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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. THERMAL OSCILLATIONS IN LIQUID HELIUM TARGETS.

    SciTech Connect

    WANG,L.; JIA,L.X.

    2001-07-16

    A liquid helium target for the high-energy physics was built and installed in the proton beam line at the Alternate Gradient Synchrotron of Brookhaven National Laboratory in 2001. The target flask has a liquid volume of 8.25 liters and is made of thin Mylar film. A G-M/J-T cryocooler of five-watts at 4.2K was used to produce liquid helium and refrigerate the target. A thermosyphon circuit for the target was connected to the J-T circuit by a liquid/gas separator. Because of the large heat load to the target and its long transfer lines, thermal oscillations were observed during the system tests. To eliminate the oscillation, a series of tests and analyses were carried out. This paper describes the phenomena and provides the understanding of the thermal oscillations in the target system.

  3. Positronium Formation from positron impact off hydrogen and helium targets

    NASA Astrophysics Data System (ADS)

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

    2014-03-01

    Charge exchange cross sections are presented for collisions of positron and protons with hydrogen, neutral and singly ionized helium targets, using a variant of the classical trajectory monte carlo (CTMC) approach. The basic physics of e+; e- creation and annihilation is overviewed. It is shown that for atomic hydrogen and helium targets electron capture by a free positron to form Positronium is vastly more probable than inflight annihilation. Good agreement with available experiment is found and the charge cross section for positron of He+ predicted.

  4. 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.

  5. 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.

  6. 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.

  7. Optimization of Spin-Polarization of Helium-3 Target Cell by Thermal Convection Processes

    NASA Astrophysics Data System (ADS)

    Karthas, Stacy

    2013-10-01

    Polarized Helium-3 (3He) is an effective polarized neutron target that has been used in particle accelerators like the Thomas Jefferson National Accelerator Facility (TJNAF) for the past three decades to study properties of the neutron. Due to the spin structure of its nucleons, the nucleus of 3He can be approximated as a single polarized neutron. The previous generations of 3He targets have reached their limit in polarization and are not ideal for use as targets with the 12 GeV update at TJNAF due to large polarization gradients. The new target cell uses thermal convection to transfer polarized gas to the target chamber quickly. The focus of this project was to study the effects of the new convection system, at various gas velocities, on Adiabatic Fast Passage (AFP) polarization loss that results from measuring the polarization of 3He with Nuclear Magnetic Resonance (NMR). Gas velocities were varied by using a Kapton flexible heater to induce thermal convection. This target cell loses less than one percent of its polarization by measurement when convection is induced at a gas velocity under 6 cm/min thereby verifying the possible use of convection induction for the future experiments. Research conducted at Thomas Jefferson National Accelerator Facility funded through a grant from NSF by the Old Dominion University Research Experience for Undergraduates Program.

  8. 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.

  9. Study of the New Pulse NMR System for the Jefferson Lab Helium-3 Polarized Target

    NASA Astrophysics Data System (ADS)

    Newton, Joseph

    2013-10-01

    At Jefferson Lab, a polarized Helium-3 target is used to study the neutron. The Helium-3 target is undergoing an upgrade to improve its polarization. Measuring it involved a new technique known as pulse Nuclear Magnetic Resonance (NMR). The focus of this project was to find noise in the Pulse NMR signal and to compute the calibration constant to make the polarization easier to deduce. Pulse NMR calibration tests were performed by doing AFP NMR measurements followed by Pulse NMR measurements while varying certain conditions. These included the convection heater, the operation of the oven, and the operation of the laser. Data analysis was done by fitting the pulse NMR signal from the oscilloscope and utilizing the Fourier Transform. Noise was analyzed in the fitting and the Fourier Transform. The calibration constants were affected by the convection heater. The values deviated between the pumping and target chambers of the cell when there was no convection but the values were closer when convection was induced. As far as the noise, it was found to be significant. These results will enable the calculation of the polarization with pulse NMR. In addition, the signal analysis provided insight into the influence of background noise on the pulse NMR measurement. This research was done though the SULI program of the Department of Energy.

  10. 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.

  11. 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.

  12. 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.

  13. Zero Degree Target Electron Spectroscopy: Double Excitation-Autoionization of Helium in Fast Electron, Hydrogen Ion, HELIUM(+) Ion and HELIUM(+2) Ion Collisions

    NASA Astrophysics Data System (ADS)

    Wang, Houle

    The purpose of this work is to investigate few -body dynamical effects in fast ion-atom and electron-atom collisions using zero-degree high-resolution Auger electron spectroscopy. In this study we report the first zero degree high-resolution spectra and double differential cross sections (DDCS) measurement for double excitation-autoionization of He target atoms. We also measured direct ionization DDCS at zero degree observation angle. All of our cross sections are absolutely calibrated. The projectiles used in this work are energetic electrons in the energy range 150 to 1000eV, 100KeV to 1.5MeV protons, 400KeV to 1.5MeV He^+ and 400KeV to 1.6MeV He ^{2+}. The zero degree observation angle provide a unique opportunity to maximize interaction between the emitted electron, the ionized target atom and the charged projectile particle. Using an equal or better than 0.2% instrumental energy resolution allows us to study the autoionization line profiles. In particular the doubly excited autoionizing (2lnl') states of He have been observed as a function of the collision conditions such as impact velocity, projectile charge sign and type of projectile, specifically for dominating (2p^2)^1 Dto(1sepsilon d) and (2s2p)^1P ^circto(1sepsilon p) channels. The results of our measurement clearly indicate that the three-body Coulomb interaction in the final state (CIFS) not only affect autoionizing resonance energies and line widths but also strongly influences the interference of the transition amplitudes between competing processes such as direct ionization and autoionization. We found that the Fano or Shore parametrization generally fails for zero degree autoionization by positive ion impact at medium to high projectile energy. Therefore a new post collisional three-body CIFS model has been developed as a parametrization procedure. This model has been successfully applied to double excitation processes to study single differential cross sections of the (2p^2) ^1D and (2s2p)^1P

  14. 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.

  15. 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.; Dyer, G.; Ihn, Y. S.; Cortez, J.; Aymond, F.; Gaul, E.; Donovan, M. E.; Barbui, M.; et al

    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

  16. 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.

  17. Transient absorption lineshapes in a dense, laser-dressed Helium target probed by attosecond pulse trains

    NASA Astrophysics Data System (ADS)

    Liao, Chen-Ting; Timmers, Henry; Sandhu, Arvinder

    2014-05-01

    Attosecond transient absorption is an emerging time-resolved spectroscopic technique to explore electron dynamics in atoms and molecules. In this experimental study, we used extreme ultraviolet (XUV) attosecond pulse trains (APTs) in energy range of 20-25 eV to probe the transient excited-state absorption of an optically thick Helium gas sample under the influence of moderately strong (1-3 TW/cm2) , infrared (IR), femtosecond pump pulse. We found that the resonant absorption lineshapes for Helium 1s2p, 1snp, and continuum states show rich dynamics, evolving between Lorenzian and Fano profiles with phases imposed by IR laser pulse and multi-channel quantum-path interference. Both AC Stark shifts and light-induced states were studied as a function of pump-probe delay and IR intensity. By changing the Helium gas density, we observed the lineshape modification due to the macroscopic propagation effects, which is usually not included in the single-atom response model. We found that the 13th and 15th high harmonics of XUV produce two coupled polarizations, and the relative coherence between these two polarizations changes the absorption even when the IR pulse arrives after a long time (about 500 fs) after the XUV. This work is supported by NSF Grant No. PHY-0955274.

  18. 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.

  19. 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.

  20. 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.

  1. Nuclear Reaction Analysis of Helium Retention in 6H SiC as a function of irradiation and annealing

    NASA Astrophysics Data System (ADS)

    Bissell, L. J.; Smith, R. J.; Shutthanadan, V.; Adams, E. M.; Thevuthasan, S.; Jiang, W.; Weber, W. J.; Zhang, Y.

    2002-10-01

    Silicon carbide has been proposed as a coating material in nuclear fuel, and silicon carbide composites have been proposed as cladding material in advanced gas-cooled and light water reactors. As such, the effects of irradiation and fission gases on the performance of SiC in the reactor environment are critical in several ways. Since He serves as a fission gas, low-energy He (< 50 keV) will be colliding with coolant gas and outer surface cladding layers. As such, it is important to understand He retention in SiC under advanced reactor operating conditions. We investigated He retention in single crystal 6H SiC as a function of irradiation dose and annealing temperature using nuclear reaction analysis (NRA) via the 3He(D,alpha)1H reaction. Helium ions with 40 keV energy were implanted in the SiC to a depth of ˜360 nm at room temperature under high vacuum conditions. The samples were then transferred to another high vacuum chamber where the NRA was performed using a 1.0 MeV D+ beam. Helium retention was studied as a function of D+ irradiation dose from 5 x 10^(16) to 4 x 10^(18) D+ /cm2, and as a function of annealing temperature ranging from 300 1600 K. No significant helium loss was observed under this dosage range, and only annealing temperatures above 1400 K caused measurable loss of helium. These results will be discussed along with the details associated with the 3He(D,alpha)1H nuclear reaction.

  2. Ordered helium trapping and bonding in compressed arsenolite: Synthesis of A s4O6.2 He

    NASA Astrophysics Data System (ADS)

    Sans, Juan A.; Manjón, Francisco J.; Popescu, Catalin; Cuenca-Gotor, Vanesa P.; Gomis, Oscar; Muñoz, Alfonso; Rodríguez-Hernández, Plácida; Contreras-García, Julia; Pellicer-Porres, Julio; Pereira, Andre L. J.; Santamaría-Pérez, David; Segura, Alfredo

    2016-02-01

    Compression of arsenolite has been studied from a joint experimental and theoretical point of view. Experiments on this molecular solid at high pressures with different pressure-transmitting media have been interpreted thanks to state-of-the-art ab initio calculations. Our results confirm arsenolite as one of the most compressible minerals and provide evidence for ordered helium trapping above 3 GPa between adamantane-type A s4O6 cages. Our calculations indicate that, at relatively small pressures, helium establishes rather localized structural bonds with arsenic forming a compound with stoichiometry A s4O6.2 He . All properties of A s4O6.2 He are different from those of parent A s4O6 . In particular, pressure-induced amorphization, which occurs in arsenolite above 15 GPa, is impeded in A s4O6.2 He , thus resulting in a mechanical stability of A s4O6.2 He beyond 30 GPa. Our work paves the way to explore the formation of alternative compounds by pressure-induced trapping and reaction of gases, small atomic or molecular species, in the voids of molecular solids containing active lone electron pairs.

  3. 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.

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

    NASA Astrophysics Data System (ADS)

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

    2015-01-01

    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.

  5. 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.

  6. First Nuclear Reaction Experiment with Stored Radioactive 56Ni Beam and Internal Hydrogen and Helium Targets

    NASA Astrophysics Data System (ADS)

    Egelhof, P.; Bagchi, S.; Bönig, S.; Csatlós, M.; Dillmann, I.; Dimopoulou, C.; Eremin, V.; Furuno, T.; Geissel, H.; Gernhäuser, R.; Harakeh, M. N.; Hartig, A.-L.; Ilieva, S.; Kalantar-Nayestanaki, N.; Kiselev, O.; Kollmus, H.; Kozhuharov, C.; Krasznahorkay, A.; Kröll, T.; Kuilman, M.; Litvinov, S.; Litvinov, Yu. A.; Mahjour-Shafiei, M.; Mutterer, M.; Nagae, D.; Najafi, M. A.; Nociforo, C.; Nolden, F.; Popp, U.; Rigollet, C.; Roy, S.; Scheidenberger, C.; Von Schmid, M.; Steck, M.; Streicher, B.; Stuhl, L.; Thürauf, M.; Uesaka, T.; Weick, H.; Winfield, J. S.; Winters, D.; Woods, P. J.; Yamaguchi, T.; Yue, K.; Zamora, J. C.; Zenihiro, J.

    The investigation of light-ion induced direct reactions using stored and cooled radioactive beams, interacting with internal targets of storage rings, can lead to substantial advantages over external target experiments, in particular for direct reaction experiments in inverse kinematics at very low momentum transfer, q. This new and challenging experimental technique enables high-resolution measurements down to very low q and provides a gain in luminosity from accumulation and recirculation of the stored beams. For performing first experiments of this kind a dedicated experimental setup housing several DSSD (Double-sided Silicon Strip Detector) and Si(Li) detectors for recoil particles, well suited for meeting the demanding UHV (Ultra High Vacuum) conditions of a storage ring, was recently designed, constructed and installed at the internal target of the ESR storage ring at GSI. From the interaction of a stored 56Ni beam with an internal H2 target, good quality differential cross section data for elastic proton scattering, measured with the aim to determine the radial shape of the nuclear matter distribution of 56Ni, were obtained. Preliminary results are presented. Being the first reaction experiment ever performed with a stored radioactive beam on a world-wide scale, this experiment can be considered as a breakthrough for nuclear structure and astrophysics studies, and, in addition, as a successful proof-of-principle of the new experimental concept. In addition, preliminary results from a feasibility study on inelastic α-scattering from 58Ni in inverse kinematics, where it was demonstrated that the Isoscalar Giant Monopole Resonance in 58Ni can be investigated by the present technique down to CM angles below 1 degree, are discussed. Such an experiment, performed in the future with the doubly magic 56Ni, would provide important information on the EOS of nuclear matter.

  7. 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)].

  8. 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

  9. 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. PMID:16187342

  10. 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

  11. 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...

  12. 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...

  13. 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...

  14. 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...

  15. 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...

  16. 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

  17. 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.

  18. Helium-3 emission related to volcanic activity

    SciTech Connect

    Sano, Y.; Nakamura, Y.; Wakita, H.; Urabe, A.; Tominaga, T.

    1984-04-13

    The helium-3/helium-4 ratio in bubbling gases from ten hot springs located around Mount Ontake, an active volcano in central Japan, ranges from 1.71 R/sub atm/ (1.71 times the atmospheric ratio of 1.40 x 10/sup -6/) to 6.15 R/sub atm/. The value of the ratio decreases with distance from the central cone of the volcano. Such a tendency may be a characteristic of helium-3 emission in volcanic areas and suggests more primitive helium-3 is carried with fluid flowing through a conduit during volcanic activity. 6 references, 1 figure, 1 table.

  19. Tritium and decay helium effects on the fracture toughness properties of types 316L, 304L and 21Cr-6Ni-9Mn stainless steels

    SciTech Connect

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

    1994-10-01

    J-integral fracture mechanics techniques and electron microscopy observations were used to investigate the effects of tritium and its radioactive decay product, {sup 3}He, on Types 316L, 304L and 21Cr-6Ni-9Mn stainless steels. Tritium-exposed-and-aged steels had lower fracture-toughness values and shallower sloped crack-growth-resistance curves than unexposed steels. Both fracture-toughness parameters decreased with increasing concentrations of {sup 3}He. The fracture-toughness reductions were accompanied by a change in fracture mode from microvoid-nucleation-and-growth processes in control samples to grain-and-twin-boundary fracture in tritium-charged-and-aged samples. Type 316L stainless steel had the highest fracture-toughness values and Type 21Cr-6Ni-9Mn had the lowest. Samples containing {sup 3}He but degassed of tritium had fracture toughness properties that were similar to uncharged samples. The results indicate that helium bubbles enhance the embrittlement effects of hydrogen by affecting the deformation properties and by increasing localized hydrogen concentrations through trapping effects.

  20. Interleukin-6: a multifunctional targetable cytokine in human prostate cancer.

    PubMed

    Culig, Zoran; Puhr, Martin

    2012-09-01

    Several cytokines are involved in regulation of cellular events in prostate cancer. Interleukin-6 (IL-6) was frequently investigated in prostate cancer models because of its increased expression in cancer tissue at early stages of the disease. In patients with metastatic prostate cancer, it is well-known that IL-6 levels increase in serum. High levels of IL-6 were measured in the supernatants of cells which do not respond to androgenic stimulation. IL-6 expression in prostate cancer increases due to enhanced expression of transforming growth factor-beta, and members of the activating protein-1 complex, and loss of the retinoblastoma tumour suppressor. IL-6 activation of androgen receptor (AR) may contribute to progression of a subgroup of prostate cancers. Results obtained with two prostate cancer cell lines, LNCaP and MDA PCa 2b, indicate that IL-6 activation of AR may cause either stimulatory or inhibitory responses on proliferation. Interestingly, prolonged treatment with IL-6 led to establishment of an IL-6 autocrine loop, suppressed signal transducer and activator of transcription (STAT)3 activation, and increased mitogen-activated protein kinase phosphorylation. In several cell lines IL-6 acts as a survival molecule through activation of the signalling pathway of phosphotidylinositol 3-kinase. Expression of suppressors of cytokine signalling (SOCS) has been studied in prostate cancer. SOCS-3 prevents phosphorylation of STAT3 and is an important anti-apoptotic factor in AR-negative prostate cancer cells. Experimental therapy against IL-6 in prostate cancer is based on the use of the monoclonal antibody siltuximab which may be used for personalised therapy coming in the future. PMID:21664423

  1. 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.

  2. Electron-impact ionization mass-spectrometry of molecules and clusters in a pulsed helium droplet source

    NASA Astrophysics Data System (ADS)

    Yang, Shengfu; Brereton, Scott; Ellis, Andrew M.

    2006-03-01

    A pulsed helium droplet source has been developed and characterized. The nozzle geometry was found to be critical in allowing controlled tuning of helium nanodroplet size by variation of the stagnation pressure and temperature. The average droplet size scales according to a simple p,T scaling law, placing pulsed helium nanodroplet sources on a par with cw sources for the first time. Using this pulsed source, the ability of helium nanodroplets to impede ion fragmentation in electron impact mass spectrometry has been explored. A number of haloalkanes and C1--C6 alcohols were selected as the target species. The presence of helium alters the fragmentation patterns when compared with the gas phase, with some ion product channels being more strongly affected than others. Parent ion intensities are also enhanced by the helium for alcohols, but only for the two cyclic alcohols studied, cyclopentanol and cyclohexanol, is this effect large enough to transform the parent ion from a minor product (in the gas phase) into the most abundant ion in the helium droplet experiments. The results obtained are difficult to explain solely by rapid cooling of the excited parent ions by the surrounding superfluid helium, although this undoubtedly takes place. A second factor also seems to be involved, a cage effect which favors hydrogen atom loss over other fragmentation channels.

  3. 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.

  4. 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.

  5. The BIRC6 gene as a novel target for therapy of prostate cancer: dual targeting of inhibitors of apoptosis

    PubMed Central

    Iris Luk, Sze Ue; Xue, Hui; Cheng, Hongwei; Lin, Dong; Gout, Peter W.; Fazli, Ladan; Collins, Colin C.; Gleave, Martin E.; Wang, Yuzhuo

    2014-01-01

    Treatment resistance, the major challenge in the management of advanced prostate cancer, is in part based on resistance to apoptosis. The Inhibitor of Apoptosis (IAP) protein family is thought to play key roles in survival and drug resistance of cancer via inhibition of apoptosis. Of the IAP family members, cIAP1, cIAP2, XIAP and survivin are known to be up-regulated in prostate cancer. BIRC6, a much less studied IAP member, was recently shown to be elevated in castration-resistant prostate cancer (CRPC). In the present study, we showed a correlation between elevated BIRC6 expression in clinical prostate cancer specimens and poor patient prognostic factors, as well as co-upregulation of certain IAP members. In view of this, we designed antisense oligonucleotides that simultaneously target BIRC6 and another co-upregulated IAP member (dASOs). Two dASOs, targeting BIRC6+cIAP1 and BIRC6+survivin, showed substantial inhibition of CRPC cell proliferation, exceeding that obtained with single BIRC6 targeting. The growth inhibition was associated with increased apoptosis, cell cycle arrest and suppression of NFkB activation. Moreover, treatment with either dASO led to significantly lower viable tumor volume in vivo, without major host toxicity. This study shows that BIRC6-based dual IAP-targeting ASOs represent potential novel therapeutic agents against advanced prostate cancer. PMID:25071009

  6. Observations of solar-wind helium

    NASA Technical Reports Server (NTRS)

    Neugebauer, M.

    1981-01-01

    It is pointed out that the concentration of helium in the solar wind relative to hydrogen fluctuates wildly. Under certain circumstances, the helium to hydrogen abundance ratio is strongly enhanced over probable solar values; at other times, the amount of helium in the solar wind is immeasurably small. In spite of the fact that helium is heavier than hydrogen, solar-wind helium often leaves the solar gravitational field with a higher velocity than does the hydrogen. It is thought that the mechanisms responsible for helium behavior may contain clues to unanswered questions concerning the acceleration and energy exchange processes of the entire solar wind. A brief review is given of the principal features and theories of the solar wind as a whole. In addition, measurement techniques are discussed. Emphasis throughout is on the experimental data concerning the dynamics of solar-wind helium. On the basis of coronal temperatures, it is shown that helium in the solar wind is almost always doubly ionized. It is also shown that the average abundance of helium ions in the solar wind is usually in the range of 3 to 6% by number.

  7. 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.

  8. 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.

  9. Helium-3 and diffuse Helium-4 emissions prior the 2014-15 Fogo eruption, Cape Verde

    NASA Astrophysics Data System (ADS)

    Asensio-Ramos, María; Padrón, Eleazar; Dionis, Samara; Sumino, Hirochika; Fernandes, Paulo; Melián, Gladys V.; Barrancos, José; Hernández, Pedro A.; Rodríguez, Fátima; Silva, Sónia; Pérez, Nemesio M.; Padilla, Germán; Bandomo, Zuleyka; Cabral, Jeremias; Calvo, David; Pereira, José Manuel; Semedo, Helio

    2015-04-01

    On November 23, 2014 a new volcanic eruption started at the southwestern flank of Pico do Fogo volcano (Fogo Island, Cape Verde) after 19 years of the last eruptive event. Helium-3 emission from fumarole discharges and diffuse helium-4 degassing studies have been carried out regularly at the summit crater of Pico do Fogo since May 2007 until March 2014. The first published data on helium isotopes and diffuse helium-4 degassing from Pico do Fogo volcano is related to the field work performed on February 2010 which shows already relatively high helium-3 emission, 8.53 ± 0.9 R/RA (being R and RA the sample and atmospheric 3He/4He isotope ratio, respectively), and diffuse helium-4 degassing rate, 4.2 ± 0.2 kg d-1 (Dionis et al., 2015). During the eight year period 2007-2014, helium-4 emission rate was measured yearly at 50 different sampling sites selected in the surface environment of the summit crater of Pico do Fogo (0.14 km2) following the Darcy's law, and assuming that helium-4 emission is mainly governed by convection. The distribution of the sampling sites was carefully chosen to homogeneously cover the target area, allowing the computation of the total helium-4 emission by sequential Gaussian simulation (sGs). In addition, helium-3 emission was measured in the fumarole gases following the method described by Sumino et al. (2001). During the eight year period, convective helium-4 emission ranged between 1.2 and 5.7 kg d-1, and helium-3 emission between 7.73 and 8.82 R/RA. Both helium-4 and helium-3 emission showed significant increases on February 2010, suggesting a potential magma intrusion into the volcanic system of Pico do Fogo. However, the highest observed values of both parameters were observed on November, 2013 (helium-3 emission) and on March 2014 (diffuse helium-4 emission) suggesting a second magma intrusion giving rise to the volcanic eruption on November 23, 2014. As was observed in other volcanic systems (Padrón et al., 2013), helium degassing

  10. Helium technology issues

    NASA Technical Reports Server (NTRS)

    Kittel, Peter

    1987-01-01

    A number of future space missions require liquid helium for cooling scientific payloads. These missions will require the long term storage and resupply of liquid helium at temperatures of 1.4 - 2.1 Kelvin. In addition, some of the proposed instruments will require refrigeration to temperatures as low as 50 mK. A variety of liquid helium based refrigerator systems could provide this subkelvin cooling. The status of helium storage and refrigeration technologies and of several alternative technologies is presented here along with areas where further research and development are needed. (Helium resupply technologies are the topic of another presentation at this symposium). The technologies covered include passive and dynamic liquid helium storage, alternatives to liquid helium storage, He -3 refrigerators, He -3/He -4 dilution refrigerators, and alternative sub-kelvin coolers.

  11. Counting Electrons on Liquid Helium

    NASA Astrophysics Data System (ADS)

    Glasson, Phillip

    2004-03-01

    Electrons on liquid helium, localised in an array of quantum dots, have been proposed as condensed matter qubits [M.I.Dykman et al. Phys.Rev. B 67, 155402 (2003)]. The ground and first excited Rydberg states in the vertical potential well on the helium surface would represent |0> and |1>. This requires (a) novel electronic devices on helium using microstructured substrates, (b) excitation of Rydberg states using millimetric microwaves and (c) detection of individual electrons and their quantum states. Progress in meeting these challenges will be presented. An AC-coupled Field Effect Transistor (FET) has been made on GaAs, using free electrons on suspended liquid helium microchannels, 16 micron wide and 1.6 microns deep [P.Glasson et al, Phys.Rev.Lett. 87 176802 (2001)]. The microwave absorption to the first excited Rydberg state near 200 GHz has been measured below 1 K [E.Collin et al. Phys.Rev.Lett. 89, 245301 (2002)], where the temperature-dependent contribution to the linewidth is small. High values of the ratio of the Rabi frequency to the linewidth are obtained. Electrons are trapped on a 5 micron diameter pool of superfluid helium, above a single-electron-transistor (SET) as a detector. The pool is charged from a surface electron reservoir and we count the electrons into and out of the trap. Individual electrons can be stored, detected and counted: the next stage is quantum state detection. The prospects for qubits and quantum information processing with electrons on helium will be assessed.

  12. A Novel Small-Molecule Inhibitor Targeting the IL-6 Receptor β Subunit, Glycoprotein 130.

    PubMed

    Hong, Soon-Sun; Choi, Jung Ho; Lee, Sung Yoon; Park, Yeon-Hwa; Park, Kyung-Yeon; Lee, Joo Young; Kim, Juyoung; Gajulapati, Veeraswamy; Goo, Ja-Il; Singh, Sarbjit; Lee, Kyeong; Kim, Young-Kook; Im, So Hee; Ahn, Sung-Hoon; Rose-John, Stefan; Heo, Tae-Hwe; Choi, Yongseok

    2015-07-01

    IL-6 is a major causative factor of inflammatory disease. Although IL-6 and its signaling pathways are promising targets, orally available small-molecule drugs specific for IL-6 have not been developed. To discover IL-6 antagonists, we screened our in-house chemical library and identified LMT-28, a novel synthetic compound, as a candidate IL-6 blocker. The activity, mechanism of action, and direct molecular target of LMT-28 were investigated. A reporter gene assay showed that LMT-28 suppressed activation of STAT3 induced by IL-6, but not activation induced by leukemia inhibitory factor. In addition, LMT-28 downregulated IL-6-stimulated phosphorylation of STAT3, gp130, and JAK2 protein and substantially inhibited IL-6-dependent TF-1 cell proliferation. LMT-28 antagonized IL-6-induced TNF-α production in vivo. In pathologic models, oral administration of LMT-28 alleviated collagen-induced arthritis and acute pancreatitis in mice. Based on the observation of upstream IL-6 signal inhibition by LMT-28, we hypothesized IL-6, IL-6Rα, or gp130 to be putative molecular targets. We subsequently demonstrated direct interaction of LMT-28 with gp130 and specific reduction of IL-6/IL-6Rα complex binding to gp130 in the presence of LMT-28, which was measured by surface plasmon resonance analysis. Taken together, our data suggest that LMT-28 is a novel synthetic IL-6 inhibitor that functions through direct binding to gp130. PMID:26026064

  13. 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.

  14. Histone deacetylase 6 represents a novel drug target in the oncogenic Hedgehog signaling pathway.

    PubMed

    Dhanyamraju, Pavan Kumar; Holz, Philipp Simon; Finkernagel, Florian; Fendrich, Volker; Lauth, Matthias

    2015-03-01

    Uncontrolled Hedgehog (Hh) signaling is the cause of several malignancies, including the pediatric cancer medulloblastoma, a neuroectodermal tumor affecting the cerebellum. Despite the development of potent Hh pathway antagonists, medulloblastoma drug resistance is still an unresolved issue that requires the identification of novel drug targets. Following up on our observation that histone deacetylase 6 (HDAC6) expression was increased in Hh-driven medulloblastoma, we found that this enzyme is essential for full Hh pathway activation. Intriguingly, these stimulatory effects of HDAC6 are partly integrated downstream of primary cilia, a known HDAC6-regulated structure. In addition, HDAC6 is also required for the complete repression of basal Hh target gene expression. These contrasting effects are mediated by HDAC6's impact on Gli2 mRNA and GLI3 protein expression. As a result of this complex interaction with Hh signaling, global transcriptome analysis revealed that HDAC6 regulates only a subset of Smoothened- and Gli-driven genes, including all well-established Hh targets such as Ptch1 or Gli1. Importantly, medulloblastoma cell survival was severely compromised by HDAC6 inhibition in vitro and pharmacologic HDAC6 blockade strongly reduced tumor growth in an in vivo allograft model. In summary, our data describe an important role for HDAC6 in regulating the mammalian Hh pathway and encourage further studies focusing on HDAC6 as a novel drug target in medulloblastoma. PMID:25552369

  15. 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.

  16. Geomagnetically trapped energetic helium nuclei

    SciTech Connect

    Chen, J.; Gregory Guzik, T.; Wefel, J.P.; Roger Pyle, K.; Cooper, J.F.

    1996-07-01

    Geomagnetically trapped helium nuclei, at high energy ({approximately}40{endash}100 MeV/nucleon), have been measured by the ONR-604 instrument during the 1990/1991 CRRES mission. The ONR-604 instrument resolved the isotopes of helium with a mass resolution of 0.1 amu. The energetic helium observed at {ital L}{lt}2.3 have a pitch angle distribution peaking perpendicular to the local magnetic field, which is characteristic of a trapped population. Both the trapped {sup 3}He and {sup 4}He show two peaks at {ital L}=1.2 and 1.9. Each isotope{close_quote}s flux, in each peak, can be characterized by a power law energy spectrum. The energy spectrum of the {sup 3}He is different from that of {sup 4}He, indicating that the {sup 3}He/{sup 4}He ratio is energy dependent. Over the energy range of 51{endash}86 MeV/nucleon, the {sup 3}He/{sup 4}He ratio is 8.7{plus_minus}3.1 at {ital L}=1.1{endash}1.5 and is 2.4{plus_minus}0.6 at {ital L}=1.5{endash}2.3. The trapped helium counting rates decrease gradually with time during the CRRES mission, when the anomalous component is excluded from the inner heliosphere, indicating that these high energy ions were not injected by flares during this time period. The decrease in intensity is attributed mainly to the events around {ital L}=1.9. The helium around {ital L}=1.2, dominated by {sup 3}He, does not show a significant temporal evolution, which implies a long-term energetic trapped {sup 3}He population. Two possible origins of the geomagnetically trapped helium isotopes are the interactions of energetic protons with the upper atmosphere and/or the inward diffusion and acceleration of helium ions due to electric-field fluctuations. {copyright} {ital 1996 American Institute of Physics.}

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

    PubMed

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

    2014-08-01

    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.

  18. 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

  19. System Review of Safety Function Components for the Design of the Cask MCO Helium Purge System Project A.5 and A.6

    SciTech Connect

    LEW, B.S.

    2000-03-27

    The design of the Cask/Multiple Canister Overpack (MCO) Helium Purge System (HPS) is assessed for the appropriate designated safety function classification of its components. The purpose of this review is to determine appropriate safety function classifications for the system's components or to identify actions to be taken to reasonably assure that the system/component safety function(s) will be performed as intended. This review also includes consideration that the HPS would perform consistent with its analytical assumptions and basis in HNF-2833, Rev. 0.

  20. 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.

  1. Proteomic identification of E6AP as a molecular target of tamoxifen in MCF7 cells.

    PubMed

    Lochab, Savita; Pal, Pooja; Kanaujiya, Jitendra K; Tripathi, Shashi B; Kapoor, Isha; Bhatt, Madan L B; Sanyal, Sabyasachi; Behre, Gerhard; Trivedi, Arun K

    2012-05-01

    Tamoxifen (Tam) is most widely used selective estrogen receptor modulator (SERM) for treatment of hormone-responsive breast cancer. Despite being regularly used in clinical therapy for breast cancer since 1971, the mechanism of Tam action remains largely unclear. In order to gain insights into Tam-mediated antibreast cancer actions, we applied 2DE and MS based proteomics approach to identify target proteins of Tam. We identified E6-associated protein, i.e. E6AP (UBE3A) among others to be regulated by Tam that otherwise is upregulated in breast tumors. We confirmed our 2DE finding by immunoblotting and further show that Tam leads to inhibition of E6AP expression presumably by promoting its autoubiquitination, which is coupled with nuclear export and subsequent proteasome-mediated degradation. Furthermore, we show that Tam- and siE6AP-mediated inhibition of E6AP leads to enhanced G0-G1 growth arrest and apoptosis, which is also evident from significant upregulation of cytochrome-c, Bax, p21, and PARP cleavage. Taken together, our data suggest that, Tam-targeted E6AP inhibition is in fact required for Tam-mediated antibreast cancer actions. Thus, E6AP may be a therapeutic target in breast cancer.

  2. 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.

  3. MicroRNA-183 suppresses retinoblastoma cell growth, invasion and migration by targeting LRP6.

    PubMed

    Wang, Jianwen; Wang, Xiaochun; Li, Zhongji; Liu, Hongtao; Teng, Yan

    2014-03-01

    Our study demonstrates the downregulation of microRNA-183 (miR-183) in retinoblastoma (RB) tissues and RB cell lines compared with normal retinal tissues. The ectopic expression of miR-183 in the RB cell lines Y79, SO-RB50 and WERI-RB1 suppresses cell viability, migration and invasion. Furthermore, the Wnt co-receptor low-density lipoprotein receptor-related protein 6 (LRP6) was identified as a new target of miR-183, and restoration of the expression of LRP6 rescues the effects induced by miR-183 in RB cells. These results indicate that miR-183 targets and downregulates LRP6 in the growth, migration and invasion of RB cells. PMID:24289859

  4. 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.

  5. 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…

  6. 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

  7. Lrp1/LDL Receptor Play Critical Roles in Mannose 6-Phosphate-Independent Lysosomal Enzyme Targeting.

    PubMed

    Markmann, Sandra; Thelen, Melanie; Cornils, Kerstin; Schweizer, Michaela; Brocke-Ahmadinejad, Nahal; Willnow, Thomas; Heeren, Joerg; Gieselmann, Volkmar; Braulke, Thomas; Kollmann, Katrin

    2015-07-01

    Most lysosomal enzymes require mannose 6-phosphate (M6P) residues for efficient receptor-mediated lysosomal targeting. Although the lack of M6P residues results in missorting and hypersecretion, selected lysosomal enzymes reach normal levels in lysosomes of various cell types, suggesting the existence of M6P-independent transport routes. Here, we quantify the lysosomal proteome in M6P-deficient mouse fibroblasts (PT(ki)) using Stable Isotope Labeling by Amino acids in Cell culture (SILAC)-based comparative mass spectrometry, and find unchanged amounts of 20% of lysosomal enzymes, including cathepsins D and B (Ctsd and Ctsb). Examination of fibroblasts from a new mouse line lacking both M6P and sortilin, a candidate for M6P-independent transport of lysosomal enzymes, revealed that sortilin does not act as cargo receptor for Ctsb and Ctsd. Using fibroblast lines deficient for endocytic lipoprotein receptors, we could demonstrate that both LDL receptor and Lrp1 mediate the internalization of non-phosphorylated Ctsb and Ctsd. Furthermore, the presence of Lrp1 inhibitor increased the secretion of Ctsd from PT(ki) cells. These findings establish Lrp1 and LDL receptors in M6P-independent secretion-recapture targeting mechanism for lysosomal enzymes.

  8. Core helium flash

    SciTech Connect

    Cole, P.W.; Deupree, R.G.

