters and helium gas by detecting Rayleigh scattering signals. The average cluster size from the gas mixture was comparable to that from a pure deuterium gas when the total backing pressure and temperature of the gas mixture were the same as those of the pure deuterium gas. According to these measurements, the average size of deuterium clusters depends on the total pressure and not the partial pressure of deuterium in the gas mixture. To characterize the cluster source size further, a Faraday cup was used to measure the average kinetic energy of the ions resulting from Coulomb explosion of deuterium clusters upon irradiation by an intense ultrashort pulse. The deuterium ions indeed acquired a similar amount of energy from the mixture target, corroborating our measurements of the average cluster size. As the addition of helium atoms did not reduce the resulting ion kinetic energies, the reported results confirm the utility of using a known cluster source for beam-target-fusion experiments by introducing a secondary target gas.

  8. Characterization of deuterium clusters mixed with helium gas for an application in beam-target-fusion experiments

    DOE PAGES

    Bang, W.; Quevedo, H. J.; Bernstein, A. C.; ...

    2014-12-10

    We measured the average deuterium cluster size within a mixture of deuterium clusters and helium gas by detecting Rayleigh scattering signals. The average cluster size from the gas mixture was comparable to that from a pure deuterium gas when the total backing pressure and temperature of the gas mixture were the same as those of the pure deuterium gas. According to these measurements, the average size of deuterium clusters depends on the total pressure and not the partial pressure of deuterium in the gas mixture. To characterize the cluster source size further, a Faraday cup was used to measure themore » average kinetic energy of the ions resulting from Coulomb explosion of deuterium clusters upon irradiation by an intense ultrashort pulse. The deuterium ions indeed acquired a similar amount of energy from the mixture target, corroborating our measurements of the average cluster size. As the addition of helium atoms did not reduce the resulting ion kinetic energies, the reported results confirm the utility of using a known cluster source for beam-target-fusion experiments by introducing a secondary target gas.« less

  9. Characterization of deuterium clusters mixed with helium gas for an application in beam-target-fusion experiments

    NASA Astrophysics Data System (ADS)

    Bang, W.; Quevedo, H. J.; Bernstein, A. C.; Dyer, G.; Ihn, Y. S.; Cortez, J.; Aymond, F.; Gaul, E.; Donovan, M. E.; Barbui, M.; Bonasera, A.; Natowitz, J. B.; Albright, B. J.; Fernández, J. C.; Ditmire, T.

    2014-12-01

    We measured the average deuterium cluster size within a mixture of deuterium clusters and helium gas by detecting Rayleigh scattering signals. The average cluster size from the gas mixture was comparable to that from a pure deuterium gas when the total backing pressure and temperature of the gas mixture were the same as those of the pure deuterium gas. According to these measurements, the average size of deuterium clusters depends on the total pressure and not the partial pressure of deuterium in the gas mixture. To characterize the cluster source size further, a Faraday cup was used to measure the average kinetic energy of the ions resulting from Coulomb explosion of deuterium clusters upon irradiation by an intense ultrashort pulse. The deuterium ions indeed acquired a similar amount of energy from the mixture target, corroborating our measurements of the average cluster size. As the addition of helium atoms did not reduce the resulting ion kinetic energies, the reported results confirm the utility of using a known cluster source for beam-target-fusion experiments by introducing a secondary target gas.

  10. Characterization of deuterium clusters mixed with helium gas for an application in beam-target-fusion experiments.

    PubMed

    Bang, W; Quevedo, H J; Bernstein, A C; Dyer, G; Ihn, Y S; Cortez, J; Aymond, F; Gaul, E; Donovan, M E; Barbui, M; Bonasera, A; Natowitz, J B; Albright, B J; Fernández, J C; Ditmire, T

    2014-12-01

    We measured the average deuterium cluster size within a mixture of deuterium clusters and helium gas by detecting Rayleigh scattering signals. The average cluster size from the gas mixture was comparable to that from a pure deuterium gas when the total backing pressure and temperature of the gas mixture were the same as those of the pure deuterium gas. According to these measurements, the average size of deuterium clusters depends on the total pressure and not the partial pressure of deuterium in the gas mixture. To characterize the cluster source size further, a Faraday cup was used to measure the average kinetic energy of the ions resulting from Coulomb explosion of deuterium clusters upon irradiation by an intense ultrashort pulse. The deuterium ions indeed acquired a similar amount of energy from the mixture target, corroborating our measurements of the average cluster size. As the addition of helium atoms did not reduce the resulting ion kinetic energies, the reported results confirm the utility of using a known cluster source for beam-target-fusion experiments by introducing a secondary target gas.

  11. Investigation of mixed ion fields in the forward direction for 220.5 MeV/u helium ion beams: comparison between water and PMMA targets.

    PubMed

    Aricò, G; Gehrke, T; Jakubek, J; Gallas, R; Berke, S; Jäkel, O; Mairani, A; Ferrari, A; Martišíková, M

    2017-10-03

    Currently there is a rising interest in helium ion beams for radiotherapy. For benchmarking of the physical beam models used in treatment planning, there is a need for experimental data on the composition and spatial distribution of mixed ion fields. Of particular interest are the attenuation of the primary helium ion fluence and the build-up of secondary hydrogen ions due to nuclear interactions. The aim of this work was to provide such data with an enhanced precision. Moreover, the validity and limits of the mixed ion field equivalence between water and PMMA targets were investigated. Experiments with a 220.5 MeV/u helium ion pencil beam were performed at the Heidelberg Ion-Beam Therapy Center in Germany. The compact detection system used for ion tracking and identification was solely based on Timepix position-sensitive semiconductor detectors. In comparison to standard techniques, this system is two orders of magnitude smaller, and provides higher precision and flexibility. The numbers of outgoing helium and hydrogen ions per primary helium ion as well as the lateral particle distributions were quantitatively investigated in the forward direction behind water and PMMA targets with 5.2-18 cm water equivalent thickness (WET). Comparing water and PMMA targets with the same WET, we found that significant differences in the amount of outgoing helium and hydrogen ions and in the lateral particle distributions arise for target thicknesses above 10 cm WET. The experimental results concerning hydrogen ions emerging from the targets were reproduced reasonably well by Monte Carlo simulations using the FLUKA code. Concerning the amount of outgoing helium ions, significant differences of 3-15% were found between experiments and simulations. We conclude that if PMMA is used in place of water in dosimetry, differences in the dose distributions could arise close to the edges of the field, in particular for deep seated targets.

  12. Description and initial operating performance of the Langley 6-inch expansion tube using heated helium driver gas

    NASA Technical Reports Server (NTRS)

    Moore, J. A.

    1975-01-01

    A general description of the Langley 6-inch expansion tube is presented along with discussion of the basic components, internal resistance heater, arc-discharge assemblies, instrumentation, and operating procedure. Preliminary results using unheated and resistance-heated helium as the driver gas are presented. The driver-gas pressure ranged from approximately 17 to 59 MPa and its temperature ranged from 300 to 510 K. Interface velocities of approximately 3.8 to 6.7 km/sec were generated between the test gas and the acceleration gas using air as the test gas and helium as the acceleration gas. Test flow quality and comparison of measured and predicted expansion-tube flow quantities are discussed.

  13. IR spectroscopy of protonated leu-enkephalin and its 18-crown-6 complex embedded in helium droplets.

    PubMed

    González Flórez, Ana Isabel; Ahn, Doo-Sik; Gewinner, Sandy; Schöllkopf, Wieland; von Helden, Gert

    2015-09-14

    Ultracold IR spectra of the protonated five amino acid peptide leu-enkephalin (Tyr-Gly-Gly-Phe-Leu) embedded in superfluid helium droplets have been recorded using a free-electron laser as radiation source. The results show resolved spectra, which are in good agreement with theoretical calculations, as well as with the available gas-phase data indicating that the helium environment does not induce a significant matrix-shift. In addition, the effect of the interaction between the charge and the peptide backbone has been further investigated by complexing protonated leu-enkephalin with one 18-crown-6 molecule. Good agreement between the experimental and theoretical results allow for an assignment of a preferred molecular structure.

  14. Helium and hydrogen measurements on pure materials irradiated in SINQ Target 4

    NASA Astrophysics Data System (ADS)

    Oliver, B. M.; Dai, Y.

    2009-04-01

    Several irradiations have been performed in the Swiss Spallation Neutron Source (SINQ) to establish a materials database for mixed proton and neutron fluxes for future spallation neutron and other accelerator sources. Pure metal dosimetry materials from the second irradiation (STIP-II) have been analyzed for their total helium and hydrogen contents and their release characteristics with temperature (TDS). Total helium results are similar to those observed earlier from the first irradiation experiment (STIP-I), with concentrations ranging from ˜500 to ˜1000 appm. Hydrogen contents varied over a larger range from ˜100 to ˜60 000. 3He/ 4He ratios were generally consistent with expectations, except for Ti, Nb, and Ta which showed lower values due to 3He from decay of irradiation-generated tritium. Some differences were observed in the hydrogen TDS data for the control and irradiated materials, including some evidence for additional lower-temperature release and for multiple release peaks. Additionally, differences were noted in the releases for irradiated material that been cleaned versus material that had no cleaning.

  15. Evolution of Helium Bubbles and Discs in Irradiated 6H-SiC during Post-Implantation Annealing

    PubMed Central

    Shen, Qiang; Zhou, Wei; Ran, Guang; Li, Ruixiang; Feng, Qijie; Li, Ning

    2017-01-01

    The single crystal 6H-SiC with [0001] crystal direction irradiated by 400 keV He+ ions with 1 × 1017 ions/cm2 fluence at 400 °C were annealed at 600, 900, 1200 and 1400 °C for different durations. The evolution of helium bubbles and discs was investigated by transmission electron microscopy. An irradiated layer distributed with fine helium bubbles was formed with a width of ~170 nm after helium ion irradiation. The size of gas bubbles increased with increasing annealing time and temperature and finally reached stable values at a given annealing temperature. According to the relationship between the bubble radii and annealing time, an empirical formula for calculating the bubble radii at the annealing temperature ranged from 600 to 1400 °C was given by fitting the experiment data. Planar bubble clusters (discs) were found to form on (0001) crystal plane at both sides of the bubble layer when the annealing temperature was at the range of 800–1200 °C. The mechanism of bubble growth during post-implantation annealing and the formation of bubble discs were also analyzed and discussed. PMID:28772459

  16. Evolution of Helium Bubbles and Discs in Irradiated 6H-SiC during Post-Implantation Annealing.

    PubMed

    Shen, Qiang; Zhou, Wei; Ran, Guang; Li, Ruixiang; Feng, Qijie; Li, Ning

    2017-01-24

    The single crystal 6H-SiC with [0001] crystal direction irradiated by 400 keV He⁺ ions with 1 × 10(17) ions/cm² fluence at 400 °C were annealed at 600, 900, 1200 and 1400 °C for different durations. The evolution of helium bubbles and discs was investigated by transmission electron microscopy. An irradiated layer distributed with fine helium bubbles was formed with a width of ~170 nm after helium ion irradiation. The size of gas bubbles increased with increasing annealing time and temperature and finally reached stable values at a given annealing temperature. According to the relationship between the bubble radii and annealing time, an empirical formula for calculating the bubble radii at the annealing temperature ranged from 600 to 1400 °C was given by fitting the experiment data. Planar bubble clusters (discs) were found to form on (0001) crystal plane at both sides of the bubble layer when the annealing temperature was at the range of 800-1200 °C. The mechanism of bubble growth during post-implantation annealing and the formation of bubble discs were also analyzed and discussed.

  17. Manufacture of a 6-m superconducting solenoid indirectly cooled by supercritical helium

    SciTech Connect

    Satow, T.; Kawaguchi, T.; Kawamura, T.; Ogino, O.

    1982-01-01

    A design study is presented as performed with the superconducting solenoid for a pulsed muon channel. The main part of the development was the construction and testing of epoxy-impregnated model soils and supercritical helium experiments. The solenoide operates satisfactorily and has been used on a high-flux pulsed muon beam. Continuous operation for 2500 hours has been achieved. This is the first long-term operation of a large scale superconducting magnet system in Japan.

  18. Effect of initial-state target polarization on the single ionization of helium by 1-keV electron impact

    NASA Astrophysics Data System (ADS)

    Sun, Shi-Yan; Ma, Xiao-Yan; Li, Xia; Miao, Xiang-Yang; Jia, Xiang-Fu

    2012-07-01

    We report new results of triple differential cross sections for the single ionization of helium by 1-KeV electron impact at the ejection energy of 10 eV. Investigations have been made for both the perpendicular plane and the plane perpendicular to the momentum transfer geometries. The present calculation is based on the three-Coulomb wave function. Here we have also incorporated the effect of target polarization in the initial state. A comparison is made between the present calculation with the results of other theoretical methods and a recent experiment [Dürr M, Dimopoulou C, Najjari B, Dorn A, Bartschat K, Bray I, Fursa D V, Chen Z, Madison D H and Ullrich J 2008 Phys. Rev. A 77 032717]. At an impact energy of 1 KeV, the target polarization is found to induce a substantial change of the cross section for the ionization process. We observe that the effect of target polarization plays a dominant role in deciding the shape of triple differential cross sections.

  19. Efficient charge-breeding of helium-6 in an EBIT for precision measurement of the beta-neutrino correlation

    SciTech Connect

    Schmidt, M.; Hass, M.; Rappaport, M. L.; Heber, O.; Prygarin, A.; Shachar, Y.; Vaintraub, S.; Zschornack, G.

    2015-01-09

    The precise determination of the beta-neutrino correlation in the decay of radioactive nuclei is an important tool in the effort to probe fundamental interactions for possible deviation from the Standard Model of particles and fields. In order to realize this, a novel scheme for precision measurement of such correlation in the decay of radioactive helium-6 (half-life 0.8 s) using an electrostatic ion beam trap (EIBT) is being constructed at the Weizmann Institute. Efficient ionization of the expected weak flux of helium-6, together with a bunching characteristic suitable for injection into the EIBT, is thereby essential. Both of these requirements are optimally met by an electron beam ion source/trap (EBIT). In this contribution we present the design of a modified DREEBIT (Dresden EBIT) featuring a direct, nearly closed gas intake into the drift tube assembly for maximum trapping and ionization efficiency for low flux rates, without diminishing the bunching phase space of the EBIT. First tests already indicate significant ion production at a minimal gas flow rate observable by a marginal pressure increase that is close to the detection limit of a Leybold extractor gauge located in close proximity to the drift tube assembly. This is a necessary precondition in order to exploit even tiny amounts of rare isotopes.

  20. Converged cross-section results for double photoionization of helium atoms in hyperspherical partial wave theory at 6 eV above threshold

    SciTech Connect

    Das, J.N.; Paul, S.; Chakrabarti, K.

    2004-04-01

    Here we report a set of converged cross-section results for double photoionization of helium atoms obtained in the hyperspherical partial wave theory for equal energy sharing kinematics at 6 eV energy above threshold. The calculated cross section results are generally in excellent agreement with the absolute measured results of Doerner et al. [Phys. Rev. 57, 1074 (1998)].

  1. Proton-helium correlation in 94 MeV/nucleon sup 16 O-induced reactions on Al, Ni, and Au targets

    SciTech Connect

    Badala, A.; Barbera, R.; Palmeri, A.; Pappalardo, G.S. ); Riggi, F. ); Bizard, G.; Durand, D.; Laville, J.L. )

    1992-04-01

    Azimuthal distributions of helium ions have been measured in coincidence with high-energy protons in reactions induced by {sup 16}O at 94 MeV/nucleon on {sup 27}Al, {sup 58}Ni, and {sup 197}Au. Helium ions have been detected in a large area multidetector. Protons have been observed at 90{degree}. Mean multiplicities of light charged particles (H and He) are found slightly dependent on the target mass. Strong azimuthal asymmetries whose intensity is larger for the Al target and vanishes with the increasing of the target mass are observed in the He distributions. Experimental data are discussed in the framework of the participant-spectator picture of a modified fireball model, taking into account intermediate energy corrections. In this framework the behavior of the azimuthal asymmetries, as a function of the target mass, indicates a strong final-state interaction between participant and spectator fragments. Such a result is found in agreement with interaction time predictions of a microscopical calculation based on the Boltzmann-Nordheim-Vlasov equation.

  2. Helium cryogenics

    SciTech Connect

    Van Sciver, S.W.

    1986-01-01

    The goal of this work is to bridge the gap between physics and engineering aspects of helium fluids to encourage their use and enhance their usefulness in low-temperature systems. Topics covered include thermodynamic laws, electrical and thermal conductivities, spin systems, virial expansion, liquid He I, transport properties, density of helium as a quantum fluid, vortices and turbulence in He II, Kapitza conductance, acoustic mismatch theory, nucleate boiling heta transfer, surface effects, general considerations of internal flow, ideal liquefaction, stirling cycle, and the helium-3 isotope.

  3. Optical detection of magnetic field with Mn4+:K2SiF6 phosphor from room to liquid helium temperatures

    NASA Astrophysics Data System (ADS)

    Zhong, Zhiqiang; Wang, Xia; Zhang, Junpei; Zhong, Haizheng; Han, Jun-Bo

    2017-05-01

    An optical method for detecting magnetic fields is developed based on the photoluminescence (PL) properties of a Mn4+:K2SiF6 phosphor. Under excitation by a 457-nm argon laser, strong red PL was observed in Mn4+:K2SiF6 microcrystals from room to liquid helium temperatures. The Lande factor (g) of the Zeeman splitting peaks remained close to 2 within the measured temperature range. These features make this Mn4+:K2SiF6 phosphor an idea optical material for remote sensing of high magnetic fields over a broad temperature range.

  4. Helium diffusion in carbonates

    NASA Astrophysics Data System (ADS)

    Amidon, W. H.; Cherniak, D. J.; Watson, E. B.; Hobbs, D.

    2013-12-01

    The abundance and large grain size of carbonate minerals make them a potentially attractive target for 4He thermochronology and 3He cosmogenic dating, although the diffusive properties of helium in carbonates remain poorly understood. This work characterizes helium diffusion in calcite and dolomite to better understand the crystal-chemical factors controlling He transport and retentivity. Slabs of cleaved natural calcite and dolomite, and polished sections of calcite cut parallel or normal to c, were implanted with 3He at 3 MeV with a dose of 5x1015/cm2. Implanted carbonates were heated in 1-atm furnaces, and 3He distributions following diffusion anneals were profiled with Nuclear Reaction Analysis using the reaction 3He(d,p)4He. For 3He transport normal to cleavage surfaces in calcite, we obtain the following Arrhenius relation over the temperature range 78-300°C: Dcalcite = 9.0x10-9exp(-55 × 6 kJ mol-1/RT) m2sec-1. Diffusion in calcite exhibits marked anisotropy, with diffusion parallel to c about two orders of magnitude slower than diffusion normal to cleavage faces. He diffusivities for transport normal to the c-axis are similar in value to those normal to cleavage surfaces. Our findings are broadly consistent with helium diffusivities from step-heating measurements of calcite by Copeland et al. (2007); these bulk degassing data may reflect varying effects of diffusional anisotropy. Helium diffusion normal to cleavage surfaces in dolomite is significantly slower than diffusion in calcite, and has a much higher activation energy for diffusion. For dolomite, we obtain the following Arrhenius relation for He diffusion over the temperature range 150-400°C: Ddolomite = 9.0x10-8exp(-92 × 9 kJ mol-1/RT) m2sec-1. The role of crystallographic structure in influencing these differences among diffusivities was evaluated using the maximum aperture approach of Cherniak and Watson (2011), in which crystallographic structures are sectioned along possible diffusion

  5. 6. VIEW, LOOKING SOUTHEAST, SHOWING DETAIL OF RANGE 1 TARGET ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    6. VIEW, LOOKING SOUTHEAST, SHOWING DETAIL OF RANGE 1 TARGET END, Interior - Winchester Repeating Arms Company, Tract K Shooting Range, 125 Munson Street (rear section), New Haven, New Haven County, CT

  6. Targeting interleukin-6 in inflammatory autoimmune diseases and cancers.

    PubMed

    Yao, Xin; Huang, Jiaqi; Zhong, Haihong; Shen, Nan; Faggioni, Raffaella; Fung, Michael; Yao, Yihong

    2014-02-01

    Interleukin-6 (IL-6) is a pleiotropic cytokine with significant functions in the regulation of the immune system. As a potent pro-inflammatory cytokine, IL-6 plays a pivotal role in host defense against pathogens and acute stress. However, increased or deregulated expression of IL-6 significantly contributes to the pathogenesis of various human diseases. Numerous preclinical and clinical studies have revealed the pathological roles of the IL-6 pathway in inflammation, autoimmunity, and cancer. Based on the rich body of studies on biological activities of IL-6 and its pathological roles, therapeutic strategies targeting the IL-6 pathway are in development for cancers, inflammatory and autoimmune diseases. Several anti-IL-6/IL-6 receptor monoclonal antibodies developed for targeted therapy have demonstrated promising results in both preclinical studies and clinical trials. Tocilizumab, an anti-IL-6 receptor antibody, is effective in the treatment of various autoimmune and inflammatory conditions notably rheumatoid arthritis. It is the only IL-6 pathway targeting agent approved by the regulatory agencies for clinical use. Siltuximab, an anti-IL-6 antibody, has been shown to have potential benefits treating various human cancers either as a single agent or in combination with other chemotherapy drugs. Several other anti-IL-6-based therapies are also under clinical development for various diseases. IL-6 antagonism has been shown to be a potential therapy for these disorders refractory to conventional drugs. New strategies, such as combination of IL-6 blockade with inhibition of other signaling pathways, may further improve IL-6-targeted immunotherapy of human diseases. © 2013.

  7. 21 CFR 582.1355 - Helium.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Helium. 582.1355 Section 582.1355 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS... Helium. (a) Product. Helium. (b) Conditions of use. This substance is generally recognized as safe when...

  8. 21 CFR 582.1355 - Helium.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Helium. 582.1355 Section 582.1355 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS... Helium. (a) Product. Helium. (b) Conditions of use. This substance is generally recognized as safe when...

  9. 21 CFR 582.1355 - Helium.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Helium. 582.1355 Section 582.1355 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS... Helium. (a) Product. Helium. (b) Conditions of use. This substance is generally recognized as safe when...

  10. 21 CFR 582.1355 - Helium.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Helium. 582.1355 Section 582.1355 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS... Helium. (a) Product. Helium. (b) Conditions of use. This substance is generally recognized as safe when...

  11. 21 CFR 582.1355 - Helium.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Helium. 582.1355 Section 582.1355 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS... Helium. (a) Product. Helium. (b) Conditions of use. This substance is generally recognized as safe when...

  12. Domain definition and target classification for CASP6.

    PubMed

    Tress, Michael; Tai, Chin-Hsien; Wang, Guoli; Ezkurdia, Iakes; López, Gonzalo; Valencia, Alfonso; Lee, Byungkook; Dunbrack, Roland L

    2005-01-01

    Assessment of structure predictions in CASP6 was based on single domains isolated from experimentally determined structures, which were categorized into comparative modeling, fold recognition, and new fold targets. Domain definitions were defined upon visual examination of the structures with the aid of automated domain-parsing programs. Domain categorization was determined by comparison of the target structures with those in the Protein Data Bank at the time each target expired and a variety of sequence and structure-based methods to determine potential homologous relationships. 2005 Wiley-Liss, Inc.

  13. Helium tables.

    NASA Technical Reports Server (NTRS)

    Havill, Clinton H

    1928-01-01

    These tables are intended to provide a standard method and to facilitate the calculation of the quantity of "Standard Helium" in high pressure containers. The research data and the formulas used in the preparation of the tables were furnished by the Research Laboratory of Physical Chemistry, of the Massachusetts Institute of Technology.

  14. Amorphization of Al[sub 6]Mn phase in an Al-14 a/o Mn alloy during low energy helium ion bombardment

    SciTech Connect

    Nair, K.G.M.; Krishan, K. . Materials Science Division); Vijayalakshmi, M. . Metallurgy Division)

    1993-10-01

    Amorphization of ordered intermetallic compounds has been observed during ion, electron and neutron irradiations. Investigations have been carried out in a number of systems. It has been generally observed that intermetallic compounds with a narrow range of homogeneity (line compounds) amorphize on irradiation. The present paper reports the observation of irradiation-induced amorphization in the Al[sub 6]Mn phase in an Al-14 a/o Mn alloy. The dose and energy dependence of the amorphization process are discussed. The present studies suggest that the defects produced during irradiation rather than the implanted atoms (helium) play a major role in the crystalline to amorphous transition.

  15. Thrombospondin-1 Is a Transcriptional Repression Target of PRMT6*

    PubMed Central

    Michaud-Levesque, Jonathan; Richard, Stéphane

    2009-01-01

    Protein arginine methyltransferase 6 (PRMT6) is known to catalyze the generation of asymmetric dimethylarginine in polypeptides. Although the cellular role of PRMT6 is not well understood, it has been implicated in human immunodeficiency virus pathogenesis, DNA repair, and transcriptional regulation. PRMT6 is known to methylate histone H3 Arg-2 (H3R2), and this negatively regulates the lysine methylation of H3K4 resulting in gene repression. To identify in a nonbiased manner genes regulated by PRMT6 expression, we performed a microarray analysis on U2OS osteosarcoma cells transfected with control and PRMT6 small interfering RNAs. We identified thrombospondin-1 (TSP-1), a potent natural inhibitor of angiogenesis, as a transcriptional repression target of PRMT6. Moreover, we show that PRMT6-deficient U2OS cells exhibited cell migration defects that were rescued by blocking the secreted TSP-1 with a neutralizing peptide or blocking α-TSP-1 antibody. PRMT6 associates with the TSP-1 promoter and regulates the balance of methylation of H3R2 and H3K4, such that in PRMT6-deficient cells H3R2 was hypomethylated and H3K4 was trimethylated at the TSP-1 promoter. Using a TSP-1 promoter reporter gene, we further show that PRMT6 directly regulates the TSP-1 promoter activity. These findings show that TSP-1 is a transcriptional repression target of PRMT6 and suggest that neutralizing the activity of PRMT6 could inhibit tumor progression and therefore may be of cancer therapeutic significance. PMID:19509293

  16. Helium Atom Scattering from C2H6, F2HCCH3, F3CCH2F and C2F6 in Crossed Molecular Beams

    NASA Astrophysics Data System (ADS)

    Hammer, Markus; Seidel, Wolfhart

    1997-10-01

    Rotationally unresolved differential cross sections were measured in crossed molecular beam experiments by scattering Helium atoms from Ethane, 1,1-Difluoroethane, 1,1,1,2-Tetrafluoroethane and Hexafluoroethane. The damping of observed diffraction oscillations was used to extract anisotropic interaction potentials for these scattering systems applying the infinite order sudden approximation (IOSA). Binary macroscopic parameters such as second heterogeneous virial coefficients and the coefficients of diffusion and viscosity were computed from these potentials and compared to results from macroscopic experiments.

  17. CD6 as a potential target for treating multiple sclerosis.

    PubMed

    Li, Yan; Singer, Nora G; Whitbred, Joy; Bowen, Michael A; Fox, David A; Lin, Feng

    2017-03-07

    CD6 was established as a marker of T cells more than three decades ago, and recent studies have identified CD6 as a risk gene for multiple sclerosis (MS), a disease in which autoreactive T cells are integrally involved. Nevertheless, the precise role of CD6 in regulating T-cell responses is controversial and its significance in the pathogenesis of various diseases remains elusive, partly due to the lack of animals engineered to alter expression of the CD6 gene. In this report, we found that CD6 KO mice showed decreased pathogenic T-cell responses, reduced spinal cord T-cell infiltration, and attenuated disease severity in experimental autoimmune encephalomyelitis (EAE), an animal model of MS. CD6-deficient T cells exhibited augmented activation, but also significantly reduced survival and proliferation after activation, leading to overall decreased Th1 and Th17 polarization. Activated CD6-deficient T cells also showed impaired infiltration through brain microvascular endothelial cell monolayers. Furthermore, by developing CD6 humanized mice, we identified a mouse anti-human CD6 monoclonal antibody that is highly effective in treating established EAE without depleting T cells. These results suggest that (i) CD6 is a negative regulator of T-cell activation, (ii) at the same time, CD6 is a positive regulator of activated T-cell survival/proliferation and infiltration; and (iii) CD6 is a potential new target for treating MS and potentially other T-cell-driven autoimmune conditions.

  18. Divertor Configurations which Optimize Helium Pumping

    NASA Astrophysics Data System (ADS)

    Strachan, James

    2008-11-01

    Helium accumulation in DT plasmas is often presumed to be one limitation to the fusion power production. The core helium density has an unavoidable central source and a confinement time which tends to be long as is consistent with the required energy confinement times. Any pumping of the helium can only act to reduce the helium recycling. Within that constraint, however, it is still valuable to efficiently pump helium. Helium pumping can be aided by optimal placement of the helium pump in the divertor. The pump should be on the SOL side of the separatrix displaced into the region where the current of impurity particles enters into the divertor and initially strike the target. A numerical example will be given of helium pumping by the ITER divertor. A factor-of-two reduction in core helium densities is possible by optimal pump placement. One difficulty is the need for low temperatures along the targets to prevent their erosion. On ITER, recycled DT near the strike points is hoped to cool this region. The angle between the separatrix and the target is such that recycled neutrals cause ionization, excitation, and dissociation power losses along the target. The ITER solution constrains the choice of pump locations. Alternatively, the strike point cooling can be achieved by local DT (or low Z impurity) injection at the strike point.

  19. Development of AN Active 238UF6 Gas Target

    NASA Astrophysics Data System (ADS)

    Eckardt, C.; Enders, J.; Freudenberger, M.; Göök, A.; von Neumann-Cosel, P.; Oberstedt, A.; Oberstedt, S.

    2014-09-01

    Detailed studies of the fission process, e.g., the search for parity nonconservation (PNC) effects, the energy dependence of fission modes or the population of fission isomers, depend on high quality data, therefore requiring high luminosities. An active gas target containing uranium may overcome the deterioration of energy and angular resolution caused by large solid target thicknesses. A single Frisch-grid ionization chamber has been built to test a mixture of standard counting gases (e.g., argon) with depleted uranium hexafluoride (238UF6), utilizing a triple alpha source to evaluate signal quality and drift velocity. For mass fractions of up to 4 percent of 238U the drift velocity increases with rising UF6 content, while a good signal quality and energy resolution is preserved.

  20. E5/E6 Target Generation Study (TARGEN)

    DTIC Science & Technology

    1988-07-01

    submit DD Form 1498 (Research and Technology Work Unit Summary) and final study documents to Defense Technical Information Center DTIC). 8 B-8 CAA-SR...OAA-SR-88-19 cv) 0 E5/E6 TARGET GENERATION STUDY ev (TARGEN) DTIC JULY 1988 LJAN2198 9’S. PREPARED BY FORCE SYSTEMS DIRECTORATE US ARMY CONCEPTS...MBF 6c. ADDRESS (City, State, and ZIP Code) 10. SOURCE OF FUNDING NUMBERS Headquarters, Department of the Army PROGRAM PROJECT TASK WORK UNIT

  1. TARGETING CDK4 AND CDK6: FROM DISCOVERY TO THERAPY

    PubMed Central

    Sherr, Charles J.; Beach, David; Shapiro, Geoffrey I.

    2015-01-01

    Biochemical and genetic characterization of D-type cyclins, their cyclin D-dependent kinases (CDK4 and CDK6), and the polypeptide CDK4/6 inhibitor p16INK4 over two decades ago revealed how mammalian cells regulate entry into the DNA synthetic (S) phase of the cell division cycle in a retinoblastoma protein (RB)-dependent manner. These investigations provided proof-of-principle that CDK4/6 inhibitors, particularly when combined with co-inhibition of allied mitogen-dependent signal transduction pathways, might prove valuable in cancer therapy. FDA-approval of the CDK4/6 inhibitor palbociclib used with the aromatase inhibitor letrozole for breast cancer treatment highlights long sought success. The newest findings herald clinical trials targeting other cancers. PMID:26658964

  2. Nuclear and nucleolar targeting of human ribosomal protein S6.

    PubMed Central

    Schmidt, C; Lipsius, E; Kruppa, J

    1995-01-01

    Chimeric proteins were constructed to define the nuclear localization signals (NLSs) of human ribosomal protein S6. The complete cDNA sequence, different cDNA fragments and oligonucleotides of the human ribosomal proteins S6, respectively, were joined to the 5' end of the entire LacZ gene of Escherichia coli by using recombinant techniques. The hybrid genes were transfected into L cells, transiently expressed, and the intracellular location of the fusion proteins was determined by their beta-galactosidase activity. Three NLSs were identified in the C-terminal half of the S6 protein. Deletion mutagenesis demonstrated that a single NLS is sufficient for targeting the corresponding S6-beta-galactosidase chimera into the nucleus. Removal of all three putative NLSs completely blocked the nuclear import of the resulting S6-beta-galactosidase fusion protein, which instead became evenly distributed in the cytoplasm. Chimeras containing deletion mutants of S6 with at least one single NLS or unmodified S6 accumulated in the nucleolus. Analysis of several constructs reveals the existence of a specific domain that is essential but not sufficient for nucleolar accumulation of S6. Images PMID:8590812

  3. Helium Plants and Storage. Design Manual 24.2.

    DTIC Science & Technology

    1980-06-01

    Helium Air Separation System for a Supersonic Wind Tunnel.. 24.2-6 4 Four-Way Four-Port Valve ................................... 24.2-11 5 Friction...7) Weather and climatic conditions. 5. FACTS ON HELIUM. Federal agencies use helium in helium-shielded arc weld- ing, supersonic wind tunnels, and...station at the nearest railroad connection for transferring helium from railroad tank car to truck trailer. c. Compressor Station. Generally , the initial

  4. The Serotonin-6 Receptor as a Novel Therapeutic Target

    PubMed Central

    Yun, Hyung-Mun

    2011-01-01

    Serotonin (5-hydroxytryptamine, 5-HT) is an important neurotransmitter that is found in both the central and peripheral nervous systems. 5-HT mediates its diverse physiological responses through 7 different 5-HT receptor families: 5-HT1, 5-HT2, 5-HT3, 5-HT4, 5-HT5, 5-HT6, and 5-HT7 receptors. Among them, the 5-HT6 receptor (5-HT6R) is the most recently cloned serotonin receptor and plays important roles in the central nervous system (CNS) and in the etiology of neurological diseases. Compared to other 5-HT receptors, the 5-HT6R has been considered as an attractive CNS therapeutic target because it is expressed exclusively in the CNS and has no known isoforms. This review evaluates in detail the role of the 5-HT6R in the physiology and pathophysiology of the CNS and the potential usefulness of 5-HT6R ligands in the development of therapeutic strategies for the treatment of CNS disorders. Preclinical studies provide support for the use of 5-HT6R ligands as promising medications to treat the cognitive dysfunction associated with Alzheimer's disease, obesity, depression, and anxiety. PMID:22355260

  5. Design of oil-free simple turbo type 65 K/6 KW helium and neon mixture gas refrigerator for high temperature superconducting power cable cooling

    NASA Astrophysics Data System (ADS)

    Saji, N.; Asakura, H.; Yoshinaga, S.; Ishizawa, T.; Miyake, A.; Obata, M.; Nagaya, S.

    2002-05-01

    For the requirement of HTS facility cooling, we propose oil-free simple turbo-type refrigerator. The working gas is a helium and neon mixture. Two single-stage turbo compressors and two expansion turbines are applied to the cycle. The rotor consists of the compressor impeller, turbine impeller and driving motor, and is supported by foil type gas bearing. The refrigerator requires two rotating machines with excellent reliability and compactness, and the motor power required is 72.5 kW for a refrigeration load of 6 kW. For the cooling of power cable, sub-cooled pressurized liquid nitrogen and a circulation pump must be provided. If the estimated distance between inter-cooling stations is quite long, for example 5 km, plural refrigerators may be set up on one cooling station.

  6. Description and operating performance of a parallel-rail electric-arc system with helium driver gas for the Langley 6-inch expansion tube

    NASA Technical Reports Server (NTRS)

    Moore, J. A.

    1976-01-01

    A parallel-rail arc-discharge system to heat and pressurize the initial helium driver gas of the Langley 6-inch expansion tube is described. This system was designed for a 2.44-m-long driver vessel rated at 138 MPa, with a distance between rails of 20.3 cm. Electric energy was obtained from a capacitor storage system rated at 12,000 V with a maximum energy of 5 MJ. Tests were performed over a range of energy from 1.74 MJ to the maximum value. The operating experience and system performance are discussed, along with results from a limited number of expansion-tube tests with air and carbon dioxide as test gases.

  7. Shock shapes on blunt bodies in hypersonic-hypervelocity helium, air, and CO2 flows, and calibration results in Langley 6-inch expansion tube

    NASA Technical Reports Server (NTRS)

    Miller, C. G., III

    1975-01-01

    Shock shape results for flat-faced cylinders, spheres, and spherically blunted cones in various test gases, along with preliminary results from a calibration study performed in the Langley 6-inch expansion tube are presented. Free-stream velocities from 5 to 7 km/sec are generated at hypersonic conditions with helium, air, and CO2, resulting in normal shock density ratios from 4 to 19. Ideal-gas shock shape predictions, in which an effective ratio of specific heats is used as input, are compared with the measured results. The effect of model diameter is examined to provide insight to the thermochemical state of the flow in the shock layer. The regime for which equilibrium exists in the shock layer for the present air and CO2 test conditions is defined. Test core flow quality, test repeatability, and comparison of measured and predicted expansion-tube flow quantities are discussed.

  8. Induced ferromagnetism in helium bombarded graphite.

    PubMed

    Makarova, Tatiana L; Shelankov, Andrei L; Lyubchik, Svetlana B; Serenkov, Igor T; Sakharov, Vladimir I

    2012-06-01

    Irradiation with helium ions is an effective method for triggering ferromagnetism in graphite. Chemical inertness of helium suggests that local magnetic moment formation is determined solely by the intrinsic carbon defects created during the target damage. Interacting moments are located in two places: in the vicinity of the sample surface and near the point of maximum defect generation.

  9. Spatial coherence measurements of the EUV emission from laser-plasma source based on xenon/helium gas puff target

    NASA Astrophysics Data System (ADS)

    Wachulak, P.; Sarzyński, A.; Bartnik, A.; Fok, T.; Węgrzynski, Ł.; Kostecki, J.; Fiedorowicz, H.

    2017-08-01

    In this paper, we present the first measurements of the partial spatial coherence of the EUV emission from xenon plasma in laser-plasma source, based on a double stream gas puff target. The Young double slit approach was employed to measure complex coherence factor of the EUV Xe emission at 13.5-nm wavelength in two orthogonal directions. The radius of coherence of 60 μm was estimated at the distance of 2.1 m from the source. The number of coherently emitted photons was sufficient to demonstrate coherent imaging. Using partially coherent radiation from such source Gabor EUV holography was successfully demonstrated.

  10. TRAF6 Activation in Multiple Myeloma: A Potential Therapeutic Target

    PubMed Central

    Liu, Hong; Tamashiro, Samantha; Baritaki, Stavroula; Penichet, Manuel; Yu, Youhua; Chen, Haiming; Berenson, James; Bonavida, Benjamin

    2013-01-01

    Multiple myeloma (MM) is an incurable B-lymphocyte malignancy. New therapeutic options have become available during the past several years; however nearly all patients acquire resistance to currently available therapeutic agents. Mechanisms contributing to the pathogenesis and chemoresistance of MM include genetic abnormalities, chromosomal translocations, gene mutations, the interaction between MM cells and the bone marrow microenvironment, and defects in the apoptotic signaling pathways. Survival signaling pathways associated with the pathogenesis of MM and bone marrow stromal cells play crucial roles in promoting growth, survival, adhesion, immortalization, angiogenesis, and drug resistance. The receptor activator of nuclear factor-kappa B/receptor activator of nuclear factor-kappa B ligand/tumor necrosis factor receptor-associated factor (RANK/RANKL-TRAF6) signal pathway mediates osteolytic bone lesions through the activation of the NF-κB and Janus kinase/signal transducer and activator of transcription (JNK) pathways in osteoclast precursor cells and thus contributes to the main clinical manifestations of bone disease. TRAF6 has also been identified as a ligase for Akt ubiquitination and membrane recruitment and its phosphorylation on growth factor stimulation. The inhibition of TRAF6 by silencing RNA or by decoy peptides decreases MM tumor cell proliferation and increases apoptosis as well as bone resorption. Some proteasome inhibitors and benzoxadiazole derivatives showed inhibitory effects on the activity and function of TRAF6. Overall, we propose that TRAF6 may be considered as a potential therapeutic target for the treatment of MM. PMID:22440007

  11. Development of an Active 238UF6 Gas Target

    NASA Astrophysics Data System (ADS)

    Eckardt, C.; Enders, J.; Freudenberger, M.; Gook, A.; von Neumann-Cosel, P.; Oberstedt, A.; Oberstedt, S.

    At the superconducting 130 MeV Darmstadt electron linac S-DALINAC a new source of spin-polarized electrons using a GaAs cathode has been installed, opening the path for experiments with polarized electron and photon beams for nuclear structure studies at low momentum transfers, e.g., the search for forward-backward asymmetries originating from parity non-conservation (PNC) in the photon-induced fission process of 238U.Detailed studies of different properties, e.g., the energy dependence of fission modes, the population of fission isomers, or the search for (PNC) effects in the photon-induced fission process of 238U, depends on high quality data, therefore needing high luminosities. An active gas target containing uranium may overcome the problem that large solid target thicknesses cause poor energy and angular resolution.A single Frisch-grid ionization chamber has been built to test a mixture of standard counting gases (e.g., argon) with depleted uraniumhexafluoride (238UF6) using a triple alpha source, evaluating signal quality and drift velocity. For mass fractions up to 2 percent of 238U in the counting gas. The drift velocity increases with rising UF6 content, while a good signal quality and energy resolution is preserved.

  12. Ras Laffan helium recovery unit 2

    NASA Astrophysics Data System (ADS)

    Fauve, Eric Arnaud; Grabié, Veronique; Grillot, David; Delcayre, Franck; Deschildre, Cindy

    2012-06-01

    In May 2010, Air Liquide was awarded a contract for the Engineering Procurement and Construction (Turnkey EPC) for a second helium recovery unit [RLH II] dedicated to the Ras Laffan refinery in Qatar. This unit will come in addition to the one [RLH I] delivered and commissioned by Air Liquide in 2005. It will increase the helium production of Qatar from 10% to 28% of worldwide production. RLH I and RLH II use Air Liquide Advanced Technologies helium liquefiers. With a production of 8 tons of liquid helium per day, the RLH I liquefier is the world largest, but not for long. Thanks to the newly developed turbine TC7, Air Liquide was able to propose for RLH II a single liquefier able to produce over 20 tons per day of liquid helium without liquid nitrogen pre-cooling. This liquefier using 6 Air Liquide turbines (TC series) will set a new record in the world of helium liquefaction.

  13. The Collection 6 'dark-target' MODIS Aerosol Products

    NASA Technical Reports Server (NTRS)

    Levy, Robert C.; Mattoo, Shana; Munchak, Leigh A.; Kleidman, Richard G.; Patadia, Falguni; Gupta, Pawan; Remer, Lorraine

    2013-01-01

    Aerosol retrieval algorithms are applied to Moderate resolution Imaging Spectroradiometer (MODIS) sensors on both Terra and Aqua, creating two streams of decade-plus aerosol information. Products of aerosol optical depth (AOD) and aerosol size are used for many applications, but the primary concern is that these global products are comprehensive and consistent enough for use in climate studies. One of our major customers is the international modeling comparison study known as AEROCOM, which relies on the MODIS data as a benchmark. In order to keep up with the needs of AEROCOM and other MODIS data users, while utilizing new science and tools, we have improved the algorithms and products. The code, and the associated products, will be known as Collection 6 (C6). While not a major overhaul from the previous Collection 5 (C5) version, there are enough changes that there are significant impacts to the products and their interpretation. In its entirety, the C6 algorithm is comprised of three sub-algorithms for retrieving aerosol properties over different surfaces: These include the dark-target DT algorithms to retrieve over (1) ocean and (2) vegetated-dark-soiled land, plus the (3) Deep Blue (DB) algorithm, originally developed to retrieve over desert-arid land. Focusing on the two DT algorithms, we have updated assumptions for central wavelengths, Rayleigh optical depths and gas (H2O, O3, CO2, etc.) absorption corrections, while relaxing the solar zenith angle limit (up to 84) to increase pole-ward coverage. For DT-land, we have updated the cloud mask to allow heavy smoke retrievals, fine-tuned the assignments for aerosol type as function of season location, corrected bugs in the Quality Assurance (QA) logic, and added diagnostic parameters such as topographic altitude. For DT-ocean, improvements include a revised cloud mask for thin-cirrus detection, inclusion of wind speed dependence in the retrieval, updates to logic of QA Confidence flag (QAC) assignment, and

  14. HDAC6 regulates IL-17 expression in T lymphocytes: implications for HDAC6-targeted therapies

    PubMed Central

    Yan, Bing; Liu, Yang; Bai, Hong; Chen, Miao; Xie, Songbo; Li, Dengwen; Liu, Min; Zhou, Jun

    2017-01-01

    The pro-inflammatory cytokine interleukin 17 (IL-17) is critically involved in immunity and inflammation. T-helper 17 and γδ T cells are the predominant sources of IL-17 in the immune system. However, the mechanisms by which the expression of IL-17 is regulated in T cells remain elusive. Here, we demonstrate that loss of histone deacetylase 6 (HDAC6) in mice does not affect the generation of CD4+ or CD8+ T cells, but stimulates the development of IL-17-producing γδ T cells. Our data further show that HDAC6 deficiency increases the production of IL-17 by Vγ4+ γδ T cells in the spleen and lymph nodes. Consistent with these observations, small-molecule inhibition of HDAC6 activity in γδ T cells promotes the expression of IL-17 in vitro. These data thus reveal that HDAC6 represses IL-17 production in T cells, providing novel insights into the role of HDAC6 in the immune system. These findings also have important implications for the clinical investigation of HDAC6-targeted therapies.

  15. Approximating the Helium Wavefunction in Positronium-Helium Scattering

    NASA Technical Reports Server (NTRS)

    DiRienzi, Joseph; Drachman, Richard J.

    2003-01-01

    In the Kohn variational treatment of the positronium- hydrogen scattering problem the scattering wave function is approximated by an expansion in some appropriate basis set, but the target and projectile wave functions are known exactly. In the positronium-helium case, however, a difficulty immediately arises in that the wave function of the helium target atom is not known exactly, and there are several ways to deal with the associated eigenvalue in formulating the variational scattering equations to be solved. In this work we will use the Kohn variational principle in the static exchange approximation to d e t e e the zero-energy scattering length for the Ps-He system, using a suite of approximate target functions. The results we obtain will be compared with each other and with corresponding values found by other approximation techniques.

  16. Federal helium program: The reaction over an inert gas. Final report

    SciTech Connect

    Mielke, J.E.

    1996-10-09

    Helium, present in relatively high concentrations in only a few natural gas fields, is released to the atmosphere and wasted when the natural gas is burned as fuel. Government involvement in helium conservation dates to the Helium Act of 1925 which authorized the Bureau of Mines to build and operate a large-scale helium extraction and purification plant. From 1929 until 1960 the federal government was the only domestic helium producer. In 1960, Congress amended the Helium Act to provide incentives to natural gas producers for stripping natural gas of its helium, for purchase of the separated helium by the government, and for its long-term storage. With over 960 million cubic meters (34.6 billion cubic feet) of helium in government storage and a large private helium recovery industry, questions arise as to the need for either the federal helium extraction program or the federally maintained helium stockpile.

  17. Ultra-Narrow Negative Flare Front Observed in Helium-10830 Å Using the1.6m New Solar Telescope

    NASA Astrophysics Data System (ADS)

    Xu, Yan; Cao, Wenda; Ding, Mingde; Kleint, Lucia; Su, Jiangtao; Liu, Chang; Ji, Haisheng; Chae, Jongchul; Jing, Ju; Cho, Kyuhyoun; Cho, Kyung-Suk; Gary, Dale E.; Wang, Haimin

    2016-05-01

    Solar flares are sudden flashes of brightness on the Sun and are often associated with coronal mass ejections and solar energetic particles that have adverse effects on the near-Earth environment. By definition, flares are usually referred to as bright features resulting from excess emission. Using the newly commissioned 1.6-m New Solar Telescope at Big Bear Solar Observatory, we show a striking “negative” flare with a narrow but unambiguous “dark” moving front observed in He I 10830 Å, which is as narrow as 340 km and is associated with distinct spectral characteristics in Hα and Mg II lines. Theoretically, such negative contrast in He I 10830 Å can be produced under special circumstances by nonthermal electron collisions or photoionization followed by recombination. Our discovery, made possible due to unprecedented spatial resolution, confirms the presence of the required plasma conditions and provides unique information in understanding the energy release and radiative transfer in solar flares.

  18. Ultra-narrow Negative Flare Front Observed in Helium-10830 Å Using the 1.6 m New Solar Telescope

    NASA Astrophysics Data System (ADS)

    Xu, Yan; Cao, Wenda; Ding, Mingde; Kleint, Lucia; Su, Jiangtao; Liu, Chang; Ji, Haisheng; Chae, Jongchul; Jing, Ju; Cho, Kyuhyoun; Cho, Kyungsuk; Gary, Dale; Wang, Haimin

    2016-03-01

    Solar flares are sudden flashes of brightness on the Sun and are often associated with coronal mass ejections and solar energetic particles that have adverse effects on the near-Earth environment. By definition, flares are usually referred to as bright features resulting from excess emission. Using the newly commissioned 1.6 m New Solar Telescope at Big Bear Solar Observatory, we show a striking “negative” flare with a narrow but unambiguous “dark” moving front observed in He i 10830 Å, which is as narrow as 340 km and is associated with distinct spectral characteristics in Hα and Mg ii lines. Theoretically, such negative contrast in He i 10830 Å can be produced under special circumstances by nonthermal electron collisions or photoionization followed by recombination. Our discovery, made possible due to unprecedented spatial resolution, confirms the presence of the required plasma conditions and provides unique information in understanding the energy release and radiative transfer in astronomical objects.

  19. Helium-Recycling Plant

    NASA Technical Reports Server (NTRS)

    Cook, Joseph

    1996-01-01

    Proposed system recovers and stores helium gas for reuse. Maintains helium at 99.99-percent purity, preventing water vapor from atmosphere or lubricating oil from pumps from contaminating gas. System takes in gas at nearly constant low back pressure near atmospheric pressure; introduces little or no back pressure into source of helium. Concept also extended to recycling of other gases.

  20. COSMIC-RAY HELIUM HARDENING

    SciTech Connect

    Ohira, Yutaka; Ioka, Kunihito

    2011-03-01

    Recent observations by the CREAM and ATIC-2 experiments suggest that (1) the spectrum of cosmic-ray (CR) helium is harder than that of CR protons below the knee energy, 10{sup 15}eV, and (2) all CR spectra become hard at {approx}>10{sup 11}eV nucleon{sup -1}. We propose a new idea, that higher energy CRs are generated in a more helium-rich region, to explain the hardening without introducing different sources for CR helium. The helium-to-proton ratio at {approx}100 TeV exceeds the Big Bang abundance Y = 0.25 by several times, and the different spectrum is not reproduced within the diffusive shock acceleration theory. We argue that CRs are produced in a chemically enriched region, such as a superbubble, and the outward-decreasing abundance naturally leads to the hard spectrum of CR helium if CRs escape from the supernova remnant shock in an energy-dependent way. We provide a simple analytical spectrum that also fits well the hardening due to the decreasing Mach number in the hot superbubble with {approx}10{sup 6} K. Our model predicts hard and concave spectra for heavier CR elements.

  1. Region 6 Targeted Brownfields Assessment Form and Consent for Access to Property

    EPA Pesticide Factsheets

    To request Region 6 to perform a Targeted Brownfields Assessment, complete and submit the Region 6 Targeted Brownfields Assessment Form. To grant the EPA access to your property, complete and submit the Consent to Access to Property form.

  2. ULTRA-NARROW NEGATIVE FLARE FRONT OBSERVED IN HELIUM-10830 Å USING THE 1.6 m NEW SOLAR TELESCOPE

    SciTech Connect

    Xu, Yan; Liu, Chang; Jing, Ju; Wang, Haimin; Cao, Wenda; Gary, Dale; Ding, Mingde; Kleint, Lucia; Su, Jiangtao; Ji, Haisheng; Chae, Jongchul; Cho, Kyuhyoun; Cho, Kyungsuk

    2016-03-10

    Solar flares are sudden flashes of brightness on the Sun and are often associated with coronal mass ejections and solar energetic particles that have adverse effects on the near-Earth environment. By definition, flares are usually referred to as bright features resulting from excess emission. Using the newly commissioned 1.6 m New Solar Telescope at Big Bear Solar Observatory, we show a striking “negative” flare with a narrow but unambiguous “dark” moving front observed in He i 10830 Å, which is as narrow as 340 km and is associated with distinct spectral characteristics in Hα and Mg ii lines. Theoretically, such negative contrast in He i 10830 Å can be produced under special circumstances by nonthermal electron collisions or photoionization followed by recombination. Our discovery, made possible due to unprecedented spatial resolution, confirms the presence of the required plasma conditions and provides unique information in understanding the energy release and radiative transfer in astronomical objects.

  3. Interleukin-6 as a therapeutic target in human ovarian cancer.

    PubMed

    Coward, Jermaine; Kulbe, Hagen; Chakravarty, Probir; Leader, David; Vassileva, Vessela; Leinster, D Andrew; Thompson, Richard; Schioppa, Tiziana; Nemeth, Jeffery; Vermeulen, Jessica; Singh, Naveena; Avril, Norbert; Cummings, Jeff; Rexhepaj, Elton; Jirström, Karin; Gallagher, William M; Brennan, Donal J; McNeish, Iain A; Balkwill, Frances R

    2011-09-15

    We investigated whether inhibition of interleukin 6 (IL-6) has therapeutic activity in ovarian cancer via abrogation of a tumor-promoting cytokine network. We combined preclinical and in silico experiments with a phase 2 clinical trial of the anti-IL-6 antibody siltuximab in patients with platinum-resistant ovarian cancer. Automated immunohistochemistry on tissue microarrays from 221 ovarian cancer cases showed that intensity of IL-6 staining in malignant cells significantly associated with poor prognosis. Treatment of ovarian cancer cells with siltuximab reduced constitutive cytokine and chemokine production and also inhibited IL-6 signaling, tumor growth, the tumor-associated macrophage infiltrate and angiogenesis in IL-6-producing intraperitoneal ovarian cancer xenografts. In the clinical trial, the primary endpoint was response rate as assessed by combined RECIST and CA125 criteria. One patient of eighteen evaluable had a partial response, while seven others had periods of disease stabilization. In patients treated for 6 months, there was a significant decline in plasma levels of IL-6-regulated CCL2, CXCL12, and VEGF. Gene expression levels of factors that were reduced by siltuximab treatment in the patients significantly correlated with high IL-6 pathway gene expression and macrophage markers in microarray analyses of ovarian cancer biopsies. IL-6 stimulates inflammatory cytokine production, tumor angiogenesis, and the tumor macrophage infiltrate in ovarian cancer and these actions can be inhibited by a neutralizing anti-IL-6 antibody in preclinical and clinical studies. ©2011 AACR.

  4. Targeted deletion of kidney glucose-6 phosphatase leads to nephropathy.

    PubMed

    Clar, Julie; Gri, Blandine; Calderaro, Julien; Birling, Marie-Christine; Hérault, Yann; Smit, G Peter A; Mithieux, Gilles; Rajas, Fabienne

    2014-10-01

    Renal failure is a major complication that arises with aging in glycogen storage disease type 1a and type 1b patients. In the kidneys, glucose-6 phosphatase catalytic subunit (encoded by G6pc) deficiency leads to the accumulation of glycogen, an effect resulting in marked nephromegaly and progressive glomerular hyperperfusion and hyperfiltration preceding the development of microalbuminuria and proteinuria. To better understand the end-stage nephropathy in glycogen storage disease type 1a, we generated a novel kidney-specific G6pc knockout (K-G6pc(-/-)) mouse, which exhibited normal life expectancy. After 6 months, K-G6pc(-/-) mice showed glycogen overload leading to nephromegaly and tubular dilation. Moreover, renal accumulation of lipids due to activation of de novo lipogenesis was observed. This led to the activation of the renin-angiotensin system and the development of epithelial-mesenchymal transition process and podocyte injury by transforming growth factor β1 signaling. The K-G6pc(-/-) mice developed microalbuminuria caused by the impairment of the glomerular filtration barrier. Thus, renal G6pc deficiency alone is sufficient to induce the development of the early-onset nephropathy observed in glycogen storage disease type 1a, independent of the liver disease. The K-G6pc(-/-) mouse model is a unique tool to decipher the molecular mechanisms underlying renal failure and to evaluate potential therapeutic strategies.

  5. Interleukin-6 as a therapeutic target in human ovarian cancer

    PubMed Central

    Coward, Jermaine; Kulbe, Hagen; Chakravarty, Probir; Leader, David; Vassileva, Vessela; Leinster, D. Andrew; Thompson, Richard; Schioppa, Tiziana; Nemeth, Jeffery; Vermeulen, Jessica; Singh, Naveena; Avril, Norbert; Cummings, Jeff; Rexhepaj, Elton; Jirström, Karin; Gallagher, William M; Brennan, Donal J.; McNeish, Iain A.; Balkwill, Fran

    2011-01-01

    Purpose We investigated whether inhibition of IL-6 has therapeutic activity in ovarian cancer via abrogation of a tumor-promoting cytokine network. Experimental Design We combined pre-clinical and in silico experiments with a phase II clinical trial of the anti-IL-6 antibody siltuximab in patients with platinum-resistant ovarian cancer. Results Automated immunohistochemistry on tissue microarrays from 221 ovarian cancer cases demonstrated that intensity of IL-6 staining in malignant cells significantly associated with poor prognosis. Treatment of ovarian cancer cells with siltuximab reduced constitutive cytokine and chemokine production and also inhibited IL-6 signalling, tumor growth, the tumor-associated macrophage infiltrate and angiogenesis in IL-6-producing intraperitoneal ovarian cancer xenografts. In the clinical trial, the primary endpoint was response rate as assessed by combined RECIST and CA125 criteria. One patient of eighteen evaluable had a partial response, whilst seven others had periods of disease stabilization. In patients treated for six months, there was a significant decline in plasma levels of IL-6-regulated CCL2, CXCL12 and VEGF. Gene expression levels of factors that were reduced by siltuximab treatment in the patients significantly correlated with high IL-6 pathway gene expression and macrophage markers in microarray analyses of ovarian cancer biopsies. Conclusions IL-6 stimulates inflammatory cytokine production, tumor angiogenesis and the tumor macrophage infiltrate in ovarian cancer and these actions can be inhibited by a neutralising anti-IL-6 antibody in pre-clinical and clinical studies. PMID:21795409

  6. Reprogramming metabolism by targeting sirtuin 6 attenuates retinal degeneration

    PubMed Central

    Zhang, Lijuan; Du, Jianhai; Justus, Sally; Hsu, Chun-Wei; Bonet-Ponce, Luis; Wu, Wen-Hsuan; Tsai, Yi-Ting; Wu, Wei-Pu; Jia, Yading; Duong, Jimmy K.; Mahajan, Vinit B.; Lin, Chyuan-Sheng; Wang, Shuang; Hurley, James B.

    2016-01-01

    Retinitis pigmentosa (RP) encompasses a diverse group of Mendelian disorders leading to progressive degeneration of rods and then cones. For reasons that remain unclear, diseased RP photoreceptors begin to deteriorate, eventually leading to cell death and, consequently, loss of vision. Here, we have hypothesized that RP associated with mutations in phosphodiesterase-6 (PDE6) provokes a metabolic aberration in rod cells that promotes the pathological consequences of elevated cGMP and Ca2+, which are induced by the Pde6 mutation. Inhibition of sirtuin 6 (SIRT6), a histone deacetylase repressor of glycolytic flux, reprogrammed rods into perpetual glycolysis, thereby driving the accumulation of biosynthetic intermediates, improving outer segment (OS) length, enhancing photoreceptor survival, and preserving vision. In mouse retinae lacking Sirt6, effectors of glycolytic flux were dramatically increased, leading to upregulation of key intermediates in glycolysis, TCA cycle, and glutaminolysis. Both transgenic and AAV2/8 gene therapy–mediated ablation of Sirt6 in rods provided electrophysiological and anatomic rescue of both rod and cone photoreceptors in a preclinical model of RP. Due to the extensive network of downstream effectors of Sirt6, this study motivates further research into the role that these pathways play in retinal degeneration. Because reprogramming metabolism by enhancing glycolysis is not gene specific, this strategy may be applicable to a wide range of neurodegenerative disorders. PMID:27841758

  7. Comparative effects of 60Co gamma-rays and neon and helium ions on cycle duration and division probability of EMT 6 cells. A time-lapse cinematography study.

    PubMed

    Collyn-d'Hooghe, M; Hemon, D; Gilet, R; Curtis, S B; Valleron, A J; Malaise, E P

    1981-03-01

    Exponentially growing cultures of EMT 6 cells were irradiated in vitro with neon ions, helium ions or 60Co gamma-rays. Time-lapse cinematography allowed the determination, for individual cells, of cycle duration, success of the mitotic division and the age of the cell at the moment of irradiation. Irradiation induced a significant mitotic delay increasing proportionally with the delivered dose. Using mitotic delay as an endpoint, the r.b.e. for neon ions with respect to 60Co gamma-rays was 3.3 +/- 0.2 while for helium ions it was 1.2 +/- 0.1. Mitotic delay was greatest in those cells that had progressed furthest in their cycle at the time of irradiation. No significant mitotic delay was observed in the post-irradiation generation. Division probability was significantly reduced by irradiation both in the irradiated and in the post-irradiated generation. The reduction in division probability obtained with 3 Gy of neon ions was similar to that obtained after irradiation with 6 Gy of helium ions or 60Co gamma-rays.

  8. Helium transport in plasma edge regions

    NASA Astrophysics Data System (ADS)

    Abou-Gabal, Hanaa Hassan

    The transport of neutral helium atoms near diverter or limiter target plates in fusion devices was studied. Two simulation codes, based on Monte Carlo techniques, were developed. The first treats the problem in one-dimensional geometry and the second considers two-dimensional effects. The atomic processes of ionization of helium atoms by electron impact and elastic scattering with plasma ions are included. The total and differential elastic scattering cross-sections were calculated classically using an ab initio calculation of the interatomic potential. The thermal motion and the streaming of the ions along the magnetic field, which can be at an angle to the target plate, are included. Results obtained with the one-dimensional code show significant effects of elastic collisions below about 10 eV, causing a substantial fraction of the helium atoms to be reflected back to the target plate. This effect can be beneficial for the pumping of helium from the discharge chamber. The two-dimensional Monte Carlo code was used to study helium recycling near a flat, vented target plate. A parametric study is performed to examine the dependence of the pumping efficiency on plasma parameters and geometric aspects. Results show that the pumping of neutral helium can be increased by shortening and widening the ports as well as by increasing the angle between the magnetic field and the target plate. Also, keeping the ion temperature below about 10 eV and the plasma density around a few 10(exp 14) cu cm near the targe plate can be beneficial for the pumping of helium gas.

  9. The Nucleosynthesis of Helium

    NASA Astrophysics Data System (ADS)

    Kneller, James

    2007-04-01

    The large cosmic abundance of Helium - second only to Hydrogen - is a testament to the importance of its formation in the cosmos. Both Helium-3 and Helium-4 emerge from Big Bang Nucleosynthesis in considerable quantities, the synthesis of the isotopes are links in the pp chain and other stellar nucleosynthesis processes, and they are also created during the initial stages of the r-process. The importance of Helium formation in these settings provides us with valuable information upon the environments in which it occurs. We survey the role of the synthesis of Helium in nuclear astrophysics, how its manufacture is affected by many diverse factors, and what we have learnt from observations of Helium abundances.

  10. National Ignition Facility subsystem design requirements target area auxiliary subsystem SSDR 1.8.6

    SciTech Connect

    Reitz, T.

    1996-10-20

    This Subsystem Design Requirement (SSDR) establishes the performance, design, development, and test requirements for the Target Area Auxiliary Subsystems (WBS 1.8.6), which is part of the NIF Target Experimental System (WBS 1.8). This document responds directly to the requirements detailed in NIF Target Experimental System SDR 003 document. Key elements of the Target Area Auxiliary Subsystems include: WBS 1.8.6.1 Local Utility Services; WBS 1.8.6.2 Cable Trays; WBS 1.8.6.3 Personnel, Safety, and Occupational Access; WBS 1.8.6.4 Assembly, Installation, and Maintenance Equipment; WBS 1.8.6.4.1 Target Chamber Service System; WBS 1.8.6.4.2 Target Bay Service Systems.

  11. Particle Detection in Superfluid Helium: R&D for Low Energy Solar Neutrinos

    SciTech Connect

    Lanou, Robert E., Jr.

    2006-03-31

    This report presents a summary of the results from R&D conducted as a feasibility study in the Department of Physics of Brown University for detection of low energy solar neutrinos utilizing a superfluid helium target. The report outlines the results in several areas: 1) development of experimental facilities, 2) energy deposition by electrons and alphas in superfluid helium, 3) development of wafer and metallic magnetic calorimeters, 4) background studies, 5) coded apertures and conceptual design, 6) Detection of single electrons and 7) a simulation of expected performance of a full scale device. Recommendations for possible future work are also presented. A bibliography of published papers and unpublished doctoral theses is included.

  12. Helium resources of Mare Tranquillitatis

    NASA Astrophysics Data System (ADS)

    Cameron, Eugene N.

    Wisconsin Center for Space Automation and Robotics, Univ. of Wisc., Madison, Wisc. Mare Tranquillitatis, about 300000 sq km in area, is currently the most promising lunar source of He-3 for fueling fusion power plants on Earth. About 60 pct. of the mare regolith consists of particles 100 microns or less in diameter. Helium and other gases derived from the solar wind are concentrated in the fine size fractions. Studies of very small craters indicate that the average regolith exceeds 3 m in areas away from larger craters and other mare features not amenable to mining. There is no evidence of decrease of helium content of regolith and depth. Helium is known to be enriched in regoliths that are high in TiO2 content. Remote sensing indicates that about 90 pct. of Mare Tranquillitatis is covered by regolith ranging from about 6 to +7.5 pct. TiO2; inferred He contents range from 20 to at least 45 wppm total helium (7 to 18 wppb He-3). Detailed studies of craters and inferred ejecta halos displayed on high resolution photographs of the Apollo 11 and Ranger 8 areas suggest that as much as 50 pct. of the mare regolith may be physically minable, on average, with appropriate mining equipment. Assuming that the average thickness of regolith is 3 m, and that 50 pct. of the mare area is minable, the He-3 content of minable regolith containing 20 to 45 wppm total He is estimated at about 94,000 tonnes.

  13. Superfluid Helium Heat Pipe

    NASA Astrophysics Data System (ADS)

    Gully, P.

    This paper reports on the development and the thermal tests of three superfluid helium heat pipes. Two of them are designed to provide a large transport capacity (4 mW at 1.7 K). They feature a copper braid located inside a 6 mm outer diameter stainless tube fitted with copper ends for mechanical anchoring. The other heat pipe has no copper braid and is designed to get much smaller heat transport capacity (0.5 mW) and to explore lower temperature (0.7 - 1 K). The copper braid and the tube wall is the support of the Rollin superfluid helium film in which the heat is transferred. The low filling pressure makes the technology very simple with the possibility to easily bend the tube. We present the design and discuss the thermal performance of the heat pipes tested in the 0.7 to 2.0 K temperature range. The long heat pipe (1.2 m with copper braid) and the short one (0.25 m with copper braid) have similar thermal performance in the range 0.7 - 2.0 K. At 1.7 K the long heat pipe, 120 g in weight, reaches a heat transfer capacity of 6.2 mW and a thermal conductance of 600 mW/K for 4 mW transferred power. Due to the pressure drop of the vapor flow and Kapitza thermal resistance, the conductance of the third heat pipe dramatically decreases when the temperature decreases. A 3.8 mW/K is obtained at 0.7 K for 0.5 mW transferred power.

  14. Molecular dynamics study of helium bubble pressure in tungsten

    NASA Astrophysics Data System (ADS)

    Cui, Jiechao; Li, Min; Wang, Jun; Hou, Qing

    2015-06-01

    Molecular dynamics simulations were performed to calculate the stress field in a tungsten matrix containing a nano-scale helium bubble. A helium bubble in tungsten is found to consist of a core and an interface of finite thickness of approximately 0.6 nm. The core contains only helium atoms that are uniformly distributed. The interface is composed of both helium and tungsten atoms. In the periphery region of the helium bubble, the stress filed is found to follow the stress formula based on the elasticity theory of solid. The pressure difference between both sides of the interface can be well described by the Young-Laplace equation for the core size of a helium bubble as small as 0.48 nm. A comparison was performed between the pressure in the helium bubble core and the pressure in pure helium. For a core size larger than 0.3 nm, the pressure in the core of a helium bubble is in good agreement with the pressure in pure helium of the same helium density. These results provide guidance to larger scale simulation methods, such as in kinetic Monte Carlo methods and rate theory.

  15. Therapeutic Targeting of the IL-6 Trans-Signaling/Mechanistic Target of Rapamycin Complex 1 Axis in Pulmonary Emphysema.

    PubMed

    Ruwanpura, Saleela M; McLeod, Louise; Dousha, Lovisa F; Seow, Huei J; Alhayyani, Sultan; Tate, Michelle D; Deswaerte, Virginie; Brooks, Gavin D; Bozinovski, Steven; MacDonald, Martin; Garbers, Christoph; King, Paul T; Bardin, Philip G; Vlahos, Ross; Rose-John, Stefan; Anderson, Gary P; Jenkins, Brendan J

    2016-12-15

    The potent immunomodulatory cytokine IL-6 is consistently up-regulated in human lungs with emphysema and in mouse emphysema models; however, the mechanisms by which IL-6 promotes emphysema remain obscure. IL-6 signals using two distinct modes: classical signaling via its membrane-bound IL-6 receptor (IL-6R), and trans-signaling via a naturally occurring soluble IL-6R. To identify whether IL-6 trans-signaling and/or classical signaling contribute to the pathogenesis of emphysema. We used the gp130(F/F) genetic mouse model for spontaneous emphysema and cigarette smoke-induced emphysema models. Emphysema in mice was quantified by various methods including in vivo lung function and stereology, and terminal deoxynucleotidyl transferase dUTP nick end labeling assay was used to assess alveolar cell apoptosis. In mouse and human lung tissues, the expression level and location of IL-6 signaling-related genes and proteins were measured, and the levels of IL-6 and related proteins in sera from emphysematous mice and patients were also assessed. Lung tissues from patients with emphysema, and from spontaneous and cigarette smoke-induced emphysema mouse models, were characterized by excessive production of soluble IL-6R. Genetic blockade of IL-6 trans-signaling in emphysema mouse models and therapy with the IL-6 trans-signaling antagonist sgp130Fc ameliorated emphysema by suppressing augmented alveolar type II cell apoptosis. Furthermore, IL-6 trans-signaling-driven emphysematous changes in the lung correlated with mechanistic target of rapamycin complex 1 hyperactivation, and treatment of emphysema mouse models with the mechanistic target of rapamycin complex 1 inhibitor rapamycin attenuated emphysematous changes. Collectively, our data reveal that specific targeting of IL-6 trans-signaling may represent a novel treatment strategy for emphysema.