    1980-01-01

    The role of convection in the core helium flash is simulated by two-dimensional eddies interacting with the thermonuclear runaway. These eddies are followed by the explicit solution of the 2D conservation laws with a 2D finite difference hydrodynamics code. Thus, no phenomenological theory of convection such as the local mixing length theory is required. The core helium flash is violent, producing a deflagration wave. This differs from the detonation wave (and subsequent disruption of the entire star) produced in previous spherically symmetric violent core helium flashes as the second dimension provides a degree of relief which allows the expansion wave to decouple itself from the burning front. Our results predict that a considerable amount of helium in the core will be burned before the horizontal branch is reached and that some envelope mass loss is likely.

  9. 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.

  10. The Cell Cycle Regulator CCDC6 Is a Key Target of RNA-Binding Protein EWS

    PubMed Central

    Duggimpudi, Sujitha; Larsson, Erik; Nabhani, Schafiq; Borkhardt, Arndt; Hoell, Jessica I

    2015-01-01

    Genetic translocation of EWSR1 to ETS transcription factor coding region is considered as primary cause for Ewing sarcoma. Previous studies focused on the biology of chimeric transcription factors formed due to this translocation. However, the physiological consequences of heterozygous EWSR1 loss in these tumors have largely remained elusive. Previously, we have identified various mRNAs bound to EWS using PAR-CLIP. In this study, we demonstrate CCDC6, a known cell cycle regulator protein, as a novel target regulated by EWS. siRNA mediated down regulation of EWS caused an elevated apoptosis in cells in a CCDC6-dependant manner. This effect was rescued upon re-expression of CCDC6. This study provides evidence for a novel functional link through which wild-type EWS operates in a target-dependant manner in Ewing sarcoma. PMID:25751255

  11. 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.

  12. THPP target assignment reveals EchA6 as an essential fatty acid shuttle in mycobacteria.

    PubMed

    Cox, Jonathan A G; Abrahams, Katherine A; Alemparte, Carlos; Ghidelli-Disse, Sonja; Rullas, Joaquín; Angulo-Barturen, Iñigo; Singh, Albel; Gurcha, Sudagar S; Nataraj, Vijayashankar; Bethell, Stephen; Remuiñán, Modesto J; Encinas, Lourdes; Jervis, Peter J; Cammack, Nicholas C; Bhatt, Apoorva; Kruse, Ulrich; Bantscheff, Marcus; Fütterer, Klaus; Barros, David; Ballell, Lluis; Drewes, Gerard; Besra, Gurdyal S

    2016-01-01

    Phenotypic screens for bactericidal compounds against drug-resistant tuberculosis are beginning to yield novel inhibitors. However, reliable target identification remains challenging. Here, we show that tetrahydropyrazo[1,5-a]pyrimidine-3-carboxamide (THPP) selectively pulls down EchA6 in a stereospecific manner, instead of the previously assigned target Mycobacterium tuberculosis MmpL3. While homologous to mammalian enoyl-coenzyme A (CoA) hydratases, EchA6 is non-catalytic yet essential and binds long-chain acyl-CoAs. THPP inhibitors compete with CoA-binding, suppress mycolic acid synthesis, and are bactericidal in a mouse model of chronic tuberculosis infection. A point mutation, W133A, abrogated THPP-binding and increased both the in vitro minimum inhibitory concentration and the in vivo effective dose 99 in mice. Surprisingly, EchA6 interacts with selected enzymes of fatty acid synthase II (FAS-II) in bacterial two-hybrid assays, suggesting essentiality may be linked to feeding long-chain fatty acids to FAS-II. Finally, our data show that spontaneous resistance-conferring mutations can potentially obscure the actual target or alternative targets of small molecule inhibitors. PMID:27571973

  13. Advances in Helium Cryogenics

    NASA Astrophysics Data System (ADS)

    Sciver, S. W. Van

    This review provides a survey of major advances that have occurred in recent years in the area of helium cryogenics. Helium-temperature cryogenics is the enabling technology for a substantial and growing number of low-temperature systems from superconducting magnets to space-based experimental facilities. In recent years there have been many advances in the technology of low-temperature helium, driven mostly by new applications. However, to keep the review from being too broad, this presentation focuses mainly on three of the most significant advances. These are: (1) the development of large-scale recuperative refrigeration systems mainly for superconducting magnet applications in accelerators and other research facilities; (2) the use of stored superfluid helium (He II) as a coolant for spacebased astrophysics experiments; and (3) the application of regenerative cryocoolers operating at liquid helium temperatures primarily for cooling superconducting devices. In each case, the reader should observe that critical technologies were developed to facilitate these applications. In addition to these three primary advances, other significant helium cryogenic technologies are briefly reviewed at the end of this chapter, along with some vision for future developments in these areas.

  14. The Chemical Evolution of Helium

    NASA Astrophysics Data System (ADS)

    Balser, Dana S.

    2006-12-01

    We report on measurements of the 4He abundance toward the outer Galaxy H II region S206 with the NRAO Green Bank Telescope. Observations of hydrogen and helium radio recombination lines between 8 and 10 GHz were made toward the peak radio continuum position in S206. We derive 4He/H=0.08459+/-0.00088 (random)+/-0.0010 (known systematic), 20% lower than optical recombination line results. It is difficult to reconcile the large discrepancy between the optical and radio values even when accounting for temperature, density, and ionization structure or for optical extinction by dust. Using only M17 and S206 we determine ΔY/ΔZ=1.41+/-0.62 in the Galaxy, consistent with standard chemical evolution models. High helium abundances in the old stellar population of elliptical galaxies can help explain the increase in UV emission with shorter wavelength between 2000 and 1200 Å, called the ``UV upturn'' or UVX. Our lower values of ΔY/ΔZ are consistent with a normal helium abundance at higher metallicity and suggest that other factors, such as a variable red giant branch mass loss with metallicity, may be important. When combined with 4He abundances in metal-poor galaxy H II regions, Magellanic Cloud H II regions, and M17 that have been determined from optical recombination lines, including the effects of temperature fluctuations, our radio 4He/H abundance ratio for S206 is consistent with a helium evolution of ΔY/ΔZ=1.6. A linear extrapolation to zero metallicity predicts a 4He/H primordial abundance ratio about 5% lower than that given by the Wilkinson Microwave Anisotropy Probe and standard big bang nucleosynthesis. The measured 4He abundances may be systematically underestimated by a few percent if clumping exists in these H II regions.

  15. 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.

  16. Targeted ablation of the abcc6 gene results in ectopic mineralization of connective tissues.

    PubMed

    Klement, John F; Matsuzaki, Yasushi; Jiang, Qiu-Jie; Terlizzi, Joseph; Choi, Hae Young; Fujimoto, Norihiro; Li, Kehua; Pulkkinen, Leena; Birk, David E; Sundberg, John P; Uitto, Jouni

    2005-09-01

    Pseudoxanthoma elasticum (PXE), characterized by connective tissue mineralization of the skin, eyes, and cardiovascular system, is caused by mutations in the ABCC6 gene. ABCC6 encodes multidrug resistance-associated protein 6 (MRP6), which is expressed primarily in the liver and kidneys. Mechanisms producing ectopic mineralization as a result of these mutations remain unclear. To elucidate this complex disease, a transgenic mouse was generated by targeted ablation of the mouse Abcc6 gene. Abcc6 null mice were negative for Mrp6 expression in the liver, and complete necropsies revealed profound mineralization of several tissues, including skin, arterial blood vessels, and retina, while heterozygous animals were indistinguishable from the wild-type mice. Particularly striking was the mineralization of vibrissae, as confirmed by von Kossa and alizarin red stains. Electron microscopy revealed mineralization affecting both elastic structures and collagen fibers. Mineralization of vibrissae was noted as early as 5 weeks of age and was progressive with age in Abcc6(-/-) mice but was not observed in Abcc6(+/-) or Abcc6(+/+) mice up to 2 years of age. A total body computerized tomography scan of Abcc6(-/-) mice revealed mineralization in skin and subcutaneous tissue as well as in the kidneys. These data demonstrate aberrant mineralization of soft tissues in PXE-affected organs, and, consequently, these mice recapitulate features of this complex disease.

  17. 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.

  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. PMID:25850020

  19. Helium liquefaction with a 4 K pulse tube cryocooler

    NASA Astrophysics Data System (ADS)

    Wang, Chao

    2001-07-01

    Helium liquefaction with a two-stage 4 K pulse tube cryocooler is introduced in this paper. The helium liquefier has a feature of precooling helium gas to be liquefied by using inefficiency of the second stage regenerator in the pulse tube cryocooler. This process reduces enthalpy of the incoming helium gas when entering the condenser and significantly increases the condensation rate. Numerical analysis predicts the precooling heat load on the second stage regenerator, decreases the PTC second stage cooling capacity by only 11% of the heat actually absorbed into the regenerator. A prototype pulse tube helium liquefier was built, which has two precooling heat exchangers on the first stage cold head and the second stage regenerator. It continuously liquefies helium with a rate of 4.8 l/day under normal pressure while consumes 4.6 kW power input.

  20. 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

  1. 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

  2. Interleukin 6 receptor is an independent prognostic factor and a potential therapeutic target of ovarian cancer.

    PubMed

    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

  3. Sporothrix schenckii: purification and partial biochemical characterization of glucosamine-6-phosphate synthase, a potential antifungal target.

    PubMed

    González-Ibarra, Joaquín; Milewski, Sławomir; Villagómez-Castro, Julio C; Cano-Canchola, Carmen; López-Romero, Everardo

    2010-02-01

    The first committed step of the biosynthetic pathway leading to uridine-5'-diphospho-N-acetyl-D-glucosamine (UDP-GlcNAc) is catalyzed by glucosamine-6-phosphate synthase (GlcN-6-P synthase), an enzyme proposed as a potential antifungal chemotherapy target. Here, we describe the purification and biochemical characterization of the native enzyme from the dimorphic pathogenic fungus Sporothrix schenckii. The availability of the pure protein facilitated its biochemical characterization. The enzyme exhibited subunit and native molecular masses of 79 and 350+/-5 kDa, respectively, suggesting a homotetrameric structure. Isoelectric point was 6.26 and K(m) values for fructose-6-phosphate and L-glutamine were 1.12+/-0.3 and 2.2+/-0.7 mM, respectively. Inhibition of activity by UDP-GlcNAc was enhanced by Glc-6-P and phosphorylation stimulated GlcN-6-P synthase activity without affecting the enzyme sensitivity to the aminosugar. A glutamine analogue, FMDP [N(3)-(4-methoxyfumaroyl)-L-2,3-diaminopropanoic acid] was a more potent inhibitor of activity than ADMP (2-Amino-2-deoxy-D-mannitol-6-phosphate) but the latter was a stronger inhibitor of growth in two culture media. To our knowledge, this is the first report on the purification and biochemical characterization of a non-recombinant GlcN-6-P synthase from a true dimorphic fungus. Inhibition of enzyme activity and fungal growth by specific inhibitors of GlcN-6-P synthase strongly reinforces the role of this enzyme as a potential target for antifungal chemotherapy. PMID:19353425

  4. 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.

  5. HDAC6 is a target for protection and regeneration following injury in the nervous system

    PubMed Central

    Rivieccio, Mark A.; Brochier, Camille; Willis, Dianna E.; Walker, Breset A.; D'Annibale, Melissa A.; McLaughlin, Kathryn; Siddiq, Ambreena; Kozikowski, Alan P.; Jaffrey, Samie R.; Twiss, Jeffery L.; Ratan, Rajiv R.; Langley, Brett

    2009-01-01

    Central nervous system (CNS) trauma can result in tissue disruption, neuronal and axonal degeneration, and neurological dysfunction. The limited spontaneous CNS repair in adulthood and aging is often insufficient to overcome disability. Several investigations have demonstrated that targeting HDAC activity can protect neurons and glia and improve outcomes in CNS injury and disease models. However, the enthusiasm for pan-HDAC inhibition in treating neurological conditions is tempered by their toxicity toward a host of CNS cell types –a biological extension of their anticancer properties. Identification of the HDAC isoform, or isoforms, that specifically mediate the beneficial effects of pan-HDAC inhibition could overcome this concern. Here, we show that pan-HDAC inhibition not only promotes neuronal protection against oxidative stress, a common mediator of injury in many neurological conditions, but also promotes neurite growth on myelin-associated glycoprotein and chondroitin sulfate proteoglycan substrates. Real-time PCR revealed a robust and selective increase in HDAC6 expression due to injury in neurons. Accordingly, we have used pharmacological and genetic approaches to demonstrate that inhibition of HDAC6 can promote survival and regeneration of neurons. Consistent with a cytoplasmic localization, the biological effects of HDAC6 inhibition appear transcription-independent. Notably, we find that selective inhibition of HDAC6 avoids cell death associated with pan-HDAC inhibition. Together, these findings define HDAC6 as a potential nontoxic therapeutic target for ameliorating CNS injury characterized by oxidative stress-induced neurodegeneration and insufficient axonal regeneration. PMID:19884510

  6. miR-10a regulates proliferation of human cardiomyocyte progenitor cells by targeting GATA6.

    PubMed

    Liang, Dandan; Zhen, Lixiao; Yuan, Tianyou; Huang, Jian; Deng, Fangfei; Wuyahan; Zhang, Hong; Pan, Lei; Liu, Yi; The, Erlinda; Yu, Zuoren; Zhu, Weidong; Zhang, Yuzhen; Li, Li; Peng, Luying; Li, Jun; Chen, Yi-Han

    2014-01-01

    microRNAs (miRNAs) play essential roles in cardiogenesis. The altered expression of miRNAs can result in cardiac malformations by inducing abnormalities in the behavior of cardiac cells. However, the role of miR-10a in the regulation of cardiomyocyte progenitor cells (CMPCs) remains undetermined. In the present study, we found that up- or down-regulation of miR-10a inhibited or promoted the proliferation of human CMPCs, respectively, without affecting their differentiation toward cardiomyocytes. miR-10a bound to GATA6 directly and reduced GATA6 expression. Over-expression of GATA6 greatly attenuated the miR-10a-mediated inhibitory effect on the proliferation of human CMPCs. Thus, our results indicate that miR-10a could effectively modulate the proliferation of human CMPCs by targeting GATA6. The finding provides novel insights into the potency of miR-10a during heart development.

  7. Variation in Atmospheric Helium Isotopes

    NASA Astrophysics Data System (ADS)

    Mabry, J. C.; Marty, B.; Burnard, P.; Blard, P.

    2010-12-01

    Anthropogenic activity such as oil and gas exploitation releases crustal helium, which has excess 4He compared to atmospheric helium. This may give rise to both spatial and temporal variations in the atmospheric 3He/4He. Helium is present in trace quantities in the air (5 ppm) and has a very low ratio (3He/4Heair = 1.38 x 10-6), consequently high precision measurements of atmospheric He presents a significant analytical challenge. Recent work by Sano et al. [1] has endeavored to experimentally quantify these potential variations in the atmospheric 3He/4He by measuring the helium isotopes from air samples collected around the globe and from samples of ancient trapped atmosphere. Their results indicate an increase in the atmospheric 3He/4He from northern to southern latitudes of the order 2 - 4 ‰, which they attribute to greater use of fossil fuels in the northern hemisphere. However, since most of their data points overlap at the 2-3 ‰ (2σ) level, additional measurements (with increased precision if possible) are needed. We have constructed an automated extraction line dedicated to measuring He in samples of air which can rapidly switch between measuring aliquots of sample with standards. It additionally features an adjustable bellows on the sample aliquot volume that enables us to adjust the size of a sample aliquot to precisely match the standard, eliminating biases arising from nonlinear pressure effects in the mass spectrometer. The measurements are made using a Helix SFT multi-collector mass spectrometer. At present, repeat measurements of 3He/4He from our standard (purified air) have a reproducibility of 2‰ (2σ), while measurements of local (Nancy, France) air samples have a reproducibility of 3He/4He of 3‰ (2σ), which are at a similar level to the uncertainties reported by Sano. Modifications are underway to improve 3He measurements which are the principal source of error. We have collected atmospheric samples from around the globe over a wide

  8. 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

  9. 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

  10. 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.

  11. Microglia-specific targeting by novel capsid-modified AAV6 vectors

    PubMed Central

    Rosario, Awilda M; Cruz, Pedro E; Ceballos-Diaz, Carolina; Strickland, Michael R; Siemienski, Zoe; Pardo, Meghan; Schob, Keri-Lyn; Li, Andrew; Aslanidi, George V; Srivastava, Arun; Golde, Todd E; Chakrabarty, Paramita

    2016-01-01

    Recombinant adeno-associated viruses (rAAV) have been widely used in gene therapy applications for central nervous system diseases. Though rAAV can efficiently target neurons and astrocytes in mouse brains, microglia, the immune cells of the brain, are refractile to rAAV. To identify AAV capsids with microglia-specific transduction properties, we initially screened the most commonly used serotypes, AAV1–9 and rh10, on primary mouse microglia cultures. While these capsids were not permissive, we then tested the microglial targeting properties of a newly characterized set of modified rAAV6 capsid variants with high tropism for monocytes. Indeed, these newly characterized rAAV6 capsid variants, specially a triply mutated Y731F/Y705F/T492V form, carrying a self-complementary genome and microglia-specific promoters (F4/80 or CD68) could efficiently and selectively transduce microglia in vitro. Delivery of these constructs in mice brains resulted in microglia-specific expression of green fluorescent protein, albeit at modest levels. We further show that CD68 promoter–driven expression of the inflammatory cytokine, interleukin-6, using this capsid variant leads to increased astrogliosis in the brains of wild-type mice. Our study describes the first instance of AAV-targeted microglial gene expression leading to functional modulation of the innate immune system in mice brains. This provides the rationale for utilizing these unique capsid/promoter combinations for microglia-specific gene targeting for modeling or functional studies. PMID:27308302

  12. Proton Intensity Spectra during the May 17th, 2012 and January 6th, 2014 Solar Energetic Particle Events - Measurement Capabilities of the Electron Proton Helium Telescope on Board SOHO

    NASA Astrophysics Data System (ADS)

    Kühl, P.; Banjac, S.; Dresing, N.; Gomez-Herrero, R.; Heber, B.; Klassen, A.; Terasa, C.

    2014-12-01

    Ground Level Enhancements are solar energetic particle events that show a significant intensity increase at energies that can be measured by ground based instrumentation, i.e. neutron monitors. In the recent history 71 GLEs have been recorded. The last one was the May 17, 2012 event that has not only been measured by more than one neutron monitor but also by sophisticated instrumentation in space like PAMELA and the Electron Proton Helium INstrument (EPHIN) aboard SOHO. The January 6, 2014 solar energetic particle (SEP) event led to an intensity increase of about 3 percent at both South Pole neutron monitors and was considered by Thakur et al. (2014) to be a GLE. Since only one pair of neutron monitors show an unambiguous increase the energy spectra for this event can only be determined by spacecraft like e.g. PAMELA or SOHO/EPHIN. We show that the Electron Proton Helium INstrument at Langragian point L1 is capable to measure the proton energy spectra of solar energetic particle events at energies between 150 MeV and above 700 MeV. A GEANT Monte Carlo simulation has been performed to determine the energy response function of EPHIN for electrons, protons and heavier ions. As a result of this calculation we developed a method using energy loss information of particles measured in the detector stack that allow to derive the proton energy spectra in the range from about 150 MeV to more than 700 MeV. In order to validate our method we compared our results to the one obtained by PAMELA that was published by Bazilevskaya et al. (2013) for the May 2012 event. Furthermore, the January 6, 2014 event spectrum in the given energy range is presented and discussed in comparison to the May 2012 event.

  13. 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

  14. Histone acetyltransferase inhibitor CPTH6 preferentially targets lung cancer stem-like cells

    PubMed Central

    Di Martile, Marta; Desideri, Marianna; De Luca, Teresa; Gabellini, Chiara; Buglioni, Simonetta; Eramo, Adriana; Sette, Giovanni; Milella, Michele; Rotili, Dante; Mai, Antonello; Carradori, Simone; Secci, Daniela; De Maria, Ruggero; Del Bufalo, Donatella; Trisciuoglio, Daniela

    2016-01-01

    Cancer stem cells (CSCs) play an important role in tumor initiation, progression, therapeutic failure and tumor relapse. In this study, we evaluated the efficacy of the thiazole derivative 3-methylcyclopentylidene-[4-(4′-chlorophenyl)thiazol-2-yl]hydrazone (CPTH6), a novel pCAF and Gcn5 histone acetyltransferase inhibitor, as a small molecule that preferentially targets lung cancer stem-like cells (LCSCs) derived from non-small cell lung cancer (NSCLC) patients. Notably, although CPTH6 inhibits the growth of both LCSC and NSCLC cell lines, LCSCs exhibit greater growth inhibition than established NSCLC cells. Growth inhibitory effect of CPTH6 in LCSC lines is primarily due to apoptosis induction. Of note, differentiated progeny of LCSC lines is more resistant to CPTH6 in terms of loss of cell viability and reduction of protein acetylation, when compared to their undifferentiated counterparts. Interestingly, in LCSC lines CPTH6 treatment is also associated with a reduction of stemness markers. By using different HAT inhibitors we provide clear evidence that inhibition of HAT confers a strong preferential inhibitory effect on cell viability of undifferentiated LCSC lines when compared to their differentiated progeny. In vivo, CPTH6 is able to inhibit the growth of LCSC-derived xenografts and to reduce cancer stem cell content in treated tumors, as evidenced by marked reduction of tumor-initiating capacity in limiting dilution assays. Strikingly, the ability of CPTH6 to inhibit tubulin acetylation is also confirmed in vivo. Overall, our studies propose histone acetyltransferase inhibition as an attractive target for cancer therapy of NSCLC. PMID:26870991

  15. Eupatilin inhibits EGF-induced JB6 cell transformation by targeting PI3K.

    PubMed

    Li, Feng; Tao, Ya; Qiao, Yan; Li, Ke; Jiang, Yanan; Cao, Chang; Ren, Shuxin; Chang, Xiaobin; Wang, Xiaona; Wang, Yanhong; Xie, Yifei; Dong, Ziming; Zhao, Jimin; Liu, Kangdong

    2016-09-01

    Phosphatidylinositol 3-kinases (PI3Ks) are lipid kinases that play fundamental roles in regulation of multiple signaling pathways, including cell proliferation, survival and cell cycle. Increasing evidence has shown that abnormal activation of PI3K pathway contributes to tumorigenesis and progression of various malignant tumors. Therefore, it is an attractive target of chemoprevention and chemotherapy. Eupatilin, a natural flavone compound extracted from Artemisia vulgaris, has antitumor and anti-inflammation efficacy. However, the direct target(s) of eupatilin in cancer chemoprevention are still elusive. In the present study, we reported eupatilin suppressed JB6 cell proliferation and its EGF-induced colony formation. Eupatilin attenuated phosphorylation of PI3K downstream signaling molecules. Downregulation of cyclin D1 expression and arresting in G1 phase were induced through eupatilin treatment. Furthermore, we found it could bind to the p110α, a catalytic subunit of PI3K, by computational docking methods. Pull down assay outcomes also verified the binding of eupatilin with PI3K. Taken together, our results suggest that epatilin is a potential chemopreventive agent in inhibition of skin cell transformation by targeting PI3K. PMID:27573489

  16. 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

  17. Therapeutic Targeting of the Cyclin D3:CDK4/6 Complex in T Cell Leukemia

    PubMed Central

    Sawai, Catherine; Freund, Jacquelyn; Oh, Philmo; Ndiaye-Lobry, Delphine; Bretz, Jamieson C.; Strikoudis, Alexandros; Genesca, Lali; Trimarchi, Thomas; Kelliher, Michelle A.; Clark, Marcus; Soulier, Jean; Chen-Kiang, Selina; Aifantis, Iannis

    2012-01-01

    SUMMARY D-type cyclins form complexes with cyclin dependent kinases (CDK4/6), and promote cell cycle progression. Although cyclin D functions appear largely tissue specific, we demonstrate that cyclin D3 has unique functions in lymphocyte development and cannot be replaced by cyclin D2, which is also expressed during blood differentiation. We show that only combined deletion of p27Kip1 and Rb is sufficient to rescue the development of Ccnd3−/− thymocytes. Furthermore, we show that a small molecule targeting the kinase function of cyclin D3:CDK4/6 inhibits both cell cycle entry in human T cell acute lymphoblastic leukemia (T-ALL) and disease progression in animal models of T-ALL. These studies identify unique functions for cyclin D3:CDK4/6 complexes and suggest potential therapeutic protocols for this devastating blood tumor. PMID:23079656

  18. 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.

  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. 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 .

  1. Targeted photodestruction of human colon cancer cells using charged Dougherty chlorine6immunoconjugates

    PubMed Central

    Governatore, M Del; Hamblin, MR; Piccinini, EE; Ugolini, G; Hasan, T

    1999-01-01

    The goal of this study was to develop a strategy for the selective destruction of colorectal cancer cells. Towards this end, photoimmunoconjugates were prepared between the anti-colon cancer monoclonal antibody 17.1A and the photosensitizer (PS) chlorine6(ce6). Polylysine linkers bearing several ce6molecules were covalently attached in a site-specific manner to partially reduced IgG molecules, which allowed photoimmunoconjugates to bear either cationic or anionic charges. The conjugates retained immunoreactivity as shown by enzyme-linked immunosorbent assays and by competition studies with native antibody. The overall charge on the photoimmunoconjugate was an important determinant of PS delivery. The cationic photoimmunoconjugate delivered 4 times more ce6to the cells than the anionic photoimmunoconjugate, and both 17.1A conjugates showed, in comparison to non-specific rabbit IgG conjugates, selectivity for antigen-positive target cells. Illumination with only 3 J cm−2of 666 nm light reduced the number of colony forming cells by more than 90% for the cationic 17.1A conjugate and by 73% for the anionic 17.1A conjugate after incubation with 1 μM ce6equivalent of the respective conjugates. By contrast, 1 μM free ce6gave only a 35% reduction in colonies. These data suggest photoimmunoconjugates may have applications in photoimmunotherapy where destruction of colorectal cancer cells is required. © 2000 Cancer Research Campaign PMID:10638967

  2. Targeting the FOXO1/KLF6 axis regulates EGFR signaling and treatment response

    PubMed Central

    Sangodkar, Jaya; Dhawan, Neil S.; Melville, Heather; Singh, Varan J.; Yuan, Eric; Rana, Huma; Izadmehr, Sudeh; Farrington, Caroline; Mazhar, Sahar; Katz, Suzanna; Albano, Tara; Arnovitz, Pearlann; Okrent, Rachel; Ohlmeyer, Michael; Galsky, Matthew; Burstein, David; Zhang, David; Politi, Katerina; DiFeo, Analisa; Narla, Goutham

    2012-01-01

    EGFR activation is both a key molecular driver of disease progression and the target of a broad class of molecular agents designed to treat advanced cancer. Nevertheless, resistance develops through several mechanisms, including activation of AKT signaling. Though much is known about the specific molecular lesions conferring resistance to anti-EGFR–based therapies, additional molecular characterization of the downstream mediators of EGFR signaling may lead to the development of new classes of targeted molecular therapies to treat resistant disease. We identified a transcriptional network involving the tumor suppressors Krüppel-like factor 6 (KLF6) and forkhead box O1 (FOXO1) that negatively regulates activated EGFR signaling in both cell culture and in vivo models. Furthermore, the use of the FDA-approved drug trifluoperazine hydrochloride (TFP), which has been shown to inhibit FOXO1 nuclear export, restored sensitivity to AKT-driven erlotinib resistance through modulation of the KLF6/FOXO1 signaling cascade in both cell culture and xenograft models of lung adenocarcinoma. Combined, these findings define a novel transcriptional network regulating oncogenic EGFR signaling and identify a class of FDA-approved drugs as capable of restoring chemosensitivity to anti-EGFR–based therapy for the treatment of metastatic lung adenocarcinoma. PMID:22653055

  3. 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.

  4. 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.

  5. Er81 is a downstream target of Pax6 in cortical progenitors

    PubMed Central

    Tuoc, Tran Cong; Stoykova, Anastassia

    2008-01-01

    Background Although the transcription factor Pax6 plays an essential role in neurogenesis, layer formation and arealization in the developing mammalian cortex, the mechanisms by which it accomplishes these regulatory functions are largely unknown. Pax6 and the ETS family transcription factor Er81, which is presumed to play a role in the specification of a sublineage of layer 5 projection neurons, are expressed with a prominent rostrolateral-high to caudomedial-low gradient in cortical progenitors. In the absence of functional Pax6, progenitors do not express Er81 and the rostrolateral cortex lacks Er81-positive layer 5 neurons. In this study, we investigated the transcriptional regulation of Er81 and provide evidence that Er81 is a direct target of Pax6. Results We identified and analyzed the regulatory function of an evolutionarily conserved upstream DNA sequence in the putative mouse Er81 promoter. Three potential Pax6 binding sites were identified in this region. We found that the presence of one of these sites is necessary and sufficient for full activation of the Er81 promoter in Pax6-transfected HeLa cells, while other still unknown factors appear to contribute to Er81 promoter activity in cortical progenitors and neuronal cells. The results suggest that endogenous Pax6, which is expressed at the highest level in progenitors of the rostrolateral cortex, exerts region-specific control of Er81 activity, thus specifying a subpopulation of layer 5 projection neurons. Conclusion We conclude that the genetic interplay between the transcription factors, Pax6 and Er81, is responsible, in part, for the regional specification of a distinct sublineage of layer 5 projection neurons. PMID:18307776

  6. Glucose-6-phosphate dehydrogenase is the target for the trypanocidal action of human steroids.

    PubMed

    Gupta, Shreedhara; Cordeiro, Artur T; Michels, Paul A M

    2011-04-01

    Steroids such as dehydroepiandrosterone (DHEA) and epiandrosterone (EA) exert multiple effects in mammals including the inhibition of glucose-6-phosphate dehydrogenase (G6PDH). Initially, the inhibition was considered specific for the mammalian enzyme. The beneficial effect of these steroids on infections by protists and nematodes was attributed to stimulation of the immune system. However, we showed previously that DHEA and EA also inhibit Trypanosoma brucei and T. cruzi G6PDH, with low micromolar K(i)' values, but not the enzyme from Leishmania species, and kill in vitro cultured trypanosomes. We report here that, contrary to wild-type trypanosomes, mutant bloodstream-form T. brucei cells expressing L. mexicana G6PDH are not susceptible to the steroids, proving that G6PDH is the in situ target. Moreover, bromo-derivatives of the steroids show 50-100 fold lower K(i)' values for the enzyme and display an increased potency to kill the parasites. Therefore, the compounds offer promise for use in development of parasite-selective drugs.

  7. Computer aided screening of natural compounds targeting the E6 protein of HPV using molecular docking

    PubMed Central

    Mamgain, Saril; Sharma, Pushpendra; Pathak, Rajesh Kumar; Baunthiyal, Mamta

    2015-01-01

    The cancer profile in the Indian state of Uttarakhand reveals that the breast cancer is the most prevalent type of cancers in females followed by cervical and ovarian type. Literature survey shows that the E6 protein of Human Papilloma Virus-16 (HPV-16) is responsible for causing several forms of cancer in human. Therefore, it is of interest to screen HPV-16 E6 target protein with known natural compounds using computer aided molecular modeling and docking tools. The complete structure of E6 is unknown. Hence, the E6 structure model was constructed using different online servers followed by molecular docking of Colchine, Curcumin, Daphnoretin, Ellipticine and Epigallocatechin-3-gallate; five known natural compounds with best E6 protein model predicted by Phyre2 server. The screening exercise shows that Daphnoretin (with binding free energy of -8.3 kcal/mol), a natural compound derived from Wikstroemia indica has the top binding properties. Thus, it is of interest to consider the compound for further validation. PMID:26124567

  8. 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.

  9. 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.

  10. Multipurpose closed-cycle cryocooler for liquefying hydrogen, helium-4 or helium-3

    NASA Astrophysics Data System (ADS)

    Winter, Calvin

    1990-08-01

    A cryogenic refrigerator utilizing helium-4 gas in closed-cycle Gifford-McMahon and Joule-Thomson cooling loops was built and achieves continuous operating temperatures of 2.8R. The object cooled is a thin walled (0.1mm) seamless electroformed nickel target sample cell with a volume of 160m1. Room temperature hydrogen, helium-4 or helium-3 gas, supplied at a pressure slightly above atmospheric, is liquefied by the cryocooler and fills the cell. Unusual features include: horizontal operation; a long narrow extension on the vacuum shroud (900mm long, 76mm diameter) and special valves to select an operating temperature appropriate to the sample gas and maximize the cooling power available at that temperature.

  11. Small Helium Liquefiers Using 4 K Pulse Tube Cryocoolers

    NASA Astrophysics Data System (ADS)

    Wang, C.

    2006-04-01

    Two small helium liquefiers using 4 K pulse tube cryocooler have been developed and commercialized at Cryomech, Inc. Model PT405 and PT410 pulse tube cryocoolers used for the liquefiers have cooling capacities of 0.5 W and 1.0 W at 4.2 K respectively. One distinctive advantage of the pulse tube liquefiers is efficient precooling of helium gas to be liquefied with the 1st stage heat exchanger and the 2nd stage regenerator of the cold head. The liquefier with the PT405 liquefies helium from room temperature at a rate of 7.2 Liter/day for 4.6 kW power input. The liquefier with the PT410 has a liquefaction rate of 14.0 liter/day for 8.0 kW power input. The helium liquefiers have been used for a few challenging applications to liquefy and re-condense helium.

  12. 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.

  13. From CRP to IL-6 to IL-1: Moving Upstream To Identify Novel Targets for Atheroprotection

    PubMed Central

    Ridker, Paul M

    2016-01-01

    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 HDL 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 LDL cholesterol. Yet, while 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 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 NLRP3 inflammasome. Cholesterol crystals, neutrophil extracellular traps (NETs), atheroprone flow, and local tissue hypoxia activate the NLRP3 inflammasome. As such, a unifying concept of hsCRP as a downstream surrogate biomarker 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 no 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 employing alternative anti-inflammatory agents active against the CRP/IL-6/IL-1 axis including low dose methotrexate and colchicine are being explored. If successful

  14. Pseudotyped αvβ6 integrin-targeted adenovirus vectors for ovarian cancer therapies

    PubMed Central

    Uusi-Kerttula, Hanni; Davies, James; Coughlan, Lynda; Hulin-Curtis, Sarah; Jones, Rachel; Hanna, Louise; Chester, John D.; Parker, Alan L.

    2016-01-01

    Encouraging results from recent clinical trials are revitalizing the field of oncolytic virotherapies. Human adenovirus type 5 (HAdV-C5/Ad5) is a common vector for its ease of manipulation, high production titers and capacity to transduce multiple cell types. However, effective clinical applications are hindered by poor tumor-selectivity and vector neutralization. We generated Ad5/kn48 by pseudotyping Ad5 with the fiber knob domain from the less seroprevalent HAdV-D48 (Ad48). The vector was shown to utilize coxsackie and adenovirus receptor (CAR) but not CD46 for cell entry. A 20-amino acid peptide NAVPNLRGDLQVLAQKVART (A20) was inserted into the Ad5. Luc HI loop (Ad5.HI.A20) and Ad5/kn48 DG loop (Ad5/kn48.DG.A20) to target a prognostic cancer cell marker, αvβ6 integrin. Relative to the Ad5.Luc parent vector, Ad5.HI.A20, Ad5.KO1.HI.A20 (KO1, ablated CAR-binding) and Ad5/kn48.DG.A20 showed ∼ 160-, 270- and 180-fold increased transduction in BT-20 breast carcinoma cells (αvβ6high). Primary human epithelial ovarian cancer (EOC) cultures derived from clinical ascites provided a useful ex vivo model for intraperitoneal virotherapy. Ad5.HI.A20, Ad5.KO1.HI.A20 and Ad5/kn48.DG.A20 transduction was ∼ 70-, 60- and 16-fold increased relative to Ad5.Luc in EOC cells (αvβ6high), respectively. A20 vectors transduced EOC cells at up to ∼ 950-fold higher efficiency in the presence of neutralizing ovarian ascites, as compared to Ad5.Luc. Efficient transduction and enhanced cancer-selectivity via a non-native αvβ6-mediated route was demonstrated, even in the presence of pre-existing anti-Ad5 immunity. Consequently, αvβ6-targeted Ad vectors may represent a promising platform for local intraperitoneal treatment of ovarian cancer metastases. PMID:27056886

  15. 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

  16. 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.

  17. 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.

  18. 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.