  16. Proton-Helium Elastic Electromagnetic Cross-Section

    SciTech Connect

    Huang, Burn; Ng, Kingyuen B.

    2015-11-01

    In the test facility of the C-ADS project, A 25-MeV proton beam is directed to hit a target consisting of 1-mm tungsten balls lubricated by 100-Pa helium gas. To estimate the power loss to the helium gas, an accurate collision cross section is computed.

  17. Helium damage and helium effusion in fully stabilised zirconia

    NASA Astrophysics Data System (ADS)

    Damen, P. M. G.; Matzke, Hj.; Ronchi, C.; Hiernaut, J.-P.; Wiss, T.; Fromknecht, R.; van Veen, A.; Labohm, F.

    2002-05-01

    Fully stabilised zirconia (FSZ) samples have been implanted with helium-ions of different energies (200 keV and 1 MeV) and with different fluences (1.4×10 13-1.4×10 16 He +/cm 2). Neutron depth profiling (NDP) for different annealing temperatures and effusion experiments in two different experimental systems with different thermal annealings have been performed on these samples. The samples were analysed by electron microscopy during the various annealing stages. For the low-fluence samples, the diffusion of helium is probably caused by vacancy assisted interstitial diffusion with an activation energy of 1.6 eV. In the highest fluence samples probably high pressure bubbles are formed during thermal annealing.

  18. Emerging Role and Targeting of Carcinoembryonic Antigen-related Cell Adhesion Molecule 6 (CEACAM6) in Human Malignancies

    PubMed Central

    Johnson, Benny; Mahadevan, Daruka

    2015-01-01

    Background: Carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6) is a member of the CEA family of cell adhesion proteins that belong to the immunoglobulin superfamily. CEACAM6 is normally expressed on the surface of myeloid (CD66c) and epithelial surfaces. Stiochiomertic expression of members of the CEA family (CEACAM1, 5, 6, 7) on epithelia maintains normal tissue architecture through homo-and hetero-philic interactions. Dysregulated over-expression of CEACAM6 is oncogenic, is associated with anoikis resistance and an invasive phenotype mediated by excessive TGFβ, AKT, FAK and SRC signaling in human malignancies. Methods: Extensive literature review through PubMed was conducted to identify relevant preclinical and clinical research publications regarding CEACAM6 over the last decade and was summarized in this manuscript. Results: CEACAM5 and 6 are over-expressed in nearly 70% of epithelial malignancies including colorectal cancer (CRC), pancreatic ductal adenocarcinoma (PDA), hepatobiliary, gastric, breast, non-small cell lung and head/neck cancers. Importantly, CEACAM6 is a poor prognostic marker in CRC, while its expression correlates with tumor stage, metastasis and post-operative survival in PDA. CEACAM6 appears to be an immune checkpoint suppressor in hematologic malignancies including acute lymphoblastic leukemia and multiple myeloma. Several therapeutic monoclonal antibodies or antibody fragments targeting CEACAM6 have been designed and developed as a targeted therapy for human malignancies. A Llama antibody targeting CEACAM6 is being evaluated in early phase clinical trials. Conclusion: This review focuses on the role of CEACAM6 in the pathogenesis and signaling of the malignant phenotype in solid and hematologic malignancies and highlights its potential as a therapeutic target for anti-cancer therapy. PMID:27595061

  19. Rapidly pulsed helium droplet source

    SciTech Connect

    Pentlehner, Dominik; Riechers, Ricarda; Dick, Bernhard; Slenczka, Alkwin; Even, Uzi; Lavie, Nachum; Brown, Raviv; Luria, Kfir

    2009-04-15

    A pulsed valve connected to a closed-cycle cryostat was optimized for producing helium droplets. The pulsed droplet beam appeared with a bimodal size distribution. The leading part of the pulse consists of droplets suitable for doping with molecules. The average size of this part can be varied between 10{sup 4} and 10{sup 6} helium atoms, and the width of the distribution is smaller as compared to a continuous-flow droplet source. The system has been tested in a single pulse mode and at repetition rates of up to 500 Hz with almost constant intensity. The droplet density was found to be increased by more than an order of magnitude as compared to a continuous-flow droplet source.

  20. Noncavitating Pump For Liquid Helium

    NASA Technical Reports Server (NTRS)

    Hasenbein, Robert; Izenson, Michael; Swift, Walter; Sixsmith, Herbert

    1996-01-01

    Immersion pump features high efficiency in cryogenic service. Simple and reliable centrifugal pump transfers liquid helium with mass-transfer efficiency of 99 percent. Liquid helium drawn into pump by helical inducer, which pressurizes helium slightly to prevent cavitation when liquid enters impeller. Impeller then pressurizes liquid. Purpose of pump to transfer liquid helium from supply to receiver vessel, or to provide liquid helium flow for testing and experimentation.

  1. The Descending Helium Balloon

    ERIC Educational Resources Information Center

    Helseth, Lars Egil

    2014-01-01

    I describe a simple and fascinating experiment wherein helium leaks out of a rubber balloon, thereby causing it to descend. An estimate of the volumetric leakage rate is made by measuring its rate of descent.

  2. The Descending Helium Balloon

    ERIC Educational Resources Information Center

    Helseth, Lars Egil

    2014-01-01

    I describe a simple and fascinating experiment wherein helium leaks out of a rubber balloon, thereby causing it to descend. An estimate of the volumetric leakage rate is made by measuring its rate of descent.

  3. The descending helium balloon

    NASA Astrophysics Data System (ADS)

    Helseth, Lars Egil

    2014-07-01

    I describe a simple and fascinating experiment wherein helium leaks out of a rubber balloon, thereby causing it to descend. An estimate of the volumetric leakage rate is made by measuring its rate of descent.

  4. Astrocyte-targeted expression of interleukin-6 protects the central nervous system during neuroglial degeneration induced by 6-aminonicotinamide.

    PubMed

    Penkowa, Milena; Camats, Jordi; Hadberg, Hanne; Quintana, Albert; Rojas, Santiago; Giralt, Mercedes; Molinero, Amalia; Campbell, Iain L; Hidalgo, Juan

    2003-08-15

    6-aminonicotinamide (6-AN) is a niacin antagonist, which leads to degeneration of gray matter astrocytes mainly in the brainstem. We have examined the role of interleukin-6 (IL-6) in this degenerative process by using transgenic mice with astrocyte-targeted IL-6 expression (GFAP-IL6 mice). This study demonstrates that transgenic IL-6 expression significantly increases the 6-AN-induced inflammatory response of reactive astrocytes, microglia/macrophages, and lymphocytes in the brainstem. Also, IL-6 induced significant increases in proinflammatory cytokines IL-1, IL-12, and tumor necrosis factor-alpha as well as growth factors basic fibroblast growth factor (bFGF), transforming growth factor-beta, neurotrophin-3, angiopoietin, vascular endothelial growth factor, and the receptor for bFGF. In accordance, angiogenesis was increased in GFAP-IL6 mice relative to controls after 6-AN. Moreover, oxidative stress and apoptotic cell death were significantly reduced by transgenic IL-6 expression. IL-6 is also a major inducer in the CNS of metallothionein I and II (MT-I+II), which were significantly increased in the GFAP-IL6 mice. MT-I+II are antioxidants and neuroregenerative factors in the CNS, so increased MT-I+II levels in GFAP-IL6 mice could contribute to the reduction of oxidative stress and cell death in these mice.

  5. Modeling of helium transport and exhaust in the LHD edge

    NASA Astrophysics Data System (ADS)

    Bader, A.; Kobayashi, M.; Schmitz, O.; Akerson, A. R.; Effenberg, F.; Frerichs, H.; Feng, Y.; Hegna, C. C.; Ida, K.; The LHD Experimental Group

    2016-12-01

    Experimental results from LHD show a reduction of helium concentration in the plasma with the introduction of a magnetic island on the m/n  =  1/1 resonant surface in the plasma edge. Simulations of the plasma with and without the island are carried out with the coupled code EMC3-EIRENE and compared to charge exchange recombination spectroscopy measurements of ionized core helium, and visible spectroscopy measurements of edge neutral helium. The numerical simulations indicate that the experimental parameters lie in a high density regime where the impurity transport is dominated by the outward directed friction force. The EMC3-EIRENE simulations capture the reduction in helium transport well and indicate that: (1) the reduction in core helium is a result of increased outward transport caused by the magnetic island and an increased opening of the edge-surface layer to the divertor plates; (2) the dominant source of neutral helium is best modeled by recycled helium at the targets; and (3) ionized helium density profiles are best matched in the simulations when there is a large core helium source in addition to a smaller edge source.

  6. MicroRNA-374a Promotes Hepatocellular Carcinoma Cell Proliferation by Targeting Mitogen-Inducible Gene-6 (MIG-6).

    PubMed

    Li, Hui; Chen, Huicheng; Wang, Haibin; Dong, Yilong; Yin, Min; Zhang, Liang; Wei, Jia

    2017-07-21

    Hepatocellular carcinoma (HCC) is a dreadful disease with poor prognosis rates and ineffective therapeutic options. Previous studies have reported the involvement of mitogeninducible gene 6 (MIG-6) as a negative regulator in tumor formation. MicroRNAs (miRNAs) play crucial roles in the development of different types of cancer. However, the underlying mechanisms of miRNAs in HCC are poorly understood. This study was aimed to investigate the role of miR-374a in HCC and its role in regulation of expression of MIG-6. The results showed that MIG-6 overexpression significantly inhibited cell viability of HepG2 cells after 4 day of post-transfection. Moreover, MIG-6 was a direct target of miR-374a and the expression of MIG-6 was remarkably down-regulated by overexpression of miR-374a in HepG2 cells. Furthermore, we found that overexpression of miR-374a promoted cell viability, however, the protective effect was abolished by MIG-6 overexpression. Besides, overexpression of miR-374a activated EGFR and AKT/ERK signal pathways by regulation of MIG-6. Our findings suggest that miR-374a could promote cell viability by targeting MIG-6 and activating EGFR and AKT/ERK signal pathways. These data will provide a promising therapeutic strategy for HCC treatment.

  7. Probing of the neutrino magnetic moment at the level of 10{sup -22} μ{sub B} with an intense tritium source of (anti)neutrino and helium target (project)

    SciTech Connect

    Martemyanov, V.P.; Aleshin, V.I.; Tarasenko, V.G.; Tsinoev, V.G.; Sabelnikov, A.A.; Yukhimchuk, A.A.; Popov, V.V.; Baluev, V.V.; Golubkov, A.N.; Klevtsov, V.G.; Kuryakin, A.V.; Sitdikov, D.T.; Bogdanova, L.N.

    2015-03-15

    We present research results of the preparation project for the experimental measurement of the (anti)neutrino magnetic moment at the level of 10{sup -12} μ{sub B} using an intense tritium source of antineutrinos and a liquid helium scintillation detector. The neutrino detection in the scintillation detector is based on the scattering of neutrinos by the electrons of the helium atoms that produces fast electrons able to ionize and exciting helium atoms. The detection of the atomic radiation emitted during the relaxation process of the helium atoms and the knowledge of its parameters will allow us to conclude on the neutrino properties.

  8. Generation of hard x rays by femtosecond laser pulse interaction with Cu in laminar helium flow in ambient air

    SciTech Connect

    Hou Bixue; Easter, James; Krushelnick, Karl; Nees, John A.

    2008-04-21

    Hard x rays are generated in laminar helium flow in atmosphere (without a vacuum vessel) through the interaction of tightly focused 35 fs laser pulses of varying energy with a Cu target. The energy conversion efficiency from laser to K{alpha} x rays is measured to be 5.4x10{sup -6}, giving a flux of 5.9x10{sup 9} photons/s into 2{pi} sr from a source measuring approximately 9x12 {mu}m{sup 2} in size (verticalxhorizontal). Results are compared to those measured in vacuum and in static helium environments.

  9. Suicide by asphyxiation due to helium inhalation.

    PubMed

    Howard, Matthew O; Hall, Martin T; Edwards, Jeffrey D; Vaughn, Michael G; Perron, Brian E; Winecker, Ruth E

    2011-03-01

    Suicide by asphyxiation using helium is the most widely-promoted method of "self-deliverance" by right-to-die advocates. However, little is known about persons committing such suicides or the circumstances and manner in which they are completed. Prior reports of suicides by asphyxiation involving helium were reviewed and deaths determined by the North Carolina Office of the Chief Medical Examiner to be helium-associated asphyxial suicides occurring between January 1, 2000 and December 31, 2008 were included in a new case series examined in this article. The 10 asphyxial suicides involving helium identified in North Carolina tended to occur almost exclusively in non-Hispanic, white men who were relatively young (M age = 41.1 T 11.6). In 6 of 10 cases, decedents suffered from significant psychiatric dysfunction; in 3 of these 6 cases, psychiatric disorders were present comorbidly with substance abuse. In none of these cases were decedents suffering from terminal illness. Most persons committing suicide with helium were free of terminal illness but suffered from psychiatric and/or substance use disorders.

  10. Annual Cosmic Ray Spectra from 250 MeV up to 1.6 GeV from 1995 - 2014 Measured with the Electron Proton Helium Instrument onboard SOHO

    NASA Astrophysics Data System (ADS)

    Kühl, P.; Gómez-Herrero, R.; Heber, B.

    2016-03-01

    The solar modulation of galactic cosmic rays (GCR) can be studied in detail by examining long-term variations of the GCR energy spectrum ( e.g. on the scales of a solar cycle). With almost 20 years of data, the Electron Proton Helium INstrument (EPHIN) onboard the SOlar and Heliospheric Observatory (SOHO) is well suited for this kind of investigation. Although the design of the instrument is optimised to measure proton and helium isotope spectra up to 50 MeV nucleon^{-1}, the capability exists to determine proton energy spectra from 250 MeV up to above 1.6 GeV. Therefore we developed a sophisticated inversion method to calculate such proton spectra. The method relies on a GEANT4 Monte Carlo simulation of the instrument and a simplified spacecraft model that calculates the energy-response function of EPHIN for electrons, protons, and heavier ions. For validation purposes, proton spectra based on this method are compared to various balloon missions and space instrumentation. As a result we present annual galactic cosmic-ray spectra from 1995 to 2014.

  11. HPV E6 Proteins Target Ubc9, the SUMO Conjugating Enzyme

    PubMed Central

    Heaton, Phillip R.; Deyrieux, Adeline F.; Bian, Xue-Lin; Wilson, Van G.

    2011-01-01

    The human papillomavirus oncogenic protein, E6, interacts with a number of cellular proteins, and for some targets, E6 directs their degradation through the ubiquitin-proteasome pathway. Post-translational modification with ubiquitin-like modifiers, such as SUMO, also influences protein activities, protein-protein interactions, and protein stability. We report that the high risk HPVE6 proteins reduce the intracellular quantity of the sole SUMO conjugation enzyme, Ubc9, concomitant with decreased host sumoylation. E6 did not significantly influence transcription of Ubc9, indicating that the effects were likely at the protein level. Consistent with typical E6-mediated proteasomal degradation, E6 bound to Ubc9 in vitro, and required E6AP for reduction of Ubc9 levels. Under stable E6 expression conditions in differentiating keratinocytes there was a decrease in Ubc9 and a loss of numerous sumoylated targets indicating a significant perturbation of the normal sumoylation profile. While E6 is known to inhibit PIASy, a SUMO ligase, our results suggest that HPV E6 also targets the Ubc9 protein to modulate host cell sumoylation, suggesting that the sumoylation system may be an important target during viral reproduction and possibly the subsequent development of cervical cancer. PMID:21510985

  12. Helium on Venus - Implications for uranium and thorium

    NASA Technical Reports Server (NTRS)

    Prather, M. J.; Mcelroy, M. B.

    1983-01-01

    Helium is removed at an average rate of 10 to the 6th atoms per square centimeter per second from Venus's atmosphere by the solar wind following ionization above the plasmapause. The surface source of helium-4 on Venus is similar to that on earth, suggesting comparable abundances of crustal uranium and thorium.

  13. Helium on Venus - Implications for uranium and thorium

    NASA Technical Reports Server (NTRS)

    Prather, M. J.; Mcelroy, M. B.

    1983-01-01

    Helium is removed at an average rate of 10 to the 6th atoms per square centimeter per second from Venus's atmosphere by the solar wind following ionization above the plasmapause. The surface source of helium-4 on Venus is similar to that on earth, suggesting comparable abundances of crustal uranium and thorium.

  14. Rationally designed BCL6 inhibitors target activated B cell diffuse large B cell lymphoma.

    PubMed

    Cardenas, Mariano G; Yu, Wenbo; Beguelin, Wendy; Teater, Matthew R; Geng, Huimin; Goldstein, Rebecca L; Oswald, Erin; Hatzi, Katerina; Yang, Shao-Ning; Cohen, Joanna; Shaknovich, Rita; Vanommeslaeghe, Kenno; Cheng, Huimin; Liang, Dongdong; Cho, Hyo Je; Abbott, Joshua; Tam, Wayne; Du, Wei; Leonard, John P; Elemento, Olivier; Cerchietti, Leandro; Cierpicki, Tomasz; Xue, Fengtian; MacKerell, Alexander D; Melnick, Ari M

    2016-09-01

    Diffuse large B cell lymphomas (DLBCLs) arise from proliferating B cells transiting different stages of the germinal center reaction. In activated B cell DLBCLs (ABC-DLBCLs), a class of DLBCLs that respond poorly to current therapies, chromosomal translocations and amplification lead to constitutive expression of the B cell lymphoma 6 (BCL6) oncogene. The role of BCL6 in maintaining these lymphomas has not been investigated. Here, we designed small-molecule inhibitors that display higher affinity for BCL6 than its endogenous corepressor ligands to evaluate their therapeutic efficacy for targeting ABC-DLBCL. We used an in silico drug design functional-group mapping approach called SILCS to create a specific BCL6 inhibitor called FX1 that has 10-fold greater potency than endogenous corepressors and binds an essential region of the BCL6 lateral groove. FX1 disrupted formation of the BCL6 repression complex, reactivated BCL6 target genes, and mimicked the phenotype of mice engineered to express BCL6 with corepressor binding site mutations. Low doses of FX1 induced regression of established tumors in mice bearing DLBCL xenografts. Furthermore, FX1 suppressed ABC-DLBCL cells in vitro and in vivo, as well as primary human ABC-DLBCL specimens ex vivo. These findings indicate that ABC-DLBCL is a BCL6-dependent disease that can be targeted by rationally designed inhibitors that exceed the binding affinity of natural BCL6 ligands.

  15. Rationally designed BCL6 inhibitors target activated B cell diffuse large B cell lymphoma

    PubMed Central

    Cardenas, Mariano G.; Yu, Wenbo; Beguelin, Wendy; Teater, Matthew R.; Geng, Huimin; Goldstein, Rebecca L.; Oswald, Erin; Hatzi, Katerina; Yang, Shao-Ning; Cohen, Joanna; Shaknovich, Rita; Vanommeslaeghe, Kenno; Cheng, Huimin; Liang, Dongdong; Cho, Hyo Je; Tam, Wayne; Du, Wei; Leonard, John P.; Elemento, Olivier; Cierpicki, Tomasz; Xue, Fengtian; MacKerell, Alexander D.; Melnick, Ari M.

    2016-01-01

    Diffuse large B cell lymphomas (DLBCLs) arise from proliferating B cells transiting different stages of the germinal center reaction. In activated B cell DLBCLs (ABC-DLBCLs), a class of DLBCLs that respond poorly to current therapies, chromosomal translocations and amplification lead to constitutive expression of the B cell lymphoma 6 (BCL6) oncogene. The role of BCL6 in maintaining these lymphomas has not been investigated. Here, we designed small-molecule inhibitors that display higher affinity for BCL6 than its endogenous corepressor ligands to evaluate their therapeutic efficacy for targeting ABC-DLBCL. We used an in silico drug design functional-group mapping approach called SILCS to create a specific BCL6 inhibitor called FX1 that has 10-fold greater potency than endogenous corepressors and binds an essential region of the BCL6 lateral groove. FX1 disrupted formation of the BCL6 repression complex, reactivated BCL6 target genes, and mimicked the phenotype of mice engineered to express BCL6 with corepressor binding site mutations. Low doses of FX1 induced regression of established tumors in mice bearing DLBCL xenografts. Furthermore, FX1 suppressed ABC-DLBCL cells in vitro and in vivo, as well as primary human ABC-DLBCL specimens ex vivo. These findings indicate that ABC-DLBCL is a BCL6-dependent disease that can be targeted by rationally designed inhibitors that exceed the binding affinity of natural BCL6 ligands. PMID:27482887

  16. Helium resources of the United States, 1989. Information Circular/1990

    SciTech Connect

    Miller, R.D.; Hamak, J.E.

    1990-01-01

    The helium resources base of the United States was estimated by the Bureau of Mines to be 894.6 Bcf as of January 1, 1989. These resources are divided into four categories in decreasing degree of the assurance of their existence: (1) helium in storage and in proved natural gas reserves, 282.4 Bcf, (2) helium in probable natural gas resources, estimated at 237.7 Bcf, (3) helium in possible natural gas resources, estimated to be 263.1 Bcf, and (4) helium in speculative natural gas resources, 111.4 Bcf. These helium resources are further divided into depleting and nondepleting, with the helium in storage being in a separate classification. The depleting resources are those associated with natural gasfields that are, or will be, produced for the natural gas they contain. Almost all of the helium in potential (probable, possible, and speculative) natural gas resources is included in this classification. These depleting resources are estimated to contain 775 Bcf of the total helium resource base.

  17. Helium Storage and Transfer Subsystem design description. Revision

    SciTech Connect

    1987-07-01

    The Helium Storage and Transfer Subsystem (HSTS) consists of two parts. The first consists of nine (9) high pressure storage tanks containing helium at 15.6 MPa (2250 psig). These tanks provide makeup and purge helium at a rate of 1216 kg per y (2680 lb/y) to the various helium users, including circulator bearing seals, analysis packages, and cooling system surge tanks. The second, larger part of the system, provides for the low pressure storage of 6078 kg (13,400 lb) of primary coolant helium in 180 storage tanks at 7.0 MPa (1000 psig). The system serves all four (4) reactor modules. The low pressure storage part of the system receives helium from the discharge of Helium Purification Subsystem (HPS) and is activated during depressurization and pumpup operations only. It is not required to operate continuously. Storage capacity is provided for primary helium coolant from two reactor modules. However, since depressurization and pumpup operations are performed for only one reactor module at a time, two 50% capacity low pressure transfer compressors are provided having a total transfer capacity of 340 am{sup 3}/h (200 acfm) which is sufficient to service one module. High pressure helium is supplied continuously to all the four reactor modules simultaneously from the high pressure storage tanks. These tanks are replaced periodically with fresh tanks.

  18. Mannose-6-phosphate receptor: a target for theranostics of prostate cancer.

    PubMed

    Vaillant, Ophélie; El Cheikh, Khaled; Warther, David; Brevet, David; Maynadier, Marie; Bouffard, Elise; Salgues, Frédéric; Jeanjean, Audrey; Puche, Pierre; Mazerolles, Catherine; Maillard, Philippe; Mongin, Olivier; Blanchard-Desce, Mireille; Raehm, Laurence; Rébillard, Xavier; Durand, Jean-Olivier; Gary-Bobo, Magali; Morère, Alain; Garcia, Marcel

    2015-05-11

    The development of personalized and non-invasive cancer therapies based on new targets combined with nanodevices is a major challenge in nanomedicine. In this work, the over-expression of a membrane lectin, the cation-independent mannose 6-phosphate receptor (M6PR), was specifically demonstrated in prostate cancer cell lines and tissues. To efficiently target this lectin a mannose-6-phosphate analogue was synthesized in six steps and grafted onto the surface of functionalized mesoporous silica nanoparticles (MSNs). These MSNs were used for in vitro and ex vivo photodynamic therapy to treat prostate cancer cell lines and primary cell cultures prepared from patient biopsies. The results demonstrated the efficiency of M6PR targeting for prostate cancer theranostic. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  19. Is solid helium a supersolid?

    SciTech Connect

    Hallock, Robert

    2015-05-15

    Recent experiments suggest that helium-4 atoms can flow through an experimental cell filled with solid helium. But that incompletely understood flow is quite different from the reported superfluid-like motion that so excited physicists a decade ago.

  20. Targeted Analysis of KLF6/KLF6-SV1 Regulating Pathways in Prostrate Cancer Development and Metastasis

    DTIC Science & Technology

    2010-09-01

    gene   frequently   inactivated  in  prostate  cancer  (PCa).  A  single  germline  SNP  increases  PCa...risk  and  KLF6   gene  alternative  splicing  to  produce  KLF6-­‐SV1,   which   promotes   tumor   cell   growth   and...of  c-­‐Myc  target   genes .   In   sum,   these   results   when   taken   together   begin   to  

  1. Helium-refrigeration system

    SciTech Connect

    Specht, J.R.; Millar, B.; Sutherland, A.

    1995-08-01

    The design, procurement, and preliminary construction was completed for adding two more wet expansion engines to two helium refrigerators. These will be added in mid-year FY 1995. In addition a variable speed drive will be added to an existing helium compressor. This is part of an energy conservation upgrade project to reduce operating costs from the use of electricity and liquid nitrogen. This project involves the replacement of Joule-Thompson valves in the refrigerators with expansion engines resulting in system efficiency improvements of about 30% and improved system reliability.

  2. Helium Diffusion in Olivine

    NASA Astrophysics Data System (ADS)

    Cherniak, D. J.; Watson, E. B.

    2011-12-01

    Diffusion of helium has been characterized in natural Fe-bearing olivine (~Fo90) and synthetic forsterite. Polished, oriented slabs of olivine were implanted with 3He, at 100 keV at a dose of 5x1015/cm2 or at 3.0 MeV at a dose of 1x1016/cm2. A set of experiments on the implanted olivine were run in 1-atm furnaces. In addition to the one-atm experiments, experiments on implanted samples were also run at higher pressures (2.6 and 2.7 GPa) to assess the potential effects of pressure on He diffusion and the applicability of the measured diffusivities in describing He transport in the mantle. The high-pressure experiments were conducted in a piston-cylinder apparatus using an "ultra-soft" pressure cell, with the diffusion sample directly surrounded by AgCl. 3He distributions following experiments were measured with Nuclear Reaction Analysis using the reaction 3He(d,p)4He. This direct profiling method permits us to evaluate anisotropy of diffusion, which cannot be easily assessed using bulk-release methods. For diffusion in forsterite parallel to c we obtain the following Arrhenius relation over the temperatures 250-950°C: D = 3.91x10-6exp(-159 ± 4 kJ mol-1/RT) m2/sec. The data define a single Arrhenius line spanning more than 7 orders of magnitude in D and 700°C in temperature. Diffusion parallel to a appears slightly slower, yielding an activation energy for diffusion of 135 kJ/mol and a pre-exponential factor of 3.73x10-8 m2/sec. Diffusion parallel to b is slower than diffusion parallel to a (by about two-thirds of a log unit); for this orientation an activation energy of 138 kJ/mol and a pre-exponential factor of 1.34x10-8 m2/sec are obtained. This anisotropy is broadly consistent with observations for diffusion of Ni and Fe-Mg in olivine. Diffusion in Fe-bearing olivine (transport parallel to b) agrees within uncertainty with findings for He diffusion in forsterite. The higher-pressure experiments yield diffusivities in agreement with those from the 1-atm

  3. The Expanding Role of the BCL6 Oncoprotein as a Cancer Therapeutic Target.

    PubMed

    Cardenas, Mariano G; Oswald, Erin; Yu, Wenbo; Xue, Fengtian; MacKerell, Alexander D; Melnick, Ari M

    2017-02-15

    BCL6 was initially discovered as an oncogene in B-cell lymphomas, where it drives the malignant phenotype by repressing proliferation and DNA damage checkpoints and blocking B-cell terminal differentiation. BCL6 mediates its effects by binding to hundreds of target genes and then repressing these genes by recruiting several different chromatin-modifying corepressor complexes. Structural characterization of BCL6-corepressor complexes suggested that BCL6 might be a druggable target. Accordingly, a number of compounds have been designed to bind to BCL6 and block corepressor recruitment. These compounds, based on peptide or small-molecule scaffolds, can potently block BCL6 repression of target genes and kill lymphoma cells. In the case of diffuse large B-cell lymphomas (DLBCL), BCL6 inhibitors are equally effective in suppressing both the germinal center B-cell (GCB)- and the more aggressive activated B-cell (ABC)-DLBCL subtypes, both of which require BCL6 to maintain their survival. In addition, BCL6 is implicated in an expanding scope of hematologic and solid tumors. These include, but are not limited to, B-acute lymphoblastic leukemia, chronic myeloid leukemia, breast cancer, and non-small cell lung cancer. BCL6 inhibitors have been shown to exert potent effects against these tumor types. Moreover, mechanism-based combinations of BCL6 inhibitors with other agents have yielded synergistic and often quite dramatic activity. Hence, there is a compelling case to accelerate the development of BCL6-targeted therapies for translation to the clinical setting. Clin Cancer Res; 23(4); 885-93. ©2016 AACR.

  4. Cavitation in flowing superfluid helium

    NASA Technical Reports Server (NTRS)

    Daney, D. E.

    1988-01-01

    Flowing superfluid helium cavitates much more readily than normal liquid helium, and there is a marked difference in the cavitation behavior of the two fluids as the lambda point is traversed. Examples of cavitation in a turbine meter and centrifugal pump are given, together with measurements of the cavitation strength of flowing superfluid helium. The unusual cavitation behavior of superfluid helium is attributed to its immense thermal conductivity .

  5. Preclinical validation of interleukin 6 as a therapeutic target in multiple myeloma

    PubMed Central

    Rosean, Timothy R.; Tompkins, Van S.; Tricot, Guido; Holman, Carol J.; Olivier, Alicia K.; Zhan, Fenghuang; Janz, Siegfried

    2014-01-01

    Studies on the biologic and molecular genetic underpinnings of multiple myeloma (MM) have identified the pleiotropic, pro-inflammatory cytokine, interleukin-6 (IL-6), as a factor crucial to the growth, proliferation and survival of myeloma cells. IL-6 is also a potent stimulator of osteoclastogenesis and a sculptor of the tumor microenvironment in the bone marrow of patients with myeloma. This knowledge has engendered considerable interest in targeting IL-6 for therapeutic purposes, using a variety of antibody- and small-molecule-based therapies. However, despite the early recognition of the importance of IL-6 for myeloma and the steady progress in our knowledge of IL-6 in normal and malignant development of plasma cells, additional efforts will be required to translate the promise of IL-6 as a target for new myeloma therapies into significant clinical benefits for patients with myeloma. This review summarizes published research on the role of IL-6 in myeloma development and describes ongoing efforts by the University of Iowa Myeloma Multidisciplinary Oncology Group to develop new approaches to the design and testing of IL-6-targeted therapies and preventions of MM. PMID:24845460

  6. Asymptotic and near-target direct breakup of 6Li and 7Li

    NASA Astrophysics Data System (ADS)

    Kalkal, Sunil; Simpson, E. C.; Luong, D. H.; Cook, K. J.; Dasgupta, M.; Hinde, D. J.; Carter, I. P.; Jeung, D. Y.; Mohanto, G.; Palshetkar, C. S.; Prasad, E.; Rafferty, D. C.; Simenel, C.; Vo-Phuoc, K.; Williams, E.; Gasques, L. R.; Gomes, P. R. S.; Linares, R.

    2016-04-01

    Background: Li,76 and 9Be are weakly bound against breakup into their cluster constituents. Breakup location is important for determining the role of breakup in above-barrier complete fusion suppression. Recent works have pointed out that experimental observables can be used to separate near-target and asymptotic breakup. Purpose: Our purpose is to distinguish near-target and asymptotic direct breakup of Li,76 in reactions with nuclei in different mass regions. Method: Charged particle coincidence measurements are carried out with pulsed Li,76 beams on 58Ni and 64Zn targets at sub-barrier energies and compared with previous measurements using 208Pb and 209Bi targets. A detector array providing a large angular coverage is used, along with time-of-flight information to give definitive particle identification of the direct breakup fragments. Results: In interactions of 6Li with 58Ni and 64Zn, direct breakup occurs only asymptotically far away from the target. However, in interactions with 208Pb and 209Bi, near-target breakup occurs in addition to asymptotic breakup. Direct breakup of 7Li into α -t is not observed in interactions with 58Ni and 64Zn. However, near-target dominated direct breakup was observed in measurements with 208Pb and 209Bi. A modified version of the Monte Carlo classical trajectory model code platypus, which explicitly takes into account lifetimes associated with unbound states, is used to simulate sub-barrier breakup reactions. Conclusions: Near-target breakup in interactions with Li,76 is an important mechanism only for the heavy targets 208Pb and 209Bi. There is insignificant near-target direct breakup of 6Li and no direct breakup of 7Li in reactions with 58Ni and 64Zn. Therefore, direct breakup is unlikely to suppress the above-barrier fusion cross section in reactions of Li,76 with 58Ni and 64Zn nuclei.

  7. Helium-Shrouded Planets Artist Concept

    NASA Image and Video Library

    2015-06-11

    Planets having atmospheres rich in helium may be common in our galaxy, according to a new theory based on data from NASA's Spitzer Space Telescope. These planets would be around the mass of Neptune, or lighter, and would orbit close to their stars, basking in their searing heat. According to the new theory, radiation from the stars would boil off hydrogen in the planets' atmospheres. Both hydrogen and helium are common ingredients of gas planets like these. Hydrogen is lighter than helium and thus more likely to escape. After billions of years of losing hydrogen, the planet's atmosphere would become enriched with helium. Scientists predict the planets would appear covered in white or gray clouds. This is in contrast to our own Neptune, which is blue due to the presence of methane. Methane absorbs the color red, leaving blue. Neptune is far from our sun and hasn't lost its hydrogen. The hydrogen bonds with carbon to form methane. This artist's concept depicts a proposed helium-atmosphere planet called GJ 436b, which was found by Spitzer to lack in methane -- a first clue about its lack of hydrogen. The planet orbits every 2.6 days around its star, which is cooler than our sun and thus appears more yellow-orange in color. http://photojournal.jpl.nasa.gov/catalog/PIA19344

  8. Thermal Performance of the XRS Helium Insert

    NASA Technical Reports Server (NTRS)

    Breon, Susan R.; DiPirro, Michael J.; Tuttle, James G.; Shirron, Peter J.; Warner, Brent A.; Boyle, Robert F.; Canavan, Edgar R.

    1999-01-01

    The X-Ray Spectrometer (XRS) is an instrument on the Japanese Astro-E satellite, scheduled for launch early in the year 2000. The XRS Helium Insert comprises a superfluid helium cryostat, an Adiabatic Demagnetization Refrigerator (ADR), and the XRS calorimeters with their cold electronics. The calorimeters are capable of detecting X-rays over the energy range 0.1 to 10 keV with a resolution of 12 eV. The Helium Insert completed its performance and verification testing at Goddard in January 1999. It was shipped to Japan, where it has been integrated with the neon dewar built by Sumitomo Heavy Industries. The Helium Insert was given a challenging lifetime requirement of 2.0 years with a goal of 2.5 years. Based on the results of the thermal performance tests, the predicted on-orbit lifetime is 2.6 years with a margin of 30%. This is the result of both higher efficiency in the ADR cycle and the low temperature top-off, more than compensating for an increase in the parasitic heat load. This paper presents a summary of the key design features and the results of the thermal testing of the XRS Helium Insert.

  9. Superfluid helium-4 in one dimensional channel

    NASA Astrophysics Data System (ADS)

    Kim, Duk Y.; Banavar, Samhita; Chan, Moses H. W.; Hayes, John; Sazio, Pier

    2013-03-01

    Superfluidity, as superconductivity, cannot exist in a strict one-dimensional system. However, the experiments employing porous media showed that superfluid helium can flow through the pores of nanometer size. Here we report a study of the flow of liquid helium through a single hollow glass fiber of 4 cm in length with an open id of 150 nm between 1.6 and 2.3 K. We found the superfluid transition temperature was suppressed in the hollow cylinder and that there is no flow above the transition. Critical velocity at temperature below the transition temperature was determined. Our results bear some similarity to that found by Savard et. al. studying the flow of helium through a nanohole in a silicon nitrite membrane. Experimental study at Penn State is supported by NSF Grants No. DMR 1103159.

  10. Thermodynamic properties of hydrogen-helium plasmas

    NASA Technical Reports Server (NTRS)

    Nelson, H. F.

    1971-01-01

    The thermodynamic properties of an atomic hydrogen-helium plasma are calculated and tabulated for temperatures from 10,000 to 100,000 K as a function of the mass fraction ratio of atomic hydrogen. The tabulation is for densities from 10 to the minus 10th power to 10 to the minus 6th power gm/cu cm and for hydrogen mass fraction ratios of 0, 0.333, 0.600, 0.800, and 1.0, which correspond to pure helium, 50 percent hydrogen per unit volume, 75 percent hydrogen per unit volume, 89 percent hydrogen per unit volume, and pure hydrogen plasmas, respectively. From an appended computer program, calculations can be made at other densities and mass fractions. The program output agrees well with previous thermodynamic property calculations for limiting cases of pure hydrogen and pure helium plasmas.

  11. An Assessment of Helium Evolution from Helium-Saturated Propellant Depressurization in Space

    NASA Technical Reports Server (NTRS)

    Nguyen, Bich N.; Best, Frederick; Wong, Tony; Kurwitz, Cable; McConnaughey, H. (Technical Monitor)

    2001-01-01

    Helium evolution from the transfer of helium-saturated propellant in space is quantified to assess its impacts from creating two-phase gas/liquid flow from the supply tank, gas injection into the receiving tank, and liquid discharge from the receiving tank. Propellant transfer takes place between two similar tanks whose maximum storage capacity is approximately 2.55 cubic meters each. The maximum on-orbit propellants transfer capability is 9000 lbm (fuel and oxidizer). The transfer line is approximately 1.27 cm in diameter and 6096 cm in length and comprised of the fluid interconnect system (FICS), the orbiter propellant transfer system (OPTS), and the International Space Station (ISS) propulsion module (ISSPM). The propellant transfer rate begins at approximately 11 liter per minute (lpm) and subsequently drops to approximately 0.5 lpm. The tank nominal operating pressure is approximately 1827 kPa (absolute). The line pressure drops for Monomethy1hydrazine (MMH) and Nitrogen tetroxide (NTO) at 11.3 lpm are approximately 202 kPa and 302 kPa, respectively. The pressure-drop results are based on a single-phase flow. The receiving tank is required to vent from approximately 1827 kPa to a lower pressure to affect propellant transfer. These pressure-drop scenarios cause the helium-saturated propellants to release excess helium. For tank ullage venting, the maximum volumes of helium evolved at tank pressure are approximately 0.5 ft3 for MMH and 2 ft3 for NTO. In microgravity environment, due to lack of body force, the helium evolution from a liquid body acts to propel it, which influences its fluid dynamics. For propellant transfer, the volume fractions of helium evolved at line pressure are 0.1% by volume for MMH and 0.6 % by volume for NTO at 11.3 lpm. The void fraction of helium evolved varies as an approximate second order power function of flow rate.

  12. Pharmacologic targeting of S6K1 in PTEN-deficient neoplasia

    PubMed Central

    Liu, Hongqi; Feng, Xizhi; Ennis, Kelli N.; Behrmann, Catherine A.; Sarma, Pranjal; Jiang, Tony T.; Kofuji, Satoshi; Niu, Liang; Stratton, Yiwen; Thomas, Hala Elnakat; Yoon, Sang-Oh; Sasaki, Atsuo T.; Plas, David R.

    2017-01-01

    SUMMARY Genetic S6K1 inactivation can induce apoptosis in PTEN-deficient cells. We analyzed the therapeutic potential of S6K1 inhibitors in PTEN-deficient T cell leukemia and glioblastoma. Results revealed that the S6K1 inhibitor LY-2779964 was relatively ineffective as a single agent, while S6K1-targeting AD80 induced cytotoxicity selectively in PTEN-deficient cells. In vivo, AD80 rescued 50% of mice transplanted with PTEN-deficient leukemia cells. Cells surviving LY-2779964 treatment exhibited inhibitor-induced S6K1 phosphorylation due to increased mTOR-S6K1 co-association, which primed rapid recovery of S6K1 signaling. In contrast, AD80 avoided S6K1 phosphorylation and mTOR co-association, resulting in durable suppression of S6K1-induced signaling and protein synthesis. Kinome analysis revealed that AD80 coordinately inhibits S6K1 together with the TAM family tyrosine kinase AXL. TAM suppression by BMS-777607 or genetic knockdown potentiated cytotoxic responses to LY-2779964 in PTEN-deficient glioblastoma cells. These results reveal that combination targeting of S6K1 and TAMs is a potential strategy for treatment of PTEN-deficient malignancy. PMID:28249155

  13. Production of Doubly Excited Projectile States in Collisions of 0.1 Mev/u SILVER(+4) Ions with Helium, Hydrogen, and Argon Gas Target

    NASA Astrophysics Data System (ADS)

    Underwood-Lemons, Theresa Ann

    An important problem in atomic dynamics is the structure of very high doubly excited states, in which two electrons are excited away from the rest of the electrons in the ionic core, making their mutual interaction and correlation as important as their individual interaction with the remaining core. In this work, we study the formation of doubly excited projectile states near the double escape threshold in collisions of 0.1 MeV/u Ag^{+4} ions with He, H_2, and Ar gas targets. We detect projectile states in which one electron occupies a high Rydberg state and a second electron (a cusp electron) occupies a low lying continuum state. Cusp electrons are characterized by a velocity which is nearly equal in magnitude and direction to the projectile velocity. Cusp electrons are energy analyzed with a 30 ^circ parallel plate energy analyzer, and Rydberg electrons are field ionized in a spherical ionizer before being energy analyzed in a 160^ circ^herical sector analyzer. Standard coincidence measurements between a cusp and a Rydberg electron signal the production of a doubly excited projectile state. The cross sections for producing these doubly excited projectile states are on the order of 10 ^{-20} cm^2. The production probabilities are measured as a function of cusp electron laboratory frame energy with the detected Rydberg electrons arising from a fixed band of principal quantum numbers. The laboratory frame energy distributions of cusp electrons associated with these doubly excited states are then compared to the energy distribution of cusp electrons measured without imposing a Rydberg electron coincidence requirement. For the He target, the shapes of the two energy distributions are the same. However, the width of the energy distribution of cusp electrons measured in coincidence with Rydberg electrons is smaller than the width of the cusp electron energy distribution without a coincidence requirement for the H_2 and Ar gas targets, the difference being greatest for

  14. A Measurement of the neutron electric form factor at very large momentum transfer using polaried electrions scattering from a polarized helium-3 target

    SciTech Connect

    Kelleher, Aidan

    2010-02-01

    Knowledge of the electric and magnetic elastic form factors of the nucleon is essential for an understanding of nucleon structure. Of the form factors, the electric form factor of the neutron has been measured over the smallest range in Q2 and with the lowest precision. Jefferson Lab experiment 02-013 used a novel new polarized 3 He target to nearly double the range of momentum transfer in which the neutron form factor has been studied and to measure it with much higher precision. Polarized electrons were scattered off this target, and both the scattered electron and neutron were detected. Gn E was measured to be 0.0242 ± 0.0020(stat) ± 0.0061(sys) and 0.0247 ± 0.0029(stat) ± 0.0031(sys) at Q2 = 1.7 and 2.5 GeV2 , respectively.

  15. High-Level Transient Expression of ER-Targeted Human Interleukin 6 in Nicotiana benthamiana

    PubMed Central

    Nausch, Henrik; Mikschofsky, Heike; Koslowski, Roswitha; Meyer, Udo; Broer, Inge; Huckauf, Jana

    2012-01-01

    Tobacco plants can be used to express recombinant proteins that cannot be produced in a soluble and active form using traditional platforms such as Escherichia coli. We therefore expressed the human glycoprotein interleukin 6 (IL6) in two commercial tobacco cultivars (Nicotiana tabacum cv. Virginia and cv. Geudertheimer) as well as the model host N. benthamiana to compare different transformation strategies (stable vs. transient expression) and subcellular targeting (apoplast, endoplasmic reticulum (ER) and vacuole). In T0 transgenic plants, the highest expression levels were achieved by ER targeting but the overall yields of IL6 were still low in the leaves (0.005% TSP in the ER, 0.0008% in the vacuole and 0.0005% in the apoplast). The apoplast variant accumulated to similar levels in leaves and seeds, whereas the ER-targeted variant was 1.2-fold more abundant in seeds and the vacuolar variant was 6-fold more abundant in seeds. The yields improved in subsequent generations, with the best-performing T2 plants producing the ER-targeted IL6 at 0.14% TSP in both leaves and seeds. Transient expression of ER-targeted IL6 in leaves using the MagnICON system resulted in yields of up to 7% TSP in N. benthamiana, but only 1% in N. tabacum cv. Virginia and 0.5% in cv. Geudertheimer. Although the commercial tobacco cultivars produced up to threefold more biomass than N. benthamiana, this was not enough to compensate for the lower overall yields. The recombinant IL6 produced by transient and stable expression in plants was biologically active and presented as two alternative bands matching the corresponding native protein. PMID:23152824

  16. THE VISCOSITY OF HELIUM-CESIUM MIXTURES,

    DTIC Science & Technology

    The viscosities of helium-cesium mixtures having mole fractions of cesium from zero to unity were evaluated using a Lennard - Jones 6-12 interaction potential for all encounters in the Enskog Chapman expressions for the viscosity of a binary mixture. (Author)

  17. Helium anion formation inside helium droplets

    NASA Astrophysics Data System (ADS)

    Jabbour Al Maalouf, Elias; Reitshammer, Julia; Ribar, Anita; Scheier, Paul; Denifl, Stephan

    2016-07-01

    The formation of He∗- is examined with improved electron energy resolution of about 100 meV utilizing a hemispherical electron monochromator. The work presented provides a precise determination of the three previously determined resonance peak positions that significantly contribute to the formation of He∗- inside helium nanodroplets in the energy range from 20 eV to 29.5 eV. In addition, a new feature is identified located at 27.69 ± 0.18 eV that we assign to the presence of O2 as a dopant inside the droplet. With increasing droplet size a small blue shift of the resonance positions is observed. Also for the relatively low electron currents used in the present study (i.e., 15-70 nA) a quadratic dependence of the He∗- ion yield on the electron current is observed.

  18. Radiation effects on microstructure and hardness of a titanium aluminide alloy irradiated by helium ions at room and elevated temperatures

    NASA Astrophysics Data System (ADS)

    Wei, Tao; Zhu, Hanliang; Ionescu, Mihail; Dayal, Pranesh; Davis, Joel; Carr, David; Harrison, Robert; Edwards, Lyndon

    2015-04-01

    A 45XD TiAl alloy possessing a lamellar microstructure was irradiated using 5 MeV helium ions to a fluence of 5 × 1021 ion m-2 (5000 appm) with a dose of about 1 dpa (displacements per atom). A uniform helium ion stopping damage region about 17 μm deep from the target surface was achieved by applying an energy degrading wheel. Radiation damage defects including helium-vacancy clusters and small helium bubbles were found in the microstructure of the samples irradiated at room temperature. With increasing irradiation temperature to 300 °C and 500 °C helium bubbles were clearly observed in both the α2 and γ phases of the irradiated microstructure. By means of nanoindentation significant irradiation hardening was measured. For the samples irradiated at room temperature the hardness increased from 5.6 GPa to 8.5 GPa and the irradiation-hardening effect reduced to approximately 8.0 GPa for the samples irradiated at 300 °C and 500 °C.

  19. Recent developments for an active UF6 gas target for photon-induced fission experiments

    NASA Astrophysics Data System (ADS)

    Freudenberger, M.; Eckardt, C.; Enders, J.; Göök, A.; von Neumann-Cosel, P.; Oberstedt, A.; Oberstedt, S.

    2013-12-01

    Recent developments for an active uranium-hexafluoride-loaded gas target as well as results on the detector gas properties are presented. The gas of choice is a mixture of argon with small amounts of UF6. This contribution presents the experimental setup and focusses on the electron drift velocity with increasing UF6 content. A time-dependent decrease in electron drift velocity is observed in our setup.

  20. A data integration framework for prediction of transcription factor targets: a BCL6 case study

    PubMed Central

    Nykter, Matti; Lähdesmäki, Harri; Rust, Alistair; Thorsson, Vesteinn; Shmulevich, Ilya

    2009-01-01

    We present a computational framework for predicting targets of transcription factor regulation. The framework is based on the integration of a number of sources of evidence, derived from DNA sequence and gene expression data, using a weighted sum approach. Sources of evidence are prioritized based on a training set, and their relative contributions are then optimized. The performance of the proposed framework is demonstrated in the context of BCL6 target prediction. We show that this framework is able to uncover BCL6 targets reliably when biological prior information is utilized effectively, particularly in the case of sequence analysis. The framework results in a considerable gain in performance over scores in which sequence information was not incorporated. This analysis shows that with assessment of the quality and biological relevance of the data, reliable predictions can be obtained with this computational framework. PMID:19348642

  1. Teens on Target Violence Prevention Curriculum for Grades 6-12.

    ERIC Educational Resources Information Center

    Becker, Marla G.; Calhoun, Deane

    This curriculum is designed to help schools implement programs to prevent violence among students in grades 6-12. It is a six-session, school based curriculum intended for adolescents who are living in communities experiencing high rates of violence. It is facilitated by trained Teens on Target (TNT) members/peer educators, young people who are…

  2. Teens on Target Violence Prevention Curriculum for Grades 6-12.

    ERIC Educational Resources Information Center

    Becker, Marla G.; Calhoun, Deane

    This curriculum is designed to help schools implement programs to prevent violence among students in grades 6-12. It is a six-session, school based curriculum intended for adolescents who are living in communities experiencing high rates of violence. It is facilitated by trained Teens on Target (TNT) members/peer educators, young people who are…

  3. miR-1299 suppresses cell proliferation of hepatocellular carcinoma (HCC) by targeting CDK6.

    PubMed

    Zhu, Huaqiang; Wang, Guangchuan; Zhou, Xu; Song, Xie; Gao, Hengjun; Ma, Chaoqun; Chang, Hong; Li, Hongguang; Liu, Fang-Feng; Lu, Jun; Ma, Jinben

    2016-10-01

    microRNA (miRNA) plays critical role in HCC initiation and development, many miRNAs have been reported to regulate HCC progression. In this study, we studied the role of miR-1299 in cell proliferation of HCC. We found miR-1299 was significantly downregulated in HCC cells and tissues. miR-1299 overexpression inhibited cell proliferation and arrested cell cycle in G0/G1 phase analyzed by MTT assay, soft agar assay, BrdU cell proliferation assay and cell cycle assay, while miR-1299 knockdown promoted cell proliferation and accelerated G1/S transition. Further analysis suggested the key regulator of G1/S transition, cyclin-dependent kinase 6 (CDK6) was the target of miR-1299, miR-1299 inhibited CDK6 expression and bound to the 3'UTR of CDK6. When double knockdown of miR-1299 and CDK6 promoted cell proliferation copied the phenotype caused by miR-1299 overexpression, suggesting miR-1299 inhibits cell proliferation by targeting CDK6. In summary, our data revealed miR-1299 inhibits cell proliferation, and might be a target for HCC therapy.

  4. Production of thorium-229 using helium nuclei

    DOEpatents

    Mirzadeh, Saed [Knoxville, TN; Garland, Marc Alan [Knoxville, TN

    2010-12-14

    A method for producing .sup.229Th includes the steps of providing .sup.226Ra as a target material, and bombarding the target material with alpha particles, helium-3, or neutrons to form .sup.229Th. When neutrons are used, the neutrons preferably include an epithermal neutron flux of at least 1.times.10.sup.13 n s.sup.-1cm.sup.-2. .sup.228Ra can also be bombarded with thermal and/or energetic neutrons to result in a neutron capture reaction to form .sup.229Th. Using .sup.230Th as a target material, .sup.229Th can be formed using neutron, gamma ray, proton or deuteron bombardment.

  5. The adsorption of helium atoms on coronene cations

    NASA Astrophysics Data System (ADS)

    Kurzthaler, Thomas; Rasul, Bilal; Kuhn, Martin; Lindinger, Albrecht; Scheier, Paul; Ellis, Andrew M.

    2016-08-01

    We report the first experimental study of the attachment of multiple foreign atoms to a cationic polycyclic aromatic hydrocarbon (PAH). The chosen PAH was coronene, C24H12, which was added to liquid helium nanodroplets and then subjected to electron bombardment. Using mass spectrometry, coronene cations decorated with helium atoms were clearly seen and the spectrum shows peaks with anomalously high intensities ("magic number" peaks), which represent ion-helium complexes with added stability. The data suggest the formation of a rigid helium layer consisting of 38 helium atoms that completely cover both faces of the coronene ion. Additional magic numbers can be seen for the further addition of 3 and 6 helium atoms, which are thought to attach to the edge of the coronene. The observation of magic numbers for the addition of 38 and 44 helium atoms is in good agreement with a recent path integral Monte Carlo prediction for helium atoms on neutral coronene. An understanding of how atoms and molecules attach to PAH ions is important for a number of reasons including the potential role such complexes might play in the chemistry of the interstellar medium.

  6. Targeting synthetic lethality between the SRC kinase and the EPHB6 receptor may benefit cancer treatment

    PubMed Central

    Bhanumathy, Kalpana Kalyanasundaram; Li, Yue; Gerger, Courtney; Zawily, Amr El; Freywald, Tanya; Anderson, Deborah H.; Mousseau, Darrell; Kanthan, Rani; Zhang, Zhaolei; Vizeacoumar, Franco J.; Freywald, Andrew

    2016-01-01

    Application of tumor genome sequencing has identified numerous loss-of-function alterations in cancer cells. While these alterations are difficult to target using direct interventions, they may be attacked with the help of the synthetic lethality (SL) approach. In this approach, inhibition of one gene causes lethality only when another gene is also completely or partially inactivated. The EPHB6 receptor tyrosine kinase has been shown to have anti-malignant properties and to be downregulated in multiple cancers, which makes it a very attractive target for SL applications. In our work, we used a genome-wide SL screen combined with expression and interaction network analyses, and identified the SRC kinase as a SL partner of EPHB6 in triple-negative breast cancer (TNBC) cells. Our experiments also reveal that this SL interaction can be targeted by small molecule SRC inhibitors, SU6656 and KX2-391, and can be used to improve elimination of human TNBC tumors in a xenograft model. Our observations are of potential practical importance, since TNBC is an aggressive heterogeneous malignancy with a very high rate of patient mortality due to the lack of targeted therapies, and our work indicates that FDA-approved SRC inhibitors may potentially be used in a personalized manner for treating patients with EPHB6-deficient TNBC. Our findings are also of a general interest, as EPHB6 is downregulated in multiple malignancies and our data serve as a proof of principle that EPHB6 deficiency may be targeted by small molecule inhibitors in the SL approach. PMID:27418135

  7. The transcriptional modulator BCL6 as a molecular target for breast cancer therapy

    PubMed Central

    Walker, Sarah R.; Liu, Suhu; Xiang, Michael; Nicolais, Maria; Hatzi, Katerina; Giannopoulou, Eugenia; Elemento, Olivier; Cerchietti, Leandro; Melnick, Ari; Frank, David A.

    2014-01-01

    Inappropriate expression or activation of transcription factors can drive patterns of gene expression leading to the malignant behavior of breast cancer cells. We have found that the transcriptional repressor BCL6 is highly expressed in breast cancer cell lines, and its locus is amplified in about half of primary breast cancers. To understand how BCL6 regulates gene expression in breast cancer cells, we utilized ChIP-seq to identify the BCL6 binding sites on a genomic scale. This revealed that BCL6 regulates a unique cohort of genes in breast cancer cell lines compared to B cell lymphomas. Furthermore, BCL6 expression promotes the survival of breast cancer cells, and targeting BCL6 with a peptidomimetic inhibitor leads to apoptosis of these cells. Finally, combining a BCL6 inhibitor and a STAT3 inhibitor provided enhanced cell killing in triple negative breast cancer cell lines, suggesting that combination therapy may be particularly useful. Thus, targeting BCL6 alone or in conjunction with other signaling pathways may be a useful therapeutic strategy for treating breast cancer. PMID:24662818

  8. Sirt6 deficiency exacerbates podocyte injury and proteinuria through targeting Notch signaling.

    PubMed

    Liu, Min; Liang, Kaili; Zhen, Junhui; Zhou, Meng; Wang, Xiaojie; Wang, Ziying; Wei, Xinbing; Zhang, Yan; Sun, Yu; Zhou, Zhuanli; Su, Hua; Zhang, Chun; Li, Ningjun; Gao, Chengjiang; Peng, Jun; Yi, Fan

    2017-09-04

    Podocyte injury is a major determinant of proteinuric kidney disease and the identification of potential therapeutic targets for preventing podocyte injury has clinical importance. Here, we show that histone deacetylase Sirt6 protects against podocyte injury through epigenetic regulation of Notch signaling. Sirt6 is downregulated in renal biopsies from patients with podocytopathies and its expression correlates with glomerular filtration rate. Podocyte-specific deletion of Sirt6 exacerbates podocyte injury and proteinuria in two independent mouse models, diabetic nephropathy, and adriamycin-induced nephropathy. Sirt6 has pleiotropic protective actions in podocytes, including anti-inflammatory and anti-apoptotic effects, is involved in actin cytoskeleton maintenance and promotes autophagy. Sirt6 also reduces urokinase plasminogen activator receptor expression, which is a key factor for podocyte foot process effacement and proteinuria. Mechanistically, Sirt6 inhibits Notch1 and Notch4 transcription by deacetylating histone H3K9. We propose Sirt6 as a potential therapeutic target for the treatment of proteinuric kidney disease.Podocytes are essential components of the renal glomerular filtration barrier and podocyte dysfunction leads to proteinuric kidney disease. Here Liu et al. show that Sirt6 protects podocytes from apoptosis and inflammation by increasing autophagic flux through inhibition of the Notch pathway.

  9. Epigallocatechin-3-gallate(EGCG) suppresses melanoma cell growth and metastasis by targeting TRAF6 activity

    PubMed Central

    Zhang, Xu; Zhou, Youyou; Luo, Zhongling; Zeng, Weiqi; Su, Juan; Peng, Cong; Chen, Xiang

    2016-01-01

    TRAF6 (TNF Receptor-Associated Factor 6) is an E3 ubiquitin ligase that contains a Ring domain, induces K63-linked polyubiquitination, and plays a critical role in signaling transduction. Our previous results demonstrated that TRAF6 is overexpressed in melanoma and that TRAF6 knockdown dramatically attenuates tumor cell growth and metastasis. In this study, we found that EGCG can directly bind to TRAF6, and a computational model of the interaction between EGCG and TRAF6 revealed that EGCG probably interacts with TRAF6 at the residues of Gln54, Gly55, Asp57 ILe72, Cys73 and Lys96. Among these amino acids, mutation of Gln54, Asp57, ILe72 in TRAF6 could destroy EGCG bound to TRAF6, furthermore, our results demonstrated that EGCG significantly attenuates interaction between TRAF6 and UBC13(E2) and suppresses TRAF6 E3 ubiquitin ligase activity in vivo and in vitro. Additionally, the phosphorylation of IκBα, p-TAK1 expression are decreased and the nuclear translocation of p65 and p50 is blocked by treatment with EGCG, leading to inactivation of the NF-κB pathway. Moreover, EGCG significantly inhibits cell growth as well as the migration and invasion of melanoma cells. Taken together, these findings show that EGCG is a novel E3 ubiquitin ligase inhibitor that could be used to target TRAF6 for chemotherapy or the prevention of melanoma. PMID:27791197

  10. Auroral helium precipitation.

    NASA Technical Reports Server (NTRS)

    Axford, W. I.; Chivers, H. J. A.; Eberhardt, P.; Geiss, J.; Buehler, F.

    1972-01-01

    Application of the metal foil sampling technique, which has been used to measure helium, neon, and argon fluxes in the solar wind, to the problem of measuring the fluxes of these gases in the auroral primary radiation. Aluminum and platinum foils have been flown into two bright auroras and have been recovered. The foils have been analyzed for helium and neon isotopes with a mass spectrometer; so far only He4 has been detected. In the first flight the precipitating flux of He4 with particle energies above about 1 keV was approximately 1,000,000 per sq cm per sec, and the backscattered flux was smaller by about a factor of 10. In the second flight the aurora was less bright, and the He4 fluxes were lower by a factor of about 2. A rough analysis suggests that the mean energy of the incident particles was greater than 3 keV.

  11. Auroral helium precipitation.

    NASA Technical Reports Server (NTRS)

    Axford, W. I.; Chivers, H. J. A.; Eberhardt, P.; Geiss, J.; Buehler, F.

    1972-01-01

    Application of the metal foil sampling technique, which has been used to measure helium, neon, and argon fluxes in the solar wind, to the problem of measuring the fluxes of these gases in the auroral primary radiation. Aluminum and platinum foils have been flown into two bright auroras and have been recovered. The foils have been analyzed for helium and neon isotopes with a mass spectrometer; so far only He4 has been detected. In the first flight the precipitating flux of He4 with particle energies above about 1 keV was approximately 1,000,000 per sq cm per sec, and the backscattered flux was smaller by about a factor of 10. In the second flight the aurora was less bright, and the He4 fluxes were lower by a factor of about 2. A rough analysis suggests that the mean energy of the incident particles was greater than 3 keV.

  12. Feasibility of lunar Helium-3 mining

    NASA Astrophysics Data System (ADS)

    Kleinschneider, Andreas; Van Overstraeten, Dmitry; Van der Reijnst, Roy; Van Hoorn, Niels; Lamers, Marvin; Hubert, Laurent; Dijk, Bert; Blangé, Joey; Hogeveen, Joel; De Boer, Lennaert; Noomen, Ron

    -3 fusion were calculated using a predicted minimum energy price in 2040 of 30.4 Euro/MWh. Annual costs are between 427.7 to 1,347.9 billion Euro, with annual expected profit ranging from -724.0 to 260.0 billion Euro. Due to the large scale of the mission, it has also been evaluated for providing 0.1% and 1% of the global energy demand in 2040. For 1%, the annual costs are 45.6 to 140.3 billion Euro and the expected annual profits are -78.0 to 23.1 billion Euro. For 0.1%, the annual costs are 7.7 to 20.5 billion Euro. The annual expected profits are -14.3 to -0.8 billion Euro. Feasibility has been addressed in three aspects. Technically, the mission is extremely challenging and complex. However, most required technologies exist or could be developed within a reasonable time span. From a political and legal perspective, the current international treaties hardly provide any framework for a lunar mining operation. Financially, the mission only produces a net profit in the best case, and only for medium- to large-scale operations, which require a very large initial investment. To make lunar Helium-3 usage possible, further research should concentrate on the mining operation and costs of fusion plants, as their impact by far outranks all other mission elements. Different transportation concepts may be investigated nevertheless. Many - not only technical - challenges concerning Helium-3 mining are still to be addressed. Although only a starting point for further investigations, this study shows that, despite popular claims, lunar Helium-3 is unsuitable to provide a significant percentage of the global energy demand in 2040.

  13. Targets of AtWRKY6 regulation during plant senescence and pathogen defense

    PubMed Central

    Robatzek, Silke; Somssich, Imre E.

    2002-01-01

    In Arabidopsis, WRKY factors comprise a large gene family of plant-specific transcriptional regulators controlling several types of plant stress responses. To understand the regulatory role of WRKY proteins during such processes, we identified targets of the senescence- and defense-associated WRKY6 factor. WRKY6 was found to suppress its own promoter activity as well as that of a closely related WRKY family member, indicating negative autoregulation. On the other hand, WRKY6 positively influenced the senescence- and pathogen defense-associated PR1 promoter activity, most likely involving NPR1 function. One novel identified target gene, SIRK, encodes a receptor-like protein kinase, whose developmental expression is strongly induced specifically during leaf senescence. The transcriptional activation of SIRK is dependent on WRKY6 function. Senescing leaves of wrky6 knockout mutants showed a drastic reduction, and green leaves of WRKY6 overexpression lines showed clearly elevated SIRK transcript levels. Furthermore, the SIRK gene promoter was specifically activated by WRKY6 in vivo, functioning very likely through direct W-box interactions. PMID:12000796

  14. Education in Helium Refrigeration

    NASA Astrophysics Data System (ADS)

    Gistau Baguer, G. M.

    2004-06-01

    On the one hand, at the end of the time I was active in helium refrigeration, I noticed that cryogenics was stepping into places where it was not yet used. For example, a conventional accelerator, operating at room temperature, was to be upgraded to reach higher particle energy. On the other hand, I was a little bit worried to let what I had so passionately learned during these years to be lost. Retirement made time available, and I came gradually to the idea to teach about what was my basic job. I thought also about other kinds of people who could be interested in such lessons: operators of refrigerators or liquefiers who, often by lack of time, did not get a proper introduction to their job when they started, young engineers who begin to work in cryogenics… and so on. Consequently, I have assembled a series of lessons about helium refrigeration. As the audiences have different levels of knowledge in the field of cryogenics, I looked for a way of teaching that is acceptable for all of them. The course is split into theory of heat exchangers, refrigeration cycles, technology and operation of main components, process control, and helium purity.

  15. Applications of Groundwater Helium

    USGS Publications Warehouse

    Kulongoski, Justin T.; Hilton, David R.

    2011-01-01

    Helium abundance and isotope variations have widespread application in groundwater-related studies. This stems from the inert nature of this noble gas and the fact that its two isotopes ? helium-3 and helium-4 ? have distinct origins and vary widely in different terrestrial reservoirs. These attributes allow He concentrations and 3He/4He isotope ratios to be used to recognize and quantify the influence of a number of potential contributors to the total He budget of a groundwater sample. These are atmospheric components, such as air-equilibrated and air-entrained He, as well as terrigenic components, including in situ (aquifer) He, deep crustal and/or mantle He and tritiogenic 3He. Each of these components can be exploited to reveal information on a number of topics, from groundwater chronology, through degassing of the Earth?s crust to the role of faults in the transfer of mantle-derived volatiles to the surface. In this review, we present a guide to how groundwater He is collected from aquifer systems and quantitatively measured in the laboratory. We then illustrate the approach of resolving the measured He characteristics into its component structures using assumptions of endmember compositions. This is followed by a discussion of the application of groundwater He to the types of topics mentioned above using case studies from aquifers in California and Australia. Finally, we present possible future research directions involving dissolved He in groundwater.

  16. Education in Helium Refrigeration

    SciTech Connect

    Gistau Baguer, G. M.

    2004-06-23

    On the one hand, at the end of the time I was active in helium refrigeration, I noticed that cryogenics was stepping into places where it was not yet used. For example, a conventional accelerator, operating at room temperature, was to be upgraded to reach higher particle energy. On the other hand, I was a little bit worried to let what I had so passionately learned during these years to be lost. Retirement made time available, and I came gradually to the idea to teach about what was my basic job. I thought also about other kinds of people who could be interested in such lessons: operators of refrigerators or liquefiers who, often by lack of time, did not get a proper introduction to their job when they started, young engineers who begin to work in cryogenics... and so on.Consequently, I have assembled a series of lessons about helium refrigeration. As the audiences have different levels of knowledge in the field of cryogenics, I looked for a way of teaching that is acceptable for all of them. The course is split into theory of heat exchangers, refrigeration cycles, technology and operation of main components, process control, and helium purity.

  17. Identification of proteasomal catalytic subunit PSMA6 as a therapeutic target for lung cancer.

    PubMed

    Kakumu, Tomohiko; Sato, Mitsuo; Goto, Daiki; Kato, Toshio; Yogo, Naoyuki; Hase, Tetsunari; Morise, Masahiro; Fukui, Takayuki; Yokoi, Kohei; Sekido, Yoshitaka; Girard, Luc; Minna, John D; Byers, Lauren A; Heymach, John V; Coombes, Kevin R; Kondo, Masashi; Hasegawa, Yoshinori

    2017-04-01

    To identify potential therapeutic targets for lung cancer, we performed semi-genome-wide shRNA screening combined with the utilization of genome-wide expression and copy number data. shRNA screening targeting 5043 genes in NCI-H460 identified 51 genes as candidates. Pathway analysis revealed that the 51 genes were enriched for the five pathways, including ribosome, proteasome, RNA polymerase, pyrimidine metabolism and spliceosome pathways. We focused on the proteasome pathway that involved six candidate genes because its activation has been demonstrated in diverse human malignancies, including lung cancer. Microarray expression and array CGH data showed that PSMA6, a proteasomal subunit of a 20S catalytic core complex, was highly expressed in lung cancer cell lines, with recurrent gene amplifications in some cases. Therefore, we further examined the roles of PSMA6 in lung cancer. Silencing of PSMA6 induced apoptosis or G2/M cell cycle arrest in cancer cell lines but not in an immortalized normal lung cell line. These results suggested that PSMA6 serves as an attractive target with a high therapeutic index for lung cancer. © 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

  18. Targeting of rotavirus VP6 to DEC-205 induces protection against the infection in mice.

    PubMed

    Badillo-Godinez, O; Gutierrez-Xicotencatl, L; Plett-Torres, T; Pedroza-Saavedra, A; Gonzalez-Jaimes, A; Chihu-Amparan, L; Maldonado-Gama, M; Espino-Solis, G; Bonifaz, L C; Esquivel-Guadarrama, F

    2015-08-20

    Rotavirus (RV) is the primary etiologic agent of severe gastroenteritis in human infants. Although two attenuated RV-based vaccines have been licensed to be applied worldwide, they are not so effective in low-income countries, and the induced protection mechanisms have not been clearly established. Thus, it is important to develop new generation vaccines that induce long lasting heterotypic immunity. VP6 constitutes the middle layer protein of the RV virion. It is the most conserved protein and it is the target of protective T-cells; therefore, it is a potential candidate antigen for a new generation vaccine against the RV infection. We determined whether targeting the DEC-205 present in dendritic cells (DCs) with RV VP6 could induce protection at the intestinal level. VP6 was cross-linked to a monoclonal antibody (mAb) against murine DEC-205 (αDEC-205:VP6), and BALB/c mice were inoculated subcutaneously (s.c.) twice with the conjugated containing 1.5 μg of VP6 in the presence of polyinosinic-polycytidylic acid (Poly I:C) as adjuvant. As controls and following the same protocol, mice were immunized with ovalbumin (OVA) cross-linked to the mAb anti-DEC-205 (αDEC-205:OVA), VP6 cross-linked to a control isotype mAb (Isotype:VP6), 3 μg of VP6 alone, Poly I:C or PBS. Two weeks after the last inoculation, mice were orally challenged with a murine RV. Mice immunized with α-DEC-205:VP6 and VP6 alone presented similar levels of serum Abs to VP6 previous to the virus challenge. However, after the virus challenge, only α-DEC-205:VP6 induced up to a 45% IgA-independent protection. Memory T-helper (Th) cells from the spleen and the mesenteric lymph node (MLN) showed a Th1-type response upon antigen stimulation in vitro. These results show that when VP6 is administered parenterally targeting DEC-205, it can induce protection at the intestinal level at a very low dose, and this protection may be Th1-type cell dependent. Copyright © 2015 Elsevier Ltd. All rights reserved.

  19. Helium anion formation inside helium droplets

    NASA Astrophysics Data System (ADS)

    Maalouf, Elias Jabbour Al; Reitshammer, Julia; Ribar, Anita; Scheier, Paul; Denifl, Stephan

    2016-07-01

    The formation of He∗- is examined with improved electron energy resolution of about 100 meV utilizing a hemispherical electron monochromator. The work presented provides a precise determination of the three previously determined resonance peak positions that significantly contribute to the formation of He∗- inside helium nanodroplets in the energy range from 20 eV to 29.5 eV. In addition, a new feature is identified located at 27.69 ± 0.18 eV that we assign to the presence of O2 as a dopant inside the droplet. With increasing droplet size a small blue shift of the resonance positions is observed. Also for the relatively low electron currents used in the present study (i.e., 15-70 nA) a quadratic dependence of the He∗- ion yield on the electron current is observed. Contribution to the Topical Issue "Advances in Positron and Electron Scattering", edited by Paulo Limao-Vieira, Gustavo Garcia, E. Krishnakumar, James Sullivan, Hajime Tanuma and Zoran Petrovic.

  20. RGS6 as a Novel Therapeutic Target in CNS Diseases and Cancer.

    PubMed

    Ahlers, Katelin E; Chakravarti, Bandana; Fisher, Rory A

    2016-05-01

    Regulator of G protein signaling (RGS) proteins are gatekeepers regulating the cellular responses induced by G protein-coupled receptor (GPCR)-mediated activation of heterotrimeric G proteins. Specifically, RGS proteins determine the magnitude and duration of GPCR signaling by acting as a GTPase-activating protein for Gα subunits, an activity facilitated by their semiconserved RGS domain. The R7 subfamily of RGS proteins is distinguished by two unique domains, DEP/DHEX and GGL, which mediate membrane targeting and stability of these proteins. RGS6, a member of the R7 subfamily, has been shown to specifically modulate Gαi/o protein activity which is critically important in the central nervous system (CNS) for neuronal responses to a wide array of neurotransmitters. As such, RGS6 has been implicated in several CNS pathologies associated with altered neurotransmission, including the following: alcoholism, anxiety/depression, and Parkinson's disease. In addition, unlike other members of the R7 subfamily, RGS6 has been shown to regulate G protein-independent signaling mechanisms which appear to promote both apoptotic and growth-suppressive pathways that are important in its tumor suppressor function in breast and possibly other tissues. Further highlighting the importance of RGS6 as a target in cancer, RGS6 mediates the chemotherapeutic actions of doxorubicin and blocks reticular activating system (Ras)-induced cellular transformation by promoting degradation of DNA (cytosine-5)-methyltransferase 1 (DNMT1) to prevent its silencing of pro-apoptotic and tumor suppressor genes. Together, these findings demonstrate the critical role of RGS6 in regulating both G protein-dependent CNS pathology and G protein-independent cancer pathology implicating RGS6 as a novel therapeutic target.

  1. The winter helium bulge revisited

    NASA Astrophysics Data System (ADS)

    Liu, Xianjing; Wang, Wenbin; Thayer, Jeffrey P.; Burns, Alan; Sutton, Eric; Solomon, Stanley C.; Qian, Liying; Lucas, Greg

    2014-10-01

    A newly implemented helium module in the National Center for Atmospheric Research-Thermosphere Ionosphere Electrodynamics general circulation model offers the first opportunity in three decades to describe helium behavior in the context of a first principles, self-consistent model and to test early theories of wintertime helium bulge formation. This study shows general agreement with the findings of Reber and Hays (1973) but articulates the definitive role of vertical advection in the bulge formation. Our findings indicate vertical advection and molecular diffusion are the dominate processes responsible for the solstice helium distribution. Horizontal winds indirectly contribute to the helium bulge formation by their divergent wind field that leads to vertical winds in order to maintain thermosphere mass continuity. As a minor gas, thermospheric helium does not contribute to mass continuity and its distribution is dictated by more local interactions and constraints.

  2. Helium and multiple populations in the massive globular cluster NGC 6266 (M 62)

    NASA Astrophysics Data System (ADS)

    Milone, A. P.

    2015-01-01

    Recent studies suggest that the helium content of multiple stellar populations in globular clusters (GCs) is not uniform. The range of helium varies from cluster to cluster with more massive GCs having, preferentially, large helium spread. GCs with large helium variations also show extended-blue horizontal branch (HB). I exploit Hubble Space Telescope photometry to investigate multiple stellar populations in NGC 6266 and infer their relative helium abundance. This cluster is an ideal target to investigate the possible connection between helium, cluster mass, and HB morphology, as it exhibits an extended HB and is among the 10 more luminous GCs in the Milky Way. The analysis of colour-magnitude diagrams from multiwavelength photometry reveals that also NGC 6266, similarly to other massive GCs, hosts a double main sequence (MS), with the red and the blue component made up of the 79 ± 1 per cent and the 21 ± 1 per cent of stars, respectively. The red MS is consistent with a stellar population with primordial helium while the blue MS is highly helium-enhanced by ΔY = 0.08 ± 0.01. Furthermore, the red MS exhibits an intrinsic broadening that cannot be attributed to photometric errors only and is consistent with a spread in helium of ˜0.025 dex. The comparison between NGC 6266 and other GCs hosting helium-enriched stellar populations supports the presence of a correlation among helium variations, cluster mass, and HB extension.

  3. Molecular Targeting of CEACAM6 Using Antibody Probes of Different Sizes

    PubMed Central

    Niu, Gang; Murad, Yanal M.; Gao, Haokao; Hu, Shuo; Guo, Ning; Jacobson, Orit; Nguyen, Thanh-Dung; Zhang, Jianbing; Chen, Xiaoyuan

    2012-01-01

    Carcinocinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6) is overexpressed in a number of human malignancies, especially in pancreatic cancer. It has been demonstrated that CEACAM6 is a potential target for monoclonal antibody (mAb) therapy with a safe therapeutic index. Here, we labeled three anti-CEACAM6 antibodies of different sizes, including a single-domain antibody 2A3 (16 kDa), a heavy chain antibody 2A3-mFc (80 kDa) and a full length antibody 9A6 (150 kDa), with 64Cu to image CEACAM6 expression in a xenografted pancreatic tumor model. For positron emission tomography (PET) imaging, the tumor mice were intravenously injected with 64Cu-DOTA-antibodies and static scans were obtained at 5 min, 0.5, 1, 2, 4, 8 and 24 h post-injection (p.i.). All three antibodies showed strong CEACAM6 binding. Ex vivo immunostaining on tumor sections at 24 h after Ab injection demonstrated specific tumor targeting of both 2A3-mFc and 9A6. 64Cu-DOTA-2A3 showed fast BxPC3 tumor uptake and rapid whole-body clearance. At 24 h p.i., the tumor uptakes were 98.2 ± 6.12 %ID/g for 64Cu-DOTA-2A3-mFc and 57.8 ± 3.73 %ID/g for 64Cu-DOTA-9A6, respectively. Compared with the full length antibody 9A6, the heavy chain antibody 2A3-mFc showed higher tumor uptake, lower liver uptake and shorter circulation half-life. All the data supported that the heavy chain antibody 2A3-mFc is superior to the single domain antibody and the full-length antibody with regard to tumor detection and pharmacokinetics, which has great potential to be developed for CEACAM6-targeted pancreatic cancer imaging and therapy. PMID:22568933

  4. Correlation of Helium Solubility in Liquid Nitrogen

    NASA Technical Reports Server (NTRS)

    VanDresar, Neil T.; Zimmerli, Gregory A.

    2012-01-01

    A correlation has been developed for the equilibrium mole fraction of soluble gaseous helium in liquid nitrogen as a function of temperature and pressure. Experimental solubility data was compiled and provided by National Institute of Standards and Technology (NIST). Data from six sources was used to develop a correlation within the range of 0.5 to 9.9 MPa and 72.0 to 119.6 K. The relative standard deviation of the correlation is 6.9 percent.

  5. Interleukin 6 Receptor Is an Independent Prognostic Factor and a Potential Therapeutic Target of Ovarian Cancer

    PubMed Central

    Isobe, Aki; Sawada, Kenjiro; Kinose, Yasuto; Ohyagi-Hara, Chifumi; Nakatsuka, Erika; Makino, Hiroshi; Ogura, Tomonori; Mizuno, Tomoko; Suzuki, Noriko; Morii, Eiichi; Nakamura, Koji; Sawada, Ikuko; Toda, Aska; Hashimoto, Kae; Mabuchi, Seiji; Ohta, Tsuyoshi; Morishige, Ken-ichirou; Kurachi, Hirohisa; Kimura, Tadashi

    2015-01-01

    Ovarian cancer remains the most lethal gynecologic cancer and new targeted molecular therapies against this miserable disease continue to be challenging. In this study, we analyzed the expressional patterns of Interleukin-6 (IL-6) and its receptor (IL-6R) expression in ovarian cancer tissues, evaluated the impact of these expressions on clinical outcomes of patients, and found that a high-level of IL-6R expression but not IL-6 expression in cancer cells is an independent prognostic factor. In in vitro analyses using ovarian cell lines, while six (RMUG-S, RMG-1, OVISE, A2780, SKOV3ip1 and OVCAR-3) of seven overexpressed IL-6R compared with a primary normal ovarian surface epithelium, only two (RMG-1, OVISE) of seven cell lines overexpressed IL-6, suggesting that IL-6/IL-6R signaling exerts in a paracrine manner in certain types of ovarian cancer cells. Ovarian cancer ascites were collected from patients, and we found that primary CD11b+CD14+ cells, which were predominantly M2-polarized macrophages, are the major source of IL-6 production in an ovarian cancer microenvironment. When CD11b+CD14+ cells were co-cultured with cancer cells, both the invasion and the proliferation of cancer cells were robustly promoted and these promotions were almost completely inhibited by pretreatment with anti-IL-6R antibody (tocilizumab). The data presented herein suggest a rationale for anti-IL-6/IL-6R therapy to suppress the peritoneal spread of ovarian cancer, and represent evidence of the therapeutic potential of anti-IL-6R therapy for ovarian cancer treatment. PMID:25658637

  6. Helium runaways in white dwarfs

    NASA Technical Reports Server (NTRS)

    Taam, R. E.

    1979-01-01

    The long term evolution of an accreting carbon white dwarf was studied from the onset of accretion to the ignition of helium. The variations in the details of the helium shell flash examined with respect to variations in mass accretion rate. For intermediate rates the helium flash is potentially explosive whereas for high rates the shell flash is relatively weak. The results are discussed in the context of the long term evolution of novae.

  7. 48 CFR 52.208-8 - Required Sources for Helium and Helium Usage Data.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... Helium and Helium Usage Data. 52.208-8 Section 52.208-8 Federal Acquisition Regulations System FEDERAL... Provisions and Clauses 52.208-8 Required Sources for Helium and Helium Usage Data. As prescribed in 8.505, insert the following clause: Required Sources for Helium and Helium Usage Data (APR 2002) (a) Definitions...

  8. 48 CFR 52.208-8 - Required Sources for Helium and Helium Usage Data.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... Helium and Helium Usage Data. 52.208-8 Section 52.208-8 Federal Acquisition Regulations System FEDERAL... Provisions and Clauses 52.208-8 Required Sources for Helium and Helium Usage Data. As prescribed in 8.505, insert the following clause: Required Sources for Helium and Helium Usage Data (APR 2002) (a) Definitions...

  9. 48 CFR 52.208-8 - Required Sources for Helium and Helium Usage Data.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... Helium and Helium Usage Data. 52.208-8 Section 52.208-8 Federal Acquisition Regulations System FEDERAL... Provisions and Clauses 52.208-8 Required Sources for Helium and Helium Usage Data. As prescribed in 8.505, insert the following clause: Required Sources for Helium and Helium Usage Data (APR 2014) (a) Definitions...

  10. 48 CFR 52.208-8 - Required Sources for Helium and Helium Usage Data.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... Helium and Helium Usage Data. 52.208-8 Section 52.208-8 Federal Acquisition Regulations System FEDERAL... Provisions and Clauses 52.208-8 Required Sources for Helium and Helium Usage Data. As prescribed in 8.505, insert the following clause: Required Sources for Helium and Helium Usage Data (APR 2002) (a) Definitions...

  11. Do CDK4/6 inhibitors have potential as targeted therapeutics for squamous cell cancers?

    PubMed

    Kalu, Nene N; Johnson, Faye M

    2017-02-01

    Introduction Dysregulation of cell cycle progression has an established link to neoplasia and cancer progression. Components of the cyclin D-CDK4/6-INK4-Rb pathway are frequently altered in squamous cell carcinomas (SCCs) by diverse mechanisms, including viral oncogene-induced degradation, mutation, deletion, and amplification. Activation of the CDK4/6 pathway may predict response to CDK4/6 inhibitors and provide clinical biomarkers. Recently, the CDK4/6 inhibitor palbociclib showed clinical efficacy in combination with cetuximab in HNSCC patients. Areas covered This review focuses on the current research on the use of CDK4/6 inhibitors, comprising preclinical animal studies through phase II clinical trials across all SCCs. Expert opinion CDK4/6 inhibitors have a proven clinical benefit in breast cancer, but data on SCCs are sparse. Although frequent dysregulation of the cyclin D-CDK4/6-INK4-Rb pathway in SCCs suggests that targeting CDK4/6 may hold promise for improved clinical outcomes, single-agent activity has been modest in preclinical studies and absent in clinical studies. Combinations with immunotherapy or inhibitors of the PI3 K/mTOR or EGFR pathway may be effective. Given that SCCs caused by human papillomavirus have high levels of p16 and low levels of Rb, the CDK4/6 inhibitors are predicted to be ineffective in these cancers.

  12. Helium in Earth's early core

    NASA Astrophysics Data System (ADS)

    Bouhifd, M. A.; Jephcoat, Andrew P.; Heber, Veronika S.; Kelley, Simon P.

    2013-11-01

    The observed escape of the primordial helium isotope, 3He, from the Earth's interior indicates that primordial helium survived the energetic process of planetary accretion and has been trapped within the Earth to the present day. Two distinct reservoirs in the Earth's interior have been invoked to account for variations in the 3He/4He ratio observed at the surface in ocean basalts: a conventional depleted mantle source and a deep, still enigmatic, source that must have been isolated from processing throughout Earth history. The Earth's iron-based core has not been considered a potential helium source because partitioning of helium into metal liquid has been assumed to be negligible. Here we determine helium partitioning in experiments between molten silicates and iron-rich metal liquids at conditions up to 16GPa and 3,000K. Analyses of the samples by ultraviolet laser ablation mass spectrometry yield metal-silicate helium partition coefficients that range between 4.7×10-3 and 1.7×10-2 and suggest that significant quantities of helium may reside in the core. Based on estimated concentrations of primordial helium, we conclude that the early core could have incorporated enough helium to supply deep-rooted plumes enriched in 3He throughout the age of the Earth.

  13. Helium jet dispersion to atmosphere

    NASA Astrophysics Data System (ADS)

    Khan, Hasna J.

    On the event of loss of vacuum guard of superinsulated helium dewar, high rate of heat transfer into the tank occurs. The rapid boiling of liquid helium causes the burst disk to rupture at four atmospheres and consequently the helium passes to the atmosphere through vent lines. The gaseous helium forms a vertical buoyant jet as it exits the vent line into a stagnant environment. Characterization of the gaseous jet is achieved by detailed analysis of the axial and radial dependence of the flow parameters.

  14. Genetic targeting of the endoderm with claudin-6CreER

    PubMed Central

    Anderson, William J; Zhou, Qiao; Alcalde, Victor; Kaneko, Osamu F; Blank, Leah J; Sherwood, Richard I; Guseh, J Sawalla; Rajagopal, Jayaraj; Melton, Douglas A

    2008-01-01

    A full description of the ontogeny of the β cell would guide efforts to generate β cells from embryonic stem cells (ESCs). The first step requires an understanding of definitive endoderm: the genes and signals responsible for its specification, proliferation, and patterning. This report describes a global marker of definitive endoderm, Claudin-6 (Cldn6). We report its expression in early development with particular attention to definitive endoderm derivatives. To create a genetic system to drive gene expression throughout the definitive endoderm with both spatial and temporal control, we target the endogenous locus with an inducible Cre recombinase (Cre-ERT2) cassette. Cldn6 null mice are viable and fertile with no obvious phenotypic abnormalities. We also report a lineage analysis of the fate of Cldn6-expressing embryonic cells, which is relevant to the development of the pancreas, lung, and liver. PMID:18213590

  15. Energetic helium particles trapped in the magnetosphere

    NASA Technical Reports Server (NTRS)

    Chen, Jiasheng; Guzik, T. Gregory; Sang, Yeming; Wefel, John P.; Cooper, John F.

    1994-01-01

    High energy (approximately 40-100 MeV/nucleon) geomagnetically trapped helium nuclei have been measured, for the first time, by the ONR-604 instrument during the 1990/1991 Combined Release and Radiation Effects Satellite (CRRES) mission. The helium events observed at L less than 2.3 have a pitch angle distribution peaking perpendicular to the local magnetic field and are contained in peaks located at L = 1.2 and 1.9. The events in each peak can be characterized by power law energy spectra with indices of 10.0 +/- 0.7 for L = 1.9-2.3 and 6.8 +/- 1.0 for L = 1.15-1.3, before the large storm of 24 March 1991. CRRES was active during solar maximum when the anomalous component is excluded from the inner heliosphere, making it unlikely that the observed events derived from the anomalous component. The trapped helium counting rates decrease gradually with time indicating that these high energy ions were not injected by flares during the 1990/91 mission. Flare injection prior to mid-1990 may account for the highest energy particles, while solar wind injection during magnetic storms and subsequent acceleration could account for the helium at lower energies.

  16. Formation of Positively Charged Liquid Helium Clusters in Supercritical Helium and their Solidification upon Compression.

    PubMed

    Tarchouna, Hejer Gharbi; Bonifaci, Nelly; Aitken, Frédéric; Mendoza Luna, Luis Guillermo; von Haeften, Klaus

    2015-08-06

    Positively charged ions were produced in supercritical helium at temperatures from 6 to 10 K and up to 2 MPa using a corona discharge. Their mobility was measured via current-voltage curves, and the hydrodynamic radius was derived using Stokes law. An initial increase and subsequent decrease of hydrodynamic radius was observed and interpreted in terms of growth, compression and solidification of ion clusters. The mobility was modeled using a van der Waals-type thermodynamic state equation for the ion-in-helium mixed system and a temperature-dependent Millikan-Cunningham factor, describing experimental data both in the Knudsen and the Stokes flow region. Regions of maximum hydrodynamic radius and large compressibility were interpreted as boiling points. These points were modeled over a large range of pressures and found to match the Frenkel line of pure helium up to 0.7 MPa, reflecting similarity of density fluctuations in pure supercritical helium and gas-liquid phase transitions of ionic helium clusters.

  17. HDAC6 as a target for neurodegenerative diseases: what makes it different from the other HDACs?

    PubMed Central

    2013-01-01

    Histone deacetylase (HDAC) inhibitors have been demonstrated to be beneficial in animal models of neurodegenerative diseases. Such results were mainly associated with the epigenetic modulation caused by HDACs, especially those from class I, via chromatin deacetylation. However, other mechanisms may contribute to the neuroprotective effect of HDAC inhibitors, since each HDAC may present distinct specific functions within the neurodegenerative cascades. Such an example is HDAC6 for which the role in neurodegeneration has been partially elucidated so far. The strategy to be adopted in promising therapeutics targeting HDAC6 is still controversial. Specific inhibitors exert neuroprotection by increasing the acetylation levels of α-tubulin with subsequent improvement of the axonal transport, which is usually impaired in neurodegenerative disorders. On the other hand, an induction of HDAC6 would theoretically contribute to the degradation of protein aggregates which characterize various neurodegenerative disorders, including Alzheimer’s, Parkinson’s and Hutington’s diseases. This review describes the specific role of HDAC6 compared to the other HDACs in the context of neurodegeneration, by collecting in silico, in vitro and in vivo results regarding the inhibition and/or knockdown of HDAC6 and other HDACs. Moreover, structure, function, subcellular localization, as well as the level of HDAC6 expression within brain regions are reviewed and compared to the other HDAC isoforms. In various neurodegenerative diseases, the mechanisms underlying HDAC6 interaction with other proteins seem to be a promising approach in understanding the modulation of HDAC6 activity. PMID:23356410

  18. HDAC6 as a target for neurodegenerative diseases: what makes it different from the other HDACs?

    PubMed

    Simões-Pires, Claudia; Zwick, Vincent; Nurisso, Alessandra; Schenker, Esther; Carrupt, Pierre-Alain; Cuendet, Muriel

    2013-01-29

    Histone deacetylase (HDAC) inhibitors have been demonstrated to be beneficial in animal models of neurodegenerative diseases. Such results were mainly associated with the epigenetic modulation caused by HDACs, especially those from class I, via chromatin deacetylation. However, other mechanisms may contribute to the neuroprotective effect of HDAC inhibitors, since each HDAC may present distinct specific functions within the neurodegenerative cascades. Such an example is HDAC6 for which the role in neurodegeneration has been partially elucidated so far. The strategy to be adopted in promising therapeutics targeting HDAC6 is still controversial. Specific inhibitors exert neuroprotection by increasing the acetylation levels of α-tubulin with subsequent improvement of the axonal transport, which is usually impaired in neurodegenerative disorders. On the other hand, an induction of HDAC6 would theoretically contribute to the degradation of protein aggregates which characterize various neurodegenerative disorders, including Alzheimer's, Parkinson's and Hutington's diseases. This review describes the specific role of HDAC6 compared to the other HDACs in the context of neurodegeneration, by collecting in silico, in vitro and in vivo results regarding the inhibition and/or knockdown of HDAC6 and other HDACs. Moreover, structure, function, subcellular localization, as well as the level of HDAC6 expression within brain regions are reviewed and compared to the other HDAC isoforms. In various neurodegenerative diseases, the mechanisms underlying HDAC6 interaction with other proteins seem to be a promising approach in understanding the modulation of HDAC6 activity.

  19. Targeting ceramide synthase 6–dependent metastasis-prone phenotype in lung cancer cells

    PubMed Central

    Suzuki, Motoshi; Cao, Ke; Kato, Seiichi; Komizu, Yuji; Mizutani, Naoki; Tanaka, Kouji; Arima, Chinatsu; Tai, Mei Chee; Yanagisawa, Kiyoshi; Togawa, Norie; Shiraishi, Takahiro; Usami, Noriyasu; Taniguchi, Tetsuo; Fukui, Takayuki; Yokoi, Kohei; Wakahara, Keiko; Hasegawa, Yoshinori; Mizutani, Yukiko; Igarashi, Yasuyuki; Inokuchi, Jin-ichi; Iwaki, Soichiro; Fujii, Satoshi; Satou, Akira; Matsumoto, Yoko; Ueoka, Ryuichi; Tamiya-Koizumi, Keiko; Murate, Takashi; Nakamura, Mitsuhiro; Kyogashima, Mamoru; Takahashi, Takashi

    2015-01-01

    Sphingolipids make up a family of molecules associated with an array of biological functions, including cell death and migration. Sphingolipids are often altered in cancer, though how these alterations lead to tumor formation and progression is largely unknown. Here, we analyzed non–small-cell lung cancer (NSCLC) specimens and cell lines and determined that ceramide synthase 6 (CERS6) is markedly overexpressed compared with controls. Elevated CERS6 expression was due in part to reduction of microRNA-101 (miR-101) and was associated with increased invasion and poor prognosis. CERS6 knockdown in NSCLC cells altered the ceramide profile, resulting in decreased cell migration and invasion in vitro, and decreased the frequency of RAC1-positive lamellipodia formation while CERS6 overexpression promoted it. In murine models, CERS6 knockdown in transplanted NSCLC cells attenuated lung metastasis. Furthermore, combined treatment with l-α-dimyristoylphosphatidylcholine liposome and the glucosylceramide synthase inhibitor D-PDMP induced cell death in association with ceramide accumulation and promoted cancer cell apoptosis and tumor regression in murine models. Together, these results indicate that CERS6-dependent ceramide synthesis and maintenance of ceramide in the cellular membrane are essential for lamellipodia formation and metastasis. Moreover, these results suggest that targeting this homeostasis has potential as a therapeutic strategy for CERS6-overexpressing NSCLC. PMID:26650179

  20. Targeting ceramide synthase 6-dependent metastasis-prone phenotype in lung cancer cells.

    PubMed

    Suzuki, Motoshi; Cao, Ke; Kato, Seiichi; Komizu, Yuji; Mizutani, Naoki; Tanaka, Kouji; Arima, Chinatsu; Tai, Mei Chee; Yanagisawa, Kiyoshi; Togawa, Norie; Shiraishi, Takahiro; Usami, Noriyasu; Taniguchi, Tetsuo; Fukui, Takayuki; Yokoi, Kohei; Wakahara, Keiko; Hasegawa, Yoshinori; Mizutani, Yukiko; Igarashi, Yasuyuki; Inokuchi, Jin-ichi; Iwaki, Soichiro; Fujii, Satoshi; Satou, Akira; Matsumoto, Yoko; Ueoka, Ryuichi; Tamiya-Koizumi, Keiko; Murate, Takashi; Nakamura, Mitsuhiro; Kyogashima, Mamoru; Takahashi, Takashi

    2016-01-01

    Sphingolipids make up a family of molecules associated with an array of biological functions, including cell death and migration. Sphingolipids are often altered in cancer, though how these alterations lead to tumor formation and progression is largely unknown. Here, we analyzed non-small-cell lung cancer (NSCLC) specimens and cell lines and determined that ceramide synthase 6 (CERS6) is markedly overexpressed compared with controls. Elevated CERS6 expression was due in part to reduction of microRNA-101 (miR-101) and was associated with increased invasion and poor prognosis. CERS6 knockdown in NSCLC cells altered the ceramide profile, resulting in decreased cell migration and invasion in vitro, and decreased the frequency of RAC1-positive lamellipodia formation while CERS6 overexpression promoted it. In murine models, CERS6 knockdown in transplanted NSCLC cells attenuated lung metastasis. Furthermore, combined treatment with l-α-dimyristoylphosphatidylcholine liposome and the glucosylceramide synthase inhibitor D-PDMP induced cell death in association with ceramide accumulation and promoted cancer cell apoptosis and tumor regression in murine models. Together, these results indicate that CERS6-dependent ceramide synthesis and maintenance of ceramide in the cellular membrane are essential for lamellipodia formation and metastasis. Moreover, these results suggest that targeting this homeostasis has potential as a therapeutic strategy for CERS6-overexpressing NSCLC.

  1. In vitro antigene therapy targeting HPV-16 E6 and E7 in cervical carcinoma.

    PubMed

    Madrigal, M; Janicek, M F; Sevin, B U; Perras, J; Estape, R; Peñalver, M; Averette, H E

    1997-01-01

    Human papillomavirus (HPV) infection is believed to play a central role in cervical carcinogenesis. Specifically, two viral oncoproteins, E6 and E7, possess transforming ability and have been shown to interact with the cellular tumor suppressors p53 and p105, the retinoblastoma (Rb) gene product. To test the hypothesis that E6 and E7 play an active role in the maintenance of the malignant phenotype and may be ideal targets for antigene therapy, we tested the antiproliferative effects of phosphorothioate oligodeoxynucleotides (oligos) targeting HPV-16 E6 and E7 in cervical cancer cell lines and primary tumor explants. The ATP cell viability assay was used to measure growth effects of 27-mer antisense oligos targeting the ATG translational start region of HPV-16 E6 and E7 sequences in HPV-16-positive cell lines SiHa and CaSki and four advanced, primary cervical tumor explants. A random oligo sequence, an HPV-18-positive and HPV-negative cell line, one histologically confirmed endometrial and two ovarian tumors were used as negative controls. HPV type was confirmed by hybrid capture techniques. Cell lines and sterile (staging laparotomy) tumor cells were plated at 5000 cells/0.1 ml and 100,000 cells/0.5 ml in 96-well plates or soft agar, respectively, and incubated at 37 degrees C with a single treatment of oligos at 0-16 microM. E6/E7 combinations at a fixed ratio of 1:1 were used at 0-8 microM for each oligo. Cellular ATP was measured by luciferin/luciferase fluorescence on Day 6. HPV-16 E6 and E7 oligos showed antiproliferative effects in all HPV-16-positive cell lines and primary tumor explants (IC50s 6.9-9.5 microM for cell lines, 9.1-12.1 microM primary cervical tumors), while the HPV-negative C33-A cell line and HPV-18-positive cell line HeLa were relatively insensitive to the HPV-16 oligos (IC50s > 30 microM extrapolated). The endometrial and two ovarian primary tumors were also insensitive to the HPV E6 and E7 oligos (IC50s > 25 microM extrapolated). Random

  2. Regimes of Helium Burning

    NASA Astrophysics Data System (ADS)

    Timmes, F. X.; Niemeyer, J. C.

    2000-07-01

    The burning regimes encountered by laminar deflagrations and Zeldovich von Neumann Döring (ZND) detonations propagating through helium-rich compositions in the presence of buoyancy-driven turbulence are analyzed. Particular attention is given to models of X-ray bursts that start with a thermonuclear runaway on the surface of a neutron star and to the thin-shell helium instability of intermediate-mass stars. In the X-ray burst case, turbulent deflagrations propagating in the lateral or radial direction encounter a transition from the distributed regime to the flamelet regime at a density of ~108 g cm-3. In the radial direction, the purely laminar deflagration width is larger than the pressure scale height for densities smaller than ~106 g cm-3. Self-sustained laminar deflagrations traveling in the radial direction cannot exist below this density. Similarly, the planar ZND detonation width becomes larger than the pressure scale height at ~107 g cm-3, suggesting that steady state, self-sustained detonations cannot come into existence in the radial direction. In the thin helium shell case, turbulent deflagrations traveling in the lateral or radial direction encounter the distributed regime at densities below ~107 g cm-3 and the flamelet regime at larger densities. In the radial direction, the purely laminar deflagration width is larger than the pressure scale height for densities smaller than ~104 g cm-3, indicating that steady state laminar deflagrations cannot form below this density. The planar ZND detonation width becomes larger than the pressure scale height at ~5×104 g cm-3, suggesting that steady state, self-sustained detonations cannot come into existence in the radial direction.

  3. Regimes of Helium Burning

    SciTech Connect

    Timmes, F. X.; Niemeyer, J. C.

    2000-07-10

    The burning regimes encountered by laminar deflagrations and Zeldovich von Neumann Doering [ZND] detonations propagating through helium-rich compositions in the presence of buoyancy-driven turbulence are analyzed. Particular attention is given to models of X-ray bursts that start with a thermonuclear runaway on the surface of a neutron star and to the thin-shell helium instability of intermediate-mass stars. In the X-ray burst case, turbulent deflagrations propagating in the lateral or radial direction encounter a transition from the distributed regime to the flamelet regime at a density of {approx}108 g cm-3. In the radial direction, the purely laminar deflagration width is larger than the pressure scale height for densities smaller than {approx}106 g cm-3. Self-sustained laminar deflagrations traveling in the radial direction cannot exist below this density. Similarly, the planar ZND detonation width becomes larger than the pressure scale height at {approx}107 g cm-3, suggesting that steady state, self-sustained detonations cannot come into existence in the radial direction. In the thin helium shell case, turbulent deflagrations traveling in the lateral or radial direction encounter the distributed regime at densities below {approx}107 g cm-3 and the flamelet regime at larger densities. In the radial direction, the purely laminar deflagration width is larger than the pressure scale height for densities smaller than {approx}104 g cm-3, indicating that steady state laminar deflagrations cannot form below this density. The planar ZND detonation width becomes larger than the pressure scale height at {approx}5x10{sup 4} g cm-3, suggesting that steady state, self-sustained detonations cannot come into existence in the radial direction. (c) 2000 The American Astronomical Society.

  4. Helium Removal and Recycling

    SciTech Connect

    Reiter, D.; Wiesen, S

    2004-03-15

    Removal of helium, the ash from the D-T-fusion reaction, from a burning plasma flame, is one of the critical issues for future thermonuclear burning plasma. Even in plasmas driven by additional heating to large Q-values this is a severe problem. Recombination of fuel and ash ions at plasma exposed surfaces, re-emission as neutral particles and subsequent pumping (''recycling'') provides, at least in principle, the mechanism to flush the plasma from its ash. However, plasma surface interaction has to be limited in order to protect vessel components from excessive thermal load, often a conflicting requirement.

  5. PREVENTION OF COLITIS-ASSOCIATED CANCER: NATURAL COMPOUNDS THAT TARGET THE IL-6 SOLUBLE RECEPTOR

    PubMed Central

    Moriasi, Cate; Subramaniam, Dharmalingam; Awasthi, Shanjana; Anant, Shrikant; Ramalingam, Satish

    2014-01-01

    The risk of developing colorectal cancer increases in patients with inflammatory bowel disease (IBD) and a growing body of evidence shows the critical role of interleukin (IL-6) in this process. IL-6 is both a pro- and anti-inflammatory cytokine whose effects are mediated through activation of STAT3. Recent studies have also demonstrated that IL-6 trans-signaling through its soluble receptor occurs in IBD and cancer. IL-6 trans-signaling therefore is emerging as an attractive approach to diminish the inflammatory signals in conditions of chronic inflammation. The purpose of cancer chemoprevention is to either delay the onset or progression from precancerous lesions. Natural compounds because of their low toxicity render themselves excellent candidates that can be administered over the lifetime of an individual. With the focus of managing IBD over a long time and preventing onset of colitis-associated cancer, we believe that there should be increased research focus on identifying chemopreventive compounds that can render themselves to long term use possibly for the lifetime of predisposed individuals. Here, we review the role of IL-6 signaling in IBD and colitis-associated cancer and underscore the importance of searching for natural compounds that would target the IL-6 trans-signaling pathway as a way to diminish chronic inflammatory conditions in the gastrointestinal tract and possibly hamper the progression to colon cancer. We propose that effective screening and identification of natural chemopreventive compounds that target IL-6 trans-signaling has important implications for the development of optimal strategies against cancer development triggered by inflammation. PMID:22583410

  6. Feasibility Study for an Active 238UF6 Gas Target for Photo-Fission Experiments

    NASA Astrophysics Data System (ADS)

    Freudenberger, M.; Eckardt, C.; Göök, A.; Enders, J.; Hehner, J.; von Neumann-Cosel, P.; Oberstedt, A.; Oberstedt, S.; Simon, H.

    A series of fission experiments in the actinide region has been started at the superconducting Darmstadt linear accelerator S-DALINAC. For detailed investigations on, e.g., the energy dependence of fission modes, the population of fission isomers, or even the search for parity non-conservation effects (PNC) in the photon-induced fission process of 238U, high luminosities are needed. Increasing target thickness reduces mass and angular resolutions. One possible solution is the utilization of an active gas target containing UF6. In order to test UF6 as an admixture to standard counting gases (e.g. argon) and to study its properties, an ionization chamber has been built at Technische Universität Darmstadt. After testing the chamber with pure argon as a counting gas to evaluate signal quality and to determine the drift velocity, gaseous UF6 was filled into the chamber in steps of one mass-percent uranium for each measurement, where both signal quality and drift velocity at different admixtures have been determined. Up to two percent of uranium in the counting gas one finds that the drift velocity increases with UF6 content, while overall a good signal quality and energy resolution of the ionization chamber is preserved.

  7. Targeting prostate cancer with compounds possessing dual activity as androgen receptor antagonists and HDAC6 inhibitors.

    PubMed

    Jadhavar, Pradeep S; Ramachandran, Sreekanth A; Riquelme, Eduardo; Gupta, Ashu; Quinn, Kevin P; Shivakumar, Devleena; Ray, Soumya; Zende, Dnyaneshwar; Nayak, Anjan K; Miglani, Sandeep K; Sathe, Balaji D; Raja, Mohd; Farias, Olivia; Alfaro, Ivan; Belmar, Sebastián; Guerrero, Javier; Bernales, Sebastián; Chakravarty, Sarvajit; Hung, David T; Lindquist, Jeffrey N; Rai, Roopa

    2016-11-01

    While enzalutamide and abiraterone are approved for treatment of metastatic castration-resistant prostate cancer (mCRPC), approximately 20-40% of patients have no response to these agents. It has been stipulated that the lack of response and the development of secondary resistance to these drugs may be due to the presence of AR splice variants. HDAC6 has a role in regulating the androgen receptor (AR) by modulating heat shock protein 90 (Hsp90) acetylation, which controls the nuclear localization and activation of the AR in androgen-dependent and independent scenarios. With dual-acting AR-HDAC6 inhibitors it should be possible to target patients who don't respond to enzalutamide. Herein, we describe the design, synthesis and biological evaluation of dual-acting compounds which target AR and are also specific towards HDAC6. Our efforts led to compound 10 which was found to have potent dual activity (HDAC6 IC50=0.0356μM and AR binding IC50=<0.03μM). Compound 10 was further evaluated for antagonist and other cell-based activities, in vitro stability and pharmacokinetics.

  8. Caspase-6 as a novel early target in the treatment of Alzheimer's disease.

    PubMed

    LeBlanc, Andrea C

    2013-06-01

    A recent paradigm shift appears to be underway on what scientists believe to be the cause of Alzheimer's disease (AD). The amyloid hypothesis has dominated the field of basic research for the last 25 years, and although these massive efforts have culminated in efficient removal of amyloid from the brains of patients, the absence of beneficial effects for the patient have been greatly disappointing. This has created a shift in the focus on amyloid to a much greater focus on Tau protein, in the hope that preventing tangle formation may inhibit or delay the progression of AD. Although there are promising developments in this area of research, diversifying our efforts to identify novel early targets by understanding the upstream molecular mechanisms that lead to, or occur with, neurofibrillary tangle and plaque formation may provide more efficient therapies against AD. Among many areas in development, an emphasis on the role of caspase-6 (Casp6) activity in early neurodegenerative mechanisms brings hope of a novel target against AD. Casp6 activity is intimately associated with the pathologies that define AD, correlates well with lower cognitive performance in aged individuals, and is involved in axonal degeneration in several cellular and in vivo animal models. This is a review of the evidence showing the relevance of Casp6 activation as an early event that could be inhibited to prevent the progression of AD.

  9. miR-127 regulates cell proliferation and senescence by targeting BCL6.

    PubMed

    Chen, Jingwen; Wang, Miao; Guo, Mingzhou; Xie, Yuntao; Cong, Yu-Sheng

    2013-01-01

    Cellular senescence occurs as a response to extracellular and intracellular stresses and contributes to aging and age-related pathologies. Emerging evidence suggests that cellular senescence also acts as a potent tumor suppression mechanism that prevents the oncogenic transformation of primary human cells. Recent reports have indicated that miRNAsact as key modulators of cellular senescence by targeting critical regulators of the senescence pathways. We previously reported that miR-127 is up-regulated in senescent fibroblasts. In this report, we identified miR-127 as a novel regulator of cellular senescence that directly targets BCL6. We further showed that miR-127 is down-regulated in breast cancer tissues and that this down-regulation is associated with up-regulation of BCL6. Over-expression of miR-127 or depletion of BCL6 inhibits breast cancer cell proliferation. Our data suggest that miR-127 may function as a tumor suppressor that modulates the oncogene BCL6.

  10. Rayleigh Scattering by Helium in Stellar Atmospheres

    NASA Astrophysics Data System (ADS)

    Fišák, J.; Kubát, J.; Krtička, J.

    2017-02-01

    We study the influence of Rayleigh scattering by helium on synthetic spectra and stellar atmosphere models. Rayleigh scattering by helium is often neglected in hot star atmosphere models. This approximation is justified by the small population of helium in stars with solar composition (about 10% by number) and lower Rayleigh scattering total cross section of helium with respect to neutral hydrogen. However, for stars with large helium abundances Rayleigh scattering by helium can be a significant opacity source.

  11. Targeting 6-phosphogluconate dehydrogenase in the oxidative PPP sensitizes leukemia cells to antimalarial agent dihydroartemisinin.

    PubMed

    Elf, S; Lin, R; Xia, S; Pan, Y; Shan, C; Wu, S; Lonial, S; Gaddh, M; Arellano, M L; Khoury, H J; Khuri, F R; Lee, B H; Boggon, T J; Fan, J; Chen, J

    2017-01-12

    The oxidative pentose phosphate pathway (PPP) is crucial for cancer cell metabolism and tumor growth. We recently reported that targeting a key oxidative PPP enzyme, 6-phosphogluconate dehydrogenase (6PGD), using our novel small-molecule 6PGD inhibitors Physcion and its derivative S3, shows anticancer effects. Notably, humans with genetic deficiency of either 6PGD or another oxidative PPP enzyme, glucose-6-phosphate dehydrogenase, exhibit non-immune hemolytic anemia upon exposure to aspirin and various antimalarial drugs. Inspired by these clinical observations, we examined the anticancer potential of combined treatment with 6PGD inhibitors and antimalarial drugs. We found that stable knockdown of 6PGD sensitizes leukemia cells to antimalarial agent dihydroartemisinin (DHA). Combined treatment with DHA and Physcion activates AMP-activated protein kinase, leading to synergistic inhibition of human leukemia cell viability. Moreover, our combined therapy synergistically attenuates tumor growth in xenograft nude mice injected with human K562 leukemia cells and cell viability of primary leukemia cells from human patients, but shows minimal toxicity to normal hematopoietic cells in mice as well as red blood cells and mononucleocytes from healthy human donors. Our findings reveal the potential for combined therapy using optimized doses of Physcion and DHA as a novel antileukemia treatment without inducing hemolysis.

  12. The HPV E6 oncoprotein targets histone methyltransferases for modulating specific gene transcription

    PubMed Central

    Hsu, C-H; Peng, K-L; Jhang, H-C; Lin, C-H; Wu, S-Y; Chiang, C-M; Lee, S-C; Yu, W C Y; Juan, L-J

    2012-01-01

    Expression of viral proteins causes important epigenetic changes leading to abnormal cell growth. Whether viral proteins directly target histone methyltransferases (HMTs), a key family enzyme for epigenetic regulation, and modulate their enzymatic activities remains elusive. Here we show that the E6 proteins of both low-risk and high-risk human papillomavirus (HPV) interact with three coactivator HMTs, CARM1, PRMT1 and SET7, and downregulate their enzymatic activities in vitro and in HPV-transformed HeLa cells. Furthermore, these three HMTs are required for E6 to attenuate p53 transactivation function. Mechanistically, E6 hampers CARM1- and PRMT1-catalyzed histone methylation at p53-responsive promoters, and suppresses the binding of p53 to chromatinized DNA independently of E6-mediated p53 degradation. p53 pre-methylated at lysine-372 (p53K372 mono-methylation) by SET7 protects p53 from E6-induced degradation. Consistently, E6 downregulates p53K372 mono-methylation and thus reduces p53 protein stability. As a result of the E6-mediated inhibition of HMT activity, expression of p53 downstream genes is suppressed. Together, our results not only reveal a clever approach for the virus to interfere with p53 function, but also demonstrate the modulation of HMT activity as a novel mechanism of epigenetic regulation by a viral oncoprotein. PMID:21963854

  13. The HPV E6 oncoprotein targets histone methyltransferases for modulating specific gene transcription.

    PubMed

    Hsu, C-H; Peng, K-L; Jhang, H-C; Lin, C-H; Wu, S-Y; Chiang, C-M; Lee, S-C; Yu, W C Y; Juan, L-J

    2012-05-03

    Expression of viral proteins causes important epigenetic changes leading to abnormal cell growth. Whether viral proteins directly target histone methyltransferases (HMTs), a key family enzyme for epigenetic regulation, and modulate their enzymatic activities remains elusive. Here we show that the E6 proteins of both low-risk and high-risk human papillomavirus (HPV) interact with three coactivator HMTs, CARM1, PRMT1 and SET7, and downregulate their enzymatic activities in vitro and in HPV-transformed HeLa cells. Furthermore, these three HMTs are required for E6 to attenuate p53 transactivation function. Mechanistically, E6 hampers CARM1- and PRMT1-catalyzed histone methylation at p53-responsive promoters, and suppresses the binding of p53 to chromatinized DNA independently of E6-mediated p53 degradation. p53 pre-methylated at lysine-372 (p53K372 mono-methylation) by SET7 protects p53 from E6-induced degradation. Consistently, E6 downregulates p53K372 mono-methylation and thus reduces p53 protein stability. As a result of the E6-mediated inhibition of HMT activity, expression of p53 downstream genes is suppressed. Together, our results not only reveal a clever approach for the virus to interfere with p53 function, but also demonstrate the modulation of HMT activity as a novel mechanism of epigenetic regulation by a viral oncoprotein.

  14. EPHA7, a new target gene for 6q deletion in T-cell lymphoblastic lymphomas.

    PubMed

    López-Nieva, Pilar; Vaquero, Concepción; Fernández-Navarro, Pablo; González-Sánchez, Laura; Villa-Morales, María; Santos, Javier; Esteller, Manel; Fernández-Piqueras, José

    2012-02-01

    Cryptic deletions at chromosome 6q are common cytogenetic abnormalities in T-cell lymphoblastic leukemia/lymphoma (T-LBL), but the target genes have not been formally identified. Our results build on detection of specific chromosomal losses in a mouse model of γ-radiation-induced T-LBLs and provide interesting clues for new putative susceptibility genes in a region orthologous to human 6q15-6q16.3. Among these, Epha7 emerges as a bona fide candidate tumor suppressor gene because it is inactivated in practically all the T-LBLs analyzed (100% in mouse and 95.23% in human). We provide evidence showing that Epha7 downregulation may occur, at least in part, by loss of heterozygosity (19.35% in mouse and 12.5% in human) or promoter hypermethylation (51.61% in mouse and 43.75% in human) or a combination of both mechanisms (12.90% in mouse and 6.25% in human). These results indicate that EPHA7 might be considered a new tumor suppressor gene for 6q deletions in T-LBLs. Notably, this gene is located in 6q16.1 proximal to GRIK2 and CASP8AP2, other candidate genes identified in this region. Thus, del6q seems to be a complex region where inactivation of multiple genes may cooperatively contribute to the onset of T-cell lymphomas.

  15. gga-miR-26a targets NEK6 and suppresses Marek's disease lymphoma cell proliferation.

    PubMed

    Li, Xin; Lian, Ling; Zhang, Daixi; Qu, Lujiang; Yang, Ning

    2014-05-01

    MicroRNA (miRNA) are a class of highly conserved, small noncoding RNA that emerge as key posttranscriptional regulators in various neoplastic transformations. Our previous study profiling the miRNA transcriptome in Marek's disease virus (MDV)-induced lymphoma revealed many novel and differentially expressed miRNA, including gga-miR-26a, which was downregulated in MDV-infected spleens of chickens. In this study, differential expression of gga-miR-26a between MDV-infected and noninfected spleens at 4, 7, 14, 21, and 28 d postinfection was analyzed by real-time PCR. The results showed gga-miR-26a were downregulated in MDV-infected spleens at cytolytic infection, latency, and tumor transformation phases. Subsequent cell proliferation assay revealed cell viability was lower in gga-miR-26a mimic transfection group than that in negative controls. Target genes of gga-miR-26a were identified by luciferase reporter gene assay. The results showed significant interaction between gga-miR-26a and Never In Mitosis Gene A (NIMA)-related kinase 6 (NEK6) gene. Subsequent gain of function experiment and Western blot assay showed that mRNA and protein levels of NEK6 were downregulated after gga-miR-26 mimic was transfected into MDV-transformed lymphoid cell line (MSB-1), indicating that NEK6 was modulated by gga-miR-26a. The expression of NEK6 showed a higher trend in MDV-infected samples including tumorous spleen and MD lymphoma from liver than that in noninfected controls. The results suggested that gga-miR-26a inhibited MSB-1 cell proliferation. Gga-miR-26a and its direct target, NEK6, might play important roles in MDV infection.

  16. Liquid Oxygen Thermodynamic Vent System Testing with Helium Pressurization

    NASA Technical Reports Server (NTRS)

    VanDresar, Neil T.

    2014-01-01

    This report presents the results of several thermodynamic vent system (TVS) tests with liquid oxygen plus a test with liquid nitrogen. In all tests, the liquid was heated above its normal boiling point to 111 K for oxygen and 100 K for nitrogen. The elevated temperature was representative of tank conditions for a candidate lunar lander ascent stage. An initial test series was conducted with saturated oxygen liquid and vapor at 0.6 MPa. The initial series was followed by tests where the test tank was pressurized with gaseous helium to 1.4 to 1.6 MPa. For these tests, the helium mole fraction in the ullage was quite high, about 0.57 to 0.62. TVS behavior is different when helium is present than when helium is absent. The tank pressure becomes the sum of the vapor pressure and the partial pressure of helium. Therefore, tank pressure depends not only on temperature, as is the case for a pure liquid-vapor system, but also on helium density (i.e., the mass of helium divided by the ullage volume). Thus, properly controlling TVS operation is more challenging with helium pressurization than without helium pressurization. When helium was present, the liquid temperature would rise with each successive TVS cycle if tank pressure was kept within a constant control band. Alternatively, if the liquid temperature was maintained within a constant TVS control band, the tank pressure would drop with each TVS cycle. The final test series, which was conducted with liquid nitrogen pressurized with helium, demonstrated simultaneous pressure and temperature control during TVS operation. The simultaneous control was achieved by systematic injection of additional helium during each TVS cycle. Adding helium maintained the helium partial pressure as the liquid volume decreased because of TVS operation. The TVS demonstrations with liquid oxygen pressurized with helium were conducted with three different fluid-mixer configurations-a submerged axial jet mixer, a pair of spray hoops in the tank

  17. Helium dilution refrigeration system

    DOEpatents

    Roach, P.R.; Gray, K.E.

    1988-09-13

    A helium dilution refrigeration system operable over a limited time period, and recyclable for a next period of operation is disclosed. The refrigeration system is compact with a self-contained pumping system and heaters for operation of the system. A mixing chamber contains [sup 3]He and [sup 4]He liquids which are precooled by a coupled container containing [sup 3]He liquid, enabling the phase separation of a [sup 3]He rich liquid phase from a dilute [sup 3]He-[sup 4]He liquid phase which leads to the final stage of a dilution cooling process for obtaining low temperatures. The mixing chamber and a still are coupled by a fluid line and are maintained at substantially the same level with the still cross sectional area being smaller than that of the mixing chamber. This configuration provides maximum cooling power and efficiency by the cooling period ending when the [sup 3]He liquid is depleted from the mixing chamber with the mixing chamber nearly empty of liquid helium, thus avoiding unnecessary and inefficient cooling of a large amount of the dilute [sup 3]He-[sup 4]He liquid phase. 2 figs.

  18. Helium dilution refrigeration system

    DOEpatents

    Roach, Patrick R.; Gray, Kenneth E.

    1988-01-01

    A helium dilution refrigeration system operable over a limited time period, and recyclable for a next period of operation. The refrigeration system is compact with a self-contained pumping system and heaters for operation of the system. A mixing chamber contains .sup.3 He and .sup.4 He liquids which are precooled by a coupled container containing .sup.3 He liquid, enabling the phase separation of a .sup.3 He rich liquid phase from a dilute .sup.3 He-.sup.4 He liquid phase which leads to the final stage of a dilution cooling process for obtaining low temperatures. The mixing chamber and a still are coupled by a fluid line and are maintained at substantially the same level with the still cross sectional area being smaller than that of the mixing chamber. This configuration provides maximum cooling power and efficiency by the cooling period ending when the .sup.3 He liquid is depleted from the mixing chamber with the mixing chamber nearly empty of liquid helium, thus avoiding unnecessary and inefficient cooling of a large amount of the dilute .sup.3 He-.sup.4 He liquid phase.

  19. Operations aspects of the Fermilab Central Helium Liquefier Facility

    SciTech Connect

    Geynisman, M.G.; Makara, J.N.

    1995-03-01

    The Fermilab Central Helium Liquefier (CHL) facility consists of helium and nitrogen reliquefier plants operated 24 hours-a-day to supply LHe at 4.6{degrees}K and LN{sub 2} for the Fermilab Tevatron superconducting proton-antiproton collider ring and to recover warm return gases. Operating aspects of CHL, including different equipment and systems reliability, availability, maintenance experience, safety concerns, and economics aspects are discussed.

  20. Effect of carbon and alloying solute atoms on helium behaviors in α-Fe

    NASA Astrophysics Data System (ADS)

    Zhang, Yange; You, Yu-Wei; Xu, Yichun; Liu, C. S.; Chen, J. L.; Luo, G.-N.

    2017-02-01

    Helium bubbles could strongly degrade the mechanical properties of ferritic steels in fission and fusion systems. The formation of helium bubble is directly affected by the interactions between helium and the compositions in steels, such as solute atoms, carbon and irradiation defects. We thereby performed systematical first-principles calculations to investigate the interactions of solute-helium and carbon-solute-helium. It is found that substitutional helium is more attractive than interstitial helium to all the considered 3p, 4p, 5p and 6p solutes. The attraction between carbon and substitutional helium suggests the carbon-solute-helium complex can be formed stably. By examining the charge density difference and thermal stability, it is found that the ternary complex shows stronger attraction with He than that of solute-helium pair for some solutes (S, Se, In, Te, Pb and Bi) and the complex could existed in iron stably at 700 K. The present theoretical results may be helpful for exploring alloy additions to mitigate the formation of large helium bubbles.

  1. Targeting interleukin-6: all the way to treat autoimmune and inflammatory diseases.

    PubMed

    Tanaka, Toshio; Kishimoto, Tadamitsu

    2012-01-01

    Interleukin (IL)-6, a cytokine featuring redundancy and pleiotropic activity, contributes to host defense against acute environmental stress, while dysregulated persistent IL-6 production has been demonstrated to play a pathological role in various autoimmune and chronic inflammatory diseases. Targeting IL-6 is thus a rational approach to the treatment of these diseases. Indeed, clinical trials of tocilizumab, a humanized anti-IL-6 receptor antibody have verified its efficacy and tolerable safety for patients with rheumatoid arthritis, Castleman's disease and systemic juvenile idiopathic arthritis, resulting in approval of this innovative biologic for treatment of these diseases. Moreover, a considerable number of case reports and pilot studies of off-label use of tocilizumab point to the beneficial effects of tocilizumab for a variety of other phenotypically different autoimmune and chronic inflammatory diseases. Elucidation of the source of IL-6 and of mechanisms through which IL-6 production is dysregulated can thus be expected to lead to clarification of the pathogenesis of various diseases.

  2. Interactions of satellite-speed helium atoms with satellite surfaces. 2: Energy distributions of reflected helium atoms

    NASA Technical Reports Server (NTRS)

    Liu, S. M.; Knuth, E. L.

    1976-01-01

    Energy transfer in collisions of satellite-speed (7,000 m/sec) helium atoms with a cleaned 6061-T6 satellite-type aluminum surface was investigated using the molecular-beam technique. The amount of energy transferred was determined from the measured energy of the molecular-beam and the measured spatial and energy distributions of the reflected atoms. Spatial distributions of helium atoms scattered from a 6061-T6 aluminum surface were measured. The scattering pattern exhibits a prominent backscattering, probably due to the gross surface roughness and/or the relative lattice softness of the aluminum surface. Energy distributions of reflected helium atoms from the same surface were measured for six different incidence angles. For each incidence angle, distributions were measured at approximately sixty scattering positions. At a given scattering position, the energy spectra of the reflected helium atoms and the background gas were obtained using the retarding-field energy analyzer.

  3. RNA interference targeting Bcl-6 ameliorates experimental autoimmune myasthenia gravis in mice.

    PubMed

    Xin, Ning; Fu, Linlin; Shao, Zhen; Guo, Mingfeng; Zhang, Xiuying; Zhang, Yong; Dou, Changxin; Zheng, Shuangshuang; Shen, Xia; Yao, Yuanhu; Wang, Jiao; Wang, Jinhua; Cui, Guiyun; Liu, Yonghai; Geng, Deqin; Xiao, Chenghua; Zhang, Zunsheng; Dong, Ruiguo

    2014-01-01

    Follicular helper T (Tfh) cells are dedicated to providing help to B cells and are strongly associated with antibody-mediated autoimmune disease. B cell lymphoma 6 (Bcl-6) is a key transcription factor of Tfh cells, and IL-21 is known to be a critical cytokine produced by Tfh cells. We silenced Bcl-6 gene expression using RNA interference (RNAi) delivered by a lentiviral vector, to evaluate the therapeutic role of Bcl-6 short hairpin RNAs (shRNAs) in experimental autoimmune myasthenia gravis (EAMG). Our data demonstrate that CD4(+)CXCR5(+)PD-1(+) Tfh cells, Bcl-6 and IL-21 were significantly increased in EAMG mice, compared with controls. In addition, we found that frequencies of Tfh cells were positively correlated with the levels of serum anti-AChR Ab. In-vivo transduction of lenti-siRNA-Bcl6 ameliorates the severity of ongoing EAMG with decreased Tfh cells, Bcl-6 and IL-21 expression, and leads to decreased anti-AChR antibody levels. Furthermore, we found that siRNA knockdown of Bcl-6 expression increases the expression of Th1(IFN-γ, T-bet) and Th2 markers (IL-4 and GATA3), but failed to alter the expression of Th17-related markers (RORγt, IL-17) and Treg markers (FoxP3). Our study suggests that Tfh cells contribute to the antibody production and could be one of the most important T cell subsets responsible for development and progression of EAMG or MG. Bcl-6 provides a promising therapeutic target for immunotherapy not only for MG, but also for other antibody-mediated autoimmune diseases. Copyright © 2013 Elsevier Inc. All rights reserved.

  4. Preclinical validation of a novel compound targeting p70S6 kinase in breast cancer

    PubMed Central

    Segatto, Ilenia; Massarut, Samuele; Boyle, Robert; Baldassarre, Gustavo; Walker, David; Belletti, Barbara

    2016-01-01

    Breast cancer is a frequent and treatable disease. However, when recurrent, breast cancer often becomes refractory to therapy and progresses into metastatic forms that are typically incurable. Thus, understanding and targeting the critical pathways underlying breast cancer recurrence is urgently needed to eradicate primary disease and achieve better prognosis. Recently, we have demonstrated that the ribosomal protein p70S6K is activated in residual breast cancer cells as a result of post-surgical inflammation and that interfering with its activity in the peri-operative setting strongly suppresses recurrence in a mouse model. In order to develop clinically-exploitable treatments targeting p70S6K, we have tested a newly generated compound, called FS-115. FS-115 potently inhibited p70S6K1 (IC50 35nM) with high selectivity over other AGC kinases or PI3K pathway kinases. In vitro, treatment with FS-115 efficiently blocked p70S6K activity in breast cancer cell lines and impaired colony formation and anchorage independent growth. Pharmacokinetic profiling showed that FS-115 exhibited high oral bioavailability, optimal plasma distribution and high brain penetrance. In nude mice, FS-115 strongly suppressed tumor take-rate and primary tumor growth. Oral dosing with FS-115 in a peri-operative schedule was effective in decreasing local recurrence of breast cancer and a long-term treatment schedule was well tolerated and efficiently suppressed distant metastasis formation. Altogether, we propose that FS-115 might be a good candidate for the treatment of breast cancer patients at high risk to relapse. Summary Statement Our results confirm that inhibition of p70S6K represents a valuable opportunity for restraining loco-regional relapse and metastasis in breast cancer and identify in FS-115 a promising candidate-inhibitor to move from preclinical to clinical treatments. PMID:27155197

  5. Helium isotope ratios in Ethiopian Rift basalts

    NASA Astrophysics Data System (ADS)

    Scarsi, P.; Craig, H.

    1996-11-01

    Helium isotope ratios were measured in olivine and pyroxene phenocrysts from basalts of the Ethiopian Rift Valley and Afar Depression between 6° and 15°N and 37° and 43°E. 3He/4He ratios range from 6 to 17 times the atmospheric value (RA = 1.4 × 10-6), that is, from ratios less than typical MORB (depleted mantle) helium (R/RA= 8 ± 1) to ratios similar to high-3He hotspots and to the Yellowstone hotspot (R/RA= 16.5). The high 3He/4He ratios occur all along the Ethiopian Rift and well up into the Afar Depression, with a maximum value of 17.0 RA at 8°N in the Rift Axis and a high value of 14.2 RA in the central Tat'Ali sector of the Afar Depression. The ratios decrease to MORB-like values near the edge of the Red Sea, and to sub-MORB ratios (5-6 RA) at the northern end of the Rift (Zula Peninsula) and at the southern end, at lakes Abaya and Chamo. The Ethiopian Rift provides the only continental hotspot terrain in which helium isotope ratios can be compared in detail between volcanic lavas and associated geothermal and volcanic gases, a primary motivation for this work. Comparison with our previously measured ratios in fluids and gases (range 2-15 RA) shows excellent agreement in the areas sampled for both lavas and fluids, and indicates that high-temperature volcanic fluids can be used for establishing helium isotope signatures in such terrains. The high-3He values in both fluids and basalts show that a Primitive Mantle (PM) component is required and that a Lower Mantle High-3He plume is strongly involved as a driving force in the rifting process of the East African Rift System.

  6. Helium-3 and helium-4 acceleration by high power laser pulses for hadron therapy

    DOE PAGES

    Bulanov, S. S.; Esarey, E.; Schroeder, C. B.; ...

    2015-06-24

    The laser driven acceleration of ions is considered a promising candidate for an ion source for hadron therapy of oncological diseases. Though proton and carbon ion sources are conventionally used for therapy, other light ions can also be utilized. Whereas carbon ions require 400 MeV per nucleon to reach the same penetration depth as 250 MeV protons, helium ions require only 250 MeV per nucleon, which is the lowest energy per nucleon among the light ions (heavier than protons). This fact along with the larger biological damage to cancer cells achieved by helium ions, than that by protons, makes thismore » species an interesting candidate for the laser driven ion source. Two mechanisms (magnetic vortex acceleration and hole-boring radiation pressure acceleration) of PW-class laser driven ion acceleration from liquid and gaseous helium targets are studied with the goal of producing 250 MeV per nucleon helium ion beams that meet the hadron therapy requirements. We show that He3 ions, having almost the same penetration depth as He4 with the same energy per nucleon, require less laser power to be accelerated to the required energy for the hadron therapy.« less

  7. Novel IRF6 Mutations Detected in Orofacial Cleft Patients by Targeted Massively Parallel Sequencing.

    PubMed

    Khandelwal, K D; Ishorst, N; Zhou, H; Ludwig, K U; Venselaar, H; Gilissen, C; Thonissen, M; van Rooij, I A L M; Dreesen, K; Steehouwer, M; van de Vorst, M; Bloemen, M; van Beusekom, E; Roosenboom, J; Borstlap, W; Admiraal, R; Dormaar, T; Schoenaers, J; Vander Poorten, V; Hens, G; Verdonck, A; Bergé, S; Roeleveldt, N; Vriend, G; Devriendt, K; Brunner, H G; Mangold, E; Hoischen, A; van Bokhoven, H; Carels, C E L

    2017-02-01

    Common variants in interferon regulatory factor 6 ( IRF6) have been associated with nonsyndromic cleft lip with or without cleft palate (NSCL/P) as well as with tooth agenesis (TA). These variants contribute a small risk towards the 2 congenital conditions and explain only a small percentage of heritability. On the other hand, many IRF6 mutations are known to be a monogenic cause of disease for syndromic orofacial clefting (OFC). We hypothesize that IRF6 mutations in some rare instances could also cause nonsyndromic OFC. To find novel rare variants in IRF6 responsible for nonsyndromic OFC and TA, we performed targeted multiplex sequencing using molecular inversion probes (MIPs) in 1,072 OFC patients, 67 TA patients, and 706 controls. We identified 3 potentially pathogenic de novo mutations in OFC patients. In addition, 3 rare missense variants were identified, for which pathogenicity could not unequivocally be shown, as all variants were either inherited from an unaffected parent or the parental DNA was not available. Retrospective investigation of the patients with these variants revealed the presence of lip pits in one of the patients with a de novo mutation suggesting a Van der Woude syndrome (VWS) phenotype, whereas, in other patients, no lip pits were identified.

  8. Integrin α6 promotes esophageal cancer metastasis and is targeted by miR-92b

    PubMed Central

    Huang, Furong; Li, Xukun; Cao, Xiufeng; Liu, Zhihua

    2017-01-01

    Tumor invasion and metastasis is responsible for the poor prognosis of esophageal squamous cell carcinoma (ESCC); therefore, exploring the mechanisms by which malignant cells disseminate, spread and flourish in secondary sites, as well as translating the bench results to clinical practice are in urgent need. Previous reports showed that integrin α6 increases in ESCC specimens and its dysregulated spatial localization correlates positively with the unfavorable outcome of ESCC patients. Here, we clarify that integrin α6 promotes invasion and metastasis of ESCC cells In vitro and in vivo. Mechanistically, decreased integrin α6 attenuates motility of malignant cells partially through deactivating Akt pathway, which is essential for ESCC cells motility. Moreover, integrin α6 serves as a genuine target of miR-92b in suppressing ESCC motility. Our results for the first time describe that miR-92b/integrin α6/Akt axis controls the motility of ESCC, thereby providing a promising diagnosis or therapeutic option. PMID:28036265

  9. DVCS with longitudinally polarized target using CLAS at 6 GeV

    SciTech Connect

    Biselli, Angela

    2009-08-04

    Deeply Virtual Compton Scattering (DVCS) is one of the simplest processes that can be described in terms of Generalized Parton Distributions (GPDs). The target single-spin asymmetry (target SSA) in the reaction ep-vector{yields}ep{gamma} is directly proportional to the imaginary part of the DVCS amplitude, and gives access to a combination of GPDs namely H-tilde, H, and E. This asymmetry will be measured in a dedicated experiment at Jefferson Lab using the CEBAF 6-GeV polarized electron beam, a polarized solid-state {sup 14}NH{sub 3} target, and the CEBAF Large Acceptance Spectrometer (CLAS) together with the Inner Calorimeter (IC). The expected asymmetry from leading-order calculations is in the range of 20% to 40%, depending on the kinematics and on the GPD model used. The DVCS amplitude will be mapped out in the Q{sup 2} region from 1 to 4 GeV{sup 2}, x{sub B} from 0.15 to 0.55 and -t from 0.1 to 2 GeV{sup 2} providing new constraints on the GPDs.

  10. DVCS with longitudinally polarized target using CLAS at 6 GeV

    SciTech Connect

    Angela Biselli

    2009-08-01

    Deeply Virtual Compton Scattering (DVCS) is one of the simplest processes that can be described in terms of Generalized Parton Distributions (GPDs). The target single-spin asymmetry (target SSA) in the reaction $e\\vec{p} \\rightarrow e p \\gamma$ is directly proportional to the imaginary part of the DVCS amplitude, and gives access to a combination of GPDs namely $\\tilde H$, $H$, and $E$. This asymmetry will be measured in a dedicated experiment at Jefferson Lab using the CEBAF 6-GeV polarized electron beam, a polarized solid-state ${}^{14}NH_3$ target, and the CEBAF Large Acceptance Spectrometer (CLAS) together with the Inner Calorimeter (IC). The expected asymmetry from leading-order calculations is in the range of 20\\% to 40\\%, depending on the kinematics and on the GPD model used. The DVCS amplitude will be mapped out in the $Q^2$ region from 1 to 4 GeV${}^2$, $x_B$ from 0.15 to 0.55 and $-t$ from 0.1 to 2 GeV${}^2$ providing new constraints on the GPDs.

  11. Comparing MODIS C6 'Deep Blue' and 'Dark Target' Aerosol Data

    NASA Technical Reports Server (NTRS)

    Hsu, N. C.; Sayer, A. M.; Bettenhausen, C.; Lee, J.; Levy, R. C.; Mattoo, S.; Munchak, L. A.; Kleidman, R.

    2014-01-01

    The MODIS Collection 6 Atmospheres product suite includes refined versions of both 'Deep Blue' (DB) and 'Dark Target' (DT) aerosol algorithms, with the DB dataset now expanded to include coverage over vegetated land surfaces. This means that, over much of the global land surface, users will have both DB and DT data to choose from. A 'merged' dataset is also provided, primarily for visualization purposes, which takes retrievals from either or both algorithms based on regional and seasonal climatologies of normalized difference vegetation index (NDVI). This poster present some comparisons of these two C6 aerosol algorithms, focusing on AOD at 550 nm derived from MODIS Aqua measurements, with each other and with Aerosol Robotic Network (AERONET) data, with the intent to facilitate user decisions about the suitability of the two datasets for their desired applications.

  12. Helium segregation on surfaces of plasma-exposed tungsten

    SciTech Connect

    Maroudas, Dimitrios; Blondel, Sophie; Hu, Lin; Hammond, Karl D.; Wirth, Brian D.

    2016-01-21

    Here we report a hierarchical multi-scale modeling study of implanted helium segregation on surfaces of tungsten, considered as a plasma facing component in nuclear fusion reactors. We employ a hierarchy of atomic-scale simulations based on a reliable interatomic interaction potential, including molecular-statics simulations to understand the origin of helium surface segregation, targeted molecular-dynamics (MD) simulations of near-surface cluster reactions, and large-scale MD simulations of implanted helium evolution in plasma-exposed tungsten. We find that small, mobile He-n (1 <= n <= 7) clusters in the near-surface region are attracted to the surface due to an elastic interaction force that provides the thermodynamic driving force for surface segregation. Elastic interaction force induces drift fluxes of these mobile Hen clusters, which increase substantially as the migrating clusters approach the surface, facilitating helium segregation on the surface. Moreover, the clusters' drift toward the surface enables cluster reactions, most importantly trap mutation, in the near-surface region at rates much higher than in the bulk material. Moreover, these near-surface cluster dynamics have significant effects on the surface morphology, near-surface defect structures, and the amount of helium retained in the material upon plasma exposure. We integrate the findings of such atomic-scale simulations into a properly parameterized and validated spatially dependent, continuum-scale reaction-diffusion cluster dynamics model, capable of predicting implanted helium evolution, surface segregation, and its near-surface effects in tungsten. This cluster-dynamics model sets the stage for development of fully atomistically informed coarse-grained models for computationally efficient simulation predictions of helium surface segregation, as well as helium retention and surface morphological evolution, toward optimal design of plasma facing components.