  19. Helium, Carbon, and Helium Isotopes in the Northern Lau Basin

    NASA Astrophysics Data System (ADS)

    Lupton, J. E.; Butterfield, D. A.; Lilley, M. D.; Resing, J.; Embley, R. W.; Arculus, R. J.; Rubin, K. H.; Evans, L.; Greene, R.

    2009-12-01

    Helium isotope ratios in hydrothermal fluids and volcanic rocks in the northern Lau Basin show a complex pattern reflecting influences from diverse mantle sources, including the Samoan hotspot, the Tofua Arc, and mid-ocean ridge (MOR)-type upper mantle. The Samoan Islands represent a “high 3He” hotspot with 3He/4He ratios up to 38 Ra (where Ra is the 3He/4He ratio in air, 1.39 x 10-6) [Farley et al, 1992; Jackson et al., 2007]. In contrast to the 3He-rich helium in Samoa, typical back-arc spreading centers have MOR-type helium values of 7-9 Ra, while volcanic arcs have lower ratios of 5-7 Ra. In the northwestern part of the Lau Basin, basalt samples from the Northwest Lau Spreading Center and the Rochambeau Rifts have 3He/4He varying from 11 to 28 Ra, far above typical back-arc or MOR values. These elevated 3He/4He ratios indicate that the Samoan hotspot signal has somehow penetrated southward into the northern Lau Basin, presumably through a tear in the subducting Pacific Plate. In the northeastern Lau Basin, 3He/4He ratios in hydrothermal fluids from two sites on the Northeast Lau Spreading Center have 3He/4He of 8.0 and 8.7 Ra. These are MOR-type values typical for a back-arc spreading center. At the actively erupting West Mata volcano, vent fluids have 3He/4He of 7.3 Ra, while farther east at Volcano P analysis of water-column plume samples gave a value of 6.7 Ra for the estimated end-member 3He/4He value. This decrease in 3He/4He going toward the east indicates increasing arc influence with increasing proximity to the Tofua Arc. This interpretation is supported by the C/3He ratios in the hydrothermal fluids, which average 1-3 x 109 at vent sites on the NELSC (typical MOR values) and increase to a typical arc value of 2 x 1010 at West Mata. Analyses of volcanic rocks from the eruption sites on the NELSC and West Mata are in progress and should help to further define these variations.

  20. 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.

  1. CDK4/6 inhibition provides a potent adjunct to Her2-targeted therapies in preclinical breast cancer models

    PubMed Central

    Witkiewicz, Agnieszka K.; Cox, Derek; Knudsen, Erik S.

    2014-01-01

    In spite of the efficacy of Her2-targeted therapies, recurrence and progression remain a challenge for treatment of Her2 positive breast cancer. CDK4/6 controls pathway downstream of Her2, Inhibition of these kinases could represent an important therapeutic approach to augment the effectiveness of standard therapies. In models of acquired resistance to Her2-targeted therapies, Cyclin D1 was inappropriately activated and CDK4/6 inhibition was effective at blocking proliferation by targeting this common pathway associated with resistance. These data were recapitulated in Her2 positive xenografts. Furthermore, in a series of 35 primary breast tumor explants, treatment with PD-0332991 resulted in a greater than 4-fold suppression of the Ki67. The effects of CDK4/6 inhibition were dependent on an intact RB-pathway, and consonantly, loss of RB and high-levels of p16 were associated with resistance to CDK4/6 inhibition. Combination studies illustrated that CDK4/6 inhibition is cooperative with multiple Her2-targeted agents and provides a complementary mechanism of action to T-DM1 to efficiently suppresses the proliferation of residual Her2-positive tumor cell populations that survive T-DM1. Together, these data indicate CDK4/6 is a viable therapeutic target that functions downstream of Her2, and tissue based markers are available to direct rational utilization of CDK4/6 inhibitors in combination with Her2-targeted agents. PMID:25221644

  2. 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.

  3. The DNA virus Invertebrate iridescent virus 6 is a target of the Drosophila RNAi machinery.

    PubMed

    Bronkhorst, Alfred W; van Cleef, Koen W R; Vodovar, Nicolas; Ince, Ikbal Agah; Blanc, Hervé; Vlak, Just M; Saleh, Maria-Carla; van Rij, Ronald P

    2012-12-18

    RNA viruses in insects are targets of an RNA interference (RNAi)-based antiviral immune response, in which viral replication intermediates or viral dsRNA genomes are processed by Dicer-2 (Dcr-2) into viral small interfering RNAs (vsiRNAs). Whether dsDNA virus infections are controlled by the RNAi pathway remains to be determined. Here, we analyzed the role of RNAi in DNA virus infection using Drosophila melanogaster infected with Invertebrate iridescent virus 6 (IIV-6) as a model. We show that Dcr-2 and Argonaute-2 mutant flies are more sensitive to virus infection, suggesting that vsiRNAs contribute to the control of DNA virus infection. Indeed, small RNA sequencing of IIV-6-infected WT and RNAi mutant flies identified abundant vsiRNAs that were produced in a Dcr-2-dependent manner. We observed a highly uneven distribution with strong clustering of vsiRNAs to small defined regions (hotspots) and modest coverage at other regions (coldspots). vsiRNAs mapped in similar proportions to both strands of the viral genome, suggesting that long dsRNA derived from convergent overlapping transcripts serves as a substrate for Dcr-2. In agreement, strand-specific RT-PCR and Northern blot analyses indicated that antisense transcripts are produced during infection. Moreover, we show that vsiRNAs are functional in silencing reporter constructs carrying fragments of the IIV-6 genome. Together, our data indicate that RNAi provides antiviral defense against dsDNA viruses in animals. Thus, RNAi is the predominant antiviral defense mechanism in insects that provides protection against all major classes of viruses. PMID:23151511

  4. Concerted genomic targeting of H3K27 demethylase REF6 and chromatin-remodeling ATPase BRM in Arabidopsis.

    PubMed

    Li, Chenlong; Gu, Lianfeng; Gao, Lei; Chen, Chen; Wei, Chuang-Qi; Qiu, Qi; Chien, Chih-Wei; Wang, Suikang; Jiang, Lihua; Ai, Lian-Feng; Chen, Chia-Yang; Yang, Songguang; Nguyen, Vi; Qi, Yanhua; Snyder, Michael P; Burlingame, Alma L; Kohalmi, Susanne E; Huang, Shangzhi; Cao, Xiaofeng; Wang, Zhi-Yong; Wu, Keqiang; Chen, Xuemei; Cui, Yuhai

    2016-06-01

    SWI/SNF-type chromatin remodelers, such as BRAHMA (BRM), and H3K27 demethylases both have active roles in regulating gene expression at the chromatin level, but how they are recruited to specific genomic sites remains largely unknown. Here we show that RELATIVE OF EARLY FLOWERING 6 (REF6), a plant-unique H3K27 demethylase, targets genomic loci containing a CTCTGYTY motif via its zinc-finger (ZnF) domains and facilitates the recruitment of BRM. Genome-wide analyses showed that REF6 colocalizes with BRM at many genomic sites with the CTCTGYTY motif. Loss of REF6 results in decreased BRM occupancy at BRM-REF6 co-targets. Furthermore, REF6 directly binds to the CTCTGYTY motif in vitro, and deletion of the motif from a target gene renders it inaccessible to REF6 in vivo. Finally, we show that, when its ZnF domains are deleted, REF6 loses its genomic targeting ability. Thus, our work identifies a new genomic targeting mechanism for an H3K27 demethylase and demonstrates its key role in recruiting the BRM chromatin remodeler. PMID:27111034

  5. 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

  6. 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

  7. Low-Density Lipoprotein Receptor-Related Protein 6 (LRP6) Is a Novel Nutritional Therapeutic Target for Hyperlipidemia, Non-Alcoholic Fatty Liver Disease, and Atherosclerosis.

    PubMed

    Go, Gwang-woong

    2015-06-01

    Low-density lipoprotein receptor-related protein 6 (LRP6) is a member of the low-density lipoprotein receptor family and has a unique structure, which facilitates its multiple functions as a co-receptor for Wnt/β-catenin signaling and as a ligand receptor for endocytosis. The role LRP6 plays in metabolic regulation, specifically in the nutrient-sensing pathway, has recently garnered considerable interest. Patients carrying an LRP6 mutation exhibit elevated levels of LDL cholesterol, triglycerides, and fasting glucose, which cooperatively constitute the risk factors of metabolic syndrome and atherosclerosis. Since the discovery of this mutation, the general role of LRP6 in lipid homeostasis, glucose metabolism, and atherosclerosis has been thoroughly researched. These studies have demonstrated that LRP6 plays a role in LDL receptor-mediated LDL uptake. In addition, when the LRP6 mutant impaired Wnt-LRP6 signaling, hyperlipidemia, non-alcoholic fatty liver disease, and atherosclerosis developed. LRP6 regulates lipid homeostasis and body fat mass via the nutrient-sensing mechanistic target of the rapamycin (mTOR) pathway. Furthermore, the mutant LRP6 triggers atherosclerosis by activating platelet-derived growth factor (PDGF)-dependent vascular smooth muscle cell differentiation. This review highlights the exceptional opportunities to study the pathophysiologic contributions of LRP6 to metabolic syndrome and cardiovascular diseases, which implicate LRP6 as a latent regulator of lipid metabolism and a novel therapeutic target for nutritional intervention. PMID:26046396

  8. 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.

  9. Helium cryopumping for fusion applications

    SciTech Connect

    Sedgley, D.W.; Batzer, T.H.; Call, W.R.

    1988-05-01

    Large quantities of helium and hydrogen isotopes will be exhausted continuously from fusion power reactors. This paper summarizes two development programs undertaken to address vacuum pumping for this application: (i) A continuous duty cryopump for pumping helium and/or hydrogen species using charcoal sorbent and (ii) a cryopump configuration with an alternative shielding arrangement using charcoal sorbent or argon spray. A test program evaluated automatic pumping of helium, helium pumping by charcoal cryosorption and with argon spray, and cryosorption of helium/hydrogen mixtures. The continuous duty cryopump pumped helium continuously and conveniently. Helium pumping speed was 7.7 l/s/cm/sup 2/ of charcoal, compared to 5.8 l/s/cm/sup 2/ for the alternative pump. Helium speed using argon spray was 18% of that obtained by charcoal cryosorption in the same (W-panel) pump. During continuous duty cryopump mixture tests with helium and hydrogen copumped on charcoal, gas was released sporadically. Testing was insufficient to explain this unacceptable event.

  10. Helium jet dispersion to atmosphere

    NASA Technical Reports Server (NTRS)

    Khan, Hasna J.

    1986-01-01

    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.

  11. 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

  12. 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)...

  13. 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)...

  14. 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)...

  15. 48 CFR 52.208-8 - Required Sources for Helium and Helium Usage Data.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 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)...

  16. 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)...

  17. 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

    2015-08-01

    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. PMID:26267199

  18. 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

    2015-08-01

    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.

  19. Photoionization from excited states of helium

    NASA Technical Reports Server (NTRS)

    Jacobs, V. L.

    1973-01-01

    The cross sections for photoionization from the 2 1S, 2 3S, 2 1P and 2 3P excited states of helium are calculated for photoelectron energies below the n = 2 threshold of He(+) using Hylleraas bound state wave functions and 1s-2s-2p close coupling final state wave functions. The resonant structures associated with the lowest-lying 1S, 1P, 3P, and 1D autoionizing states of helium are found to be characterized by large values of the line profile parameter q. The cross sections and the photoelectron angular distribution asymmetry parameters for the P-states are calculated for various polarization states of the target atom and the incident photon. Experiments which would lead to the separate determinations of the S- and D- wave partial photoionization cross sections are discussed.

  20. Liquid Helium Acoustic Microscope.

    NASA Astrophysics Data System (ADS)

    Steer, Andrew Paul

    Available from UMI in association with The British Library. In an acoustic microscope, images are generated by monitoring the intensity of the ultrasonic reflection, or echo, from the surface of a sample. In order to achieve this a pulse of acoustic energy is produced by the excitation of a thin film transducer. The pulse thus generated propagates through a crystal and is incident upon the acoustic lens surface, which is the boundary between the crystal and an acoustic coupling liquid. The acoustic lens is a converging element, and brings the ultrasonic beam to a focus within the liquid. A sample, placed at the focus, can act as a reflector, and the returned pulse then contains information regarding the acoustic reflectivity of this specimen. Acoustic pulses are repeatedly launched and detected while the acoustic lens is scanned over the surface of the sample. In this manner an acoustic image is constructed. Acoustic losses in room temperature liquid coupling media represent a considerable source of difficulty in the recovery of acoustic echo signals. At the frequencies of operation required in a microscope which is capable of high resolution, the ultrasonic attenuation is not only large but increases with the square of frequency. In superfluid liquid helium at temperatures below 0.1 K, however, the ultrasonic attenuation becomes negligible. Furthermore, the low sound velocity in liquid helium results in an increase in resolution, since the acoustic wavelength is proportional to velocity. A liquid helium acoustic microscope has been designed and constructed. Details of the various possible detection methods are given, and comparisons are made between them. Measurements of the performance of the system that was adopted are reported. The development of a cooled preamplifier is also described. The variation of reflected signal with object distance has been measured and compared with theoretical predictions. This variation is important in the analysis of acoustic

  1. 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

  2. RPGR, a prenylated retinal ciliopathy protein, is targeted to cilia in a prenylation- and PDE6D-dependent manner

    PubMed Central

    Dutta, Nirmal

    2016-01-01

    ABSTRACT RPGR (retinitis pigmentosa GTPase regulator) is a ciliary protein associated with several forms of inherited retinal degenerative diseases. PDE6D is a ubiquitously expressed prenyl-binding protein and involved in ciliary targeting of prenylated proteins. The current working model for the RPGR function depicts that RPGR acts as a scaffold protein to recruit cargo-loaded PDE6D to primary cilia. Here, we present evidence demonstrating an alternative relationship between RPGR and PDE6D, in which RPGR is a cargo of PDE6D for ciliary targeting. We found that the constitutive isoform of RPGR, which is prenylated, requires prenylation for its ciliary localization. We also found that there are at least two independent ciliary targeting signals in RPGR: one within the N-terminal region that contains the RCC1-like domain and the other near the prenylation site at the C-terminus. Ablation of PDE6D blocked ciliary targeting of RPGR. Our study indicates that prenylated RPGR is one of the cargos of PDE6D for ciliary trafficking and provides insight into the mechanisms by which RPGR is targeted to cilia. PMID:27493202

  3. RPGR, a prenylated retinal ciliopathy protein, is targeted to cilia in a prenylation- and PDE6D-dependent manner.

    PubMed

    Dutta, Nirmal; Seo, Seongjin

    2016-09-15

    RPGR (retinitis pigmentosa GTPase regulator) is a ciliary protein associated with several forms of inherited retinal degenerative diseases. PDE6D is a ubiquitously expressed prenyl-binding protein and involved in ciliary targeting of prenylated proteins. The current working model for the RPGR function depicts that RPGR acts as a scaffold protein to recruit cargo-loaded PDE6D to primary cilia. Here, we present evidence demonstrating an alternative relationship between RPGR and PDE6D, in which RPGR is a cargo of PDE6D for ciliary targeting. We found that the constitutive isoform of RPGR, which is prenylated, requires prenylation for its ciliary localization. We also found that there are at least two independent ciliary targeting signals in RPGR: one within the N-terminal region that contains the RCC1-like domain and the other near the prenylation site at the C-terminus. Ablation of PDE6D blocked ciliary targeting of RPGR. Our study indicates that prenylated RPGR is one of the cargos of PDE6D for ciliary trafficking and provides insight into the mechanisms by which RPGR is targeted to cilia.

  4. RPGR, a prenylated retinal ciliopathy protein, is targeted to cilia in a prenylation- and PDE6D-dependent manner.

    PubMed

    Dutta, Nirmal; Seo, Seongjin

    2016-01-01

    RPGR (retinitis pigmentosa GTPase regulator) is a ciliary protein associated with several forms of inherited retinal degenerative diseases. PDE6D is a ubiquitously expressed prenyl-binding protein and involved in ciliary targeting of prenylated proteins. The current working model for the RPGR function depicts that RPGR acts as a scaffold protein to recruit cargo-loaded PDE6D to primary cilia. Here, we present evidence demonstrating an alternative relationship between RPGR and PDE6D, in which RPGR is a cargo of PDE6D for ciliary targeting. We found that the constitutive isoform of RPGR, which is prenylated, requires prenylation for its ciliary localization. We also found that there are at least two independent ciliary targeting signals in RPGR: one within the N-terminal region that contains the RCC1-like domain and the other near the prenylation site at the C-terminus. Ablation of PDE6D blocked ciliary targeting of RPGR. Our study indicates that prenylated RPGR is one of the cargos of PDE6D for ciliary trafficking and provides insight into the mechanisms by which RPGR is targeted to cilia. PMID:27493202

  5. Targeted antitumoral dehydrocrotonin nanoparticles with L-ascorbic acid 6-stearate.

    PubMed

    Frungillo, Lucas; Martins, Dorival; Teixeira, Sérgio; Anazetti, Maristela Conti; Melo, Patrícia da Silva; Durán, Nelson

    2009-12-01

    Tumoral cells are known to have a higher ascorbic acid uptake than normal cells. Therefore, the aim of this study was to obtain polymeric nanoparticles containing the antitumoral compound trans-dehydrocrotonin (DHC) functionalized with L-ascorbic acid 6-stearate (AAS) to specifically target this system tumoral cells. Nanoparticle suspensions (NP-AAS-DHC) were prepared by the nanoprecipitation method. The systems were characterized for AAS presence by thin-layer chromatography and for drug loading (81-88%) by UV-Vis spectroscopy. To further characterize these systems, in vitro release kinetics, size distribution (100-140 nm) and Zeta potential by photon-correlation spectroscopic method were used. In vitro toxicity against HL60 cells was evaluated by tetrazolium reduction and Trypan blue exclusion assays. Cell death by apoptosis was quantified and characterized by flow cytometry and caspase activity. Zeta potential analyses showed that the system has a negatively charged outer surface and also indicate that AAS is incorporated on the external surface of the nanoparticles. In vitro release kinetics assay showed that DHC loaded in nanoparticles had sustained release behavior. In vitro toxicity assays showed that NP-AAS-DHC suspension was more effective as an antitumoral than free DHC or NP-DHC and increased apoptosis induction by receptor-mediated pathway.

  6. 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.

  7. 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.

  8. 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.

  9. 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

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

    PubMed

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

    2016-05-01

    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

  11. 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. PMID:23457867

  12. Characterization of Regulatory Events Associated with Membrane Targeting of p90 Ribosomal S6 Kinase 1

    PubMed Central

    Richards, Stephanie A.; Dreisbach, Valley C.; Murphy, Leon O.; Blenis, John

    2001-01-01

    RSK is a serine/threonine kinase containing two distinct catalytic domains. Found at the terminus of the Ras/extracellular signal-regulated kinase (ERK)–mitogen-activated protein kinase (MAPK) kinase cascade, mitogen-stimulated ribosomal S6 kinase (RSK) activity requires multiple inputs. These inputs include phosphorylation of the C-terminal kinase domain activation loop by ERK1/2 and phosphorylation of the N-terminal kinase domain activation loop by phosphoinositide-dependent protein kinase-1 (PDK1). Previous work has shown that upon mitogen stimulation, RSK accumulates in the nucleus. Here we show that prior to nuclear translocation, epidermal growth factor-stimulated RSK1 transiently associates with the plasma membrane. Myristylation of wild-type RSK1 results in an activated enzyme in the absence of added growth factors. When RSK is truncated at the C terminus, the characterized ERK docking is removed and RSK phosphotransferase activity is completely abolished. When myristylated, however, this myristylated C-terminal truncated form (myrCTT) is activated at a level equivalent to myristylated wild-type (myrWT) RSK. Both myrWT RSK and myrCTT RSK can signal to the RSK substrate c-Fos in the absence of mitogen activation. Unlike myrWT RSK, myrCTT RSK is not further activated by serum. Only the myristylated RSK proteins are basally phosphorylated on avian RSK1 serine 381, a site critical for RSK activity. The myristylated and unmyristylated RSK constructs interact with PDK1 upon mitogen stimulation, and this interaction is insensitive to the MEK inhibitor UO126. Because a kinase-inactive CTT RSK can be constitutively activated by targeting to the membrane, we propose that ERK may have a dual role in early RSK activation events: preliminary phosphorylation of RSK and escorting RSK to a membrane-associated complex, where additional MEK/ERK-independent activating inputs are encountered. PMID:11585927

  13. Pharmacological targeting of glucose-6-phosphate dehydrogenase in human erythrocytes by Bay 11-7082, parthenolide and dimethyl fumarate.

    PubMed

    Ghashghaeinia, Mehrdad; Giustarini, Daniela; Koralkova, Pavla; Köberle, Martin; Alzoubi, Kousi; Bissinger, Rosi; Hosseinzadeh, Zohreh; Dreischer, Peter; Bernhardt, Ingolf; Lang, Florian; Toulany, Mahmoud; Wieder, Thomas; Mojzikova, Renata; Rossi, Ranieri; Mrowietz, Ulrich

    2016-01-01

    In mature erythrocytes, glucose-6-phosphate dehydrogenase (G6PDH) and 6-phosphogluconate dehydrogenase (6PGDH) yield NADPH, a crucial cofactor of the enzyme glutathione reductase (GR) converting glutathione disulfide (GSSG) into its reduced state (GSH). GSH is essential for detoxification processes in and survival of erythrocytes. We explored whether the anti-inflammatory compounds Bay 11-7082, parthenolide and dimethyl fumarate (DMF) were able to completely deplete a common target (GSH), and to impair the function of upstream enzymes of GSH recycling and replenishment. Treatment of erythrocytes with Bay 11-7082, parthenolide or DMF led to concentration-dependent eryptosis resulting from complete depletion of GSH. GSH depletion was due to strong inhibition of G6PDH activity. Bay 11-7082 and DMF, but not parthenolide, were able to inhibit the GR activity. This approach "Inhibitors, Detection of their common target that is completely depleted or inactivated when pharmacologically relevant concentrations of each single inhibitor are applied, Subsequent functional analysis of upstream enzymes for this target" (IDS), can be applied to a broad range of inhibitors and cell types according to the selected target. The specific G6PDH inhibitory effect of these compounds may be exploited for the treatment of human diseases with high NADPH and GSH consumption rates, including malaria, trypanosomiasis, cancer or obesity. PMID:27353740

  14. 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)].

  15. Helium segregation on surfaces of plasma-exposed tungsten.

    PubMed

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

    2016-02-17

    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. PMID:26794828

  16. Helium segregation on surfaces of plasma-exposed tungsten

    DOE PAGES

    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 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

  17. Helium segregation on surfaces of plasma-exposed tungsten.

    PubMed

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

    2016-02-17

    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.

  18. Detached divertor operation in DIII-D helium plasmas

    SciTech Connect

    Hill, D. N., LLNL

    1998-05-01

    This paper presents results from operating helium plasmas in DIII-D in which helium gas puffing is used to reduce the peak divertor heat flux by factors of four or more. The threshold density for achieving these conditions is nearly the same as for deuterium plasmas, which is surprising given the fact that lack of chemical sputtering reduces the carbon concentration in the plasma by more than a factor of five. Spectroscopic analysis shows that helium becomes the primary radiation in these plasmas, which is possible because, unlike carbon, it is the primary species present. These plasmas differ from the usual partially detached divertor (PDD) plasmas in that there is no concomitant reduction in target plate ion flux with target plate heat flux in the scrape off later outside the separatrix.

  19. 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.; Dodge, G.; Fersch, R.; Guler, N.; Kuhn, S. E.; Pierce, J.; Prok, Y.; Zheng, X.; et al

    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

  20. 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.

  1. System for target irradiation in the Iskra-6 high-power laser facility

    SciTech Connect

    Bondarenko, S V; Garanin, Sergey G; Eroshenko, V A; Kochemasov, G G; L'vov, L V; Mochalov, M R

    1999-03-31

    An analysis is made of various systems for direct irradiation of a target enabling achievement of a high degree of the irradiation uniformity. The required departure from uniformity of target irradiation, {delta}I/I {<=} 1% - 2%, may be attained when the number of laser beams is N {>=} 80, the diameter of the waist is approximately equal to the target diameter, and the intensity profile in the waist is Gaussian or super-Gaussian. Various methods of forming the necessary intensity distribution in a transverse cross section of a beam are considered. (interaction of laser radiation with matter. laser plasma)

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

    PubMed Central

    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. PMID:27376031

  3. 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. PMID:27376031

  4. 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.

  5. 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…

  6. Resistor monitors transfer of liquid helium

    NASA Technical Reports Server (NTRS)

    Hesketh, W. D.

    1966-01-01

    Large resistance change of a carbon resistor at the liquid helium temperature distinguishes between the transfer of liquid helium and gaseous helium into a closed Dewar. The resistor should be physically as small as possible to reduce the heat load to the helium.

  7. Pharmacological targeting of glucose-6-phosphate dehydrogenase in human erythrocytes by Bay 11–7082, parthenolide and dimethyl fumarate

    PubMed Central

    Ghashghaeinia, Mehrdad; Giustarini, Daniela; Koralkova, Pavla; Köberle, Martin; Alzoubi, Kousi; Bissinger, Rosi; Hosseinzadeh, Zohreh; Dreischer, Peter; Bernhardt, Ingolf; Lang, Florian; Toulany, Mahmoud; Wieder, Thomas; Mojzikova, Renata; Rossi, Ranieri; Mrowietz, Ulrich

    2016-01-01

    In mature erythrocytes, glucose-6-phosphate dehydrogenase (G6PDH) and 6-phosphogluconate dehydrogenase (6PGDH) yield NADPH, a crucial cofactor of the enzyme glutathione reductase (GR) converting glutathione disulfide (GSSG) into its reduced state (GSH). GSH is essential for detoxification processes in and survival of erythrocytes. We explored whether the anti-inflammatory compounds Bay 11–7082, parthenolide and dimethyl fumarate (DMF) were able to completely deplete a common target (GSH), and to impair the function of upstream enzymes of GSH recycling and replenishment. Treatment of erythrocytes with Bay 11–7082, parthenolide or DMF led to concentration-dependent eryptosis resulting from complete depletion of GSH. GSH depletion was due to strong inhibition of G6PDH activity. Bay 11–7082 and DMF, but not parthenolide, were able to inhibit the GR activity. This approach “Inhibitors, Detection of their common target that is completely depleted or inactivated when pharmacologically relevant concentrations of each single inhibitor are applied, Subsequent functional analysis of upstream enzymes for this target” (IDS), can be applied to a broad range of inhibitors and cell types according to the selected target. The specific G6PDH inhibitory effect of these compounds may be exploited for the treatment of human diseases with high NADPH and GSH consumption rates, including malaria, trypanosomiasis, cancer or obesity. PMID:27353740

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

    PubMed

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

    2015-09-01

    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.

  9. Mechanistic Target of Rapamycin Complex 1/S6 Kinase 1 Signals Influence T Cell Activation Independently of Ribosomal Protein S6 Phosphorylation

    PubMed Central

    Salmond, Robert J.; Brownlie, Rebecca J.; Meyuhas, Oded

    2015-01-01

    Ag-dependent activation of naive T cells induces dramatic changes in cellular metabolism that are essential for cell growth, division, and differentiation. In recent years, the serine/threonine kinase mechanistic target of rapamycin (mTOR) has emerged as a key integrator of signaling pathways that regulate these metabolic processes. However, the role of specific downstream effectors of mTOR function in T cells is poorly understood. Ribosomal protein S6 (rpS6) is an essential component of the ribosome and is inducibly phosphorylated following mTOR activation in eukaryotic cells. In the current work, we addressed the role of phosphorylation of rpS6 as an effector of mTOR function in T cell development, growth, proliferation, and differentiation using knockin and TCR transgenic mice. Surprisingly, we demonstrate that rpS6 phosphorylation is not required for any of these processes either in vitro or in vivo. Indeed, rpS6 knockin mice are completely sensitive to the inhibitory effects of rapamycin and an S6 kinase 1 (S6K1)–specific inhibitor on T cell activation and proliferation. These results place the mTOR complex 1-S6K1 axis as a crucial determinant of T cell activation independently of its ability to regulate rpS6 phosphorylation. PMID:26453749

  10. 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

  11. Targeting CDK6 in cancer: State of the art and new insights

    PubMed Central

    Tadesse, Solomon; Yu, Mingfeng; Kumarasiri, Malika; Le, Bich Thuy; Wang, Shudong

    2015-01-01

    Cyclin-dependent kinase 6 (CDK6) plays a vital role in regulating the progression of the cell cycle. More recently, CDK6 has also been shown to have a transcriptional role in tumor angiogenesis. Up-regulated CDK6 activity is associated with the development of several types of cancers. While CDK6 is over-expressed in cancer cells, it has a low detectable level in non-cancerous cells and CDK6-null mice develop normally, suggesting a specific oncogenic role of CDK6, and that its inhibition may represent an ideal mechanism-based and low toxic therapeutic strategy in cancer treatment. Identification of selective small molecule inhibitors of CDK6 is thus needed for drug development. Herein, we review the latest understandings of the biological regulation and oncogenic roles of CDK6. The potential clinical relevance of CDK6 inhibition, the progress in the development of small-molecule CDK6 inhibitors and the rational design of potential selective CDK6 inhibitors are also discussed. PMID:26315616

  12. Low temperature uses of helium

    NASA Technical Reports Server (NTRS)

    Brown, G. V.

    1970-01-01

    Helium is used for purging and pressurizing cryogenic rocket propellants, welding, atmosphere control, leak detection, and refrigeration. It provides the lowest possible liquid-bath temperature and produces superconductivity in certain materials. Its superfluid effects are used in superconducting magnets.

  13. 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.

  14. Influence of Helium in Gravitational Instabilities

    NASA Astrophysics Data System (ADS)

    Corona-Galindo, M. G.; Cardona, O.; Klapp, J.

    1990-11-01

    RESUMEN. Hemos analizado los modos hid rod inamicos de un modelo de fluido de dos componentes (hidr6geno y helio), y hemos obtenido la condici6n de inestabilidad para masas mayores que 1.39 veces la bien conocida masa dejeans. ABSTRACT, We have analysed the hydrodynamical modes of a two component fluid model (hydrogen and helium), and we have obtained the instability condition for masses greater than 1.39 times the well-known Jeans mass. K words: COSMOLOGY - GRAVITATION - INSTABILITIES

  15. 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.

  16. MicroRNA-328 directly targets p21-activated protein kinase 6 inhibiting prostate cancer proliferation and enhancing docetaxel sensitivity

    PubMed Central

    LIU, CHUNHUI; ZHANG, LEI; HUANG, YEQING; LU, KAI; TAO, TAO; CHEN, SHUQIU; ZHANG, XIAOWEN; GUAN, HAN; CHEN, MING; XU, BIN

    2015-01-01

    Prostate cancer (Pca) has one of the highest mortality rates for malignant cancers worldwide. Previous research has demonstrated that numerous genes are aberrantly expressed during Pca onset and development. p21-activated protein kinase 6 (PAK6) is known to be overexpressed in primary and metastatic Pca, however the mechanism of this aberrant expression remains unknown. In the present study, immunohistochemistry demonstrated that PAK6 is overexpressed in castration-resistant Pca (CRPC). Furthermore, PAK6 overexpression was regulated by microRNA (miR)-328. Luciferase reporter assay and western blot analysis indicated that PAK6 was directly targeted by miR-328. Forced expression of miR-328 enhanced docetaxel sensitivity, inhibited cell proliferation and promoted cell apoptosis without affecting the cell cycle. This indicates that miR-328 performs important functions in CRPC progression via PAK6 regulation. This mechanism may be used to enhance the effect of docetaxel. PMID:26459798

  17. 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.

  18. 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

  19. 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

  20. Convergent close-coupling calculations of helium single ionization by antiproton impact

    SciTech Connect

    Abdurakhmanov, I. B.; Kadyrov, A. S.; Fursa, D. V.; Bray, I.; Stelbovics, A. T.

    2011-12-15

    We apply the fully quantum-mechanical convergent close-coupling method to the calculation of antiproton scattering on the ground state of helium. The helium target is treated as a three-body Coulomb system using frozen-core and multiconfiguration approximations. The electron-electron correlation of the target is fully treated in both cases. Though both calculations yield generally good agreement with experiment for the total ionization cross sections, the multiconfiguration results are substantially higher at the lower energies than the frozen-core ones. Calculated longitudinal ejected electron and recoil-ion momentum distributions for the single ionization of helium are in good agreement with the experiment.

  1. Scattering of helium atoms by liquid helium

    NASA Astrophysics Data System (ADS)

    Goodman, Frank O.; Garcia, Nicolas

    1986-04-01

    We present results from a new He-liquid-He single-atom effective potential for scattering, obtained from an integration, over the region occupied by the liquid, of a standard Lennard-Jones 6-12 pairwise potential combined with a simple model of the pair-correlation function. The new potential is consistent with (a) the accepted internal energy (the negative of the latent heat) of liquid He, (b) the accepted long-range (-C3/z3 van der Waals) atom-surface interaction potential, and (c) the scattering (reflectivity) data of Edwards et al. Production of excitons (ripplons) at the surface is not necessary to interpret the data. The theory is unsymmetrized; that is, no account is taken of the fact that scattering among identical particles is being considered.

  2. Helium effects on neutron-irradiated Cr-Mo ferritic steels: A review of recent results

    SciTech Connect

    Klueh, R.L.; Maziasz, P.J.

    1988-01-01

    Large amounts of transmutation helium will be produced in the first wall of a fusion reactor by the high-energy neutrons from the fusion reaction. Since no fusion reactor is available, the effect of simultaneous helium production and displacement damage from neutron irradiation must be simulated. One method that has been used in ferritic steels is to add nickel to the steels and irradiate them in a mixed-spectrum reactor. In such reactors, the fast neutrons produce displacement damage, while helium is produced by a two-step reaction of /sup 58/Ni with thermal neutrons. This technique has been used to investigate the effect of helium on swelling, tensile properties, impact properties, and elevated-temperature embrittlement. Results indicate that helium accelerates swelling and affects tensile and impact properties of Cr-Mo ferritic steels below /approximately/450/degree/C. However, these steels are highly resistant to elevated-temperature helium embrittlement. 44 refs., 6 figs., 3 tabs.

  3. First-principles study of the interaction between helium and the defects in tantalum

    NASA Astrophysics Data System (ADS)

    Yin, Wen; Jia, Xuejun; Yu, Quanzhi; Liang, Tianjiao

    2016-11-01

    As a low power spallation target or target cladding material, tantalum has almost the same defects productions as tungsten under irradiation. In this paper, the detailed analysis of helium behavior in tantalum has been conducted based on density functional theory. The formation energy of tetrahedral interstitial configuration of helium is 0.3 eV lower than that of octahedral interstitial configuration, which means the tetrahedral interstitial configuration of helium is more stable than the octahedral configuration. Tetrahedral helium atoms in tantalum are predicted to have a very low migration, about 0.09 eV. A large binding energy between He and vacancy 2.03 eV indicates that He atom is easily trapped by vacancy, and a tetrahedral interstitial helium atom need overcome about 0.19 eV energy barriers when it directly jumps into the vacancy. Finally, the helium behavior in tantalum is compared with that in tungsten. It is obvious that the binding energy in tantalum is significantly different from those in tungsten. The interaction between two helium atoms in tantalum shows repulsive or weak repulsive other than attractive in tungsten, which suggests that helium atoms are easy to move other than to be a cluster in tantalum.

  4. Targeted GAS6 Delivery to the CNS Protects Axons from Damage during Experimental Autoimmune Encephalomyelitis

    PubMed Central

    Gruber, Ross C.; Ray, Alex K.; Johndrow, Christopher T.; Guzik, Hillary; Burek, Dominika; de Frutos, Pablo García

    2014-01-01

    Growth arrest-specific protein 6 (GAS6) is a soluble agonist of the TYRO3, AXL, MERTK (TAM) family of receptor tyrosine kinases identified to have anti-inflammatory, neuroprotective, and promyelinating properties. During experimental autoimmune encephalomyelitis (EAE), wild-type (WT) mice demonstrate a significant induction of Gas6, Axl, and Mertk but not Pros1 or Tyro3 mRNA. We tested the hypothesis that intracerebroventricular delivery of GAS6 directly into the CNS of WT mice during myelin oligodendrocyte glycoprotein (MOG)-induced EAE would improve the clinical course of disease relative to artificial CSF (ACSF)-treated mice. GAS6 did not delay disease onset, but significantly reduced the clinical scores during peak and chronic EAE. Mice receiving GAS6 for 28 d had preserved SMI31+ neurofilament immunoreactivity, significantly fewer SMI32+ axonal swellings and spheroids and less demyelination relative to ACSF-treated mice. Alternate-day subcutaneous IFNβ injection did not enhance GAS6 treatment effectiveness. Gas6−/− mice sensitized with MOG35-55 peptide exhibit higher clinical scores during late peak to early chronic disease, with significantly increased SMI32+ axonal swellings and Iba1+ microglia/macrophages, enhanced expression of several proinflammatory mRNA molecules, and decreased expression of early oligodendrocyte maturation markers relative to WT mouse spinal cords with scores for 8 consecutive days. During acute EAE, flow cytometry showed significantly more macrophages but not T-cell infiltrates in Gas6−/− spinal cords than WT spinal cords. Our data are consistent with GAS6 being protective during EAE by dampening the inflammatory response, thereby preserving axonal integrity and myelination. PMID:25471571

  5. Targeted GAS6 delivery to the CNS protects axons from damage during experimental autoimmune encephalomyelitis.

    PubMed

    Gruber, Ross C; Ray, Alex K; Johndrow, Christopher T; Guzik, Hillary; Burek, Dominika; de Frutos, Pablo García; Shafit-Zagardo, Bridget

    2014-12-01

    Growth arrest-specific protein 6 (GAS6) is a soluble agonist of the TYRO3, AXL, MERTK (TAM) family of receptor tyrosine kinases identified to have anti-inflammatory, neuroprotective, and promyelinating properties. During experimental autoimmune encephalomyelitis (EAE), wild-type (WT) mice demonstrate a significant induction of Gas6, Axl, and Mertk but not Pros1 or Tyro3 mRNA. We tested the hypothesis that intracerebroventricular delivery of GAS6 directly into the CNS of WT mice during myelin oligodendrocyte glycoprotein (MOG)-induced EAE would improve the clinical course of disease relative to artificial CSF (ACSF)-treated mice. GAS6 did not delay disease onset, but significantly reduced the clinical scores during peak and chronic EAE. Mice receiving GAS6 for 28 d had preserved SMI31(+) neurofilament immunoreactivity, significantly fewer SMI32(+) axonal swellings and spheroids and less demyelination relative to ACSF-treated mice. Alternate-day subcutaneous IFNβ injection did not enhance GAS6 treatment effectiveness. Gas6(-/-) mice sensitized with MOG35-55 peptide exhibit higher clinical scores during late peak to early chronic disease, with significantly increased SMI32(+) axonal swellings and Iba1(+) microglia/macrophages, enhanced expression of several proinflammatory mRNA molecules, and decreased expression of early oligodendrocyte maturation markers relative to WT mouse spinal cords with scores for 8 consecutive days. During acute EAE, flow cytometry showed significantly more macrophages but not T-cell infiltrates in Gas6(-/-) spinal cords than WT spinal cords. Our data are consistent with GAS6 being protective during EAE by dampening the inflammatory response, thereby preserving axonal integrity and myelination. PMID:25471571

  6. 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. PMID:23886520

  7. 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. PMID:26670944

  8. 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

  9. 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.

  10. Targets of the StBEL5 Transcription Factor Include the FT Ortholog StSP6A1[OPEN

    PubMed Central

    Lin, Tian

    2016-01-01

    The BEL1-like family of transcription factors is ubiquitous in plants and plays important roles in regulating development. They function in tandem with KNOTTED1 types to bind to a double TTGAC motif in the upstream sequence of target genes. StBEL5 of potato (Solanum tuberosum) functions as a mobile RNA signal that is transcribed in leaves, moves down into stolons in response to short days, and induces tuber formation. Despite their importance, however, very little is known about the targets of BEL1-like transcription factors. To better understand this network, we made use of a phloem-mobile BEL5 induction model, an ethanol-inducible system coupled with RNA sequencing analysis, and a screen for tandem TTGAC cis-elements in the upstream sequence to catalog StBEL5 target genes. Induction of StBEL5 activated several genes that are also induced by StSP6A (S. tuberosum SELF-PRUNING 6A), a FLOWERING LOCUS T coregulator that functions as a signal for tuberization. Both enhancement and suppression of StBEL5 expression were also closely linked to StSP6A transcriptional activity. Site mutagenesis in tandem TTGAC motifs located in the upstream sequence of StSP6A suppressed the short day-induced activity of its promoter in both young tubers and leaves. The expression profile of StBEL5 induced in stolons from plants grown under long-day conditions revealed almost 10,000 differentially expressed genes, including important tuber marker genes and genes involved in cell growth, transcription, floral development, and hormone metabolism. In a random screen of 200 differentially expressed targets of StBEL5, 92% contained tandem TTGAC motifs in the upstream sequence within 3 kb of the transcription start site. PMID:26553650

  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. 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.

  13. Elastic scattering of {sup 6}He and {sup 7}Be on a {sup 9}Be target

    SciTech Connect

    Pires, K. C. C.; Lichtenthaeler, R.; Mukha, I.; Moro, A. M.; Gomez-Camacho, J.

    2010-04-26

    The elastic scattering data for the {sup 6}He+{sup 9}Be and {sup 7}Be+{sup 9}Be reactions, measured at E{sub lab} = 16.2 MeV and E{sub lab} = 23.7 MeV respectively, are presented and analyzed using the optical model and coupled-channels formalisms.

  14. 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

  15. The interaction between AMPKβ2 and the PP1-targeting subunit R6 is dynamically regulated by intracellular glycogen content.

    PubMed

    Oligschlaeger, Yvonne; Miglianico, Marie; Dahlmans, Vivian; Rubio-Villena, Carla; Chanda, Dipanjan; Garcia-Gimeno, Maria Adelaida; Coumans, Will A; Liu, Yilin; Voncken, J Willem; Luiken, Joost J F P; Glatz, Jan F C; Sanz, Pascual; Neumann, Dietbert

    2016-04-01

    AMP-activated protein kinase (AMPK) is a metabolic stress-sensing kinase. We previously showed that glucose deprivation induces autophosphorylation of AMPKβ at Thr-148, which prevents the binding of AMPK to glycogen. Furthermore, in MIN6 cells, AMPKβ1 binds to R6 (PPP1R3D), a glycogen-targeting subunit of protein phosphatase type 1 (PP1), thereby regulating the glucose-induced inactivation of AMPK. In the present study, we further investigated the interaction of R6 with AMPKβ and the possible dependency on Thr-148 phosphorylation status. Yeast two-hybrid (Y2H) analyses and co-immunoprecipitation (IP) of the overexpressed proteins in human embryonic kidney (HEK) 293T) cells revealed that both AMPKβ1 and AMPK-β2 wild-type (WT) isoforms bind to R6. The AMPKβ-R6 interaction was stronger with the muscle-specific AMPKβ2-WT and required association with the substrate-binding motif of R6. When HEK293T cells or C2C12 myotubes were cultured in high-glucose medium, AMPKβ2-WT and R6 weakly interacted. In contrast, glycogen depletion significantly enhanced this protein interaction. Mutation of AMPKβ2 Thr-148 prevented the interaction with R6 irrespective of the intracellular glycogen content. Treatment with the AMPK activator oligomycin enhanced the AMPKβ2-R6 interaction in conjunction with increased Thr-148 phosphorylation in cells grown in low-glucose medium. These data are in accordance with R6 binding directly to AMPKβ2 when both proteins detach from the diminishing glycogen particle, which is simultaneous with increased AMPKβ2 Thr-148 autophosphorylation. Such a model points to a possible control of AMPK by PP1-R6 upon glycogen depletion in muscle.

  16. 26 CFR 1.338-6 - Allocation of ADSP and AGUB among target assets.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... and on or after September 15, 2004, see § 1.338-6T as contained in 26 CFR part 1 in effect on April 1... 26 CFR part 1 in effect on April 1, 2004. (d) Examples. The following examples illustrate §§ 1.338-4... $800 Land 200 Investment in T1 450 Total 1,450 (vii) T has no Class VI assets. The amount of ADSP...

  17. 26 CFR 1.338-6 - Allocation of ADSP and AGUB among target assets.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... Regulatory Commission in a report described in 10 CFR 50.75(b) as providing assurance that funds will be... be used only as permitted by 10 CFR 50.82(a)(8). (iii) Availability of election. P may make the... and on or after September 15, 2004, see § 1.338-6T as contained in 26 CFR part 1 in effect on April...

  18. 26 CFR 1.338-6 - Allocation of ADSP and AGUB among target assets.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... Regulatory Commission in a report described in 10 CFR 50.75(b) as providing assurance that funds will be... be used only as permitted by 10 CFR 50.82(a)(8). (iii) Availability of election. P may make the... and on or after September 15, 2004, see § 1.338-6T as contained in 26 CFR part 1 in effect on April...

  19. 26 CFR 1.338-6 - Allocation of ADSP and AGUB among target assets.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... Regulatory Commission in a report described in 10 CFR 50.75(b) as providing assurance that funds will be... be used only as permitted by 10 CFR 50.82(a)(8). (iii) Availability of election. P may make the... and on or after September 15, 2004, see § 1.338-6T as contained in 26 CFR part 1 in effect on April...

  20. 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.

  1. In planta differential targeting analysis of Thermotoga maritima Cel5A and CBM6-engineered Cel5A for autohydrolysis.

    PubMed

    Mahadevan, Shobana Arumugam; Wi, Seung Gon; Kim, Yeon Ok; Lee, Kwang Ho; Bae, Hyeun-Jong

    2011-08-01

    The heterologous expression of glycosyl hydrolases in bioenergy crops can improve the lignocellulosic conversion process for ethanol production. We attempted to obtain high-level expression of an intact Thermotoga maritima endoglucanase, Cel5A, and CBM6-engineered Cel5A in transgenic tobacco plants for the mass production and autohydrolysis of endoglucanase. Cel5A expression was targeted to different subcellular compartments, namely, the cytosol, apoplast, and chloroplast, using the native form of the pathogenesis-related protein 1a (PR1a) and Rubisco activase (RA) transit peptides. Cel5A transgenic tobacco plants with the chloroplast transit peptide showed the highest average endoglucanase activity and protein accumulation up to 4.5% total soluble protein. Cel5A-CBM6 was targeted to the chloroplast and accumulated up to 5.2% total soluble protein. In terms of the direct conversion of plant tissue into free sugar, the Cel5A-CBM6 transgenic plant was 33% more efficient than the Cel5A transgenic plant. The protein stability of Cel5A and Cel5A-CBM6 in lyophilized leaf material is an additional advantage in the bioconversion process.

  2. 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.

  3. 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.

  4. 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.

  5. 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

  6. miR-130b-3p Upregulation Contributes to the Development of Thyroid Adenomas Targeting CCDC6 Gene

    PubMed Central

    Leone, Vincenza; Langella, Concetta; Esposito, Francesco; De Martino, Marco; Decaussin-Petrucci, Myriam; Chiappetta, Gennaro; Bianco, Antonio; Fusco, Alfredo

    2015-01-01

    We have previously studied the function of microRNAs (miRNAs) in thyroid cells using the differentiated rat thyroid PC Cl 3 cells that need thyrotropin (TSH) for their growth. The miRNA expression profile examination allowed the detection of a set of miRNAs downregulated and upregulated by TSH. Here, we first demonstrated that upregulation of miR-130b-3p occurs through a protein kinase A-cAMP-responsive element binding protein (CREB)-dependent mechanism. Then, we analyzed its expression in human thyroid follicular adenomas, where a constitutive CREB activation is frequently present. miR-130b-3p results in upregulation with a high fold-change in most thyroid follicular adenomas. Then, we identified CCDC6, coding for a protein that interacts with CREB1 leading to the transcriptional repression of CREB1 target genes, as a target of this miRNA. The targeting of CCDC6 by miR-130b-3p likely accounts for the mechanism by which its upregulation contributes to the development of thyroid adenomas increasing CREB1 activity. PMID:26835423

  7. Chemoproteomics Reveals Novel Protein and Lipid Kinase Targets of Clinical CDK4/6 Inhibitors in Lung Cancer.

    PubMed

    Sumi, Natalia J; Kuenzi, Brent M; Knezevic, Claire E; Remsing Rix, Lily L; Rix, Uwe

    2015-12-18

    Several selective CDK4/6 inhibitors are in clinical trials for non-small cell lung cancer (NSCLC). Palbociclib (PD0332991) is included in the phase II/III Lung-MAP trial for squamous cell lung carcinoma (LUSQ). We noted differential cellular activity between palbociclib and the structurally related ribociclib (LEE011) in LUSQ cells. Applying an unbiased mass spectrometry-based chemoproteomics approach in H157 cells and primary tumor samples, we here report distinct proteome-wide target profiles of these two drug candidates in LUSQ, which encompass novel protein and, for palbociclib only, lipid kinases. In addition to CDK4 and 6, we observed CDK9 as a potent target of both drugs. Palbociclib interacted with several kinases not targeted by ribociclib, such as casein kinase 2 and PIK3R4, which regulate autophagy. Furthermore, palbociclib engaged several lipid kinases, most notably, PIK3CD and PIP4K2A/B/C. Accordingly, we observed modulation of autophagy and inhibition of AKT signaling by palbociclib but not ribociclib.

  8. MicroRNA-320 family is downregulated in colorectal adenoma and affects tumor proliferation by targeting CDK6

    PubMed Central

    Tadano, Toshihiro; Kakuta, Yoichi; Hamada, Shin; Shimodaira, Yosuke; Kuroha, Masatake; Kawakami, Yoko; Kimura, Tomoya; Shiga, Hisashi; Endo, Katsuya; Masamune, Atsushi; Takahashi, Seiichi; Kinouchi, Yoshitaka; Shimosegawa, Tooru

    2016-01-01

    AIM: To investigate the microRNA (miRNA) expression during histological progression from colorectal normal mucosa through adenoma to carcinoma within a lesion. METHODS: Using microarray, the sequential changes in miRNA expression profiles were compared in colonic lesions from matched samples; histologically, non-neoplastic mucosa, adenoma, and submucosal invasive carcinoma were microdissected from a tissue sample. Cell proliferation assay was performed to observe the effect of miRNA, and its target genes were predicted using bioinformatics approaches and the expression profile of SW480 transfected with the miRNA mimics. mRNA and protein levels of the target gene in colon cancer cell lines with a mimic control or miRNA mimics were measured using qRT-PCR and Western blotting. The expression levels of miRNA and target gene in colorectal tissue samples were also measured. RESULTS: Microarray analysis identified that the miR-320 family, including miR-320a, miR-320b, miR-320c, miR-320d and miR-320e, were differentially expressed in adenoma and submucosal invasive carcinoma. The miR-320 family, which inhibits cell proliferation, is frequently downregulated in colorectal adenoma and submucosal invasive carcinoma tissues. Seven genes including CDK6 were identified to be common in the results of gene expression array and bioinformatics analyses performed to find the target gene of the miR-320 family. We confirmed that mRNA and protein levels of CDK6 were significantly suppressed in colon cancer cell lines with miR-320 family mimics. CDK6 expression was found to increase from non-neoplastic mucosa through adenoma to submucosal invasive carcinoma tissues and showed an inverse correlation with miR-320 family expression. CONCLUSION: MiR-320 family affects colorectal tumor proliferation by targeting CDK6, plays important role in its growth, and is considered to be a biomarker for its early detection. PMID:27559432

  9. 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. PMID:27544589

  10. 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

    2016-08-01

    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.

  11. Automatic Refilling System For Liquid Helium

    NASA Technical Reports Server (NTRS)

    Serlemitsos, Aristides; Sansebastian, Mark; Geagen, Jay; Warner, Brent

    1990-01-01

    Cryogenic experiments left unattended for days. System automatically replenishes liquid helium in cryogenic experimental apparatus as liquid evaporates. Automatic filling system transfers liquid helium from storage vessel to experimental apparatus under computer control. Gaseous helium from cylinder supplies pumping pressure. Circuit senses level of liquid helium by sensing voltage across measuring resistors in series with silicon resistance thermometers (SRT's). Low voltage indicates SRT covered, while high voltage indicates uncovered.

  12. 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.

  13. Operation of a THGEM-based detector in low-pressure Helium

    NASA Astrophysics Data System (ADS)

    Cortesi, M.; Yurkon, J.; Stolz, A.

    2015-02-01

    In view of a possible application as a charge-particle track readout for an Active Target Time Projection Chamber (AT-TPC), the operating properties of THick Gaseous Electron Multipliers (THGEM) in pure low-pressure Helium were investigated. This paper includes the effective gain dependence on pressure for different detector configurations (single-, double-, triple-cascade setup), long-term gain stability and energy resolution from tracks of 5.5 MeV alpha particles. Stable operational conditions and maximum detector gains of 104-107 have been achieved in pure Helium at pressure ranging from 100 torr up to 760 torr. Energy resolution of 6.65% (FWHM) for 690 keV of energy deposited by 5.5 MeV alpha particles at 350 torr was measured. The expected energy resolution for the full track is around 2.4% (FWHM). These results, together with the robustness of THGEM electrodes against spark damage, make THGEM structures highly competitive compared to other technologies considered for TPC applications in an active target operating with pure noble gases, requiring a high dynamic range and a wide operating pressure range down to few hundred torr.

  14. 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. PMID:27153346

  15. 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.

  16. 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.

  17. 43 CFR 3100.1 - Helium.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 43 Public Lands: Interior 2 2013-10-01 2013-10-01 false Helium. 3100.1 Section 3100.1 Public Lands: Interior Regulations Relating to Public Lands (Continued) BUREAU OF LAND MANAGEMENT, DEPARTMENT OF THE... Helium. The ownership of and the right to extract helium from all gas produced from lands leased...

  18. 43 CFR 3100.1 - Helium.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 43 Public Lands: Interior 2 2014-10-01 2014-10-01 false Helium. 3100.1 Section 3100.1 Public Lands: Interior Regulations Relating to Public Lands (Continued) BUREAU OF LAND MANAGEMENT, DEPARTMENT OF THE... Helium. The ownership of and the right to extract helium from all gas produced from lands leased...

  19. 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...

  20. 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...

  1. 43 CFR 3100.1 - Helium.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 43 Public Lands: Interior 2 2012-10-01 2012-10-01 false Helium. 3100.1 Section 3100.1 Public Lands: Interior Regulations Relating to Public Lands (Continued) BUREAU OF LAND MANAGEMENT, DEPARTMENT OF THE... Helium. The ownership of and the right to extract helium from all gas produced from lands leased...

  2. 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...

  3. Multipurpose top for liquid helium Dewar

    NASA Technical Reports Server (NTRS)

    Murphy, R. S.; Anderholm, J. R.

    1972-01-01

    Multipurpose top was fabricated for liquid helium Dewar flask which guards against flash vaporization of liquid helium and allows boiling temperature of liquid helium to be lowered by reduction of ambient pressure in Dewar flask. Device is rugged and simple, and does not require frequent calibrations or adjustments.

  4. 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.

  5. 43 CFR 3100.1 - Helium.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 43 Public Lands: Interior 2 2011-10-01 2011-10-01 false Helium. 3100.1 Section 3100.1 Public Lands: Interior Regulations Relating to Public Lands (Continued) BUREAU OF LAND MANAGEMENT, DEPARTMENT OF THE... Helium. The ownership of and the right to extract helium from all gas produced from lands leased...

  6. 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

  7. State-Selective and Total Single-Capture Cross Sections for Fast Collisions of Multiply Charged Ions with Helium Atoms

    NASA Astrophysics Data System (ADS)

    Mančev, Ivan; Milojević, Nenad; Belkić, Dževad

    2013-11-01

    The four-body boundary corrected first Born approximation (CB1-4B) is used to calculate the single electron capture cross sections for collisions between fully stripped ions (He2+, Be4+, B5+ and C6+) and helium target at intermediate and high impact energies. The main goal of this study is to assess the usefulness of the CB1-4B method at intermediate and high impact energies for these collisions. Detailed comparisons with the measurements are carried out and the obtained theoretical cross sections are in reasonable agreement with the available experimental data.

  8. Vortex Rings in Superfluid Helium

    NASA Astrophysics Data System (ADS)

    Alamri, Sultan Z.; Barenghi, Carlo F.

    2008-11-01

    We present results of numerical simulations of large-scale vortex rings in superfluid helium. These large-scale vortex rings consists of many discrete (quantized) vortex filaments which interact with each other moving according to the Biot-Savart law. Lifetime, structural stability and speed of large-scale vortex rings will be discussed and compared to experimental results.

  9. 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".

  10. 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.

  11. 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.

  12. 6-(Azaindol-2-yl)pyridine-3-sulfonamides as potent and selective inhibitors targeting hepatitis C virus NS4B.

    PubMed

    Chen, Guangming; Ren, Hongyu; Zhang, Nanjing; Lennox, William; Turpoff, Anthony; Paget, Steven; Li, Chunshi; Almstead, Neil; Njoroge, F George; Gu, Zhengxian; Graci, Jason; Jung, Stephen P; Colacino, Joseph; Lahser, Fred; Zhao, Xin; Weetall, Marla; Nomeir, Amin; Karp, Gary M

    2015-02-15

    A structure-activity relationship investigation of various 6-(azaindol-2-yl)pyridine-3-sulfonamides using the HCV replicon cell culture assay led to the identification of a potent series of 7-azaindoles that target the hepatitis C virus NS4B. Compound 2ac, identified via further optimization of the series, has excellent potency against the HCV 1b replicon with an EC50 of 2nM and a selectivity index of >5000 with respect to cellular GAPDH RNA. Compound 2ac also has excellent oral plasma exposure levels in rats, dogs and monkeys and has a favorable liver to plasma distribution profile in rats. PMID:25613678

  13. 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

  14. 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.

  15. Targeted photocytotoxicity by copper(II) complexes having vitamin B6 and photoactive acridine moieties.

    PubMed

    Mukherjee, Nandini; Podder, Santosh; Banerjee, Samya; Majumdar, Shamik; Nandi, Dipankar; Chakravarty, Akhil R

    2016-10-21

    Copper(II) pyridoxal Schiff base complexes [Cu(L(1)/L(2))(B)]ClO4 (1-4), where HL(1) is 4-(((2-(1H-imidazol-4-yl)ethyl)imino)methyl)-5-(hydroxymethyl)-2-methylpyridin-3-ol (in 1 and 2), HL(2) is 2-(((2-(1H-imidazol-4-yl)ethyl)imino)methyl)phenol (in 3, 4), B is 11-(9-acridinyl)dipyrido[3,2-a:2',3'-c]phenazine (acdppz in 1 and 3), dipyrido[3,2-a:2',3'-c]phenazine (in 2) and 1,10-phenanthroline (in 4), were synthesized, characterized and their photocytotoxicity in visible light, intracellular localization, cellular uptake and DNA photocleavage activity were studied. Complex 4 was characterized by X-ray crystallography. Complexes 1 and 3 having acdppz as photosensitizer showed significant photocytotoxicity in visible light in HeLa and MCF7 cells giving IC50 value of <0.6 μM, while being relatively non-toxic in dark. The complexes were non-toxic to non-tumorigenic HPL1D cells both in light and dark conditions. Complex 1 showed significant localization in the cytoplasm of HeLa cells within 4 h of treatment, as evidenced from confocal microscopy. DCFDA assay on 1 suggested generation of intracellular reactive oxygen species in HeLa cells upon photo-exposure. Importantly, Annexin-V-FITC/PI assay indicated photo-induced apoptotic cell death. PMID:27423638

  16. 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

  17. 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

  18. Single ionization of helium by electron impact

    SciTech Connect

    Bray, I.; Fursa, D. V.; Kadyrov, A. S.; Stelbovics, A. T.

    2010-06-15

    We suggest that the problem of single ionization of helium by electron impact, leaving the ion in the ground state, has been solved theoretically for the full range of kinematics and collision geometries of practical interest. Following the emphasis on the study of out-of-plane geometries where the cross sections are very small [Schulz et al., Nature 422, 48 (2003)], we find that the convergent close-coupling calculations, in either a frozen- or a multicore treatment of the target, are in excellent agreement with the available measurements. Curiously, some systematic discrepancies are identified for some in-plane cases where the cross sections are an order of magnitude larger. Further measurements are required to resolve these discrepancies. If subsequent measurements confirm the present calculations, then we would have a strong case that the problem has been solved.

  19. Development of Pre-Clinical Models for Evaluating the Therapeutic Potential of Candidate siRNA Targeting STAT6

    PubMed Central

    Healey, Gareth D.; Lockridge, Jennifer A.; Zinnen, Shawn; Hopkin, Julian M.; Richards, Ivan; Walker, William

    2014-01-01

    Developing siRNA therapeutics poses technical challenges including appropriate molecular design and testing in suitable pre-clinical models. We previously detailed sequence-selection and modification strategies for siRNA candidates targeting STAT6. Here, we describe methodology that evaluates the suitability of candidate siRNA for respiratory administration. Chemically-modified siRNA exhibited similar inhibitory activity (IC50) against STAT6 in vitro compared to unmodified siRNA and apical exposure testing with Caco-2 cell monolayers showed modification was not associated with cellular toxicity. Use of a modified RNA extraction protocol improved the sensitivity of a PCR-based bio-analytical assay (lower limit of siRNA strand quantification  =  0.01 pg/µl) which was used to demonstrate that lung distribution profiles for both siRNAs were similar following intra-tracheal administration. However, after 6 hours, modified siRNA was detected in lung tissue at concentrations >1000-fold higher than unmodified siRNA. Evaluation in a rat model of allergic inflammation confirmed the persistence of modified siRNA in vivo, which was detectable in broncho-alveolar lavage (BAL) fluid, BAL cells and lung tissue samples, 72 hours after dosing. Based upon the concept of respiratory allergy as a single airway disease, we considered nasal delivery as a route for respiratory targeting, evaluating an intra-nasal exposure model that involved simple dosing followed by fine dissection of the nasal cavity. Notably, endogenous STAT6 expression was invariant throughout the nasal cavities and modified siRNA persisted for at least 3 days after administration. Coupled with our previous findings showing upregulated expression of inflammatory markers in nasal samples from asthmatics, these findings support the potential of intranasal siRNA delivery. In summary, we demonstrate the successful chemical modification of STAT6 targeting siRNA, which enhanced bio-availability without cellular

  20. 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.

  1. 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.

  2. Lysosome sorting of β-glucocerebrosidase by LIMP-2 is targeted by the mannose 6-phosphate receptor

    PubMed Central

    Zhao, Yuguang; Ren, Jingshan; Padilla-Parra, Sergi; Fry, Elizabeth E.; Stuart, David I.

    2014-01-01

    The integral membrane protein LIMP-2 has been a paradigm for mannose 6-phosphate receptor (MPR) independent lysosomal targeting, binding to β-glucocerebrosidase (β-GCase) and directing it to the lysosome, before dissociating in the late-endosomal/lysosomal compartments. Here we report structural results illuminating how LIMP-2 binds and releases β-GCase according to changes in pH, via a histidine trigger, and suggesting that LIMP-2 localizes the ceramide portion of the substrate adjacent to the β-GCase catalytic site. Remarkably, we find that LIMP-2 bears P-Man9GlcNAc2 covalently attached to residue N325, and that it binds MPR, via mannose 6-phosphate, with a similar affinity to that observed between LIMP-2 and β-GCase. The binding sites for β-GCase and the MPR are functionally separate, so that a stable ternary complex can be formed. By fluorescence lifetime imaging microscopy, we also demonstrate that LIMP-2 interacts with MPR in living cells. These results revise the accepted view of LIMP-2–β-GCase lysosomal targeting. PMID:25027712

  3. Two domain-disrupted hda6 alleles have opposite epigenetic effects on transgenes and some endogenous targets

    PubMed Central

    Zhang, Shoudong; Zhan, Xiangqiang; Xu, Xiaoming; Cui, Peng; Zhu, Jian-Kang; Xia, Yiji; Xiong, Liming

    2015-01-01

    HDA6 is a RPD3-like histone deacetylase. In Arabidopsis, it mediates transgene and some endogenous target transcriptional gene silencing (TGS) via histone deacetylation and DNA methylation. Here, we characterized two hda6 mutant alleles that were recovered as second-site suppressors of the DNA demethylation mutant ros1–1. Although both alleles derepressed 35S::NPTII and RD29A::LUC in the ros1–1 background, they had distinct effects on the expression of these two transgenes. In accordance to expression profiles of two transgenes, the alleles have distinct opposite methylation profiles on two reporter gene promoters. Furthermore, both alleles could interact in vitro and in vivo with the DNA methyltransferase1 with differential interactive strength and patterns. Although these alleles accumulated different levels of repressive/active histone marks, DNA methylation but not histone modifications in the two transgene promoters was found to correlate with the level of derepression of the reporter genes between the two had6 alleles. Our study reveals that mutations in different domains of HDA6 convey different epigenetic status that in turn controls the expression of the transgenes as well as some endogenous loci. PMID:26666962

  4. Two domain-disrupted hda6 alleles have opposite epigenetic effects on transgenes and some endogenous targets.

    PubMed

    Zhang, Shoudong; Zhan, Xiangqiang; Xu, Xiaoming; Cui, Peng; Zhu, Jian-Kang; Xia, Yiji; Xiong, Liming

    2015-12-15

    HDA6 is a RPD3-like histone deacetylase. In Arabidopsis, it mediates transgene and some endogenous target transcriptional gene silencing (TGS) via histone deacetylation and DNA methylation. Here, we characterized two hda6 mutant alleles that were recovered as second-site suppressors of the DNA demethylation mutant ros1-1. Although both alleles derepressed 35S::NPTII and RD29A::LUC in the ros1-1 background, they had distinct effects on the expression of these two transgenes. In accordance to expression profiles of two transgenes, the alleles have distinct opposite methylation profiles on two reporter gene promoters. Furthermore, both alleles could interact in vitro and in vivo with the DNA methyltransferase1 with differential interactive strength and patterns. Although these alleles accumulated different levels of repressive/active histone marks, DNA methylation but not histone modifications in the two transgene promoters was found to correlate with the level of derepression of the reporter genes between the two had6 alleles. Our study reveals that mutations in different domains of HDA6 convey different epigenetic status that in turn controls the expression of the transgenes as well as some endogenous loci.

  5. 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

  6. 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.

  7. PET radiotracer [18F]-P6 selectively targeting COX-1 as a novel biomarker in ovarian cancer: Preliminary investigation

    PubMed Central

    Uddin, Jashim; Vitale, Paola; Panella, Andrea; Crews, Brenda C.; Daniel, Cristina K.; Ghebreselasie, Kebreab; Nickels, Mike; Tantawy, Mohammed N.; Manning, H. Charles; Marnett, Lawrence J.; Scilimati, Antonio

    2015-01-01

    Cyclooxygenase-1 (COX-1), but not COX-2, is expressed at high levels in the early stages of human epithelial ovarian cancer where it seems to play a key role in cancer onset and progression. As a consequence, COX-1 is an ideal biomarker for early ovarian cancer detection. A series of novel fluorinated COX-1-targeted imaging agents derived from P6 was developed by using a highly selective COX-1 inhibitor as a lead compound. Among these new compounds, designed by structural modification of P6, 3-(5-chlorofuran-2-yl)-5-(fluoromethyl)-4-phenylisoxazole ([18/19F]-P6) is the most promising derivative [IC50 = 2.0 μM (purified oCOX-1) and 1.37 μM (hOVCAR-3 cell COX-1)]. Its tosylate precursor was also prepared and, a method for radio[18F]chemistry was developed and optimized. The radiochemistry was carried out using a carrier-free K18F/Kryptofix 2.2.2 complex, that afforded [18F]-P6 in good radio-chemical yield (18%) and high purity (>95%). In vivo PET/CT imaging data showed that the radiotracer [18F]-P6 was selectively taken up by COX-1-expressing ovarian carcinoma (OVCAR 3) tumor xenografts as compared with the normal leg muscle. Our results suggest that [18F]-P6 might be an useful radiotracer in preclinical and clinical settings for in vivo PET-CT imaging of tissues that express elevated levels of COX-1. PMID:24832612

  8. 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

  9. Comparison of helium leak test and vacuum leak test using canned foods: collaborative study.

    PubMed

    Rhea, U S; Gilchrist, J E; Peeler, J T; Shah, D B

    1984-01-01

    Two can leak tests were compared by 7 collaborators. In the helium leak test, pressurized helium is applied to the outside of the container, and a headspace gas sample from the can is then analyzed for the presence of helium. The vacuum test is described in the Bacteriological Analytical Manual. Ninety No. 303 cans of creamed-style corn, green beans, carrots, fruit cocktail, and whole-kernel corn were shipped in 3 groups. Two groups of 30 cans had 10 dented flat cans, 5 flat controls (nondented), 10 dented swollen cans, and 5 swollen control cans (nondented). The third group had 10 dented swollen cans and 5 swollen control cans. Of 600 cans analyzed, 37 (6.2%) were deleted from the analysis because results were not available for both tests. One laboratory was constrained by scheduling to analyze 15 of 45 swollen cans. The helium leak test found 12 (13%) positives of 92 nondented swollen cans. One pressurization test yielded 7 of those 12 positives. Of the 400 dented cans sent as possible leakers, the helium test found 267 positives, and the vacuum test found 181. Five of the 7 analysts had significantly (alpha = 0.05) higher percent positive helium results. One analyst found more leakers by the vacuum leak test. Both tests found fewer positives in the swollen dented cans than in the flat dented cans. After exposure to pressurized helium, all cans with greater than 8 psi headspace pressure were positive helium leakers. The method was adopted official first action.

  10. 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.

  11. A Cryogen Recycler with Pulse Tube Cryocooler for Recondensing Helium and Nitrogen

    NASA Astrophysics Data System (ADS)

    Wang, C.; Lichtenwalter, B.

    2015-12-01

    We have developed a cryogen recycler using a 4 K pulse tube cryocooler for recondensing helium and nitrogen in a NMR magnet. The liquid helium cooled NMR magnet has a liquid nitrogen cooled radiation shield. The magnet boils off 0.84 L/day of liquid helium and 6 L/day of liquid nitrogen. The recycler is designed with both a liquid helium return tube and a liquid nitrogen return tube, which are inserted into the fill ports of liquid helium and nitrogen. Therefore the recycler forms closed loops for helium and nitrogen. A two-stage 4 K pulse tube cryocooler, Cryomech model PT407 (0.7W at 4.2 K), is selected for the recycler. The recycler was first tested with a Cryomech's test cryostat and resulted in the capacities of recondensing 8.2 L/day of nitrogen and liquefying 4 L/day of helium from room temperature gas. The recycler has been installed in the NMR magnet at University of Sydney since August, 2014 and continuously maintains a zero boil off for helium and nitrogen.

  12. 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.

  13. 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.

  14. Exotic Ions in Superfluid Helium

    NASA Astrophysics Data System (ADS)

    Wei, Wanchun; Xie, Zhuolin; Cooper, Leon N.; Maris, Humphrey J.

    2016-11-01

    Exotic ions are negatively charged objects which have been detected in superfluid helium-4 at temperatures in the vicinity of 1 K. Mobility experiments in several different labs have revealed the existence of at least 18 such objects. These ions have a higher mobility than the normal negative ion and appear to be singly charged and smaller. We summarize the experimental situation, the possible structure of these objects, and how these objects might be formed.

  15. 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.

  16. Cryopumping of hydrogen and helium

    SciTech Connect

    Halama, H.J.; Hseuh, H.C.; Chou, T.S.

    1981-01-01

    Results obtained in numerous tests on small (approx. 1000 l/S) and large (approx. 10/sup 5/ l/S) cryopumps cooled to 4.2/sup 0/K by LHe or between 10 to 20/sup 0/K by closed-cycle helium refrigerator are summarized. Then, measurements of the compound cryopump, designed to work on Tokamaks to handle the exhaust gases from the Torus are presented.

  17. Helium in interplanetary dust particles

    NASA Technical Reports Server (NTRS)

    Nier, A. O.; Schlutter, D. J.