  13. Helium segregation on surfaces of plasma-exposed tungsten

    DOE PAGES

    Maroudas, Dimitrios; Blondel, Sophie; Hu, Lin; ...

    2016-01-21

    Here we report a hierarchical multi-scale modeling study of implanted helium segregation on surfaces of tungsten, considered as a plasma facing component in nuclear fusion reactors. We employ a hierarchy of atomic-scale simulations based on a reliable interatomic interaction potential, including molecular-statics simulations to understand the origin of helium surface segregation, targeted molecular-dynamics (MD) simulations of near-surface cluster reactions, and large-scale MD simulations of implanted helium evolution in plasma-exposed tungsten. We find that small, mobile He-n (1 <= n <= 7) clusters in the near-surface region are attracted to the surface due to an elastic interaction force that provides themore » thermodynamic driving force for surface segregation. Elastic interaction force induces drift fluxes of these mobile Hen clusters, which increase substantially as the migrating clusters approach the surface, facilitating helium segregation on the surface. Moreover, the clusters' drift toward the surface enables cluster reactions, most importantly trap mutation, in the near-surface region at rates much higher than in the bulk material. Moreover, these near-surface cluster dynamics have significant effects on the surface morphology, near-surface defect structures, and the amount of helium retained in the material upon plasma exposure. We integrate the findings of such atomic-scale simulations into a properly parameterized and validated spatially dependent, continuum-scale reaction-diffusion cluster dynamics model, capable of predicting implanted helium evolution, surface segregation, and its near-surface effects in tungsten. This cluster-dynamics model sets the stage for development of fully atomistically informed coarse-grained models for computationally efficient simulation predictions of helium surface segregation, as well as helium retention and surface morphological evolution, toward optimal design of plasma facing components.« less

  14. Helium segregation on surfaces of plasma-exposed tungsten

    NASA Astrophysics Data System (ADS)

    Maroudas, Dimitrios; Blondel, Sophie; Hu, Lin; Hammond, Karl D.; Wirth, Brian D.

    2016-02-01

    We report a hierarchical multi-scale modeling study of implanted helium segregation on surfaces of tungsten, considered as a plasma facing component in nuclear fusion reactors. We employ a hierarchy of atomic-scale simulations based on a reliable interatomic interaction potential, including molecular-statics simulations to understand the origin of helium surface segregation, targeted molecular-dynamics (MD) simulations of near-surface cluster reactions, and large-scale MD simulations of implanted helium evolution in plasma-exposed tungsten. We find that small, mobile He n (1  ⩽  n  ⩽  7) clusters in the near-surface region are attracted to the surface due to an elastic interaction force that provides the thermodynamic driving force for surface segregation. This elastic interaction force induces drift fluxes of these mobile He n clusters, which increase substantially as the migrating clusters approach the surface, facilitating helium segregation on the surface. Moreover, the clusters’ drift toward the surface enables cluster reactions, most importantly trap mutation, in the near-surface region at rates much higher than in the bulk material. These near-surface cluster dynamics have significant effects on the surface morphology, near-surface defect structures, and the amount of helium retained in the material upon plasma exposure. We integrate the findings of such atomic-scale simulations into a properly parameterized and validated spatially dependent, continuum-scale reaction-diffusion cluster dynamics model, capable of predicting implanted helium evolution, surface segregation, and its near-surface effects in tungsten. This cluster-dynamics model sets the stage for development of fully atomistically informed coarse-grained models for computationally efficient simulation predictions of helium surface segregation, as well as helium retention and surface morphological evolution, toward optimal design of plasma facing components.

  15. Targeting Steroidogenic Cytochromes P450 (CYPs) with 6-Substituted 1-Imidazolylmethylxanthones.

    PubMed

    Gobbi, Silvia; Hu, Qingzhong; Zimmer, Christina; Belluti, Federica; Rampa, Angela; Hartmann, Rolf W; Bisi, Alessandra

    2016-08-19

    Abnormally high corticosteroid levels are responsible for the onset of serious hormone-related diseases, and the inhibition of their biosynthesis by targeting cytochrome P450 (CYP) isoforms CYP11B1 and CYP11B2 has emerged as a promising strategy to restore healthy physiological levels of corticosteroids. With the aim of exploiting the xanthone scaffold as a privileged structure in medicinal chemistry and to further explore the chemical space of inhibitors of these CYPs, a small library of imidazolylmethylxanthones was designed based on the results of a previously described compound series. Assuming the capacity for an additional interaction with these enzymes, a properly selected substituent was introduced at position 6 of the xanthone core, maintaining the key imidazolylmethyl moiety at position 1. The 6-fluoro and 6-nitro derivatives [1-(1H-imidazol-1-yl)methyl-6-fluoro-9H-xanthen-9-one (1 a) and 1-(1H-imidazol-1-yl)methyl-6-nitro-9H-xanthen-9-one (1 d), respectively] proved to be active in the low nanomolar range, showing selectivity toward the related steroidogenic enzymes CYP19 and CYP17, even if the problem of selectivity between the two CYP11B isoforms remains unsolved. On the other hand, the 6-chloro derivative 1-(1H-imidazol-1-yl)methyl-6-chloro-9H-xanthen-9-one (1 b) was found to be a fairly potent and somewhat selective CYP19 inhibitor, confirming the versatility of the scaffold.

  16. Somatostatin receptor targeted liposomes with Diacerein inhibit IL-6 for breast cancer therapy.

    PubMed

    Bharti, Rashmi; Dey, Goutam; Banerjee, Indranil; Dey, Kaushik Kumar; Parida, Sheetal; Kumar, B N Prashanth; Das, Chandan Kanta; Pal, Ipsita; Mukherjee, Manabendra; Misra, Mridula; Pradhan, Anjan K; Emdad, Luni; Das, Swadesh K; Fisher, Paul B; Mandal, Mahitosh

    2017-03-01

    Selective targeting to the tumor niche remains a major challenge in successful cancer therapy. Somatostatin receptor 2 (SSTR2) is overexpressed in breast cancer cells thus making this receptor an attractive target for selective guidance of ligand-conjugated drug liposomes to the tumor site. In this study, a synthetic somatostatin analogue (SST) was used as SSTR2 targeting agent and Diacerein was employed as therapeutic molecule. Diacerein loaded liposomes (DNL) were prepared and they were further decorated with the synthetic and stable analogue of somatostatin (SST-DNL). Fabricated liposomes were nano-size in range and biocompatible. SST-DNL displayed significantly better anti-tumor efficacy as compared to free Diacerein (DN) and DNL in breast cancer models. Enhanced apoptosis in breast cancer cells was detected in SST-DNL treated groups as monitored by cell cycle analysis and changes in expression level of apoptotic/anti-apoptotic proteins Bcl-2, Bax, cleaved Caspase 3 and PARP. SST-DNL more effectively inhibited the oncogenic IL-6/IL-6R/STAT3/MAPK/Akt signalling pathways as compared to DN or DNL in cancer cells. In addition, SST-DNL effectively suppressed angiogenesis and cancer cell invasion. In vivo tumor growth in a MDA-MB-231 mouse xenograft model was significantly suppressed following SST-DNL treatment. In xenograft model, immunohistochemistry of Ki-67 and CD-31 indicated that SST-DNL improved the anti-proliferative and anti-angiogenic impacts of Diacerein. In vivo pharmacokinetic studies in rats showed enhanced circulation time in the DNL or SST-DNL treated groups as compared to free DN. Considering all of these findings, we conclude that SST-DNL provides a novel strategy with better efficacy for breast cancer therapy.

  17. Characterization of gaseous helium jet dispersion to atmosphere

    NASA Astrophysics Data System (ADS)

    Khan, H. J.; Figueroa, O.; Rhee, M.

    A major ground-based experiment to be performed for the Superfluid Helium On Orbit Transfer (SHOOT) program is the accidental loss of the vacuum guard of the super-insulated dewar. The design of the dewar vent-path requires adequate mass removal after a preset pressure is reached due to external heat transfer. The existing helium creates a turbulent buoyant jet, expanding in air with entrainment of the jet interface to the surrounding. Transient analysis is performed for axial and radial jet temperature prediction using the self-similarity assumption applied to mass, momentum, and the energy-balance equations of helium. The predicted jet temperature profiles with vertical and radial expansion up to 1.6 and 1.0 m, respectively, demonstrate the low temperature core established by gaseous helium. For all time steps, the axial and radial temperature predictions are observed to be within 8 and 20 percent, respectively.

  18. Precision spectroscopy of Helium

    SciTech Connect

    Cancio, P.; Giusfredi, G.; Mazzotti, D.; De Natale, P.; De Mauro, C.; Krachmalnicoff, V.; Inguscio, M.

    2005-05-05

    Accurate Quantum-Electrodynamics (QED) tests of the simplest bound three body atomic system are performed by precise laser spectroscopic measurements in atomic Helium. In this paper, we present a review of measurements between triplet states at 1083 nm (23S-23P) and at 389 nm (23S-33P). In 4He, such data have been used to measure the fine structure of the triplet P levels and, then, to determine the fine structure constant when compared with equally accurate theoretical calculations. Moreover, the absolute frequencies of the optical transitions have been used for Lamb-shift determinations of the levels involved with unprecedented accuracy. Finally, determination of the He isotopes nuclear structure and, in particular, a measurement of the nuclear charge radius, are performed by using hyperfine structure and isotope-shift measurements.

  19. Liquid helium fluid dynamics studies

    SciTech Connect

    Van Sciver, S.W.

    1989-01-01

    The main focus of the first three year period of this research program was to set up our liquid helium flow facility and begin experiments on the flow of liquid helium within this system. The first task of our experimental program involved the set up and check out of the liquid helium flow facility (LHFF). This facility is the centerpost of our fluid dynamics experiments. The LHFF is designed to allow a variety of experiments which test important helium fluid dynamics behavior on a scale close to that involved in large scale applications. To achieve this goal, we chose a horizontal dewar configuration with a cold bore access on either end. A nominal length of five meters was selected with a sufficiently large inner diameter to allow insertion of various tubing configurations, flow metering devices and heat exchangers. Further, to minimize consumption of liquid helium, the dewar design includes two actively cooled shields; one cooled by LN/sub 2/ to 77 K and one at 4.5 K maintained by a closed cycle helium refrigerator. Helium flow is to be provided by a cold centrifugal pump. 4 refs., 2 figs.

  20. Spectrophotometry of Helium Peculiar Stars

    NASA Astrophysics Data System (ADS)

    Shore, Steven N.

    The mechanism for the spectrum and photometric variations of the magnetic helium peculiar stars is not a settled question. For the cooler stars the primary cause appears to be changes, due to surface inhomogeneities, of Si continuous opacity. For the hotter helium rich stars it appears linked to the helium anomaly and its photosoheric distribution. The connection between the helium weak and helium rich stars is not well understood but appears to be linked to effective temperature on the main sequence via a diffusion mechanism. The purpose of this study is to explore the relation between magnetic field strength and configuration, effective temperature and abundance anomaly using groups of matched He weak and He rich stars. It will, using this sample, also study the relation between the UV variations and the broad continuum features known in the optical at 5200 and 6300 A. The constancy of the stellar flux will also be studied, linking this survey with the OAO-2 and TD-1 studies of a few Si stars. A subsidiary goal is the calibration of high dispersion IUE Spectra obtained in the previous programs (APBSA, HRDPB, and HEESS) for the helium rich stars. The photometric observations made with OAO-2, TD-1, ANS, and the COPERNICUS spectra will all serve as links between the helium rich and weak phenomenology.

  1. Scattering of H(1s) off metastable helium atom at thermal energies

    SciTech Connect

    Sinha, Prabal K.; Ghosh, A. S.

    2006-06-15

    Quantal calculations for scattering of ground-state antihydrogen by metastable (n=2S) helium atoms have been performed using the nonadiabatic, atomic orbital expansion technique at thermal energies. The zero-energy elastic cross sections of the present systems are much greater than the corresponding value for the ground-state helium target. The low-energy elastic cross section for the singlet metastable helium [He(2 {sup 1}S)] target is higher than the corresponding value when the target is in the metastable triplet state [He(2 {sup 3}S)].

  2. Helium runaways in white dwarfs

    NASA Technical Reports Server (NTRS)

    Taam, R. E.

    1980-01-01

    The long-term evolution of a carbon-accreting white dwarf (M = 0.5 solar mass) has been studied from the onset of accretion to the ignition of helium. The variations in the details of the helium-shell flash have been examined with respect to variations in mass accretion rate. For intermediate rates (10 to the -9th to 10 to the -8th solar mass/yr) the helium flash is potentially explosive, whereas for high rates (5 x 10 to the -8th solar mass/yr) the shell flash is relatively weak. The results are discussed in the context of the long-term evolution of novae.

  3. Resource Letter SH-1: Superfluid Helium.

    ERIC Educational Resources Information Center

    Hallock, Robert B.

    1982-01-01

    Provides an annotated list of books, textbooks, and films on superfluid helium. Also lists research reports/reviews arranged by category, including among others, early history, microscopic understanding, ions in helium, helium in rotation, vortices and quantization, helium films and constricted geometrics, persistence flow, and superfluid helium…

  4. Resource Letter SH-1: Superfluid Helium.

    ERIC Educational Resources Information Center

    Hallock, Robert B.

    1982-01-01

    Provides an annotated list of books, textbooks, and films on superfluid helium. Also lists research reports/reviews arranged by category, including among others, early history, microscopic understanding, ions in helium, helium in rotation, vortices and quantization, helium films and constricted geometrics, persistence flow, and superfluid helium…

  5. Growth rate effects on the formation of dislocation loops around deep helium bubbles in Tungsten

    SciTech Connect

    Sandoval, Luis; Perez, Danny; Uberuaga, Blas P.; Voter, Arthur Ford

    2016-11-15

    Here, the growth process of spherical helium bubbles located 6 nm below a (100) surface is studied using molecular dynamics and parallel replica dynamics simulations, over growth rates from 106 to 1012 helium atoms per second. Slower growth rates lead to a release of pressure and lower helium content as compared with fast growth cases. In addition, at slower growth rates, helium bubbles are not decorated by multiple dislocation loops, as these tend to merge or emit given sufficient time. At faster rates, dislocation loops nucleate faster than they can emit, leading to a more complicated dislocation structure around the bubble.

  6. Testing fundamental interactions on the helium atom

    NASA Astrophysics Data System (ADS)

    Pachucki, Krzysztof; Patkóš, Vojtěch; Yerokhin, Vladimir A.

    2017-06-01

    We critically examine the current status of theoretical calculations of the energies, the fine structure, and the isotope shift of the lowest-lying states of helium, searching for unresolved discrepancies with experiments. Calculations are performed within the quantum electrodynamics expansion in powers of the fine structure constant α and the electron-to-nucleus mass ratio m /M . For energies, theoretical results are complete through orders α6m and α6m2/M , with the resulting accuracy ranging from 0.5 to 2 MHz for the n =2 states. The fine-structure splitting of the 2 3P state is predicted with a much better accuracy, 1.7 kHz, as a consequence of a calculation of the next-order α7m effect. An excellent agreement of the theoretical predictions with the recent measurements of the fine structure provides one of the best tests of the bound-state QED in few-electron systems. The isotope shift between 3He and 4He is treated with a subkilohertz accuracy, which allows for a high-precision determination of the differences of the nuclear charge radii δ r2 . Several such determinations, however, yield results that are in a 4 σ disagreement with each other, which remains unexplained. Apart from this, we find no significant discrepancies between theory and experiment for the helium atom. A further calculation of the yet unknown α7m correction to energy levels will provide a sensitive test of universality in electromagnetic interactions of leptons by comparison of nuclear charge radii obtained by the helium and muonic helium spectroscopy.

  7. Experimental Impacts into Chondritic Targets. Part 1; Disruption of an L6 Chondrite by Multiple Impacts

    NASA Technical Reports Server (NTRS)

    Cintala, Mark J.; Horz, Friedrich

    2007-01-01

    A fragment of an L6 chondrite (ALH 85017,13) with an initial mass (M(sub 0)) of 464.1 g was the target in a series of experimental impacts in which the largest remaining fragment (M(sub R)) after each shot was impacted by a 3.18-mm ceramic sphere at a nominal speed of 2 km/s. This continued until the mass of the largest remaining piece was less than half the mass of the target presented to that shot (M(sub S)). Two chunks of Bushveldt gabbro with similar initial masses were also impacted under the same conditions until M(sub R) was less than half M(sub 0). The two gabbro targets required a total of 1.51x10(exp 7) and 1.75x10(exp 7) erg/g to attain 0.27 and 0.33 M(sub R)/M(sub 0), respectively; the chondrite, however, was considerably tougher, reaching 0.40 and 0.21 M(sub R)/M(sub 0) only after receiving 2.37x10(exp 7) and 3.10x10(exp 7) erg g-1, respectively. The combined ejecta and spallation products from the gabbro impacts were coarser than those from the chondrite and in sufficient quantities that the new surface areas exceeded those from the meteorite until the fifth shot in the chondrite series, which was the number of impacts required to disrupt each gabbro target (i.e., MR/M0 = 0.5). Unlike the behavior shown in previous regolith-evolution series, neither gabbro target produced an enhancement in the size fraction reflecting the mean size of the crystals composing the rock (about 3 mm), an effect possibly related to the width of the shock pulse. The original chondrite was so fine-grained and fractured, and the variance in its grain-size distribution so large, that effects related to grain-size were relegated to the <63- m fraction. Impacts into ALH 85017 produced abundant, fine-grained debris, but otherwise the slopes of its size distributions were comparable to those from other experiments involving natural and fabricated terrestrial targets. The characteristic slopes of the chondrite's size distributions, however, were notably more constant over the entire

  8. Experimental impacts into chondritic targets, part I: Disruption of an L6 chondrite by multiple impacts

    NASA Astrophysics Data System (ADS)

    Cintala, Mark J.; Hörz, Friedrich

    2008-04-01

    A fragment of an L6 chondrite (Allan Hills [ALH] 85017,13) with an initial mass (M0) of 464.1 g was the target in a series of experimental impacts in which the largest remaining fragment (MR) after each shot was impacted by a 3.18 mm ceramic sphere at a nominal speed of 2 km s-1. This continued until the mass of the largest remaining piece was less than half the mass of the target presented to that shot (MS). Two chunks of Bushveldt gabbro with similar initial masses were also impacted under the same conditions until MR was less than half M0. The two gabbro targets required a total of 1.51 × 107 and 1.75 × 107 erg g-1 to attain 0.27 and 0.33 MR/M0, respectively; the chondrite, however, was considerably tougher, reaching 0.40 and 0.21 MR/M0 only after receiving 2.37 × 107 and 3.10 × 107 erg g-1, respectively. The combined ejecta and spallation products from the gabbro impacts were coarser than those from the chondrite and in sufficient quantities that the new surface areas exceeded those from the meteorite until the fifth shot in the chondrite series, which was the number of impacts required to disrupt each gabbro target (i.e., MR/M0 ≤ 0.5). Unlike the behavior shown in previous regolith-evolution series, neither gabbro target produced an enhancement in the size fraction reflecting the mean size of the crystals composing the rock (about 3 mm), an effect possibly related to the width of the shock pulse. The original chondrite was so fine-grained and fractured, and the variance in its grain-size distribution so large, that effects related to grain size were relegated to the <63 μm fraction. Impacts into ALH 85017 produced abundant, fine-grained debris, but otherwise the slopes of its size distributions were comparable to those from other experiments involving natural and fabricated terrestrial targets. The characteristic slopes of the chondrite’s size distributions, however, were notably more constant over the entire nine-impact series than those from any of

  9. Mitochondria targeted peptides protect against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine neurotoxicity.

    PubMed

    Yang, Lichuan; Zhao, Kesheng; Calingasan, Noel Y; Luo, Guoxiong; Szeto, Hazel H; Beal, M Flint

    2009-09-01

    A large body of evidence suggests that mitochondrial dysfunction and oxidative damage play a role in the pathogenesis of Parkinson's disease (PD). A number of antioxidants have been effective in animal models of PD. We have developed a family of mitochondria-targeted peptides that can protect against mitochondrial swelling and apoptosis (SS peptides). In this study, we examined the ability of two peptides, SS-31 and SS-20, to protect against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) neurotoxicity in mice. SS-31 produced dose-dependent complete protection against loss of dopamine and its metabolites in striatum, as well as loss of tyrosine hydroxylase immunoreactive neurons in substantia nigra pars compacta. SS-20, which does not possess intrinsic ability in scavenging reactive oxygen species, also demonstrated significant neuroprotective effects on dopaminergic neurons of MPTP-treated mice. Both SS-31 and SS-20 were very potent (nM) in preventing MPP+ (1-methyl-4-phenylpyridinium)-induced cell death in cultured dopamine cells (SN4741). Studies with isolated mitochondria showed that both SS-31 and SS-20 prevented MPP+-induced inhibition of oxygen consumption and ATP production, and mitochondrial swelling. These findings provide strong evidence that these neuroprotective peptides, which target both mitochondrial dysfunction and oxidative damage, are a promising approach for the treatment of PD.

  10. Mitochondria Targeted Peptides Protect Against 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine Neurotoxicity

    PubMed Central

    Yang, Lichuan; Zhao, Kesheng; Calingasan, Noel Y.; Luo, Guoxiong; Szeto, Hazel H.

    2009-01-01

    Abstract A large body of evidence suggests that mitochondrial dysfunction and oxidative damage play a role in the pathogenesis of Parkinson's disease (PD). A number of antioxidants have been effective in animal models of PD. We have developed a family of mitochondria-targeted peptides that can protect against mitochondrial swelling and apoptosis (SS peptides). In this study, we examined the ability of two peptides, SS-31 and SS-20, to protect against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) neurotoxicity in mice. SS-31 produced dose-dependent complete protection against loss of dopamine and its metabolites in striatum, as well as loss of tyrosine hydroxylase immunoreactive neurons in substantia nigra pars compacta. SS-20, which does not possess intrinsic ability in scavenging reactive oxygen species, also demonstrated significant neuroprotective effects on dopaminergic neurons of MPTP-treated mice. Both SS-31 and SS-20 were very potent (nM) in preventing MPP+ (1-methyl-4-phenylpyridinium)-induced cell death in cultured dopamine cells (SN4741). Studies with isolated mitochondria showed that both SS-31 and SS-20 prevented MPP+-induced inhibition of oxygen consumption and ATP production, and mitochondrial swelling. These findings provide strong evidence that these neuroprotective peptides, which target both mitochondrial dysfunction and oxidative damage, are a promising approach for the treatment of PD. Antioxid. Redox Signal. 11, 2095–2104. PMID:19203217

  11. Quercetin-3-methyl ether suppresses proliferation of mouse epidermal JB6 P+ cells by targeting ERKs

    PubMed Central

    Mottamal, Madhusoodanan; Liu, Kangdong; Zhu, Feng; Cho, Yong-Yeon; Sosa, Carlos P.; Zhou, Keyuan; Bowden, G.Tim; Bode, Ann M.; Dong, Zigang

    2012-01-01

    Chemoprevention has been acknowledged as an important and practical strategy for the management of skin cancer. Quercetin-3-methyl ether, a naturally occurring compound present in various plants, has potent anticancer-promoting activity. We identified this compound by in silico virtual screening of the Traditional Chinese Medicine Database using extracellular signal-regulated kinase 2 (ERK2) as the target protein. Here, we showed that quercetin-3-methyl ether inhibited proliferation of mouse skin epidermal JB6 P+ cells in a dose- and time-dependent manner by inducing cell cycle G2–M phase accumulation. It also suppressed 12-O-tetradecanoylphorbol-13-acetate-induced neoplastic cell transformation in a dose-dependent manner. Its inhibitory effect was greater than quercetin. The activation of activator protein-1 was dose-dependently suppressed by quercetin-3-methyl ether treatment. Western blot and kinase assay data revealed that quercetin-3-methyl ether inhibited ERKs kinase activity and attenuated phosphorylation of ERKs. Pull-down assays revealed that quercetin-3-methyl ether directly binds with ERKs. Furthermore, a loss-of-function ERK2 mutation inhibited the effectiveness of the quercetin-3-methyl ether. Overall, these results indicated that quercetin-3-methyl ether exerts potent chemopreventive activity by targeting ERKs. PMID:22139441

  12. Radiation source for helium magnetometers

    NASA Technical Reports Server (NTRS)

    Slocum, Robert E. (Inventor)

    1991-01-01

    A radiation source (12) for optical magnetometers (10) which use helium isotopes as the resonance element (30) includes an electronically pumped semiconductor laser (12) which produces a single narrow line of radiation which is frequency stabilized to the center frequency of the helium resonance line to be optically pumped. The frequency stabilization is accomplished using electronic feedback (34, 40, 42, 44) to control a current sources (20) thus eliminating the need for mechanical frequency tuning.

  13. Liquid Helium 3 and Solid Helium at Yale and Beyond

    NASA Astrophysics Data System (ADS)

    Lee, D. M.

    2006-03-01

    Many of the foundations of low temperature physics in the latter half of the twentieth century were built at Yale University under the leadership of Professor Cecil T. Lane who came to Yale in 1932 and Henry A. Fairbank who obtained his Ph.D. at Yale in 1944 under Lane's guidance. This discussion will mainly treat the contributions of Henry Fairbank and his students during the period between 1954 and 1963, when Henry Fairbank left Yale to become chairman of the Physics Dept. at Duke University. Following World War II small amounts of helium three became available to low temperature experimenters. Henry Fairbank’s graduate students were provided with the opportunity to investigate second sound in dilute and later concentrated mixtures of helium three in superfluid helium four. These measurements showed strong effects of the phase separation in helium 3 - helium 4 mixtures previously discovered in the laboratory of William Fairbank (a student of Lane and a brother of Henry Fairbank). As more helium three became available, studies of pure helium three were performed, including measurements of the thermal conductivity, the density and the specific heat. Early evidence for the melting curve minimum was found. The main emphasis in this work was to search for Fermi liquid behavior. Much of the later work in this area was performed by the group of John Wheatley at the University of Illinois. In studies of solid helium four at Yale, a surprising observation was made. Hitherto it had been thought that hcp was the stable phase throughout the low temperature part of the phase diagram. It was found via ultrasound experiments that a small silver of bcc solid existed at the lowest pressures. While this author was a graduate student at Yale, Henry Fairbank pointed out to him the possibility of cooling helium three via adiabatic compression from the liquid into the solid phase. (Pomeranchuk Cooling). A brief discussion is given of the use of this technique in the discovery of

  14. Cryogenic filter method produces super-pure helium and helium isotopes

    NASA Technical Reports Server (NTRS)

    Hildebrandt, A. F.

    1964-01-01

    Helium is purified when cooled in a low pressure environment until it becomes superfluid. The liquid helium is then filtered through iron oxide particles. Heating, cooling and filtering processes continue until the purified liquid helium is heated to a gas.

  15. Interleukin-6 is a potential therapeutic target in interleukin-6 dependent, estrogen receptor-α-positive breast cancer

    PubMed Central

    Casneuf, Tineke; Axel, Amy E; King, Peter; Alvarez, John D; Werbeck, Jillian L; Verhulst, Tinne; Verstraeten, Karin; Hall, Brett M; Sasser, A Kate

    2016-01-01

    Introduction Interleukin-6 (IL-6) is an important growth factor for estrogen receptor-α (ERα)-positive breast cancer, and elevated serum IL-6 is associated with poor prognosis. Methods The role of the phosphorylated signal transducer and activator of transcription 3 pathway was investigated in ERα-positive breast cancer. A panel of cell lines was treated with exogenous IL-6. An IL-6 specific gene signature was generated by profiling ten ERα-positive breast cancer cell lines alone or following treatment with 10 ng/mL recombinant IL-6 or human marrow stromal cell-conditioned media, with or without siltuximab (a neutralizing anti-IL-6 antibody) and grown in three-dimensional tumor microenvironment-aligned cultures for 4 days, 5 days, or 6 days. The established IL-6 signature was validated against 36 human ERα-positive breast tumor samples with matched serum. A comparative MCF-7 xenograft murine model was utilized to determine the role of IL-6 in estrogen-supplemented ERα-positive breast cancer to assess the efficacy of anti-IL-6 therapy in vivo. Results In eight of nine ERα-positive breast cancer cell lines, recombinant IL-6 increased phosphorylation of tyrosine 705 of STAT3. Differential gene expression analysis identified 17 genes that could be used to determine IL-6 pathway activation by combining their expression intensity into a pathway activation score. The gene signature included a variety of genes involved in immune cell function and migration, cell growth and apoptosis, and the tumor microenvironment. Validation of the IL-6 gene signature in 36 matched human serum and ERα-positive breast tumor samples showed that patients with a high IL-6 pathway activation score were also enriched for elevated serum IL-6 (≥10 pg/mL). When human IL-6 was provided in vivo, MCF-7 cells engrafted without the need for estrogen supplementation, and addition of estrogen to IL-6 did not further enhance engraftment. Subsequently, we prophylactically treated mice at MCF-7

  16. Perspectives on Lunar Helium-3

    NASA Astrophysics Data System (ADS)

    Schmitt, Harrison H.

    1999-01-01

    Global demand for energy will likely increase by a factor of six or eight by the mid-point of the 21st Century due to a combination of population increase, new energy intensive technologies, and aspirations for improved standards of living in the less-developed world (1). Lunar helium-3 (3He), with a resource base in the Tranquillitatis titanium-rich lunar maria (2,3) of at least 10,000 tonnes (4), represents one potential energy source to meet this rapidly escalating demand. The energy equivalent value of 3He delivered to operating fusion power plants on Earth would be about 3 billion per tonne relative to today's coal which supplies most of the approximately 90 billion domestic electrical power market (5). These numbers illustrate the magnitude of the business opportunity. The results from the Lunar Prospector neutron spectrometer (6) suggests that 3He also may be concentrated at the lunar poles along with solar wind hydrogen (7). Mining, extraction, processing, and transportation of helium to Earth requires new innovations in engineering but no known new engineering concepts (1). By-products of lunar 3He extraction, largely hydrogen, oxygen, and water, have large potential markets in space and ultimately will add to the economic attractiveness of this business opportunity (5). Inertial electrostatic confinement (IEC) fusion technology appears to be the most attractive and least capital intensive approach to terrestrial fusion power plants (8). Heavy lift launch costs comprise the largest cost uncertainty facing initial business planning, however, many factors, particularly long term production contracts, promise to lower these costs into the range of 1-2000 per kilogram versus about 70,000 per kilogram fully burdened for the Apollo Saturn V rocket (1). A private enterprise approach to developing lunar 3He and terrestrial IEC fusion power would be the most expeditious means of realizing this unique opportunity (9). In spite of the large, long-term potential

  17. ITER helium ash accumulation

    SciTech Connect

    Hogan, J.T.; Hillis, D.L.; Galambos, J.; Uckan, N.A. ); Dippel, K.H.; Finken, K.H. . Inst. fuer Plasmaphysik); Hulse, R.A.; Budny, R.V. . Plasma Physics Lab.)

    1990-01-01

    Many studies have shown the importance of the ratio {upsilon}{sub He}/{upsilon}{sub E} in determining the level of He ash accumulation in future reactor systems. Results of the first tokamak He removal experiments have been analysed, and a first estimate of the ratio {upsilon}{sub He}/{upsilon}{sub E} to be expected for future reactor systems has been made. The experiments were carried out for neutral beam heated plasmas in the TEXTOR tokamak, at KFA/Julich. Helium was injected both as a short puff and continuously, and subsequently extracted with the Advanced Limiter Test-II pump limiter. The rate at which the He density decays has been determined with absolutely calibrated charge exchange spectroscopy, and compared with theoretical models, using the Multiple Impurity Species Transport (MIST) code. An analysis of energy confinement has been made with PPPL TRANSP code, to distinguish beam from thermal confinement, especially for low density cases. The ALT-II pump limiter system is found to exhaust the He with maximum exhaust efficiency (8 pumps) of {approximately}8%. We find 1<{upsilon}{sub He}/{upsilon}{sub E}<3.3 for the database of cases analysed to date. Analysis with the ITER TETRA systems code shows that these values would be adequate to achieve the required He concentration with the present ITER divertor He extraction system.

  18. Carbon Nanotubes Immersed in Superfluid Helium: The Impact of Quantum Confinement on Wetting and Capillary Action.

    PubMed

    Hauser, Andreas W; de Lara-Castells, María Pilar

    2016-12-01

    A recent experimental study [ Ohba, Sci. Rep. 2016, 6, 28992 ] of gas adsorption on single-walled carbon nanotubes at temperatures between 2 and 5 K reported a quenched propagation of helium through carbon nanotubes with diameters below 7 Å despite the small kinetic diameter of helium atoms. After assessing the performance of a potential model for the He-nanotube interaction via ab initio calculations with density functional theory-based symmetry adapted perturbation theory, we apply orbital-free helium density functional theory to show that the counterintuitive experimental result is a consequence of the exceptionally high zero-point energy of helium and its tendency to form spatially separated layers of helium upon adsorption at the lowest temperatures. Helium filling factors are derived for a series of carbon nanotubes and compared to the available experimental data.

  19. Quasi-elastic pn scattering in 6LiD and 6LiH targets from 1.1 to 2.4 GeV

    NASA Astrophysics Data System (ADS)

    de Lesquen, A.; Allgower, C. E.; Ball, J.; Beddo, M.; Bystrický, J.; Combet, M.; Demierre, Ph.; Durand, G.; Fontaine, J.-M.; Grosnick, D.; Hess, R.; Janout, Z.; Janout, Z. F.; Kalinnikov, V. A.; Kasprzyk, T. E.; Khachaturov, B. A.; Kunne, R.; Lehar, F.; Lopiano, D.; Matafonov, V. N.; Pisarev, I. L.; Popov, A. A.; Prokofiev, A. N.; Rapin, D.; Sans, J.-L.; Spinka, H. M.; Usov, Yu. A.; Vikhrov, V. V.; Vuaridel, B.; Zhdanov, A. A.

    1999-11-01

    A polarized proton beam from SATURNE II, the Saclay polarized targets with ^6Li compounds, and an unpolarized CH_2 target were used to measure spin-dependent observables for protons scattered on bound nucleons. The beam and target polarizations were oriented vertically. The analyzing power A_{oono} and the depolarization D_{nono} were determined at seven energies between 1.1 and 2.4 GeV. The spin correlation parameter A_{oonn} was measured at only 1.1 and 1.6 GeV. Measurements with the CH_2 target at 1.1 GeV provided A_{oono} data for scattering of polarized protons on neutrons in carbon. The quasi-elastic observables are compared with previous elastic scattering measurements and at 1.1 GeV with predictions of phase shift analyses.

  20. Early Secreted Antigenic Target of 6-kDa of Mycobacterium tuberculosis Stimulates IL-6 Production by Macrophages through Activation of STAT3

    PubMed Central

    Jung, Bock-Gie; Wang, Xisheng; Yi, Na; Ma, Justin; Turner, Joanne; Samten, Buka

    2017-01-01

    As early secreted antigenic target of 6 kDa (ESAT-6) of Mycobacterium tuberculosis (Mtb) is an essential virulence factor and macrophages are critical for tuberculosis infection and immunity, we studied ESAT-6 stimulated IL-6 production by macrophages. ESAT-6 stimulated significantly higher IL-6 secretion by murine bone marrow derived macrophages (BMDM) compared to culture filtrate protein 10 kDa (CFP10) and antigen 85A. Polymyxin B, an LPS blocker, did not affect ESAT-6 stimulated macrophage IL-6 production. ESAT-6 but not Pam3CSK4 induced IL-6 by TLR2 knockout BMDM. ESAT-6 induced phosphorylation and DNA binding of STAT3 and this was blocked by STAT3 inhibitors but not by rapamycin. STAT3 inhibitors suppressed ESAT-6-induced IL-6 transcription and secretion without affecting cell viability. This was confirmed by silencing STAT3 in macrophages. Blocking neither IL-6Rα/IL-6 nor IL-10 affected ESAT-6-induced STAT3 activation and IL-6 production. Infection of BMDM and human macrophages with Mtb with esat-6 deletion induced diminished STAT3 activation and reduced IL-6 production compared to wild type and esat-6 complemented Mtb strains. Administration of ESAT-6 but not CFP10 induced STAT3 phosphorylation and IL-6 expression in the mouse lungs, consistent with expression of ESAT-6, IL-6 and phosphorylated-STAT3 in Mtb-infected mouse lungs. We conclude that ESAT-6 stimulates macrophage IL-6 production through STAT3 activation. PMID:28106119

  1. Growth rate effects on the formation of dislocation loops around deep helium bubbles in Tungsten

    DOE PAGES

    Sandoval, Luis; Perez, Danny; Uberuaga, Blas P.; ...

    2016-11-15

    Here, the growth process of spherical helium bubbles located 6 nm below a (100) surface is studied using molecular dynamics and parallel replica dynamics simulations, over growth rates from 106 to 1012 helium atoms per second. Slower growth rates lead to a release of pressure and lower helium content as compared with fast growth cases. In addition, at slower growth rates, helium bubbles are not decorated by multiple dislocation loops, as these tend to merge or emit given sufficient time. At faster rates, dislocation loops nucleate faster than they can emit, leading to a more complicated dislocation structure around themore » bubble.« less

  2. Energetic ionized helium in the quiet time radiation belts - Theory and comparison with observation

    NASA Technical Reports Server (NTRS)

    Spjeldvik, W. N.; Fritz, T. A.

    1978-01-01

    Theoretical calculations of helium ion distributions in the inner magnetosphere are compared to observations made by ATS-6 and Explorer-45. Coupled transport equations for equatorially mirroring singly and doubly ionized helium ions in the steady state limit with an outer boundary of L = 7 are solved. Radial profiles and energy spectra are computed at all lower L values. Theoretical quiet time predictions are compared to satellite observations of energetic helium ions in the lower MeV range. It is found that the theory adequately represents the principal characteristics of the radiation belt helium ion population.

  3. Revealing Different Roles of the mTOR-Targets S6K1 and S6K2 in Breast Cancer by Expression Profiling and Structural Analysis

    PubMed Central

    Karlsson, Elin; Magić, Ivana; Bostner, Josefine; Dyrager, Christine; Lysholm, Fredrik; Hallbeck, Anna-Lotta; Stål, Olle; Lundström, Patrik

    2015-01-01

    Background The AKT/mTORC1/S6K pathway is frequently overstimulated in breast cancer, constituting a promising therapeutic target. The benefit from mTOR inhibitors varies, likely as a consequence of tumour heterogeneity, and upregulation of several compensatory feed-back mechanisms. The mTORC1 downstream effectors S6K1, S6K2, and 4EBP1 are amplified and overexpressed in breast cancer, associated with a poor outcome and divergent endocrine treatment benefit. S6K1 and S6K2 share high sequence homology, but evidence of partly distinct biological functions is emerging. The aim of this work was to explore possible different roles and treatment target potentials of S6K1 and S6K2 in breast cancer. Materials and methods Whole-genome expression profiles were compared for breast tumours expressing high levels of S6K1, S6K2 or 4EBP1, using public datasets, as well as after in vitro siRNA downregulation of S6K1 and/or S6K2 in ZR751 breast cancer cells. In silico homology modelling of the S6K2 kinase domain was used to evaluate its possible structural divergences to S6K1. Results Genome expression profiles were highly different in S6K1 and S6K2 high tumours, whereas S6K2 and 4EBP1 profiles showed significant overlaps, both correlated to genes involved in cell cycle progression, among these the master regulator E2F1. S6K2 and 4EBP1 were inversely associated with IGF1 levels, and their prognostic value was shown to be restricted to tumours positive for IGFR and/or HER2. In vitro, S6K1 and S6K2 silencing resulted in upregulation of genes in the mTORC1 and mTORC2 complexes. Isoform-specific silencing also showed distinct patterns, e.g. S6K2 downregulation lead to upregulation of several cell cycle associated genes. Structural analyses of the S6K2 kinase domain showed unique structure patterns, deviating from those of S6K1, facilitating the development of isoform-specific inhibitors. Our data support emerging proposals of distinct biological features of S6K1 and S6K2, suggesting

  4. Metabolism of 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine by Mitochondrion-targeted Cytochrome P450 2D6

    PubMed Central

    Bajpai, Prachi; Sangar, Michelle C.; Singh, Shilpee; Tang, Weigang; Bansal, Seema; Chowdhury, Goutam; Cheng, Qian; Fang, Ji-Kang; Martin, Martha V.; Guengerich, F. Peter; Avadhani, Narayan G.

    2013-01-01

    1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is a neurotoxic side product formed in the chemical synthesis of desmethylprodine opioid analgesic, which induces Parkinson disease. Monoamine oxidase B, present in the mitochondrial outer membrane of glial cells, catalyzes the oxidation of MPTP to the toxic 1-methyl-4-phenylpyridinium ion (MPP+), which then targets the dopaminergic neurons causing neuronal death. Here, we demonstrate that mitochondrion-targeted human cytochrome P450 2D6 (CYP2D6), supported by mitochondrial adrenodoxin and adrenodoxin reductase, can efficiently catalyze the metabolism of MPTP to MPP+, as shown with purified enzymes and also in cells expressing mitochondrial CYP2D6. Neuro-2A cells stably expressing predominantly mitochondrion-targeted CYP2D6 were more sensitive to MPTP-mediated mitochondrial respiratory dysfunction and complex I inhibition than cells expressing predominantly endoplasmic reticulum-targeted CYP2D6. Mitochondrial CYP2D6 expressing Neuro-2A cells produced higher levels of reactive oxygen species and showed abnormal mitochondrial structures. MPTP treatment also induced mitochondrial translocation of an autophagic marker, Parkin, and a mitochondrial fission marker, Drp1, in differentiated neurons expressing mitochondrial CYP2D6. MPTP-mediated toxicity in primary dopaminergic neurons was attenuated by CYP2D6 inhibitor, quinidine, and also partly by monoamine oxidase B inhibitors deprenyl and pargyline. These studies show for the first time that dopaminergic neurons expressing mitochondrial CYP2D6 are fully capable of activating the pro-neurotoxin MPTP and inducing neuronal damage, which is effectively prevented by the CYP2D6 inhibitor quinidine. PMID:23258538

  5. Thermal annealing behaviour and defect evolution of helium in fully stabilised zirconia

    NASA Astrophysics Data System (ADS)

    Damen, P. M. G.; van Veen, A.; Labohm, F.; Schut, H.; van Huis, M. A.

    2003-06-01

    Helium implantations in fully stabilised zirconia have been performed with 30 keV ions with high doses (5.1 × 10 16 and 2.6 × 10 16 cm -2) and low doses (6.3 × 10 15 and 1.7 × 10 15 cm -2). The retained amount of helium and depth profiles have been monitored with neutron depth profiling and the damage distribution with positron beam analysis (PBA) after several annealing steps. The temperature dependent helium release was investigated by thermal helium desorption spectrometry. In the low dose samples, helium is released through diffusion as seen by a broadening of the helium distribution peak. PBA, performed with a two-layer model, shows shrinkage of the damage layer during annealing. For the high dose samples the helium peak does not broaden after annealing. Helium is retained up to high temperatures which is ascribed to bubble formation during thermal annealing. Fitting of the PBA results to a three-layer model shows that the ion implanted layer gets narrower after annealing at 600 K, up to 1000 K the S-parameter is increasing because helium is released from the bubbles, whereby vacancy clusters are left behind.

  6. Early Secretory Antigenic Target-6 Drives Matrix Metalloproteinase-10 Gene Expression and Secretion in Tuberculosis.

    PubMed

    Brilha, Sara; Sathyamoorthy, Tarangini; Stuttaford, Laura H; Walker, Naomi F; Wilkinson, Robert J; Singh, Shivani; Moores, Rachel C; Elkington, Paul T; Friedland, Jon S

    2017-02-01

    Tuberculosis (TB) causes disease worldwide, and multidrug resistance is an increasing problem. Matrix metalloproteinases (MMPs), particularly the collagenase MMP-1, cause lung extracellular matrix destruction, which drives disease transmission and morbidity. The role in such tissue damage of the stromelysin MMP-10, a key activator of the collagenase MMP-1, was investigated in direct Mycobacterium tuberculosis (Mtb)-infected macrophages and in conditioned medium from Mtb-infected monocyte-stimulated cells. Mtb infection increased MMP-10 secretion from primary human macrophages 29-fold, whereas Mtb-infected monocytes increased secretion by 4.5-fold from pulmonary epithelial cells and 10.5-fold from fibroblasts. Inhibition of MMP-10 activity decreased collagen breakdown. In two independent cohorts of patients with TB from different continents, MMP-10 was increased in both induced sputum and bronchoalveolar lavage fluid compared with control subjects and patients with other respiratory diseases (both P < 0.05). Mtb drove 3.5-fold greater MMP-10 secretion from human macrophages than the vaccine strain bacillus Calmette-Guerin (P < 0.001), whereas both mycobacteria up-regulated TNF-α secretion equally. Using overlapping, short, linear peptides covering the sequence of early secretory antigenic target-6, a virulence factor secreted by Mtb, but not bacillus Calmette-Guerin, we found that stimulation of human macrophages with a single specific 15-amino acid peptide sequence drove threefold greater MMP-10 secretion than any other peptide (P < 0.001). Mtb-driven MMP-10 secretion was inhibited in a dose-dependent manner by p38 and extracellular signal-related kinase mitogen-activated protein kinase blockade (P < 0.001 and P < 0.01 respectively), but it was not affected by inhibition of NF-κB. In summary, Mtb activates inflammatory and stromal cells to secrete MMP-10, and this is partly driven by the virulence factor early secretory antigenic target-6

  7. a Measurement of Cross-Sections for Charge Transfer in Proton + Helium ---> Helium Ion + Hydrogen

    NASA Astrophysics Data System (ADS)

    Brower, Michael Chadbourne

    A microwave-resonance, optical-detection technique is used to measure the cross sections for charge transfer into the n = 3,L,m(,L) states of hydrogen by protons colliding with a helium gas target at energies between 30 and 80 keV. The feeding of the n = 3 states by states in higher n manifolds created by the collisions has been taken into account for the first time in this type of measurement, with a significant effect on the results. The final cross sections are one of only two measurements of the L,m(,L) cross sections in this system, and the only one to be able to resolve the 3d cross sections. The. uncertainties are 10% to 30% of the cross sections at all energies. The results are (UNFORMATTED TABLE FOLLOWS). Energy (keV). 30 50 60 80. (sigma)(,3s). 10('-18)cm('2) 1.6(3) 2.4(5) 2.0(4) 1.4(3). 3s(,0) 1 1 1 1. p(,0) 0.58(8) 0.19(2) 0.18(2) 0.13(1). p(,1) 0.36(6) 0.08(1) 0.04(1) 0.05(1). TOTAL 0.94(10) 0.27(2) 0.22(2) 0.18(1). d(,0) 0.055(10) 0.017(4) 0.019(4) 0.013(3). d(,1) 0.046(7) 0.014(3) 0.014(3) 0.010(2). d(,2) 0.022(4) 0.001(2) -0.002(2) -0.002(2). TOTAL 0.123(12) 0.032(5) 0.031(5) 0.021(4). (TABLE ENDS).

  8. Helium superfluidity. Shapes and vorticities of superfluid helium nanodroplets.

    PubMed

    Gomez, Luis F; Ferguson, Ken R; Cryan, James P; Bacellar, Camila; Tanyag, Rico Mayro P; Jones, Curtis; Schorb, Sebastian; Anielski, Denis; Belkacem, Ali; Bernando, Charles; Boll, Rebecca; Bozek, John; Carron, Sebastian; Chen, Gang; Delmas, Tjark; Englert, Lars; Epp, Sascha W; Erk, Benjamin; Foucar, Lutz; Hartmann, Robert; Hexemer, Alexander; Huth, Martin; Kwok, Justin; Leone, Stephen R; Ma, Jonathan H S; Maia, Filipe R N C; Malmerberg, Erik; Marchesini, Stefano; Neumark, Daniel M; Poon, Billy; Prell, James; Rolles, Daniel; Rudek, Benedikt; Rudenko, Artem; Seifrid, Martin; Siefermann, Katrin R; Sturm, Felix P; Swiggers, Michele; Ullrich, Joachim; Weise, Fabian; Zwart, Petrus; Bostedt, Christoph; Gessner, Oliver; Vilesov, Andrey F

    2014-08-22

    Helium nanodroplets are considered ideal model systems to explore quantum hydrodynamics in self-contained, isolated superfluids. However, exploring the dynamic properties of individual droplets is experimentally challenging. In this work, we used single-shot femtosecond x-ray coherent diffractive imaging to investigate the rotation of single, isolated superfluid helium-4 droplets containing ~10(8) to 10(11) atoms. The formation of quantum vortex lattices inside the droplets is confirmed by observing characteristic Bragg patterns from xenon clusters trapped in the vortex cores. The vortex densities are up to five orders of magnitude larger than those observed in bulk liquid helium. The droplets exhibit large centrifugal deformations but retain axially symmetric shapes at angular velocities well beyond the stability range of viscous classical droplets. Copyright © 2014, American Association for the Advancement of Science.

  9. Proposed method for laser spectroscopy of pionic helium atoms to determine the charged-pion mass

    NASA Astrophysics Data System (ADS)

    Hori, Masaki; Sótér, Anna; Korobov, Vladimir I.

    2014-04-01

    Metastable pionic helium (πHe+) is a three-body atom composed of a helium nucleus, an electron occupying the 1s ground state, and a negatively charged pion π- in a Rydberg state with principal and orbital angular momentum quantum numbers of n ˜ℓ+1˜16. We calculate the spin-independent energies of the π3He+ and π4He+ isotopes in the region n =15-19. These include relativistic and quantum electrodynamics corrections of orders R∞α2 and R∞α3 in atomic units, where R∞ and α denote the Rydberg and fine structure constants. The fine-structure splitting due to the coupling between the electron spin and the orbital angular momentum of the π- and the radiative and Auger decay rates of the states are also calculated. Some states (n,ℓ)=(16,15) and (17,16) retain nanosecond-scale lifetimes against π- absorption into the helium nucleus. We propose the use of laser pulses to induce π- transitions from these metastable states to states with large (˜1011 s-1) Auger rates. The πHe2+ ion that remains after Auger emission of the 1s electron undergoes Stark mixing with the s, p, and d states during collisions with the helium atoms in the experimental target. This leads to immediate nuclear absorption of the π -. The resonance condition between the laser beam and the atom is thus revealed as a sharp spike in the rates of neutrons, protons, deuterons, and tritons that emerge. A resonance curve is obtained from which the πHe+ transition frequency can in principle be determined with a fractional precision of 10-8-10-6 provided the systematic uncertainties can be controlled. By comparing the measured πHe+ frequencies with the calculated values, the π- mass may be determined with a similar precision. The πHe+ will be synthesized by allowing a high-intensity (>108 s-1) beam of π-produced by a cyclotron to come to rest in a helium target. The precise time structure of the π- beam is used to ensure a sufficient rate of coincidence between the resonant laser pulses

  10. O(6)-Methylguanine-DNA methyltransferase (MGMT): A drugable target in lung cancer?

    PubMed

    Hiddinga, Birgitta I; Pauwels, Patrick; Janssens, Annelies; van Meerbeeck, Jan P

    2016-07-18

    This manuscript addresses the role of O(6)-methylguanine-DNA methyltransferase (MGMT) as a biomarker in the oncogenesis of cancer and the opportunity of turning this gene into a drugable target in neuroendocrine tumours of the lung. Studies in brain tumours conclude that MGMT promoter methylation is considered a strong predictive factor for a favourable outcome for treatment with temozolomide, e.g. alkylating agent. We conducted a systematic review of MGMT in non-small cell lung cancer (NSCLC), small-cell lung cancer (SCLC) and other pulmonary neuroendocrine tumours (NETs) to evaluate whether MGMT is a prognostic and/or predictive factor to select patients with lung cancer who can benefit from treatment with temozolomide. In NSCLC MGMT promoter methylation is not a prognostic and predictive factor, hence temozolomide has no place. In SCLC and NET patients with a MGMT promoter methylation benefit of temozolomide has to be confirmed.Temozolomide can be considered a 'personalized' treatment if the predictive role of MGMT is further confirmed.

  11. Cellular senescence or EGFR signaling induces Interleukin 6 (IL-6) receptor expression controlled by mammalian target of rapamycin (mTOR)

    PubMed Central

    Garbers, Christoph; Kuck, Fabian; Aparicio-Siegmund, Samadhi; Konzak, Kirstin; Kessenbrock, Mareike; Sommerfeld, Annika; Häussinger, Dieter; Lang, Philipp A; Brenner, Dirk; Mak, Tak W.; Rose-John, Stefan; Essmann, Frank; Schulze-Osthoff, Klaus; Piekorz, Roland P; Scheller, Jürgen

    2013-01-01

    Interleukin 6 (IL-6) signaling plays a role in inflammation, cancer, and senescence. Here, we identified soluble IL-6 receptor (sIL-6R) as a member of the senescence-associated secretory phenotype (SASP). Senescence-associated sIL-6R upregulation was mediated by mammalian target of rapamycin (mTOR). sIL-6R was mainly generated by a disintegrin and metalloprotease 10 (ADAM10)-dependent ectodomain shedding to enable IL-6 trans-signaling. In vivo, heterozygous PTEN-knockout mice exhibited higher mTOR activity and increased sIL-6R levels. Moreover, aberrant EGF receptor (EGFR) activation triggered IL-6 synthesis. In analogy to senescence, EGFR-induced activation of mTOR also induced IL-6R expression and sIL-6R generation. Hence, mTOR activation reprograms IL-6 non-responder cells into IL-6 responder cells. Our data suggest that mTOR serves as a central molecular switch to facilitate cellular IL-6 classic and trans-signaling via IL-6R upregulation with direct implications for cellular senescence and tumor development. PMID:24047696

  12. A report on the Zimbabwe Antiretroviral Therapy (ART) programme progress towards achieving MGD6 target 6B: achievement and challenges.

    PubMed

    Apollo, T; Takarinda, K; Mugurungi, O; Chakanyuka, C; Simbini, T; Harries, A D

    2010-01-01

    Zimbabwe's target to achieve Universal Access to treatment for HIV and AIDS, was severely affected by a decade long economic recession that threatened to reverse all the country's social and economic indicators. Despite these challenges, by September 2010, 282,916 adults and children (47.7% of those in need of treatment) were on treatment at 509 sites countrywide since national scale up started. ART services are predominantly offered through the public sector, with the private sector being an untapped potential resource for ART services for the future. Challenges of skilled and adequately trained human resources have hindered progress towards service availability. Providing access to children in particular has been constrained by lack of clinical mentorship for health workers, weak systems for support supervision, and inadequate HIV diagnostic services especially for children under 18 months and challenges with follow up of the HIV-exposed infants. Though the country has not met its target of Universal Access by 2010, significant progress has been made with over a 30-fold increase in service availability.

  13. CD44v6-targeted T cells mediate potent antitumor effects against acute myeloid leukemia and multiple myeloma.

    PubMed

    Casucci, Monica; Nicolis di Robilant, Benedetta; Falcone, Laura; Camisa, Barbara; Norelli, Margherita; Genovese, Pietro; Gentner, Bernhard; Gullotta, Fabiana; Ponzoni, Maurilio; Bernardi, Massimo; Marcatti, Magda; Saudemont, Aurore; Bordignon, Claudio; Savoldo, Barbara; Ciceri, Fabio; Naldini, Luigi; Dotti, Gianpietro; Bonini, Chiara; Bondanza, Attilio

    2013-11-14

    Genetically targeted T cells promise to solve the feasibility and efficacy hurdles of adoptive T-cell therapy for cancer. Selecting a target expressed in multiple-tumor types and that is required for tumor growth would widen disease indications and prevent immune escape caused by the emergence of antigen-loss variants. The adhesive receptor CD44 is broadly expressed in hematologic and epithelial tumors, where it contributes to the cancer stem/initiating phenotype. In this study, silencing of its isoform variant 6 (CD44v6) prevented engraftment of human acute myeloid leukemia (AML) and multiple myeloma (MM) cells in immunocompromised mice. Accordingly, T cells targeted to CD44v6 by means of a chimeric antigen receptor containing a CD28 signaling domain mediated potent antitumor effects against primary AML and MM while sparing normal hematopoietic stem cells and CD44v6-expressing keratinocytes. Importantly, in vitro activation with CD3/CD28 beads and interleukin (IL)-7/IL-15 was required for antitumor efficacy in vivo. Finally, coexpressing a suicide gene enabled fast and efficient pharmacologic ablation of CD44v6-targeted T cells and complete rescue from hyperacute xenogeneic graft-versus-host disease modeling early and generalized toxicity. These results warrant the clinical investigation of suicidal CD44v6-targeted T cells in AML and MM.

  14. Effect of ion flux on helium retention in helium-irradiated tungsten

    NASA Astrophysics Data System (ADS)

    Rivera, A.; Valles, G.; Caturla, M. J.; Martin-Bragado, I.

    2013-05-01

    Helium retention in irradiated tungsten leads to swelling, pore formation, sample exfoliation and embrittlement with deleterious consequences in many applications. In particular, the use of tungsten in future nuclear fusion plants is proposed due to its good refractory properties. However, serious concerns about tungsten survivability stems from the fact that it must withstand severe irradiation conditions. In magnetic fusion as well as in inertial fusion (particularly with direct drive targets), tungsten components will be exposed to low and high energy ion irradiation (helium), respectively. A common feature is that the most detrimental situations will take place in pulsed mode, i.e., high flux irradiation. There is increasing evidence of a correlation between a high helium flux and an enhancement of detrimental effects on tungsten. Nevertheless, the nature of these effects is not well understood due to the subtleties imposed by the exact temperature profile evolution, ion energy, pulse duration, existence of impurities and simultaneous irradiation with other species. Object Kinetic Monte Carlo is the technique of choice to simulate the evolution of radiation-induced damage inside solids in large temporal and space scales. We have used the recently developed code MMonCa (Modular Monte Carlo simulator), presented at COSIRES 2012 for the first time, to study He retention (and in general defect evolution) in tungsten samples irradiated with high intensity helium pulses. The code simulates the interactions among a large variety of defects and during the irradiation stage and the subsequent annealing steps. The results show that the pulsed mode leads to significantly higher He retention at temperatures higher than 700 K. In this paper we discuss the process of He retention in terms of trap evolution. In addition, we discuss the implications of these findings for inertial fusion.

  15. Migration and release of helium-3 implanted in single-crystal nickel

    SciTech Connect

    Maki, J.T.

    1987-01-01

    Several nickel single-crystal samples were implanted with 150-keV helium-3 ions to doses between 9.2 x 10/sup 18/ and 2.0 x 10/sup 20/ m/sup -2/. After implantation, the samples were isochronally annealed at various temperatures between 300 and 1300/sup 0/C. Following each annealing step, helium distributions were measured by a nuclear-reaction technique called neutron depth profiling. The technique determines a helium profile from the measured energy distribution of emitted protons produced by the /sup 3/He(n,p)/sup 3/H reaction when a sample is placed in a thermal-neutron beam. The measured profiles were then deconvoluted by an iterative chi-square minimization method. The helium depth profiles can be compared to illustrate helium migration or loss as a function of annealing temperature. Two new results were determined by this experiment and may be summarized as follows. The first results was the demonstration of a helium-concentration-dependent release pattern where one sample with an initial helium dose of about 6 x 10/sup 19/ m/sup -2/ was the most stable and displayed the least amount of helium release up to annealing temperatures as high as 1300/sup 0/C. The second result was the observation that profile peaking (a narrowing of the helium distribution with an increase in peak concentration) occurred for samples with initial doses within a certain range when annealed at 1000/sup 0/C.ng-tool

  16. Properties of helium bubbles in covalent systems at the nanoscale: A combined numerical and experimental study

    NASA Astrophysics Data System (ADS)

    Dérès, J.; David, M.-L.; Alix, K.; Hébert, C.; Alexander, D. T. L.; Pizzagalli, L.

    2017-07-01

    The properties of nanometric-sized helium bubbles in silicon have been investigated using both spatially resolved electron-energy-loss spectroscopy combined with a recently developed method, and molecular-dynamics simulations. The experiments allowed for an accurate determination of size, aspect ratio, and helium density for a large number of single bubbles, whose diameters ranged from 6 to 20 nm. Very high helium densities, from 60 to 180 He nm-3, have been measured depending on the conditions, in stark contrast with previous investigations of helium bubbles in metal with similar sizes. To supplement experiments on a smaller scale, and to obtain insights into the silicon matrix state, atomistic calculations have been performed for helium bubbles in the diameter range 1-13 nm. Molecular-dynamics simulations revealed that the maximum attainable helium density is critically related to the strength of the silicon matrix, which tends to yield by amorphization at the highest density levels. Calculations give helium density values for isolated single bubbles that are typically lower than measurements. However, excellent agreement is recovered when the interactions between bubbles and the presence of helium interstitials in the matrix are taken into account. Both experiments and numerical simulations suggest that the Laplace-Young law cannot be used to predict helium density in nanometric-sized bubbles in a covalent material such as silicon.

  17. Lamb shift in the muonic helium ion

    SciTech Connect

    Martynenko, A. P.

    2007-07-15

    The Lamb shift (2P{sub 1/2}-2S{sub 1/2}) in the muonic helium ion ({mu}-{sub 2}{sup 4}He){sup +} is calculated with the account of contributions of orders {alpha}{sup 3}, {alpha}{sup 4}, {alpha}{sup 5}, and {alpha}{sup 6}. Special attention is given to corrections of the electron vacuum polarization, the nuclear structure, and recoil effects. The obtained numerical value of the Lamb shift 1381.72 meV can be considered as a reliable estimate for the comparison with experimental data.

  18. Rogue mantle helium and neon.

    PubMed

    Albarède, Francis

    2008-02-15

    The canonical model of helium isotope geochemistry describes the lower mantle as undegassed, but this view conflicts with evidence of recycled material in the source of ocean island basalts. Because mantle helium is efficiently extracted by magmatic activity, it cannot remain in fertile mantle rocks for long periods of time. Here, I suggest that helium with high 3He/4He ratios, as well as neon rich in the solar component, diffused early in Earth's history from low-melting-point primordial material into residual refractory "reservoir" rocks, such as dunites. The difference in 3He/4He ratios of ocean-island and mid-ocean ridge basalts and the preservation of solar neon are ascribed to the reservoir rocks being stretched and tapped to different extents during melting.

  19. Two Components of the RNA-Directed DNA Methylation Pathway Associate with MORC6 and Silence Loci Targeted by MORC6 in Arabidopsis

    PubMed Central

    Liu, Zhang-Wei; Zhou, Jin-Xing; Huang, Huan-Wei; Li, Yong-Qiang; Shao, Chang-Rong; Li, Lin; Cai, Tao; Chen, She

    2016-01-01

    The SU(VAR)3-9 homolog SUVH9 and the double-stranded RNA-binding protein IDN2 were thought to be components of an RNA-directed DNA methylation (RdDM) pathway in Arabidopsis. We previously found that SUVH9 interacts with MORC6 but how the interaction contributes to transcriptional silencing remains elusive. Here, our genetic analysis indicates that SUVH2 and SUVH9 can either act in the same pathway as MORC6 or act synergistically with MORC6 to mediate transcriptional silencing. Moreover, we demonstrate that IDN2 interacts with MORC6 and mediates the silencing of a subset of MORC6 target loci. Like SUVH2, SUVH9, and IDN2, other RdDM components including Pol IV, Pol V, RDR2, and DRM2 are also required for transcriptional silencing at a subset of MORC6 target loci. MORC6 was previously shown to mediate transcriptional silencing through heterochromatin condensation. We demonstrate that the SWI/SNF chromatin-remodeling complex components SWI3B, SWI3C, and SWI3D interact with MORC6 as well as with SUVH9 and then mediate transcriptional silencing. These results suggest that the RdDM components are involved not only in DNA methylation but also in MORC6-mediated heterochromatin condensation. This study illustrates how DNA methylation is linked to heterochromatin condensation and thereby enhances transcriptional silencing at methylated genomic regions. PMID:27171427

  20. Hopping diffusion of helium isotopes from samples of lunar soil

    NASA Astrophysics Data System (ADS)

    Anufriev, G. S.

    2010-10-01

    This paper reports on a detailed study of diffusion of helium isotopes from a sample of lunar soil (weight, 3.3 mg; bulk grain size, <74 μm; sampling depth, 118 cm in a 1.6-m-long core of lunar soil brought from the Moon by the Soviet automatic station Luna-24). The studies have been performed using step heating in the temperature range 300-1000°C in combination with a mass spectrometric isotope analysis of helium extracted at each temperature step. It has been demonstrated that the diffusion does not obey Fick’s law, which should be attributed to a large number of radiation damages in crystals of lunar soil minerals and can be described in terms of the formalism accepted for jump diffusion. The diffusion activation energy for both helium isotopes (4He, 3He) has been found to be identical and equal to 0.5 eV, and the frequency factors amount to 0.51 and 0.59 s-1, respectively. The random errors σ in the determination of these parameters are approximately equal to 5%. The lunar soil delivered to the Earth loses helium during the storage. At the beginning of the storage at room temperature, one gram of the lunar material under investigation loses approximately 3 × 109 helium atoms every second. It has been revealed that the jump diffusion of helium exhibits a strong isotopic effect: the light isotope 3He escapes at substantially higher rates. In order to prevent helium losses accompanied by isotope fractionation, the brought lunar soil should be stored at a low temperature.

  1. 26 CFR 1.338-6 - Allocation of ADSP and AGUB among target assets.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ..., III, IV, VI, and VII assets. (vi) Class VI assets. Class VI assets are all section 197 intangibles, as... 26 Internal Revenue 4 2010-04-01 2010-04-01 false Allocation of ADSP and AGUB among target assets... among target assets. (a) Scope—(1) In general. This section prescribes rules for allocating ADSP...

  2. Helium release during shale deformation: Experimental validation

    NASA Astrophysics Data System (ADS)

    Bauer, Stephen J.; Gardner, W. Payton; Heath, Jason E.

    2016-07-01

    This work describes initial experimental results of helium tracer release monitoring during deformation of shale. Naturally occurring radiogenic 4He is present in high concentration in most shales. During rock deformation, accumulated helium could be released as fractures are created and new transport pathways are created. We present the results of an experimental study in which confined reservoir shale samples, cored parallel and perpendicular to bedding, which were initially saturated with helium to simulate reservoir conditions, are subjected to triaxial compressive deformation. During the deformation experiment, differential stress, axial, and radial strains are systematically tracked. Release of helium is dynamically measured using a helium mass spectrometer leak detector. Helium released during deformation is observable at the laboratory scale and the release is tightly coupled to the shale deformation. These first measurements of dynamic helium release from rocks undergoing deformation show that helium provides information on the evolution of microstructure as a function of changes in stress and strain.

  3. Nickel-Salen supported paramagnetic nanoparticles for 6-His-target recombinant protein affinity purification.

    PubMed

    Rashid, Zahra; Ghahremanzadeh, Ramin; Nejadmoghaddam, Mohammad-Reza; Nazari, Mahboobeh; Shokri, Mohammad-Reza; Naeimi, Hossein; Zarnani, Amir-Hassan

    2017-03-24

    In this research, a simple, efficient, inexpensive, rapid and high yield method for the purification of 6×histidine-tagged recombinant protein was developed. For this purpose, manganese ferrite magnetic nanoparticles (MNPs) were synthesized through a co-precipitation method and then they were conveniently surface-modified with tetraethyl orthosilicate (TEOS) in order to prevent oxidation and form high density of hydroxyl groups. Next, the salen ligand was prepared from condensation reaction of salicylaldehyde and 3-aminopropyl (trimethoxy) silane (APTMS) in 1:1 molar ratio; followed by complexation with Ni(OAc)2.4H2O. Finally, the prepared Ni(II)-salen complex conjugated to silica coated MNPs and MnFe2O4@SiO2@Ni-Salen complex nanoparticles were obtained. The functionalized nanoparticles were spherical with an average diameter around 70nm. The obtained MNPs had a saturation magnetization about 54 emu/g and had super paramagnetic character. These MNPs were used efficiently to enrich recombinant histidine-tagged (His-tagged) protein-A from bacterial cell lysate. In about 45min, highly pure His-tagged recombinant protein was obtained, as judged by SDS-PAGE analysis and silver staining. The amount of target protein in flow through and washing fractions was minimal denoting the high efficiency of purification process. The average capacity of the matrix was found to be high and about 180±15mgg(-1) (protein/MnFe2O4@SiO2@Ni-Salen complex). Collectively, purification process with MnFe2O4@SiO2@Ni-Salen complex nanoparticles is rapid, efficient, selective and whole purification can be carried out in only a single tube without the need for expensive systems.

  4. Pulsed helium ionization detection system

    DOEpatents

    Ramsey, R.S.; Todd, R.A.

    1985-04-09

    A helium ionization detection system is provided which produces stable operation of a conventional helium ionization detector while providing improved sensitivity and linearity. Stability is improved by applying pulsed dc supply voltage across the ionization detector, thereby modifying the sampling of the detectors output current. A unique pulse generator is used to supply pulsed dc to the detector which has variable width and interval adjust features that allows up to 500 V to be applied in pulse widths ranging from about 150 nsec to about dc conditions.

  5. Pulsed helium ionization detection system

    DOEpatents

    Ramsey, Roswitha S.; Todd, Richard A.

    1987-01-01

    A helium ionization detection system is provided which produces stable operation of a conventional helium ionization detector while providing improved sensitivity and linearity. Stability is improved by applying pulsed dc supply voltage across the ionization detector, thereby modifying the sampling of the detectors output current. A unique pulse generator is used to supply pulsed dc to the detector which has variable width and interval adjust features that allows up to 500 V to be applied in pulse widths ranging from about 150 nsec to about dc conditions.

  6. Negative ions in liquid helium

    NASA Astrophysics Data System (ADS)

    Khrapak, A. G.; Schmidt, W. F.

    2011-05-01

    The structure of negative ions in liquid 4He is analyzed. The possibility of cluster or bubble formation around impurity ions of both signs is discussed. It is shown that in superfluid helium, bubbles form around negative alkaline earth metal ions and clusters form around halogen ions. The nature of "fast" and "exotic" negative ions is also discussed. It is assumed that "fast" ions are negative ions of helium excimer molecules localized inside bubbles. "Exotic" ions are stable negative impurity ions, which are always present in small amounts in gas discharge plasmas. Bubbles or clusters with radii smaller the radius of electron bubbles develop around these ions.

  7. 43 CFR 3195.20 - Who must purchase major helium requirements from Federal helium suppliers?

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 43 Public Lands: Interior 2 2013-10-01 2013-10-01 false Who must purchase major helium requirements from Federal helium suppliers? 3195.20 Section 3195.20 Public Lands: Interior Regulations Relating... (3000) HELIUM CONTRACTS Federal Agency Requirements § 3195.20 Who must purchase major helium...

  8. 43 CFR 3195.20 - Who must purchase major helium requirements from Federal helium suppliers?

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 43 Public Lands: Interior 2 2014-10-01 2014-10-01 false Who must purchase major helium requirements from Federal helium suppliers? 3195.20 Section 3195.20 Public Lands: Interior Regulations Relating... (3000) HELIUM CONTRACTS Federal Agency Requirements § 3195.20 Who must purchase major helium...

  9. 43 CFR 3195.20 - Who must purchase major helium requirements from Federal helium suppliers?

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 43 Public Lands: Interior 2 2011-10-01 2011-10-01 false Who must purchase major helium requirements from Federal helium suppliers? 3195.20 Section 3195.20 Public Lands: Interior Regulations Relating... (3000) HELIUM CONTRACTS Federal Agency Requirements § 3195.20 Who must purchase major helium...

  10. 43 CFR 3195.20 - Who must purchase major helium requirements from Federal helium suppliers?

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 43 Public Lands: Interior 2 2012-10-01 2012-10-01 false Who must purchase major helium requirements from Federal helium suppliers? 3195.20 Section 3195.20 Public Lands: Interior Regulations Relating... (3000) HELIUM CONTRACTS Federal Agency Requirements § 3195.20 Who must purchase major helium...

  11. 48 CFR 52.208-8 - Required Sources for Helium and Helium Usage Data.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... Management, Amarillo Field Office, Helium Operations, located at 801 South Fillmore Street, Suite 500... helium sales contract with the Bureau of Land Management (BLM) and that is on the BLM Amarillo Field.../www/amfo/amfo_home.html. Major helium requirement means an estimated refined helium requirement...

  12. Importance of the continuum-continuum couplings in the 6Li elastic breakup on different target masses

    NASA Astrophysics Data System (ADS)

    Mukeru, B.; Lekala, M. L.

    2017-09-01

    A theoretical study of 6Li breakup on target masses ranging from A = 58 to 208 is performed. It is obtained that when continuum-continuum couplings are included in the potential coupling matrix, they substantially reduce the total and nuclear breakup cross sections, while the Coulomb breakup cross sections for the medium and heavy target masses are increased. When these couplings are excluded, we show that the total and nuclear breakup cross sections depend linearly on AT1/3, namely they decrease linearly as the mass of the target increases. In the same case, the Coulomb breakup cross section depends linearly with the charge of the target ZT (decreases as ZT increases). We found that this linearity is destroyed when these couplings are included. However, in this case, it is the Coulomb-nuclear interference that also depends linearly with the target charge (increase with ZT).

  13. The ITM2B (BRI2) gene is a target of BCL6 repression: Implications for lymphomas and neurodegenerative diseases.

    PubMed

    Baron, Beverly W; Baron, Rebecca M; Baron, Joseph M

    2015-05-01

    The human BCL6 gene encodes a transcriptional repressor that is crucial for germinal center B cell development and T follicular helper cell differentiation. It is involved in the pathogenesis of certain human lymphomas. In an effort to identify targets of BCL6 repression, we used a previously described cell system in which BCL6 repressive effects are inhibited, followed by subtractive hybridization, and identified the integral membrane 2B gene (ITM2B, formerly BRI2) as a potential target. Here we show that BCL6 can bind to its preferential consensus binding site within the first intron of ITM2B and represses its transcription. Knockdown of endogenous BCL6 in a human B cell lymphoma line increases ITM2B expression. Further, there is an inverse relationship between the expression levels of BCL6 and ITM2B proteins in 16 human B- and T-cell lymphomas studied by immunohistochemistry. Both the BCL6 and ITM2B proteins are expressed ubiquitously. Similar to some other targets of BCL6, a short form of the ITM2B protein generated by alternative splicing induces apoptosis in hematopoietic cell lines. Molecular alterations in the ITM2B gene are associated with two neurodegenerative diseases, Familial British and Familial Danish dementia. ITM2B dysfunction also may be relevant for the development of Alzheimer's disease. Our data confirm ITM2B as a target of BCL6 repression in lymphoma. A further understanding of the genes that function as regulators of the ITM2B protein may provide insights for the development of new molecular tools not only for targeted lymphoma therapy but also for the treatment of these dementias.

  14. Helium in deep circulating groundwater in the Great Hungarian Plain: Flow dynamics and crustal and mantle helium fluxes

    NASA Astrophysics Data System (ADS)

    Stute, M.; Sonntag, C.; Deák, J.; Schlosser, P.

    1992-05-01

    Observed helium concentrations in deep circulating groundwater of the sedimentary basin of the Great Hungarian Plain (GHP), Hungary, cover a range of three orders of magnitude (≈4 ·10 -8 to 4 · 10 -5 ccSTP g-1). 3He /4He ratios and noble gas concentrations are used to separate helium components originating from the atmosphere, tritium decay, crustal production, and mantle degassing. The characteristic distribution of measured helium concentrations and isotope ratios can be reproduced qualitatively by a simple two-dimensional advection/diffusion model. Other simple models isolating parts of the regional flow domain (recharge, discharge, and horizontal flow) are discussed and applied to derive quantitative information on helium fluxes due to degassing of the Earth's crust /mantle and on the dynamics of groundwater flow. The estimated helium flux of 0.7-4.5 · 10 9 atoms 4He m -2 s -1 is lower than values derived from other deep groundwater circulation systems, probably because the relatively young upper few thousand meters of the sedimentary basin (Tertiary to Quaternary age) shield the flux from the deeper crust. The high mantle helium flux of up to 4.2 · 10 8 atoms 4He m -2 s -1 is probably related to the Miocene volcanism or to continuing intrusion accompanying extension. By fitting calculated helium depth profiles to measured data in the discharge area, vertical flow velocities of the order of 1.5 mm y -1 are estimated. Assuming that a flux of 0.7-4.5 · 10 9 atoms 4He m -2 s -1 is representative for the entire basin, the turnover time of the regional groundwater flow system is estimated to be about 10 6 y.

  15. Applying the helium ionization detector in chromatography

    NASA Technical Reports Server (NTRS)

    Gibson, E. K.; Andrawes, F. F.; Brazell, R. S.

    1981-01-01

    High noise levels and oversensitivity of helium detector make flame-ionization and thermal-conductivity detectors more suitable for chromotography. Deficiencies are eliminated by modifying helium device to operate in saturation rather than multiplication mode. Result is low background current, low noise, high stability, and high sensitivity. Detector analyzes halocarbons, hydrocarbons, hydrogen cyanide, ammonia, and inorganics without requiring expensive research-grade helium.

  16. 30 CFR 556.11 - Helium.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 30 Mineral Resources 2 2013-07-01 2013-07-01 false Helium. 556.11 Section 556.11 Mineral Resources... § 556.11 Helium. (a) Each lease issued or continued under these regulations shall be subject to a... helium from all gas produced from the leased area. (b) In case the United States elects to take...

  17. 30 CFR 556.11 - Helium.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 30 Mineral Resources 2 2012-07-01 2012-07-01 false Helium. 556.11 Section 556.11 Mineral Resources... § 556.11 Helium. (a) Each lease issued or continued under these regulations shall be subject to a... helium from all gas produced from the leased area. (b) In case the United States elects to take...

  18. 30 CFR 556.11 - Helium.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 30 Mineral Resources 2 2014-07-01 2014-07-01 false Helium. 556.11 Section 556.11 Mineral Resources... § 556.11 Helium. (a) Each lease issued or continued under these regulations shall be subject to a... helium from all gas produced from the leased area. (b) In case the United States elects to take...

  19. 30 CFR 256.11 - Helium.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 30 Mineral Resources 2 2011-07-01 2011-07-01 false Helium. 256.11 Section 256.11 Mineral Resources... Sulphur Management, General § 256.11 Helium. (a) Each lease issued or continued under these regulations... of and the right to extract helium from all gas produced from the leased area. (b) In case the...

  20. 21 CFR 184.1355 - Helium.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Helium. 184.1355 Section 184.1355 Food and Drugs....1355 Helium. (a) Helium (empirical formula He, CAS Reg. No. 7440-59-7) is a colorless, odorless, flavorless, nonflammable, inert gas. It is lighter than air and is produced by the liquefaction and...

  1. 21 CFR 184.1355 - Helium.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 3 2011-04-01 2011-04-01 false Helium. 184.1355 Section 184.1355 Food and Drugs... Substances Affirmed as GRAS § 184.1355 Helium. (a) Helium (empirical formula He, CAS Reg. No. 7440-59-7) is a colorless, odorless, flavorless, nonflammable, inert gas. It is lighter than air and is produced by the...

  2. 43 CFR 3100.1 - Helium.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... INTERIOR MINERALS MANAGEMENT (3000) OIL AND GAS LEASING Onshore Oil and Gas Leasing: General § 3100.1 Helium. The ownership of and the right to extract helium from all gas produced from lands leased or... 43 Public Lands: Interior 2 2011-10-01 2011-10-01 false Helium. 3100.1 Section 3100.1 Public Lands...

  3. 21 CFR 184.1355 - Helium.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 3 2012-04-01 2012-04-01 false Helium. 184.1355 Section 184.1355 Food and Drugs... Substances Affirmed as GRAS § 184.1355 Helium. (a) Helium (empirical formula He, CAS Reg. No. 7440-59-7) is a colorless, odorless, flavorless, nonflammable, inert gas. It is lighter than air and is produced by the...

  4. 43 CFR 3100.1 - Helium.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... INTERIOR MINERALS MANAGEMENT (3000) OIL AND GAS LEASING Onshore Oil and Gas Leasing: General § 3100.1 Helium. The ownership of and the right to extract helium from all gas produced from lands leased or... 43 Public Lands: Interior 2 2013-10-01 2013-10-01 false Helium. 3100.1 Section 3100.1 Public Lands...

  5. 21 CFR 184.1355 - Helium.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Helium. 184.1355 Section 184.1355 Food and Drugs... Substances Affirmed as GRAS § 184.1355 Helium. (a) Helium (empirical formula He, CAS Reg. No. 7440-59-7) is a colorless, odorless, flavorless, nonflammable, inert gas. It is lighter than air and is produced by the...

  6. 43 CFR 3100.1 - Helium.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... INTERIOR MINERALS MANAGEMENT (3000) OIL AND GAS LEASING Onshore Oil and Gas Leasing: General § 3100.1 Helium. The ownership of and the right to extract helium from all gas produced from lands leased or... 43 Public Lands: Interior 2 2014-10-01 2014-10-01 false Helium. 3100.1 Section 3100.1 Public Lands...

  7. 21 CFR 184.1355 - Helium.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 3 2013-04-01 2013-04-01 false Helium. 184.1355 Section 184.1355 Food and Drugs... Substances Affirmed as GRAS § 184.1355 Helium. (a) Helium (empirical formula He, CAS Reg. No. 7440-59-7) is a colorless, odorless, flavorless, nonflammable, inert gas. It is lighter than air and is produced by the...

  8. 43 CFR 3100.1 - Helium.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... INTERIOR MINERALS MANAGEMENT (3000) OIL AND GAS LEASING Onshore Oil and Gas Leasing: General § 3100.1 Helium. The ownership of and the right to extract helium from all gas produced from lands leased or... 43 Public Lands: Interior 2 2012-10-01 2012-10-01 false Helium. 3100.1 Section 3100.1 Public Lands...

  9. A helium-3 refrigerator employing capillary confinement of liquid cryogen

    NASA Technical Reports Server (NTRS)

    Ennis, D. J.; Kittel, P.; Brooks, W.; Miller, A.; Spivak, A. L.

    1983-01-01

    A condensation refrigerator suitable for operation in a zero gravity space environment was constructed. The condensed liquid refrigerant is confined by surface tension inside a porous metal matrix. Helium-4 and helium-3 gases were condensed and held in a copper matrix. Evaporative cooling of confined liquid helium-4 resulted in a temperature of 1.4K. Using a zeolite adsorption pump external to the cryostat, a temperature of 0.6 K was achieved through evaporative cooling of liquid helium-3. The amount of time required for complete evaporation of a controlled mass of liquid helium-4 contained in the copper matrix was measured as a function of the applied background power. For heating powers below 18 mW the measured times are consistent with the normal boiling of the confined volume of liquid refrigerant. At background powers above 18 mW the rapid rise in the temperature of the copper matrix the signature of the absence of confined liquid occurs in a time a factor of two shorter than that expected on the basis of an extrapolation of the low power data.

  10. Helium and ground temperature surveys at Steamboat Springs, Colorado

    SciTech Connect

    McCarthy, K.P.; Been, J.; Reimer, G.M.; Bowles, C.G.; Murrey, D.G.; Ruscetta, C.A.

    1982-07-01

    As demonstrated in Steamboat Springs, Colorado, helium and shallow temperature surveys are quick, inexpensive geothermal exploration methods that can be used together with excellent results. Steamboat Springs, in northwestern Colorado, lies primarily upon terrace gravels and alluvium with the major structure being a north-trending normal fault passing through the western portion of the city. Work by Christopherson (1979) indicates that the Steamboat warm springs are not laterally connected at shallow depth with Routt Hot Springs, 6 km to the north, although both resource areas are fault controlled. A shallow temperature survey was conducted in the city to determine the usefulness of this method in a low temperature resource area. Several extraneous factors influencing shallow temperature measurements were dealt with by field technique or subsequent analysis. A helium survey was conducted to compare with temperature results. Sixty-two soil helium samples were taken, using an interval of .1 to .2 Km, twice the density of the 18 temperature probe stations. A mobile spectrometer allowed immediate analysis of helium samples. A direct correlation of temperature to helium value at each site is not valid due to the high solubility of this gas. The contoured data from each method does correlate well and indicates that two faults control the resource in Steamboat Springs. Although these surveys should always be used to supplement other data, their utility in this study was readily apparent.

  11. 43 CFR 3195.35 - What happens if I have an outstanding obligation to purchase refined helium under a Helium...

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... obligation to purchase refined helium under a Helium Distribution Contract? 3195.35 Section 3195.35 Public... OF THE INTERIOR MINERALS MANAGEMENT (3000) HELIUM CONTRACTS Federal Helium Supplier Requirements § 3195.35 What happens if I have an outstanding obligation to purchase refined helium under a Helium...

  12. Target and beam-target spin asymmetries in exclusive π+ and π– electroproduction with 1.6- to 5.7-GeV electrons

    DOE PAGES

    Bosted, P. E.; Biselli, A. S.; Careccia, S.; ...

    2016-11-01

    Here, beam-target double-spin asymmetries and target single-spin asymmetries in exclusive π+ and quasiexclusive π– electroproduction were obtained from scattering of 1.6- to 5.7-GeV longitudinally polarized electrons from longitudinally polarized protons (for π+) and deuterons (for π–) using the CEBAF Large Acceptance Spectrometer (CLAS) at Jefferson Lab. The kinematic range covered is 1.1 < W < 2.6 GeV and 0.05 < Q2 < 5GeV2, with good angular coverage in the forward hemisphere. The asymmetry results were divided into approximately 40 000 kinematic bins for π+ from free protons and 15 000 bins for π– production from bound nucleons in the deuteron.more » The present results are found to be in reasonable agreement with fits to previous world data for W < 1.7 GeV and Q2 < 0.5GeV2, with discrepancies increasing at higher values of Q2, especially for W > 1.5 GeV. Very large target-spin asymmetries are observed for W > 1.6 GeV. When combined with cross-section measurements, the present results can provide powerful constraints on nucleon resonance amplitudes at moderate and large values of Q2, for resonances with masses as high as 2.3 GeV.« less

  13. Target and beam-target spin asymmetries in exclusive π+ and π- electroproduction with 1.6- to 5.7-GeV electrons

    NASA Astrophysics Data System (ADS)

    Bosted, P. E.; Biselli, A. S.; Careccia, S.; Dodge, G.; Fersch, R.; Guler, N.; Kuhn, S. E.; Pierce, J.; Prok, Y.; Zheng, X.; Adhikari, K. P.; Adikaram, D.; Akbar, Z.; Amaryan, M. J.; Anefalos Pereira, S.; Asryan, G.; Avakian, H.; Badui, R. A.; Ball, J.; Baltzell, N. A.; Battaglieri, M.; Batourine, V.; Bedlinskiy, I.; Boiarinov, S.; Briscoe, W. J.; Bültmann, S.; Burkert, V. D.; Cao, T.; Carman, D. S.; Celentano, A.; Chandavar, S.; Charles, G.; Chetry, T.; Ciullo, G.; Clark, L.; Colaneri, L.; Cole, P. L.; Contalbrigo, M.; Cortes, O.; Crede, V.; D'Angelo, A.; Dashyan, N.; De Vita, R.; Deur, A.; Djalali, C.; Dupre, R.; Egiyan, H.; El Alaoui, A.; El Fassi, L.; Eugenio, P.; Fanchini, E.; Fedotov, G.; Filippi, A.; Fleming, J. A.; Forest, T. A.; Fradi, A.; Garçon, M.; Gevorgyan, N.; Ghandilyan, Y.; Gilfoyle, G. P.; Giovanetti, K. L.; Girod, F. X.; Gleason, C.; Gohn, W.; Golovatch, E.; Gothe, R. W.; Griffioen, K. A.; Guo, L.; Hafidi, K.; Hanretty, C.; Harrison, N.; Hattawy, M.; Heddle, D.; Hicks, K.; Holtrop, M.; Hughes, S. M.; Ilieva, Y.; Ireland, D. G.; Ishkhanov, B. S.; Isupov, E. L.; Jenkins, D.; Jiang, H.; Jo, H. S.; Joo, K.; Joosten, S.; Keller, D.; Khandaker, M.; Kim, W.; Klein, A.; Klein, F. J.; Kubarovsky, V.; Kuleshov, S. V.; Lanza, L.; Lenisa, P.; Livingston, K.; Lu, H. Y.; MacGregor, I. J. D.; Markov, N.; McCracken, M. E.; McKinnon, B.; Meyer, C. A.; Minehart, R.; Mirazita, M.; Mokeev, V.; Movsisyan, A.; Munevar, E.; Munoz Camacho, C.; Nadel-Turonski, P.; Net, L. A.; Ni, A.; Niccolai, S.; Niculescu, G.; Niculescu, I.; Osipenko, M.; Ostrovidov, A. I.; Paremuzyan, R.; Park, K.; Pasyuk, E.; Peng, P.; Phelps, W.; Pisano, S.; Pogorelko, O.; Price, J. W.; Procureur, S.; Protopopescu, D.; Puckett, A. J. R.; Raue, B. A.; Ripani, M.; Rizzo, A.; Rosner, G.; Rossi, P.; Roy, P.; Sabatié, F.; Salgado, C.; Schumacher, R. A.; Seder, E.; Sharabian, Y. G.; Simonyan, A.; Skorodumina, Iu.; Smith, G. D.; Sparveris, N.; Stankovic, Ivana; Stepanyan, S.; Strakovsky, I. I.; Strauch, S.; Sytnik, V.; Taiuti, M.; Tian, Ye; Torayev, B.; Ungaro, M.; Voskanyan, H.; Voutier, E.; Walford, N. K.; Watts, D. P.; Wei, X.; Weinstein, L. B.; Wood, M. H.; Zachariou, N.; Zana, L.; Zhang, J.; Zhao, Z. W.; Zonta, I.; CLAS Collaboration

    2016-11-01

    Beam-target double-spin asymmetries and target single-spin asymmetries in exclusive π+ and quasiexclusive π- electroproduction were obtained from scattering of 1.6- to 5.7-GeV longitudinally polarized electrons from longitudinally polarized protons (for π+) and deuterons (for π-) using the CEBAF Large Acceptance Spectrometer (CLAS) at Jefferson Lab. The kinematic range covered is 1.1 6 GeV and 0.05 1.5 GeV. Very large target-spin asymmetries are observed for W >1.6 GeV. When combined with cross-section measurements, the present results can provide powerful constraints on nucleon resonance amplitudes at moderate and large values of Q2, for resonances with masses as high as 2.3 GeV.

  14. Spectroscopy of barium atoms in liquid and solid helium matrices

    NASA Astrophysics Data System (ADS)

    Lebedev, V.; Moroshkin, P.; Weis, A.

    2011-08-01

    We present an exhaustive overview of optical absorption and laser-induced fluorescence lines of Ba atoms in liquid and solid helium matrices in visible and near-infrared spectral ranges. Due to the increased density of isolated atoms, we have found a large number of spectral lines that were not observed in condensed helium matrices before. We have also measured the lifetimes of metastable states. The lowest 3D1 metastable state has lifetime of 2.6 s and can be used as an intermediate state in two-step excitations of high-lying states. Various matrix-induced radiationless population transfer channels have been identified.

  15. Why Helium Ends in "-Ium"

    ERIC Educational Resources Information Center

    Jensen, William B.; Holme, Thomas; Cooper, Melanie; White, Carol

    2004-01-01

    Edward Frankland and Norman Lockyer researched upon a gaseous spectra in relation to the physical constitution of the sun and named it as "helium" (from Greek "helios" meaning "sun"). Since Lockyer apparently never formally proposed the name in print, it is not known why he chose to use a metallic end "ium".

  16. Why Helium Ends in "-Ium"

    ERIC Educational Resources Information Center

    Jensen, William B.; Holme, Thomas; Cooper, Melanie; White, Carol

    2004-01-01

    Edward Frankland and Norman Lockyer researched upon a gaseous spectra in relation to the physical constitution of the sun and named it as "helium" (from Greek "helios" meaning "sun"). Since Lockyer apparently never formally proposed the name in print, it is not known why he chose to use a metallic end "ium".

  17. Specific heat of solid helium

    NASA Astrophysics Data System (ADS)

    Lin, Xi; Clark, Anthony; Kim, Eunseong; Chan, Moses

    2006-03-01

    Recently superflow in solid ^4He was found below 200mK via a torsional oscillator technique^1. While there were a number of measurements on the specific heat of solid helium carried out down to 100mK, there is no evidence of a heat capacity signature related to the onset of the supersolid phase^2. A serious experimental challenge is discerning the small specific heat of solid helium from that of the metallic cells which are typically used to confine the solid. We have recently begun a new measurement of the heat capacity of solid helium contained in a silicon cell. The heat capacity of the silicon cell below 300mK is always less than that of the solid helium sample. Results of the measurement will be presented. This work is supported by NSF under grant number 0207071. [1] E. Kim and M. H. W. Chan, Nature 427, 225 (2004); E. Kim and M. H. W. Chan, Science 305, 1941 (2004); E. Kim and M. H. W. Chan, J. Low Temp. Phys. 138, 859 (2005). [2] S. H. Castles and E. D. Adams, J. Low Temp. Phys. 19, 397 (1975); B. H'ebral et al., Phonons in Condensed Matter, edited by H. J. Maris (Plenum, New York, 1980), pg. 169; A. C. Clark and M. H. W. Chan, J. Low Temp. Phys. 138, 853 (2005).

  18. Helium diffusion in the sun

    NASA Technical Reports Server (NTRS)

    Bahcall, J. N.; Pinsonneault, M. H.

    1992-01-01

    We calculate improved standard solar models using the new Livermore (OPAL) opacity tables, an accurate (exportable) nuclear energy generation routine which takes account of recent measurements and analyses, and the recent Anders-Grevesse determination of heavy element abundances. We also evaluate directly the effect of the diffusion of helium with respect to hydrogen on the calculated neutrino fluxes, on the primordial solar helium abundance, and on the depth of the convective zone. Helium diffusion increases the predicted event rates by about 0.8 SNU, or 11 percent of the total rate, in the chlorine solar neutrino experiment, by about 3.5 SNU, or 3 percent, in the gallium solar neutrino experiments, and by about 12 percent in the Kamiokande and SNO solar neutrino experiments. The best standard solar model including helium diffusion and the most accurate nuclear parameters, element abundances, and radiative opacity predicts a value of 8.0 SNU +/- 3.0 SNU for the C1-37 experiment and 132 +21/-17 SNU for the Ga - 71 experiment, where the uncertainties include 3 sigma errors for all measured input parameters.

  19. Design and operation of a horizontal liquid helium flow facility

    SciTech Connect

    Van Sciver, S.W.; Wiesend, J.G. II

    1988-01-01

    The University of Wisconsin horizontal liquid helium flow facility (LHFF) consists of a five meter long 20 cm ID horizontal dewar connected to two end boxes. Several heat exchanger inserts have been built to allow variable temperature operation of 1.6 K less than or equal to T less than or equal to 4.2 K. A centrifugal pump is installed at one end of the facility permitting experiments in forced flow liquid helium up to 100 gm/s. The horizontal design allows experimentation on long straight test sections which may be used either to study fundamental properties of heat and mass transfer in helium or prototype cryogenic components under realistic conditions. A detailed description of the design and operating experience of the LHFF is presented. 5 refs., 5 figs.

  20. An automatic purification system for laboratory helium gas recovery

    SciTech Connect

    Kadi, F.J.

    1982-01-01

    An automatic liquid nitrogen cooled helium purifier is described. It can handle up to 20% air contaminants by volume while delivering up to 0.8 g/s of helium with less than 50 ppm by volume of impurities. A unique fast regenerating adsorption column was employed which permits an 80% on-stream time for all contamination levels greater than 2%. Liquid nitrogen consumption for a 2% air contamination test case averaged 0.6 liquid liters of nitrogen per equivalent liquid liter of pure helium produced. Subsequent recorded discussion concerned the regeneration gas discharged to the atmostphere. A purifier flowsheet is presented as well as a photo of the automatic purifier.

  1. Measurements of the nonthermal helium escape from Mars

    NASA Astrophysics Data System (ADS)

    Barabash, S.; Kallio, E.; Lundin, R.; Koskinen, H.

    1995-11-01

    The automatic space plasma experiment with a rotating analyzer (ASPERA) onboard the Phobos 2 spacecraft has recently revealed the presence of planetary He+ ions at Mars (Barabash and Norberg, 1994). In the present work the analysis is continued in order to estimate the total outflow of the He+ ions which are swept away by the solar wind. For the Phobos epoch the total He+ outflow rate was found to be (1.2+/-0.6)×1024 ions/s. The escape occurs mainly near the Martian magnetopause. Considering extreme errors in the measurements, the maximum helium outflow could range up to 2.4×1024 s-1. From a scaling of the helium profile suggested by Moroz et al. (1990) to obtain the measured loss rate, one can deduce the helium abundance in the Martian upper atmosphere. It turns out that helium is a dominant gas in the Martian exosphere at altitudes between 500 and 1250 km. However, recently reported observations of the weak EUV emissions (108 photons) from the Martian He I suggest an abundance that is 18.5 times lower (Krasnopolsky et al., 1994). Possible reasons for this disagreement are discussed. The helium production rate near Mars can, in turn, be roughly estimated from the production rate for the Earth by using a scaling argument, since the only source of helium in the atmospheres of the terrestrial planets is radioactive decay of certain isotopes of uranium and thorium. Present estimates suggest a degassing rate of 8×1022 atoms/s only (Krasnopolsky et al., 1993). However, under steady state conditions one would expect the production and loss rates to be equal. The discrepancy leads us to the conclusion that either the helium degassing rate should be corrected (or the amount of uranium is higher on Mars than anticipated) or helium may also be delivered on Mars by other sources, for example, as solar wind α particles. The observed high total outflow of ions which are 4 times heavier than protons may result in an effective mass loading. Thus helium may play an important

  2. Interactions of satellite-speed helium atoms with satellite-surfaces. 1: Spatial distributions of reflected helium atoms

    NASA Technical Reports Server (NTRS)

    Liu, S. M.; Rodgers, W. E.; Knuth, E. L.

    1975-01-01

    Interactions of satellite-speed helium atoms with practical satellite surfaces were investigated experimentally, and spatial distributions of satellite-speed helium beams scattered from four different engineering surfaces were measured. The 7000 m/sec helium beams were produced using an arc-heated supersonic molecular beam source. The test surfaces included cleaned 6061-T6 aluminum plate, anodized aluminum foil, white paint, and quartz surfaces. Both in-plane (in the plane containing the incident beam and the surface normal) and out-of-plane spatial distributions of reflected helium atoms were measured for six different incidence angles (0, 15, 30, 45, 60, and 75 deg from the surface normal). It was found that a large fraction of the incident helium atoms were scattered back in the vicinity of the incoming beam, particularly in the case of glancing incidence angles. This unexpected scattering feature results perhaps from the gross roughness of these test surfaces. This prominent backscattering could yield drag coefficients which are higher than for surfaces with either forward-lobed or diffusive (cosine) scattering patterns.

  3. A critical role for alternative polyadenylation factor CPSF6 in targeting HIV-1 integration to transcriptionally active chromatin.

    PubMed

    Sowd, Gregory A; Serrao, Erik; Wang, Hao; Wang, Weifeng; Fadel, Hind J; Poeschla, Eric M; Engelman, Alan N

    2016-02-23

    Integration is vital to retroviral replication and influences the establishment of the latent HIV reservoir. HIV-1 integration favors active genes, which is in part determined by the interaction between integrase and lens epithelium-derived growth factor (LEDGF)/p75. Because gene targeting remains significantly enriched, relative to random in LEDGF/p75 deficient cells, other host factors likely contribute to gene-tropic integration. Nucleoporins 153 and 358, which bind HIV-1 capsid, play comparatively minor roles in integration targeting, but the influence of another capsid binding protein, cleavage and polyadenylation specificity factor 6 (CPSF6), has not been reported. In this study we knocked down or knocked out CPSF6 in parallel or in tandem with LEDGF/p75. CPSF6 knockout changed viral infectivity kinetics, decreased proviral formation, and preferentially decreased integration into transcriptionally active genes, spliced genes, and regions of chromatin enriched in genes and activating histone modifications. LEDGF/p75 depletion by contrast preferentially altered positional integration targeting within gene bodies. Dual factor knockout reduced integration into genes to below the levels observed with either single knockout and revealed that CPSF6 played a more dominant role than LEDGF/p75 in directing integration to euchromatin. CPSF6 complementation rescued HIV-1 integration site distribution in CPSF6 knockout cells, but complementation with a capsid binding mutant of CPSF6 did not. We conclude that integration targeting proceeds via two distinct mechanisms: capsid-CPSF6 binding directs HIV-1 to actively transcribed euchromatin, where the integrase-LEDGF/p75 interaction drives integration into gene bodies.

  4. Plasma action on helium flow in cold atmospheric pressure plasma jet experiments

    NASA Astrophysics Data System (ADS)

    Darny, T.; Pouvesle, J.-M.; Fontane, J.; Joly, L.; Dozias, S.; Robert, E.

    2017-10-01

    In this work, helium flow modifications, visualized by schlieren imaging, induced by the plasma generated in a plasma jet have been studied in conditions used for biomedical treatments (jet being directed downwards with a low helium flow rate). It has been shown that the plasma action can shift up to few centimeters downstream the effects of buoyancy, which allows to the helium flow to reach a target below in conditions for which it is not the case when the plasma is off. This study reveals the critical role of large and long lifetime negative ions during repetitive operations in the kHz regime, inducing strong modifications in the gas propagation. The cumulative added streamwise momentum transferred to ambient air surrounding molecules resulting from a series of applied voltage pulses induces a gradual built up of a helium channel on tens of millisecond timescale. In some conditions, a remarkable stable cylindrical helium channel can be generated to the target with plasma supplied by negative polarity voltage pulses whereas a disturbed flow results from positive polarity operation. This has a direct effect on air penetration in the helium channel and then on the reactive species production over the target which is of great importance for biomedical applications. It has also been shown that with an appropriate combination of negative and positive polarity pulses, it is possible to benefit from both polarity features in order to optimize the plasma plume propagation and plasma delivery to a target.

  5. Helium embrittlement of a lamellar titanium aluminide

    NASA Astrophysics Data System (ADS)

    Magnusson, P.; Chen, J.; Jung, P.; Sauvage, T.; Hoffelner, W.; Spätig, Ph.

    2013-03-01

    Embrittlement by helium was investigated in a lamellar TiAl alloy under two conditions: Specimens were implanted to various amounts of helium up to 762 appm at temperatures from 630 °C to 1000 °C and some of them subsequently creep-tested at the same temperature under stresses from 150 to 300 MPa. The microstructure and fracture surfaces of creep-deformed and non-creep-deformed specimens were then studied by transmission electron microscopy (TEM) and by scanning electron microscopy (SEM), respectively. Specimens were implanted to various amounts of helium at a low temperature (150 °C) and post-implantation annealed at elevated temperatures for TEM studies. Embrittlement was revealed by reduction in time- and strain-to-rupture and by a transition in fracture surface from ductile to an inter-lamellar appearance. Embrittlement occurred above a critical He concentration, which decreased from about 10 appm at 700 °C to below 6 appm at 900 °C. TEM showed that embrittlement could be associated to reaching a critical bubble diameter of about 5 nm. Bubble diameters increased with increasing temperature ranging in high-temperature implanted specimens from about 3 nm (630 °C) to 20 nm (1000 °C) and in post-implantation annealed ones from 1.2 nm (600 °C) to 2.2 nm (900 °C), respectively. With increasing temperature, the bubble distribution grew less homogenous with a lower density of larger bubbles situated preferentially at interfaces and sinks. This was ascribed to a change in bubble nucleation mode from homogeneous di-atomic nucleation at lower temperatures to multi-atomic nucleation at sinks at higher temperature.

  6. Photosensitizer delivery to vulnerable atherosclerotic plaque: comparison of macrophage-targeted conjugate versus free chlorin(e6).

    PubMed

    Tawakol, Ahmed; Castano, Ana P; Anatelli, Florencia; Bashian, Gregory; Stern, Jeremy; Zahra, Touqir; Gad, Faten; Chirico, Stephanie; Ahmadi, Atosa; Fischman, Alan J; Muller, James E; Hamblin, Michael R

    2006-01-01

    We have previously shown that a conjugate (MA-ce6) between maleylated serum albumin and the photosensitizer chlorin(e6) (ce6) is targeted in vitro to macrophages via class A scavenger receptors. We now report on the ability of this conjugate to localize in macrophage-rich atherosclerotic plaques in vivo. Both the conjugate and the free photosensitizer ce6 are studied after injection into New Zealand White rabbits that are rendered atherosclerotic by a combination of aortic endothelial injury and cholesterol feeding into normal rabbits. Rabbits are sacrificed at 6 and 24 h after injection and intravascular fluorescence spectroscopy is carried out by fiber-based fluorimetry in intact blood-filled arteries. Surface spectrofluorimetry of numbered excised aortic segments together with injured and normal iliac arteries is carried out, and quantified ce6 content by subsequent extraction and quantitative fluorescence determination of the arterial segments and also of nontarget organs. There is good agreement between the various techniques for quantifying ce6 localization, and high contrast between arteries from atherosclerotic and normal rabbits is obtained. Fluorescence correlates with the highest burden of plaque in the aorta and the injured iliac artery. The highest accumulation in plaques is obtained using MA-ce6 at 24 h. Free ce6 gives better accumulation at 6 h compared to 24 h. The liver, spleen, lung, and gall bladder have the highest uptake in nontarget organs. Macrophage-targeted photosensitizer conjugates may have applications in both detecting and treating inflamed vulnerable plaque.

  7. The T6SSs of Pseudomonas aeruginosa Strain PAO1 and Their Effectors: Beyond Bacterial-Cell Targeting.

    PubMed

    Sana, Thibault G; Berni, Benjamin; Bleves, Sophie

    2016-01-01

    Pseudomonas aeruginosa is an opportunistic pathogen responsible for many diseases such as chronic lung colonization in cystic fibrosis patients and acute infections in hospitals. The capacity of P. aeruginosa to be pathogenic toward several hosts is notably due to different secretion systems. Amongst them, P. aeruginosa encodes three Type Six Secretion Systems (T6SS), named H1- to H3-T6SS, that act against either prokaryotes and/or eukaryotic cells. They are independent from each other and inject diverse toxins that interact with different components in the host cell. Here we summarize the roles of these T6SSs in the PAO1 strain, as well as the toxins injected and their targets. While H1-T6SS is only involved in antiprokaryotic activity through at least seven different toxins, H2-T6SS and H3-T6SS are also able to target prokaryotic as well as eukaryotic cells. Moreover, recent studies proposed that H2- and H3-T6SS have a role in epithelial cells invasion by injecting at least three different toxins. The diversity of T6SS effectors is astounding and other effectors still remain to be discovered. In this review, we present a table with other putative P. aeruginosa strain PAO1 T6SS-dependent effectors. Altogether, the T6SSs of P. aeruginosa are important systems that help fight other bacteria for their ecological niche, and are important in the pathogenicity process.

  8. Photosensitizer delivery to vulnerable atherosclerotic plaque: comparison of macrophage-targeted conjugate versus free chlorine(e6)

    NASA Astrophysics Data System (ADS)

    Tawakol, Ahmed; Castano, Ana P.; Anatelli, Florencia; Bashian, Gregory; Stern, Jeremy; Zahra, Touqir; Gad, Faten; Chirico, Stephanie; Ahmadi, Atosa; Fischman, Alan J.; Muller, James E.; Hamblin, Michael R.

    2006-03-01

    We have previously shown that a conjugate (MA-ce6) between maleylated serum albumin and the photosensitizer chlorin(e6) (ce6) is targeted in vitro to macrophages via class A scavenger receptors. We now report on the ability of this conjugate to localize in macrophage-rich atherosclerotic plaques in vivo. Both the conjugate and the free photosensitizer ce6 are studied after injection into New Zealand White rabbits that are rendered atherosclerotic by a combination of aortic endothelial injury and cholesterol feeding into normal rabbits. Rabbits are sacrificed at 6 and 24 h after injection and intravascular fluorescence spectroscopy is carried out by fiber-based fluorimetry in intact blood-filled arteries. Surface spectrofluorimetry of numbered excised aortic segments together with injured and normal iliac arteries is carried out, and quantified ce6 content by subsequent extraction and quantitative fluorescence determination of the arterial segments and also of nontarget organs. There is good agreement between the various techniques for quantifying ce6 localization, and high contrast between arteries from atherosclerotic and normal rabbits is obtained. Fluorescence correlates with the highest burden of plaque in the aorta and the injured iliac artery. The highest accumulation in plaques is obtained using MA-ce6 at 24 h. Free ce6 gives better accumulation at 6 h compared to 24 h. The liver, spleen, lung, and gall bladder have the highest uptake in nontarget organs. Macrophage-targeted photosensitizer conjugates may have applications in both detecting and treating inflamed vulnerable plaque.

  9. A helium-carbon correlation on the extreme horizontal branch in ω Centauri

    SciTech Connect

    Latour, M.; Fontaine, G.; Brassard, P.; Randall, S. K.; Bono, G.; Calamida, A.

    2014-11-10

    Taking advantage of a recent FORS2/VLT spectroscopic sample of extreme horizontal branch (EHB) stars in ω Cen, we isolate 38 spectra well suited for detailed atmospheric studies and determine their fundamental parameters (T {sub eff}, log g, and log N(He)/N(H)) using NLTE, metal line-blanketed models. We find that our targets can be divided into three groups: 6 stars are hot (T {sub eff} ≳ 45,000 K) H-rich subdwarf O stars, 7 stars are typical H-rich sdB stars (T {sub eff} ≲ 35,000 K), and the remaining 25 targets at intermediate effective temperatures are He-rich (log N(He)/N(H) ≳ –1.0) subdwarfs. Surprisingly, and quite interestingly, these He-rich hot subdwarfs in ω Cen cluster in a narrow temperature range (∼35,000 K to ∼40,000 K). We additionally measure the atmospheric carbon abundance and find a most interesting positive correlation between the carbon and helium atmospheric abundances. This correlation certainly bears the signature of diffusion processes—most likely gravitational settling impeded by stellar winds or internal turbulence—but also constrains possible formation scenarios proposed for EHB stars in ω Cen. For the He-rich objects in particular, the clear link between helium and carbon enhancement points toward a late hot flasher evolutionary history.

  10. A Helium-Carbon Correlation on the Extreme Horizontal Branch in ω Centauri

    NASA Astrophysics Data System (ADS)

    Latour, M.; Randall, S. K.; Fontaine, G.; Bono, G.; Calamida, A.; Brassard, P.

    2014-11-01

    Taking advantage of a recent FORS2/VLT spectroscopic sample of extreme horizontal branch (EHB) stars in ω Cen, we isolate 38 spectra well suited for detailed atmospheric studies and determine their fundamental parameters (T eff, log g, and log N(He)/N(H)) using NLTE, metal line-blanketed models. We find that our targets can be divided into three groups: 6 stars are hot (T eff >~ 45,000 K) H-rich subdwarf O stars, 7 stars are typical H-rich sdB stars (T eff <~ 35,000 K), and the remaining 25 targets at intermediate effective temperatures are He-rich (log N(He)/N(H) >~ -1.0) subdwarfs. Surprisingly, and quite interestingly, these He-rich hot subdwarfs in ω Cen cluster in a narrow temperature range (~35,000 K to ~40,000 K). We additionally measure the atmospheric carbon abundance and find a most interesting positive correlation between the carbon and helium atmospheric abundances. This correlation certainly bears the signature of diffusion processes—most likely gravitational settling impeded by stellar winds or internal turbulence—but also constrains possible formation scenarios proposed for EHB stars in ω Cen. For the He-rich objects in particular, the clear link between helium and carbon enhancement points toward a late hot flasher evolutionary history. Based on observations collected at the European Organisation for Astronomical Research in the Southern Hemisphere, Chile (proposal IDs 386.D-0669 and 091.D-0791).

  11. Communication: Barium ions and helium nanodroplets: Solvation and desolvation

    SciTech Connect

    Zhang Xiaohang; Drabbels, Marcel

    2012-08-07

    The solvation of Ba{sup +} ions created by the photoionization of barium atoms located on the surface of helium nanodroplets has been investigated. The excitation spectra corresponding to the 6p {sup 2}P{sub 1/2} Leftwards-Arrow 6s {sup 2}S{sub 1/2} and 6p {sup 2}P{sub 3/2} Leftwards-Arrow 6s {sup 2}S{sub 1/2} transitions of Ba{sup +} are found to be identical to those recorded in bulk He II [H. J. Reyher, H. Bauer, C. Huber, R. Mayer, A. Schafer, and A. Winnacker, Phys. Lett. A 115, 238 (1986)], indicating that the ions formed at the surface of the helium droplets become fully solvated by the helium. Time-of-flight mass spectra suggest that following the excitation of the solvated Ba{sup +} ions, these are being ejected from the helium droplets either as bare Ba{sup +} ions or as small Ba{sup +}He{sub n} (n < 20) complexes.

  12. The antimicrobial effects of helium and helium-air plasma on Staphylococcus aureus and Clostridium difficile.

    PubMed

    Galvin, S; Cahill, O; O'Connor, N; Cafolla, A A; Daniels, S; Humphreys, H

    2013-08-01

    Healthcare-associated infections (HCAI) affect 5-10% of acute hospital admissions. Environmental decontamination is an important component of all strategies to prevent HCAI as many bacterial causes survive and persist in the environment, which serve as ongoing reservoirs of infection. Current approaches such as cleaning with detergents and the use of chemical disinfectant are suboptimal. We assessed the efficacy of helium and helium-air plasma in killing Staphylococcus aureus and Clostridium difficile on a glass surface and studied the impact on bacterial cells using atomic force microscopy (AFM). Both plasma types exhibited bactericidal effects on Staph. aureus (log3·6 - >log7), with increased activity against methicillin-resistant strains, but had a negligible effect on Cl. difficile spores (<1log). AFM demonstrated cell surface disruption. The addition of air increased the microbicidal activity of the plasma and decreased the exposure time required for an equivalent log reduction. Further evaluation of cold plasma systems is warranted with, for example, different bacteria and on surfaces more reminiscent of the health care environment as this approach has potential as an effective decontaminant. Many bacterial causes of healthcare infection can survive in the inanimate environment for lengthy periods and be transmitted to patients. Furthermore, current methods of environmental decontamination such as detergents, chemical disinfectants or gaseous fumigation are suboptimal for a variety of reasons. We assessed the efficacy of helium and helium-air plasma as a decontaminant and demonstrated a significant reduction in bacterial counts of Staphylococcus aureus on a glass surface. Atomic force microscopy morphologically confirmed the impact on bacterial cells. This approach warrants further study as an alternative to current options for hospital hygiene. © 2013 The Society for Applied Microbiology.

  13. Discharge characteristics in liquid helium, liquid nitrogen and pure water preparatory to fabrication of carbon nanomaterials

    NASA Astrophysics Data System (ADS)

    Kawasaki, Hiroharu; Shigematsu, Toshinobu; Imasaka, Kiminobu; Ohshima, Tamiko; Yagyu, Yoshihito; Suda, Yoshiaki

    2012-12-01

    Discharge characteristics and emission spectra of the discharges in low-temperature liquid such as liquid helium have been measured to investigate the conditions for fabrication of carbon nanomaterial by arc discharge in low-temperature liquid. Measurements of the discharge characteristics of the resulting plasma and observation of the associated optical emission spectra show that the behaviour of discharge current over time and the associated spectra depend strongly on discharge voltage and both may be related to the temperature of the carbon target. However, discharge voltage and current with time are almost the same regardless of whether the liquid is pure water, liquid nitrogen, liquid helium and superfluid liquid helium

  14. Diffuse Helium Emission as a Precursory Sign of Volcanic Unrest

    NASA Astrophysics Data System (ADS)

    Padron, E.; Perez, N.; Hernandez Perez, P. A.; Sumino, H.; Melian Rodriguez, G.; Barrancos, J.; Nolasco, D.; Padilla, G.; Dionis, S.; Rodriguez, F.; Hernandez, I.; Calvo, D.; Peraza, M.; Nagao, K.

    2012-12-01

    Since July 16, 2011, an anomalous seismicity at El Hierro island, the youngest and smallest of the Canary Islands, was recorded by IGN seismic network. After the occurrence of more than 10,000 seismic events, volcanic tremor was recorded since 05:15 of the October 10, by all of the seismic stations on the island, with highest amplitudes recorded in the southernmost station. During the afternoon of October 12 a large light-green coloured area was observed in the sea to the souht of La Restinga village (at the southernmost part of El Hierro island), suggesting the existence of a submarine eruption. Since October 12, frequent episodes of, turbulent gas emission and foaming, and the appearance of steamy lava fragments has been observed on the sea surface. As part of the volcanic surveillance of the island, the Instituto Volcanologico de Canarias (INVOLCAN) geochemical monitoring program is carrying out diffuse helium surveys on the surface environment of El Hierro (soil atmosphere). This nobel gas has been investigated because it has been considered an almost ideal geochemical indicator because it is chemically inert, physically stable, nonbiogenic, sparingly soluble in water under ambient conditions and almost non-adsorbable. At each survey, 600 sampling sites covering the whole island and following an homogeneous distribution are selected for helium measurements in the soil gases, The helium concentration gradients with respect to its value on air (5.24 ppm) allow us to estimate a pure diffusive emission rate of helium throughout the island. The first survey was carried out on the summer of 2003, when the island was on a quiescence period. At this survey, the amount of helium released by the volcanic system of El Hierro was estimated in 6 kg/d. Since the beginning of the seismic unrest, 13 helium emission surveys have been carried out. The helium emission rate has shown an excellent agreement with the evolution of the volcanic crisis of the island, reaching 30 kg

  15. Helium on Mars and Venus: EUVE observations and modeling

    NASA Astrophysics Data System (ADS)

    Krasnopolsky, Vladimir A.; Gladstone, G. Randall

    2005-08-01

    Long-exposure spectroscopy of Mars and Venus with the Extreme Ultraviolet Explorer (EUVE) has revealed emissions of He 584 Å on both planets and He 537 Å/O + 539 Å and He + 304 Å on Venus. Our knowledge of the solar emission at 584 Å, eddy diffusion in Mars' upper atmosphere, electron energy distributions above Mars' ionopause, and hot oxygen densities in Mars' exosphere has been significantly improved since our analysis of the first EUVE observation of Mars [Krasnopolsky, Gladstone, 1996, Helium on Mars: EUVE and Phobos data and implications for Mars' evolution, J. Geophys. Res. 101, 15,765-15,772]. These new results and a more recent EUVE observation of Mars are the motivation for us to revisit the problem in this paper. We find that the abundance of helium in the upper atmosphere, where the main loss processes occur, is similar to that in the previous paper, though the mixing ratio in the lower and middle atmosphere is now better estimated at 10±6 ppm. Our estimate of the total loss of helium is almost unchanged at 8×10 s, because a significant decrease in the loss by electron impact ionization above the ionopause is compensated by a higher loss in collisions with hot oxygen. We neglect the outgassing of helium produced by radioactive decay of U and Th because of the absence of current volcanism and a very low upper limit to the seepage of volcanic gases. The capture of solar wind α-particles is currently the only substantial source of helium on Mars, and its efficiency remains at 0.3. A similar analysis of EUV emissions from Venus results in a helium abundance in the upper atmosphere which is equal to the mean of the abundances measured previously with two optical and two mass spectrometers, and a derived helium mixing ratio in the middle and lower atmosphere of 9±6 ppm. Helium escape by ionization and sweeping out of helium ions by the solar wind above the ionopause is smaller than that calculated by Prather and McElroy [1983, Helium on Venus

  16. High-temperature helium-loop facility

    SciTech Connect

    Tokarz, R.D.

    1981-09-01

    The high-temperature helium loop is a facility for materials testing in ultrapure helium gas at high temperatures. The closed loop system is capable of recirculating high-purity helium or helium with controlled impurities. The gas loop maximum operating conditions are as follows: 300 psi pressure, 500 lb/h flow rate, and 2100/sup 0/F temperature. The two test sections can accept samples up to 3.5 in. diameter and 5 ft long. The gas loop is fully instrumented to continuously monitor all parameters of loop operation as well as helium impurities. The loop is fully automated to operate continuously and requires only a daily servicing by a qualified operator to replenish recorder charts and helium makeup gas. Because of its versatility and high degree of parameter control, the helium loop is applicable to many types of materials research. This report describes the test apparatus, operating parameters, peripheral systems, and instrumentation system.

  17. An Interaction between RRP6 and SU(VAR)3-9 Targets RRP6 to Heterochromatin and Contributes to Heterochromatin Maintenance in Drosophila melanogaster

    PubMed Central

    Eberle, Andrea B.; Jordán-Pla, Antonio; Gañez-Zapater, Antoni; Hessle, Viktoria; Silberberg, Gilad; von Euler, Anne; Silverstein, Rebecca A.; Visa, Neus

    2015-01-01

    RNA surveillance factors are involved in heterochromatin regulation in yeast and plants, but less is known about the possible roles of ribonucleases in the heterochromatin of animal cells. Here we show that RRP6, one of the catalytic subunits of the exosome, is necessary for silencing heterochromatic repeats in the genome of Drosophila melanogaster. We show that a fraction of RRP6 is associated with heterochromatin, and the analysis of the RRP6 interaction network revealed physical links between RRP6 and the heterochromatin factors HP1a, SU(VAR)3-9 and RPD3. Moreover, genome-wide studies of RRP6 occupancy in cells depleted of SU(VAR)3-9 demonstrated that SU(VAR)3-9 contributes to the tethering of RRP6 to a subset of heterochromatic loci. Depletion of the exosome ribonucleases RRP6 and DIS3 stabilizes heterochromatic transcripts derived from transposons and repetitive sequences, and renders the heterochromatin less compact, as shown by micrococcal nuclease and proximity-ligation assays. Such depletion also increases the amount of HP1a bound to heterochromatic transcripts. Taken together, our results suggest that SU(VAR)3-9 targets RRP6 to a subset of heterochromatic loci where RRP6 degrades chromatin-associated non-coding RNAs in a process that is necessary to maintain the packaging of the heterochromatin. PMID:26389589

  18. MiR-181a regulates blood-tumor barrier permeability by targeting Krüppel-like factor 6

    PubMed Central

    Ma, Jun; Yao, Yilong; Wang, Ping; Liu, Yunhui; Zhao, Lini; Li, Zhen; Li, Zhiqing; Xue, Yixue

    2014-01-01

    Blood–tumor barrier (BTB) constitutes an efficient organization of tight junctions that impairs the delivery of therapeutic drugs. However, the methods and molecular mechanisms underlying the BTB opening remain elusive. MicroRNAs (miRNAs) have recently emerged as key regulators of various biologic processes and therapeutic targets. In this study, we have identified microRNA-181a (miR-181a) as a critical miRNA in opening BTB. MicroRNA-181a expression was upregulated in glioma endothelial cells (GECs), which were obtained by coculturing endothelial cells (ECs) with glioma cells. Overexpression of miR-181a resulted in an impaired and permeability increased BTB, and meanwhile reduced the expression of zonula occluden (ZO)-1, occludin, and claudin-5. Kruppel-like factor 6 (KLF6), a transcription factor of the zinc-finger family, was downregulated in GECs. Mechanistic investigations defined it as a direct and functional downstream target of miR-181a, which was involved in the regulation of BTB permeability and the expression of ZO-1, occludin, and claudin-5. Furthermore, luciferase assays and chromatin immunoprecipitation assays showed that KLF6 upregulated the promoter activities and interacted with the promoters of ZO-1, occludin, and claudin-5 in GECs. Collectively, we showed the possibility that overexpression of miR-181a contributes to the increased permeability of BTB by targeting KLF6, thereby revealing potential therapeutic targets for the treatment of brain gliomas. PMID:25182666

  19. Production Target Design Report

    SciTech Connect

    Woloshun, Keith Albert; Dale, Gregory E.; Olivas, Eric Richard

    2015-07-28

    The Northstar 99Mo production target, a cylindrical length of 100Mo rod, has evolved considerably since its first conception.  The cylinder was very early sliced into disks to increase the heat transfer area, first to 1 mm thick disks then to the current 0.5 mm thick.  The coolant was changed early in the target development from water to helium to eliminate corrosion and dissolution.  The diameter has increased from initially 6 mm to 12 mm, the current diameter of the test target now at ANL, to nominally 28 mm (26-30.6 mm, depending upon optimal beam spot size and shape).  The length has also changed to improve the production to cost ratio, so now the target is nominally 41 mm long (excluding coolant gaps between disks), and irradiated on both ends.  This report summarizes the current status of the plant target design.

  20. 26 CFR 1.338-6 - Allocation of ADSP and AGUB among target assets.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... corporation bore the responsibility for decommissioning one or more nuclear power plants to the extent assets... funding the decommissioning of one or more nuclear power plants; (B) That is described to the Nuclear...). However, for purposes of determining the amount of old target's deemed sale tax consequences, the fair...

  1. Helium Loop Cooling Channel Hydraulic Characterization

    SciTech Connect

    Olivas, Eric Richard; Morgan, Robert Vaughn; Woloshun, Keith Albert

    2015-07-02

    New methods for generating ⁹⁹Mo are being explored in an effort to eliminate proliferation issues and provide a domestic supply of ⁹⁹mTc for medical imaging. Electron accelerating technology is used by sending an electron beam through a series of ¹⁰⁰Mo targets. During this process a large amount of heat is created, which directly affects the operating temperature set for the system. In order to maintain the required temperature range, helium gas is used to serve as a cooling agent that flows through narrow channels between the target disks. Currently we are tailoring the cooling channel entrance and exits to decrease the pressure drop through the targets. Currently all hardware has be procured and manufactured to conduct flow measurements and visualization via solid particle seeder. Pressure drop will be studied as a function of mass flow and diffuser angle. The results from these experiments will help in determining target cooling geometry and validate CFD code results.

  2. Comparison of the effects of couplings to breakup channels in reactions induced by {sup 6}Li and {sup 6}He on the same {sup 64}Zn target

    SciTech Connect

    Fernández-García, J. P. Di Pietro, A.; Figuera, P.; Fisichella, M.; Lattuada, M.; Musumarra, A.; Pellegriti, M. G.; Scuderi, V.; Torresi, D.; Moro, A. M.; Zadro, M.

    2015-10-15

    The experimental elastic scattering angular distributions for the weakly bound nuclei {sup 6,7}Li and for the halo nucleus {sup 6}He on the same {sup 64}Zn target at several energies around the Coulomb barrier were measured at the Laboratori Nazionali del Sud (LNS, Italy) and at the Cyclotron Research Center, Louvain La Neuve (Belgium), respectively. The measured elastic scattering angular distributions of these three systems at the same center of mass energy have been compared. The experimental data of the {sup 6,7}Li+ {sup 64}Zn systems have been analyzed within the CDCC method, while the {sup 6}He+{sup 64}Zn data have been compared with both both CDCC and CRC calculations.

  3. Atomistic studies of formation and diffusion of helium clusters and bubbles in BCC iron

    SciTech Connect

    Stewart, David M; Stoller, Roger E; Osetskiy, Yury N

    2011-01-01

    In fusion applications, helium created by transmutation plays an important role in the response of reduced-activation ferritic/martensitic (RAFM) steels to neutron radiation damage. We have performed extensive atomistic simulations using the ORNL 3-body Fe He interatomic potential combined with three interatomic potentials for the iron matrix. Some of the results obtained are summarized in this review. Interstitial helium is very mobile and coalesces together to form interstitial clusters. We have investigated the mobility of these clusters. When an interstitial He cluster reaches sufficient size, it punches out an Fe interstitial, creating an immobile helium vacancy cluster. If more helium atoms join it, more Fe interstitials can be created; the He V defect is a nascent bubble. These mechanisms are investigated together in simulations that examine the nucleation of He defects. Mobile interstitial He clusters and helium bubbles 1 to 6 nm across are also simulated separately. Results are compared based on temperature and interatomic potentials used.

  4. Physical water scarcity metrics for monitoring progress towards SDG target 6.4: An evaluation of indicator 6.4.2 "Level of water stress".

    PubMed

    Vanham, D; Hoekstra, A Y; Wada, Y; Bouraoui, F; de Roo, A; Mekonnen, M M; van de Bund, W J; Batelaan, O; Pavelic, P; Bastiaanssen, W G M; Kummu, M; Rockström, J; Liu, J; Bisselink, B; Ronco, P; Pistocchi, A; Bidoglio, G

    2017-09-12

    Target 6.4 of the recently adopted Sustainable Development Goals (SDGs) deals with the reduction of water scarcity. To monitor progress towards this target, two indicators are used: Indicator 6.4.1 measuring water use efficiency and 6.4.2 measuring the level of water stress (WS). This paper aims to identify whether the currently proposed indicator 6.4.2 considers the different elements that need to be accounted for in a WS indicator. WS indicators compare water use with water availability. We identify seven essential elements: 1) both gross and net water abstraction (or withdrawal) provide important information to understand WS; 2) WS indicators need to incorporate environmental flow requirements (EFR); 3) temporal and 4) spatial disaggregation is required in a WS assessment; 5) both renewable surface water and groundwater resources, including their interaction, need to be accounted for as renewable water availability; 6) alternative available water resources need to be accounted for as well, like fossil groundwater and desalinated water; 7) WS indicators need to account for water storage in reservoirs, water recycling and managed aquifer recharge. Indicator 6.4.2 considers many of these elements, but there is need for improvement. It is recommended that WS is measured based on net abstraction as well, in addition to currently only measuring WS based on gross abstraction. It does incorporate EFR. Temporal and spatial disaggregation is indeed defined as a goal in more advanced monitoring levels, in which it is also called for a differentiation between surface and groundwater resources. However, regarding element 6 and 7 there are some shortcomings for which we provide recommendations. In addition, indicator 6.4.2 is only one indicator, which monitors blue WS, but does not give information on green or green-blue water scarcity or on water quality. Within the SDG indicator framework, some of these topics are covered with other indicators. Copyright © 2017 The Authors

  5. Interaction of Helium Rydberg State Molecules with Dense Helium.

    PubMed

    Bonifaci, Nelly; Li, Zhiling; Eloranta, Jussi; Fiedler, Steven L

    2016-11-17

    The interaction potentials of the He2(*) excimer, in the a(3)Σu, b(3)Πg, c(3)Σg, and d(3)Σu electronic states with a ground state helium atom are presented. The symmetry of the interaction potentials closely follows the excimer Rydberg electron density with pronounced short-range minima appearing along the nodal planes of the Rydberg orbital. In such cases, a combination of the electrostatic short-range attraction combined with Pauli repulsion leads to the appearance of unusual long-range maxima in the potentials. Bosonic density functional calculations show that the (3)d state excimer resides in a localized solvation bubble in dense helium at 4.5 K, with radii varying from 12.7 Å at 0.1 MPa to 10.8 Å at 2.4 MPa. The calculated (3)d → (3)b pressure-induced fluorescence band shifts are in good agreement with experimental results determined by application of corona discharge. The magnitude of the spectral shifts indicate that the observed He2(*) molecules emit from dense helium whereas the corresponding fluorescence signal from the discharge zone appears quenched. This implies that fluorescence spectroscopy involving this electronic transition can only be used to probe the state of the surrounding medium rather than the discharge zone itself.

  6. Gravitational and radiative effects on the escape of helium from the moon

    NASA Technical Reports Server (NTRS)

    Hodges, R. R., Jr.

    1978-01-01

    On the moon, and probably on Mercury and other similar regolith-covered bodies with tenuous atmosphere, the dominant gas is He-4. It arises as the radiogenic product of the decay of uranium and thorium within any planet, but its major source appears to be the alpha particle flux of the solar wind. The moon intercepts solar wind helium at an average rate of 1.1 times 10 to the 24th atom/sec, and loses it at the same rate. Some helium may escape directly as the result of the process of solar wind soil bombardment which may release previously trapped helium at superthermal speeds. Atmospheric models have been calculated with the total helium influx as source. Subsequent comparison of model and measured helium concentrations indicates that the fraction of helium escaping via the atmosphere may range from 20% to 100% of the solar wind influx. Of the escaping atmosphere, most of the helium (about 93%) becomes trapped in earth orbit, while about 5% gets trapped in satellite orbits about the moon. Owing to a 6 month lifetime for helium in solar radiation, the satellite atoms form a lunar corona that exceeds the lunar atmosphere in total abundance by a factor of 4 to 5.

  7. Genus Beta Human Papillomavirus E6 Proteins Vary in Their Effects on the Transactivation of p53 Target Genes

    PubMed Central

    White, Elizabeth A.; Walther, Johanna; Javanbakht, Hassan

    2014-01-01

    ABSTRACT The genus beta human papillomaviruses (beta HPVs) cause cutaneous lesions and are thought to be involved in the initiation of some nonmelanoma skin cancers (NMSCs), particularly in patients with the genetic disorder epidermodysplasia verruciformis (EV). We have previously reported that at least two of the genus beta HPV E6 proteins bind to and/or increase the steady-state levels of p53 in squamous epithelial cells. This is in contrast to a well-characterized ability of the E6 proteins of cancer-associated HPVs of genus alpha HPV, which inactivate p53 by targeting its ubiquitin-mediated proteolysis. In this study, we have investigated the ability of genus beta E6 proteins from eight different HPV types to block the transactivation of p53 target genes following DNA damage. We find that the E6 proteins from diverse beta HPV species and types vary in their capacity to block the induction of MDM2, p21, and proapoptotic genes after genotoxic stress. We conclude that some genus beta HPV E6 proteins inhibit at least some p53 target genes, although perhaps not by the same mechanism or to the same degree as the high-risk genus alpha HPV E6 proteins. IMPORTANCE This study addresses the ability of various human papillomavirus E6 proteins to block the activation of p53-responsive cellular genes following DNA damage in human keratinocytes, the normal host cell for HPVs. The E6 proteins encoded by the high-risk, cancer-associated HPV types of genus alpha HPV have a well-established activity to target p53 degradation and thereby inhibit the response to DNA damage. In this study, we have investigated the ability of genus beta HPV E6 proteins from eight different HPV types to block the ability of p53 to transactivate downstream genes following DNA damage. We find that some, but not all, genus beta HPV E6 proteins can block the transactivation of some p53 target genes. This differential response to DNA damage furthers the understanding of cutaneous HPV biology and may help

  8. Genus beta human papillomavirus E6 proteins vary in their effects on the transactivation of p53 target genes.

    PubMed

    White, Elizabeth A; Walther, Johanna; Javanbakht, Hassan; Howley, Peter M

    2014-08-01

    The genus beta human papillomaviruses (beta HPVs) cause cutaneous lesions and are thought to be involved in the initiation of some nonmelanoma skin cancers (NMSCs), particularly in patients with the genetic disorder epidermodysplasia verruciformis (EV). We have previously reported that at least two of the genus beta HPV E6 proteins bind to and/or increase the steady-state levels of p53 in squamous epithelial cells. This is in contrast to a well-characterized ability of the E6 proteins of cancer-associated HPVs of genus alpha HPV, which inactivate p53 by targeting its ubiquitin-mediated proteolysis. In this study, we have investigated the ability of genus beta E6 proteins from eight different HPV types to block the transactivation of p53 target genes following DNA damage. We find that the E6 proteins from diverse beta HPV species and types vary in their capacity to block the induction of MDM2, p21, and proapoptotic genes after genotoxic stress. We conclude that some genus beta HPV E6 proteins inhibit at least some p53 target genes, although perhaps not by the same mechanism or to the same degree as the high-risk genus alpha HPV E6 proteins. This study addresses the ability of various human papillomavirus E6 proteins to block the activation of p53-responsive cellular genes following DNA damage in human keratinocytes, the normal host cell for HPVs. The E6 proteins encoded by the high-risk, cancer-associated HPV types of genus alpha HPV have a well-established activity to target p53 degradation and thereby inhibit the response to DNA damage. In this study, we have investigated the ability of genus beta HPV E6 proteins from eight different HPV types to block the ability of p53 to transactivate downstream genes following DNA damage. We find that some, but not all, genus beta HPV E6 proteins can block the transactivation of some p53 target genes. This differential response to DNA damage furthers the understanding of cutaneous HPV biology and may help to explain the

  9. Glucose-6-Phosphate Dehydrogenase of Trypanosomatids: Characterization, Target Validation, and Drug Discovery

    PubMed Central

    Gupta, Shreedhara; Igoillo-Esteve, Mariana; Michels, Paul A. M.; Cordeiro, Artur T.

    2011-01-01

    In trypanosomatids, glucose-6-phosphate dehydrogenase (G6PDH), the first enzyme of the pentosephosphate pathway, is essential for the defense of the parasite against oxidative stress. Trypanosoma brucei, Trypanosoma cruzi, and Leishmania mexicana G6PDHs have been characterized. The parasites' G6PDHs contain a unique 37 amino acid long N-terminal extension that in T. cruzi seems to regulate the enzyme activity in a redox-state-dependent manner. T. brucei and T. cruzi G6PDHs, but not their Leishmania spp. counterpart, are inhibited, in an uncompetitive way, by steroids such as dehydroepiandrosterone and derivatives. The Trypanosoma enzymes are more susceptible to inhibition by these compounds than the human G6PDH. The steroids also effectively kill cultured trypanosomes but not Leishmania and are presently considered as promising leads for the development of new parasite-selective chemotherapeutic agents. PMID:22091394

  10. Lifetime of a Chemically Bound Helium Compound

    NASA Technical Reports Server (NTRS)

    Chaban, Galina M.; Lundell, Jan; Gerber, R. Benny; Kwak, Dochan (Technical Monitor)

    2001-01-01

    The rare-gas atoms are chemically inert, to an extent unique among all elements. This is due to the stable electronic structure of the atoms. Stable molecules with chemically bound rare-gas atoms are, however, known. A first such compound, XePtF6, W2S prepared in 1962 and since then a range of molecules containing radon, xenon and krypton have been obtained. Most recently, a first stable chemically bound compound of argon was prepared, leaving neon and helium as the only elements for which stable chemically bound molecules are not yet known. Electronic structure calculations predict that a metastable species HHeF exists, but significance of the result depends on the unknown lifetime. Here we report quantum dynamics calculations of the lifetime of HHeF, using accurate interactions computed from electronic structure theory. HHeF is shown to disintegrate by tunneling through energy barriers into He + HF and H + He + F the first channel greatly dominating. The lifetime of HHeF is more than 120 picoseconds, that of DHeF is 14 nanoseconds. The relatively long lifetimes are encouraging for the preparation prospects of this first chemically bound helium compound.

  11. Cycle design for the ISABELLE helium refrigerator

    SciTech Connect

    Brown, D.P.; Schlafke, A.P.; Wu, K.C.; Moore, R.W.

    1981-01-01

    The superconducting magnets for the ISABELLE storage ring/accelerator are designed to be operated at 3.8/sup 0/K using a forced-flow supercritical helium cooling system. The ISABELLE refrigerator has been designed subject to these special requirements. The design output is 13.65 KW of refrigeration below 4.2/sup 0/K (for cooling the magnet and distribution system), 55 KW at 55/sup 0/K (to cool heat shields for the whole system) and 100 g/s of liquefaction (for magnet power leads cooling). The system incorporates a subcooler section that produces liquid helium at 5.3 atm and 2.6 K and circulates it through the loads, and a Claude-type main refrigerator section. The main refrigerator section has five stages of cooling, with four of them below liquid nitrogen temperature. Liquid nitrogen precooling is not used. With 60% isothermal compressors the efficiency of the refrigerator system will be about 26% of Carnot.

  12. 6-Oxooxazolidine-quinazolines as noncovalent inhibitors with the potential to target mutant forms of EGFR.

    PubMed

    Shao, Jiaan; Chen, En; Shu, Ke; Chen, Wenteng; Zhang, Guolin; Yu, Yongping

    2016-08-15

    Despite the remarkable benefits of gefitinib, the clinical efficacy is eventually diminished due to the acquired point mutations in the EGFR (T790M). To address this unmet medical need, we demonstrated a strategy to prepare a hybrid analogue consisting of the oxooxazolidine ring and the quinazoline scaffold and provided alternative noncovalent inhibitors targeting mutant forms of EGFR. Most of the derivatives displayed moderate to good anti-proliferative activity against gefitinib-resistant NCI-H1975. Some of them exhibited potent EGFR kinase inhibitory activities, especially on EGFR(T790M) and EGFR(L858R) kinases. SAR studies led to the identification of a hit 9a that can target both of the most common EGFR mutants: L858R and T790M. Also, 9a displayed weaker inhibitory against cancer cell lines with low level of EGFR expression and good chemical stability under different pH conditions. The work presented herein showed the potential for developing noncovalent inhibitors targeting EGFR mutants. Copyright © 2016. Published by Elsevier Ltd.