    1993-01-01

    Helium and neon were extracted from fragments of individual stratosphere-collected interplanetary dust particles (IDP's) by subjecting them to increasing temperature by applying short-duration pulses of power in increasing amounts to the ovens containing the fragments. The experiment was designed to see whether differences in release temperatures could be observed which might provide clues as to the asteroidal or cometary origin of the particles. Variations were observed which show promise for elucidating the problem.

  18. 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.

  19. MMP2-Targeting and Redox-Responsive PEGylated Chlorin e6 Nanoparticles for Cancer Near-Infrared Imaging and Photodynamic Therapy.

    PubMed

    Hou, Wenxiu; Xia, Fangfang; Alves, Carla S; Qian, Xiaoqing; Yang, Yuming; Cui, Daxiang

    2016-01-20

    A unique matrix metalloproteinase 2-targeted photosensitizer delivery platform was developed in this study for tumor-targeting imaging and photodynamic therapy. The model photosensitizer therapeutic agent chlorin e6 (Ce6) was first covalently conjugated with matrix metalloproteinase 2-cleavable polypeptide and then modified with polyethylene glycol via a redox-responsive cleavable disulfide linker. The resultant matrix metalloproteinase 2-cleavable polypeptide modified PEGylated Ce6 (PEG-SS-Ce6-MMP2) nanoparticles, which formed via self-assembly, were observed to be monodisperse and significantly stable in aqueous solution. In addition, owing to their cellular redox-responsiveness at the cleavable disulfide linker, the PEG-SS-Ce6-MMP2 nanoparticles were able to release Ce6 rapidly. Despite displaying enhanced intracellular internalization, the synthesized PEG-SS-Ce6-MMP2 nanoparticles did not compromise their phototoxic effects toward A549 cancer cells when compared with free Ce6 and PEGylated Ce6 nanoparticles. In vivo experiments further revealed that, in contrast with the free Ce6 or with the PEGylated Ce6 nanoparticles, the PEG-SS-Ce6-MMP2 nanoparticles showed a remarkable increase in tumor-targeting ability and a significantly improved photodynamic therapeutic efficiency in A549 tumor-bearing mice. These results suggest that the PEG-SS-Ce6-MMP2 nanoparticles hold great potential for tumor-targeting imaging and photodynamic therapy.

  20. GCAP1, Rab6, and HSP27: Novel Autoantibody Targets in Cancer-Associated Retinopathy and Autoimmune Retinopathy

    PubMed Central

    Yang, Sufang; Dizhoor, Alexander; Wilson, David J.; Adamus, Grazyna

    2016-01-01

    Purpose Autoantibodies (AAbs) with different retinal specificities were reported in cancer-associated retinopathy (CAR) and autoimmune retinopathy (AR). The goal was to identify the small retinal proteins of apparent molecular mass of 23-kDa often recognized by patients' AAbs. Methods Sera specific for a 23-kDa retinal protein of 173 patients were investigated retrospectively by Western blotting and double immunofluorescence confocal microscopy. A proteomic analysis revealed new 23-kDa protein candidates, including guanylyl cyclase-activating proteins (GCAPs), heat shock protein 27 (HSP27), and Rab6A GTPase (Rab6A). Results Among the cohort of 173 patients, only 68 had anti-recoverin AAbs and the remaining 105 reacted with 4 unique proteins, which were identified as a Rab6A, HSP27, GCAP1, and GCAP2. Confocal images from a double labeling study confirmed the reactivity of AAbs with different types of cells in human retina, consistent with the target protein's respective cellular functions. Patients (62/173) had been diagnosed with various kinds of cancer, including 20% of patients who had anti-recoverin, 11% anti-Rab6A, and 5% anti-HSP27 AAbs. Only 50% of recoverin-seropositive patients had cancer and the individuals with anti-recoverin AAbs had a significantly higher likelihood to be diagnosed with cancer than patients with other anti-23-kDa AAbs. Conclusions The newly discovered retinal autoantigens may be involved in pathogenicity of CAR and AR. The recognition of AAbs against various retinal proteins associated with autoimmune retinal degeneration broadens the group of proteins related with these entities. Translational Relevance Patients with anti-recoverin, anti-GCAP1, anti-Rab6A, and anti-HSP27 AAbs represented diverse clinical phenotypes, so the presence of disease-associated AAbs provides important information for molecular diagnosis. PMID:27152249

  1. 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.'

  2. Particle detection using superfluid helium

    SciTech Connect

    Bandler, S.R.; Lanou, R.E.; Maris, H.J.; More, T.; Porter, F.S.; Seidel, G.M.; Torii, R.

    1991-01-01

    We have observed 5 MeV {alpha} particles stopped in volumes-up to two liters of liquid helium at 70 mK. A fraction of the kinetic energy of an {alpha} particle is converted to elementary excitations (rotons and phonons), which progagate ballistically in isotopically pure {sup 4}He below 0.1 K. Most of these excitations have sufficient energy to evaporate helium atoms on hitting a free surface. The evaporated helium atoms can be detected calorimetrically when adsorbed on a thin silicon wafer ({approximately}1.7 g, 35 cm{sup 2}) suspended above the liquid. Temperature changes of the silicon are measured with a NTD germanium bolometer. For the geometry studied the observed temperature change of the silicon resulting from an {alpha} event in the liquid is approximately 5% of the temperature rise from an {alpha} hitting the silicon directly. The implications of these measurements will be discussed as they relate to the possible construction of a large scale detector of solar neutrinos.

  3. Particle detection using superfluid helium

    SciTech Connect

    Bandler, S.R.; Lanou, R.E.; Maris, H.J.; More, T.; Porter, F.S.; Seidel, G.M.; Torii, R.

    1991-12-31

    We have observed 5 MeV {alpha} particles stopped in volumes-up to two liters of liquid helium at 70 mK. A fraction of the kinetic energy of an {alpha} particle is converted to elementary excitations (rotons and phonons), which progagate ballistically in isotopically pure {sup 4}He below 0.1 K. Most of these excitations have sufficient energy to evaporate helium atoms on hitting a free surface. The evaporated helium atoms can be detected calorimetrically when adsorbed on a thin silicon wafer ({approximately}1.7 g, 35 cm{sup 2}) suspended above the liquid. Temperature changes of the silicon are measured with a NTD germanium bolometer. For the geometry studied the observed temperature change of the silicon resulting from an {alpha} event in the liquid is approximately 5% of the temperature rise from an {alpha} hitting the silicon directly. The implications of these measurements will be discussed as they relate to the possible construction of a large scale detector of solar neutrinos.

  4. Rapid-releasing of HI-6 via brain-targeted mesoporous silica nanoparticles for nerve agent detoxification.

    PubMed

    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.

  5. Functional cross-talk between Cdc42 and two downstream targets, Par6B and PAK4.

    PubMed

    Jin, Dan; Durgan, Joanne; Hall, Alan

    2015-04-15

    The establishment of polarity is an essential step in epithelial morphogenesis. Polarity proteins promote an apical/basal axis, which, together with the assembly of apical adherens and tight junctions, directed vesicle transport and the reorganization of the actomyosin filament network, generate a stable epithelium. The regulation of these cellular activities is complex, but the Rho family GTPase Cdc42 (cell division cycle 42) is known to play a key role in the establishment of polarity from yeast to humans. Two Cdc42 target proteins, the kinase PAK4 [p21 protein (Cdc42/Rac)-activated kinase 4] and the scaffold partitioning defective (Par) 6B, are required to promote the assembly of apical junctions in human bronchial epithelial cells. We show in the present paper that PAK4 phosphorylates Par6B at Ser143 blocking its interaction with Cdc42. This provides a potential new mechanism for controlling the subcellular localization of Par6B and its interaction with other proteins.

  6. Par6G suppresses cell proliferation and is targeted by loss-of-function mutations in multiple cancers

    PubMed Central

    Marques, E; Englund, J I; Tervonen, T A; Virkunen, E; Laakso, M; Myllynen, M; Mäkelä, A; Ahvenainen, M; Lepikhova, T; Monni, O; Hautaniemi, S; Klefström, J

    2016-01-01

    Differentiated epithelial structure communicates with individual constituent epithelial cells to suppress their proliferation activity. However, the pathways linking epithelial structure to cessation of the cell proliferation machinery or to unscheduled proliferation in the context of tumorigenesis are not well defined. Here we demonstrate the strong impact of compromised epithelial integrity on normal and oncogenic Myc-driven proliferation in three-dimensional mammary epithelial organoid culture. Systematic silencing of 34 human homologs of Drosophila genes, with previously established functions in control of epithelial integrity, demonstrates a role for human genes of apico-basal polarity, Wnt and Hippo pathways and actin dynamics in regulation of the size, integrity and cell proliferation in organoids. Perturbation of these pathways leads to diverse functional interactions with Myc: manifested as a RhoA-dependent synthetic lethality and Par6-dependent effects on the cell cycle. Furthermore, we show a role for Par6G as a negative regulator of the phosphatidylinositol 3′-kinase/phosphoinositide-dependent protein kinase 1/Akt pathway and epithelial cell proliferation and evidence for frequent inactivation of Par6G gene in epithelial cancers. The findings demonstrate that determinants of epithelial structure regulate the cell proliferation activity via conserved and cancer-relevant regulatory circuitries, which are important for epithelial cell cycle restriction and may provide new targets for therapeutic intervention. PMID:26073086

  7. Targeting cancer metabolism at the plasma membrane by limiting amino acid access through SLC6A14.

    PubMed

    McCracken, Alison N; Edinger, Aimee L

    2015-09-15

    Rapidly proliferating cancer cells increase flux through anabolic pathways to build the mass necessary to support cell division. Imported amino acids and glucose lie at the apex of the anabolic pyramid. Consistent with this, elevated expression of nutrient transporter proteins is characteristic of aggressive and highly malignant cancers. Because tumour cells are more dependent than their normal neighbours on accelerated nutrient import, these up-regulated transporters could be excellent targets for selective anti-cancer therapies. A study by Babu et al. in a recent issue of the Biochemical Journal definitively shows that SLC6A14 (where SLC is solute carrier) is one such cancer-specific amino acid transporter. Although mice completely lacking SLC6A14 are viable and exhibit normal mammary gland development, these animals are highly resistant to mammary tumour initiation and progression driven by potent oncogenes. Because SLC6A14 is essential for tumour growth yet dispensable for normal development and tissue maintenance, small molecules that block amino acid import through this transporter could be effective and selective anti-cancer agents, particularly as components of rational drug combinations.

  8. Targeting cancer metabolism at the plasma membrane by limiting amino acid access through SLC6A14

    PubMed Central

    McCracken, Alison N.; Edinger, Aimee L.

    2015-01-01

    Rapidly proliferating cancer cells increase flux through anabolic pathways to build the mass necessary to support cell division. Imported amino acids and glucose lie at the apex of the anabolic pyramid. Consistent with this, elevated expression of nutrient transporter proteins is characteristic of aggressive and highly malignant cancers. Because tumour cells are more dependent than their normal neighbours on accelerated nutrient import, these up-regulated transporters could be excellent targets for selective anti-cancer therapies. A study by Babu et al. in a recent issue of the Biochemical Journal definitively shows that SLC6A14 (where SLC is solute carrier) is one such cancer-specific amino acid transporter. Although mice completely lacking SLC6A14 are viable and exhibit normal mammary gland development, these animals are highly resistant to mammary tumour initiation and progression driven by potent oncogenes. Because SLC6A14 is essential for tumour growth yet dispensable for normal development and tissue maintenance, small molecules that block amino acid import through this transporter could be effective and selective anti-cancer agents, particularly as components of rational drug combinations. PMID:26341486

  9. 6p22.3 amplification as a biomarker and potential therapeutic target of advanced stage bladder cancer

    PubMed Central

    Zhang, Jianmin; Underwood, Willie; Yang, Nuo; Frangou, Costa; Eng, Kevin; Head, Karen; Bollag, Roni J.; Kavuri, Sravan K.; Rojiani, Amyn M.; Li, Yingwei; Yan, Li; Hill, Annette; Woloszynska-Read, Anna; Wang, Jianmin; Liu, Song; Trump, Donald L.; Candace, Johnson S.

    2013-01-01

    Genetic and epigenetic alterations have been identified as to contribute directly or indirectly to the generation of transitional cell carcinoma of the urinary bladder (TCC-UB). In a comparative fashion much less is known about copy number alterations in TCC-UB, but it appears that amplification of chromosome 6p22 is one of the most frequent changes. Using fluorescence in situ hybridization (FISH) analyses, we evaluated chromosomal 6p22 amplification in a large cohort of bladder cancer patients with complete surgical staging and outcome data. We have also used shRNA knockdown candidate oncogenes in the cell based study. We found that amplification of chromosome 6p22.3 is significantly associated with the muscle-invasive transitional cell carcinoma of the urinary bladder (TCC-UB) (22%) in contrast to superficial TCC-UB (9%) (p=7.2-04). The rate of 6p22.3 amplification in pN>1 patients (32%) is more than twice that in pN0 (16%) patients (p=0.05). Interestingly, we found that 6p22.3 amplification is as twice as high (p=0.0201) in African American (AA) than European American (EA) TCC-UB patients. Moreover, we showed that the expression of some candidate genes (E2F3, CDKAL1 and Sox4) in the 6p22.3 region is highly correlated with the chromosomal amplification. In particular, knockdown of E2F3 inhibits cell proliferation in a 6p22.3-dependent manner, whereas knockdown of CDKAL1 and Sox4 has no effect on cell proliferation. Using gene expression profiling, we further identified some common as well as distinctive subset targets of the E2F3 family members. In summary, our data indicate that E2F3 is a key regulator of cell proliferation in a subset of bladder cancer and the 6p22.3 amplicon is a biomarker of aggressive phenotype in this tumor type. PMID:24231253

  10. α6β2* and α4β2* Nicotinic Acetylcholine Receptors As Drug Targets for Parkinson's Disease

    PubMed Central

    Wonnacott, Susan

    2011-01-01

    Parkinson's disease is a debilitating movement disorder characterized by a generalized dysfunction of the nervous system, with a particularly prominent decline in the nigrostriatal dopaminergic pathway. Although there is currently no cure, drugs targeting the dopaminergic system provide major symptomatic relief. As well, agents directed to other neurotransmitter systems are of therapeutic benefit. Such drugs may act by directly improving functional deficits in these other systems, or they may restore aberrant motor activity that arises as a result of a dopaminergic imbalance. Recent research attention has focused on a role for drugs targeting the nicotinic cholinergic systems. The rationale for such work stems from basic research findings that there is an extensive overlap in the organization and function of the nicotinic cholinergic and dopaminergic systems in the basal ganglia. In addition, nicotinic acetylcholine receptor (nAChR) drugs could have clinical potential for Parkinson's disease. Evidence for this proposition stems from studies with experimental animal models showing that nicotine protects against neurotoxin-induced nigrostriatal damage and improves motor complications associated with l-DOPA, the “gold standard” for Parkinson's disease treatment. Nicotine interacts with multiple central nervous system receptors to generate therapeutic responses but also produces side effects. It is important therefore to identify the nAChR subtypes most beneficial for treating Parkinson's disease. Here we review nAChRs with particular emphasis on the subtypes that contribute to basal ganglia function. Accumulating evidence suggests that drugs targeting α6β2* and α4β2* nAChR may prove useful in the management of Parkinson's disease. PMID:21969327

  11. Live cell imaging of interleukin-6-induced targeting of "transcription factor" STAT3 to sequestering endosomes in the cytoplasm.

    PubMed

    Xu, Fang; Mukhopadhyay, Somshuvra; Sehgal, Pravin B

    2007-10-01

    Signal transducer and activator of transcription (STAT) family transcription factors are classically viewed as transducing cytokine- and growth factor-activated signals from the plasma membrane to the cell nucleus for the purpose of activating transcription. We report live cell imaging studies of fluorescently labeled STAT3 expressed in Hep3B hepatocytes that reveal interleukin (IL)-6-activated targeting of STAT3 and PY-STAT3 to relatively long-lived sequestering endosomes in the cytoplasm. This targeting was rapid but transient, required phosphorylation and integrity of Tyr 705 in STAT3, and was blocked by nocodazole, geldanamycin, and indirubin E804 and by overexpression of wild-type caveolin-1. Strikingly, overexpression of the dominant-negative (DN) mutant K44A of the GTPase dynamin II led to marked constitutive accumulation of STAT3 in the endocytic compartment with depletion of the STAT3 nuclear pool. Subsets of the native and K44A-generated STAT3- and PY-STAT3-sequestering endosomes colocalized with MyD88, an adapter protein that integrates pathways of Toll-like receptor and IL-1 transcriptional signaling and stabilization of mRNAs. These data provide direct evidence for the cytokine-induced "signal transduction" by STAT3 from the plasma membrane to a cytoplasmic membrane destination for yet to be elucidated function(s) in the cytoplasm including prolongation of signaling and/or cross talk.

  12. Laser measurements of distances from the ORELA neutron target to experiment stations along flight paths 1 and 6

    SciTech Connect

    Larson, D.C.; Larson, N.M.; Harvey, J.A.; Perey, F.G.; Pierce, D.E.; Seals, R.H.

    1985-03-01

    Flight-path lengths have been measured by laser techniques for the 200-, 80-, and 18-m stations along flight path 1, and for the 5-, 20-, 40-, and 150-m stations along flight path 6 at the Oak Ridge Electron Linear Accelerator (ORELA). In each case the distance evaluated from the measurements is the slope distance from the center of the neutron-producing target to a position along the beam path, directly above a suitable benchmark at the experiment station. A total of 25 laser measurements were performed between the various stations. These data, along with appropriate uncertainties, were combined using Bayes' method. From this analysis we obtained the desired flight-path lengths, which typically have uncertainties less than 1.5 mm. The measurment technique, uncertainties, analysis method, and results are documented in detail in this report.

  13. Redox-responsive magnetic nanoparticle for targeted convection-enhanced delivery of O6-benzylguanine to brain tumors.

    PubMed

    Stephen, Zachary R; Kievit, Forrest M; Veiseh, Omid; Chiarelli, Peter A; Fang, Chen; Wang, Kui; Hatzinger, Shelby J; Ellenbogen, Richard G; Silber, John R; Zhang, Miqin

    2014-10-28

    Resistance to temozolomide (TMZ) based chemotherapy in glioblastoma multiforme (GBM) has been attributed to the upregulation of the DNA repair protein O(6)-methylguanine-DNA methyltransferase (MGMT). Inhibition of MGMT using O(6)-benzylguanine (BG) has shown promise in these patients, but its clinical use is hindered by poor pharmacokinetics that leads to unacceptable toxicity. To improve BG biodistribution and efficacy, we developed superparamagnetic iron oxide nanoparticles (NP) for targeted convection-enhanced delivery (CED) of BG to GBM. The nanoparticles (NPCP-BG-CTX) consist of a magnetic core coated with a redox-responsive, cross-linked, biocompatible chitosan-PEG copolymer surface coating (NPCP). NPCP was modified through covalent attachment of BG and tumor targeting peptide chlorotoxin (CTX). Controlled, localized BG release was achieved under reductive intracellular conditions and NPCP-BG-CTX demonstrated proper trafficking of BG in human GBM cells in vitro. NPCP-BG-CTX treated cells showed a significant reduction in MGMT activity and the potentiation of TMZ toxicity. In vivo, CED of NPCP-BG-CTX produced an excellent volume of distribution (Vd) within the brain of mice bearing orthotopic human primary GBM xenografts. Significantly, concurrent treatment with NPCP-BG-CTX and TMZ showed a 3-fold increase in median overall survival in comparison to NPCP-CTX/TMZ treated and untreated animals. Furthermore, NPCP-BG-CTX mitigated the myelosuppression observed with free BG in wild-type mice when administered concurrently with TMZ. The combination of favorable physicochemical properties, tumor cell specific BG delivery, controlled BG release, and improved in vivo efficacy demonstrates the great potential of these NPs as a treatment option that could lead to improved clinical outcomes.

  14. Redox-Responsive Magnetic Nanoparticle for Targeted Convection-Enhanced Delivery of O6-Benzylguanine to Brain Tumors

    PubMed Central

    2015-01-01

    Resistance to temozolomide (TMZ) based chemotherapy in glioblastoma multiforme (GBM) has been attributed to the upregulation of the DNA repair protein O6-methylguanine-DNA methyltransferase (MGMT). Inhibition of MGMT using O6-benzylguanine (BG) has shown promise in these patients, but its clinical use is hindered by poor pharmacokinetics that leads to unacceptable toxicity. To improve BG biodistribution and efficacy, we developed superparamagnetic iron oxide nanoparticles (NP) for targeted convection-enhanced delivery (CED) of BG to GBM. The nanoparticles (NPCP-BG-CTX) consist of a magnetic core coated with a redox-responsive, cross-linked, biocompatible chitosan-PEG copolymer surface coating (NPCP). NPCP was modified through covalent attachment of BG and tumor targeting peptide chlorotoxin (CTX). Controlled, localized BG release was achieved under reductive intracellular conditions and NPCP-BG-CTX demonstrated proper trafficking of BG in human GBM cells in vitro. NPCP-BG-CTX treated cells showed a significant reduction in MGMT activity and the potentiation of TMZ toxicity. In vivo, CED of NPCP-BG-CTX produced an excellent volume of distribution (Vd) within the brain of mice bearing orthotopic human primary GBM xenografts. Significantly, concurrent treatment with NPCP-BG-CTX and TMZ showed a 3-fold increase in median overall survival in comparison to NPCP-CTX/TMZ treated and untreated animals. Furthermore, NPCP-BG-CTX mitigated the myelosuppression observed with free BG in wild-type mice when administered concurrently with TMZ. The combination of favorable physicochemical properties, tumor cell specific BG delivery, controlled BG release, and improved in vivo efficacy demonstrates the great potential of these NPs as a treatment option that could lead to improved clinical outcomes. PMID:25247850

  15. Redox-responsive magnetic nanoparticle for targeted convection-enhanced delivery of O6-benzylguanine to brain tumors.

    PubMed

    Stephen, Zachary R; Kievit, Forrest M; Veiseh, Omid; Chiarelli, Peter A; Fang, Chen; Wang, Kui; Hatzinger, Shelby J; Ellenbogen, Richard G; Silber, John R; Zhang, Miqin

    2014-10-28

    Resistance to temozolomide (TMZ) based chemotherapy in glioblastoma multiforme (GBM) has been attributed to the upregulation of the DNA repair protein O(6)-methylguanine-DNA methyltransferase (MGMT). Inhibition of MGMT using O(6)-benzylguanine (BG) has shown promise in these patients, but its clinical use is hindered by poor pharmacokinetics that leads to unacceptable toxicity. To improve BG biodistribution and efficacy, we developed superparamagnetic iron oxide nanoparticles (NP) for targeted convection-enhanced delivery (CED) of BG to GBM. The nanoparticles (NPCP-BG-CTX) consist of a magnetic core coated with a redox-responsive, cross-linked, biocompatible chitosan-PEG copolymer surface coating (NPCP). NPCP was modified through covalent attachment of BG and tumor targeting peptide chlorotoxin (CTX). Controlled, localized BG release was achieved under reductive intracellular conditions and NPCP-BG-CTX demonstrated proper trafficking of BG in human GBM cells in vitro. NPCP-BG-CTX treated cells showed a significant reduction in MGMT activity and the potentiation of TMZ toxicity. In vivo, CED of NPCP-BG-CTX produced an excellent volume of distribution (Vd) within the brain of mice bearing orthotopic human primary GBM xenografts. Significantly, concurrent treatment with NPCP-BG-CTX and TMZ showed a 3-fold increase in median overall survival in comparison to NPCP-CTX/TMZ treated and untreated animals. Furthermore, NPCP-BG-CTX mitigated the myelosuppression observed with free BG in wild-type mice when administered concurrently with TMZ. The combination of favorable physicochemical properties, tumor cell specific BG delivery, controlled BG release, and improved in vivo efficacy demonstrates the great potential of these NPs as a treatment option that could lead to improved clinical outcomes. PMID:25247850

  16. 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.

  17. External Guide Sequences Targeting the aac(6′)-Ib mRNA Induce Inhibition of Amikacin Resistance▿

    PubMed Central

    Bistué, Alfonso J. C. Soler; Ha, Hongphuc; Sarno, Renee; Don, Michelle; Zorreguieta, Angeles; Tolmasky, Marcelo E.

    2007-01-01

    The dissemination of AAC(6′)-I-type acetyltransferases have rendered amikacin and other aminoglycosides all but useless in some parts of the world. Antisense technologies could be an alternative to extend the life of these antibiotics. External guide sequences are short antisense oligoribonucleotides that induce RNase P-mediated cleavage of a target RNA by forming a precursor tRNA-like complex. Thirteen-nucleotide external guide sequences complementary to locations within five regions accessible for interaction with antisense oligonucleotides in the mRNA that encodes AAC(6′)-Ib were analyzed. While small variations in the location targeted by different external guide sequences resulted in big changes in efficiency of binding to native aac(6′)-Ib mRNA, most of them induced high levels of RNase P-mediated cleavage in vitro. Recombinant plasmids coding for selected external guide sequences were introduced into Escherichia coli harboring aac(6′)-Ib, and the transformant strains were tested to determine their resistance to amikacin. The two external guide sequences that showed the strongest binding efficiency to the mRNA in vitro, EGSC3 and EGSA2, interfered with expression of the resistance phenotype at different degrees. Growth curve experiments showed that E. coli cells harboring a plasmid coding for EGSC3, the external guide sequence with the highest mRNA binding affinity in vitro, did not grow for at least 300 min in the presence of 15 μg of amikacin/ml. EGSA2, which had a lower mRNA-binding affinity in vitro than EGSC3, inhibited the expression of amikacin resistance at a lesser level; growth of E. coli harboring a plasmid coding for EGSA2, in the presence of 15 μg of amikacin/ml was undetectable for 200 min but reached an optical density at 600 nm of 0.5 after 5 h of incubation. Our results indicate that the use of external guide sequences could be a viable strategy to preserve the efficacy of amikacin. PMID:17387154

  18. Critical Landau velocity in helium nanodroplets.

    PubMed

    Brauer, Nils B; Smolarek, Szymon; Loginov, Evgeniy; Mateo, David; Hernando, Alberto; Pi, Marti; Barranco, Manuel; Buma, Wybren J; Drabbels, Marcel

    2013-10-11

    The best-known property of superfluid helium is the vanishing viscosity that objects experience while moving through the liquid with speeds below the so-called critical Landau velocity. This critical velocity is generally considered a macroscopic property as it is related to the collective excitations of the helium atoms in the liquid. In the present work we determine to what extent this concept can still be applied to nanometer-scale, finite size helium systems. To this end, atoms and molecules embedded in helium nanodroplets of various sizes are accelerated out of the droplets by means of optical excitation, and the speed distributions of the ejected particles are determined. The measurements reveal the existence of a critical velocity in these systems, even for nanodroplets consisting of only a thousand helium atoms. Accompanying theoretical simulations based on a time-dependent density functional description of the helium confirm and further elucidate this experimental finding.

  19. 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.

  20. 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,...

  1. 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,...

  2. 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,...

  3. 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,...

  4. 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,...

  5. Limited Quantum Helium Transportation through Nano-channels by Quantum Fluctuation

    NASA Astrophysics Data System (ADS)

    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.

  6. Limited Quantum Helium Transportation through Nano-channels by Quantum Fluctuation.

    PubMed

    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

  7. 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

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. Radiolysis of cyclooctane with [gamma]-rays and helium ions

    SciTech Connect

    Wojnarovits, L.; LaVerne, J.A. )

    1994-08-18

    Iodine scavenging techniques have been used to examine the role of the cyclooctyl radical in the radiolysis of cyclooctane with [gamma]-rays and with 5-20-MeV helium ions. In [gamma]-radiolysis about 70% of the total yield of 6.6 cyclooctyl radicals/100 eV are scavenged with 10[sup [minus]4] M iodine, which agrees well with other studies on cycloalkanes that show most of the radicals produced in these systems react in the bulk medium at times longer than 1 [nu]s. However, it is found that 2.5 radicals/100 eV (38%) are produced by H atom precursors as compared to a value of 1.5 cyclohexyl radicals/100 eV (25%) in cyclohexane. With 10-MeV helium ions (average LET of 106 eV/nm), only 8% of the cyclooctyl radicals survive longer than a few microseconds due to the increased initial radical concentration in the helium ion track. The yield of the cross-bridged product bicyclo[3.3.0]octane (pentalane) was found to be independent of iodine concentration up to 0.03 M with both types of radiation. However, the pentalane yield found with 10-MeV helium ions was only one-third of that found in [gamma]-radiolysis. The most likely reason for this result is the decreased yield of singlet-state formation due to the enhanced probability of cross combination reactions of electron-cation pairs in the high-density region of the helium ion track. 29 refs., 4 figs., 1 tab.

  15. Targeting histone deacetylase 6 mediates a dual anti-melanoma effect: Enhanced antitumor immunity and impaired cell proliferation

    PubMed Central

    Perez-Villaroel, P.; Lee, C.; Cheng, F.; Knox, T.; Woods, D.M.; Barrios, K.; Powers, J.; Sahakian, E.; Wang, H.W.; Canales, J.; Marante, D.; Smalley, K.S.M.; Bergman, J.; Seto, E.; Kozikowski, A.; Pinilla-Ibarz, J.; Sarnaik, A.; Celis, E.; Weber, J.; Sotomayor, E.M.; Villagra, A.

    2015-01-01

    The median survival for metastatic melanoma is in the realm of 8–16 months and there are few therapies that offer significant improvement in overall survival. One of the recent advances in cancer treatment focuses on epigenetic modifiers to alter the survivability and immunogenicity of cancer cells. Our group and others have previously demonstrated that pan-HDAC inhibitors induce apoptosis, cell cycle arrest and changes in the immunogenicity of melanoma cells. Here we interrogated specific HDACs which may be responsible for this effect. We found that both genetic abrogation and pharmacologic inhibition of HDAC6 decreases in vitro proliferation and induces G1 arrest of melanoma cell lines without inducing apoptosis. Moreover, targeting this molecule led to an important upregulation in the expression of tumor associated antigens and MHC class I, suggesting a potential improvement in the immunogenicity of these cells. Of note, this anti-melanoma activity was operative regardless of mutational status of the cells. These effects translated into a pronounced delay of in vivo melanoma tumor growth which was, at least in part, dependent on intact immunity as evidenced by the restoration of tumor growth after CD4+ and CD8+ depletion. Given our findings, we provide the initial rationale for the further development of selective HDAC6 inhibitors as potential therapeutic anti-melanoma agents. PMID:25957812

  16. MicroRNA-26a prevents endothelial cell apoptosis by directly targeting TRPC6 in the setting of atherosclerosis

    PubMed Central

    Zhang, Yong; Qin, Wei; Zhang, Longyin; Wu, Xianxian; Du, Ning; Hu, Yingying; Li, Xiaoguang; Shen, Nannan; Xiao, Dan; Zhang, Haiying; Li, Zhange; Zhang, Yue; Yang, Huan; Gao, Feng; Du, Zhimin; Xu, Chaoqian; Yang, Baofeng

    2015-01-01

    Atherosclerosis, a chronic inflammatory disease, is the major cause of life-threatening complications such as myocardial infarction and stroke. Endothelial apoptosis plays a vital role in the initiation and progression of atherosclerotic lesions. Although a subset of microRNAs (miRs) have been identified as critical regulators of atherosclerosis, studies on their participation in endothelial apoptosis in atherosclerosis have been limited. In our study, we found that miR-26a expression was substantially reduced in the aortic intima of ApoE−/− mice fed with a high-fat diet (HFD). Treatment of human aortic endothelial cells (HAECs) with oxidized low-density lipoprotein (ox-LDL) suppressed miR-26a expression. Forced expression of miR-26a inhibited endothelial apoptosis as evidenced by MTT assay and TUNEL staining results. Further analysis identified TRPC6 as a target of miR-26a, and TRPC6 overexpression abolished the anti-apoptotic effect of miR-26a. Moreover, the cytosolic calcium and the mitochondrial apoptotic pathway were found to mediate the beneficial effects of miR-26a on endothelial apoptosis. Taken together, our study reveals a novel role of miR-26a in endothelial apoptosis and indicates a therapeutic potential of miR-26a for atherosclerosis associated with apoptotic cell death. PMID:25801675

  17. MicroRNA-26a prevents endothelial cell apoptosis by directly targeting TRPC6 in the setting of atherosclerosis

    NASA Astrophysics Data System (ADS)

    Zhang, Yong; Qin, Wei; Zhang, Longyin; Wu, Xianxian; Du, Ning; Hu, Yingying; Li, Xiaoguang; Shen, Nannan; Xiao, Dan; Zhang, Haiying; Li, Zhange; Zhang, Yue; Yang, Huan; Gao, Feng; Du, Zhimin; Xu, Chaoqian; Yang, Baofeng

    2015-03-01

    Atherosclerosis, a chronic inflammatory disease, is the major cause of life-threatening complications such as myocardial infarction and stroke. Endothelial apoptosis plays a vital role in the initiation and progression of atherosclerotic lesions. Although a subset of microRNAs (miRs) have been identified as critical regulators of atherosclerosis, studies on their participation in endothelial apoptosis in atherosclerosis have been limited. In our study, we found that miR-26a expression was substantially reduced in the aortic intima of ApoE-/- mice fed with a high-fat diet (HFD). Treatment of human aortic endothelial cells (HAECs) with oxidized low-density lipoprotein (ox-LDL) suppressed miR-26a expression. Forced expression of miR-26a inhibited endothelial apoptosis as evidenced by MTT assay and TUNEL staining results. Further analysis identified TRPC6 as a target of miR-26a, and TRPC6 overexpression abolished the anti-apoptotic effect of miR-26a. Moreover, the cytosolic calcium and the mitochondrial apoptotic pathway were found to mediate the beneficial effects of miR-26a on endothelial apoptosis. Taken together, our study reveals a novel role of miR-26a in endothelial apoptosis and indicates a therapeutic potential of miR-26a for atherosclerosis associated with apoptotic cell death.

  18. Recruitment of Tup1p and Cti6p regulates heme-deficient expression of Aft1p target genes

    PubMed Central

    Crisp, Robert J; Adkins, Erika M; Kimmel, Emily; Kaplan, Jerry

    2006-01-01

    In the budding yeast Saccharomyces cerevisiae, transcription of genes encoding for the high-affinity iron (FET3, FTR1) and copper (CTR1) transporters does not occur in the absence of heme. We show that the Aft1p binding region of the FET3 promoter or the Mac1p binding region of the CTR1 promoter is necessary and sufficient to mediate heme-deficient repression. Transcription is repressed in the absence of heme, and a genetic screen identified Tup1p and Hda1p as being required for transcriptional repression. In contrast to FET3 and CTR1, Aft1p target genes ARN1 and FIT1 are transcribed in the absence of heme. A 14 bp sequence in the ARN1 promoter is necessary and sufficient to permit transcription in the absence of heme. Transcription in the absence of heme required the presence of Cti6p to overcome the effect of Tup1p, and Cti6p was recruited to the ARN1 promoter in the absence of heme. We hypothesize that transcription of the siderophore transporter ARN1 permits yeast to accumulate iron in the absence of oxygen and to deny iron to competing organisms. PMID:16437160

  19. 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.

  20. 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.

  1. Helium transport studies on DIII-D

    SciTech Connect

    Finkenthal, D.F.; Hillis, D.L.; Wade, M.R.; Hogan, J.T.; Klepper, C.C.; Mioduszewski, P.K.; West, W.P.; Burrell, K.H.; Seraydarian, R.P.; Groebner, R.J.; Gohil, P.

    1992-05-01

    The measurement of Helium density profiles in tokamak plasmas is necessary for helium transport studies. These studies are important in predicting the helium ash transport properties for ITER and win have important implications for the design. Poor helium transport in reactors could lead to a buildup of fusion ash, causing fuel dilution and increased radiation that will result in degraded fusion power and possibly quench ignition altogether. Present estimates indicate that He concentrations in the core must be kept below 10% in order to maintain continuous reactor operation. Helium transport studies have begun on the DM-D tokamak using charge exchange recombination (CER) spectroscopy for helium density measurements. Helium transport behavior has been observed by injecting helium gas puffs into DM-D plasmas and measuring the He density profile evolution. The profiles are used to calculate the relevant helium transport properties. This paper covers the results obtained from puffing He gas into L-mode plasmas of various electron densities. The results obtained in DIII-D L-mode plasmas are similar to measurements made at TEXTOR and JT-60.