  13. A Dual Target-directed Agent against Interleukin-6 Receptor and Tumor Necrosis Factor α ameliorates experimental arthritis

    PubMed Central

    Kim, Youngkyun; Yi, Hyoju; Jung, Hyerin; Rim, Yeri Alice; Park, Narae; Kim, Juryun; Jung, Seung Min; Park, Sung-Hwan; Park, Young Woo; Ju, Ji Hyeon

    2016-01-01

    A considerable proportion of patients with rheumatoid arthritis (RA) do not respond to monospecific agents. The purpose of our study was to generate a hybrid form of biologics, targeting tumor-necrosis factor alpha (TNFα) and interleukin-6 receptor (IL-6R), and determine its anti-arthritic properties in vitro and in vivo. A novel dual target-directed agent (DTA(A7/sTNFR2)) was generated by conjugating soluble TNF receptor 2 (sTNFR2) to the Fc region of A7, a new anti-IL-6R antibody obtained by screening the phage display human antibody library. DTA(A7/sTNFR2) inhibited the proliferation and migration of fibroblast-like synoviocytes from patients with RA (RA-FLS) more efficiently than single target-directed agents. DTA(A7/sTNFR2) also blocked osteoclastogenesis from bone marrow cells. The arthritis severity scores of the experimental arthritis mice with DTA(A7/sTNFR2) tended to be lower than those of mice with IgG, A7, or sTNFR2. Histological data suggested that DTA(A7/sTNFR2) is more efficient than single-target drugs in preventing joint destruction and bone loss. These results were confirmed in vivo using the minicircle system. Taken together, the results show that DTA(A7/sTNFR2) may be a promising therapeutic agent for the treatment of RA. PMID:26841833

  14. Confined helium on Lagrange meshes.

    PubMed

    Baye, D; Dohet-Eraly, J

    2015-12-21

    The Lagrange-mesh method has the simplicity of a calculation on a mesh and can have the accuracy of a variational method. It is applied to the study of a confined helium atom. Two types of confinement are considered. Soft confinements by potentials are studied in perimetric coordinates. Hard confinement in impenetrable spherical cavities is studied in a system of rescaled perimetric coordinates varying in [0,1] intervals. Energies and mean values of the distances between electrons and between an electron and the helium nucleus are calculated. A high accuracy of 11 to 15 significant figures is obtained with small computing times. Pressures acting on the confined atom are also computed. For sphere radii smaller than 1, their relative accuracies are better than 10(-10). For larger radii up to 10, they progressively decrease to 10(-3), still improving the best literature results.

  15. Superfluid helium leak sealant study

    NASA Technical Reports Server (NTRS)

    Vorreiter, J. W.

    1981-01-01

    Twenty-one leak specimens were fabricated in the ends of stainless steel and aluminum tubes. Eighteen of these tubes were coated with a copolymer material to seal the leak. The other three specimens were left uncoated and served as control specimens. All 21 tubes were cold shocked in liquid helium 50 times and then the leak rate was measured while the tubes were submerged in superfluid helium at 1.7 K. During the cold shocks two of the coated specimens were mechanically damaged and eliminated from the test program. Of the remaining 16 coated specimens one suffered a total coating failure and resulting high leak rate. Another three of the coated specimens suffered partial coating failures. The leak rates of the uncoated specimens were also measured and reported. The significance of various leak rates is discussed in view of the infrared astronomical satellite (IRAS) Dewar performance.

  16. Mg impurity in helium droplets

    NASA Astrophysics Data System (ADS)

    Navarro, J.; Mateo, D.; Barranco, M.; Sarsa, A.

    2012-02-01

    Within the diffusion Monte Carlo approach, we have determined the structure of isotopically pure and mixed helium droplets doped with one magnesium atom. For pure 4He clusters, our results confirm those of Mella et al. [J. Chem. Phys. 123, 054328 (2005), 10.1063/1.1982787] that the impurity experiences a transition from a surface to a bulk location as the number of helium atoms in the droplet increases. Contrarily, for pure 3He clusters Mg resides in the bulk of the droplet due to the smaller surface tension of this isotope. Results for mixed droplets are presented. We have also obtained the absorption spectrum of Mg around the 3s3p 1P1 ← 3s2 1S0 transition.

  17. Self-trapping of helium in metals

    SciTech Connect

    Wilson, W.D.; Bisson, C.L.; Baskes, M.I.

    1981-11-15

    Atomistic calculations are presented which demonstrate that helium atoms in a metal lattice are able to cluster with each other, producing vacancies and nearby self-interstitial defects. Even a small number of helium atoms is found to be sufficient to create these large distortions. As few as five interstitial helium can spontaneously produce a lattice vacancy and nearby self-interstitial. An eight-helium-atom cluster gives rise to two such defects, and 16 helium atoms to more than five self-interstitial vacancy pairs. It was noted that the self-interstitials prefer to agglomerate on the same ''side'' of the helium cluster rather than to spread themselves out uniformly. The binding energy of each additional helium atom to these clusters increases with helium concentration and the trap is apparently unsaturable. A rate theory using these atomistic binding energies has been used to calculate the kinetics of helium-bubble nucleation and growth. The results are consistent with measurements of the properties of helium resulting from tritium decay.

  18. Superfluid Helium Tanker (SFHT) study

    NASA Technical Reports Server (NTRS)

    Eberhardt, Ralph N.; Dominick, Sam M.; Anderson, John E.; Gille, John P.; Martin, Tim A.; Marino, John S.; Paynter, Howard L.; Traill, R. Eric; Herzl, Alfred; Gotlib, Sam

    1988-01-01

    Replenishment of superfluid helium (SFHe) offers the potential of extending the on-orbit life of observatories, satellite instruments, sensors and laboratories which operate in the 2 K temperature regime. A reference set of resupply customers was identified as representing realistic helium servicing requirements and interfaces for the first 10 years of superfluid helium tanker (SFHT) operations. These included the Space Infrared Telescope Facility (SIRTF), the Advanced X-ray Astrophysics Facility (AXAF), the Particle Astrophysics Magnet Facility (Astromag), and the Microgravity and Materials Processing Sciences Facility (MMPS)/Critical Point Phenomena Facility (CPPF). A mixed-fleet approach to SFHT utilization was considered. The tanker permits servicing from the Shuttle cargo bay, in situ when attached to the OMV and carried to the user spacecraft, and as a depot at the Space Station. A SFHT Dewar ground servicing concept was developed which uses a dedicated ground cooling heat exchanger to convert all the liquid, after initial fill as normal fluid, to superfluid for launch. This concept permits the tanker to be filled to a near full condition, and then cooled without any loss of fluid. The final load condition can be saturated superfluid with any desired ullage volume, or the tank can be totally filed and pressurized. The SFHT Dewar and helium plumbing system design has sufficient component redundancy to meet fail-operational, fail-safe requirements, and is designed structurally to meet a 50 mission life usage requirement. Technology development recommendations were made for the selected SFHT concept, and a Program Plan and cost estimate prepared for a phase C/D program spanning 72 months from initiation through first launch in 1997.

  19. Detecting scintillations in liquid helium

    NASA Astrophysics Data System (ADS)

    Huffman, P. R.; McKinsey, D. N.

    2013-09-01

    We review our work in developing a tetraphenyl butadiene (TPB)-based detection system for a measurement of the neutron lifetime using magnetically confined ultracold neutrons (UCN). As part of the development of the detection system for this experiment, we studied the scintillation properties of liquid helium itself, characterized the fluorescent efficiencies of different fluors, and built and tested three detector geometries. We provide an overview of the results from these studies as well as references for additional information.

  20. Development of a Novel PET Tracer [18F]AlF-NOTA-C6 Targeting MMP2 for Tumor Imaging.

    PubMed

    Liu, Qinghua; Pan, Donghui; Cheng, Chao; Zhang, Dazhi; Zhang, Anyu; Wang, Lizhen; Jiang, Hongdie; Wang, Tao; Liu, Hongrui; Xu, Yuping; Yang, Runlin; Chen, Fei; Yang, Min; Zuo, Changjing

    2015-01-01

    The overexpression of gelatinases, that is, matrix metalloproteinase MMP2 and MMP9, has been associated with tumor progression, invasion, and metastasis. To image MMP2 in tumors, we developed a novel ligand termed [18F]AlF-NOTA-C6, with consideration that: c(KAHWGFTLD)NH2 (herein, C6) is a selective gelatinase inhibitor; Cy5.5-C6 has been visualized in many in vivo tumor models; positron emission tomography (PET) has a higher detection sensitivity and a wider field of view than optical imaging; fluorine-18 (18F) is the optimal PET radioisotope, and the creation of a [18F]AlF-peptide complex is a simple procedure. C6 was conjugated to the bifunctional chelator NOTA (1, 4, 7-triazacyclononanetriacetic acid) for radiolabeling [18F]AlF conjugation. The MMP2-binding characteristics and tumor-targeting efficacy of [18F]AlF-NOTA-C6 were tested in vitro and in vivo. The non-decay corrected yield of [18F]AlF-NOTA-C6 was 46.2-64.2%, and the radiochemical purity exceeded 95%. [18F]AlF-NOTA-C6 was favorably retained in SKOV3 and PC3 cells, determined by cell uptake. Using NOTA-C6 as a competitive ligand, the uptake of [18F]AlF-NOTA-C6 in SKOV3 cells decreased in a dose-dependent manner. In biodistribution and PET imaging studies, higher radioactivity concentrations were observed in tumors. Pre-injection of C6 caused a marked reduction in tumor tissue uptake. Immunohistochemistry showed MMP2 in tumor tissues. [18F]AlF-NOTA-C6 was easy to synthesize and has substantial potential as an imaging agent that targets MMP2 in tumors.

  1. Development of a Novel PET Tracer [18F]AlF-NOTA-C6 Targeting MMP2 for Tumor Imaging

    PubMed Central

    Cheng, Chao; Zhang, Dazhi; Zhang, Anyu; Wang, Lizhen; Jiang, Hongdie; Wang, Tao; Liu, Hongrui; Xu, Yuping; Yang, Runlin; Chen, Fei; Yang, Min; Zuo, Changjing

    2015-01-01

    Background and Objective The overexpression of gelatinases, that is, matrix metalloproteinase MMP2 and MMP9, has been associated with tumor progression, invasion, and metastasis. To image MMP2 in tumors, we developed a novel ligand termed [18F]AlF-NOTA-C6, with consideration that: c(KAHWGFTLD)NH2 (herein, C6) is a selective gelatinase inhibitor; Cy5.5-C6 has been visualized in many in vivo tumor models; positron emission tomography (PET) has a higher detection sensitivity and a wider field of view than optical imaging; fluorine-18 (18F) is the optimal PET radioisotope, and the creation of a [18F]AlF-peptide complex is a simple procedure. Methods C6 was conjugated to the bifunctional chelator NOTA (1, 4, 7-triazacyclononanetriacetic acid) for radiolabeling [18F]AlF conjugation. The MMP2-binding characteristics and tumor-targeting efficacy of [18F]AlF-NOTA-C6 were tested in vitro and in vivo. Results The non-decay corrected yield of [18F]AlF-NOTA-C6 was 46.2–64.2%, and the radiochemical purity exceeded 95%. [18F]AlF-NOTA-C6 was favorably retained in SKOV3 and PC3 cells, determined by cell uptake. Using NOTA-C6 as a competitive ligand, the uptake of [18F]AlF-NOTA-C6 in SKOV3 cells decreased in a dose-dependent manner. In biodistribution and PET imaging studies, higher radioactivity concentrations were observed in tumors. Pre-injection of C6 caused a marked reduction in tumor tissue uptake. Immunohistochemistry showed MMP2 in tumor tissues. Conclusions [18F]AlF-NOTA-C6 was easy to synthesize and has substantial potential as an imaging agent that targets MMP2 in tumors. PMID:26540114

  2. Vorticity matching in superfluid helium

    NASA Astrophysics Data System (ADS)

    Samuels, David C.

    1991-12-01

    Recent experiments have rekindled interest in high Reynolds number flows using superfluid helium. In a continuing series of experiments, the flow of helium II through various devices (smooth pipes, corrugated pipes, valves, venturies, turbine flowmeters, and coanda flowmeters for example) was investigated. In all cases, the measured values (typically, mass flow rates and pressure drops) were found to be well described by classical relations for high Reynolds flows. This is unexpected since helium II consists of two interpenetrating fluids; one fluid with nonzero viscosity (the normal fluid) and one with zero viscosity (the superfluid). Only the normal fluid component should directly obey classical relations. Since the experiments listed above only measure the external behavior of the flow (i.e., pressure drops over devices), there is a great deal of room for interpretation of their results. One possible interpretation is that in turbulent flows the normal fluid and the superfluid velocity fields are somehow 'locked' together, presumably by the mutual friction force between the superfluid vortex filaments and the normal fluid. We refer to this locking together of the two fluids as 'vorticity matching.'

  3. Rab6-mediated retrograde transport regulates inner nuclear membrane targeting of caveolin-2 in response to insulin.

    PubMed

    Jeong, Kyuho; Kwon, Hayeong; Lee, Jaewoong; Jang, Donghwan; Hwang, Eun Mi; Park, Jae-Yong; Pak, Yunbae

    2012-09-01

    Here, we have identified a retrograde transport pathway of caveolin-2 (cav-2) for its regulatory function in the nucleus. Confocal microscopy analysis, photoactivation experiments and subcellular fractionation revealed that cav-2 localized in the Golgi was transported to the inner nuclear membrane (INM) in response to insulin. Exogenous caveolin-1 (cav-1) and P132L-cav-1 expression did not affect the Golgi localization and insulin-induced INM targeting of cav-2. Cav-2(DKV) mutant in the endoplasmic reticulum (ER) was unable to translocate to the INM in response to insulin. The GTP-bound form of Rab6 promoted, but Rab6 siRNA and the GDP-bound form of Rab6 abrogated, retrograde trafficking of cav-2 from the Golgi to ER. Colchicine or nocodazole treatment abolished insulin-induced INM targeting of cav-2. Knock down of gp210 inhibited insulin-induced import of cav-2 from ER/outer nuclear membrane (ONM) to the INM. The INM-targeted cav-2 prevented heterochromatinization and promoted transcriptional activation of Elk-1 and signal transducer and activator of transcription 3 (STAT3). The results provide molecular mechanisms for insulin-induced INM translocation of cav-2 initiated (i) by Golgi-to-ER retrograde trafficking of cav-2 via microtubule-based Rab6-GTP-dependent transport and subsequently processed (ii) by gp210-mediated import of cav-2 from ER/ONM to INM. © 2012 John Wiley & Sons A/S.

  4. IL-6 as a Druggable Target in Psoriasis: Focus on Pustular Variants

    PubMed Central

    2014-01-01

    Psoriasis vulgaris (PV) is a cutaneous inflammatory disorder stemming from abnormal, persistent activation of the interleukin- (IL-)23/Th17 axis. Pustular psoriasis (PP) is a clinicopathological variant of psoriasis, histopathologically defined by the predominance of intraepidermal collections of neutrophils. Although PP pathogenesis is thought to largely follow that of (PV), recent evidences point to a more central role for IL-1, IL-36, and IL-6 in the development of PP. We review the role of IL-6 in the pathogenesis of PV and PP, focusing on its cross-talk with cytokines of the IL-23/Th17 axis. Clinical inhibitors of IL-6 signaling, including tocilizumab, have shown significant effectiveness in the treatment of several inflammatory rheumatic diseases, including rheumatoid arthritis and juvenile idiopathic arthritis; accordingly, anti-IL-6 agents may potentially represent future promising therapies for the treatment of PP. PMID:25126586

  5. Comparison of C5 and C6 Aqua-MODIS Dark Target Aerosol Validation

    NASA Technical Reports Server (NTRS)

    Munchak, Leigh A.; Levy, Robert C.; Mattoo, Shana

    2014-01-01

    We compare C5 and C6 validation to compare the C6 10 km aerosol product against the well validated and trusted aerosol product on global and regional scales. Only the 10 km aerosol product is evaluated in this study, validation of the new C6 3 km aerosol product still needs to be performed. Not all of the time series has processed yet for C5 or C6, and the years processed for the 2 products is not exactly the same (this work is preliminary!). To reduce the impact of outlier observations, MODIS is spatially averaged within 27.5 km of the AERONET site, and AERONET is temporatally averaged within 30 minutes of the MODIS overpass time. Only high quality (QA = 3 over land, QA greater than 0 over ocean) pixels are included in the mean.

  6. Ceramide Synthase 6 Is a Novel Target of Methotrexate Mediating Its Antiproliferative Effect in a p53-Dependent Manner.

    PubMed

    Fekry, Baharan; Esmaeilniakooshkghazi, Amin; Krupenko, Sergey A; Krupenko, Natalia I

    2016-01-01

    We previously reported that ceramide synthase 6 (CerS6) is elevated in response to folate stress in cancer cells, leading to enhanced production of C16-ceramide and apoptosis. Antifolate methotrexate (MTX), a drug commonly used in chemotherapy of several types of cancer, is a strong inhibitor of folate metabolism. Here we investigated whether this drug targets CerS6. We observed that CerS6 protein was markedly elevated in several cancer cell lines treated with MTX. In agreement with the enzyme elevation, its product C16-ceramide was also strongly elevated, so as several other ceramide species. The increase in C16-ceramide, however, was eliminated in MTX-treated cells lacking CerS6 through siRNA silencing, while the increase in other ceramides sustained. Furthermore, the siRNA silencing of CerS6 robustly protected A549 lung adenocarcinoma cells from MTX toxicity, while the silencing of another ceramide synthase, CerS4, which was also responsive to folate stress in our previous study, did not interfere with the MTX effect. The rescue effect of CerS6 silencing upon MTX treatment was further confirmed in HCT116 and HepG2 cell lines. Interestingly, CerS6 itself, but not CerS4, induced strong antiproliferative effect in several cancer cell lines if elevated by transient transfection. The effect of MTX on CerS6 elevation was likely p53 dependent, which is in agreement with the hypothesis that the protein is a transcriptional target of p53. In line with this notion, lometrexol, the antifolate inducing cytotoxicity through the p53-independent mechanism, did not affect CerS6 levels. We have also found that MTX induces the formation of ER aggregates, enriched with CerS6 protein. We further demonstrated that such aggregation requires CerS6 and suggests that it is an indication of ER stress. Overall, our study identified CerS6 and ceramide pathways as a novel MTX target.

  7. Ceramide Synthase 6 Is a Novel Target of Methotrexate Mediating Its Antiproliferative Effect in a p53-Dependent Manner

    PubMed Central

    Fekry, Baharan; Esmaeilniakooshkghazi, Amin; Krupenko, Sergey A.; Krupenko, Natalia I.

    2016-01-01

    We previously reported that ceramide synthase 6 (CerS6) is elevated in response to folate stress in cancer cells, leading to enhanced production of C16-ceramide and apoptosis. Antifolate methotrexate (MTX), a drug commonly used in chemotherapy of several types of cancer, is a strong inhibitor of folate metabolism. Here we investigated whether this drug targets CerS6. We observed that CerS6 protein was markedly elevated in several cancer cell lines treated with MTX. In agreement with the enzyme elevation, its product C16-ceramide was also strongly elevated, so as several other ceramide species. The increase in C16-ceramide, however, was eliminated in MTX-treated cells lacking CerS6 through siRNA silencing, while the increase in other ceramides sustained. Furthermore, the siRNA silencing of CerS6 robustly protected A549 lung adenocarcinoma cells from MTX toxicity, while the silencing of another ceramide synthase, CerS4, which was also responsive to folate stress in our previous study, did not interfere with the MTX effect. The rescue effect of CerS6 silencing upon MTX treatment was further confirmed in HCT116 and HepG2 cell lines. Interestingly, CerS6 itself, but not CerS4, induced strong antiproliferative effect in several cancer cell lines if elevated by transient transfection. The effect of MTX on CerS6 elevation was likely p53 dependent, which is in agreement with the hypothesis that the protein is a transcriptional target of p53. In line with this notion, lometrexol, the antifolate inducing cytotoxicity through the p53-independent mechanism, did not affect CerS6 levels. We have also found that MTX induces the formation of ER aggregates, enriched with CerS6 protein. We further demonstrated that such aggregation requires CerS6 and suggests that it is an indication of ER stress. Overall, our study identified CerS6 and ceramide pathways as a novel MTX target. PMID:26783755

  8. Targeted alteration of dietary n-3 and n-6 fatty acids for the treatment of chronic headaches: a randomized trial.

    PubMed

    Ramsden, Christopher E; Faurot, Keturah R; Zamora, Daisy; Suchindran, Chirayath M; Macintosh, Beth A; Gaylord, Susan; Ringel, Amit; Hibbeln, Joseph R; Feldstein, Ariel E; Mori, Trevor A; Barden, Anne; Lynch, Chanee; Coble, Rebecca; Mas, Emilie; Palsson, Olafur; Barrow, David A; Mann, J Douglas

    2013-11-01

    Omega-3 and n-6 fatty acids are biosynthetic precursors to lipid mediators with antinociceptive and pronociceptive properties. We conducted a randomized, single-blinded, parallel-group clinical trial to assess clinical and biochemical effects of targeted alteration in dietary n-3 and n-6 fatty acids for treatment of chronic headaches. After a 4-week preintervention phase, ambulatory patients with chronic daily headache undergoing usual care were randomized to 1 of 2 intensive, food-based 12-week dietary interventions: a high n-3 plus low n-6 (H3-L6) intervention, or a low n-6 (L6) intervention. Clinical outcomes included the Headache Impact Test (HIT-6, primary clinical outcome), Headache Days per month, and Headache Hours per day. Biochemical outcomes included the erythrocyte n-6 in highly unsaturated fatty acids (HUFA) score (primary biochemical outcome) and bioactive n-3 and n-6 derivatives. Fifty-six of 67 patients completed the intervention. Both groups achieved targeted intakes of n-3 and n-6 fatty acids. In intention-to-treat analysis, the H3-L6 intervention produced significantly greater improvement in the HIT-6 score (-7.5 vs -2.1; P<0.001) and the number of Headache Days per month (-8.8 vs -4.0; P=0.02), compared to the L6 group. The H3-L6 intervention also produced significantly greater reductions in Headache Hours per day (-4.6 vs -1.2; P=0.01) and the n-6 in HUFA score (-21.0 vs -4.0%; P<0.001), and greater increases in antinociceptive n-3 pathway markers 18-hydroxy-eicosapentaenoic acid (+118.4 vs +61.1%; P<0.001) and 17-hydroxy-docosahexaenoic acid (+170.2 vs +27.2; P<0.001). A dietary intervention increasing n-3 and reducing n-6 fatty acids reduced headache pain, altered antinociceptive lipid mediators, and improved quality-of-life in this population.

  9. A Universal Stress Protein Involved in Oxidative Stress Is a Phosphorylation Target for Protein Kinase CIPK6.

    PubMed

    Gutiérrez-Beltrán, Emilio; Personat, José María; de la Torre, Fernando; Del Pozo, Olga

    2017-01-01

    Calcineurin B-like interacting protein kinases (CIPKs) decode calcium signals upon interaction with the calcium sensors calcineurin B like proteins into phosphorylation events that result into adaptation to environmental stresses. Few phosphorylation targets of CIPKs are known and therefore the molecular mechanisms underlying their downstream output responses are not fully understood. Tomato (Solanum lycopersicum) Cipk6 regulates immune and susceptible Programmed cell death in immunity transforming Ca(2+) signals into reactive oxygen species (ROS) signaling. To investigate SlCipk6-induced molecular mechanisms and identify putative substrates, a yeast two-hybrid approach was carried on and a protein was identified that contained a Universal stress protein (Usp) domain present in bacteria, protozoa and plants, which we named "SlRd2". SlRd2 was an ATP-binding protein that formed homodimers in planta. SlCipk6 and SlRd2 interacted using coimmunoprecipitation and bimolecular fluorescence complementation (BiFC) assays in Nicotiana benthamiana leaves and the complex localized in the cytosol. SlCipk6 phosphorylated SlRd2 in vitro, thus defining, to our knowledge, a novel target for CIPKs. Heterologous SlRd2 overexpression in yeast conferred resistance to highly toxic LiCl, whereas SlRd2 expression in Escherichia coli UspA mutant restored bacterial viability in response to H2O2 treatment. Finally, transient expression of SlCipk6 in transgenic N benthamiana SlRd2 overexpressors resulted in reduced ROS accumulation as compared to wild-type plants. Taken together, our results establish that SlRd2, a tomato UspA, is, to our knowledge, a novel interactor and phosphorylation target of a member of the CIPK family, SlCipk6, and functionally regulates SlCipk6-mediated ROS generation.

  10. Hypoxia-Targeted Drug Q6 Induces G2-M Arrest and Apoptosis via Poisoning Topoisomerase II under Hypoxia

    PubMed Central

    Wang, Dandan; Ma, Jian; Zhou, Tianyi; Chen, Ying; Sheng, Rong; Hu, Yongzhou; Du, Ying; He, Qiaojun; Yang, Bo; Zhu, Hong

    2015-01-01

    In spite of the tremendous efforts dedicated to developing hypoxia-activated prodrugs, no agents yet have been approved for clinical therapy. In the present study, the hypoxic selective anti-cancer activity as well as the cellular target of a novel tirapazamine (TPZ) analogue, 7-methyl-3-(3-chlorophenyl)-quinoxaline-2-carbonitrile 1,4-dioxide (Q6) were investigated. Q6 implemented anti-cancer effects via poisoning topoisomerase II (topo II) under hypoxia. Modified trapped in agarose DNA immunostaining (TARDIS) assay showed more topo II–DNA cleavage complexes trapped by Q6 than TPZ at even lower concentration. In addition, by introducing ataxia-telangiectasia-mutated (ATM) kinase inhibitors caffeine and KU-60019, we displayed that Q6-triggered apoptosis was attributed, at least partially, to DNA double-strand breaks generated by the topo II-targeting effect. Collectively, Q6 stood out for its better hypoxia-selectivity and topo II-poisoning than the parental compound TPZ. All these data shed light on the research of Q6 as a promising hypoxia-activated prodrug candidate for human hepatocellular carcinoma therapy. PMID:26649750

  11. Hypoxia-Targeted Drug Q6 Induces G2-M Arrest and Apoptosis via Poisoning Topoisomerase II under Hypoxia.

    PubMed

    Chang, Linlin; Liu, Xiaowen; Wang, Dandan; Ma, Jian; Zhou, Tianyi; Chen, Ying; Sheng, Rong; Hu, Yongzhou; Du, Ying; He, Qiaojun; Yang, Bo; Zhu, Hong

    2015-01-01

    In spite of the tremendous efforts dedicated to developing hypoxia-activated prodrugs, no agents yet have been approved for clinical therapy. In the present study, the hypoxic selective anti-cancer activity as well as the cellular target of a novel tirapazamine (TPZ) analogue, 7-methyl-3-(3-chlorophenyl)-quinoxaline-2-carbonitrile 1,4-dioxide (Q6) were investigated. Q6 implemented anti-cancer effects via poisoning topoisomerase II (topo II) under hypoxia. Modified trapped in agarose DNA immunostaining (TARDIS) assay showed more topo II-DNA cleavage complexes trapped by Q6 than TPZ at even lower concentration. In addition, by introducing ataxia-telangiectasia-mutated (ATM) kinase inhibitors caffeine and KU-60019, we displayed that Q6-triggered apoptosis was attributed, at least partially, to DNA double-strand breaks generated by the topo II-targeting effect. Collectively, Q6 stood out for its better hypoxia-selectivity and topo II-poisoning than the parental compound TPZ. All these data shed light on the research of Q6 as a promising hypoxia-activated prodrug candidate for human hepatocellular carcinoma therapy.

  12. The construction of the multifunctional targeting ursolic acids liposomes and its apoptosis effects to C6 glioma stem cells

    PubMed Central

    Ying, Xue; Wang, Yahua; Xu, Haolun; Li, Xia; Yan, Helu; Tang, Hui; Wen, Chen; Li, Yingchun

    2017-01-01

    Brain gliomas, one of the most fatal tumors to human, severely threat the health and life of human. They are capable of extremely strong invasion ability. And invasive glioma cells could rapidly penetrate into normal brain tissues and break them. We prepared a kind of functional liposomes, which could be transported acrossing the blood-brain barrier (BBB) and afterwards induce the apoptosis of glioma stem cells. In this research, we chose ursolic acids (UA) as an anti-cancer drug to inhibit the growth of C6 glioma cells, while epigallocatechin 3-gallate(EGCG) as the agent that could induce the apoptosis of C6 glioma stem cells. With the targeting ability of MAN, the liposomes could be delivered through the BBB and finally were concentrated on the brain gliomas. Cell experiments in vitro demonstrated that the functional liposomes were able to significantly enhance the anti-cancer effects of the drugs due to promoting the apoptosis and endocytosis effects of C6 glioma cells and C6 glioma stem cells at the same time. Furthermore, the evaluations through animal models showed that the drugs could obviously prolong the survival period of brain glioma-bearing mice and inhibit the tumor growth. Consequently, multifunctional targeting ursolic acids liposomes could potentially improve the therapeutic effects on C6 glioma cells and C6 glioma stem cells. PMID:28969057

  13. IL-6 Antibody and RGD Peptide Conjugated Poly(amidoamine) Dendrimer for Targeted Drug Delivery of HeLa Cells.

    PubMed

    Mekuria, Shewaye Lakew; Debele, Tilahun Ayane; Chou, Hsiao-Ying; Tsai, Hsieh-Chih

    2016-01-14

    In this study, PAMAM dendrimer (G4.5) was conjugated with two targeting moieties, IL-6 antibody and RGD peptide (G4.5-IL6 and G4.5-RGD conjugates). Doxorubicin anticancer drug was physically loaded onto G4.5-IL6 and G4.5-RGD with the encapsulation efficiency of 51.3 and 30.1% respectively. The cellular internalization and uptake efficiency of G4.5-IL6/DOX and G4.5-RGD/DOX complexes was observed and compared by confocal microscopy and flow cytometry using HeLa cells, respectively. The lower IC50 value of G4.5-IL6/DOX in comparison to G4.5-RGD/DOX is indication that higher drug loading and faster drug release rate corresponded with greater cytotoxicity. The cytotoxic effect was further verified by increment in late apoptotic/necrotic cells due to delivery of drug through receptor-mediated endocytosis. On the basis of these results, G4.5-IL6 is a better suited carrier for targeted drug delivery of DOX to cervical cancer cells.

  14. Investigations of levitated helium drops

    NASA Astrophysics Data System (ADS)

    Whitaker, Dwight Lawrence

    1999-11-01

    We report on the development of two systems capable of levitating drops of liquid helium. Helium drops of ˜20 mum have been levitated with the radiation pressure from two counter-propagating Nd:YAG laser beams. Drops are produced with a submerged piezoelectric transducer, and could be held for up to three minutes in our optical trap. Calculations show that Brillouin and Raman scattering of the laser light in the liquid helium produces a negligible rate of evaporation of the drop. Evaporation caused by the enhanced vapor pressure of the curved drop surfaces appears to be a significant effect limiting the drop lifetimes. Helium drops as large as 2 cm in diameter have been suspended in the earth's gravitational field with a magnetic field. A commercial superconducting solenoid provides the necessary field, field-gradient product required to levitate the drops. Drops are cooled to 0.5 K with a helium-3 refrigerator, and can be held in the trap indefinitely. We have found that when two or more drops are levitated in the same magnetic trap, the drops often remain in a state of apparent contact without coalescing. This effect is a result of the evaporation of liquid from between the two drops, and is found to occur only for normal fluid drops. We can induce shape oscillations in charged, levitated drops with an applied ac electric field. We have measured the resonance frequencies and damping rates for the l = 2 mode of oscillation as function of temperature. We have also developed a theory to describe the small amplitude shape oscillations of a He II drop surrounded by its saturated vapor. In our theory, we have considered two sets of boundary conditions---one where the drop does not evaporate and another in which the liquid and vapor are in thermodynamic equilibrium. We have found that both solutions give a frequency that agrees well with experiment, but that the data for the damping rate agree better with the solution without evaporation.

  15. 43 CFR 16.2 - Applications for helium disposition agreements.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 43 Public Lands: Interior 1 2014-10-01 2014-10-01 false Applications for helium disposition... HELIUM § 16.2 Applications for helium disposition agreements. The application for a helium disposition... Secretary to determine that the proposal will conserve helium that will otherwise be wasted, drained, or...

  16. 43 CFR 16.2 - Applications for helium disposition agreements.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 43 Public Lands: Interior 1 2011-10-01 2011-10-01 false Applications for helium disposition... HELIUM § 16.2 Applications for helium disposition agreements. The application for a helium disposition... Secretary to determine that the proposal will conserve helium that will otherwise be wasted, drained, or...

  17. 43 CFR 16.2 - Applications for helium disposition agreements.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 43 Public Lands: Interior 1 2013-10-01 2013-10-01 false Applications for helium disposition... HELIUM § 16.2 Applications for helium disposition agreements. The application for a helium disposition... Secretary to determine that the proposal will conserve helium that will otherwise be wasted, drained, or...

  18. 43 CFR 16.2 - Applications for helium disposition agreements.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Applications for helium disposition... HELIUM § 16.2 Applications for helium disposition agreements. The application for a helium disposition... Secretary to determine that the proposal will conserve helium that will otherwise be wasted, drained, or...

  19. 43 CFR 16.2 - Applications for helium disposition agreements.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 43 Public Lands: Interior 1 2012-10-01 2011-10-01 true Applications for helium disposition... HELIUM § 16.2 Applications for helium disposition agreements. The application for a helium disposition... Secretary to determine that the proposal will conserve helium that will otherwise be wasted, drained, or...

  20. ETV6-NTRK3 as a therapeutic target of small molecule inhibitor PKC412

    SciTech Connect

    Chi, Hoang Thanh; Ly, Bui Thi Kim; Kano, Yasuhiko; Tojo, Arinobu; Sato, Yuko

    2012-12-07

    Highlights: Black-Right-Pointing-Pointer ETV6-NTRK3 is an oncogene with transformation activity in multiple cell lineages. Black-Right-Pointing-Pointer PKC412 could block ETV6-NTRK3 activation. Black-Right-Pointing-Pointer Loss of ETV6-NTRK3 phosphorylation leads to inactivation of its downstream signaling pathway. Black-Right-Pointing-Pointer Inhibition of ETV6-NTRK3 activation by PKC412 could be a novel strategy for the treatment. -- Abstract: The ETV6-NTRK3 (EN) fusion gene which encodes a chimeric tyrosine kinase was first identified by cloning of the t(12;15)(p13;q25) translocation in congenital fibrosarcoma (CFS). Since then, EN has been also found in congenital mesoblastic nephroma (CMN), secretory breast carcinoma (SBC) and acute myelogenous leukemia (AML). Using IMS-M2 and M0-91 cell lines harboring the EN fusion gene, and Ba/F3 cells stably transfected with EN, we demonstrated that PKC412, also known as midostaurin, is an inhibitor of EN. Inhibition of EN activity by PKC412 suppressed the activity of it downstream molecules leading to inhibition of cell proliferation and induction of apoptosis. Our data for the first time suggested that PKC412 could serve as therapeutic drug for treatment of patients with this fusion.

  1. Blocking CD40-TRAF6 signaling is a therapeutic target in obesity-associated insulin resistance

    PubMed Central

    Chatzigeorgiou, Antonios; Seijkens, Tom; Zarzycka, Barbara; Engel, David; Poggi, Marjorie; van den Berg, Susan; van den Berg, Sjoerd; Soehnlein, Oliver; Winkels, Holger; Beckers, Linda; Lievens, Dirk; Driessen, Ann; Kusters, Pascal; Biessen, Erik; Garcia-Martin, Ruben; Klotzsche-von Ameln, Anne; Gijbels, Marion; Noelle, Randolph; Boon, Louis; Hackeng, Tilman; Schulte, Klaus-Martin; Xu, Aimin; Vriend, Gert; Nabuurs, Sander; Chung, Kyoung-Jin; Willems van Dijk, Ko; Rensen, Patrick C. N.; Gerdes, Norbert; de Winther, Menno; Block, Norman L.; Schally, Andrew V.; Weber, Christian; Bornstein, Stefan R.; Nicolaes, Gerry; Chavakis, Triantafyllos; Lutgens, Esther

    2014-01-01

    The immune system plays an instrumental role in obesity and insulin resistance. Here, we unravel the role of the costimulatory molecule CD40 and its signaling intermediates, TNF receptor-associated factors (TRAFs), in diet-induced obesity (DIO). Although not exhibiting increased weight gain, male CD40−/− mice in DIO displayed worsened insulin resistance, compared with wild-type mice. This worsening was associated with excessive inflammation of adipose tissue (AT), characterized by increased accumulation of CD8+ T cells and M1 macrophages, and enhanced hepatosteatosis. Mice with deficient CD40-TRAF2/3/5 signaling in MHCII+ cells exhibited a similar phenotype in DIO as CD40−/− mice. In contrast, mice with deficient CD40-TRAF6 signaling in MHCII+ cells displayed no insulin resistance and showed a reduction in both AT inflammation and hepatosteatosis in DIO. To prove the therapeutic potential of inhibition of CD40-TRAF6 in obesity, DIO mice were treated with a small-molecule inhibitor that we designed to specifically block CD40-TRAF6 interactions; this compound improved insulin sensitivity, reduced AT inflammation, and decreased hepatosteatosis. Our study reveals that the CD40-TRAF2/3/5 signaling pathway in MHCII+ cells protects against AT inflammation and metabolic complications associated with obesity whereas CD40-TRAF6 interactions in MHCII+ cells aggravate these complications. Inhibition of CD40-TRAF6 signaling by our compound may provide a therapeutic option in obesity-associated insulin resistance. PMID:24492375

  2. Targeted inhibition of RAGE in substantia nigra of rats blocks 6-OHDA-induced dopaminergic denervation.

    PubMed

    Gasparotto, Juciano; Ribeiro, Camila Tiefensee; Bortolin, Rafael Calixto; Somensi, Nauana; Rabelo, Thallita Kelly; Kunzler, Alice; Souza, Natália Cabral; Pasquali, Matheus Augusto de Bittencourt; Moreira, José Claudio Fonseca; Gelain, Daniel Pens

    2017-08-18

    The receptor for advanced glycation endproducts (RAGE) is a pattern-recognition receptor associated with inflammation in most cell types. RAGE up-regulates the expression of proinflammatory mediators and its own expression via activation of NF-kB. Recent works have proposed a role for RAGE in Parkinson's disease (PD). In this study, we used the multimodal blocker of RAGE FPS-ZM1, which has become available recently, to selectively inhibit RAGE in the substantia nigra (SN) of rats intracranially injected with 6-hydroxydopamine (6-OHDA). FPS-ZM1 (40 μg per rat), injected concomitantly with 6-OHDA (10 μg per rat) into the SN, inhibited the increase in RAGE, activation of ERK1/2, Src and nuclear translocation of NF-kB p65 subunit in the SN. RAGE inhibition blocked glial fibrillary acidic protein and Iba-1 upregulation as well as associated astrocyte and microglia activation. Circulating cytokines in serum and CSF were also decreased by FPS-ZM1 injection. The loss of tyrosine hydroxylase and NeuN-positive neurons was significantly inhibited by RAGE blocking. Finally, FPS-ZM1 attenuated locomotory and exploratory deficits induced by 6-OHDA. Our results demonstrate that RAGE is an essential component in the neuroinflammation and dopaminergic denervation induced by 6-OHDA in the SN. Selective inhibition of RAGE may offer perspectives for therapeutic approaches.

  3. Thermodynamic properties of hydrogen-helium plasmas.

    NASA Technical Reports Server (NTRS)

    Nelson, H. F.

    1972-01-01

    Calculation of the thermodynamic properties of an atomic hydrogen-helium plasma for postulated conditions present in a stagnation shock layer of a spacecraft entering the atmosphere of Jupiter. These properties can be used to evaluate transport properties, to calculate convective heating, and to investigate nonequilibrium behavior. The calculations have been made for temperatures from 10,000 to 100,000 K, densities of 10 to the minus 7th and .00001 g cu cm, and three plasma compositions: pure hydrogen, 50% hydrogen/50% helium, and pure helium. The shock layer plasma consists of electrons, protons, atomic hydrogen, atomic helium, singly ionized helium, and doubly atomized helium. The thermodynamic properties which have been investigated are: pressure, average molecular weight, internal energy, enthalpy, entropy, specific heat, and isentropic speed of sound. A consistent model was used for the reduction of the ionization potential in the calculation of the partition functions.

  4. Solubility and trapping of helium in apatite

    NASA Astrophysics Data System (ADS)

    Zeitler, Peter K.; Enkelmann, Eva; Thomas, Jay B.; Watson, E. Bruce; Ancuta, Leonard D.; Idleman, Bruce D.

    2017-07-01

    A fundamental but unquantified assumption in U-Th/He dating of apatite is that grains do not incorporate extraneous helium by solution or other processes, but large age dispersion seen in some samples suggests that this assumption might be violated. Our laboratory experiments show that helium solubility in apatite is quite low and unlikely to lead to age dispersion in most samples. However, in some samples highly variable and sometimes large helium uptake suggests that apatite grains can trap helium in microvoids that could be derived from fluid inclusions or other microstructures, a conclusion supported by crushing and step-heating experiments. The presence of such microvoids raises the possibility that closure and age systematics could be complicated either by trapping of internally generated radiogenic helium and/or alteration of helium diffusion kinetics by impeding diffusion.

  5. Thermodynamic properties of hydrogen-helium plasmas.

    NASA Technical Reports Server (NTRS)

    Nelson, H. F.

    1972-01-01

    Calculation of the thermodynamic properties of an atomic hydrogen-helium plasma for postulated conditions present in a stagnation shock layer of a spacecraft entering the atmosphere of Jupiter. These properties can be used to evaluate transport properties, to calculate convective heating, and to investigate nonequilibrium behavior. The calculations have been made for temperatures from 10,000 to 100,000 K, densities of 10 to the minus 7th and .00001 g cu cm, and three plasma compositions: pure hydrogen, 50% hydrogen/50% helium, and pure helium. The shock layer plasma consists of electrons, protons, atomic hydrogen, atomic helium, singly ionized helium, and doubly atomized helium. The thermodynamic properties which have been investigated are: pressure, average molecular weight, internal energy, enthalpy, entropy, specific heat, and isentropic speed of sound. A consistent model was used for the reduction of the ionization potential in the calculation of the partition functions.

  6. Helium recovery and purification at CHMFL

    NASA Astrophysics Data System (ADS)

    Li, J.; Meng, Q.; Ouyang, Z.; Shi, L.; Ai, X.; Chen, X.

    2017-02-01

    Currently, rising demand and declining reserves of helium have led to dramatic increases in the helium price. The High Magnetic Field Laboratory of Chinese Academy of Sciences (CHMFL) has made efforts since its foundation to increase the percentage of helium recovered. The piping network connects all the helium experimental facilities to the recovery system, and even exhaust ports of pressure relief valves and vacuum pumps are also connected. In each year, about 30,000 cubic meters helium gas is recovered. The recovery gas is purified, liquefied and supplied to the users again. This paper will provide details about the helium recovery and purification system at CHMFL, including system flowchart, components, problems and solutions.

  7. On charged impurity structures in liquid helium

    NASA Astrophysics Data System (ADS)

    Pelmenev, A. A.; Krushinskaya, I. N.; Bykhalo, I. B.; Boltnev, R. E.

    2016-03-01

    The thermoluminescence spectra of impurity-helium condensates (IHC) submerged in superfluid helium have been observed for the first time. Thermoluminescence of impurity-helium condensates submerged in superfluid helium is explained by neutralization reactions occurring in impurity nanoclusters. Optical spectra of excited products of neutralization reactions between nitrogen cations and thermoactivated electrons were rather different from the spectra observed at higher temperatures, when the luminescence due to nitrogen atom recombination dominates. New results on current detection during the IHC destruction are presented. Two different mechanisms of nanocluster charging are proposed to describe the phenomena observed during preparation and warm-up of IHC samples in bulk superfluid helium, and destruction of IHC samples out of liquid helium.

  8. Helium Ionization in the Diffuse Ionized Gas Surrounding UCH ii Regions

    NASA Astrophysics Data System (ADS)

    Anish Roshi, D.; Churchwell, E.; Anderson, L. D.

    2017-04-01

    We present measurements of the singly ionized helium-to-hydrogen ratio ({n}{{He}+}/{n}{{{H}}+}) toward diffuse gas surrounding three ultracompact H ii (UCH ii) regions: G10.15-0.34, G23.46-0.20, and G29.96-0.02. We observe radio recombination lines of hydrogen and helium near 5 GHz using the GBT to measure the {n}{{He}+}/{n}{{{H}}+} ratio. The measurements are motivated by the low helium ionization observed in the warm ionized medium and in the inner Galaxy diffuse ionized regions. Our data indicate that the helium is not uniformly ionized in the three observed sources. Helium lines are not detected toward a few observed positions in sources G10.15-0.34 and G23.46-0.20, and the upper limits of the {n}{{He}+}/{n}{{{H}}+} ratio obtained are 0.03 and 0.05, respectively. The selected sources harbor stars of type O6 or hotter as indicated by helium line detection toward the bright radio continuum emission from the sources with mean {n}{{He}+}/{n}{{{H}}+} value 0.06 ± 0.02. Our data thus show that helium in diffuse gas located a few parsecs away from the young massive stars embedded in the observed regions is not fully ionized. We investigate the origin of the nonuniform helium ionization and rule out the possibilities (a) that the helium is doubly ionized in the observed regions and (b) that the low {n}{{He}+}/{n}{{{H}}+} values are due to additional hydrogen ionizing radiation produced by accreting low-mass stars. We find that selective absorption of ionizing photons by dust can result in low helium ionization but needs further investigation to develop a self-consistent model for dust in H ii regions.

  9. Helium Ionization in the Diffuse Ionized Gas Surrounding UCH ii Regions

    NASA Astrophysics Data System (ADS)

    Roshi, D. Anish; Churchwell, E.; Anderson, L. D.

    2017-04-01

    We present measurements of the singly ionized helium-to-hydrogen ratio ({n}{{He}+}/{n}{{{H}}+}) toward diffuse gas surrounding three ultracompact H ii (UCH ii) regions: G10.15-0.34, G23.46-0.20, and G29.96-0.02. We observe radio recombination lines of hydrogen and helium near 5 GHz using the GBT to measure the {n}{{He}+}/{n}{{{H}}+} ratio. The measurements are motivated by the low helium ionization observed in the warm ionized medium and in the inner Galaxy diffuse ionized regions. Our data indicate that the helium is not uniformly ionized in the three observed sources. Helium lines are not detected toward a few observed positions in sources G10.15-0.34 and G23.46-0.20, and the upper limits of the {n}{{He}+}/{n}{{{H}}+} ratio obtained are 0.03 and 0.05, respectively. The selected sources harbor stars of type O6 or hotter as indicated by helium line detection toward the bright radio continuum emission from the sources with mean {n}{{He}+}/{n}{{{H}}+} value 0.06 ± 0.02. Our data thus show that helium in diffuse gas located a few parsecs away from the young massive stars embedded in the observed regions is not fully ionized. We investigate the origin of the nonuniform helium ionization and rule out the possibilities (a) that the helium is doubly ionized in the observed regions and (b) that the low {n}{{He}+}/{n}{{{H}}+} values are due to additional hydrogen ionizing radiation produced by accreting low-mass stars. We find that selective absorption of ionizing photons by dust can result in low helium ionization but needs further investigation to develop a self-consistent model for dust in H ii regions.

  10. Design, synthesis and evaluation of novel 2,5,6-trisubstituted benzimidazoles targeting FtsZ as antitubercular agents.

    PubMed

    Park, Bora; Awasthi, Divya; Chowdhury, Soumya R; Melief, Eduard H; Kumar, Kunal; Knudson, Susan E; Slayden, Richard A; Ojima, Iwao

    2014-05-01

    Filamenting temperature-sensitive protein Z (FtsZ), an essential cell division protein, is a promising target for the drug discovery of new-generation antibacterial agents against various bacterial pathogens. As a part of SAR studies on benzimidazoles, we have synthesized a library of 376 novel 2,5,6-trisubstituted benzimidazoles, bearing ether or thioether linkage at the 6-position. In a preliminary HTP screening against Mtb H37Rv, 108 compounds were identified as hits at a cut off concentration of 5 μg/mL. Among those hits, 10 compounds exhibited MIC values in the range of 0.63-12.5 μg/mL. Light scattering assay and TEM analysis with the most potent compound 5a clearly indicate that its molecular target is Mtb-FtsZ. Also, the Kd of 5a with Mtb-FtsZ was determined to be 1.32 μM.

  11. MiR-361-5p acts as a tumor suppressor in prostate cancer by targeting signal transducer and activator of transcription-6(STAT6)

    SciTech Connect

    Liu, Dachuang; Tao, Tao; Xu, Bin; Chen, Shuqiu; Liu, Chunhui; Zhang, Lei; Lu, Kai; Huang, Yeqing; Jiang, Liang; Zhang, Xiaowen; Huang, Xiaoming; Zhang, Lihua; Han, Conghui; Chen, Ming

    2014-02-28

    Highlights: • The role of miR-361-5p in prostate cancer (PCa) has not been evaluated until date. • We found that the expression of miR-361-5p in CRPC was lower than in ADPC. • MiR-361-5p suppressed DU145 cell proliferation and triggered apoptosis. • STAT6 is a direct target of miR-361-5p. • STAT6 enhances the expression of Bcl-xL at the transcriptional level. - Abstract: Castration-resistant prostate cancer (CRPC), whose pathogenesis is known to be regulated by microRNAs (miRNAs), has a poor prognosis. In our present study, we found that the expression of miR-361-5p in CRPC was lower than in androgen-dependent prostate cancer (ADPC), indicating that miR-361-5p may play an important role in the progression of ADPC to CRPC. The role of miR-361-5p in prostate cancer (PCa) has not been evaluated until date. Our findings suggest that miR-361-5p is a suppressor in CRPC. Signal transducer and activator of transcription-6 (STAT6), a direct target of miR-361-5p, enhances the expression of B-cell lymphoma-extra large (Bcl-xL), while miR-361-5p inhibits its expression through STAT6. Therefore, miR-361-5p has great clinical significance in preventing the malignant progression of PCa.

  12. IL-6 Inhibits the Targeted Modulation of PDCD4 by miR-21 in Prostate Cancer.

    PubMed

    Dong, Biao; Shi, Zhihao; Wang, Jiaping; Wu, Jing; Yang, Zhaoqing; Fang, Kewei

    2015-01-01

    Prostate cancer is the most common cancer among men in the Unites States. The cytokine IL-6 activates several prostate cancer pathways, but its upstream trans-signaling pathway remains poorly understood. In this study, we evaluated the role of IL-6 in PDCD4 gene expression and how the microRNA miR-21 regulates this process in prostate cancer cell lines PC-3 and LNCaP. The expression pattern of PDCD4 from samples from human prostate cancer, precancerous lesions, and benign prostatic hyperplasia was investigated by immunohistochemistry. PDCD4 transcription and translation were detected by quantitative real-time PCR (qRT-PCR) and Western blot analysis, respectively. The targeted modulation of PDCD4 by miR-21 was analyzed in PC-3 and LNCaP cells, and the effect of IL-6 on the expression of PDCD4 was studied in vitro. PDCD4 expression in samples from the 3 tissue types progressively increased, and the expression levels of PDCD4 and prostate-specific antigen were negatively correlated. The levels of PDCD4 mRNA and protein in PC-3 and LNCaP cells transfected with anti-miR-21 constructs were lower than those in control cells. The expression of PDCD4 was inhibited by IL-6, but this effect was weakened in cell lines with low expression of miR-21. Our study demonstrates that the regulation of PDCD4 by miR-21 is targeted and IL-6 inhibits expression of the PDCD4 gene in PC-3 and LNCaP cells through the targeted function of miR-21 on PDCD4. These findings support the feasibility of future efforts for diagnosis and gene therapy for prostate cancer that are based on IL-6, miR-21, and PDCD4.

  13. Deciphering downstream gene targets of PI3K/mTOR/p70S6K pathway in breast cancer

    PubMed Central

    Heinonen, Henna; Nieminen, Anni; Saarela, Matti; Kallioniemi, Anne; Klefström, Juha; Hautaniemi, Sampsa; Monni, Outi

    2008-01-01

    Background The 70 kDa ribosomal protein S6 kinase (RPS6KB1), located at 17q23, is amplified and overexpressed in 10–30% of primary breast cancers and breast cancer cell lines. p70S6K is a serine/threonine kinase regulated by PI3K/mTOR pathway, which plays a crucial role in control of cell cycle, growth and survival. Our aim was to determine p70S6K and PI3K/mTOR/p70S6K pathway dependent gene expression profiles by microarrays using five breast cancer cell lines with predefined gene copy number and gene expression alterations. The p70S6K dependent profiles were determined by siRNA silencing of RPS6KB1 in two breast cancer cell lines overexpressing p70S6K. These profiles were further correlated with gene expression alterations caused by inhibition of PI3K/mTOR pathway with PI3K inhibitor Ly294002 or mTOR inhibitor rapamycin. Results Altogether, the silencing of p70S6K altered the expression of 109 and 173 genes in two breast cancer cell lines and 67 genes were altered in both cell lines in addition to RPS6KB1. Furthermore, 17 genes including VTCN1 and CDKN2B showed overlap with genes differentially expressed after PI3K or mTOR inhibition. The gene expression signatures responsive to both PI3K/mTOR pathway and p70S6K inhibitions revealed previously unidentified genes suggesting novel downstream targets for PI3K/mTOR/p70S6K pathway. Conclusion Since p70S6K overexpression is associated with aggressive disease and poor prognosis of breast cancer patients, the potential downstream targets of p70S6K and the whole PI3K/mTOR/p70S6K pathway identified in our study may have diagnostic value. PMID:18652687

  14. MicroRNA-181b regulates endotoxin tolerance by targeting IL-6 in macrophage RAW264.7 cells.

    PubMed

    Zhang, Wenjun; Shen, Xiaojun; Xie, Luyang; Chu, Maoping; Ma, Yanmei

    2015-01-01

    Interleukin 6 (IL-6) is a major pro-inflammatory cytokine and dysregulation of IL-6 is relevant to many inflammatory diseases. Endotoxin induced tolerance of IL-6 is an important mechanism to avoid the excessive immune reaction. But to date, the molecular mechanisms of endotoxin tolerance of IL-6 remain unclear. Here we reported that IL-6 secretion and microRNA-181b (miR-181b) expression were inversely correlated following LPS stimulation. We also demonstrated that miR-181b targeting the 3'-UTR of IL-6 transcripts and up-regulation of miR-181b was associated with NF-kB. We further demonstrated that up-regulation of miR-181b in response to LPS was required for inducing IL-6 tolerance in macrophage. Our results suggested that the post-transcriptional control mediated by miR-181b could be involved in fine tuning the critical level of IL-6 expression in endotoxin tolerance.

  15. Helium isotopic abundance variation in nature

    SciTech Connect

    Holden, N.E.

    1993-08-01

    The isotopic abundance of helium in nature has been reviewed. This atomic weight value is based on the value of helium in the atmosphere, which is invariant around the world and up to a distance of 100,000 feet. Helium does vary in natural gas, volcanic rocks and gases, ocean floor sediments, waters of various types and in radioactive minerals and ores due to {alpha} particle decay of radioactive nuclides.

  16. Helium sell-off risks future supply

    NASA Astrophysics Data System (ADS)

    Banks, Michael

    2010-03-01

    The US must stop selling off its helium reserves so that the country has enough of the gas to meet the needs of researchers and medical programmes, warns a report by the National Academy of Sciences (NAS). The report, entitled "Selling the Nation's Helium Reserve", says that failure to halt the sale of helium could lead to a drop in supply of the gas, which is vital for research into magnetic resonance imaging (MRI) techniques and low-temperature physics.

  17. Energy, helium, and the future: II

    SciTech Connect

    Krupka, M.C.; Hammel, E.F.

    1980-01-01

    The importance of helium as a critical resource material has been recognized specifically by the scientific community and more generally by the 1960 Congressional mandate to institute a long-range conservation program. A major study mandated by the Energy Reorganization Act of 1974 resulted in the publication in 1975 of the document, The Energy-Related Applications of Helium, ERDA-13. This document contained a comprehensive review and analysis relating to helium resources and present and future supply/demand relationships with particular emphasis upon those helium-dependent energy-related technologies projected to be implemented in the post-2000 year time period, e.g., fusion. An updated overview of the helium situation as it exists today is presented. Since publication of ERDA-13, important changes in the data base underlying that document have occurred. The data have since been reexamined, revised, and new information included. Potential supplies of helium from both conventional and unconventional natural gas resources, projected supply/demand relationships to the year 2030 based upon a given power-generation scenario, projected helium demand for specific energy-related technologies, and the supply options (national and international) available to meet that demand are discussed. An updated review will be given of the energy requirements for the extraction of helium from natural gas as they relate to the concentration of helium. A discussion is given concerning the technical and economic feasibility of several methods available both now and conceptually possible, to extract helium from helium-lean natural gas, the atmosphere, and outer space. Finally, a brief review is given of the 1980 Congressional activities with respect to the introduction and possible passage of new helium conservation legislation.

  18. Helium cyclotron resonance within the earth's magnetosphere

    SciTech Connect

    Mauk, B.H.; McIlwain, C.E.; McPherron, R.L.

    1981-01-01

    A histogram of electromagnetic Alfven/ion cyclotron wave frequencies, sampled within the geostationary enviroment and normalized by the equatorial proton cyclotron frequency, shows a dramatic gap centered near the helium (He/sup +/) cyclotron frequency. Also, strongly cyclotron phase bunched helium ions (20--200 eV) have been observed directly within the vicinity of wave environments. These observations are interpreted as resulting from the absorption of the waves through cyclotron resonance by cool ambient populations of helium ions.

  19. Limited Quantum Helium Transportation through Nano-channels by Quantum Fluctuation.

    PubMed

    Ohba, Tomonori

    2016-07-01

    Helium at low temperatures has unique quantum properties such as superfluidity, which causes it to behave differently from a classical fluid. Despite our deep understanding of quantum mechanics, there are many open questions concerning the properties of quantum fluids in nanoscale systems. Herein, the quantum behavior of helium transportation through one-dimensional nanopores was evaluated by measuring the adsorption of quantum helium in the nanopores of single-walled carbon nanohorns and AlPO4-5 at 2-5 K. Quantum helium was transported unimpeded through nanopores larger than 0.7 nm in diameter, whereas quantum helium transportation was significantly restricted through 0.4-nm and 0.6-nm nanopores. Conversely, nitrogen molecules diffused through the 0.4-nm nanopores at 77 K. Therefore, quantum helium behaved as a fluid comprising atoms larger than 0.4-0.6 nm. This phenomenon was remarkable, considering that helium is the smallest existing element with a (classical) size of approximately 0.27 nm. This finding revealed the presence of significant quantum fluctuations. Quantum fluctuation determined the behaviors of quantum flux and is essential to understanding unique quantum behaviors in nanoscale systems.

  20. Limited Quantum Helium Transportation through Nano-channels by Quantum Fluctuation

    PubMed Central

    Ohba, Tomonori

    2016-01-01

    Helium at low temperatures has unique quantum properties such as superfluidity, which causes it to behave differently from a classical fluid. Despite our deep understanding of quantum mechanics, there are many open questions concerning the properties of quantum fluids in nanoscale systems. Herein, the quantum behavior of helium transportation through one-dimensional nanopores was evaluated by measuring the adsorption of quantum helium in the nanopores of single-walled carbon nanohorns and AlPO4-5 at 2–5 K. Quantum helium was transported unimpeded through nanopores larger than 0.7 nm in diameter, whereas quantum helium transportation was significantly restricted through 0.4-nm and 0.6-nm nanopores. Conversely, nitrogen molecules diffused through the 0.4-nm nanopores at 77 K. Therefore, quantum helium behaved as a fluid comprising atoms larger than 0.4–0.6 nm. This phenomenon was remarkable, considering that helium is the smallest existing element with a (classical) size of approximately 0.27 nm. This finding revealed the presence of significant quantum fluctuations. Quantum fluctuation determined the behaviors of quantum flux and is essential to understanding unique quantum behaviors in nanoscale systems. PMID:27363671

  1. Toolkit for Professional Developers: Training Targets 3?6 Grade Teachers

    ERIC Educational Resources Information Center

    McMunn, Nancy; Dunnivant, Michael; Williamson, Jan; Reagan, Hope

    2004-01-01

    The professional development CAR Toolkit is focused on the assessment of reading process at the text level, rather than at the word level. Most students in grades 3-6 generally need support in comprehending text, not just decoding words. While the assessment of reading methods in the CAR Toolkit will help teachers pinpoint difficulties at the word…

  2. A fully humanized IgG-like bispecific antibody for effective dual targeting of CXCR3 and CCR6.

    PubMed

    Robert, Remy; Juglair, Laurent; Lim, Ee X; Ang, Caroline; Wang, Carl J H; Ebert, Gregor; Dolezal, Olan; Mackay, Charles R

    2017-01-01

    Chemokines and their receptors are pivotal for the trafficking of leukocytes during immune responses, and host defense. However, immune cell migration also contributes to a wide variety of autoimmune and chronic inflammatory diseases. Compelling evidence suggests that both CXCR3 and CCR6 chemokine receptors play crucial roles in the migration of pathological Th1 and Th17 cells during the course of certain inflammatory diseases. The use of two or more receptors by pathogenic cells may explain why targeting of individual receptors has proven disappointing in the clinic. We therefore hypothesized that simultaneous targeting of both CXCR3 and CCR6 with a bispecific antibody (BsAb) might result in decreased chemotaxis and/or specific depletion of pro-inflammatory T cell subsets. In this study, we designed and characterized a fully humanized BsAb. We show that the BsAb binds to both chemokine receptors, as demonstrated by Flow Cytometry and Surface Plasmon Resonance analysis. Furthermore, we demonstrate that the BsAb effectively blocks cell chemotaxis and induces specific antibody-dependent cell-mediated cytotoxicity (ADCC) in vitro. Therefore, we propose that dual targeting of CXCR3 and CCR6 with a fully humanized BsAb may display a potent interventional approach for the treatment of inflammatory and autoimmune diseases.

  3. Profiling Global Kinome Signatures of the Radioresistant MCF-7/C6 Breast Cancer Cells Using MRM-based Targeted Proteomics

    PubMed Central

    2015-01-01

    Ionizing radiation is widely used in cancer therapy; however, cancer cells often develop radioresistance, which compromises the efficacy of cancer radiation therapy. Quantitative assessment of the alteration of the entire kinome in radioresistant cancer cells relative to their radiosensitive counterparts may provide important knowledge to define the mechanism(s) underlying tumor adaptive radioresistance and uncover novel target(s) for effective prevention and treatment of tumor radioresistance. By employing a scheduled multiple-reaction monitoring analysis in conjunction with isotope-coded ATP affinity probes, we assessed the global kinome of radioresistant MCF-7/C6 cells and their parental MCF-7 human breast cancer cells. We rigorously quantified 120 kinases, of which 1/3 exhibited significant differences in expression levels or ATP binding affinities. Several kinases involved in cell cycle progression and DNA damage response were found to be overexpressed or hyperactivated, including checkpoint kinase 1 (CHK1), cyclin-dependent kinases 1 and 2 (CDK1 and CDK2), and the catalytic subunit of DNA-dependent protein kinase. The elevated expression of CHK1, CDK1, and CDK2 in MCF-7/C6 cells was further validated by Western blot analysis. Thus, the altered kinome profile of radioresistant MCF-7/C6 cells suggests the involvement of kinases on cell cycle progression and DNA repair in tumor adaptive radioresistance. The unique kinome profiling results also afforded potential effective targets for resensitizing radioresistant cancer cells and counteracting deleterious effects of ionizing radiation exposure. PMID:25341124

  4. Efficacy and selectivity of phosphodiesterase-targeted drugs to inhibit photoreceptor phosphodiesterase (PDE6) in retinal photoreceptors*

    PubMed Central

    Zhang, Xiujun; Feng, Qing; Cote, Rick H.

    2005-01-01

    Purpose: Phosphodiesterase (PDE) inhibitors are important therapeutic agents, but their effects on photoreceptor PDE (PDE6) and photoreceptor cells are poorly understood. We characterized the potency and selectivity of various classes of PDE inhibitors on purified rod and cone PDE6 and on intact rod outer segments (ROS). Methods: The inhibition constant (KI) of isozyme-selective PDE inhibitors was determined for purified rod and cone PDE6. Perturbations of cGMP levels in isolated ROS suspensions by PDE inhibitors were quantitated by a cGMP enzyme-linked immunoassay. Results: Most PDE5-selective inhibitors are excellent PDE6 inhibitors. Vardenafil, a potent PDE5 inhibitor (KI = 0.2 nM), is the most potent PDE6 inhibitor tested (KI = 0.7 nM). Zaprinast is the only drug that inhibits PDE6 more potently than PDE5. PDE1-selective inhibitors were equally effective in inhibiting PDE6. In intact ROS, PDE inhibitors elevated cGMP levels but none fully inhibited PDE6. Their potency to elevate cGMP levels in ROS was much lower than their ability to inhibit the purified enzyme. Competition between PDE5/6-selective drugs and the inhibitory γ subunit for the active site of PDE6 is proposed to reduce the effectiveness of drugs at the enzyme active site. Conclusions: Several classes of PDE inhibitors equally well inhibit PDE6 as the PDE family to which they are targeted. In intact ROS, high PDE6 concentrations, binding of the γ subunit to the active site, and calcium feedback mechanisms attenuate the effectiveness of PDE inhibitors to inhibit PDE6 and disrupt the cGMP signaling pathway during visual transduction. PMID:16123402

  5. MiR-285 targets P450 (CYP6N23) to regulate pyrethroid resistance in Culex pipiens pallens.

    PubMed

    Tian, Mengmeng; Liu, Bingqian; Hu, Hongxia; Li, Xixi; Guo, Qin; Zou, Feifei; Liu, Xianmiao; Hu, Mengxue; Guo, Juxin; Ma, Lei; Zhou, Dan; Sun, Yan; Shen, Bo; Zhu, Changliang

    2016-12-01

    MicroRNAs play critical roles in post-transcriptional regulation of gene expression, which participate in the modulation of almost all of the cellular processes. Although emerging evidence indicates that microRNAs are related with antineoplastic drugs resistance, whether microRNAs are responsible for insecticide resistance in mosquitos is poorly understood. In this paper, we found that miR-285 was significantly upregulated in the deltamethrin-resistant strain of Culex pipiens pallens, and overexpression miR-285 through microinjection increased mosquito survival rate against deltamethrin treatement. Using bioinformatic software, quantitative reverse transcription PCR, luciferase reporter assay and microinjection approaches, we conformed that CYP6N23 was the target of miR-285. Lower expression of CYP6N23 was observed in the deltamethrin-resistant strain. While, mosquito mortality rate was decreased after downregulating expression of CYP6N23 by dsRNA against CYP6N23 or miR-285 mimic microinjection. These findings revealed that miR-285 could target CYP6N23 to regulate pyrethroid resistance, providing new insights into mosquito insecticide resistance surveillance and control.

  6. Radioactive transitions in the helium isoelectronic sequence

    NASA Technical Reports Server (NTRS)

    Dalgarno, A.

    1971-01-01

    The principles of the atomic spectrum theory are used to quantitatively analyze radiation transitions in two-electron helium-like atomic systems. Quantum theoretical methods, describing absorption and emission of a single photon in a radiative transition between two stationary states of an atomic system, reproduced the energy level diagram for the low lying states of helium. Reliable values are obtained from accurate variationally determined two-electron nonrelativistic wave functions for radiative transition probabilities of 2 3p states in the helium isoelectric sequence, and for the 2 1s and 2 3s1 states of the helium sequence.

  7. 43 CFR 3195.35 - What happens if I have an outstanding obligation to purchase refined helium under a Helium...

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... obligation to purchase refined helium under a Helium Distribution Contract? 3195.35 Section 3195.35 Public... OF THE INTERIOR MINERALS MANAGEMENT (3000) HELIUM CONTRACTS Federal Helium Supplier Requirements § 3195.35 What happens if I have an outstanding obligation to purchase refined helium under a...

  8. THE GREEN BANK TELESCOPE H II REGION DISCOVERY SURVEY. IV. HELIUM AND CARBON RECOMBINATION LINES

    SciTech Connect

    Wenger, Trey V.; Bania, T. M.; Balser, Dana S.; Anderson, L. D.

    2013-02-10

    The Green Bank Telescope H II Region Discovery Survey (GBT HRDS) found hundreds of previously unknown Galactic regions of massive star formation by detecting hydrogen radio recombination line (RRL) emission from candidate H II region targets. Since the HRDS nebulae lie at large distances from the Sun, they are located in previously unprobed zones of the Galactic disk. Here, we derive the properties of helium and carbon RRL emission from HRDS nebulae. Our target sample is the subset of the HRDS that has visible helium or carbon RRLs. This criterion gives a total of 84 velocity components (14% of the HRDS) with helium emission and 52 (9%) with carbon emission. For our highest quality sources, the average {sup 4}He{sup +}/H{sup +} abundance ratio by number, (y {sup +}), is 0.068 {+-} 0.023(1{sigma}). This is the same ratio as that measured for the sample of previously known Galactic H II regions. Nebulae without detected helium emission give robust y {sup +} upper limits. There are 5 RRL emission components with y {sup +} less than 0.04 and another 12 with upper limits below this value. These H II regions must have either a very low {sup 4}He abundance or contain a significant amount of neutral helium. The HRDS has 20 nebulae with carbon RRL emission but no helium emission at its sensitivity level. There is no correlation between the carbon RRL parameters and the 8 {mu}m mid-infrared morphology of these nebulae.

  9. Detection of significant differences between absorption spectra of neutral helium and low temperature photoionized helium plasmas

    NASA Astrophysics Data System (ADS)

    Bartnik, A.; Wachulak, P.; Fiedorowicz, H.; Fok, T.; Jarocki, R.; Szczurek, M.

    2013-11-01

    In this work, spectral investigations of photoionized He plasmas were performed. The photoionized plasmas were created by irradiation of helium stream, with intense pulses from laser-plasma extreme ultraviolet (EUV) source. The EUV source was based on a double-stream Xe/Ne gas-puff target irradiated with 10 ns/10 J Nd:YAG laser pulses. The most intense emission from the source spanned a relatively narrow spectral region below 20 nm, however, spectrally integrated intensity at longer wavelengths was also significant. The EUV radiation was focused onto a gas stream, injected into a vacuum chamber synchronously with the EUV pulse. The long-wavelength part of the EUV radiation was used for backlighting of the photoionized plasmas to obtain absorption spectra. Both emission and absorption spectra in the EUV range were investigated. Significant differences between absorption spectra acquired for neutral helium and low temperature photoionized plasmas were demonstrated for the first time. Strong increase of intensities and spectral widths of absorption lines, together with a red shift of the K-edge, was shown.

  10. Detection of significant differences between absorption spectra of neutral helium and low temperature photoionized helium plasmas

    SciTech Connect

    Bartnik, A.; Wachulak, P.; Fiedorowicz, H.; Fok, T.; Jarocki, R.; Szczurek, M.

    2013-11-15

    In this work, spectral investigations of photoionized He plasmas were performed. The photoionized plasmas were created by irradiation of helium stream, with intense pulses from laser-plasma extreme ultraviolet (EUV) source. The EUV source was based on a double-stream Xe/Ne gas-puff target irradiated with 10 ns/10 J Nd:YAG laser pulses. The most intense emission from the source spanned a relatively narrow spectral region below 20 nm, however, spectrally integrated intensity at longer wavelengths was also significant. The EUV radiation was focused onto a gas stream, injected into a vacuum chamber synchronously with the EUV pulse. The long-wavelength part of the EUV radiation was used for backlighting of the photoionized plasmas to obtain absorption spectra. Both emission and absorption spectra in the EUV range were investigated. Significant differences between absorption spectra acquired for neutral helium and low temperature photoionized plasmas were demonstrated for the first time. Strong increase of intensities and spectral widths of absorption lines, together with a red shift of the K-edge, was shown.

  11. TRANSMISSION ELECTRON MICROSCOPY STUDY OF HELIUM BEARING FUSION WELDS

    SciTech Connect

    Tosten, M; Michael Morgan, M

    2008-12-12

    A transmission electron microscopy (TEM) study was conducted to characterize the helium bubble distributions in tritium-charged-and-aged 304L and 21Cr-6Ni-9Mn stainless steel fusion welds containing approximately 150 appm helium-3. TEM foils were prepared from C-shaped fracture toughness test specimens containing {delta} ferrite levels ranging from 4 to 33 volume percent. The weld microstructures in the low ferrite welds consisted mostly of austenite and discontinuous, skeletal {delta} ferrite. In welds with higher levels of {delta} ferrite, the ferrite was more continuous and, in some areas of the 33 volume percent sample, was the matrix/majority phase. The helium bubble microstructures observed were similar in all samples. Bubbles were found in the austenite but not in the {delta} ferrite. In the austenite, bubbles had nucleated homogeneously in the grain interiors and heterogeneously on dislocations. Bubbles were not found on any austenite/austenite grain boundaries or at the austenite/{delta} ferrite interphase interfaces. Bubbles were not observed in the {delta} ferrite because of the combined effects of the low solubility and rapid diffusion of tritium through the {delta} ferrite which limited the amount of helium present to form visible bubbles.

  12. Solvation of Na+, K+, and their dimers in helium.

    PubMed

    An der Lan, Lukas; Bartl, Peter; Leidlmair, Christian; Jochum, Roland; Denifl, Stephan; Echt, Olof; Scheier, Paul

    2012-04-02

    Helium atoms bind strongly to alkali cations which, when embedded in liquid helium, form so-called snowballs. Calculations suggest that helium atoms in the first solvation layer of these snowballs form rigid structures and that their number (n) is well defined, especially for the lighter alkalis. However, experiments have so far failed to accurately determine values of n. We present high-resolution mass spectra of Na(+)He(n), K(+)He(n), Na(2)(+)He(n) and K(2)(+)He(n), formed by electron ionization of doped helium droplets; the data allow for a critical comparison with several theoretical studies. For sodium and potassium monomers the spectra indicate that the value of n is slightly smaller than calculated. Na(2)(+)He(n) displays two distinct anomalies at n=2 and n=6, in agreement with theory; dissociation energies derived from experiment closely track theoretical values. K(2)(+)He(n) distributions are fairly featureless, which also agrees with predictions.

  13. Impact of neutron irradiation on thermal helium desorption from iron

    NASA Astrophysics Data System (ADS)

    Hu, Xunxiang; Field, Kevin G.; Taller, Stephen; Katoh, Yutai; Wirth, Brian D.

    2017-06-01

    The synergistic effect of neutron irradiation and transmutant helium production is an important concern for the application of iron-based alloys as structural materials in fission and fusion reactors. In this study, we investigated the impact of neutron irradiation on thermal helium desorption behavior in high purity iron. Single crystalline and polycrystalline iron samples were neutron irradiated in HFIR to 5 dpa at 300 °C and in BOR-60 to 16.6 dpa at 386 °C, respectively. Following neutron irradiation, 10 keV He ion implantation was performed at room temperature on both samples to a fluence of 7 × 1018 He/m2. Thermal desorption spectrometry (TDS) was conducted to assess the helium diffusion and clustering kinetics by analyzing the desorption spectra. The comparison of He desorption spectra between unirradiated and neutron irradiated samples showed that the major He desorption peaks shift to higher temperatures for the neutron-irradiated iron samples, implying that strong trapping sites for He were produced during neutron irradiation, which appeared to be nm-sized cavities through TEM examination. The underlying mechanisms controlling the helium trapping and desorption behavior were deduced by assessing changes in the microstructure, as characterized by TEM, of the neutron irradiated samples before and after TDS measurements.

  14. Highly Excited States of cs Atoms on Helium Nanodroplets

    NASA Astrophysics Data System (ADS)

    Lackner, F.; Theisen, M.; Koch, M.; Ernst, W. E.

    2011-06-01

    Cs atoms on the surface of helium nanodroplets have been excited to high lying nS (n = 8-11), nP (n = 8-11), and nD (n = 6-10) levels. A two-step excitation scheme via the 62P1/2(2Π1/2) state using two cw lasers was applied. This intermediate state has the advantage that a large fraction of the excited Cs atoms does not desorb from the helium nanodroplets. An absorption spectrum was recorded by detecting laser induced fluorescence light from the 62P3/2→62S1/2 transition. The pseudo-diatomic model for helium nanodroplets doped with single alkali-metal atoms holds for the observed spectrum. An investigation of spectral trends shows that the n'2P(Π)←62P1/2(2Π1/2) and n'2D(Δ)←62P1/2(2Π1/2) (n' > 9) transitions are lower in energy than the corresponding free-atom transitions. This indicates that the Cs*--HeN potential becomes attractive for these highly excited states. Our results suggest a possibility of generating an artificial super-atom with a positive ion core inside a helium nanodroplet and the electron outside, which will be subject to future experiments. M. Theisen, F. Lackner, F. Ancilotto, C. Callegari, and W.E. Ernst, Eur. Phys. J. D 61, 403-408 (2011)

  15. Selection of design and determination of quality targets for vs6 pump stages

    NASA Astrophysics Data System (ADS)

    Tverdokhleb, I.; Yelin, A.

    2017-08-01

    A comparative analysis of VS6 pump type in the range of specific speed nq = 25...55 was carried out basing on information about analogous pumps produced by the world’s leading manufacturers. The focus was made on mass-dimensional characteristics of the pump stages. It was found that rational design of a diffuser with radial vanes provides lower material consumption at similar hydraulic characteristics compared to using a semi-axial vanes diffuser in the stage.

  16. Klotho May Ameliorate Proteinuria by Targeting TRPC6 Channels in Podocytes.

    PubMed

    Kim, Ji-Hee; Xie, Jian; Hwang, Kyu-Hee; Wu, Yueh-Lin; Oliver, Noelynn; Eom, Minseob; Park, Kyu-Sang; Barrezueta, Nestor; Kong, In-Deok; Fracasso, R Paul; Huang, Chou-Long; Cha, Seung-Kuy

    2017-01-01

    Klotho is a type-1 membrane protein predominantly produced in the kidney, the extracellular domain of which is secreted into the systemic circulation. Membranous and secreted Klotho protect organs, including the kidney, but whether and how Klotho directly protects the glomerular filter is unknown. Here, we report that secreted Klotho suppressed transient receptor potential channel 6 (TRPC6)-mediated Ca(2+) influx in cultured mouse podocytes by inhibiting phosphoinositide 3-kinase-dependent exocytosis of the channel. Furthermore, soluble Klotho reduced ATP-stimulated actin cytoskeletal remodeling and transepithelial albumin leakage in these cells. Overexpression of TRPC6 by gene delivery in mice induced albuminuria, and exogenous administration of Klotho ameliorated the albuminuria. Notably, immunofluorescence and in situ hybridization revealed Klotho expression in podocytes of mouse and human kidney. Heterozygous Klotho-deficient CKD mice had aggravated albuminuria compared with that in wild-type CKD mice with a similar degree of hypertension and reduced clearance function. Finally, disrupting the integrity of glomerular filter by saline infusion-mediated extracellular fluid volume expansion increased urinary Klotho excretion. These results reveal a potential novel function of Klotho in protecting the glomerular filter, and may offer a new therapeutic strategy for treatment of proteinuria. Copyright © 2016 by the American Society of Nephrology.

  17. PVT1-derived miR-1207-5p promotes breast cancer cell growth by targeting STAT6.

    PubMed

    Yan, Chen; Chen, Yaqing; Kong, Weiwei; Fu, Liya; Liu, Yunde; Yao, Qingjuan; Yuan, Yuhua

    2017-05-01

    Accumulating evidence indicates that ectopic expression of non-coding RNAs are responsible for breast cancer progression. Increased non-coding RNA PVT1, the host gene of microRNA-1207-5p (miR-1207-5p), has been associated with breast cancer proliferation. However, how PVT1 functions in breast cancer is still not clear. In this study, we show a PVT1-derived microRNA, miR-1207-5p, that promotes the proliferation of breast cancer cells by directly regulating STAT6. We first confirm the positive correlated expression pattern between PVT1 and miR-1207-5p by observing consistent induced expression by estrogen, and overexpression in breast cancer cell lines and breast cancer patient specimens. Moreover, silence of PVT1 also decreased miR-1207-5p expression. Furthermore, increased miR-1207-5p expression promoted, while decreased miR-1207-5p expression suppressed, cell proliferation, colony formation, and cell cycle progression in breast cancer cell lines. Mechanistically, a novel target of miR-1207-5p, STAT6, was identified by a luciferase reporter assay. Overexpression of miR-1207-5p decreased the levels of STAT6, which activated CDKN1A and CDKN1B to regulate the cell cycle. We also confirmed the reverse correlation of miR-1207-5p and STAT6 expression levels in breast cancer samples. Therefore, our findings reveal that PVT1-derived miR-1207-5p promotes the proliferation of breast cancer cells by targeting STAT6, which in turn controls CDKN1A and CDKN1B expression. These findings suggest miR-1207-5p might be a potential target for breast cancer therapy. © 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

  18. Interleukin-6 in Allogeneic Stem Cell Transplantation: Its Possible Importance for Immunoregulation and As a Therapeutic Target

    PubMed Central

    Tvedt, Tor Henrik Anderson; Ersvaer, Elisabeth; Tveita, Anders Aune; Bruserud, Øystein

    2017-01-01

    Allogeneic stem cell transplantation is associated with a high risk of treatment-related mortality mainly caused by infections and graft-versus-host disease (GVHD). GVHD is characterized by severe immune dysregulation and impaired regeneration of different tissues, i.e., epithelial barriers and the liver. The balance between pro- and anti-inflammatory cytokine influences the risk of GVHD. Interleukin-6 (IL-6) is a cytokine that previously has been associated with pro-inflammatory effects. However, more recent evidence from various autoimmune diseases (e.g., inflammatory bowel disease, rheumatoid arthritis) has shown that the IL-6 activity is more complex with important effects also on tissue homeostasis, regeneration, and metabolism. This review summarizes the current understanding of how pro-inflammatory IL-6 effects exerted during the peritransplant period shapes T-cell polarization with enhancement of Th17 differentiation and suppression of regulatory T cells, and in addition we also review and discuss the results from trials exploring non-selective IL-6 inhibition in prophylaxis and treatment of GVHD. Emerging evidence suggests that the molecular strategy for targeting of IL-6-initiated intracellular signaling is important for the effect on GVHD. It will therefore be important to further characterize the role of IL-6 in the pathogenesis of GVHD to clarify whether combined IL-6 inhibition of both trans- (i.e., binding of the soluble IL-6/IL-6 receptor complex to cell surface gp130) and cis-signaling (i.e., IL-6 ligation of the IL-6 receptor/gp130 complex) or selective inhibition of trans-signaling should be tried in the prophylaxis and/or treatment of GVHD in allotransplant patients. PMID:28642760

  19. Remote operation of the GOLEM tokamak with hydrogen and helium plasmas

    NASA Astrophysics Data System (ADS)

    Svoboda, V.; Dvornova, A.; Dejarnac, R.; Prochazka, M.; Zaprianov, S.; Akhmethanov, R.; Bogdanova, M.; Dimitrova, M.; Dimitrov, Zh; Grover, O.; Hlavata, L.; Ivanov, K.; Kruglov, K.; Marinova, P.; Masherov, P.; Mogulkin, A.; Mlynar, J.; Stockel, J.; Volynets, A.

    2016-10-01

    The GOLEM tokamak was operated remotely via Internet connection during the 6th International Workshop and Summer School on Plasma Physics. Performances of hydrogen and helium discharges are compared in this paper. It is found, at similar vacuum conditions, that helium discharges are shorter but the breakdown of the working gas can be quite easily achieved at almost the same loop voltage. The plasma current in helium discharges is slightly lower than in the case of hydrogen. Turbulent fluctuations of the floating potential measured by means of an array of Langmuir probes reveal a noticeably different character in the two discharges.

  20. A small and light weight heat exchanger for on-board helium refrigerator

    NASA Technical Reports Server (NTRS)

    Koizumi, T.; Takahashi, M.; Uchida, T.; Kanazawa, Y.; Suzuki, M.

    1983-01-01

    A small and light weight heat exchanger used for small helium refrigerator has been developed by Sumitomo Heavy Industries, Ltd. This heat exchanger is a laminated metal heat exchanger which consists of perforated aluminum metal plates and glassfiber reinforced plastic separators. The size is from 100 mm to 28 mm in diameter and about 300 mm in length. The weight is from 2.5 kg to 0.6 kg. Also it can be used between room temperature and liquid helium temperature. The thermal efficiency obtained has been more than 96%. The heat exchanger has been practically used for on-board helium refrigerator in Japanese National Railways' superconducting magnetic levitated trains.

  1. 3-Phenyl substituted 6,7-dimethoxyisoquinoline derivatives as FtsZ-targeting antibacterial agents

    PubMed Central

    Kelley, Cody; Zhang, Yongzheng; Parhi, Ajit; Kaul, Malvika; Pilch, Daniel S.; LaVoie, Edmond J.

    2014-01-01

    The emergence of multidrug-resistant bacteria has created an urgent need for antibiotics with a novel mechanism of action. The bacterial cell division protein FtsZ is an attractive target for the development of novel antibiotics. The benzo[c]phenanthridinium sanguinarine and the dibenzo[a,g]quinolizin-7-ium berberine are two structurally similar plant alkaloids that alter FtsZ function. The presence of a hydrophobic functionality at either the 1-position of 5-methylbenzo[c]phenanthridinium derivatives or the 2-position of dibenzo[a,g]quinolizin-7-ium derivatives is associated with significantly enhanced antibacterial activity. 3-Phenylisoquinoline represents a subunit within the ring-systems of both of these alkaloids. Several 3-phenylisoquinolines and 3-phenylisoquinolinium derivatives have been synthesized and evaluated for antibacterial activity against Staphylococcus aureus and Enterococcus faecalis, including multidrug-resistant strains of methicillin-resistant S. aureus (MRSA) and vancomycin-resistant E. faecalis (VRE). A number of derivatives were found to have activity against both MRSA and VRE. The binding of select compounds to S. aureus FtsZ (SaFtsZ) was demonstrated and characterized using fluorescence spectroscopy. In addition, the compounds were shown to act as stabilizers of SaFtsZ polymers and concomitant inhibitors of SaFtsZ GTPase activity. Toxicological assessment of select compounds revealed minimal cross-reaction mammalian β-tubulin as well as little or no human cytotoxicity. PMID:23127490

  2. Targeted downregulation of N-acetylgalactosamine 4-sulfate 6-O-sulfotransferase (GalNAc4S6ST) significantly mitigates chondroitin sulfate proteoglycan (CSPG) mediated inhibition

    PubMed Central

    Karumbaiah, Lohitash; Anand, Sanjay; Thazhath, Rupal; Zhong, Yinghui; McKeon, Robert J.; Bellamkonda, Ravi V.

    2011-01-01

    Chondroitin Sulfate-4,6 (CS-E) glycosaminoglycan (GAG) upregulation in astroglial scars is a major contributor to CS proteoglycan (CSPG) mediated inhibition (Gilbert et al. 2005). However, the role of N-acetylgalactosamine 4-sulfate 6-O-sulfotransferase (GalNAc4S6ST) catalyzed sulfation of CS-E, and its contribution to CSPG mediated inhibition of CNS regeneration remains to be fully elucidated. Here, we used in situ hybridization to show localized upregulation of GalNAc4S6ST mRNA after CNS injury. Using in vitro spot assays with immobilized CS-E, we demonstrate dose dependent inhibition of rat embryonic day 18 (E18) cortical neurons. To determine whether selective downregulation of CS-E affected the overall inhibitory character of extracellular matrix produced by reactive astrocytes, single [against (chondroitin 4) sulfotransferase 11 (C4ST1) or GalNAc4S6ST mRNA) or double (against C4ST1 and GalNAc4S6ST mRNA] siRNA treatments were conducted and assayed using quantitative real-time PCR (qRT-PCR) and high performance liquid chromatography (HPLC) to confirm the specific downregulation of CS-4S GAG (CS-A) and CS-E. Spot and Bonhoeffer stripe assays using astrocyte conditioned media (ACM) from siRNA treated rat astrocytes showed a significant decrease in inhibition of neuronal attachment and neurite extensions when compared to untreated and TGFα treated astrocytes. These findings reveal that selective attenuation of CS-E via siRNA targeting of GalNAc4S6ST significantly mitigates CSPG mediated inhibition of neurons, potentially offering a novel intervention strategy for CNS injury. PMID:21456043

  3. ARL13B, PDE6D, and CEP164 form a functional network for INPP5E ciliary targeting

    PubMed Central

    Humbert, Melissa C.; Weihbrecht, Katie; Searby, Charles C.; Li, Yalan; Pope, Robert M.; Sheffield, Val C.; Seo, Seongjin

    2012-01-01

    Mutations affecting ciliary components cause a series of related genetic disorders in humans, including nephronophthisis (NPHP), Joubert syndrome (JBTS), Meckel-Gruber syndrome (MKS), and Bardet-Biedl syndrome (BBS), which are collectively termed “ciliopathies.” Recent protein–protein interaction studies combined with genetic analyses revealed that ciliopathy-related proteins form several functional networks/modules that build and maintain the primary cilium. However, the precise function of many ciliopathy-related proteins and the mechanisms by which these proteins are targeted to primary cilia are still not well understood. Here, we describe a protein–protein interaction network of inositol polyphosphate-5-phosphatase E (INPP5E), a prenylated protein associated with JBTS, and its ciliary targeting mechanisms. INPP5E is targeted to the primary cilium through a motif near the C terminus and prenyl-binding protein phosphodiesterase 6D (PDE6D)-dependent mechanisms. Ciliary targeting of INPP5E is facilitated by another JBTS protein, ADP-ribosylation factor-like 13B (ARL13B), but not by ARL2 or ARL3. ARL13B missense mutations that cause JBTS in humans disrupt the ARL13B–INPP5E interaction. We further demonstrate interactions of INPP5E with several ciliary and centrosomal proteins, including a recently identified ciliopathy protein centrosomal protein 164 (CEP164). These findings indicate that ARL13B, INPP5E, PDE6D, and CEP164 form a distinct functional network that is involved in JBTS and NPHP but independent of the ones previously defined by NPHP and MKS proteins. PMID:23150559

  4. Hypoxia-induced miR-181b enhances angiogenesis of retinoblastoma cells by targeting PDCD10 and GATA6.

    PubMed

    Xu, Xiaofang; Ge, Shengfang; Jia, Renbing; Zhou, Yixiong; Song, Xin; Zhang, He; Fan, Xianqun

    2015-06-01

    Previous findings showed that miR-181b is upregulated under hypoxic conditions in retinoblastoma cells. Since hypoxia is a common feature of retinoblastoma that affects tumor progression as well as tumor therapy, in the present study, we investigated the regulatory mechanism of miR-181b under hypoxic conditions, and examined the role of miR-181b in retinoblastoma responses to hypoxia (chemoresistance and angiogenesis) and possible downstream genes. The level of hypoxia-inducible factor-1α (HIF-1α) and miR-181b was detected to examine the link between them. Tube formation and cell cytotoxicity assays were used to clarify the effects of miR-181b on hypoxic responses of retinoblastoma cells. Bioinformatics analysis was performed to predict potential targets of miR-181b and western blotting was used to verify these targets. The results showed a significantly increased expression of HIF-1α in hypoxia-treated retinoblastoma cells. Downregulation of HIF-1α using a small-interfering RNA (siRNA) knockdown technology did not decrease the expression of miR-181b. Through gain- and loss-of-function studies, miR-181b was demonstrated to significantly stimulate the ability of capillary tube formation of endothelial cells. Programmed cell death-10 (PDCD10) and GATA binding protein 6 (GATA6) were identified as the target genes of miR‑181b. To the best of our knowledge, results of the present study provide the first evidence that miR-181b was upregulated by hypoxia in retinoblastoma in an HIF-1α-independent manner. miR-181b increased tumor angiogenesis of retinoblastoma cells. Additionally, miR-181b exerts its angiogenic function, at least in part, by inhibiting PDCD10 and GATA6. Thus, it is a new potentially useful therapeutic target for retinoblastoma.

  5. Long and high conductance helium heat pipe

    NASA Astrophysics Data System (ADS)

    Gully, Philippe

    2014-11-01

    This paper reports on the development and the thermal tests of two superfluid helium heat pipes. They feature a copper braid located inside a 6 mm outer diameter stainless tube fitted with copper ends for mechanical anchoring. The copper braid is the support of the Rollin superfluid helium film which is essential in the heat transfer. The extremely low thickness of the liquid film allows for a low filling pressure, making the technology very simple without the need for any external hot reservoir and with the possibility to easily bend the tube. We present the design and discuss the thermal performance of two heat pipes tested for several filling pressures, adverse tilt angles and in 1.4-2.0 K temperature range. A minimum filling pressure (0.6 MPa) is needed to get significant transport capacity. A 12 mW transport capacity is achieved for 3.0 MPa filling pressure. It is shown that the long heat pipe (1.2 m) and the short one (0.25 m) have similar thermal performance in adverse tilt. At 1.7 K the long heat pipe, 120 g in weight, reaches a transport capacity of 5.7 mW/4.2 mW for a tilt angle of 0 / 60° and a thermal conductance of 600 mW/K for 4 mW transferred power. When the condenser reaches the super-fluid transition temperature, the Rollin film accelerates the cool down of the evaporator down to 1.7 K with a heating power applied to the evaporator.

  6. MicroRNA-22 Promoted Osteogenic Differentiation of Human Periodontal Ligament Stem Cells by Targeting HDAC6.

    PubMed

    Yan, Guang-Qi; Wang, Xue; Yang, Fan; Yang, Min-Liang; Zhang, Gui-Rong; Wang, Guo-Kun; Zhou, Qing

    2017-07-01

    Stem cells transplantation is a promising therapy strategy for accelerating periodontal regeneration and reconstruction. Genetic modification could induce stem cells directional differentiation to facilitate recovery of physiological functions. In this study, we investigated the role and mechanism of miR-22 on human periodontal ligament stem cells (PDLSCs). First, a cellular model of osteogenic differentiation was first established by osteogenic inductive cocktail. Real-time PCR determined that expression of miR-22 was significantly increased during PDLSCs osteogenic differentiation. Alizirin red staining showed that overexpression of miR-22 in PDLSCs induced better mineralized nodule formation. Real-time PCR and Western blot further confirmed up-regulation of osteogenic genes Runx2 and OPN in miR-22-overexpressing PDLSCs. Conversely, inhibition of miR-22 delayed the process of PDLSCs osteogenic differentiation. Furthermore, Histone deacetylase 6 (HDAC6) was identified as a target gene of miR-22. Overexpression of miR-22 not only reduced the luciferase activity of the reporter containing the 3' untranslated region of HDAC6 mRNA, but also suppressed the endogenous protein expression of HDAC6. Rescue experiment showed that the promotion role of miR-22 in osteogenic differentiation could be relieved by overexpression of HDAC6. Meanwhile, overexpression of HDAC6 alone could also delay the osteogenic differentiation process. The results demonstrated that miR-22 promoted PDLSCs osteogenic differentiation by inhibiting HDAC6 expression, suggesting that miR-22 might be developed as a target of genetic modified stem cells therapy for periodontal diseases. J. Cell. Biochem. 118: 1653-1658, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  7. Tetrahydrobenzo[h][1,6]naphthyridine-6-chlorotacrine hybrids as a new family of anti-Alzheimer agents targeting β-amyloid, tau, and cholinesterase pathologies.

    PubMed

    Di Pietro, Ornella; Pérez-Areales, F Javier; Juárez-Jiménez, Jordi; Espargaró, Alba; Clos, M Victòria; Pérez, Belén; Lavilla, Rodolfo; Sabaté, Raimon; Luque, F Javier; Muñoz-Torrero, Diego

    2014-09-12

    Optimization of an essentially inactive 3,4-dihydro-2H-pyrano[3,2-c]quinoline carboxylic ester derivative as acetylcholinesterase (AChE) peripheral anionic site (PAS)-binding motif by double O → NH bioisosteric replacement, combined with molecular hybridization with the AChE catalytic anionic site (CAS) inhibitor 6-chlorotacrine and molecular dynamics-driven optimization of the length of the linker has resulted in the development of the trimethylene-linked 1,2,3,4-tetrahydrobenzo[h][1,6]naphthyridine-6-chlorotacrine hybrid 5a as a picomolar inhibitor of human AChE (hAChE). The tetra-, penta-, and octamethylene-linked homologues 5b-d have been also synthesized for comparison purposes, and found to retain the nanomolar hAChE inhibitory potency of the parent 6-chlorotacrine. Further biological profiling of hybrids 5a-d has shown that they are also potent inhibitors of human butyrylcholinesterase and moderately potent Aβ42 and tau anti-aggregating agents, with IC50 values in the submicromolar and low micromolar range, respectively. Also, in vitro studies using an artificial membrane model have predicted a good brain permeability for hybrids 5a-d, and hence, their ability to reach their targets in the central nervous system. The multitarget profile of the novel hybrids makes them promising leads for developing anti-Alzheimer drug candidates with more balanced biological activities. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  8. The high-risk HPV E6 oncoprotein preferentially targets phosphorylated nuclear forms of hDlg

    SciTech Connect

    Narayan, Nisha; Subbaiah, Vanitha Krishna; Banks, Lawrence

    2009-04-25

    High-risk mucosal HPV E6 oncoproteins target a number of PDZ domain-containing substrates for proteasome mediated degradation. One of these, Discs Large (Dlg), is involved in the regulation of cell polarity and proliferation control. Previous studies had suggested that Dlg when hyperphosphorylated by osmotic shock, or when present in the nucleus could be preferentially targeted by E6. In this study we use phospho-specific antibodies directed against Dlg phosphorylated at residues S158 and S442 to show that these two observations are, in fact, linked. Dlg, when phosphorylated on S158 and S442 by CDK1 or CDK2, shows a preferential nuclear accumulation. However, these forms of Dlg are absent in cells derived from HPV-induced cervical cancers. Upon either proteasome inhibition or siRNA ablation of E6 expression, we see specific rescue of these phosphorylated forms of Dlg. These results demonstrate that nuclear forms of Dlg phosphorylated on its CDK phospho-acceptor sites has enhanced susceptibility to E6-induced degradation and place previous studies on the stress-induced phosphorylation of Dlg into a relevant biological context.

  9. Destabilization of ERBB2 transcripts by targeting 3' untranslated region messenger RNA associated HuR and histone deacetylase-6.

    PubMed

    Scott, Gary K; Marx, Corina; Berger, Crystal E; Saunders, Laura R; Verdin, Eric; Schäfer, Stefan; Jung, Manfred; Benz, Christopher C

    2008-07-01

    In addition to repressing ERBB2 promoter function, histone deacetylase (HDAC) inhibitors induce the accelerated decay of mature ERBB2 transcripts; the mechanism mediating this transcript destabilization is unknown but depends on the 3' untranslated region (UTR) of ERBB2 mRNA. Using ERBB2-overexpressing human breast cancer cells (SKBR3), the mRNA stability factor HuR was shown to support ERBB2 transcript integrity, bind and endogenously associate with a conserved U-rich element within the ERBB2 transcript 3' UTR, coimmunoprecipitate with RNA-associated HDAC activity, and colocalize with HDAC6. HDAC6 also coimmunoprecipitates with HuR in an RNA-dependent manner and within 6 hours of exposure to a pan-HDAC inhibitor dose, that does not significantly alter cytosolic HuR levels or HuR binding to ERBB2 mRNA. Cellular ERBB2 transcript levels decline while remaining physically associated with HDAC6. Knockdown of HDAC6 protein by small interfering RNA partially suppressed the ERBB2 transcript decay induced by either pan-HDAC or HDAC6-selective enzymatic inhibitors. Three novel hydroxamates, ST71, ST17, and ST80 were synthesized and shown to inhibit HDAC6 with 14-fold to 31-fold greater selectivity over their binding and inhibition of HDAC1. Unlike more potent pan-HDAC inhibitors, these HDAC6-selective inhibitors produced dose-dependent growth arrest of ERBB2-overexpressing breast cancer cells by accelerating the decay of mature ERBB2 mRNA without repressing ERBB2 promoter function. In sum, these findings point to the therapeutic potential of HuR and HDAC6-selective inhibitors, contrasting ERBB2 stability effects induced by HDAC6 enzymatic inhibition and HDAC6 protein knockdown, and show that ERBB2 transcript stability mechanisms include exploitable targets for the development of novel anticancer therapies.

  10. Tumor-targeted efficiency of shRNA vector harboring chimera hTERT/U6 promoter.

    PubMed

    Zhang, Penghui; Chen, Yaqin; Jiang, Xixin; Tu, Zhiguang; Zou, Lin

    2010-05-01

    Telomerase is closely related to tumor, and hTERT is the rate-limiting factor for telomerase activity. The transcription and expression of hTERT is determined by hTERT promoter, which has the ability of anchoring telomerase positive cells. RNA interference (RNAi) has been potentially used in the functional genomics and gene therapy recently. However, the limitations of RNAi uncertain interference and safety hamper its wide applications. To overcome these limitations, we constructed shRNA vectors harboring either U6 promoter or chimera hTERT/U6 promoter aiming at EGFP and hTERT genes (shRNA-EGFP-U6, shRNA-EGFP-hTERT/U6, shRNA-hTERT-U6 and shRNA-hTERT-hTERT/U6), to suppress the expression of GFP and hTERT in telomerase negative human normal fibroblast HELF cells and telomerase positive human hepatocarcinoma SMMC-7721 and HepG2 cells, respectively. HELF-EGFP and SMMC-7721-EGFP cells stably expressing EGFP or hTERT were constructed. GFP expression was inhibited in both HELF-EGFP and SMMC-7721-EGFP cells expressing shRNA-EGFP-U6. Further results showed that GFP expression was suppressed only in telomerase positive SMMC-7721 cells and HepG2 cells, but not in telomerase negative HELF cells expressing shRNA-EGFP-hTERT/U6. Further results found that hTERT expression was effectively inhibited from liver cancer cells expressing shRNA-hTERT-U6 or shRNA-hTERT-hTERT/U6 both in vitro and in vivo. Our study illustrates the tumor-targeted efficiency of shRNA vectors harboring chimera hTERT/U6 promoter in telomerase positive cells, which will benefit tumor therapy.

  11. Superfluid Helium Tanker (SFHT) study

    NASA Technical Reports Server (NTRS)

    1988-01-01

    The accomplishments and recommendations of the two-phase Superfluid Helium Tanker (SFHT) study are presented. During the first phase of the study, the emphasis was on defining a comprehensive set of user requirements, establishing SFHT interface parameters and design requirements, and selecting a fluid subsystem design concept. During the second phase, an overall system design concept was constructed based on appropriate analyses and more detailed definition of requirements. Modifications needed to extend the baseline for use with cryogens other than SFHT have been determined, and technology development needs related to the recommended design have been assessed.

  12. Helium bubble bursting in tungsten

    SciTech Connect

    Sefta, Faiza; Juslin, Niklas; Wirth, Brian D.

    2013-12-28

    Molecular dynamics simulations have been used to systematically study the pressure evolution and bursting behavior of sub-surface helium bubbles and the resulting tungsten surface morphology. This study specifically investigates how bubble shape and size, temperature, tungsten surface orientation, and ligament thickness above the bubble influence bubble stability and surface evolution. The tungsten surface is roughened by a combination of adatom “islands,” craters, and pinholes. The present study provides insight into the mechanisms and conditions leading to various tungsten topology changes, which we believe are the initial stages of surface evolution leading to the formation of nanoscale fuzz.

  13. Helium II level measurement techniques

    NASA Astrophysics Data System (ADS)

    Celik, D.; Hilton, D. K.; Zhang, T.; Van Sciver, S. W.

    2001-05-01

    In this paper, a survey of cryogenic liquid level measurement techniques applicable to superfluid helium (He II) is given. The survey includes both continuous and discrete measurement techniques. A number of different probes and controlling circuits for this purpose have been described in the literature. They fall into one of the following categories: capacitive liquid level gauges, superconducting wire liquid level gauges, thermodynamic (heat transfer-based) liquid level gauges, resistive gauges, ultrasound and transmission line-based level detectors. The present paper reviews these techniques and their suitability for He II service. In addition to these methods, techniques for measuring the total liquid volume and mass gauging are also discussed.

  14. Quantum Dynamics of Helium Clusters

    DTIC Science & Technology

    1993-03-01

    helium clusters [10-12]. (10) DMC starts with the time - dependent Schr ~ dinger equation in imaginary time and has been employed most- The approximate...bound. (For example, the binding values may be computed by the Metropolis approach . energy of He 3 is five times greater than that of 1l1lie I We first...or four times for computational effort. If this is also the case with the the larger clusters) its original size. If the maximum en- DMC approach

  15. Ig-like domain 6 of VCAM-1 is a potential therapeutic target in TNFα-induced angiogenesis

    PubMed Central

    Kim, Taek-Keun; Park, Chang Sik; Na, Hee-Jun; Lee, Kangseung; Yoon, Aerin; Chung, Junho; Lee, Sukmook

    2017-01-01

    Tumor necrosis factor alpha (TNFα)-induced angiogenesis plays important roles in the progression of various diseases, including cancer, wet age-related macular degeneration, and rheumatoid arthritis. However, the relevance and role of vascular cell adhesion molecule-1 (VCAM-1) in angiogenesis have not yet been clearly elucidated. In this study, VCAM-1 knockdown shows VCAM-1 involvement in TNFα-induced angiogenesis. Through competitive blocking experiments with VCAM-1 Ig-like domain 6 (VCAM-1-D6) protein, we identified VCAM-1-D6 as a key domain regulating TNFα-induced vascular tube formation. We demonstrated that a monoclonal antibody specific to VCAM-1-D6 suppressed TNFα-induced endothelial cell migration and tube formation and TNFα-induced vessel sprouting in rat aortas. We also found that the antibody insignificantly affected endothelial cell viability, morphology and activation. Finally, the antibody specifically blocked VCAM-1-mediated cell–cell contacts by directly inhibiting VCAM-1-D6-mediated interaction between VCAM-1 molecules. These findings suggest that VCAM-1-D6 may be a potential novel therapeutic target in TNFα-induced angiogenesis and that antibody-based modulation of VCAM-1-D6 may be an effective strategy to suppress TNFα-induced angiogenesis. PMID:28209985

  16. Ig-like domain 6 of VCAM-1 is a potential therapeutic target in TNFα-induced angiogenesis.

    PubMed

    Kim, Taek-Keun; Park, Chang Sik; Na, Hee-Jun; Lee, Kangseung; Yoon, Aerin; Chung, Junho; Lee, Sukmook

    2017-02-17

    Tumor necrosis factor alpha (TNFα)-induced angiogenesis plays important roles in the progression of various diseases, including cancer, wet age-related macular degeneration, and rheumatoid arthritis. However, the relevance and role of vascular cell adhesion molecule-1 (VCAM-1) in angiogenesis have not yet been clearly elucidated. In this study, VCAM-1 knockdown shows VCAM-1 involvement in TNFα-induced angiogenesis. Through competitive blocking experiments with VCAM-1 Ig-like domain 6 (VCAM-1-D6) protein, we identified VCAM-1-D6 as a key domain regulating TNFα-induced vascular tube formation. We demonstrated that a monoclonal antibody specific to VCAM-1-D6 suppressed TNFα-induced endothelial cell migration and tube formation and TNFα-induced vessel sprouting in rat aortas. We also found that the antibody insignificantly affected endothelial cell viability, morphology and activation. Finally, the antibody specifically blocked VCAM-1-mediated cell-cell contacts by directly inhibiting VCAM-1-D6-mediated interaction between VCAM-1 molecules. These findings suggest that VCAM-1-D6 may be a potential novel therapeutic target in TNFα-induced angiogenesis and that antibody-based modulation of VCAM-1-D6 may be an effective strategy to suppress TNFα-induced angiogenesis.

  17. Systematic Review of Tocilizumab for Rheumatoid Arthritis: A New Biologic targeting the Interleukin-6 Receptor

    PubMed Central

    Navarro-Millán, Iris; Singh, Jasvinder A; Curtis, Jeffrey R

    2013-01-01

    Objective To summarize the efficacy and safety profile of Tocilizumab (TCZ), a humanized monoclonal antibody against interleukin-6 (IL-6), approved for the treatment of rheumatoid arthritis (RA). Methods A systematic literature review was conducted to identify English language articles within Pubmed and the Cochrane Library from January 1989 to August 2011 reporting results from phase III TCZ double-blinded randomized controlled trials (RCT), non-controlled clinical trials and open-label extensions with duration ≥ 6 months. Study outcomes had to include at least one of the following: American College of Rheumatology (ACR) 20, 50, 70; tender/swollen joint count, HAQ disability, radiographic outcomes and drug persistence. Phase II RCTs were included only if they contained relevant information not available in phase III RCTs. To review TCZ pharmacology, relevant studies were selected to evaluate pharmacokinetics and pharmacodynamics. Results Ten published clinical trials (7 phase 3, 3 phase 2) for TCZ were retrieved (7,833 articles initially identified) and 31 from Cochrane library. Compared to MTX monotherapy, TCZ 8 mg/Kg monotherapy had higher rates of ACR20 (p<0.001), ACR50 (p=0.002) and ACR70 (p<0.001) scores at week 24. TCZ 8mg/Kg IV + oral MTX had a higher ACR20 response rate than placebo + oral MTX in patients with RA that failed to respond to MTX or anti-TNF therapy (p<0.001). Patients on TCZ 8mg/Kg had less radiographic progression on Sharp-Genant Score, (85% had no progression) than the control group (67% had no progression, p<0.001). The rate of serious infections was 4.7 events /100 patient years of exposure in the TCZ groups. A greater frequency of neutropenia, thrombocytropenia, hyperlipidemia, and transaminitis was observed with TCZ compared to placebo. Conclusion The short term efficacy and safety profile of TCZ is promising. Additional long term safety data are needed to better characterize the risk-benefit profile of this agent. PMID:22444783

  18. Investigation of Cellular Interactions of Nanoparticles by Helium Ion Microscopy

    SciTech Connect

    Arey, Bruce W.; Shutthanandan, V.; Xie, Yumei; Tolic, Ana; Williams, Nolann G.; Orr, Galya

    2011-06-01

    The helium ion mircroscope (HIM) probes light elements (e.g. C, N, O, P) with high contrast due to the large variation in secondary electron yield, which minimizes the necessity of specimen staining. A defining characteristic of HIM is its remarkable capability to neutralize charge by the implementation of an electron flood gun, which eliminates the need for coating non-conductive specimens for imaging at high resolution. In addition, the small convergence angle in HeIM offers a large depth of field (~5x FE-SEM), enabling tall structures to be viewed in focus within a single image. Taking advantage of these capabilities, we investigate the interactions of engineered nanoparticles (NPs) at the surface of alveolar type II epithelial cells grown at the air-liquid interface (ALI). The increasing use of nanomaterials in a wide range of commercial applications has the potential to increase human exposure to these materials, but the impact of such exposure on human health is still unclear. One of the main routs of exposure is the respiratory tract, where alveolar epithelial cells present a vulnerable target at the interface with ambient air. Since the cellular interactions of NPs govern the cellular response and ultimately determine the impact on human health, our studies will help delineating relationships between particle properties and cellular interactions and response to better evaluate NP toxicity or biocompatibility. The Rutherford backscattered ion (RBI) is a helium ions imaging mode, which backscatters helium ions from every element except hydrogen, with a backscatter yield that depends on the atomic number of the target. Energy-sensitive backscatter analysis is being developed, which when combined with RBI image information, supports elemental identification at helium ion nanometer resolution. This capability will enable distinguishing NPs from cell surface structures with nanometer resolution.

  19. Investigation of cellular interactions of nanoparticles by helium ion microscopy

    NASA Astrophysics Data System (ADS)

    Arey, B. W.; Shutthanandan, V.; Xie, Y.; Tolic, A.; Williams, N.; Orr, G.

    2011-06-01

    The helium ion microscope (HIM) probes light elements (e.g. C, N, O, P) with high contrast due to the large variation in secondary electron yield, which minimizes the necessity of specimen staining. A defining characteristic of HIM is its remarkable capability to neutralize charge by the implementation of an electron flood gun, which eliminates the need for coating non-conductive specimens for imaging at high resolution. In addition, the small convergence angle in HeIM offers a large depth of field (~5× FE-SEM), enabling tall structures to be viewed in focus within a single image. Taking advantage of these capabilities, we investigate the interactions of engineered nanoparticles (NPs) at the surface of alveolar type II epithelial cells grown at the airliquid interface (ALI). The increasing use of nanomaterials in a wide range of commercial applications has the potential to increase human exposure to these materials, but the impact of such exposure on human health is still unclear. One of the main routs of exposure is the respiratory tract, where alveolar epithelial cells present a vulnerable target at the interface with ambient air. Since the cellular interactions of NPs govern the cellular response and ultimately determine the impact on human health, our studies will help delineating relationships between particle properties and cellular interactions and response to better evaluate NP toxicity or biocompatibility. The Rutherford backscattered ion (RBI) is a helium ions imaging mode, which backscatters helium ions from every element except hydrogen, with a backscatter yield that depends on the atomic number of the target. Energy-sensitive backscatter analysis is being developed, which when combined with RBI image information, supports elemental identification at helium ion nanometer resolution. This capability will enable distinguishing NPs from cell surface structures with nanometer resolution.

  20. Targeting the Interleukin-6/Jak/Stat Pathway in Human Malignancies

    PubMed Central

    Sansone, Pasquale; Bromberg, Jacqueline

    2012-01-01

    The Janus kinase/signal transducer and activator of transcription (Jak/Stat) pathway was discovered 20 years ago as a mediator of cytokine signaling. Since this time, more than 2,500 articles have been published demonstrating the importance of this pathway in virtually all malignancies. Although there are dozens of cytokines and cytokine receptors, four Jaks, and seven Stats, it seems that interleukin-6–mediated activation of Stat3 is a principal pathway implicated in promoting tumorigenesis. This transcription factor regulates the expression of numerous critical mediators of tumor formation and metastatic progression. This review will examine the relative importance and function of this pathway in nonmalignant conditions as well as malignancies (including tumor intrinsic and extrinsic), the influence of other Stats, the development of inhibitors to this pathway, and the potential role of inhibitors in controlling or eradicating cancers. PMID:22355058

  1. Design, synthesis, and evaluation of 4,6-diaminonicotinamide derivatives as novel and potent immunomodulators targeting JAK3.

    PubMed

    Nakajima, Yutaka; Aoyama, Naohiro; Takahashi, Fumie; Sasaki, Hiroshi; Hatanaka, Keiko; Moritomo, Ayako; Inami, Masamichi; Ito, Misato; Nakamura, Koji; Nakamori, Fumihiro; Inoue, Takayuki; Shirakami, Shohei

    2016-10-01

    In organ transplantation, T cell-mediated immune responses play a key role in the rejection of allografts. Janus kinase 3 (JAK3) is specifically expressed in hematopoietic cells and associated with regulation of T cell development via interleukin-2 signaling pathway. Here, we designed novel 4,6-diaminonicotinamide derivatives as immunomodulators targeting JAK3 for prevention of transplant rejection. Our optimization of C4- and C6-substituents and docking calculations to JAK3 protein confirmed that the 4,6-diaminonicotinamide scaffold resulted in potent inhibition of JAK3. We also investigated avoidance of human ether-a-go-go related gene (hERG) inhibitory activity. Selected compound 28 in combination with tacrolimus prevented allograft rejection in a rat heterotopic cardiac transplantation model.

  2. Design of subcooled helium II refrigerator with helium-3 cold compressor

    SciTech Connect

    Kato, D.; Saji, N.; Ohya, H.; Asakura, H.; Kubota, M.; Kaneko, Y.; Nagai, S.

    1994-12-31

    This paper will study the possibility of a He II refrigerator made up of three cold compressors by making use of helium-3 characteristics. This system is compact enough to fit inside a small cold box, so it can be easily connected with an existing helium-4 refrigerator. The authors designed the compressors, calculated the He II cooling capacity, 4.4 K refrigeration load, required inventory of helium-3, and Carnot efficiency. Though helium-3 is expensive, the required inventory of helium-3 to be filled inside this He II refrigerator was calculated to be small enough to prove practicality of constructing this refrigerator.

  3. Morphine reduces the threshold of helium preconditioning against myocardial infarction: the role of opioid receptors in rabbits

    PubMed Central

    Pagel, Paul S.; Krolikowski, John G.; Amour, Julien; Warltier, David C.; Weihrauch, Dorothee

    2015-01-01

    Objectives Brief, repetitive administration of helium before prolonged coronary artery occlusion and reperfusion protects myocardium against infarction. Opioid receptors mediate the cardioprotective effects of ischemic pre- and postconditioning, but whether these receptors also play a role in helium preconditioning is unknown. We tested the hypotheses that opioid receptors mediate helium preconditioning and that morphine (a μ1-opioid receptor agonist with δ1-opioid agonist properties) lowers the threshold of cardioprotection produced by helium in vivo. Design Randomized, prospective study. Setting University research laboratory. Participants Male New Zealand white rabbits. Interventions Rabbits (n=56) were instrumented for measurement of systemic hemodynamics and subjected to a 30 min left anterior descending coronary artery (LAD) occlusion and 3 h reperfusion. In separate experimental groups, rabbits (n=6 or 7 per group) received 0.9% saline (control), one or three cycles of 70% helium-30% oxygen administered for 5 min interspersed with 5 min of an air-oxygen mixture, morphine (0.1 mg/kg, i.v.), or the nonselective opioid antagonist naloxone (6 mg/kg, i.v.) before LAD occlusion. Other groups of rabbits received three cycles of helium or one cycle of helium plus morphine (0.1 mg/kg) in the absence or presence of naloxone (6 mg/kg) before ischemia and reperfusion. Statistical analysis of data was performed with analysis of variance for repeated measures followed by Bonferroni’s modification of Student’s t test. Measurements and Main Results Myocardial infarct size was determined using triphenyltetrazolium chloride staining and presented as a percentage of the left ventricular area at risk. Helium reduced myocardial infarct size in an exposure-related manner [36±6 (P>0.05) and 25±4% (P<0.05 versus control) for one and three cycles of helium, respectively; data are mean±SD] compared with control (44±7%). Morphine and naloxone alone did not affect infarct

  4. Morphine reduces the threshold of helium preconditioning against myocardial infarction: the role of opioid receptors in rabbits.

    PubMed

    Pagel, Paul S; Krolikowski, John G; Amour, Julien; Warltier, David C; Weihrauch, Dorothee

    2009-10-01

    Brief, repetitive administration of helium before prolonged coronary artery occlusion and reperfusion protects myocardium against infarction. Opioid receptors mediate the cardioprotective effects of ischemic pre- and postconditioning, but whether these receptors also play a role in helium preconditioning is unknown. The authors tested the hypotheses that opioid receptors mediate helium preconditioning and that morphine (a mu(1)-opioid receptor agonist with delta(1)-opioid agonist properties) lowers the threshold of cardioprotection produced by helium in vivo. A randomized, prospective study. A university research laboratory. Male New Zealand white rabbits. Rabbits (n = 56) were instrumented for the measurement of systemic hemodynamics and subjected to a 30-minute left anterior descending coronary artery (LAD) occlusion and 3 hours of reperfusion. In separate experimental groups, rabbits (n = 6 or 7 per group) received 0.9% saline (control), 1 or 3 cycles of 70% helium-30% oxygen administered for 5 minutes interspersed with 5 minutes of an air-oxygen mixture, morphine (0.1 mg/kg intravenously), or the nonselective opioid antagonist naloxone (6 mg/kg intravenously) before LAD occlusion. Other groups of rabbits received 3 cycles of helium or 1 cycle of helium plus morphine (0.1 mg/kg) in the absence or presence of naloxone (6 mg/kg) before ischemia and reperfusion. Statistical analysis of data was performed with analysis of variance for repeated measures followed by Bonferroni modification of the Student t test. Myocardial infarct size was determined by using triphenyltetrazolium chloride staining and presented as a percentage of the left ventricular area at risk. Helium reduced myocardial infarct size in an exposure-related manner (36 +/- 6 [p > 0.05] and 25% +/- 4% [p < 0.05 v control] for 1 and 3 cycles of helium, respectively; data are mean +/- standard deviation) compared with control (44% +/- 7%). Morphine and naloxone alone did not affect infarct size (45 +/- 2

  5. CerS6 Is a Novel Transcriptional Target of p53 Protein Activated by Non-genotoxic Stress.

    PubMed

    Fekry, Baharan; Jeffries, Kristen A; Esmaeilniakooshkghazi, Amin; Ogretmen, Besim; Krupenko, Sergey A; Krupenko, Natalia I

    2016-08-05

    Our previous study suggested that ceramide synthase 6 (CerS6), an enzyme in sphingolipid biosynthesis, is regulated by p53: CerS6 was elevated in several cell lines in response to transient expression of p53 or in response to folate stress, which is known to activate p53. It was not clear, however, whether CerS6 gene is a direct transcriptional target of p53 or whether this was an indirect effect through additional regulatory factors. In the present study, we have shown that the CerS6 promoter is activated by p53 in luciferase assays, whereas transcriptionally inactive R175H p53 mutant failed to induce the luciferase expression from this promoter. In vitro immunoprecipitation assays and gel shift analyses have further demonstrated that purified p53 binds within the CerS6 promoter sequence spanning 91 bp upstream and 60 bp downstream of the transcription start site. The Promo 3.0.2 online tool for the prediction of transcription factor binding sites indicated the presence of numerous putative non-canonical p53 binding motifs in the CerS6 promoter. Luciferase assays and gel shift analysis have identified a single motif upstream of the transcription start as a key p53 response element. Treatment of cells with Nutlin-3 or low concentrations of actinomycin D resulted in a strong elevation of CerS6 mRNA and protein, thus demonstrating that CerS6 is a component of the non-genotoxic p53-dependent cellular stress response. This study has shown that by direct transcriptional activation of CerS6, p53 can regulate specific ceramide biosynthesis, which contributes to the pro-apoptotic cellular response.

  6. HIV-1 selectively targets gut-homing CCR6+CD4+ T cells via mTOR-dependent mechanisms

    PubMed Central

    Planas, Delphine; Zhang, Yuwei; Monteiro, Patricia; Goulet, Jean-Philippe; Gosselin, Annie; Hope, Thomas J.; Routy, Jean-Pierre

    2017-01-01

    Gut-associated lymphoid tissues are enriched in CCR6+ Th17-polarized CD4+ T cells that contribute to HIV-1 persistence during antiretroviral therapy (ART). This raises the need for Th17-targeted immunotherapies. In an effort to identify mechanisms governing HIV-1 permissiveness/persistence in gut-homing Th17 cells, we analyzed the transcriptome of CCR6+ versus CCR6– T cells exposed to the gut-homing inducer retinoic acid (RA) and performed functional validations in colon biopsies of HIV-infected individuals receiving ART (HIV+ART). Although both CCR6+ and CCR6– T cells acquired gut-homing markers upon RA exposure, the modulation of unique sets of genes coincided with preferential HIV-1 replication in RA-treated CCR6+ T cells. This molecular signature included the upregulation of HIV-dependency factors acting at entry/postentry levels, such as the CCR5 and PI3K/Akt/mTORC1 signaling pathways. Of note, mTOR expression/phosphorylation was distinctively induced by RA in CCR6+ T cells. Consistently, mTOR inhibitors counteracted the effect of RA on HIV replication in vitro and viral reactivation in CD4+ T cells from HIV+ART individuals via postentry mechanisms independent of CCR5. Finally, CCR6+ versus CCR6– T cells infiltrating the colons of HIV+ART individuals expressed unique molecular signatures, including higher levels of CCR5, integrin β7, and mTOR phosphorylation. Together, our results identify mTOR as a druggable key regulator of HIV permissiveness in gut-homing CCR6+ T cells. PMID:28768913

  7. Testing the Interstellar Wind Helium Flow Direction with Galileo Euvs Data

    NASA Astrophysics Data System (ADS)

    Pryor, W. R.; Simmons, K. E.; Ajello, J. M.; Tobiska, W. K.; Retherford, K. D.; Stern, S. A.; Feldman, P. D.; Frisch, P. C.; Bzowski, M.; Grava, C.

    2014-12-01

    Forty years of measurements of the flow of interstellar helium through the heliosphere suggest that variations of the flow direction with time are possible. We will model Galileo Extreme Ultraviolet Spectrometer (EUVS) data to determine the best-fitting flow direction and compare it to values obtained by other spacecraft. The Galileo EUVS (Hord et al., 1992) was mounted on the spinning part of the spacecraft and obtained interstellar wind hydrogen Lyman-alpha 121.6 nm and helium 58.4 nm data on great circles passing near the ecliptic poles during the interplanetary cruise phase of the mission and also during the Jupiter orbital phase of the mission. The Galileo hydrogen cruise data have been previously published (Hord et al., 1991, Pryor et al., 1992; 1996; 2001), but the helium data have not. Our model was previously used by Ajello et al., 1978, 1979 to model Mariner 10 interstellar wind helium data, and by Stern et al., 2012 and Feldman et al., 2012 to model the interplanetary helium background near the moon in Lunar Reconnaissance Orbiter (LRO) Lyman-alpha Mapping Project (LAMP) data. The model has been updated to include recent determinations of daily helium 58.4 nm solar flux variations and helium losses due to EUV photoionization and electron impact ionization.

  8. Mutation of miR-21 targets endogenous lipoprotein receptor-related protein 6 and nonalcoholic fatty liver disease.

    PubMed

    Li, Chang-Ping; Li, Hong-Jue; Nie, Jiao; Chen, Xia; Zhou, Xian

    2017-01-01

    Nonalcoholic fatty liver disease (NAFLD) is a chronic disorder characterized by hepatic fat accumulation and abnormal lipid metabolism. Although miR-21 has been implicated in nonalcoholic fatty liver disease, it is unknown whether miR-21 could function as a therapeutic target. Here, we perform transfection analysis of miR-21 mimic or control mimic to evaluate the effects of miR-21 expression levels on human HepG2 nonalcoholic fatty liver cells. We used siRNA techniques to knock down miR-21 in HepG2 and control 293T cell lines, and then monitored lipid production and the expression levels of genes involved in lipid metabolism. The effects of miR-21 expression levels on LDL receptor-related protein 6 (LRP6) expression were evaluated using qRT-PCR and western blot analyses. Luciferase reporter assays were conducted to confirm the effects of miR-21 expression levels on LRP6. The results indicated that transfection of miR-21 mimic induced changes in the expression levels of lipogenic enzymes, including acetyl-CoA carboxylase 1 (ACC1), stearoyl CoA desaturase (1SCD1), sterol regulatory element-binding protein 1 (SREBP1), and liver X receptor alpha (LXRα). Transfection of miR-21 mimic suppressed the transcription and translation of LRP6 at the mRNA and protein levels, whereas miR-21 knockdown increased the expression levels of LRP6. Transfection of miR-21 mimic in HepG2 cells also induced lipid production and triggered the expression of critical lipid metabolic enzymes. These data suggest that mutation of miR-21 may be a new therapeutic strategy to treat nonalcoholic fatty liver diseases by targeting endogenous LRP6.

  9. Mutation of miR-21 targets endogenous lipoprotein receptor-related protein 6 and nonalcoholic fatty liver disease

    PubMed Central

    Li, Chang-Ping; Li, Hong-Jue; Nie, Jiao; Chen, Xia; Zhou, Xian

    2017-01-01

    Nonalcoholic fatty liver disease (NAFLD) is a chronic disorder characterized by hepatic fat accumulation and abnormal lipid metabolism. Although miR-21 has been implicated in nonalcoholic fatty liver disease, it is unknown whether miR-21 could function as a therapeutic target. Here, we perform transfection analysis of miR-21 mimic or control mimic to evaluate the effects of miR-21 expression levels on human HepG2 nonalcoholic fatty liver cells. We used siRNA techniques to knock down miR-21 in HepG2 and control 293T cell lines, and then monitored lipid production and the expression levels of genes involved in lipid metabolism. The effects of miR-21 expression levels on LDL receptor-related protein 6 (LRP6) expression were evaluated using qRT-PCR and western blot analyses. Luciferase reporter assays were conducted to confirm the effects of miR-21 expression levels on LRP6. The results indicated that transfection of miR-21 mimic induced changes in the expression levels of lipogenic enzymes, including acetyl-CoA carboxylase 1 (ACC1), stearoyl CoA desaturase (1SCD1), sterol regulatory element-binding protein 1 (SREBP1), and liver X receptor alpha (LXRα). Transfection of miR-21 mimic suppressed the transcription and translation of LRP6 at the mRNA and protein levels, whereas miR-21 knockdown increased the expression levels of LRP6. Transfection of miR-21 mimic in HepG2 cells also induced lipid production and triggered the expression of critical lipid metabolic enzymes. These data suggest that mutation of miR-21 may be a new therapeutic strategy to treat nonalcoholic fatty liver diseases by targeting endogenous LRP6. PMID:28337300

  10. Liquid helium-free cryostat and hermetically sealed cryogenic microwave cavity for hyperfine spectroscopy of antiprotonic helium

    PubMed Central

    Massiczek, O.; Friedreich, S.; Juhász, B.; Widmann, E.; Zmeskal, J.

    2011-01-01

    The design and properties of a new cryogenic set-up for laser–microwave–laser hyperfine structure spectroscopy of antiprotonic helium – an experiment performed at the CERN-Antiproton Decelerator (AD), Geneva, Switzerland – are described. Similar experiments for 4He have been performed at the AD for several years. Due to the usage of a liquid helium operated cryostat and therefore necessary refilling of coolants, a loss of up to 10% beamtime occurred. The decision was made to change the cooling system to a closed-circuit cryocooler. New hermetically sealed target cells with minimised 3He gas volume and different dimensions of the microwave resonator for measuring the 3He transitions were needed. A new set-up has been designed and tested at Stefan Meyer Institute in Vienna before being used for the 2009 and 2010 beamtimes at the AD. PMID:22267883

  11. Liquid helium-free cryostat and hermetically sealed cryogenic microwave cavity for hyperfine spectroscopy of antiprotonic helium.

    PubMed

    Massiczek, O; Friedreich, S; Juhász, B; Widmann, E; Zmeskal, J

    2011-12-11

    The design and properties of a new cryogenic set-up for laser-microwave-laser hyperfine structure spectroscopy of antiprotonic helium - an experiment performed at the CERN-Antiproton Decelerator (AD), Geneva, Switzerland - are described. Similar experiments for (4)He have been performed at the AD for several years. Due to the usage of a liquid helium operated cryostat and therefore necessary refilling of coolants, a loss of up to 10% beamtime occurred. The decision was made to change the cooling system to a closed-circuit cryocooler. New hermetically sealed target cells with minimised (3)He gas volume and different dimensions of the microwave resonator for measuring the (3)He transitions were needed. A new set-up has been designed and tested at Stefan Meyer Institute in Vienna before being used for the 2009 and 2010 beamtimes at the AD.

  12. Advanced polymer targets for TNSA regime producing 6 MeV protons at 1016 W/cm2 laser intensity

    NASA Astrophysics Data System (ADS)

    Torrisi, L.

    2017-02-01

    High intensity laser pulses, at an intensity of the order of 1016 W/cm2, are employed to irradiate in vacuum polyethylene terephthalate thin foils in the target normal sheath acceleration (TNSA) regime. The plasma obtained in the forward emission is investigated using ion collectors and semiconductor detectors connected in a time-of-flight configuration, Thomson parabola spectrometer, and X-ray streak camera. The results indicate that the foil thickness of 1 micron is optimal to accelerate protons of up to 6.5 MeV. The high ion acceleration can be due to different effects such as the high absorption in the advanced semicrystalline polymer containing spherulite centers, the high resonant absorption in gold nanoparticles embedded in the polymer, the optimal thickness of the used polymer to enhance the electron density in the forward plasma, and the self-focusing effect induced by preplasma created in front of the irradiated target.

  13. Novel 1,6-naphthyridin-2(1H)-ones as potential anticancer agents targeting Hsp90.

    PubMed

    Montoir, David; Barillé-Nion, Sophie; Tonnerre, Alain; Juin, Philippe; Duflos, Muriel; Bazin, Marc-Antoine

    2016-08-25

    Hsp90 is an ATP-dependent chaperone known to be overexpressed in many cancers. This way, Hsp90 is an important target for drug discovery. Novobiocin, an aminocoumarin antibiotic, was reported to inhibit Hsp90 targeting C-terminal domain, and showed anti-proliferative properties, leading to the development of new and more active compounds. Consequently, a new set of novobiocin analogs derived from 1,6-naphthyridin-2(1H)-one scaffold was designed, synthesized and evaluated against two breast cancer cell lines. Subsequently, cell cycle progression and apoptosis were conducted on best candidates, finally Western Blot analysis was performed to measure their ability to induce degradation of Hsp90 client proteins.

  14. Accretion-induced Collapse from Helium Star + White Dwarf Binaries

    NASA Astrophysics Data System (ADS)

    Brooks, Jared; Schwab, Josiah; Bildsten, Lars; Quataert, Eliot; Paxton, Bill

    2017-07-01

    Accretion-induced collapse (AIC) occurs when an O/Ne white dwarf (WD) grows to nearly the Chandrasekhar mass ({M}{Ch}), reaching central densities that trigger electron captures in the core. Using Modules for Experiments in Stellar Astrophysics (MESA), we present the first true binary simulations of He star + O/Ne WD binaries, focusing on a 1.5 {M}⊙ He star in a 3 hr orbital period with 1.1{--}1.3 {M}⊙ O/Ne WDs. The helium star fills its Roche lobe after core helium burning is completed and donates helium on its thermal timescale to the WD, \\dot{M}≈ 3× {10}-6 {M}⊙ {{yr}}-1, which is a rate high enough that the accreting helium burns stably on the WD. The accumulated carbon/oxygen ashes from the helium burning undergo an unstable shell flash that initiates an inwardly moving, carbon burning flame. This flame is only quenched when it runs out of carbon at the surface of the original O/Ne core. Subsequent accumulation of fresh carbon/oxygen layers also undergo thermal instabilities, but no mass loss is triggered, which allows {M}{WD}\\to {M}{Ch}, and then triggers the onset of AIC. We also discuss the scenario of accreting C/O WDs that experience shell carbon ignitions to become O/Ne WDs, and then, under continuing mass transfer, lead to AIC. Studies of the AIC event rate using binary population synthesis should include all of these channels, especially this latter channel, which has been previously neglected but might dominate the rate.

  15. The C1 and C2 domains target human type 6 adenylyl cyclase to lipid rafts and caveolae.

    PubMed

    Thangavel, Muthusamy; Liu, Xiaoqiu; Sun, Shu Qiang; Kaminsky, Joseph; Ostrom, Rennolds S

    2009-02-01

    Previous data has shown that adenylyl cyclase type 6 (AC6) is expressed principally in lipid rafts or caveolae of cardiac myocytes and other cell types while certain other isoforms of AC are excluded from these microdomains. The mechanism by which AC6 is localized to lipid rafts or caveolae is unknown. In this study, we show AC6 is localized in lipid rafts of COS-7 cells (expressing caveolin-1) and in HEK-293 cells or cardiac fibroblasts isolated from caveolin-1 knock-out mice (both of which lack prototypical caveolins). To determine the region of AC6 that confers raft localization, we independently expressed each of the major intracellular domains, the N-terminus, C1 and C2 domains, and examined their localization with various approaches. The N-terminus did not associate with lipid rafts or caveolae of either COS-7 or HEK-293 cells nor did it immunoprecipitate with caveolin-1 when expressed in COS-7 cells. By contrast, the C1 and C2 domains each associated with lipid rafts to varying degrees and were present in caveolin-1 immunoprecipitates. There were no differences in the pattern of localization of either the C1 or C2 domains between COS-7 and HEK-293 cells. Further dissection of the C1 domain into four individual proteins indicated that the N-terminal half of this domain is responsible for its raft localization. To probe for a role of a putative palmitoylation motif in the C-terminal portion of the C2 domain, we expressed various truncated forms of AC6 lacking most or all of the C-terminal 41 amino acids. These truncated AC6 proteins were not altered in terms of their localization in lipid rafts or their catalytic activity, implying that this C-terminal region is not required for lipid raft targeting of AC6. We conclude that while the C1 domain may be most important, both the C1 and C2 domains of AC6 play a role in targeting AC6 to lipid rafts.

  16. The left lung is preferentially targeted during experimental paracoccidioidomycosis in C57BL/6 mice

    PubMed Central

    Tristão, F.S.M.; Rocha, F.A.; Dias, F.C.; Rossi, M.A.; Silva, J.S.

    2013-01-01

    Paracoccidioidomycosis (PCM) is a chronic systemic mycosis caused by the inhalation of the thermally dimorphic fungus Paracoccidioides brasiliensis as well as the recently described P. lutzii. Because the primary infection occurs in the lungs, we investigated the differential involvement of the right and left lungs in experimental P. brasiliensis infection. Lungs were collected from C57BL/6 mice at 70 days after intravenous infection with 1×106 yeast cells of a virulent strain of P. brasiliensis (Pb18). The left lung, which in mice is smaller and has fewer lobes than the right lung, yielded increased fungal recovery associated with a predominant interleukin-4 response and diminished synthesis of interferon-γ and nitric oxide compared with the right lung. Our data indicate differential involvement of the right and left lungs during experimental PCM. This knowledge emphasizes the need for an accurate, standardized protocol for tissue collection during studies of experimental P. brasiliensis infection, since experiments using the same lungs favor the collection of comparable data among different mice. PMID:24141611

  17. Paramagnetic Attraction of Impurity-Helium Solids

    NASA Technical Reports Server (NTRS)

    Bernard, E. P.; Boltnev, R. E.; Khmelenko, V. V.; Lee, D. M.

    2003-01-01

    Impurity-helium solids are formed when a mixture of impurity and helium gases enters a volume of superfluid helium. Typical choices of impurity gas are hydrogen deuteride, deuterium, nitrogen, neon and argon, or a mixture of these. These solids consist of individual impurity atoms and molecules as well as clusters of impurity atoms and molecules covered with layers of solidified helium. The clusters have an imperfect crystalline structure and diameters ranging up to 90 angstroms, depending somewhat on the choice of impurity. Immediately following formation the clusters aggregate into loosely connected porous solids that are submerged in and completely permeated by the liquid helium. Im-He solids are extremely effective at stabilizing high concentrations of free radicals, which can be introduced by applying a high power RF dis- charge to the impurity gas mixture just before it strikes the super fluid helium. Average concentrations of 10(exp 19) nitrogen atoms/cc and 5 x 10(exp 18) deuterium atoms/cc can be achieved this way. It shows a typical sample formed from a mixture of atomic and molecular hydrogen and deuterium. It shows typical sample formed from atomic and molecular nitrogen. Much of the stability of Im-He solids is attributed to their very large surface area to volume ratio and their permeation by super fluid helium. Heat resulting from a chance meeting and recombination of free radicals is quickly dissipated by the super fluid helium instead of thermally promoting the diffusion of other nearby free radicals.

  18. 30 CFR 256.11 - Helium.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 2 2010-07-01 2010-07-01 false Helium. 256.11 Section 256.11 Mineral Resources... Helium. (a) Each lease issued or continued under these regulations shall be subject to a reservation by the United States, under section 12(f) of the Act, of the ownership of and the right to extract...

  19. Theoretical model of the helium pinhole microscope

    NASA Astrophysics Data System (ADS)

    Palau, Adrià Salvador; Bracco, Gianangelo; Holst, Bodil

    2016-12-01

    In recent years, the development of neutral helium microscopes has gained increasing interest. The low energy, charge neutrality, and inertness of the helium atoms makes helium microscopy an attractive candidate for the imaging of a range of samples. The simplest neutral helium microscope is the so-called pinhole microscope. It consists of a supersonic expansion helium beam collimated by two consecutive apertures (skimmer and pinhole), which together determine the beam spot size and hence the resolution at a given working distance to the sample. Due to the high ionization potential of neutral helium atoms, it is difficult to build efficient helium detectors. Therefore, it is crucial to optimize the microscope design to maximize the intensity for a given resolution and working distance. Here we present an optimization model for the helium pinhole microscope system. We show that for a given resolution and working distance, there is a single intensity maximum. Further we show that with present-day state-of-the-art detector technology (ionization efficiency 1 ×10-3 ), a resolution of the order of 600 nm at a working distance of 3 mm is possible. In order to make this quantification, we have assumed a Lambertian reflecting surface and calculated the beam spot size that gives a signal 100 cts/s within a solid angle of 0.02 π sr, following an existing design. Reducing the working distance to the micron range leads to an improved resolution of around 40 nm.

  20. Helium Speech: An Application of Standing Waves

    ERIC Educational Resources Information Center

    Wentworth, Christopher D.

    2011-01-01

    Taking a breath of helium gas and then speaking or singing to the class is a favorite demonstration for an introductory physics course, as it usually elicits appreciative laughter, which serves to energize the class session. Students will usually report that the helium speech "raises the frequency" of the voice. A more accurate description of the…

  1. Helium-cooled high temperature reactors

    SciTech Connect

    Trauger, D.B.