  2. Importance of non-first-order effects in the (e,3e) double ionization of helium

    SciTech Connect

    Lahmam-Bennani, A.; Duguet, A.; Dal Cappello, C.; Nebdi, H.; Piraux, B.

    2003-01-01

    Angular distributions of the two ejected electrons resulting from the double ionization of helium by electron impact have been measured by means of a multicoincidence multiangle (e,3e) spectrometer at an incident energy of about 0.6 keV and equal outgoing energies E{sub b}=E{sub c}=11 eV. We identify various regimes of kinematical parameters where substantial differences are found with respect to the first-Born convergent close-coupling calculations: an angular shift of the position of the main lobe and the presence of additional lobes. These differences are attributed to high-order contributions in the projectile-target interaction. This conclusion is supported by recent (e,3e) calculations performed within the second-Born approximation.

  3. 43 CFR 3195.35 - What happens if I have an outstanding obligation to purchase refined helium under a Helium...

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 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...

  4. 43 CFR 3195.35 - What happens if I have an outstanding obligation to purchase refined helium under a Helium...

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 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...

  5. 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...

  6. 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...

  7. 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...

  8. 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...

  9. 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...

  10. 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...

  11. Low-energy electron-impact ionization of helium

    SciTech Connect

    Schow, E.; Hazlett, K.; Childers, J. G.; Medina, C.; Vitug, G.; Khakoo, M. A.; Bray, I.; Fursa, D. V.

    2005-12-15

    Normalized doubly differential cross sections for the electron-impact ionization of helium at low energies are presented. The data are taken at the incident electron energies of 26.3, 28.3, 30.3, 32.5, 34.3, 36.5, and 40.7 eV and for scattering angles of 10 deg. -130 deg. The measurements involve the use of the moveable target method developed at California State University Fullerton to accurately determine the continuum background in the energy-loss spectra. Normalization of experimental data is made on a relative scale to well-established experimental differential cross sections for excitation of the n=2 manifold of helium and then on an absolute scale to the well-established total ionization cross sections of Shah et al. [J. Phys. B 21, 2751 (1988)]. Comparisons are made with available experimental data and the results of the convergent close-coupling theory.

  12. O6-alkylguanine-DNA transferase (SNAP) as capture module for site-specific covalent bioconjugation of targeting protein on nanoparticles

    NASA Astrophysics Data System (ADS)

    Mazzucchelli, Serena; Colombo, Miriam; Galbiati, Elisabetta; Corsi, Fabio; Montenegro, Josè M.; Parak, Wolfgang J.; Prosperi, Davide

    2013-02-01

    A bimodular genetic fusion comprising a delivery module (scFv) and a capture module (SNAP) is proposed as a novel strategy for the biologically mediated site-specific covalent conjugation of targeting proteins to nanoparticles. ScFv800E6, an scFv mutant selective for HER2 antigen overexpressed in breast cancer cells was chosen as targeting ligand. The fusion protein SNAP-scFv was irreversibly immobilized on magnetofluorescent nanoparticles through the recognition between SNAP module and pegylated O6-alkylguanine derivative. The targeting efficiency of the resulting nanoparticle against HER2-positive breast cancer cells was assessed by flow cytometry and immunofluorescence.

  13. 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.

  14. 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.

  15. 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.

  16. Helium in Earth's Early Core

    NASA Astrophysics Data System (ADS)

    Jephcoat, A. P.; Bouhifd, M. A.; Heber, V.; Kelley, S. P.

    2006-12-01

    The high 3He/4He ratios for some ocean-island basalts, and more recent observations for solar components of the other rare gases (Ne, Ar and possibly Xe), continue to raise questions on primordial source reservoirs as well as on accretionary and incorporation processes of rare gases. A number of geochemical mantle models have been made to explain the observed 3He/4He ratios, the most popular of which has been an undegassed primordial reservoir. Isotope systematics of other radiogenic elements do not support such an isolated source and changes in the accepted models of mantle convection style have made it harder to rely on the deep mantle as a reservoir. The core has remained a particularly unfavourable location either because of difficulty in constructing a retention mechanism during planetary accretion or simply because of a lack of data: Partitioning studies at pressure are rare and complicated by the difficulty in reproducing not only absolute concentrations, but confinement of gas in high-pressure apparatus and post-run analysis. We present experiments on helium solubility and partitioning between molten silicates and Fe-rich metal liquids up to 16 GPa and 3000 K, with the laser-heated diamond-anvil cell, and the quenched run products analysed by ultra-violet laser ablation mass spectrometry (UVLAMP). Our results indicate a significantly higher partition coefficient for He between molten silicates and Fe-rich alloy liquids of about 10-2 at 16 GPa and 3000~K -- two orders of magnitude more helium is measured in the metal phase compared to the only previous data of Matsuda et al., (1993). The solubility mechanism is varied and involves a distinguishable bulk component and an apparent surface signature (that may be the result of the quench process). Whether surface effects are included or not, the early Earth's core would have incorporated non-negligible amounts of primordial helium if its segregation took place under mid-depth, magma-ocean conditions. The process

  17. 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.

  18. Helium Microbeam Mixing of Bilayers.

    NASA Astrophysics Data System (ADS)

    Davis, John Baran

    This study is an experimental and theoretical investigation of room-temperature mixing of bilayers by micron-width He^+ ion beams. Bilayer targets, including Cu/Al, Cu/Si and Sb/Si, were irradiated at room temperature in the University at Albany's Dynamitron particle accelerator with 2-MeV He^+ ion beams ranging from 2 to 6 μm in width. At doses on the order of 10^ {19}/cm^2, RBS spectra revealed evidence of interface mixing in all targets to depths of several thousand A within the cylinder irradiated by the beam. Both RBS spectra and isometric RBS contour maps of the target also showed that mixing of the interface extends laterally well beyond the irradiated area. The interface mixing reaches a maximum in an annular region several times larger in diameter than the ion-beam. Standard theories of primary-recoil, secondary -cascade and thermal-spike mixing predicted interface widths two orders of magnitude smaller than observed for Cu/Al bilayers. Furthermore, He^+ irradiation of Cu/Al targets at liquid-nitrogen temperature did not produce interface mixing, further indicating that ballistic interpretations of the mixing are inadequate. Defect concentrations as a function of position and time were calculated by numerical solution of coupled rate equations for vacancies and interstitials in aluminum. The results of these calculations show that room-temperature He^+ mixing of Cu/Al results almost exclusively from interstitial migration. The numerically calculated concentration of interstitials within the damage cylinder was used to derive an approximate expression for interface width as a function of dose. Comparisons of these predicted values with the experimentally determined interface width as a function of dose agree, within uncertainties. In addition, the annular region observed on RBS maps is explained by the continued presence of a non-equilibrium concentration of interstitials after the ion beam is shut off. Interface mixing in Cu/Si targets, although

  19. 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. PMID:22267883

  20. 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.

  1. 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

  2. Overview of Serum Uric Acid Treatment Targets in Gout: Why Less Than 6 mg/dL?

    PubMed

    Ruoff, Gary; Edwards, N Lawrence

    2016-09-01

    Gout is a progressive, painful, debilitating form of inflammatory arthritis. It is caused by factors that elevate the concentration of serum uric acid (sUA), leading to hyperuricemia (sUA >6.8 mg/dL). Continued elevated sUA can result in monosodium urate (MSU) crystal deposition in joints and soft tissues, and can cause acute and chronic inflammation. The prevalence of hyperuricemia and gout has increased over the last few decades, likely due to an aging population, changes in lifestyles and diet, and an increase in gout-associated comorbidities. Untreated or improperly treated gout can lead to chronic manifestation of the disease, including persistent inflammation, increased number of flares, development of tophi, and structural joint damage. Data show that even when patients are asymptomatic, ongoing inflammation and subsequent damage occurs locally at the joint and systemically. The aim of long-term treatment of gout is to reduce sUA levels to <6 mg/dL, which is below the saturation point of MSU (6.8 mg/dL), to inhibit formation of new crystals and to promote dissolution of existing crystals. Gout treatment should improve disease outcomes by eliminating gout flares, inducing long-term resolution of tophi, and more effectively managing comorbidities, many of which are associated with hyperuricemia. A number of studies have demonstrated that treating to the target of <6 mg/dL, by using effective therapies to lower sUA, results in reduction in the incidence of gout flares as well as shrinkage and eventual disappearance of tophi. Gout is often poorly managed due to a number of factors including lack of physician and patient adherence to treatment guidelines. Patients need to be educated about their diagnosis and management of the disease, such as the influence of diet and the importance of compliance with long-term treatment. With treatment, regular sUA monitoring, and patient adherence, gout is a curable disease. PMID:27558643

  3. 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.

  4. 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.

  5. Helium release from 238PuO2 fuel particles

    NASA Astrophysics Data System (ADS)

    El-Genk, Mohamed S.; Tournier, Jean-Michel

    2000-01-01

    Coated plutonia fuel particles have recently been proposed for potential use in future space exploration missions that employ radioisotope power systems and/or radioisotope heater units (RHUs). The design of this fuel form calls for full retention of the helium generated by the natural radioactive decay of 238Pu, with the aid of a strong zirconium carbide coating. This paper reviews the potential release mechanisms of helium in small-grain (7-40 μm) plutonia pellets currently being used in the General Purpose Heat Source (GPHS) modules and RHUs, during both steady-state and transient heating conditions. The applicability of these mechanisms to large-grain and polycrystalline 238PuO2 fuel kernels is examined and estimates of helium release during a re-entry heating pulse up to 1723 K are presented. These estimates are based on the reported data for fission gas release from granular and monocrystal UO2 fuel particles irradiated at isothermal conditions up to 6.4 at.% burnup and 2030 K. It is concluded that the helium release fraction from large-grain (>=300 μm) plutonia fuel kernels heated up to 1723 K could be less than 7%, compared to ~80% from small-grain (7-40 μm) fuel. The helium release fraction from polycrystalline plutonia kernels fabricated using Sol-Gel techniques could be even lower. Sol-Gel fabrication processes are favored over powder metallurgy, because of their high precision and excellent reproducibility and the absence of a radioactive dust waste stream, significantly reducing the fabrication and post-fabrication clean-up costs. .

  6. [The effect of helium-neon laser radiation on the energy metabolic indices of the myocardium].

    PubMed

    Chizhov, G K; Koval'skaia, N I; Kozlov, V I

    1991-03-01

    It was shown in experiments on white rats, that intravenous and direct myocardium helium-neon laser irradiation leads to the some activation of lactate, glucose-6-phosphate, succinate and reduced NAD degydrogenases. During direct myocardium irradiation these changes are in a less degree. It is suggested that helium-neon laser irradiation displays some active influence on the energy metabolism enzymes of the myocardium, and the mechanisms of this action are discussed. PMID:2054512

  7. Elusive structure of helium trimers

    NASA Astrophysics Data System (ADS)

    Stipanović, Petar; Vranješ Markić, Leandra; Boronat, Jordi

    2016-09-01

    Over the years many He–He interaction potentials have been developed, some very sophisticated, including various corrections beyond the Born–Oppenheimer approximation. Most of them were used to predict properties of helium dimers and trimers, examples of exotic quantum states, whose experimental study proved to be very challenging. Recently, detailed structural properties of helium trimers were measured for the first time, allowing a comparison with theoretical predictions and possibly enabling the evaluation of different interaction potentials. The comparisons already made included adjusting the maxima of both theoretical and experimental correlation functions to one, so the overall agreement between theory and experiment appeared satisfactory. However, no attempt was made to evaluate the quality of the interaction potentials used in the calculations. In this work, we calculate the experimentally measured correlation functions using both new and old potentials, compare them with experimental data and rank the potentials. We use diffusion Monte Carlo simulations at T = 0, which give within statistical noise exact results of the ground state properties. All models predict both trimers 4He3 and 4He{}2{}3He to be in a quantum halo state.

  8. Elusive structure of helium trimers

    NASA Astrophysics Data System (ADS)

    Stipanović, Petar; Vranješ Markić, Leandra; Boronat, Jordi

    2016-09-01

    Over the years many He-He interaction potentials have been developed, some very sophisticated, including various corrections beyond the Born-Oppenheimer approximation. Most of them were used to predict properties of helium dimers and trimers, examples of exotic quantum states, whose experimental study proved to be very challenging. Recently, detailed structural properties of helium trimers were measured for the first time, allowing a comparison with theoretical predictions and possibly enabling the evaluation of different interaction potentials. The comparisons already made included adjusting the maxima of both theoretical and experimental correlation functions to one, so the overall agreement between theory and experiment appeared satisfactory. However, no attempt was made to evaluate the quality of the interaction potentials used in the calculations. In this work, we calculate the experimentally measured correlation functions using both new and old potentials, compare them with experimental data and rank the potentials. We use diffusion Monte Carlo simulations at T = 0, which give within statistical noise exact results of the ground state properties. All models predict both trimers 4He3 and 4He{}2{}3He to be in a quantum halo state.

  9. Dynamics modeling and control of a 6-DOF space robot with flexible panels for capturing a free floating target

    NASA Astrophysics Data System (ADS)

    Yu, Zhang-wei; Liu, Xiao-feng; Cai, Guo-ping

    2016-11-01

    In many kinds of on-orbit space robot tasks, capturing free floating target using space robot attracts more attention of researchers. However, most existing researches about dynamics and control of space robot concern planar problem, and the effect of flexible panel on capturing dynamics of the system is not considered. In this paper, spatial dynamics and control of a 6-DOF space robot with flexible panels are investigated and spatial impact problem is considered. Dynamic model of the system is established by the single direction recursive construction method and the Jourdain's velocity variation principle. The Hertz contact and impact theory and the method of computer graphics are used to establish the impact model. The computed torque control method is used to design active controller to suppress the spacecraft drift caused by the impact. Numerical simulation results show that the established dynamic model is effective in describing the dynamics behavior of the space robot; flexible panels have big influence on impact dynamic characteristics; the designed controller may effectively control the spacecraft drift during the capture process.

  10. Helium-flow measurement using ultrasonic technique

    NASA Astrophysics Data System (ADS)

    Sondericker, J. H.

    1983-08-01

    The ideal cryogenic instrumentation for the colliding beam accelerator helium distribution system does not add pressure drop to the system, functions over the entire temperature range, has high resolution, and delivers accurate mass flow measurement data. The design and testing of an ultrasonic flowmeter which measures helium flow under different temperatures are described.

  11. Detection of Hydrogen and Helium with EPHIN

    NASA Astrophysics Data System (ADS)

    Gómez-Herrero, R.; Rodríguez-Frías, M. D.; del Peral, L.; Sequeiros, J.; Müller-Mellin, R.; Kunow, H.; Sierks, H.

    2001-08-01

    A Monte Carlo simulation code based on GEANT 3.21 has been used to follow the SOHO (Solar and Heliospheric Observatory)/EPHIN (Electron, Proton and Helium Instrument) response to the detection of hydrogen and helium nuclei. The geometrical factor dependence on the energy has been evaluated and the contamination of the EPHIN channels has been obtained.

  12. Stability of Helium Clusters during Displacement Cascades

    SciTech Connect

    Yang, Li; Zu, Xiaotao T.; Xiao, H. Y.; Gao, Fei; Heinisch, Howard L.; Kurtz, Richard J.; Wang, Zhiguo; Liu, K. Z.

    2007-02-01

    The interaction of displacement cascades with helium-vacancy clusters is investigated using molecular dynamics simulations. The He-vacancy clusters initially consist of 20 vacancies with a Helium-to-vacancy ratio ranging from 0.2 to 3. The primary knock-on atom (PKA) energy, Ep, varies from 2 keV to 10 keV, and the PKA direction is chosen such that a displacement cascade is able to directly interact with a helium-vacancy cluster. The simulation results show that the effect of displacement cascades on a helium-vacancy cluster strongly depends on both the helium-to-vacancy ratio and the PKA energy. For the same PKA energy, the size of helium-vacancy clusters increases with the He/V ratio, but for the same ratio, the cluster size changes more significantly with increasing PKA energy. It has been observed that the He-vacancy clusters can be dissolved when the He/V ratio less than 1, but they are able to re-nucleate during the thermal spike phase, forming small He-V nuclei. When the He/V ratio is larger than 1, the He-V clusters can absorb a number of vacancies produced by displacement cascades, forming larger He-V clusters. These results are discussed in terms of PKA energy, helium-to-vacancy ratio, number of vacancies produced by cascades, and mobility of helium atoms.

  13. 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).

  14. 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…

  15. 30 CFR 256.11 - Helium.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... of and the right to extract helium from all gas produced from the leased area. (b) In case the United... helium extracted. The United States shall determine the amount of reasonable compensation. The United... substantial delays in the delivery of natural gas produced to the purchaser of that gas....

  16. 30 CFR 256.11 - Helium.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... the United States, under section 12(f) of the Act, of the ownership of and the right to extract helium... other loss for which he is not reasonably compensated, except for the value of the helium extracted. The... delivery of natural gas produced to the purchaser of that gas....

  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. Gemini helium closed cycle cooling system

    NASA Astrophysics Data System (ADS)

    Lazo, Manuel; Galvez, Ramon; Rogers, Rolando; Solis, Hernan; Tapia, Eduardo; Maltes, Diego; Collins, Paul; White, John; Cavedoni, Chas; Yamasaki, Chris; Sheehan, Michael P.; Walls, Brian

    2008-07-01

    The Gemini Observatory presents the Helium Closed Cycle Cooling System that provides cooling capacity at cryogenic temperatures for instruments and detectors. It is implemented by running three independent helium closed cycle cooling circuits with several banks of compressors in parallel to continuously supply high purity helium gas to cryocoolers located about 100-120 meters apart. This poster describes how the system has been implemented, the required helium pressures and gas flow to reach cryogenic temperature, the performance it has achieved, the helium compressors and cryocoolers in use and the level of vibration the cryocoolers produce in the telescope environment. The poster also describes the new technology for cryocoolers that Gemini is considering in the development of new instruments.

  19. Helium Migration Mechanisms in Polycrystalline Uranium Dioxide

    SciTech Connect

    Martin, Guillaume; Desgardin, Pierre; Sauvage, Thierry; Barthe, Marie-France; Garcia, Philippe; Carlot, Gaelle

    2007-07-01

    This study aims at identifying the release mechanisms of helium in uranium dioxide. Two sets of polycrystalline UO{sub 2} sintered samples presenting different microstructures were implanted with {sup 3}He ions at concentrations in the region of 0.1 at.%. Changes in helium concentrations were monitored using two Nuclear Reaction Analysis (NRA) techniques based on the {sup 3}He(d,{alpha}){sup 1}H reaction. {sup 3}He release is measured in-situ during sample annealing at temperatures ranging between 700 deg. C and 1000 deg. C. Accurate helium depth profiles are generated after each annealing stage. Results that provide data for further understanding helium release mechanisms are discussed. It is found that helium diffusion appears to be enhanced above 900 deg. C in the vicinity of grain boundaries possibly as a result of the presence of defects. (authors)

  20. 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.

  1. 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 /sup 3/He-/sup 4/He 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 concentrated /sup 3/He-/sup 4/He mixtures has been studied in detail with the x-ray measurements. Vacancy concentrations in crystals with 99%, 51%, 28%, 12%, and 0% /sup 3/He have been determined. Phase separation has been studied in mixed crystals with concentrations of 51%, 28%, and 12% /sup 3/He 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 T/sub c/, the phase separation temperature for a 50% mixture, is found to be linear: dT/sub c//dP = -34 mdeg/MPa. The x-ray measurements are used to make several comments on the low temperature phase diagram of the helium mixtures.

  2. Optical Forces on Metastable Helium

    NASA Astrophysics Data System (ADS)

    Corder, Christopher Scott

    Optical forces using lasers allow precise control over the motion of atoms. The bichromatic optical force (BF) is unique in its large magnitude and velocity range, arising from the absorption and stimulated emission processes. These properties were used to transversely collimate a beam of metastable helium (He*) using the 23S - 23P transition. The collimation created a very bright beam of He*, allowing experiments of neutral atom lithography. The He* beam was used to pattern material surfaces using a resist-based lithography technique, where the pattern was determined by either mechanical or optical masks. The optical masks produced features with a separation of half the wavelength of the light used. Patterning was successfully demonstrated with both IR and UV optical masks. The etched pattern resolution was ˜ 100 nm and limited by the material surface. Further experiments were performed studying the ability of the bichromatic force to cool. The finite velocity range of the BF allows estimation of a characteristic cooling time which is independent of the excited state lifetime, only depending on the atomic mass and optical transition energy. Past experiments, including the helium collimation used for neutral atom lithography, have demonstrated that the BF can collimate and longitudinally slow atomic beams, but required long interaction times that included many spontaneous emission (SE) events. The effect of SE can be mitigated, and is predicted to not be necessary for BF cooling. Since the BF cooling time is not related to the excited state lifetime, a transition can be chosen such that the cooling time is shorter than the SE cycle time, allowing direct laser cooling on atoms and molecules that do not have cycling transitions. Experiments using the helium 2 3S-3P transition were chosen because the BF cooling time (285 ns) is on the order of the average SE cycle time (260 ns). Numerical simulations of the experimental system were run predicting compression of the

  3. Targeting of ribosomal protein S6 to dendritic spines by in vivo high frequency stimulation to induce long-term potentiation in the dentate gyrus

    PubMed Central

    Nihonmatsu, Itsuko; Ohkawa, Noriaki; Saitoh, Yoshito; Inokuchi, Kaoru

    2015-01-01

    ABSTRACT Late phase long-term potentiation (L-LTP) in the hippocampus is believed to be the cellular basis of long-term memory. Protein synthesis is required for persistent forms of synaptic plasticity, including L-LTP. Neural activity is thought to enhance local protein synthesis in dendrites, and one of the mechanisms required to induce or maintain the long-lasting synaptic plasticity is protein translation in the dendrites. One regulator of translational processes is ribosomal protein S6 (rpS6), a component of the small 40S ribosomal subunit. Although polyribosomes containing rpS6 are observed in dendritic spines, it remains unclear whether L-LTP induction triggers selective targeting of the translational machinery to activated synapses in vivo. Therefore, we investigated synaptic targeting of the translational machinery by observing rpS6 immunoreactivity during high frequency stimulation (HFS) for L-LTP induction in vivo. Immunoelectron microscopic analysis revealed a selective but transient increase in rpS6 immunoreactivity occurring as early as 15 min after the onset of HFS in dendritic spine heads at synaptic sites receiving HFS. Concurrently, levels of the rpS6 protein rapidly declined in somata of granule cells, as determined using immunofluorescence microscopy. These results suggest that the translational machinery is rapidly targeted to activated spines and that this targeting mechanism may contribute to the establishment of L-LTP. PMID:26432888

  4. 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.

  5. 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.

  6. In Vivo Zinc Finger Nuclease-mediated Targeted Integration of a Glucose-6-phosphatase Transgene Promotes Survival in Mice With Glycogen Storage Disease Type IA.

    PubMed

    Landau, Dustin J; Brooks, Elizabeth Drake; Perez-Pinera, Pablo; Amarasekara, Hiruni; Mefferd, Adam; Li, Songtao; Bird, Andrew; Gersbach, Charles A; Koeberl, Dwight D

    2016-04-01

    Glycogen storage disease type Ia (GSD Ia) is caused by glucose-6-phosphatase (G6Pase) deficiency in association with severe, life-threatening hypoglycemia that necessitates lifelong dietary therapy. Here we show that use of a zinc-finger nuclease (ZFN) targeted to the ROSA26 safe harbor locus and a ROSA26-targeting vector containing a G6PC donor transgene, both delivered with adeno-associated virus (AAV) vectors, markedly improved survival of G6Pase knockout (G6Pase-KO) mice compared with mice receiving the donor vector alone (P < 0.04). Furthermore, transgene integration has been confirmed by sequencing in the majority of the mice treated with both vectors. Targeted alleles were 4.6-fold more common in livers of mice with GSD Ia, as compared with normal littermates, at 8 months following vector administration (P < 0.02). This suggests a selective advantage for vector-transduced hepatocytes following ZFN-mediated integration of the G6Pase vector. A short-term experiment also showed that 3-month-old mice receiving the ZFN had significantly-improved biochemical correction, in comparison with mice that received the donor vector alone. These data suggest that the use of ZFNs to drive integration of G6Pase at a safe harbor locus might improve vector persistence and efficacy, and lower mortality in GSD Ia.

  7. Mass separation of deuterium and helium with conventional quadrupole mass spectrometer by using varied ionization energy

    NASA Astrophysics Data System (ADS)

    Yu, Yaowei; Hu, Jiansheng; Wan, Zhao; Wu, Jinhua; Wang, Houyin; Cao, Bin

    2016-03-01

    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 × 10-6-5.0 × 10-2 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 (PD2) and helium partial pressure (PHe) could be obtained. The result shows that deuterium partial pressure could be measured if PD2 > 10-6 Pa (limited by ultimate pressure of calibration vessel), and helium pressure could be measured only if PHe/PD2 > 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.

  8. Mass separation of deuterium and helium with conventional quadrupole mass spectrometer by using varied ionization energy.

    PubMed

    Yu, Yaowei; Hu, Jiansheng; Wan, Zhao; Wu, Jinhua; Wang, Houyin; Cao, Bin

    2016-03-01

    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(-6)-5.0 × 10(-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(D2)) and helium partial pressure (P(He)) could be obtained. The result shows that deuterium partial pressure could be measured if P(D2) > 10(-6) Pa (limited by ultimate pressure of calibration vessel), and helium pressure could be measured only if P(He)/P(D2) > 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.

  9. 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.

  10. The Astro-E2/XRS-2 helium insert system

    NASA Astrophysics Data System (ADS)

    Shirron, P. J.; DiPirro, M. J.; Panek, J.; Kelley, R.; Mitsuda, K.; Fujimoto, R.; Hirabayashi, M.; McCammon, D.

    2006-04-01

    The X-ray Spectrometer (XRS-2) instrument on the Japanese Space Agency (JAXA) Astro-E2 spacecraft will measure faint X-ray emissions in the energy range of 0.2-10 keV. A square array of 32 X-ray microcalorimeters used will be able to distinguish individual photons to better than 10 eV at 6 keV, with a quantum efficiency near 100%. The detectors are cooled to 60 mK by means of an adiabatic demagnetization refrigerator (ADR). The ADR rejects heat to a 1.3 K superfluid helium tank, which is surrounded by a 17 K solid neon tank. A Stirling cycle cryocooler precools an outer shield around the neon tank. This system will provide an estimated 3 years of on-orbit lifetime. This paper describes the helium insert, the ADR, the high temperature superconducting leads, and early on-orbit performance.

  11. A GM cryocooler with cold helium circulation for remote cooling

    NASA Astrophysics Data System (ADS)

    Wang, Chao; Brown, Ethan

    2014-01-01

    A GM cryocooler with new cold helium circulation system has been developed at Cryomech. A set of check valves connects to the cold heat exchanger to convert a small portion of AC oscillating flow in the cold head to a DC gas flow for circulating cold helium in the remote loop. A cold finger, which is used for remote cooling, is connected to the check valves through a pair of 5 m long vacuum insulated flexible lines. The GM cryocooler, Cryomech model AL125 having 120 W at 80 K, is employed in the testing. The cold finger can provide 50 W at 81 K for the power input of 4.1 kW and 70.5 W at 81.8 K for the power input of 6 kW. This simple and low cost design is very attractive for some applications in the near future.

  12. Novel methods to create multielectron bubbles in superfluid helium

    NASA Astrophysics Data System (ADS)

    Fang, J.; Dementyev, Anatoly E.; Tempere, J.; Silvera, Isaac F.

    2011-03-01

    An equilibrium multielectron bubble (MEB) in liquid helium is a fascinating object with a spherical two-dimensional electron gas on its surface. We discuss two ways in which they have been created. For MEBs that have been observed in the dome of a cylindrical cell with an unexpectedly short lifetime, we show analytically why these MEBs can discharge by tunneling. Using a novel method, MEBs have been extracted from a vapor sheath around a hot filament in superfluid helium by applying electric fields up to 15 kV/cm, and photographed with high-speed video. Charges as high as 1.6×10-9 C (˜1010 electrons) have been measured. The latter method provides a means of capture in an electromagnetic trap to allow the study of the extensive exciting properties of these elusive objects.

  13. Experimental investigation of the heat transfer characteristics of a helium cryogenic thermosyphon

    NASA Astrophysics Data System (ADS)

    Long, Z. Q.; Zhang, P.

    2013-10-01

    The heat transfer performance of a cryogenic thermosyphon filled with helium as the working fluid is investigated experimentally with a G-M cryocooler as the heat sink in this study. The cryogenic thermosyphon acts as a thermal link between the cryocooler and the cooled target (the copper evaporator with a large mass). Helium is charged in different filling ratios, and the cooling down process and the heat transfer characteristics of the cryogenic thermosyphon are investigated. The cooling down process of the cooled target can be significantly accelerated by the presence of helium in the cryogenic thermosyphon and the cooling down period can be further shortened by the increase of filling ratio. The heat transfer mode changes from the liquid-vapor phase change to natural convection as the increase of the heating power applied on the evaporator. The heat transfer limit and thermal resistance are discussed for the liquid-vapor phase change heat transfer, and they can be estimated by empirical correlations. For the natural convection heat transfer, it can be enhanced by increasing the filling ratio, and the natural convection of supercritical helium is much stronger than that of gaseous helium.

  14. 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.

  15. Quantification of the In Vitro Radiosensitivity of Mung Bean Sprout Elongation to 6MV X-Ray: A Revised Target Model Study

    PubMed Central

    Wang, Tzu Hwei; Kittipayak, Samrit; Lin, Yu Ting; Lin, Cheng Hsun; Pan, Lung Kwang

    2015-01-01

    In this study, a revised target model for quantifying the in vitro radiosensitivity of mung bean sprout elongation to 6-MV X-rays was developed. The revised target model, which incorporated the Poisson prediction for a low probability of success, provided theoretical estimates that were highly consistent with the actual data measured in this study. The revised target model correlated different in vitro radiosensitivities to various effective target volumes and was successfully confirmed by exposing mung beans in various elongation states to various doses of 6-MV X-rays. For the experiment, 5,000 fresh mung beans were randomly distributed into 100 petri dishes, which were randomly divided into ten groups. Each group received an initial watering at a different time point prior to X-ray exposure, resulting in different effective target volumes. The bean sprouts were measured 70 hr after X-ray exposure, and the average length of the bean sprouts in each group was recorded as an index of the mung bean in vitro radiosensitivity. Mung beans that received an initial watering either six or sixteen hours before X-ray exposure had the shortest sprout length, indicating that the maximum effective target volume was formed within that specific time period. The revised target model could be also expanded to interpret the “two-hit” model of target theory, although the experimental data supported the “one-hit” model. If the “two-hit” model was sustained, theoretically, the target size would be 2.14 times larger than its original size to produce the same results. PMID:26053016

  16. MD-2 as the target of a novel small molecule, L6H21, in the attenuation of LPS-induced inflammatory response and sepsis

    PubMed Central

    Wang, Yi; Shan, Xiaoou; Chen, Gaozhi; Jiang, Lili; Wang, Zhe; Fang, Qilu; Liu, Xing; Wang, Jingying; Zhang, Yali; Wu, Wencan; Liang, Guang

    2015-01-01

    Background and Purpose Myeloid differentiation 2 (MD-2) recognizes LPS, which is required for TLR4 activation, and represents an attractive therapeutic target for severe inflammatory disorders. We previously found that a chalcone derivative, L6H21, could inhibit LPS-induced overexpression of TNF-α and IL-6 in macrophages. Here, we performed a series of biochemical experiments to investigate whether L6H21 specifically targets MD-2 and inhibits the interaction and signalling transduction of LPS-TLR4/MD-2. Experimental Approach The binding affinity of L6H21 to MD-2 protein was analysed using computer docking, surface plasmon resonance analysis, elisa, fluorescence measurements and flow cytometric analysis. The effects of L6H21 on MAPK and NF-κB signalling were determined using EMSA, fluorescence staining, Western blotting and immunoprecipitation. The anti-inflammatory effects of L6H21 were confirmed using elisa and RT-qPCR in vitro. The anti-inflammatory effects of L6H21 were also evaluated in septic C57BL/6 mice. Key Results Compound L6H21 inserted into the hydrophobic region of the MD-2 pocket, forming hydrogen bonds with Arg90 and Tyr102 in the MD-2 pocket. In vitro, L6H21 subsequently suppressed MAPK phosphorylation, NF-κB activation and cytokine expression in macrophages stimulated by LPS. In vivo, L6H21 pretreatment improved survival, prevented lung injury, decreased serum and hepatic cytokine levels in mice subjected to LPS. In addition, mice with MD-2 gene knockout were universally protected from the effects of LPS-induced septic shock. Conclusions and Implications Overall, this work demonstrated that the new chalcone derivative, L6H21, is a potential candidate for the treatment of sepsis. More importantly, the data confirmed that MD-2 is an important therapeutic target for inflammatory disorders. PMID:26076332

  17. Anomalously high retention of radiogenic helium in native platinum

    NASA Astrophysics Data System (ADS)

    Yakubovich, O. V.; Shukolyukov, Yu. A.; Mochalov, A. G.; Kotov, A. B.; Korneev, S. I.

    2012-04-01

    Relatively quick migration of helium from crystal structures has been known for a long time. However there is a group of minerals - native metals - where stability of radiogenic helium is essentially high [1]. Helium, due to its very low solubility in metals, assembles in atomic clusters - "bubbles" of nanometer size. Migration of helium "bubbles" as a whole from the crystal structures needs relatively high temperature near the melting point of metals. On that ground of special interest are platinoids with melting points (and, consequently, temperatures of "explosion-like" release of radiogenic helium) of more than 1550 oC In this respect we believe that the method based on natural radioactivity of platinum is promising. To verify the idea of anomalously high retention of radiogenic helium in native platinum and to check the efficiency of the proposed 190Pt-4He method of isotope geochronology, we studied independent mineral aggregates of native platinum from chromite-bearing dunites of Galmoenan plutonic complex (10 individual samples) (Koryak-Kamchatka belt, Russia) and Konder massif (5 individual samples) (Khabarovsk district,Russia). Because native platinum always has admixture of Fe, Cu etc. for reliable determination of concentration of platinum in the samples in our study we used electron microscope JSM-6510LA with JED 2200 add-on. Amount of 4He in native platinum was determinate on mass-spectrometer complex MSU-G-01-M. Native platinum consists of 6 isotopes. Among them two isotopes are α-radioactive and decay according to following schemes: 190Pt →4He+186Os→4He+182W 192Pt →4He+188Os Presumably, in native platinum there is always a certain amount of uranium and thorium, absorbed in the process of crystallization. However influence of helium generation from uranium becomes more marked at growing of 238U/Pt ratio and beginning with 238U/Pt ≈ 10-5 should be taken into consideration. For the same reason helium produced by the decay of 192Pt and 186Os can

  18. 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...

  19. 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...

  20. 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...

  1. 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...

  2. Understanding temporal and spatial variability of the lunar helium atmosphere using simultaneous observations from LRO, LADEE, and ARTEMIS

    NASA Astrophysics Data System (ADS)

    Hurley, Dana M.; Cook, Jason C.; Benna, Mehdi; Halekas, Jasper S.; Feldman, Paul D.; Retherford, Kurt D.; Hodges, R. Richard; Grava, Cesare; Mahaffy, Paul; Gladstone, G. Randall; Greathouse, Thomas; Kaufmann, David E.; Elphic, Richard C.; Stern, S. Alan

    2016-07-01

    Simultaneous measurements of helium in the exosphere of the Moon are made from the Lunar Reconnaissance Orbiter (LRO) Lyman Alpha Mapping Project (LAMP) and the Lunar Atmosphere and Dust Environment Explorer (LADEE) Neutral Mass Spectrometer (NMS) through the entire 5-month span of the LADEE mission. In addition, the ARTEMIS mission monitored the solar wind alpha particle flux to the Moon. Modeling the lunar helium exosphere, we relate the LAMP polar observations to the LADEE equatorial observations. Further, using the ARTEMIS alpha flux in the Monte Carlo model reproduces the temporal variations in helium density. Comparing the LAMP data to the LADEE data shows excellent agreement. Comparing those with the ARTEMIS data reveals that the solar wind alpha flux is the primary driver to variability in the helium exosphere throughout the LADEE mission. Using a decay time for exospheric helium of 5 days, we determine that the solar wind contributes 64 ± 5% of the helium to the lunar exosphere. The remaining 36 ± 5% is presumed to come from outgassing of radiogenic helium from the interior of the Moon. Furthermore, the model reproduces the measurements if 63 ± 6% of the incident alpha particles are converted to thermalized helium atoms through the interaction between the alphas and the lunar surface. However, these values are dependent on both inferred source rates from LAMP and LADEE observations and on the assumed time constant of the exospheric decay rate.

  3. Photoionization Energies and Oscillator Strengths of Helium and Helium-like Ions

    NASA Astrophysics Data System (ADS)

    Faye, N. A. B.; Ndao, A. S.; Konte, A.; Biaye, M.; Wague, A.

    2005-10-01

    We first studied the resonant photoionization of helium-like ions, such as C4+, N5+, and O6+, and determined the wave functions, the excitation energies, and the partial and total widths of the autoionizing states of these ions lying under the n = 3 thresholds of the residual ion. For more detailed analysis of the theory, and a better comprehension of the internal dynamics of atomic resonances and electronic phenomena of correlation, we extended these calculations to other helium-like ions, under higher thresholds (n = 4 and 5) of the hydrogen ions H-, and of Li+, C4+, N5+, and O6+. We were also interested in oscillator strengths. These parameters are important for interpreting the spectra and diagnosing astrophysical and laboratory plasmas, as well as for analyzing the spectra coming from space and determining the composition and relative abundance from the various elements of the stellar and interstellar environment. We sought a better comprehension of the coupling between autoionizing and continuum states and of the phenomena of electronic correlations. We used the method of diagonalization that has been used below the n = 2 threshold of the residual ion. The results are important for astrophysicists and physicists studying matter-radiation interaction and for the invention of new laser systems. We also measured laser-induced chlorophyll fluorescence (LICF) emission spectra of the leaves of some tropical plants using a compact fiber-optic fluorosensor with a continuous-wave violet diode laser as the exciting source and an integrated digital spectrometer to analyze the state of stress of the plants.

  4. Calculated Regenerator Performance at 4 K with HELIUM-4 and HELIUM-3

    NASA Astrophysics Data System (ADS)

    Radebaugh, Ray; Huang, Yonghua; O'Gallagher, Agnes; Gary, John

    2008-03-01

    The helium-4 working fluid in regenerative cryocoolers operating with the cold end near 4 K deviates considerably from an ideal gas. As a result, losses in the regenerator, given by the time-averaged enthalpy flux, are increased and are strong functions of the operating pressure and temperature. Helium-3, with its lower boiling point, behaves somewhat closer to an ideal gas in this low temperature range and can reduce the losses in 4 K regenerators. An analytical model is used to find the fluid properties that strongly influence the regenerator losses as well as the gross refrigeration power. The thermodynamic and transport properties of helium-3 were incorporated into the latest NIST regenerator numerical model, known as REGEN3.3, which was used to model regenerator performance with either helium-4 or helium-3. With this model we show how the use of helium-3 in place of helium-4 can improve the performance of 4 K regenerative cryocoolers. The effects of operating pressure, warm-end temperature, and frequency on regenerators with helium-4 and helium-3 are investigated and compared. The results are used to find optimum operating conditions. The frequency range investigated varies from 1 Hz to 30 Hz, with particular emphasis on higher frequencies.

  5. Efficient laser-induced 6-8 keV x-ray production from iron oxide aerogel and foil-lined cavity targets

    SciTech Connect

    Perez, F.; Kay, J. J.; Patterson, J. R.; Kane, J.; May, M.; Emig, J.; Colvin, J.; Gammon, S.; Satcher, J. H. Jr.; Fournier, K. B.; Villette, B.; Girard, F.; Reverdin, C.; Sorce, C.; Jaquez, J.

    2012-08-15

    The performance of new iron-based laser-driven x-ray sources has been tested at the OMEGA laser facility for production of x rays in the 6.5-8.5 keV range. Two types of targets were experimentally investigated: low-density iron oxide aerogels (density 6-16 mg/cm{sup 3}) and stainless steel foil-lined cavity targets (steel thickness 1-5 {mu}m). The targets were irradiated by 40 beams of the OMEGA laser (500 J/beam, 1 ns pulse, wavelength 351 nm). All targets showed good coupling with the laser, with <5% of the incident laser light backscattered by the resulting plasma in all cases (typically <2.5%). The aerogel targets produced T{sub e}=2 to 3 keV, n{sub e}=0.12-0.2 critical density plasmas yielding a 40%-60% laser-to-x-ray total conversion efficiency (CE) (1.2%-3% in the Fe K-shell range). The foil cavity targets produced T{sub e}{approx} 2 keV, n{sub e}{approx} 0.15 critical density plasmas yielding a 60%-75% conversion efficiency (1.6%-2.2% in the Fe K-shell range). Time-resolved images illustrate that the volumetric heating of low-density aerogels allow them to emit a higher K-shell x-ray yield even though they contain fewer Fe atoms. However, their challenging fabrication process leads to a larger shot-to-shot variation than cavity targets.

  6. Helium Dilution Cryocooler for Space Applications

    NASA Technical Reports Server (NTRS)

    Roach, Pat; Hogan, Robert (Technical Monitor)

    2001-01-01

    NASA's New Millenium Program Space Technology presents the Helium Dilution Cryocooler for Space Applications. The topics include: 1) Capability; 2) Applications; and 3) Advantages. This paper is in viewgraph form.

  7. Helium and Enhanced Image of the Sun

    NASA Video Gallery

    This video blinks between an image in Helium and an enhanced image. The original image is from AIA on SDO and the enhanced image was created at the LM Solar and Astrophysics Laboratory (LMSAL) by D...

  8. Helium Find Thaws the Cold Fusion Trail.

    ERIC Educational Resources Information Center

    Pennisi, E.

    1991-01-01

    Reported is a study of cold fusion in which trace amounts of helium, possible evidence of an actual fusion reaction, were found. Research methodology is detailed. The controversy over the validity of experimental results with cold fusion are reviewed. (CW)

  9. Commissioning of a new helium pipeline

    NASA Technical Reports Server (NTRS)

    2000-01-01

    Center Director Roy Bridges addresses the audience at the commissioning of a new high-pressure helium pipeline at Kennedy Space Center that will service launch needs at the new Delta IV Complex 37 at Cape Canaveral Air Force Station. The nine-mile- long buried pipeline will also serve as a backup helium resource for Shuttle launches. Nearly one launch's worth of helium will be available in the pipeline to support a Shuttle pad in an emergency. The line originates at the Helium Facility on KSC and terminates in a meter station at the perimeter of the Delta IV launch pad. Others at the ceremony were Jerry Jorgensen, pipeline project manager, Space Gateway Support (SGS); Col. Samuel Dick, representative of the 45th Space Wing; Ramon Lugo, acting executive director, JPMO; David Herst, director, Delta IV Launch Sites; Pierre Dufour, president and CEO, Air Liquide America Corporation; and Michael Butchko, president, SGS.

  10. Commissioning of a new helium pipeline

    NASA Technical Reports Server (NTRS)

    2000-01-01

    Jerry Jorgensen welcomes the audience to the commissioning of a new high-pressure helium pipeline at Kennedy Space Center. Jorgensen, with Space Gateway Support (SGS), is the pipeline project manager. To the right is Ramon Lugo, acting executive director, JPMO. Others at the ceremony were Center Director Roy Bridges; Col. Samuel Dick, representative of the 45th Space Wing; David Herst, director, Delta IV Launch Sites; Pierre Dufour, president and CEO, Air Liquide America Corporation; and Michael Butchko, president, SGS. The pipeline will service launch needs at the new Delta IV Complex 37 at Cape Canaveral Air Force Station. The nine-mile-long buried pipeline will also serve as a backup helium resource for Shuttle launches. Nearly one launch's worth of helium will be available in the pipeline to support a Shuttle pad in an emergency. The line originates at the Helium Facility on KSC and terminates in a meter station at the perimeter of the Delta IV launch pad.

  11. Commissioning of a new helium pipeline

    NASA Technical Reports Server (NTRS)

    2000-01-01

    At the commissioning of a new high-pressure helium pipeline at Kennedy Space Center, Ramon Lugo, acting executive director, JPMO , presents a plaque to Center Director Roy Bridges. The pipeline will service launch needs at the new Delta IV Complex 37 at Cape Canaveral Air Force Station. Others at the ceremony were Jerry Jorgensen, pipeline project manager, Space Gateway Support (SGS); Col. Samuel Dick, representative of the 45th Space Wing; David Herst, director, Delta IV Launch Sites; Pierre Dufour, president and CEO, Air Liquide America Corporation; and Michael Butchko, president, SGS. The nine-mile-long buried pipeline will also serve as a backup helium resource for Shuttle launches. Nearly one launch's worth of helium will be available in the pipeline to support a Shuttle pad in an emergency. The line originates at the Helium Facility on KSC and terminates in a meter station at the perimeter of the Delta IV launch pad.

  12. Development of charcoal sorbents for helium cryopumping

    SciTech Connect

    Sedgley, D.W.; Tobin, A.G.

    1984-01-01

    Testing of the cryogenically cooled charcoal using fusion-compatible binders for pumping helium has shown promising results. The program demonstrated comparable or improved performance with these binders compared to the charcoal (type and size) using an epoxy binder.

  13. Cryptolepine derivative-6h inhibits liver fibrosis in TGF-β1-induced HSC-T6 cells by targeting the Shh pathway.

    PubMed

    He, Ying-Hua; Li, Zeng; Ni, Ming-Ming; Zhang, Xing-Yan; Li, Ming-Fang; Meng, Xiao-Ming; Huang, Cheng; Li, Jun

    2016-09-01

    Liver fibrosis is a worldwide problem with a significant morbidity and mortality. Cryptolepis sanguinolenta (family Periplocaceae) is widely used in West African countries for the treatment of malaria, as well as for some other diseases. However, the role of C. sanguinolenta in hepatic fibrosis is still unknown. It has been reported that Methyl-CpG binding protein 2 (MeCP2) had a high expression in liver fibrosis and played a central role in its pathobiology. Interestingly, we found that a cryptolepine derivative (HZ-6h) could inhibit liver fibrosis by reducing MeCP2 expression, as evidenced by the dramatic downregulation of α-smooth muscle actin (α-SMA) and type I collagen alpha-1 (Col1α1) in protein levels in vitro. Meanwhile, we also found that HZ-6h could reduce the cell viability and promote apoptosis of hepatic stellate cells (HSCs) treated with transforming growth factor beta 1(TGF-β1). Then, we investigated the potential molecular mechanisms and found that HZ-6h blocked Shh signaling in HSC-T6 cells, resulting in the decreased protein expression of Patched-1 (PTCH-1), Sonic hedgehog (Shh), and glioma-associated oncogene homolog 1 (GLI1). In short, these results indicate that HZ-6h inhibits liver fibrosis by downregulating MeCP2 through the Shh pathway in TGF-β1-induced HSC-T6 cells. PMID:27295431

  14. CD44v6 Monoclonal Antibody-Conjugated Gold Nanostars for Targeted Photoacoustic Imaging and Plasmonic Photothermal Therapy of Gastric Cancer Stem-like Cells

    PubMed Central

    Liang, Shujing; Li, Chao; Zhang, Chunlei; Chen, Yunsheng; Xu, Liang; Bao, Chenchen; Wang, Xiaoyong; liu, Gang; zhang, Fengchun; Cui, Daxiang

    2015-01-01

    Developing safe and effective nanoprobes for targeted imaging and selective therapy of gastric cancer stem cells (GCSCs) has become one of the most promising anticancer strategies. Herein, gold nanostars-based PEGylated multifunctional nanoprobes were prepared with conjugated CD44v6 monoclonal antibodies (CD44v6-GNS) as the targeting ligands. It was observed that the prepared nanoprobes had high affinity towards GCSC spheroid colonies and destroyed them completely with a low power density upon near-infrared (NIR) laser treatment (790 nm, 1.5 W/cm2, 5 min) in vitro experiment. Orthotopic and subcutaneous xenografted nude mice models of human gastric cancer were established. Subsequently, biodistribution and photothermal therapeutic effects after being intravenously injected with the prepared nanoprobes were assessed. Photoacoustic imaging revealed that CD44v6-GNS nanoprobes could target the gastric cancer vascular system actively at 4 h post-injection, while the probes inhibited tumor growth remarkably upon NIR laser irradiation, and even extended survivability of the gastric cancer-bearing mice. The CD44v6-GNS nanoprobes exhibited great potential for applications of gastric cancer targeted imaging and photothermal therapy in the near future. PMID:26155313

  15. CD44v6 Monoclonal Antibody-Conjugated Gold Nanostars for Targeted Photoacoustic Imaging and Plasmonic Photothermal Therapy of Gastric Cancer Stem-like Cells.

    PubMed

    Liang, Shujing; Li, Chao; Zhang, Chunlei; Chen, Yunsheng; Xu, Liang; Bao, Chenchen; Wang, Xiaoyong; Liu, Gang; Zhang, Fengchun; Cui, Daxiang

    2015-01-01

    Developing safe and effective nanoprobes for targeted imaging and selective therapy of gastric cancer stem cells (GCSCs) has become one of the most promising anticancer strategies. Herein, gold nanostars-based PEGylated multifunctional nanoprobes were prepared with conjugated CD44v6 monoclonal antibodies (CD44v6-GNS) as the targeting ligands. It was observed that the prepared nanoprobes had high affinity towards GCSC spheroid colonies and destroyed them completely with a low power density upon near-infrared (NIR) laser treatment (790 nm, 1.5 W/cm(2), 5 min) in vitro experiment. Orthotopic and subcutaneous xenografted nude mice models of human gastric cancer were established. Subsequently, biodistribution and photothermal therapeutic effects after being intravenously injected with the prepared nanoprobes were assessed. Photoacoustic imaging revealed that CD44v6-GNS nanoprobes could target the gastric cancer vascular system actively at 4 h post-injection, while the probes inhibited tumor growth remarkably upon NIR laser irradiation, and even extended survivability of the gastric cancer-bearing mice. The CD44v6-GNS nanoprobes exhibited great potential for applications of gastric cancer targeted imaging and photothermal therapy in the near future. PMID:26155313

  16. Cosmogenic helium in a terrestrial igneous rock

    NASA Technical Reports Server (NTRS)

    Kurz, M. D.

    1986-01-01

    New helium isotopic measurements on samples from the Kula formation of Haleakala volcano of Hawaii are presented that are best explained by an in situ cosmogenic origin for a significant fraction of the He-3. Results from crushing and stepwise heating experiments, and consideration of the exposure age of the sample at the surface and the cosmic ray fluxes strongly support this hypothesis. Although crustal cosmogenic helium has been proposed previously, this represents its first unambiguous identification in a terrestrial sample.

  17. Trace organic impurities in gaseous helium

    NASA Technical Reports Server (NTRS)

    Schehl, T. A.

    1973-01-01

    A program to determine trace organic impurities present in helium has been initiated. The impurities were concentrated in a cryogenic trap to permit detection and identification by a gas chromatographic-mass spectrometric technique. Gaseous helium (GHe) exhibited 63 GC flame ionization response peaks. Relative GC peak heights and identifications of 25 major impurities by their mass spectra are given. As an aid to further investigation, identities are proposed for 16 other components, and their mass spectra are given.

  18. Diffusion of helium isotopes in silicate glasses and minerals: Implications for petrogenesis and geochronology. Doctoral thesis

    SciTech Connect

    Trull, T.W.

    1989-06-01

    Helium diffusivities in basaltic glasses at seafloor temperatures are about 10 to the -16th power sq cm/s suggesting only very low concentration samples will be compromised, and that U/He geochronology of submarine basalts may be feasible. Helium diffusivities at magmatic temperatures are 10 to the -11th power, to 10 to the -8th power sq cm/s in silicate minerals, too low to regionally homogenize helium in the mantle. Helium exchange rates limit xenolith origin depths and transport times. Faster He diffusion in pyroxene than olivine allows diffusive loss to be evaluated. Diffusivities of {sup 3}He produced by cosmic rays in surface rocks are less than 10 to the -20th power sq cm/s in olivine and quartz, suggesting exposure dating will not be limited by helium loss for ages up to 10,000,000 years. Similar conclusions were found for U/{sup 4}He dating of quartz. Part of the {sup 3}He/{sup 4}He variability (.01 to 9 R{sub a}) of island arc basalts from the western Pacific reflects post-eruptive helium addition. In unaltered samples, Kavachi submarine volcano has different {sup 3}He/{sup 4}He (6.9 + or - .2 R{sub a}) than the Woodlark Spreading Center (8-9 R{sub a}). A contribution from subducted Pacific lithosphere may explain this and 87 Sr/86 Sr variations.

  19. A comparison of neon versus helium ion beam induced deposition via Monte Carlo simulations.

    PubMed

    Timilsina, Rajendra; Smith, Daryl A; Rack, Philip D

    2013-03-22

    The ion beam induced nanoscale synthesis of PtCx (where x ∼ 5) using the trimethyl (methylcyclopentadienyl)platinum(IV) (MeCpPt(IV)Me3) precursor is investigated by performing Monte Carlo simulations of helium and neon ions. The helium beam leads to more lateral growth relative to the neon beam because of its larger interaction volume. The lateral growth of the nanopillars is dominated by molecules deposited via secondary electrons in both the simulations. Notably, the helium pillars are dominated by SE-I electrons whereas the neon pillars are dominated by SE-II electrons. Using a low precursor residence time of 70 μs, resulting in an equilibrium coverage of ∼4%, the neon simulation has a lower deposition efficiency (3.5%) compared to that of the helium simulation (6.5%). At larger residence time (10 ms) and consequently larger equilibrium coverage (85%) the deposition efficiencies of helium and neon increased to 49% and 21%, respectively; which is dominated by increased lateral growth rates leading to broader pillars. The nanoscale growth is further studied by varying the ion beam diameter at 10 ms precursor residence time. The study shows that total SE yield decreases with increasing beam diameters for both the ion types. However, helium has the larger SE yield as compared to that of neon in both the low and high precursor residence time, and thus pillars are wider in all the simulations studied.

  20. Mathematical modeling of a Fermilab helium liquefier coldbox

    SciTech Connect

    Geynisman, M.G.; Walker, R.J.

    1995-12-01

    Fermilab Central Helium Liquefier (CHL) facility is operated 24 hours-a-day to supply 4.6{degrees}K for the Fermilab Tevatron superconducting proton-antiproton collider Ring and to recover warm return gases. The centerpieces of the CHL are two independent cold boxes rated at 4000 and 5400 liters/hour with LN{sub 2} precool. These coldboxes are Claude cycle and have identical heat exchangers trains, but different turbo-expanders. The Tevatron cryogenics demand for higher helium supply from CHL was the driving force to investigate an installation of an expansion engine in place of the Joule-Thompson valve. A mathematical model was developed to describe the thermo- and gas-dynamic processes for the equipment included in the helium coldbox. The model is based on a finite element approach, opposite to a global variables approach, thus providing for higher accuracy and conversion stability. Though the coefficients used in thermo- and gas-dynamic equations are unique for a given coldbox, the general approach, the equations, the methods of computations, and most of the subroutines written in FORTRAN can be readily applied to different coldboxes. The simulation results are compared against actual operating data to demonstrate applicability of the model.

  1. Helium-neon laser improves skin repair in rabbits.

    PubMed

    Peccin, Maria Stella; Renno, Ana Claudia Muniz; de Oliveira, Flavia; Giusti, Paulo Ricardo; Ribeiro, Daniel Araki

    2012-12-01

    The purpose of this study was to evaluate the influence of helium-neon laser on skin injury in rabbits. For this purpose, 15 New Zealand rabbits underwent bilateral skin damage in leg. Helium-neon laser light, at a fluence of 6 J∕cm2 and wavelength of 632.8 nm, was applied on the left legs (laser group). The right leg lesions (control group) served as negative control. All sections were histopathologically analyzed using HE sections. The results showed little infiltration of inflammatory cells, with proliferation of fibroblasts forming a few fibrous connective tissue after 1 week post-injury. The lesion on the 3rd week was characterized by granulation tissue, which formed from proliferated fibrous connective tissue, congested blood vessels and mild mononuclear cell infiltration. On the 5th week, it was observed that debris material surrounded by a thick layer of connective tissue and dense collage, fibroblasts cells present in the dermis covered by a thick epidermal layer represented by keratinized epithelium. Taken together, our results suggest that helium-neon laser is able to improve skin repair in rabbits at early phases of recovery. PMID:23057697

  2. NMR Studies of Quantum Tunneling in Monolayers of Helium Three

    NASA Astrophysics Data System (ADS)

    Parks, Charles; Stachowiak, Piotr; Sullivan, Neil

    2002-03-01

    The results of NMR studies of the nuclear spin-spin relaxation are reported for commensurate monolayers of helium three adsorbed on hexagonal boron nitride. The measurements were made using pulsed NMR techniques for low temperatures, 0.01 < T < 5.0 K, and for moderately high magnetic fields (up to 6 T). The relaxation rate is independent of temperature at low temperatures, 0.12 < T < 0.85 K, and this behavior is interpreted in terms of particle-particle exchange motions of the adsorbed helium atoms. The effective exchange rates were observed to change significantly on replacing a fraction of the helium atoms with relatively immobile neon atoms. This is understood if there is a significant 3-particle exchange in addition to 2-particle exchange. The analyses of the experimental results indicate that the 3-spin exchange term in the exchange Hamiltonian is of opposite sign to that of the 2-spin exchange and also has a larger amplitude. At high temperatures, 0.8 < T < 5.0 K, an exponential temperature dependence of the rate is observed that is attributed to the thermal activation of vacancies.

  3. Helium-neon laser improves skin repair in rabbits.

    PubMed

    Peccin, Maria Stella; Renno, Ana Claudia Muniz; de Oliveira, Flavia; Giusti, Paulo Ricardo; Ribeiro, Daniel Araki

    2012-12-01

    The purpose of this study was to evaluate the influence of helium-neon laser on skin injury in rabbits. For this purpose, 15 New Zealand rabbits underwent bilateral skin damage in leg. Helium-neon laser light, at a fluence of 6 J∕cm2 and wavelength of 632.8 nm, was applied on the left legs (laser group). The right leg lesions (control group) served as negative control. All sections were histopathologically analyzed using HE sections. The results showed little infiltration of inflammatory cells, with proliferation of fibroblasts forming a few fibrous connective tissue after 1 week post-injury. The lesion on the 3rd week was characterized by granulation tissue, which formed from proliferated fibrous connective tissue, congested blood vessels and mild mononuclear cell infiltration. On the 5th week, it was observed that debris material surrounded by a thick layer of connective tissue and dense collage, fibroblasts cells present in the dermis covered by a thick epidermal layer represented by keratinized epithelium. Taken together, our results suggest that helium-neon laser is able to improve skin repair in rabbits at early phases of recovery.

  4. 6-Br-5methylindirubin-3'oxime (5-Me-6-BIO) targeting the leishmanial glycogen synthase kinase-3 (GSK-3) short form affects cell-cycle progression and induces apoptosis-like death: exploitation of GSK-3 for treating leishmaniasis.

    PubMed

    Xingi, Evangelia; Smirlis, Despina; Myrianthopoulos, Vassilios; Magiatis, Prokopios; Grant, Karen M; Meijer, Laurent; Mikros, Emmanuel; Skaltsounis, Alexios-Leandros; Soteriadou, Ketty

    2009-10-01

    Indirubins known to target mammalian cyclin-dependent kinases (CDKs) and glycogen synthase kinase (GSK-3) were tested for their antileishmanial activity. 6-Br-indirubin-3'-oxime (6-BIO), 6-Br-indirubin-3'acetoxime and 6-Br-5methylindirubin-3'oxime (5-Me-6-BIO) were the most potent inhibitors of Leishmania donovani promastigote and amastigote growth (half maximal inhibitory concentration (IC(50)) values < or =1.2 microM). Since the 6-Br substitution on the indirubin backbone greatly enhances the selectivity for mammalian GSK-3 over CDKs, we identified the leishmanial GSK-3 homologues, a short (LdGSK-3s) and a long one, focusing on LdGSK-3s which is closer to human GSK-3beta, for further studies. Kinase assays showed that 5-Me-6-BIO inhibited LdGSK-3s more potently than CRK3 (the CDK1 homologue in Leishmania), whilst 6-BIO was more selective for CRK3. Promastigotes treated with 5-Me-6-BIO accumulated in the S and G2/M cell-cycle phases and underwent apoptosis-like death. Interestingly, these phenotypes were completely reversed in parasites over-expressing LdGSK-3s. This finding strongly supports that LdGSK-3s is: (i) the intracellular target of 5-Me-6-BIO, and (ii) involved in cell-cycle control and in pathways leading to apoptosis-like death. 6-BIO treatment induced a G2/M arrest, consistent with inhibition of CRK3 and apoptosis-like death. These effects were partially reversed in parasites over-expressing LdGSK-3s suggesting that in vivo 6-BIO may also target LdGSK-3s. Molecular docking of 5-Me-6-BIO in CRK3 and 6-BIO in human GSK-3beta and LdGSK-3s active sites predict the existence of functional/structural differences that are sufficient to explain the observed difference in their affinity. In conclusion, LdGSK-3s is validated as a potential drug target in Leishmania and could be exploited for the development of selective indirubin-based leishmanicidals. PMID:19445946

  5. High efficiency pump for space helium transfer

    NASA Technical Reports Server (NTRS)

    Hasenbein, Robert; Izenson, Michael G.; Swift, Walter L.; Sixsmith, Herbert

    1991-01-01

    A centrifugal pump was developed for the efficient and reliable transfer of liquid helium in space. The pump can be used to refill cryostats on orbiting satellites which use liquid helium for refrigeration at extremely low temperatures. The pump meets the head and flow requirements of on-orbit helium transfer: a flow rate of 800 L/hr at a head of 128 J/kg. The overall pump efficiency at the design point is 0.45. The design head and flow requirements are met with zero net positive suction head, which is the condition in an orbiting helium supply Dewar. The mass transfer efficiency calculated for a space transfer operation is 0.99. Steel ball bearings are used with gas fiber-reinforced teflon retainers to provide solid lubrication. These bearings have demonstrated the longest life in liquid helium endurance tests under simulated pumping conditions. Technology developed in the project also has application for liquid helium circulation in terrestrial facilities and for transfer of cryogenic rocket propellants in space.

  6. Equation of state of metallic helium

    SciTech Connect

    Shvets, V. T.

    2013-01-15

    The effective ion-ion interaction, free energy, pressure, and electric resistance of metallic liquid helium have been calculated in wide density and temperature ranges using perturbation theory in the electron-ion interaction potential. In the case of conduction electrons, the exchange interaction has been taken into account in the random-phase approximation and correlations have been taken into account in the local-field approximation. The solid-sphere model has been used for the nuclear subsystem. The diameter of these spheres is the only parameter of this theory. The diameter and density of the system at which the transition of helium from the singly ionized to doubly ionized state occurs have been estimated by analyzing the pair effective interaction between helium atoms. The case of doubly ionized helium atoms has been considered. Terms up to the third order of perturbation theory have been taken into account in the numerical calculations. The contribution of the third-order term is significant in all cases. The electric resistance and its temperature dependence for metallic helium are characteristic of simple divalent metals in the liquid state. The thermodynamic parameters-temperature and pressure densities-are within the ranges characteristic of the central regions of giant planets. This makes it possible to assume the existence of helium in the metallic state within the solar system.

  7. Sonic helium detectors in the Fermilab Tevatron

    SciTech Connect

    Bossert, R.J.; /Fermilab

    2006-01-01

    In the Fermilab Tevatron cryogenic system there are many remotely located low-pressure plate relief valves that must vent large volumes of cold helium gas when magnet quenches occur. These valves can occasionally stick open or not reseat completely, resulting in a large helium loss. As such, the need exists for a detector to monitor the relief valve's discharge area for the presence of helium. Due to the quantity needed, cost is an important factor. A unit has been developed and built for this purpose that is quite inexpensive. Its operating principle is based on the speed of sound, where two closely matched tubes operate at their acoustic resonant frequency. When helium is introduced into one of these tubes, the resulting difference in acoustic time of flight is used to trigger an alarm. At present, there are 39 of these units installed and operating in the Tevatron. They have detected many minor and major helium leaks, and have also been found useful in detecting a rise in the helium background in the enclosed refrigerator buildings. This paper covers the construction, usage and operational experience gained with these units over the last several years.

  8. Advanced helium magnetometer for space applications

    NASA Technical Reports Server (NTRS)

    Slocum, Robert E.

    1987-01-01

    The goal of this effort was demonstration of the concepts for an advanced helium magnetometer which meets the demands of future NASA earth orbiting, interplanetary, solar, and interstellar missions. The technical effort focused on optical pumping of helium with tunable solid state lasers. We were able to demonstrate the concept of a laser pumped helium magnetometer with improved accuracy, low power, and sensitivity of the order of 1 pT. A number of technical approaches were investigated for building a solid state laser tunable to the helium absorption line at 1083 nm. The laser selected was an Nd-doped LNA crystal pumped by a diode laser. Two laboratory versions of the lanthanum neodymium hexa-aluminate (LNA) laser were fabricated and used to conduct optical pumping experiments in helium and demonstrate laser pumped magnetometer concepts for both the low field vector mode and the scalar mode of operation. A digital resonance spectrometer was designed and built in order to evaluate the helium resonance signals and observe scalar magnetometer operation. The results indicate that the laser pumped sensor in the VHM mode is 45 times more sensitive than a lamp pumped sensor for identical system noise levels. A study was made of typical laser pumped resonance signals in the conventional magnetic resonance mode. The laser pumped sensor was operated as a scalar magnetometer, and it is concluded that magnetometers with 1 pT sensitivity can be achieved with the use of laser pumping and stable laser pump sources.

  9. Helium abundance variations in the solar wind: Observations from Ulysses

    SciTech Connect

    Barraclough, B.L.; Gosling, J.T.; Mccomas, D.J.; Goldstein, B.E.

    1995-06-01

    The abundance of helium in the solar wind averages approximately 4% but has been observed to vary by more than two orders of magnitude from 0.1 to 30%. Physical processes responsible for this variability are still not clearly understood. Previous work has shown a correlation between low He abundance and coronal streamer plasma and between high He abundance and coronal mass ejections (CMEs). The authors now have out-of-ecliptic data on helium in the solar wind from the plasma experiment aboard Ulysses. Tentative results show that the average high-latitude helium concentration is comparable to the in-ecliptic value for the present phase of the solar cycle, that excursions of the hour-averaged abundance very seldom fall outside the range 2.5 to 6.5%, and that there seems to be very little abundance enhancement associated with CMEs encountered at latitudes greater than 30 deg as opposed to the situation commonly encountered with in-ecliptic CMEs. In addition, preliminary observations of a single CME by both ISEE (in-ecliptic) and Ulysses (out-of-ecliptic) show a considerable He enhancement at ISEE with little or no perturbation of the average value at Ulysses` location. This paper will first present new results from the Ulysses mission up to the time of the meeting on the average abundance of helium in the solar wind as a function of spacecraft position, and will then focus on the out-of-ecliptic results including latitudinal abundance variations and observations of abundance enhancements (or lack thereof) in high-latitude CMEs.

  10. Role of the N-terminal transmembrane domain in the endo-lysosomal targeting and function of the human ABCB6 protein

    PubMed Central

    Kiss, Katalin; Kucsma, Nora; Brozik, Anna; Tusnady, Gabor E.; Bergam, Ptissam; vanNiel, Guillaume; Szakacs, Gergely

    2015-01-01

    ATP-binding cassette, subfamily B (ABCB) 6 is a homodimeric ATP-binding cassette (ABC) transporter present in the plasma membrane and in the intracellular organelles. The intracellular localization of ABCB6 has been a matter of debate, as it has been suggested to reside in the mitochondria and the endo-lysosomal system. Using a variety of imaging modalities, including confocal microscopy and EM, we confirm the endo-lysosomal localization of ABCB6 and show that the protein is internalized from the plasma membrane through endocytosis, to be distributed to multivesicular bodies and lysosomes. In addition to the canonical nucleotide-binding domain (NBD) and transmembrane domain (TMD), ABCB6 contains a unique N-terminal TMD (TMD0), which does not show sequence homology to known proteins. We investigated the functional role of these domains through the molecular dissection of ABCB6. We find that the folding, dimerization, membrane insertion and ATP binding/hydrolysis of the core–ABCB6 complex devoid of TMD0 are preserved. However, in contrast with the full-length transporter, the core–ABCB6 construct is retained at the plasma membrane and does not appear in Rab5-positive endosomes. TMD0 is directly targeted to the lysosomes, without passage to the plasma membrane. Collectively, our results reveal that TMD0 represents an independently folding unit, which is dispensable for catalysis, but has a crucial role in the lysosomal targeting of ABCB6. PMID:25627919

  11. Electron-impact ionization of helium for equal-energy-sharing kinematics

    SciTech Connect

    Stelbovics, A.T.; Bray, I.; Fursa, D.V.; Bartschat, K.

    2005-05-15

    The close-coupling approach to electron-helium single ionization is analyzed and several ways of defining the scattering amplitudes are determined, for both equal- and unequal-energy outgoing electrons. Nevertheless, the various definitions all lead to the same cross section. The convergent close-coupling (CCC) method with Laguerre (CCC-L) and box-based (CCC-B) target functions is applied to calculate electron-impact ionization of helium for the cases where the two outgoing electrons have equal energy. Excellent absolute agreement with experiment is obtained for all available cases of comparison.

  12. Helium-Shell Nucleosynthesis and Extinct Radioactivities

    NASA Technical Reports Server (NTRS)

    Meyer, B. S.; The, L.-S.; Clayton, D. D.; ElEid, M. F.

    2004-01-01

    Although the exact site for the origin of the r-process isotopes remains mysterious, most thinking has centered on matter ejected from the cores of massive stars in core-collapse supernovae [13]. In the 1970's and 1980's, however, difficulties in understanding the yields from such models led workers to consider the possibility of r-process nucleosynthesis farther out in the exploding star, in particular, in the helium burning shell [4,5]. The essential idea was that shock passage through this shell would heat and compress this material to the point that the reactions 13C(alpha; n)16O and, especially, 22Ne(alpha; n)25Mg would generate enough neutrons to capture on preexisting seed nuclei and drive an "n process" [6], which could reproduce the r-process abundances. Subsequent work showed that the required 13C and 22Ne abundances were too large compared to the amounts available in realistic models [7] and recent thinking has returned to supernova core material or matter ejected from neutron star-neutron star collisions as the more likely r-process sites.

  13. Helium and Neon in Comets

    NASA Technical Reports Server (NTRS)

    Jewitt, David

    1996-01-01

    Two comets were observed with EUVE in late 1994. Both comet Mueller and comet Borrelly are short-period comets having well established orbital elements and accurate ephemerides. Spectra of 40 ksec were taken of each. No evidence for emission lines from either Helium or Neon was detected. We calculated limits on the production rates of these atoms (relative to solar) assuming a standard isotropic outflow model, with a gas streaming speed of 1 km/s. The 3-sigma (99.7% confidence) limits (1/100,000 for He, 0.8 for Ne) are based on a conservative estimate of the noise in the EUVE spectra. They are also weakly dependent on the precise pointing and tracking of the EUVE field of view relative to the comet during the integrations. These limits are consistent with ice formation temperatures T greater than or equal to 30 K, as judged from the gas trapping experiments of Bar-Nun. For comparison, the solar abundances of these elements are He/O = 110, Ne/O = 1/16. Neither limit was as constraining as we had initially hoped, mainly because comets Mueller and Borrelly were intrinsically less active than anticipated.