    1985-01-01

    Experience with several helium cooled reactors has been favorable, and two commercial plants are now operating. Both of these units are of the High Temperature Graphite Gas Cooled concept, one in the United States and the other in the Federal Republic of Germany. The initial helium charge for a reactor of the 1000 MW(e) size is modest, approx.15,000 kg.

  2. LOX Tank Helium Removal for Propellant Scavenging

    NASA Technical Reports Server (NTRS)

    Chato, David J.

    2009-01-01

    System studies have shown a significant advantage to reusing the hydrogen and oxygen left in these tanks after landing on the Moon in fuel cells to generate power and water for surface systems. However in the current lander concepts, the helium used to pressurize the oxygen tank can substantially degrade fuel cell power and water output by covering the reacting surface with inert gas. This presentation documents an experimental investigation of methods to remove the helium pressurant while minimizing the amount of the oxygen lost. This investigation demonstrated that significant quantities of Helium (greater than 90% mole fraction) remain in the tank after draining. Although a single vent cycle reduced the helium quantity, large amounts of helium remained. Cyclic venting appeared to be more effective. Three vent cycles were sufficient to reduce the helium to small (less than 0.2%) quantities. Two vent cycles may be sufficient since once the tank has been brought up to pressure after the second vent cycle the helium concentration has been reduced to the less than 0.2% level. The re-pressurization process seemed to contribute to diluting helium. This is as expected since in order to raise the pressure liquid oxygen must be evaporated. Estimated liquid oxygen loss is on the order of 82 pounds (assuming the third vent cycle is not required).

  3. Helium Speech: An Application of Standing Waves

    ERIC Educational Resources Information Center

    Wentworth, Christopher D.

    2011-01-01

    Taking a breath of helium gas and then speaking or singing to the class is a favorite demonstration for an introductory physics course, as it usually elicits appreciative laughter, which serves to energize the class session. Students will usually report that the helium speech "raises the frequency" of the voice. A more accurate description of the…

  4. PGE2 EP1 receptor deletion attenuates 6-OHDA-induced Parkinsonism in mice: old switch, new target.

    PubMed

    Ahmad, Abdullah Shafique; Maruyama, Takayuki; Narumiya, Shuh; Doré, Sylvain

    2013-04-01

    Recent experimental data on Parkinson's disease (PD) predicts the critical role of inflammation in the progression of neurodegeneration and the promising preventive effects of nonsteroidal anti-inflammatory drugs (NSAIDs). Previous studies suggest that NSAIDs minimize cyclooxygenase-2 (COX-2) activity and thereby attenuate free radical generation. Prostaglandin E2 (PGE2) is an important product of COX activity and plays an important role in various physiologic and pathophysiologic conditions through its EP receptors (EP1-EP4). Part of the toxic effect of PGE2 in the central nervous system has been reported to be through the EP1 receptor; however, the effect of the EP1 receptor in PD remains elusive. Therefore, in our pursuit to determine if deletion of the PGE2 EP1 receptor will attenuate 6-hydroxy dopamine (6-OHDA)-induced Parkinsonism, mice were given a unilateral 6-OHDA injection into the medial forebrain bundle. We found that apomorphine-induced contralateral rotations were significantly attenuated in the 6-OHDA-lesioned EP1(-/-) mice compared with the 6-OHDA-lesioned WT mice. Quantitative analysis showed significant protection of dopaminergic neurons in the substantia nigra pars compacta of the 6-OHDA-lesioned EP1(-/-) mice. To the best of our knowledge, this is the first in vivo study to implicate the PGE2 EP1 receptor in toxin-induced Parkinsonism. We propose the PGE2 EP1 receptor as a new target to better understand some of the mechanisms leading to PD.

  5. Gluten T cell epitope targeting by TG3 and TG6; implications for dermatitis herpetiformis and gluten ataxia.

    PubMed

    Stamnaes, Jorunn; Dorum, Siri; Fleckenstein, Burkhard; Aeschlimann, Daniel; Sollid, Ludvig M

    2010-11-01

    Transglutaminase 2 (TG2) is well characterized as the main autoantigen of celiac disease. The ability of TG2 to deamidate and crosslink gluten peptides is essential for the gluten-dependent production of TG2 specific autoantibodies. In patients with primarily extraintestinal manifestation of gluten sensitivity the repertoire of autoantibodies may be different. In dermatitis herpetiformis (DH), TG3 appears to be the target autoantigen whereas in gluten ataxia (GA) autoantibodies reactive with TG6 are present. A functional role for TG3 and TG6 in these diseases has yet to be described. It is also not known whether these enzymes can use gluten peptides implicated in the pathology as substrates. We here report that similar to TG2, TG3 and TG6 can specifically deamidate gluten T cell epitopes. However, the fine specificities of the enzymes were found to differ. TG2 can form covalent complexes with gluten by iso-peptide and thioester bonds. We found that both TG3 and TG6 were able to complex with gluten peptides through thioester linkage although less efficiently than TG2, whereas TG6 but not TG3 was able to form iso-peptide linked complexes. Our findings lend credence to the notion that TG3 and TG6 are involved in the gluten-induced autoimmune responses of DH and GA.

  6. Gas6/Axl pathway is activated in chronic liver disease and its targeting reduces fibrosis via hepatic stellate cell inactivation

    PubMed Central

    Bárcena, Cristina; Stefanovic, Milica; Tutusaus, Anna; Joannas, Leonel; Menéndez, Anghara; García-Ruiz, Carmen; Sancho-Bru, Pau; Marí, Montserrat; Caballeria, Joan; Rothlin, Carla V.; Fernández-Checa, José C.; de Frutos, Pablo García; Morales, Albert

    2015-01-01

    Background & Aims Liver fibrosis, an important health concern associated to chronic liver injury that provides a permissive environment for cancer development, is characterized by accumulation of extracellular matrix components mainly derived from activated hepatic stellate cells (HSCs). Axl, a receptor tyrosine kinase, and its ligand Gas6 are involved in cell differentiation, immune response and carcinogenesis. Methods HSCs were obtained from wild type and Axl−/− mice, treated with recombinant Gas6 protein (rGas6), Axl siRNAs or the Axl inhibitor BGB324, and analyzed by western blot and real-time PCR. Experimental fibrosis was studied in CCl4-treated wild type and Axl−/− mice, and in combination with Axl inhibitor. Gas6 and Axl serum levels were measured in alcoholic liver disease (ALD) and hepatitis C virus (HCV) patients. Results In primary mouse HSCs, Gas6 and Axl levels paralleled HSC activation. rGas6 phosphorylated Axl and AKT prior to HSC phenotypic changes, while Axl siRNA silencing reduced HSC activation. Moreover, BGB324 blocked Axl/AKT phosphorylation and diminished HSC activation. In addition, Axl KO mice displayed decreased HSC activation in vitro and liver fibrogenesis after chronic damage by CCl4 administration. Similarly, BGB324 reduced collagen deposition and CCl4-induced liver fibrosis in mice. Importantly, Gas6 and Axl serum levels increased in ALD and HCV patients, inversely correlating with liver functionality. Conclusions: The Gas6/Axl axis is required for full HSC activation. Gas6 and Axl serum levels increase in parallel to chronic liver disease progression. Axl targeting may be a therapeutic strategy for liver fibrosis management. PMID:25908269

  7. Neutral atom lithography with metastable helium

    NASA Astrophysics Data System (ADS)

    Allred, Claire Shean

    In this dissertation we describe our performance of resist assisted neutral atom lithography using a bright beam of metastable 23S1 Helium (He*). Metastable Helium atoms have 20 eV of internal energy making them easy to detect and able to destroy a resist. The He* is produced by a reverse flow DC discharge source and then collimated with the bichromatic force, followed by three optical molasses velocity compression stages. The atoms in the resulting beam have a mean longitudinal velocity of 1125 m/s and a divergence of 1.1 mrad. The typical beam flux is 2 x 109 atoms/mm2s through a 0.1mm diameter aperture 70 cm away from the source. The internal energy of the atoms damages the molecules of a self assembled monolayer (SAM) of nonanethiol. The undisturbed SAM protects a 200 A layer of gold that has been evaporated onto a prepared Silicon wafer from a wet chemical etch. Two methods are used to pattern the He* atoms before they destroy the SAM. First, a Nickel micro mesh was used to protect the SAM. These experiments established an appropriate dosage and etch time for patterning. The samples were analyzed with an atomic force microscope and found to have an edge resolution of 63 nm. Then, patterning was accomplished using the dipole force the atoms experience while traversing a standing wave of lambda = 1083nm light tuned 500MHz below the 23S 1 → 23P2 transition. Depending on the intensity of the light, the He* atoms are focused or channeled into lines separated by lambda/2. The lines cover the entire exposed length of the substrate, about 3 mm. They are about 3 mm long, corresponding to about twice the beam waist of the laser standing wave. Thus there are 6 x 10 3 lines of length 5500lambda. These results agree with our numerical simulations of the experiment.

  8. p90 ribosomal S6 kinase: a potential therapeutic target in lung cancer.

    PubMed

    Poomakkoth, Noufira; Issa, Aya; Abdulrahman, Nabeel; Abdelaziz, Somaia Gamal; Mraiche, Fatima

    2016-01-14

    A global survey of cancer has shown that lung cancer is the most common cause of the new cancer cases and cancer deaths in men worldwide. The mortality from lung cancer is more than the combined mortality from breast, prostate and colorectal cancers. The two major histological types of lung cancer are non-small cell lung cancer (NSCLC) accounting for about 85 % of cases and small cell lung cancer accounting for 15 % of cases. NSCLC, the more prevalent form of lung cancer, is often diagnosed at an advanced stage and has a very poor prognosis. Many factors have been shown to contribute to the development of lung cancer in humans including tobacco smoking, exposure to environmental carcinogens (asbestos, or radon) and genetic factors. Despite the advances in treatment, lung cancer remains one of the leading causes of cancer death worldwide. Interestingly, the overall 5 year survival from lung cancer has not changed appreciably in the past 25 years. For this reason, novel and more effective treatments and strategies for NSCLC are critically needed. p90 ribosomal S6 kinase (RSK), a serine threonine kinase that lies downstream of the Ras-MAPK (mitogen activated protein kinase) cascade, has been demonstrated to be involved in the regulation of cell proliferation in various malignancies through indirect (e.g., modulation of transcription factors) or direct effects on the cell-cycle machinery. Increased expression of RSK has been demonstrated in various cancers, including lung cancer. This review focuses on the role of RSK in lung cancer and its potential therapeutic application.

  9. Asymptotic Energies and QED Shifts for Rydberg States of Helium

    NASA Technical Reports Server (NTRS)

    Drake, G.W.F.

    2007-01-01

    This paper reviews progress that has been made in obtaining essentially exact solutions to the nonrelativistic three-body problem for helium by a combination of variational and asymptotic expansion methods. The calculation of relativistic and quantum electrodynamic corrections by perturbation theory is discussed, and in particular, methods for the accurate calculation of the Bethe logarithm part of the electron self energy are presented. As an example, the results are applied to the calculation of isotope shifts for the short-lived 'halo' nucleus He-6 relative to He-4 in order to determine the nuclear charge radius of He-6 from high precision spectroscopic measurements carried out at the Argonne National Laboratory. The results demonstrate that the high precision that is now available from atomic theory is creating new opportunities to create novel measurement tools, and helium, along with hydrogen, can be regarded as a fundamental atomic system whose spectrum is well understood for all practical purposes.

  10. UV spectra of benzene isotopomers and dimers in helium nanodroplets

    NASA Astrophysics Data System (ADS)

    Schmied, Roman; ćarçabal, Pierre; Dokter, Adriaan M.; Lonij, Vincent P. A.; Lehmann, Kevin K.; Scoles, Giacinto

    2004-08-01

    We report spectra of various benzene isotopomers and their dimers in helium nanodroplets in the region of the first Herzberg-Teller allowed vibronic transition 601 1B2u←1A1g (the A00 transition) at ˜260 nm. Excitation spectra have been recorded using both beam depletion detection and laser-induced fluorescence. Unlike for many larger aromatic molecules, the monomer spectra consist of a single "zero-phonon" line, blueshifted by ˜30 cm-1 from the gas phase position. Rotational band simulations show that the moments of inertia of C6H6 in the nanodroplets are at least six-times larger than in the gas phase. The dimer spectra present the same vibronic fine structure (though modestly compressed) as previously observed in the gas phase. The fluorescence lifetime and quantum yield of the dimer are found to be equal to those of the monomer, implying substantial inhibition of excimer formation in the dimer in helium.

  11. Methyl 6-Amino-6-deoxy-d-pyranoside-Conjugated Platinum(II) Complexes for Glucose Transporter (GLUT)-Mediated Tumor Targeting: Synthesis, Cytotoxicity, and Cellular Uptake Mechanism.

    PubMed

    Li, Taoli; Gao, Xiangqian; Yang, Liu; Shi, Yunli; Gao, Qingzhi

    2016-05-19

    Methyl 6-aminodeoxy-d-pyranoside-derived platinum(II) glycoconjugates were designed and synthesized based on the clinical drug oxaliplatin for glucose transporter (GLUT)-mediated tumor targeting. In addition to a substantial improvement in water solubility, the conjugates exhibited cytotoxicity similar to or higher than that of oxaliplatin in six different human cancer cell lines. GLUT-mediated transport of the complexes was investigated with a cell-based fluorescence competition assay and GLUT-inhibitor-mediated cytotoxicity analysis in a GLUT-overexpressing human colorectal adenocarcinoma (HT29) cell line. The antitumor effect of the aminodeoxypyranoside-conjugated platinum(II) complexes was found to depend significantly on the GLUT inhibitor, and the cellular uptake of the molecules was regulated by GLUT-mediated transport. The results from this study demonstrate the potential advantages of aminodeoxypyranosides as sugar motifs for glycoconjugation for Warburg-effect-targeted drug design. These fundamental results also support the potential of aminodeoxypyranoside-conjugated platinum(II) complexes as lead compounds for further preclinical evaluation.

  12. Targeting of HPV-16+ epithelial cancer cells by TCR gene engineered T cells directed against E6

    PubMed Central

    Draper, Lindsey M.; Kwong, Mei Li; Gros, Alena; Stevanović, Sanja; Tran, Eric; Kerkar, Sid; Raffeld, Mark; Rosenberg, Steven A.; Hinrichs, Christian S.

    2015-01-01

    Purpose The E6 and E7 oncoproteins of HPV-associated epithelial cancers are in principle ideal immunotherapeutic targets, but evidence that T cells specific for these antigens can recognize and kill HPV+ tumor cells is limited. We sought to determine if TCR gene engineered T cells directed against an HPV oncoprotein can successfully target HPV+ tumor cells. Experimental design T cell responses against the HPV-16 oncoproteins were investigated in a patient with an ongoing 22-month disease-free interval after her second resection of distant metastatic anal cancer. T cells genetically engineered to express an oncoprotein-specific TCR from this patient’s tumor-infiltrating T cells were tested for specific reactivity against HPV+ epithelial tumor cells. Results We identified, from an excised metastatic anal cancer tumor, T cells that recognized an HLA-A*02:01-restricted epitope of HPV-16 E6. The frequency of the dominant T cell clonotype from these cells was approximately 400-fold greater in the patient’s tumor than in her peripheral blood. T cells genetically engineered to express the TCR from this clonotype displayed high avidity for an HLA-A*02:01-restricted epitope of HPV-16, and they showed specific recognition and killing of HPV-16+ cervical, and head and neck cancer cell lines. Conclusion These findings demonstrate that HPV-16+ tumors can be targeted by E6-specific TCR gene engineered T cells, and they provide the foundation for a novel cellular therapy directed against HPV-16+ malignancies including cervical, oropharyngeal, anal, vulvar, vaginal, and penile cancers. PMID:26429982

  13. Tumor targeting properties of monoclonal antibodies with different affinity for target antigen CD44V6 in nude mice bearing head-and-neck cancer xenografts.

    PubMed

    Verel, Iris; Heider, Karl-Heinz; Siegmund, Miranda; Ostermann, Elínborg; Patzelt, Erik; Sproll, Marlies; Snow, Gordon B; Adolf, Günther R; van Dongen, Guus A M S

    2002-05-20

    The CD44 protein family consists of isoforms with tissue-specific expression, which are encoded by standard exons and up to 9 alternatively spliced variant exons (v2-v10) of the same gene. The murine MAbs U36 and BIWA-1, directed against overlapping epitopes within the v6 region of CD44, have previously been shown to efficiently target HNSCC. We herein report on the construction of 1 chimeric (BIWA-2) and 2 humanized (BIWA-4 and BIWA-8) derivatives of BIWA-1. Together with U36 and BIWA-1, these new antibodies were evaluated for affinity to the antigen in vitro as well as for biodistribution and efficacy in RIT using nude mice bearing the HNSCC xenograft line HNX-OE. As determined by surface plasmon resonance, the MAbs bound to CD44v6 with an up to 46-fold difference in affinity (K(d) ranging from 1.1 x 10(-8) to 2.4 x 10(-10) M) with the following ranking: mMAb U36 < hMAb BIWA-4 < hMAb BIWA-8 < mMAb BIWA-1 approximately cMAb BIWA-2. To evaluate their in vivo tumor-targeting properties, 2 MAbs with identical murine or human isotype were labeled with either (131)I or (125)I and administered simultaneously (50 microg/10 microCi each) as pairs showing a stepwise decrease in the difference in affinity: U36 vs. BIWA-1 (35.0-fold difference), BIWA-4 vs. BIWA-2 (14.0-fold) and BIWA-4 vs. BIWA-8 (4.0-fold). Biodistribution was assessed at 1, 2, 3 or 4 and 7 days after injection. Remarkably, for all 3 MAb pairs tested, the lower-affinity MAb showed a higher degree and specificity of tumor localization. The difference in tumor localization was more pronounced when the difference in affinity was larger. For example, 3 days after injection, the lower-affinity mMAb U36 showed a 50% higher tumor uptake than the higher-affinity mMAb BIWA-1, while blood levels and uptake in organs were similar. After labeling with (186)Re (300 or 400 microCi), the same MAb pairs showed RIT efficacy consistent with the biodistribution data: (186)Re-U36 was more effective than (186)Re-BIWA-1, (186)Re

  14. Cryogenic helium 2 systems for space applications

    NASA Technical Reports Server (NTRS)

    Urban, E.; Katz, L.; Hendricks, J.; Karr, G.

    1978-01-01

    Two cryogenic systems are described which will provide cooling for experiments to be flown on Spacelab 2 in the early 1980's. The first system cools a scanning infrared telescope by the transfer of cold helium gas from a separate superfluid helium storage dewar. The flexible design permits the helium storage dewar and transfer assembly to be designed independent of the infrared experiment. Where possible, modified commerical apparatus is used. The second cryogenic system utilizes a specially designed superfluid dewar in which a superfluid helium experiment chamber is immersed. Each dewar system employs a porous plug as a phase separator to hold the liquid helium within the dewar and provide cold gas to a vent line. To maintain the low vapor pressure of the superfluid, each system requires nearly continuous prelaunch vacuum pump service, and each will vent to space during the Spacelab 2 flight.

  15. Permeability of Hollow Microspherical Membranes to Helium

    NASA Astrophysics Data System (ADS)

    Zinoviev, V. N.; Kazanin, I. V.; Pak, A. Yu.; Vereshchagin, A. S.; Lebiga, V. A.; Fomin, V. M.

    2016-01-01

    This work is devoted to the study of the sorption characteristics of various hollow microspherical membranes to reveal particles most suitable for application in the membrane-sorption technologies of helium extraction from a natural gas. The permeability of the investigated sorbents to helium and their impermeability to air and methane are shown experimentally. The sorption-desorption dependences of the studied sorbents have been obtained, from which the parameters of their specific permeability to helium are calculated. It has been established that the physicochemical modification of the original particles exerts a great influence on the coefficient of the permeability of a sorbent to helium. Specially treated cenospheres have displayed high efficiency as membranes for selective extraction of helium.

  16. Modeling Secondary Neutral Helium in the Heliosphere

    NASA Astrophysics Data System (ADS)

    Müller, Hans-Reinhard; Möbius, Eberhard; Wood, Brian E.

    2016-11-01

    An accurate, analytic heliospheric neutral test-particle code for helium atoms from the interstellar medium (ISM) is coupled to global heliospheric models dominated by hydrogen and protons from the solar wind and the ISM. This coupling enables the forward-calculation of secondary helium neutrals from first principles. Secondaries are produced predominantly in the outer heliosheath, upwind of the heliopause, by charge exchange of helium ions with neutral atoms. The forward model integrates the secondary production terms along neutral trajectories and calculates the combined neutral helium phase space density in the innermost heliosphere where it can be related to in-situ observations. The phase space density of the secondary component is lower than that of primary neutral helium, but its presence can change the analysis of primaries and the ISM, and can yield valuable insight into the characteristics of the plasma in the outer heliosheath.

  17. Cryogenic helium 2 systems for space applications

    NASA Technical Reports Server (NTRS)

    Urban, E.; Katz, L.; Hendricks, J.; Karr, G.

    1978-01-01

    Two cryogenic systems are described which will provide cooling for experiments to be flown on Spacelab 2 in the early 1980's. The first system cools a scanning infrared telescope by the transfer of cold helium gas from a separate superfluid helium storage dewar. The flexible design permits the helium storage dewar and transfer assembly to be designed independent of the infrared experiment. Where possible, modified commerical apparatus is used. The second cryogenic system utilizes a specially designed superfluid dewar in which a superfluid helium experiment chamber is immersed. Each dewar system employs a porous plug as a phase separator to hold the liquid helium within the dewar and provide cold gas to a vent line. To maintain the low vapor pressure of the superfluid, each system requires nearly continuous prelaunch vacuum pump service, and each will vent to space during the Spacelab 2 flight.

  18. Cellular effects of helium in different organs.

    PubMed

    Oei, Gezina T M L; Weber, Nina C; Hollmann, Markus W; Preckel, Benedikt

    2010-06-01

    Experimental research in cardiac and neuronal tissue has shown that besides volatile anesthetics and xenon, the nonanesthetic noble gas helium also reduces ischemia-reperfusion damage. Even though the distinct mechanisms of helium-induced organ protection are not completely unraveled, several signaling pathways have been identified. Beside the protective effects on heart and brain that are mainly obtained by different pre- and postconditioning protocols, helium also exerts effects in the lungs, the immune system, and the blood vessels. Obviously, this noble gas is biochemically not inert and exerts biologic effects, although until today the question remains open on how these changes are mediated. Because of its favorable characteristics and the lack of hemodynamic side effects, helium is suitable for use also in critically ill patients. This review covers the cellular effects of helium, which may lead to new clinical strategies of tissue salvage in ischemia-reperfusion situations, both within and outside the perioperative setting.

  19. MiR-210 inhibits NF-κB signaling pathway by targeting DR6 in osteoarthritis.

    PubMed

    Zhang, Dawei; Cao, Xiaorui; Li, Jun; Zhao, Guangyue

    2015-08-05

    Osteoarthritis (OA) is characterized by degradation of articular cartilage and joint inflammation. MicroRNAs have been proved to play an important role in the regulation of chondrogenesis. Previous study showed that microRNA-210 (miR-210) was probably associated with osteoarthritis, while the function of miR-210 in osteoarthritis still remains unknown. The aim of the present study was to investigate the protective effect of miR-210 on osteoarthritis. In the in vitro study, miR-210 level in chondrocytes was decreased after treatment with lipopolysaccharide (LPS). Transfection with miR-210 mimic inhibited LPS-induced pro-inflammatory cytokines production, cell viability reduction and cell apoptosis. Results of luciferase activity assay showed that miR-210 targeted 3'-UTR of death receptor 6 (DR6) to inhibit its expression. MiR-210 mimic and DR6 siRNA transfection inhibited the activation of NF-κB pathway and cell apoptosis of chondrocytes. For the in vivo study, OA model was established on rats by anterior cruciate ligament transection (ACLT). MiR-210 expression is reduced in OA rats. MiR-210 over-expressing lentivirus was injected into the OA rats. Cytokines production, and NF-κB and DR6 expression in OA rats was inhibited by miR-210 overexpression. The results demonstrated that miR-210 decreased inflammation in articular cavity in OA rats by targeting DR6 and inhibiting NF-κB signaling pathway.

  20. Double differential cross sections for electron impact ionization of helium

    NASA Astrophysics Data System (ADS)

    Yun-fei, Yao; Zhang-jin, Chen

    1999-03-01

    The double differential cross sections for electron impact ionization of helium at incident energies of 200 eV, 100 eV and 64.6 eV have been calculated in the BBK model. The present results are found to be in generally good agreement with the latest measurements of Röder et al. and the theoretical results of the convergent close-coupling method although some quantitative discrepancy remains.

  1. Downregulation of microRNA-23a suppresses prostate cancer metastasis by targeting the PAK6-LIMK1 signaling pathway

    PubMed Central

    Li, Xiaojuan; Cai, Yi; Ye, Zhiqiang; Li, Shigeng; Li, Jun; Huang, Huaiqiu; Peng, Shubin; Wang, Jun; Tao, Yiran; Huang, Hongxing; Wen, Xinglai; Mo, Jianfeng; Deng, Zhupeng; Wang, Jian; Zhang, Yangfan; Gao, Xin; Wen, Xingqiao

    2015-01-01

    Here we found that levels of miR-23a were decreased in prostate cancer cell lines and tumor tissues. These low levels were associated with poor patients' prognosis. MiR-23a inhibited migration and invasion of prostate cancer in vivo and in orthotopic prostate cancer mice model. MiR-23a decreased levels of p21-activated kinase 6 (PAK6). Expression of miR-23a inhibited phosphorylation of LIM kinase 1 (LIMK1) and cofilin, in turn suppressing formation of stress fibers and actin filaments, which was required for cell motility and invasion. PAK6 bound to LIMK1 and activated it via phosphorylation at Thr-508. Also, PAK6 and LIMK1 were colocalized in the cytoplasma. Thus, miR-23a regulated cytoskeleton by affecting LIMK1 and cofilin. In summary, we have identified the miR-23a-PAK6-LIMK1 pathway of prostate cancer metastasis. Potential therapeutic approach by targeting miR-23 is suggested. PMID:25714010

  2. Nuclear expression of a mitochondrial DNA gene: mitochondrial targeting of allotopically expressed mutant ATP6 in transgenic mice.

    PubMed

    Dunn, David A; Pinkert, Carl A

    2012-01-01

    Nuclear encoding of mitochondrial DNA transgenes followed by mitochondrial targeting of the expressed proteins (allotopic expression; AE) represents a potentially powerful strategy for creating animal models of mtDNA disease. Mice were created that allotopically express either a mutant (A6M) or wildtype (A6W) mt-Atp6 transgene. Compared to non-transgenic controls, A6M mice displayed neuromuscular and motor deficiencies (wire hang, pole, and balance beam analyses; P < 0.05), no locomotor differences (gait analysis; P < 0.05) and enhanced endurance in Rota-Rod evaluations (P < 0.05). A6W mice exhibited inferior muscle strength (wire hang test; P < 0.05), no difference in balance beam footsteps, accelerating Rota-Rod, pole test and gait analyses; (P < 0.05) and superior performance in balance beam time-to-cross and constant velocity Rota-Rod analyses (P < 0.05) in comparison to non-transgenic control mice. Mice of both transgenic lines did not differ from non-transgenic controls in a number of bioenergetic and biochemical tests including measurements of serum lactate and mitochondrial MnSOD protein levels, ATP synthesis rate, and oxygen consumption (P > 0.05). This study illustrates a mouse model capable of circumventing in vivo mitochondrial mutations. Moreover, it provides evidence supporting AE as a tool for mtDNA disease research with implications in development of DNA-based therapeutics.

  3. IL-6 Receptor Is a Possible Target against Growth of Metastasized Lung Tumor Cells in the Brain

    PubMed Central

    Noda, Mami; Yamakawa, Yukiko; Matsunaga, Naoya; Naoe, Satoko; Jodoi, Taishi; Yamafuji, Megumi; Akimoto, Nozomi; Teramoto, Norihiro; Fujita, Kyota; Ohdo, Shigehiro; Iguchi, Haruo

    2013-01-01

    In the animal model of brain metastasis using human lung squamous cell carcinoma-derived cells (HARA-B) inoculated into the left ventricle of the heart of nude mice, metastasized tumor cells and brain resident cells interact with each other. Among them, tumor cells and astrocytes have been reported to stimulate each other, releasing soluble factors from both sides, subsequently promoting tumor growth significantly. Among the receptors for soluble factors released from astrocytes, only IL-6 receptor (IL-6R) on tumor cells was up-regulated during the activation with astrocytes. Application of monoclonal antibody against human IL-6R (tocilizumab) to the activated HARA-B cells, the growth of HARA-B cells stimulated by the conditioned medium of HARA-B/astrocytes was significantly inhibited. Injecting tocilizumab to animal models of brain metastasis starting at three weeks of inoculation of HARA-B cells, two times a week for three weeks, significantly inhibited the size of the metastasized tumor foci. The up-regulated expression of IL-6R on metastasized lung tumor cells was also observed in the tissue from postmortem patients. These results suggest that IL-6R on metastasized lung tumor cells would be a therapeutic target to inhibit the growth of the metastasized lung tumor cells in the brain. PMID:23271367

  4. IL6 Inhibits HBV Transcription by Targeting the Epigenetic Control of the Nuclear cccDNA Minichromosome

    PubMed Central

    Palumbo, Gianna Aurora; Scisciani, Cecilia; Pediconi, Natalia; Lupacchini, Leonardo; Alfalate, Dulce; Guerrieri, Francesca; Calvo, Ludovica; Salerno, Debora; Di Cocco, Silvia; Levrero, Massimo; Belloni, Laura

    2015-01-01

    The HBV covalently closed circular DNA (cccDNA) is organized as a mini-chromosome in the nuclei of infected hepatocytes by histone and non-histone proteins. Transcription from the cccDNA of the RNA replicative intermediate termed pre-genome (pgRNA), is the critical step for genome amplification and ultimately determines the rate of HBV replication. Multiple evidences suggest that cccDNA epigenetic modifications, such as histone modifications and DNA methylation, participate in regulating the transcriptional activity of the HBV cccDNA. Inflammatory cytokines (TNFα, LTβ) and the pleiotropic cytokine interleukin-6 (IL6) inhibit hepatitis B virus (HBV) replication and transcription. Here we show, in HepG2 cells transfected with linear HBV monomers and HBV-infected NTCP-HepG2 cells, that IL6 treatment leads to a reduction of cccDNA-bound histone acetylation paralleled by a rapid decrease in 3.5kb/pgRNA and subgenomic HBV RNAs transcription without affecting cccDNA chromatinization or cccDNA levels. IL6 repressive effect on HBV replication is mediated by a loss of HNF1α and HNF4α binding to the cccDNA and a redistribution of STAT3 binding from the cccDNA to IL6 cellular target genes. PMID:26580974

  5. Analysis of Helium Segregation on Surfaces of Plasma-Exposed Tungsten

    NASA Astrophysics Data System (ADS)

    Maroudas, Dimitrios; Hu, Lin; Hammond, Karl; Wirth, Brian

    2015-11-01

    We report a systematic theoretical and atomic-scale computational study of implanted helium segregation on surfaces of tungsten, which is considered as a plasma facing component in nuclear fusion reactors. We employ a hierarchy of atomic-scale simulations, including molecular statics to understand the origin of helium surface segregation, targeted molecular-dynamics (MD) simulations of near-surface cluster reactions, and large-scale MD simulations of implanted helium evolution in plasma-exposed tungsten. We find that small, mobile helium clusters (of 1-7 He atoms) in the near-surface region are attracted to the surface due to an elastic interaction force. This thermodynamic driving force induces drift fluxes of these mobile clusters toward the surface, facilitating helium segregation. Moreover, the clusters' drift toward the surface enables cluster reactions, most importantly trap mutation, at rates much higher than in the bulk material. This cluster dynamics has significant effects on the surface morphology, near-surface defect structures, and the amount of helium retained in the material upon plasma exposure.

  6. Thermal vacancies and phase separation in bcc mixtures of helium-3 and helium-4

    SciTech Connect

    Fraass, Benedick Andrew

    1980-01-01

    Thermal vacancy concentrations in crystals of 3He-4He mixtures have been determined. A new x-ray diffractometer-position sensitive detector system is used to make measurements of the absolute lattice parameter of the helium crystals with an accuracy of 300 ppM, and measurements of changes in lattice parameters to better than 60 ppM. The phase separation of the concentrated3He-4He mixtures has been studied in detail with the x-ray measurements. Vacancy concentrations in crystals with 99%, 51%, 28%, 12%, and 0% 3He have been determined. Phase separation has been studied in mixed crystals with concentrations of 51%, 28%, and 12% 3He and melting pressures between 3.0 and 6.1 MPa. The phase separation temperatures determined in this work are in general agreement with previous work. The pressure dependence of Tc, the phase separation temperature for a 50% mixture, is found to be linear: dTc/dP = -34 mdeg/MPa. The x-ray measurements are used to make several comments on the low temperature phase diagram of the helium mixtures.

  7. Helium gas bubble trapped in liquid helium in high magnetic field

    NASA Astrophysics Data System (ADS)

    Bai, H.; Hannahs, S. T.; Markiewicz, W. D.; Weijers, H. W.

    2014-03-01

    High magnetic field magnets are used widely in the area of the condensed matter physics, material science, chemistry, geochemistry, and biology at the National High Magnetic Field Laboratory. New high field magnets of state-of-the-art are being pursued and developed at the lab, such as the current developing 32 T, 32 mm bore fully superconducting magnet. Liquid Helium (LHe) is used as the coolant for superconducting magnets or samples tested in a high magnetic field. When the magnetic field reaches a relatively high value the boil-off helium gas bubble generated by heat losses in the cryostat can be trapped in the LHe bath in the region where BzdBz/dz is less than negative 2100 T2/m, instead of floating up to the top of LHe. Then the magnet or sample in the trapped bubble region may lose efficient cooling. In the development of the 32 T magnet, a prototype Yttrium Barium Copper Oxide coil of 6 double pancakes with an inner diameter of 40 mm and an outer diameter of 140 mm was fabricated and tested in a resistive magnet providing a background field of 15 T. The trapped gas bubble was observed in the tests when the prototype coil was ramped up to 7.5 T at a current of 200 A. This letter reports the test results on the trapped gas bubble and the comparison with the analytical results which shows they are in a good agreement.

  8. Interleukin-11 is the dominant IL-6 family cytokine during gastrointestinal tumorigenesis and can be targeted therapeutically.

    PubMed

    Putoczki, Tracy L; Thiem, Stefan; Loving, Andrea; Busuttil, Rita A; Wilson, Nicholas J; Ziegler, Paul K; Nguyen, Paul M; Preaudet, Adele; Farid, Ryan; Edwards, Kirsten M; Boglev, Yeliz; Luwor, Rodney B; Jarnicki, Andrew; Horst, David; Boussioutas, Alex; Heath, Joan K; Sieber, Oliver M; Pleines, Irina; Kile, Benjamin T; Nash, Andrew; Greten, Florian R; McKenzie, Brent S; Ernst, Matthias

    2013-08-12

    Among the cytokines linked to inflammation-associated cancer, interleukin (IL)-6 drives many of the cancer "hallmarks" through downstream activation of the gp130/STAT3 signaling pathway. However, we show that the related cytokine IL-11 has a stronger correlation with elevated STAT3 activation in human gastrointestinal cancers. Using genetic mouse models, we reveal that IL-11 has a more prominent role compared to IL-6 during the progression of sporadic and inflammation-associated colon and gastric cancers. Accordingly, in these models and in human tumor cell line xenograft models, pharmacologic inhibition of IL-11 signaling alleviated STAT3 activation, suppressed tumor cell proliferation, and reduced the invasive capacity and growth of tumors. Our results identify IL-11 signaling as a potential therapeutic target for the treatment of gastrointestinal cancers.

  9. Interleukin 6 (IL-6) deficiency delays lupus nephritis in MRL-Faslpr mice: the IL-6 pathway as a new therapeutic target in treatment of autoimmune kidney disease in systemic lupus erythematosus.

    PubMed

    Cash, Hannes; Relle, Manfred; Menke, Julia; Brochhausen, Christoph; Jones, Simon A; Topley, Nicholas; Galle, Peter R; Schwarting, Andreas

    2010-01-01

    To investigate the pathophysiological effect of interleukin 6 (IL-6) on lupus nephritis in MRL-Fas(lpr) mice. We generated IL-6-deficient MRL-Fas(lpr) mice using a backcross/intercross breeding scheme. Renal pathology was evaluated using immunohistochemistry detection for macrophages, lymphocytes, vascular cell adhesion molecule-1 (VCAM-1), and TUNEL (terminal deoxynucleotide transferase-mediated dUTP nick end-labeling) for apoptotic cells, and renal IgG and C3 deposition by immunofluorescence staining. Expression of inflammatory markers in the spleen was analyzed by quantitative real-time reverse transcription-polymerase chain reaction. Serum cytokine concentrations were detected by FACS analysis. IL-6 deficiency was highly effective in prolonging survival and ameliorating the clinical, immunological, and histological indicators of murine systemic lupus erythematosus. During the study period of 6 months, MRL-Fas(lpr) IL-6 -/- mice showed delayed onset of proteinuria and hematuria compared to IL-6-intact control mice. Survival rate was 100% in IL-6-deficient MRL-Fas(lpr) mice and 25% in the control group at 6 months of age. The absence of IL-6 resulted in significant reduction of infiltrating macrophages in the kidney (p < 0.05), a decrease in renal IgG and C3 deposition, and a reduction of CD4+ and CD8+ lymphocytes. The parenchymal adhesion molecule VCAM-1 was found to be downregulated in kidneys of MRL-Fas(lpr) IL-6 -/- compared to IL-6-intact mice. We found elevated serum levels of IL-10 and interferon-gamma in IL-6-deficient mice, while splenic mRNA showed an overall downregulation of immunoregulatory genes. IL-6 is a strong promoter of lupus nephritis and may be a promising new therapeutic target in the treatment of human lupus nephritis.

  10. Yeast β-1,6-Glucan Is a Primary Target for the Saccharomyces cerevisiae K2 Toxin

    PubMed Central

    Lukša, Juliana; Podoliankaitė, Monika; Vepštaitė, Iglė; Strazdaitė-Žielienė, Živilė; Urbonavičius, Jaunius

    2015-01-01

    Certain Saccharomyces cerevisiae strains secrete different killer proteins of double-stranded-RNA origin. These proteins confer a growth advantage to their host by increasing its survival. K2 toxin affects the target cell by binding to the cell surface, disrupting the plasma membrane integrity, and inducing ion leakage. In this study, we determined that K2 toxin saturates the yeast cell surface receptors in 10 min. The apparent amount of K2 toxin, bound to a single cell of wild type yeast under saturating conditions, was estimated to be 435 to 460 molecules. It was found that an increased level of β-1,6-glucan directly correlates with the number of toxin molecules bound, thereby impacting the morphology and determining the fate of the yeast cell. We observed that the binding of K2 toxin to the yeast surface receptors proceeds in a similar manner as in case of the related K1 killer protein. It was demonstrated that the externally supplied pustulan, a poly-β-1,6-glucan, but not the glucans bearing other linkage types (such as laminarin, chitin, and pullulan) efficiently inhibits the K2 toxin killing activity. In addition, the analysis of toxin binding to the intact cells and spheroplasts confirmed that majority of K2 protein molecules attach to the β-1,6-glucan, rather than the plasma membrane-localized receptors. Taken together, our results reveal that β-1,6-glucan is a primary target of K2 toxin and is important for the execution of its killing property. PMID:25710965

  11. Yeast β-1,6-glucan is a primary target for the Saccharomyces cerevisiae K2 toxin.

    PubMed

    Lukša, Juliana; Podoliankaitė, Monika; Vepštaitė, Iglė; Strazdaitė-Žielienė, Živilė; Urbonavičius, Jaunius; Servienė, Elena

    2015-04-01

    Certain Saccharomyces cerevisiae strains secrete different killer proteins of double-stranded-RNA origin. These proteins confer a growth advantage to their host by increasing its survival. K2 toxin affects the target cell by binding to the cell surface, disrupting the plasma membrane integrity, and inducing ion leakage. In this study, we determined that K2 toxin saturates the yeast cell surface receptors in 10 min. The apparent amount of K2 toxin, bound to a single cell of wild type yeast under saturating conditions, was estimated to be 435 to 460 molecules. It was found that an increased level of β-1,6-glucan directly correlates with the number of toxin molecules bound, thereby impacting the morphology and determining the fate of the yeast cell. We observed that the binding of K2 toxin to the yeast surface receptors proceeds in a similar manner as in case of the related K1 killer protein. It was demonstrated that the externally supplied pustulan, a poly-β-1,6-glucan, but not the glucans bearing other linkage types (such as laminarin, chitin, and pullulan) efficiently inhibits the K2 toxin killing activity. In addition, the analysis of toxin binding to the intact cells and spheroplasts confirmed that majority of K2 protein molecules attach to the β-1,6-glucan, rather than the plasma membrane-localized receptors. Taken together, our results reveal that β-1,6-glucan is a primary target of K2 toxin and is important for the execution of its killing property.

  12. Systematic screening of isogenic cancer cells identifies DUSP6 as context-specific synthetic lethal target in melanoma

    PubMed Central

    Wittig-Blaich, Stephanie; Wittig, Rainer; Schmidt, Steffen; Lyer, Stefan; Bewerunge-Hudler, Melanie; Gronert-Sum, Sabine; Strobel-Freidekind, Olga; Müller, Carolin; List, Markus; Jaskot, Aleksandra; Christiansen, Helle; Hafner, Mathias; Schadendorf, Dirk; Block, Ines; Mollenhauer, Jan

    2017-01-01

    Next-generation sequencing has dramatically increased genome-wide profiling options and conceptually initiates the possibility for personalized cancer therapy. State-of-the-art sequencing studies yield large candidate gene sets comprising dozens or hundreds of mutated genes. However, few technologies are available for the systematic downstream evaluation of these results to identify novel starting points of future cancer therapies. We improved and extended a site-specific recombination-based system for systematic analysis of the individual functions of a large number of candidate genes. This was facilitated by a novel system for the construction of isogenic constitutive and inducible gain- and loss-of-function cell lines. Additionally, we demonstrate the construction of isogenic cell lines with combinations of the traits for advanced functional in vitro analyses. In a proof-of-concept experiment, a library of 108 isogenic melanoma cell lines was constructed and 8 genes were identified that significantly reduced viability in a discovery screen and in an independent validation screen. Here, we demonstrate the broad applicability of this recombination-based method and we proved its potential to identify new drug targets via the identification of the tumor suppressor DUSP6 as potential synthetic lethal target in melanoma cell lines with BRAF V600E mutations and high DUSP6 expression. PMID:28423600

  13. Aberrant epilepsy-associated mutant Nav1.6 sodium channel activity can be targeted with cannabidiol.

    PubMed

    Patel, Reesha R; Barbosa, Cindy; Brustovetsky, Tatiana; Brustovetsky, Nickolay; Cummins, Theodore R

    2016-08-01

    Mutations in brain isoforms of voltage-gated sodium channels have been identified in patients with distinct epileptic phenotypes. Clinically, these patients often do not respond well to classic anti-epileptics and many remain refractory to treatment. Exogenous as well as endogenous cannabinoids have been shown to target voltage-gated sodium channels and cannabidiol has recently received attention for its potential efficacy in the treatment of childhood epilepsies. In this study, we further investigated the ability of cannabinoids to modulate sodium currents from wild-type and epilepsy-associated mutant voltage-gated sodium channels. We first determined the biophysical consequences of epilepsy-associated missense mutations in both Nav1.1 (arginine 1648 to histidine and asparagine 1788 to lysine) and Nav1.6 (asparagine 1768 to aspartic acid and leucine 1331 to valine) by obtaining whole-cell patch clamp recordings in human embryonic kidney 293T cells with 200 μM Navβ4 peptide in the pipette solution to induce resurgent sodium currents. Resurgent sodium current is an atypical near threshold current predicted to increase neuronal excitability and has been implicated in multiple disorders of excitability. We found that both mutations in Nav1.6 dramatically increased resurgent currents while mutations in Nav1.1 did not. We then examined the effects of anandamide and cannabidiol on peak transient and resurgent currents from wild-type and mutant channels. Interestingly, we found that cannabidiol can preferentially target resurgent sodium currents over peak transient currents generated by wild-type Nav1.6 as well as the aberrant resurgent and persistent current generated by Nav1.6 mutant channels. To further validate our findings, we examined the effects of cannabidiol on endogenous sodium currents from striatal neurons, and similarly we found an inhibition of resurgent and persistent current by cannabidiol. Moreover, current clamp recordings show that cannabidiol reduces

  14. Aberrant epilepsy-associated mutant Nav1.6 sodium channel activity can be targeted with cannabidiol

    PubMed Central

    Patel, Reesha R.; Barbosa, Cindy; Brustovetsky, Tatiana; Brustovetsky, Nickolay

    2016-01-01

    Mutations in brain isoforms of voltage-gated sodium channels have been identified in patients with distinct epileptic phenotypes. Clinically, these patients often do not respond well to classic anti-epileptics and many remain refractory to treatment. Exogenous as well as endogenous cannabinoids have been shown to target voltage-gated sodium channels and cannabidiol has recently received attention for its potential efficacy in the treatment of childhood epilepsies. In this study, we further investigated the ability of cannabinoids to modulate sodium currents from wild-type and epilepsy-associated mutant voltage-gated sodium channels. We first determined the biophysical consequences of epilepsy-associated missense mutations in both Nav1.1 (arginine 1648 to histidine and asparagine 1788 to lysine) and Nav1.6 (asparagine 1768 to aspartic acid and leucine 1331 to valine) by obtaining whole-cell patch clamp recordings in human embryonic kidney 293T cells with 200 μM Navβ4 peptide in the pipette solution to induce resurgent sodium currents. Resurgent sodium current is an atypical near threshold current predicted to increase neuronal excitability and has been implicated in multiple disorders of excitability. We found that both mutations in Nav1.6 dramatically increased resurgent currents while mutations in Nav1.1 did not. We then examined the effects of anandamide and cannabidiol on peak transient and resurgent currents from wild-type and mutant channels. Interestingly, we found that cannabidiol can preferentially target resurgent sodium currents over peak transient currents generated by wild-type Nav1.6 as well as the aberrant resurgent and persistent current generated by Nav1.6 mutant channels. To further validate our findings, we examined the effects of cannabidiol on endogenous sodium currents from striatal neurons, and similarly we found an inhibition of resurgent and persistent current by cannabidiol. Moreover, current clamp recordings show that cannabidiol reduces

  15. Size dependent targeted delivery of gold nanoparticles modified with the IL-6R-specific aptamer AIR-3A to IL-6R-carrying cells.

    PubMed

    Prisner, Lisa; Bohn, Nadine; Hahn, Ulrich; Mews, Alf

    2017-10-05

    The delivery of gold nanoparticles (AuNPs) to specific cells strongly depends on the properties e.g. the size of the particles and is of great interest for a large variety of biomedical applications. Here we investigated the size dependence of the receptor-ligand mediated AuNP delivery to cells by comparing very small "molecular" Au-clusters of only 2 nm to larger 7 nm and 36 nm AuNPs with a distinct surface plasmon resonance. Since the molecular weight in this range changes by almost three orders of magnitude, we show how the amount of gold relates to the number of delivered AuNPs. We attached small interleukin-6 receptor (IL-6R) specific aptamer molecules (AIR-3A) in different amounts to the particles and investigated the specificity of the delivery to IL-6R-carrying cells. To reduce unspecific interaction the particles were additionally covered with polyethylene glycol (PEG). Besides particle size and concentration we varied additional parameters such as aptamer surface coverage as well as incubation time and temperature. We found that in particular, small particles with diameters of less than 2 nm show an up to six times higher delivery rate for the aptamer-conjugated AuNPs compared to untargeted PEG-coated AuNPs. The specificity reduces with a decreasing aptamer/PEG ratio, and also with an increase in particle size where the unspecific uptake is much higher. In addition we also compared the delivery efficiency of this aptamer-mediated delivery system with an antibody-mediated system targeting the same receptor to validate the performance of this approach.

  16. Electric response in superfluid helium

    NASA Astrophysics Data System (ADS)

    Chagovets, Tymofiy V.

    2016-05-01

    We report an experimental investigation of the electric response of superfluid helium that arises in the presence of a second sound standing wave. It was found that the signal of the electric response is observed in a narrow range of second sound excitation power. The linear dependence of the signal amplitude has been derived at low excitation power, however, above some critical power, the amplitude of the signal is considerably decreased. It was established that the rapid change of the electric response is not associated with a turbulent regime generated by the second sound wave. A model of the appearance of the electric response as a result of the oscillation of electron bubbles in the normal fluid velocity field in the second sound wave is presented. Possible explanation for the decrease of the electric response are presented.

  17. Nondipole effects in helium photoionization

    NASA Astrophysics Data System (ADS)

    Argenti, Luca; Moccia, Roberto

    2010-12-01

    An accurate calculation of the nondipole anisotropy parameter γ in the photoionization of helium below the N = 2 threshold is presented. The calculated results are in fairly good agreement with the experimental results of Krässig et al (2002 Phys. Rev. Lett. 88 203002), but not as good as the accuracy of the calculation should have warranted. A careful examination of the possible causes for the observed discrepancies between theory and experiment seems to rule out any role either of the multipolar terms higher than the electric quadrupole, or of the singlet-triplet spin-orbit mixing. It is argued that such discrepancies might have an instrumental origin, due to the difficulty of measuring vanishingly small total cross sections σtot with the required accuracy. In such eventuality, it might be more appropriate to use a parameter other than γ, such as for instance the drag current, to measure the nondipole anisotropy of the photoelectron angular distribution.

  18. Atom lithography with metastable helium

    SciTech Connect

    Allred, Claire S.; Reeves, Jason; Corder, Christopher; Metcalf, Harold

    2010-02-15

    A bright metastable helium (He*) beam is collimated sequentially with the bichromatic force and three optical molasses velocity compression stages. Each He* atom in the beam has 20 eV of internal energy that can destroy a molecular resist assembled on a gold coated silicon wafer. Patterns in the resist are imprinted onto the gold layer with a standard selective etch. Patterning of the wafer with the He{sup *} was demonstrated with two methods. First, a mesh was used to protect parts of the wafer making an array of grid lines. Second, a standing wave of {lambda}=1083 nm light was used to channel and focus the He* atoms into lines separated by {lambda}/2. The patterns were measured with an atomic force microscope establishing an edge resolution of 80 nm. Our results are reliable and repeatable.

  19. Helium Saturation of Liquid Propellants

    NASA Technical Reports Server (NTRS)

    Yavrouian, A. H.; Moran, Clifford M.

    1990-01-01

    The research is in three areas which are: (1) techniques were devised for achieving the required levels of helium (He) saturation in liquid propellants (limited to monomethylhydrazine (MMH) and nitrogen tetroxide (NTO)); (2) the values were evaluated for equilibrium solubilities of He in liquid propellants as currently used in the industry; and (3) the He dissolved in liquid propellants were accurately measured. Conclusions drawn from these studies include: (1) Techniques for dissolving He in liquid propellants depending upon the capabilities of the testing facility (Verification of the quantity of gas dissolved is essential); (2) Until greater accuracy is obtained, the equilibrium solubility values of He in MMH and NTO as cited in the Air Force Propellant Handbooks should be accepted as standard (There are still enough uncertainties in the He saturation values to warrant further basic experimental studies); and (3) The manometric measurement of gas volume from a frozen sample of propellant should be the accepted method for gas analysis.

  20. The tensile strength of helium II

    SciTech Connect

    Xiong, Quan.

    1991-01-01

    The study of the negative pressure required to produce cavitation in liquid helium (i.e. the tensile strength of helium) has been of continuing interest for two reasons. Since all other elements have freezing temperatures of 14 K or higher, helium can be prepared free of gaseous impurities which can serve as centers for heterogeneous nucleation of bubbles which will reduce the tensile strength of the liquid. Secondly, helium remains a liquid even down to the absolute zero of temperature. Consequently, it has been considered that at sufficiently low temperatures there is the possibility that the rate of nucleation of bubbles is dominated by quantum tunneling. In this thesis, the authors reexamined the theory of homogeneous nucleation and made an estimate of the equation of state for negative pressure in helium. He found that the earlier theories were incorrect in that they took no account of the equation of state of liquid helium in the negative pressure regime. The tensile strength of helium at T = 0 K should be around [minus]9 bars instead of [minus]17 bars predicted by the standard theory.

  1. Rapid-releasing of HI-6 via brain-targeted mesoporous silica nanoparticles for nerve agent detoxification

    NASA Astrophysics Data System (ADS)

    Yang, Jun; Fan, Lixue; Wang, Feijian; Luo, Yuan; Sui, Xin; Li, Wanhua; Zhang, Xiaohong; Wang, Yongan

    2016-05-01

    The toxic nerve agent (NA) soman is the most toxic artificially synthesized compound that can rapidly penetrate into the brain and irreversibly inhibit acetylcholinesterase (AChE) activity, leading to immediate death. However, there are currently few brain-targeted nanodrugs that can treat acute chemical brain poisoning owing to the limited drug-releasing speed. The present study investigated the effectiveness of a nanodrug against NA toxicity that has high blood-brain barrier penetration and is capable of rapid drug release. Transferrin-modified mesoporous silica nanoparticles (TF-MSNs) were conjugated with the known AChE reactivator HI-6. This nanodrug rapidly penetrated the blood-brain barrier in zebrafish and mice and restored cerebral AChE activity via the released HI-6, preventing the brain damage caused by soman poisoning and increasing the survival rate in mice. Furthermore, there was no toxicity associated with the MSNs in mice or rats. These results demonstrate that TF-MSNs loaded with HI-6 represent the most effective antidote against NA poisoning by soman reported to date, and suggest that MSNs are a safe alternative to conventional drugs and an optimal nanocarrier for treating brain poisoning, which requires acute pulse cerebral administration.The toxic nerve agent (NA) soman is the most toxic artificially synthesized compound that can rapidly penetrate into the brain and irreversibly inhibit acetylcholinesterase (AChE) activity, leading to immediate death. However, there are currently few brain-targeted nanodrugs that can treat acute chemical brain poisoning owing to the limited drug-releasing speed. The present study investigated the effectiveness of a nanodrug against NA toxicity that has high blood-brain barrier penetration and is capable of rapid drug release. Transferrin-modified mesoporous silica nanoparticles (TF-MSNs) were conjugated with the known AChE reactivator HI-6. This nanodrug rapidly penetrated the blood-brain barrier in zebrafish and

  2. Two Photon Absorption Laser Induced Fluorescence of Helium Ions in a Microwave Assisted Helicon Source

    NASA Astrophysics Data System (ADS)

    Scime, Earl

    2014-10-01

    The spectroscopic measurement of helium ion velocity distribution functions in a low temperature plasma is problematic for a number of reasons. First and foremost is the difficulty in accessing the UV and soft x-ray transitions to the ground state. Conventional laser induced fluorescence on ions in plasmas is routinely performed in argon, neon, xenon, and barium. Two-photon absorption laser induced fluorescence (TALIF) on neutrals has been demonstrated in hydrogen, nitrogen, and oxygen plasmas. We have successfully performed LIF on helium atoms and have had some hints of success with laser absorption spectroscopy on excited states of helium ions, the n = 5 to n = 6 transition in the infrared (1012 nm). Here we report a new approach using TALIF to access the n = 2 to n = 6 transition of singly ionized helium. The fluorescence path at 656 nm completes the three-level sequence. To obtain the electron temperatures necessary to create a sufficient population of metastable helium ions trapped in the 2S state, we have increased the electron temperature of a helicon plasma with 1.2 kW of microwaves at 2.45 GHz. Here we report emission spectroscopy measurements that confirm the increase in excited state population densities and preliminary TALIF measurements on helium ions. This work is funded by the US Department of Energy through Grant DE-SC0004736.

  3. Mass separation of deuterium and helium with conventional quadrupole mass spectrometer by using varied ionization energy

    SciTech Connect

    Yu, Yaowei; Hu, Jiansheng Wan, Zhao; Wu, Jinhua; Wang, Houyin; Cao, Bin

    2016-03-15

    Deuterium pressure in deuterium-helium mixture gas is successfully measured by a common quadrupole mass spectrometer (model: RGA200) with a resolution of ∼0.5 atomic mass unit (AMU), by using varied ionization energy together with new developed software and dedicated calibration for RGA200. The new software is developed by using MATLAB with the new functions: electron energy (EE) scanning, deuterium partial pressure measurement, and automatic data saving. RGA200 with new software is calibrated in pure deuterium and pure helium 1.0 × 10{sup −6}–5.0 × 10{sup −2} Pa, and the relation between pressure and ion current of AMU4 under EE = 25 eV and EE = 70 eV is obtained. From the calibration result and RGA200 scanning with varied ionization energy in deuterium and helium mixture gas, both deuterium partial pressures (P{sub D{sub 2}}) and helium partial pressure (P{sub He}) could be obtained. The result shows that deuterium partial pressure could be measured if P{sub D{sub 2}} > 10{sup −6} Pa (limited by ultimate pressure of calibration vessel), and helium pressure could be measured only if P{sub He}/P{sub D{sub 2}} > 0.45, and the measurement error is evaluated as 15%. This method is successfully employed in EAST 2015 summer campaign to monitor deuterium outgassing/desorption during helium discharge cleaning.

  4. Stable Trapping of Multielectron Helium Bubbles in a Paul Trap

    NASA Astrophysics Data System (ADS)

    Joseph, E. M.; Vadakkumbatt, V.; Pal, A.; Ghosh, A.

    2016-11-01

    In a recent experiment, we have used a linear Paul trap to store and study multielectron bubbles (MEBs) in liquid helium. MEBs have a charge-to-mass ratio (between 10^{-4} and 10^{-2} C/kg) which is several orders of magnitude smaller than ions (between 10^6 and 10^8 C/kg) studied in traditional ion traps. In addition, MEBs experience significant drag force while moving through the liquid. As a result, the experimental parameters for stable trapping of MEBs, such as magnitude and frequency of the applied electric fields, are very different from those used in typical ion trap experiments. The purpose of this paper is to model the motion of MEBs inside a linear Paul trap in liquid helium, determine the range of working parameters of the trap, and compare the results with experiments.

  5. Diffusion and viscosity coefficients for helium. [in astrophysical gas mixtures

    NASA Technical Reports Server (NTRS)

    Roussel-Dupre, R.

    1982-01-01

    The first order Boltzmann-Fokker-Planck equation is solved numerically to obtain diffusion and viscosity coefficients for a ternary gas mixture composed of electron, protons, and helium. The coefficients are tabulated for five He/H abundances ranging from 0.01 to 10 and for both He II and He III. Comparison with Burgers's thermal diffusion coefficients reveals a maximum difference of 9-10% for both He II and He III throughout the range of helium abundances considered. The viscosity coefficients are compared to those of Chapman and Cowling and show a maximum difference of only 5-6% for He II but 15-16% for He III. For the astrophysically important gas mixtures, it is concluded that the results of existing studies which employed Burgers's or Chapman and Cowling's coefficients will remain substantially unaltered.

  6. Nucleation of bubbles in liquid helium

    SciTech Connect

    Maris, H.J. ); Balibar, S.; Pettersen, M.S. )

    1993-12-01

    The authors give a brief survey of experiments that have been performed to study the nucleation of bubbles (cavitation) in liquid helium at negative pressures. There have been two principal motivations for research in this field. Because all impurities (except [sup 3]He) freeze out of the liquid at low temperatures, it is possible to prepare helium with a much higher purity than ordinary classical liquids. In any study of a nucleation process this is an important advantage because impurities introduce the complication of heterogeneous nucleation. The second reason for interest in helium is that at low enough temperatures nucleation is expected to be dominated by quantum tunnelling rather than thermal activation.

  7. Magnesium cluster film synthesis by helium nanodroplets.

    PubMed

    Emery, Samuel B; Rider, Keith B; Little, Brian K; Schrand, Amanda M; Lindsay, C Michael

    2013-08-07

    Atomic and molecular clusters are a unique class of substances with properties that differ greatly from those of the bulk or single atoms due to changes in surface to volume ratio and finite size effects. Here, we demonstrate the ability to create cluster matter films using helium droplet mediated cluster assembly and deposition, a recently developed methodology that condenses atoms or molecules within liquid helium droplets and then gently deposits them onto a surface. In this work, we examine magnesium nanocluster films, which exhibit growth behavior comparable to low-energy cluster beam methods, and demonstrate physical properties and morphology dependent on helium droplet size.

  8. Helium refrigeration considerations for cryomodule design

    SciTech Connect

    Ganni, V.; Knudsen, P.

    2014-01-29

    Many of the present day accelerators are based on superconducting radio frequency (SRF) cavities, packaged in cryo-modules (CM), which depend on helium refrigeration at sub-atmospheric pressures, nominally 2 K. These specialized helium refrigeration systems are quite cost intensive to produce and operate. Particularly as there is typically no work extraction below the 4.5-K supply, it is important that the exergy loss between this temperature level and the CM load temperature(s) be minimized by the process configuration choices. This paper will present, compare and discuss several possible helium distribution process arrangements to support the CM loads.

  9. 21 CFR 868.1640 - Helium gas analyzer.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Helium gas analyzer. 868.1640 Section 868.1640...) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Diagnostic Devices § 868.1640 Helium gas analyzer. (a) Identification. A helium gas analyzer is a device intended to measure the concentration of helium in a...

  10. 21 CFR 868.1640 - Helium gas analyzer.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Helium gas analyzer. 868.1640 Section 868.1640...) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Diagnostic Devices § 868.1640 Helium gas analyzer. (a) Identification. A helium gas analyzer is a device intended to measure the concentration of helium in a gas...

  11. 21 CFR 868.1640 - Helium gas analyzer.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Helium gas analyzer. 868.1640 Section 868.1640...) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Diagnostic Devices § 868.1640 Helium gas analyzer. (a) Identification. A helium gas analyzer is a device intended to measure the concentration of helium in a gas...

  12. 21 CFR 868.1640 - Helium gas analyzer.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Helium gas analyzer. 868.1640 Section 868.1640...) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Diagnostic Devices § 868.1640 Helium gas analyzer. (a) Identification. A helium gas analyzer is a device intended to measure the concentration of helium in a gas...

  13. 21 CFR 868.1640 - Helium gas analyzer.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Helium gas analyzer. 868.1640 Section 868.1640...) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Diagnostic Devices § 868.1640 Helium gas analyzer. (a) Identification. A helium gas analyzer is a device intended to measure the concentration of helium in a gas...

  14. MicroRNA-29a suppresses the growth, migration, and invasion of lung adenocarcinoma cells by targeting carcinoembryonic antigen-related cell adhesion molecule 6.

    PubMed

    Han, Hye Sook; Son, Seung-Myoung; Yun, Jieun; Jo, Yeong Nang; Lee, Ok-Jun

    2014-10-16

    Carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6) is an important regulator of cell adhesion, invasion, and metastasis. The aim of this study was to evaluate the functional roles of CEACAM6 in lung adenocarcinoma and to identify miRNAs that inhibit the growth, migration, and invasion of lung adenocarcinoma cells by targeting CEACAM6. CEACAM6 expression is associated with poor prognosis of patients with lung adenocarcinoma, and CEACAM6 has important functional roles in controlling the growth, migration, and invasion of lung adenocarcinoma cells in vitro and in vivo. Furthermore, miR-29a can suppress the growth, migration, and invasion of lung adenocarcinoma cells by targeting CEACAM6. Therefore, miR-29a/CEACAM6 axis represents a potential therapeutic target for treatment of lung adenocarcinoma.

  15. In silico-guided target identification of a scaffold-focused library: 1,3,5-triazepan-2,6-diones as novel phospholipase A2 inhibitors.

    PubMed

    Muller, Pascal; Lena, Gersande; Boilard, Eric; Bezzine, Sofiane; Lambeau, Gérard; Guichard, Gilles; Rognan, Didier

    2006-11-16

    A collection of 2150 druggable active sites from the Protein Data Bank was screened by high-throughput docking to identify putative targets for five representative molecules of a combinatorial library sharing a 1,3,5-triazepan-2,6-dione scaffold. Five targets were prioritized for experimental evaluation by computing enrichment in individual protein entries among the top 2% scoring targets. Out of the five proposed proteins, secreted phospholipase A2 (sPLA2) was shown to be a true target for a panel of 1,3,5-triazepan-2,6-diones which exhibited micromolar affinities toward two human sPLA2 members.

  16. Contrasting pressure-support ventilation and helium-oxygen during exercise in severe COPD.

    PubMed

    Hussain, Omar; Collins, Eileen G; Adiguzel, Nalan; Langbein, W Edwin; Tobin, Martin J; Laghi, Franco

    2011-03-01

    Helium-oxygen mixtures and pressure-support ventilation have been used to unload the respiratory muscles and increase exercise tolerance in COPD. Considering the different characteristics of these techniques, we hypothesized that helium-oxygen would be more effective in reducing exercise-induced dynamic hyperinflation than pressure-support. We also hypothesized that patients would experience greater increases in respiratory rate and minute ventilation with helium-oxygen than with pressure-support. The hypotheses were tested in ten patients with severe COPD (FEV(1) = 28 ± 3% predicted [mean ± SE]) during constant-load cycling (80% maximal workrate) while breathing 30% oxygen-alone, helium-oxygen, and pressure-support in randomized order. As hypothesized, helium-oxygen had greater impact on dynamic hyperinflation than did pressure-support (end-exercise; p = 0.03). For the most part of exercise, respiratory rate and minute ventilation were greater with helium-oxygen than with pressure-support (p ≤ 0.008). During the initial phases of exercise, helium-oxygen caused less rib-cage muscle recruitment than did pressure-support (p < 0.03), and after the start of exercise it caused greater reduction in inspiratory reserve volume (p ≤ 0.02). Despite these different responses, helium-oxygen and pressure-support caused similar increases in exercise duration (oxygen-alone: 6.9 ± 0.8 min; helium-oxygen: 10.7 ± 1.4 min; pressure-support: 11.2 ± 1.6 min; p = 0.003) and similar decreases in inspiratory effort (esophageal pressure-time product), respiratory drive, pulmonary resistance, dyspnea and leg effort (p < 0.03). In conclusion, helium-oxygen reduced exercise-induced dynamic hyperinflation by improving the relationship between hyperinflation and minute ventilation. In contrast, pressure-support reduced hyperinflation solely as a result of lowering ventilation. Helium-oxygen was more effective in reducing exercise-induced dynamic hyperinflation in severe COPD, and was

  17. From C-Reactive Protein to Interleukin-6 to Interleukin-1: Moving Upstream To Identify Novel Targets for Atheroprotection.

    PubMed

    Ridker, Paul M

    2016-01-08

    Plasma levels of the inflammatory biomarker high-sensitivity C-reactive protein (hsCRP) predict vascular risk with an effect estimate as large as that of total or high-density lipoprotein cholesterol. Further, randomized trial data addressing hsCRP have been central to understanding the anti-inflammatory effects of statin therapy and have consistently demonstrated on-treatment hsCRP levels to be as powerful a predictor of residual cardiovascular risk as on-treatment levels of low-density lipoprotein cholesterol. Yet, although hsCRP is clinically useful as a biomarker for risk prediction, most mechanistic studies suggest that CRP itself is unlikely to be a target for intervention. Moving upstream in the inflammatory cascade from CRP to interleukin (IL)-6 to IL-1 provides novel therapeutic opportunities for atheroprotection that focus on the central IL-6 signaling system and ultimately on inhibition of the IL-1β-producing NOD-like receptor family pyrin domain containing 3 inflammasome. Cholesterol crystals, neutrophil extracellular traps, atheroprone flow, and local tissue hypoxia activate the NOD-like receptor family pyrin domain containing 3 inflammasome. As such, a unifying concept of hsCRP as a downstream surrogate biomarker for upstream IL-1β activity has emerged. From a therapeutic perspective, small ischemia studies show reductions in acute-phase hsCRP production with the IL-1 receptor antagonist anakinra and the IL-6 receptor blocker tocilizumab. A phase IIb study conducted among diabetic patients at high vascular risk indicates that canakinumab, a human monoclonal antibody that targets IL-1β, markedly reduces plasma levels of IL-6, hsCRP, and fibrinogen with little change in atherogenic lipids. Canakinumab in now being tested as a method to prevent recurrent cardiovascular events in a randomized trial of 10 065 post-myocardial infarction patients with elevated hsCRP that is fully enrolled and due to complete in 2017. Clinical trials using alternative anti

  18. Helium resources of the United States, 1987. Information Circular/1988

    SciTech Connect

    Miller, R.D.

    1987-01-01

    The helium-resources base of the United States was estimated by the Bureau of Mines to be 1040 Bcf as of January 1, 1987. These resources are divided into four categories in decreasing degree of assurance of their existence: (1) helium in storage and in proved natural gas reserves, 265 Bcf, (2) helium in probable natural gas resources, 228 Bcf, (3) helium in possible natural gas resources, 320 Bcf, and (4) helium in speculative natural gas resources, 227 Bcf. These helium resources are further divided into depleting and nondepleting, with the helium in storage being in a separate classification.

  19. 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.)

  20. PCAF-mediated acetylation of transcriptional factor HOXB9 suppresses lung adenocarcinoma progression by targeting oncogenic protein JMJD6

    PubMed Central

    Wan, Junhu; Xu, Weizhi; Zhan, Jun; Ma, Ji; Li, Xueying; Xie, Yuping; Wang, Jiadong; Zhu, Wei-guo; Luo, Jianyuan; Zhang, Hongquan

    2016-01-01

    HOXB9 is a homeobox domain-containing transcription factor, playing an important role in embryonic development and cancer progression. However, the precise post-translational modifications (PTMs) of HOXB9 and the corresponding roles are unclear. Here, we report that acetyltransferase p300/CBP-associated factor (PCAF) interacts with and acetylates HOXB9 both in vivo and in vitro. Conversely, the acetylation of HOXB9 can be reversed by deacetylase SIRT1. Furthermore, we found that HOXB9 is acetylated at lysine 27 (AcK27). Functionally, in contrast to the wild type HOXB9, AcK27-HOXB9 decreased its capacity in promoting lung cancer cell migration and tumor growth in mice. Mechanistically, AcK27-HOXB9 suppresses the transcription of its target gene Jumonji domain-containing protein 6 (JMJD6) by direct occupying the promoter of JMJD6 gene. For clinical relevance, elevated HOXB9 acetylation at K27 predicts a better prognosis in lung adenocarcinoma patients. Taken together, we identified the first PTM of HOXB9 by demonstrating that HOXB9 can be acetylated and AcK27-HOXB9 counteracts the role of the wild-type HOXB9 in regulating lung adenocarcinoma progression. PMID:27613418