  14. Pulsating Helium Atmosphere White Dwarfs

    NASA Astrophysics Data System (ADS)

    Provencal, Judith; Montgomery, Michael H.; Bischoff-Kim, Agnes; Shipman, Harry; Nitta, Atsuko; Whole Earth Telescope Collaboration

    2015-08-01

    The overwhelming majority of all stars currently on the main sequence as well as those from earlier generations will or have ended their stellar lives as white dwarf stars. White dwarfs are rich forensic laboratories linking the history and future evolution of our Galaxy. Their structure and atmospheric composition provide evidence of how the progenitors lived, how they evolved, and how they died. This information reveals details of processes governing the behavior of contemporary main sequence stars. Combined with their distribution in luminosity/temperature, white dwarfs strongly constrain models of galactic and cosmological evolution.GD358 is among the brightest (mv =13.7) and best studied of the pulsating white dwarfs. This helium atmoshere pulsator (DBV) has an extensive photometric database spanning 30 years, including nine multisite Whole Earth Telescope campaigns. GD358 exhibits a range of behaviors, from drastic changes in excited pulsation modes to variable multiplet splittings. We use GD358 as a template for an examination of the DBV class, combining photometric results with recent COS spectroscopy. The results present new questions concerning DB formation and evolution.

  15. Acceleration of protons to above 6 MeV using H{sub 2}O 'snow' nanowire targets

    SciTech Connect

    Pomerantz, I.; Schleifer, E.; Nahum, E.; Eisenmann, S.; Botton, M.; Gordon, D.; Sprangel, P.; Zigler, A.

    2012-07-09

    A scheme is presented for using H{sub 2}O 'snow' nanowire targets for the generation of fast protons. This novel method may relax the requirements for very high laser intensities, thus reducing the size and cost of laser based ion acceleration system.

  16. Simulation of the mantle and crustal helium isotope signature in the Mediterranean Sea using a high-resolution regional circulation model

    NASA Astrophysics Data System (ADS)

    Ayache, M.; Dutay, J.-C.; Jean-Baptiste, P.; Fourré, P. E.

    2015-08-01

    Helium isotopes (3He, 4He) are useful tracers for investigating the deep ocean circulation and for evaluating ocean general circulation models, because helium is a stable and conservative nuclide that does not take part in any chemical or biological process. Helium in the ocean originates from three different sources: namely, (i) gas dissolution in equilibrium with atmospheric helium, (ii) helium-3 addition by radioactive decay of tritium (called tritiugenic helium), and (iii) injection of terrigenic helium-3 and helium-4 by the submarine volcanic activity which occurs mainly at plate boundaries, and also addition of (mainly) helium-4 from the crust and sedimentary cover by α-decay of uranium and thorium contained in various minerals. We present the first simulation of the terrigenic helium isotope distribution in the whole Mediterranean Sea, using a high-resolution model (NEMO-MED12). For this simulation we build a simple source function for terrigenic helium isotopes based on published estimates of terrestrial helium fluxes. We estimate a hydrothermal flux of 3.5 mol 3He yr-1 and a lower limit for the crustal flux at 1.6 10-7 mol 4He mol m-2 yr-1. In addition to providing constraints on helium isotope degassing fluxes in the Mediterranean, our simulations provide information on the ventilation of the deep Mediterranean waters which are useful for assessing NEMO-MED12 performance. This study is part of the work carried out to assess the robustness of the NEMO-MED12 model, which will be used to study the evolution of the climate and its effect on the biogeochemical cycles in the Mediterranean Sea, and to improve our ability to predict the future evolution of the Mediterranean Sea under the increasing anthropogenic pressure.

  17. Simulation of the mantle and crustal helium isotope signature in the Mediterranean Sea using a high-resolution regional circulation model

    NASA Astrophysics Data System (ADS)

    Ayache, M.; Dutay, J.-C.; Jean-Baptiste, P.; Fourré, E.

    2015-12-01

    Helium isotopes (3He, 4He) are useful tracers for investigating the deep ocean circulation and for evaluating ocean general circulation models, because helium is a stable and conservative nuclide that does not take part in any chemical or biological process. Helium in the ocean originates from three different sources, namely, (i) gas dissolution in equilibrium with atmospheric helium, (ii) helium-3 addition by radioactive decay of tritium (called tritiugenic helium), and (iii) injection of terrigenic helium-3 and helium-4 by the submarine volcanic activity which occurs mainly at plate boundaries, and also addition of (mainly) helium-4 from the crust and sedimentary cover by α-decay of uranium and thorium contained in various minerals. We present the first simulation of the terrigenic helium isotope distribution in the whole Mediterranean Sea using a high-resolution model (NEMO-MED12). For this simulation we build a simple source function for terrigenic helium isotopes based on published estimates of terrestrial helium fluxes. We estimate a hydrothermal flux of 3.5 mol3 He yr-1 and a lower limit for the crustal flux at 1.6 × 10-7 4He mol m-2 yr-1. In addition to providing constraints on helium isotope degassing fluxes in the Mediterranean, our simulations provide information on the ventilation of the deep Mediterranean waters which is useful for assessing NEMO-MED12 performance. This study is part of the work carried out to assess the robustness of the NEMO-MED12 model, which will be used to study the evolution of the climate and its effect on the biogeochemical cycles in the Mediterranean Sea, and to improve our ability to predict the future evolution of the Mediterranean Sea under the increasing anthropogenic pressure.

  18. Targeted analysis of omega-6-derived eicosanoids in human serum by SPE-LC-MS/MS for evaluation of coronary artery disease.

    PubMed

    Fernández Peralbo, María Auxiliadora; Priego-Capote, Feliciano; Galache-Osuna, José Gabriel; Luque de Castro, María Dolores

    2013-10-01

    A targeted approach has been applied to quantitative analysis of eicosanoids derived from omega-6 fatty acids in serum from individuals diagnosed with coronary artery disease (CAD). The target metabolites were series-2 prostaglandins, thromboxane B2, hydroxyeicosatetraenoic acids, and hydroxyoctadecadienoic acids. The method was based on SPELC-MS/MS in selected reaction monitoring mode for highly selective and sensitive determination of the target eicosanoids. The combination of SPE and LC-MS/MS involved the benefits from both direct analysis of serum without a step for protein precipitation and fully automation of the analysis. The method allowed comparison of omega-6-derived eicosanoids in serum from patients diagnosed with CAD and from control individuals. The effect of treatment with aspirin on the profile of the target compounds was evaluated through its incidence on the different pathways. Finally, the serum levels of the target metabolites in patients diagnosed with CAD were also statistically examined according to the severity of the coronary lesion stratified as stable angina, non-ST-elevation acute coronary syndrome, and acute myocardial infarction. PMID:24228265

  19. Electron-impact excitation of the n 1P levels of helium - Theory and experiment

    NASA Technical Reports Server (NTRS)

    Cartwright, David C.; Csanak, George; Trajmar, Sandor; Register, D. F.

    1992-01-01

    New experimental electron-energy-loss data have been used to extract differential and integral cross sections for excitation of the 2 1P level, and for the overlapping (3 1P, 3 1D, 3 3D) levels of helium, at 30-, 50-, and 100-eV incident electron energies. First-order many-body theory (FOMBT) has been used to calculate the differential and integral cross sections for excitation of the n 1P (n = 2,...,6) levels of helium by electron impact, for incident electron energies from threshold to 500 eV. Detailed comparisons between these two new sets of data are made as well as comparisons with appropriate published experimental and theoretical results. A simple scaling relationship is derived from the FOMBT results for n = 2,...,6 that provides differential and integral cross sections for all symmetry final levels of helium with n = 6 or greater.

  20. Curious Fluid Flows: From Complex Fluid Breakup to Helium Wetting

    NASA Astrophysics Data System (ADS)

    Huisman, Fawn Mitsu

    This work encompasses three projects; pinch-off dynamics in non-Newtonian fluids; helium wetting on alkali metals; and the investigation of quartz tuning forks as cryogenic pressure transducers. Chapter 1 discusses the breakup of a non-Newtonian yield stress fluid bridge. We measured the minimum neck radius, hmin, as a function of time and fit it to a power law with exponent n 1. We then compare n1 to exponent n2, obtained from a rotational rheometer using a Herschel-Bulkley model. We confirm n1=n2 for the widest variety of non-Newtonian fluids to date. When these fluids are diluted with a Newtonian fluid n1 does not equal n2. No current models predict that behavior, identifying a new class of fluid breakup. Chapter 2 presents the first chemical potential-temperature phase diagram of helium on lithium, sodium and gold, using a novel pressure measurement system. The growth and superfluid transition of a helium film on these substrates is measured via an oscillator for isotherms (fixed temperature, varying amount of helium gas), and quenches (fixed amount of helium gas, varying temperature). The chemical potential-temperature plot is similar for gold, lithium and sodium despite the large difference in the substrate binding energies. No signs of a 2-D liquid-vapor transition were seen. Chapter 3 discusses the creation of a 32.768 kHz quartz tuning fork in situ pressure transducer. Tuning forks are used to measure pressure at room temperature, but no work addresses their potential as cryogenic pressure transducers. We mapped out the behavior of a tuning fork as a function of pressure at 298, 7.0, 2.5, 1.6, 1.0 and 0.7 K by measuring the quality factor. The fork is sensitive to pressures above 0.1 mTorr, limiting its use as a pressure gauge at 0.6 K and below. The experimental curves were compared to a theoretical Q(P, T) function that was refined using the 298 K data. At cryogenic temperatures the formula breaks down in the viscous region and becomes inaccurate. The

  1. Organic Radical Contrast Agents Based on Polyacetylenes Containing 2,2,6,6-Tetramethylpiperidine 1-Oxyl (TEMPO): Targeted Magnetic Resonance (MR)/Optical Bimodal Imaging of Folate Receptor Expressing HeLa Tumors in Vitro and in Vivo(a).

    PubMed

    Huang, Lixia; Yan, Chenggong; Cui, Danting; Yan, Yichen; Liu, Xiang; Lu, Xinwei; Tan, Xiangliang; Lu, Xiaodan; Xu, Jun; Xu, Yikai; Liu, Ruiyuan

    2015-06-01

    Nitroxides have great potential as magnetic resonance imaging (MRI) contrast agents for tumor detection. Polyacetylenes(PAs) containing 2,2,6,6-tetramethyl-piperidine oxyl (TEMPO) and poly(ethylene glycol) were synthesized via metathesis polymerization of the corresponding substituted acetylenes to be used for targeted bimodal MRI /optical imaging of tumors. The poly(ethylene glycol) in the polyacetylenes enables covalent conjugation of carboxyl fluorescein and folic acid (FA) with hydroxyl groups to develop targeted multifunctional organic radical contrast agents (ORCAs). In vitro studies confirm the excellent binding specificity and subsequent enhanced cellular internalization of the targeted ORCAs (PA-TEMPO-FI-FA) without cytotoxicity. In vivo T1-weighted MRI demonstrates the active tumor targeting ability of PA-TEMPO-FI-FA to generate specific contrast enhancement in mice bearing HeLa tumors. Moreover, longitudinal optical imaging displays high tumor accumulation after 1 h post-injection of PA-TEMPO-FI-FA. These results indicate that multifunctional ORCAs may provide a tumor-targeted delivery platform for further molecular imaging guided cancer therapy.

  2. Dielectronic recombination and resonant transfer excitation processes for helium-like krypton

    NASA Astrophysics Data System (ADS)

    Hu, Xiao-Li; Qu, Yi-Zhi; Zhang, Song-Bin; Zhang, Yu

    2012-10-01

    The relativistic configuration interaction method is employed to calculate the dielectronic recombination (DR) cross sections of helium-like krypton via the 1s2lnl' (n = 2, 3, ..., 15) resonances. Then, the resonant transfer excitation (RTE) processes of Kr34+ colliding with H, He, H2, and CHx (x = 0-4) targets are investigated under the impulse approximation. The needed Compton profiles of targets are obtained from the Hartree—Fock wave functions. The RTE cross sections are strongly dependent on DR resonant energies and strengths, and the electron momentum distributions of the target. For H2 and H targets, the ratio of their RTE cross sections changes from 1.85 for the 1s2l2l' to 1.88 for other resonances, which demonstrates the weak molecular effects on the Compton profiles of H2. For CHx (x = 0-4) targets, the main contribution to the RTE cross section comes from the carbon atom since carbon carries 6 electrons; as the number of hydrogen increases in CHx, the RTE cross section almost increases by the same value, displaying the strong separate atom character for the hydrogen. However, further comparison of the individual orbital contributions of C(2p, 2s, 1s) and CH4(1t2, 2a1, 1a1) to the RTE cross sections shows that the molecular effects induce differences of about 25.1%, 19.9%, and 0.2% between 2p-1t2, 2s-2a1, and 1s-1a1 orbitals, respectively.

  3. Development of 1.6 microm continuous-wave modulation hard-target differential absorption lidar system for CO2 sensing.

    PubMed

    Kameyama, Shumpei; Imaki, Masaharu; Hirano, Yoshihito; Ueno, Shinichi; Kawakami, Shuji; Sakaizawa, Daisuke; Nakajima, Masakatsu

    2009-05-15

    We have demonstrated the 1.6 mum cw modulation hard-target differential absorption lidar system for CO(2) sensing. In this system, ON and OFF wavelength laser lights are intensity modulated with cw signals. Received lights of the two wavelengths from the hard target are discriminated by modulation frequencies in the electrical signal domain. The optical circuit is fiber based, and this makes the system compact and reliable. It is shown that a stable CO(2) concentration measurement corresponding to a fluctuation of 4 ppm (rms) (ppm is parts per million) has been achieved in 32 s measurement intervals and the 1 km path.

  4. Beyond CTLA-4 and PD-1: Orphan nuclear receptor NR2F6 as T cell signaling switch and emerging target in cancer immunotherapy.

    PubMed

    Klepsch, Victoria; Hermann-Kleiter, Natascha; Baier, Gottfried

    2016-10-01

    Blockade of immune checkpoints has emerged as key strategy in the development of effective cancer therapies. In contrast to cell surface checkpoints like CTLA-4 and PD-1, however, additional cancer therapeutic targets are located inside the effector immune cells. Targeting these alternative checkpoints in cancer immunotherapy with the goal to strengthen the patient's immune system are likely to extend the benefits of cancer immunotherapy in the near future. Along this line, we have defined and validated the orphan nuclear receptor NR2F6 (nuclear receptor subfamily 2 group F member 6, also called Ear-2) as an intracellular immune checkpoint in effector T cells. NR2F6 acts as a novel master switch of antitumor responses against both transplantable and spontaneous tumors in mice relevant for human cancer. NR2F6 directly represses transcription of key cytokine genes in T effector cells relevant for tumor cell rejection, such as IL-2, IFN and TNFα. Thus, in the presence of NR2F6, T cell activation is limited within the tumor microenvironment. This defines NR2F6 as a key checkpoint governing the amplitude of cancer immune surveillance. Based on our study, an approach shall be initiated to identify low molecular weight compounds that selectively interfere with NR2F6 function in the clinic.

  5. Helium gas bubble trapped in liquid helium in high magnetic field

    SciTech Connect

    Bai, H. Hannahs, S. T.; Markiewicz, W. D.; Weijers, H. W.

    2014-03-31

    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 T{sup 2}/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.

  6. MicroRNA-128-3p is a novel oncomiR targeting PHF6 in T-cell acute lymphoblastic leukemia.

    PubMed

    Mets, Evelien; Van Peer, Gert; Van der Meulen, Joni; Boice, Michael; Taghon, Tom; Goossens, Steven; Mestdagh, Pieter; Benoit, Yves; De Moerloose, Barbara; Van Roy, Nadine; Poppe, Bruce; Vandesompele, Jo; Wendel, Hans-Guido; Van Vlierberghe, Pieter; Speleman, Frank; Rondou, Pieter

    2014-08-01

    T-cell acute lymphoblastic leukemia arises from the leukemic transformation of developing thymocytes and results from cooperative genetic lesions. Inactivation of the PHF6 gene is frequently observed in T-cell acute lymphoblastic leukemia, suggesting an important tumor suppressive role for PHF6 in the pathobiology of this leukemia. Although the precise function of PHF6 is still unknown, this gene is most likely involved in chromatin regulation, a strongly emerging theme in T-cell acute lymphoblastic leukemia. In this context, our previous description of a cooperative microRNA regulatory network controlling several well-known T-cell acute lymphoblastic leukemia tumor suppressor genes, including PHF6, is of great importance. Given the high frequency of PHF6 lesions in T-cell acute lymphoblastic leukemia and the integration of PHF6 in this microRNA regulatory network, we aimed to identify novel oncogenic microRNAs in T-cell acute lymphoblastic leukemia which suppress PHF6. To this end, we performed an unbiased PHF6 3'UTR-microRNA library screen and combined the results with microRNA profiling data of samples from patients with T-cell acute lymphoblastic leukemia and normal thymocyte subsets. We selected miR-128-3p as a candidate PHF6-targeting, oncogenic microRNA and demonstrated regulation of PHF6 expression upon modulation of this microRNA in T-cell acute lymphoblastic leukemia cell lines. In vivo evidence of an oncogenic role of this microRNA in T-cell acute lymphoblastic leukemia was obtained through accelerated leukemia onset in a NOTCH1-induced T-cell acute lymphoblastic leukemia mouse model upon miR-128-3p over-expression. We conclude that miR-128-3p is a strong novel candidate oncogenic microRNA in T-cell acute lymphoblastic leukemia which targets the PHF6 tumor suppressor gene.

  7. Systemic delivery of siRNA by actively targeted polyion complex micelles for silencing the E6 and E7 human papillomavirus oncogenes.

    PubMed

    Nishida, Haruka; Matsumoto, Yoko; Kawana, Kei; Christie, R James; Naito, Mitsuru; Kim, Beob Soo; Toh, Kazuko; Min, Hyun Su; Yi, Yu; Matsumoto, Yu; Kim, Hyun Jin; Miyata, Kanjiro; Taguchi, Ayumi; Tomio, Kensuke; Yamashita, Aki; Inoue, Tomoko; Nakamura, Hiroe; Fujimoto, Asaha; Sato, Masakazu; Yoshida, Mitsuyo; Adachi, Katsuyuki; Arimoto, Takahide; Wada-Hiraike, Osamu; Oda, Katsutoshi; Nagamatsu, Takeshi; Nishiyama, Nobuhiro; Kataoka, Kazunori; Osuga, Yutaka; Fujii, Tomoyuki

    2016-06-10

    Human papillomavirus (HPV) E6 and E7 oncogenes are essential for the immortalization and maintenance of HPV-associated cancer and are ubiquitously expressed in cervical cancer lesions. Small interfering RNA (siRNA) coding for E6 and E7 oncogenes is a promising approach for precise treatment of cervical cancer, yet a delivery system is required for systemic delivery to solid tumors. Here, an actively targeted polyion complex (PIC) micelle was applied to deliver siRNAs coding for HPV E6/E7 to HPV cervical cancer cell tumors in immune-incompetent tumor-bearing mice. A cell viability assay revealed that both HPV type 16 and 18 E6/E7 siRNAs (si16E6/E7 and si18E6/E7, respectively) interfered with proliferation of cervical cancer cell lines in an HPV type-specific manner. A fluorescence imaging biodistribution analysis further revealed that fluorescence dye-labeled siRNA-loaded PIC micelles efficiently accumulated within the tumor mass after systemic administration. Ultimately, intravenous injection of si16E6/E7 and si18E6/E7-loaded PIC micelles was found to significantly suppress the growth of subcutaneous SiHa and HeLa tumors, respectively. The specific activity of siRNA treatment was confirmed by the observation that p53 protein expression was restored in the tumors excised from the mice treated with si16E6/E7- and si18E6/E7-loaded PIC micelles for SiHa and HeLa tumors, respectively. Therefore, the actively targeted PIC micelle incorporating HPV E6/E7-coding siRNAs demonstrated its therapeutic potential against HPV-associated cancer. PMID:26979870

  8. Down-regulation of microRNA-9 leads to activation of IL-6/Jak/STAT3 pathway through directly targeting IL-6 in HeLa cell.

    PubMed

    Zhang, Jiangbo; Jia, Junqiao; Zhao, Lijun; Li, Xiaojun; Xie, Qing; Chen, Xiangmei; Wang, Jianliu; Lu, Fengmin

    2016-05-01

    MicroRNA-9 (miR-9) presents to exert distinct and even opposite functions in different kinds of tumors through targeting different cellular genes. However, its role in cervical adenocarcinoma remains uncertain. Here, we report that miR-9 is down-regulated in cervical adenocarcinoma due to its frequent promoter-hypermethylation and exerts its tumor suppressor role through inhibiting several novel target genes, including interleukin-6 (IL-6). The promoters of miR-9 precursors (mir-9-1, -2, and -3) were hypermethylated in cervical adenocarcinoma tissues. Demethylation treatment of HeLa dramatically increased the expression of mature miR-9. Both in vitro and in vivo functional experiments confirmed that miR-9 can inhibit the proliferation, migration, and malignant transformation abilities of HeLa cells. Bioinformatics methods and array-based RNA expression profiles were used to screen the downstream target genes of miR-9. Dual-luciferase reporting assay, real-time qPCR, and ELISA or Western blot confirmed four genes (CKAP2, HSPC159, IL-6, and TC10) to be novel direct target genes of miR-9. Pathway annotation analysis of the differently expressed genes (DEGs) induced by ectopic miR-9 expression revealed the enrichment in Jak/STAT3 pathway, which is one of the downstream pathways of IL-6. Ectopic expression of miR-9 in HeLa inhibited Jak/STAT3 signaling activity. Moreover, such effect could be partially reversed by the addition of exogenous IL-6. In conclusion, our results here present a tumor suppressor potential of miR-9 in cervical adenocarcinoma for the first time and suggest that miR-9 could repress tumorigenesis through inhibiting the activity of IL-6/Jak/STAT3 pathway.

  9. The NAB2-STAT6 gene fusion in solitary fibrous tumor can be reliably detected by anchored multiplexed PCR for targeted next-generation sequencing.

    PubMed

    Guseva, Natalya V; Tanas, Munir R; Stence, Aaron A; Sompallae, Ramakrishna; Schade, Jenna C; Bossler, Aaron D; Bellizzi, Andrew M; Ma, Deqin

    2016-01-01

    Solitary fibrous tumor (SFT) is a mesenchymal tumor of fibroblastic origin, which can affect any region of the body. 10-15% of SFTs metastasize and metastatic tumors are uniformly lethal with no effective therapies. The behavior of SFT is difficult to predict based on morphology. Recently, an intrachromosomal gene fusion between NAB2 and STAT6 was identified as the defining driving genetic event of SFT and different fusion types correlated with tumor histology and behavior. Due to the proximity of NAB2 and STAT6 on chromosome 12, this fusion may be missed by fluorescence in-situ hybridization. We evaluated 12 SFTs from 10 patients. All tumors showed strong nuclear staining for STAT6 by immunohistochemistry (IHC). The same formalin-fixed, paraffin-embedded blocks for IHC were used for gene fusion detection by a next-generation sequencing (NGS)-based assay. Targeted RNA fusion sequencing for gene fusions was performed using the Universal RNA Fusion Detection Kit, the Archer(™) FusionPlex(™) Sarcoma Panel and the Ion Torrent PGM, and data were analyzed using the Archer Analysis Pipeline 3.3. All tumors were positive for NAB2-STAT6 fusion. Six types of fusions were detected: NAB2ex4-STAT6ex2, NAB2ex2-STAT6ex5, NAB2ex6-STAT6ex16, NAB2ex6-STAT6ex17, NAB2ex3-STAT6ex18 and NAB2intron6-STAT6Ex17. The NGS findings were confirmed by RT-PCR followed by Sanger sequencing. No STAT6 fusion was detected in selected morphologic mimics of SFT. The assay also allows for detection of novel fusions and can detect NAB2-STAT6 fusions at a single-base resolution. PMID:27292373

  10. The NAB2-STAT6 gene fusion in solitary fibrous tumor can be reliably detected by anchored multiplexed PCR for targeted next-generation sequencing.

    PubMed

    Guseva, Natalya V; Tanas, Munir R; Stence, Aaron A; Sompallae, Ramakrishna; Schade, Jenna C; Bossler, Aaron D; Bellizzi, Andrew M; Ma, Deqin

    2016-01-01

    Solitary fibrous tumor (SFT) is a mesenchymal tumor of fibroblastic origin, which can affect any region of the body. 10-15% of SFTs metastasize and metastatic tumors are uniformly lethal with no effective therapies. The behavior of SFT is difficult to predict based on morphology. Recently, an intrachromosomal gene fusion between NAB2 and STAT6 was identified as the defining driving genetic event of SFT and different fusion types correlated with tumor histology and behavior. Due to the proximity of NAB2 and STAT6 on chromosome 12, this fusion may be missed by fluorescence in-situ hybridization. We evaluated 12 SFTs from 10 patients. All tumors showed strong nuclear staining for STAT6 by immunohistochemistry (IHC). The same formalin-fixed, paraffin-embedded blocks for IHC were used for gene fusion detection by a next-generation sequencing (NGS)-based assay. Targeted RNA fusion sequencing for gene fusions was performed using the Universal RNA Fusion Detection Kit, the Archer(™) FusionPlex(™) Sarcoma Panel and the Ion Torrent PGM, and data were analyzed using the Archer Analysis Pipeline 3.3. All tumors were positive for NAB2-STAT6 fusion. Six types of fusions were detected: NAB2ex4-STAT6ex2, NAB2ex2-STAT6ex5, NAB2ex6-STAT6ex16, NAB2ex6-STAT6ex17, NAB2ex3-STAT6ex18 and NAB2intron6-STAT6Ex17. The NGS findings were confirmed by RT-PCR followed by Sanger sequencing. No STAT6 fusion was detected in selected morphologic mimics of SFT. The assay also allows for detection of novel fusions and can detect NAB2-STAT6 fusions at a single-base resolution.

  11. DsRNA-mediated targeting of ribosomal transcripts RPS6 and RPL26 induces long-lasting and significant reductions in fecundity of the vector Aedes aegypti.

    PubMed

    Estep, A S; Sanscrainte, N D; Becnel, J J

    2016-07-01

    Ribosomal transcripts produce critical proteins that are involved in most cellular production processes. Targeting ribosomal transcripts has produced mortality in mites and ticks but the effect of ribosomal transcript knockdown has not been thoroughly examined in mosquitoes. We examine the effects of triggers targeting four ribosomal proteins (RP) transcripts. Although no significant mortality was observed after dsRNA microinjection and subsequent blood feeding, significant contrasts were observed on fecundity. Triggers targeting RPS6 and RPL26 effectively reduced gene expression but more importantly, reduced reproductive output by more than 96% and 91% at the first oviposition while triggers targeting RPL1 and RPS2 did not cause a reduction although gene expression was reduced. Significantly reduced fecundity continued through a second oviposition cycle in dsRPS6 and dsRPL26 cohorts, although the effect was not as strong. Relative gene expression levels confirmed specific transcript knockdown up to 20days post-injection in mosquitoes that did not oviposit or produced reduced clutch sizes. Dissections at 36h post-blood meal indicated defects in oocyte provisioning. The strong phenotype produced by dsRPS6 allowed us to examine the effects in various tissues as well as the dose response, trigger format, delivery method and trigger specificity in Aedes aegypti. Strong knockdown was observed in the abdomen and the ovaries. Greater than 50ng of dsRPS6 significantly reduced fecundity but not when delivered in a sugar meal or as an siRNA. Similar bioassays with mutated dsRPS6 triggers indicates that up to three mismatches per possible siRNA are still effective in reducing fecundity. These studies indicate that while active and effective triggers can be developed for vector species, the lack of an efficient delivery method is the biggest barrier to use as a potential control method. PMID:27180677

  12. Electron impact excitation of helium in Debye plasma

    SciTech Connect

    Diallo, S.; Gomis, L.; Faye, I. G.; Tall, M. S.; Diédhiou, I.; Diatta, C. S.; Zammit, M.

    2015-03-15

    The probability, differential, and integral scattering cross sections of the 1{sup 1}S→2{sup 1}S and 1{sup 1}S→2{sup 1}P transitions of helium have been calculated in the first Born approximation. The projectile-target interactions depending on the temperature and the density of plasma are described by the Debye-Hückel model. Wave functions of the target before and after collision were modeled by non orthogonal Hartree-Fock orbitals. The wave functions parameters are calculated with the Ritz variational method. We improve our unscreened first Born approximation integral cross sections by using the BE-scaled (B stands for binding energy and E excitation energy) method. The second Born approximation has also been used to calculate the excitation cross sections in Debye plasma. Our calculations are compared to other theoretical and experimental results where applicable.

  13. Mass Spectrometric Investigation of Anions Formed upon Free Electron Attachment to Nucleobase Molecules and Clusters Embedded in Superfluid Helium Droplets

    SciTech Connect

    Denifl, Stephan; Zappa, Fabio; Maehr, Ingo; Lecointre, Julien; Probst, Michael; Maerk, Tilmann D.; Scheier, Paul

    2006-07-28

    Here we report the first mass spectrometric study of negative ions formed via free electron attachment (EA) to nucleobases (NBs) embedded in helium clusters. Pure and mixed clusters of adenine and thymine have been formed by pickup of isolated NB molecules by cold helium droplets. In contrast to EA of isolated molecules in the gas phase we observe a long-lived parent anion NB{sup -} and, in addition, parent cluster ions NB{sub n}{sup -} up to size n=6. Moreover, we show that a low energy electron penetrating into a doped helium droplet causes efficient damage of the embedded nucleobases via resonant, site selective, dissociative electron attachment.

  14. Intravenous delivery of HIV-based lentiviral vectors preferentially transduces F4/80+ and Ly-6C+ cells in spleen, important target cells in autoimmune arthritis.

    PubMed

    van den Brand, Ben T; Vermeij, Eline A; Waterborg, Claire E J; Arntz, Onno J; Kracht, Michael; Bennink, Miranda B; van den Berg, Wim B; van de Loo, Fons A J

    2013-01-01

    Antigen presenting cells (APCs) play an important role in arthritis and APC specific gene therapeutic targeting will enable intracellular modulation of cell activity. Viral mediated overexpression is a potent approach to achieve adequate transgene expression levels and lentivirus (LV) is useful for sustained expression in target cells. Therefore, we studied the feasibility of lentiviral mediated targeting of APCs in experimental arthritis. Third generation VSV-G pseudotyped self-inactivating (SIN)-LV were injected intravenously and spleen cells were analyzed with flow cytometry for green fluorescent protein (GFP) transgene expression and cell surface markers. Collagen-induced arthritis (CIA) was induced by immunization with bovine collagen type II in complete Freund's adjuvant. Effect on inflammation was monitored macroscopically and T-cell subsets in spleen were analyzed by flow cytometry. Synovium from arthritic knee joints were analyzed for proinflammatory cytokine expression. Lentiviruses injected via the tail vein preferentially infected the spleen and transduction peaks at day 10. A dose escalating study showed that 8% of all spleen cells were targeted and further analysis showed that predominantly Ly6C+ and F4/80+ cells in spleen were targeted by the LV. To study the feasibility of blocking TAK1-dependent pathways by this approach, a catalytically inactive mutant of TAK1 (TAK1-K63W) was overexpressed during CIA. LV-TAK1-K63W significantly reduced incidence and arthritis severity macroscopically. Further histological analysis showed a significant decrease in bone erosion in LV-TAK1-K63W treated animals. Moreover, systemic Th17 levels were decreased by LV-TAK1-K63W treatment in addition to diminished IL-6 and KC production in inflamed synovium. In conclusion, systemically delivered LV efficiently targets monocytes and macrophages in spleen that are involved in autoimmune arthritis. Moreover, this study confirms efficacy of TAK1 targeting in arthritis. This

  15. Two distinct conformational states of Mycobacterium tuberculosis virulent factor early secreted antigenic target 6 kDa are behind the discrepancy around its biological functions.

    PubMed

    Refai, Amira; Haoues, Meriam; Othman, Houcemeddine; Barbouche, Mohamed Ridha; Moua, Philippe; Bondon, Arnaud; Mouret, Liza; Srairi-Abid, Najet; Essafi, Makram

    2015-11-01

    Early secreted antigenic target 6 kDa (ESAT-6) and culture filtrate protein 10 kDa (CFP-10) are complex proteins secreted by Mycobacterium tuberculosis that play a major role in the pathogenesis of tuberculosis. However, studies focusing on the biological functions of ESAT-6 led to discordant results and the role of ESAT-6 remains controversial. In the present study, we aim to address a potential explanation for this discrepancy and to highlight the physiological impact of two conformational states of ESAT-6. Analysis of a recombinant form of ESAT-6 by native gel electrophoresis, size exclusion chromatography and CD spectroscopy revealed that ESAT-6 forms dimers/multimers with higher molecular weight, which disappeared under the action of the detergent amidosulfobetaine-14 (ASB), giving rise to another conformational state of the protein. NMR has further indicated that ASB-treated versus nontreated ESAT-6 adopted distinct structural forms but with no well defined tertiary structure. However, protein-protein docking analysis favored a dimeric state of ESAT-6. Interestingly, the two preparations presented opposing effects on mycobacterial infectivity, as well as macrophage survival, interferon-γ secretion and membrane pore formation. Thereafter, we generated a recombinant form of the physiological heterodimer ESAT-6/CFP-10 that ASB was also able to dissociate and which showed functions similar to those of ESAT-6 dimers/multimers. Our data suggest that, in the absence of CFP-10, the hydrophobic regions of the ESAT-6 can form dimers/multimers, mimicking the ESAT-6/CFP-10 heterodimer, whereas their dissociation generates a protein presenting entirely different activities. Overall, the present study clarifies the intriguing divergences between reports that could be attributed to the ESAT-6 oligomeric state and sheds light on its importance for a better comprehension of the physiopathology of tuberculosis.

  16. FLUORESCENT IN SITU DETECTION OF ENCEPHALITOZOON HELLEM SPORES WITH A 6-CARBOXYFLUORESCEIN-LABELED RNA-TARGETED OLIGONUCLEOTIDE PROBE

    EPA Science Inventory

    A fluorescent in situ hybridization assay has been developed for the detection of the human-pathogenic microsporidian, Encephalitozoon hellem, in water samples using epifluorescence microscopy. The assay employs a 19-nucleotide species-specific 6-carboxyfluorescein-labeled oligo...

  17. FLUORESCENT IN SITU DETECTION OF ENCEPHALITOZOON HELLEM SPORES WITH A 6-CARBOXYFLUORESCEIN-LABELED RIBOSOMAL RNA-TARGETED OLIGONUCLEOTIDE PROBE

    EPA Science Inventory

    A fluroescent in situ hybridization assay has been developed for the detection of the human-pathogenic microsporidian, Encephalitozoon hellem in water samples using epifluorescence microscopy. The assay employs a 19-nucleotide species-specific 6-carboxyfluorescein-labeled oligonu...

  18. Helium measurements of pore-fluids obtained from SAFOD drillcore

    SciTech Connect

    Ali, S.; Stute, M.; Torgersen, T.; Winckler, G.; Kennedy, B.M.

    2010-04-15

    {sup 4}He accumulated in fluids is a well established geochemical tracer used to study crustal fluid dynamics. Direct fluid samples are not always collectable; therefore, a method to extract rare gases from matrix fluids of whole rocks by diffusion has been adapted. Helium was measured on matrix fluids extracted from sandstones and mudstones recovered during the San Andreas Fault Observatory at Depth (SAFOD) drilling in California, USA. Samples were typically collected as subcores or from drillcore fragments. Helium concentration and isotope ratios were measured 4-6 times on each sample, and indicate a bulk {sup 4}He diffusion coefficient of 3.5 {+-} 1.3 x 10{sup -8} cm{sup 2}s{sup -1} at 21 C, compared to previously published diffusion coefficients of 1.2 x 10{sup -18} cm{sup 2}s{sup -1} (21 C) to 3.0 x 10{sup -15} cm{sup 2}s{sup -1} (150 C) in the sands and clays. Correcting the diffusion coefficient of {sup 4}He{sub water} for matrix porosity ({approx}3%) and tortuosity ({approx}6-13) produces effective diffusion coefficients of 1 x 10{sup -8} cm{sup 2}s{sup -1} (21 C) and 1 x 10{sup -7} (120 C), effectively isolating pore fluid {sup 4}He from the {sup 4}He contained in the rock matrix. Model calculations indicate that <6% of helium initially dissolved in pore fluids was lost during the sampling process. Complete and quantitative extraction of the pore fluids provide minimum in situ porosity values for sandstones 2.8 {+-} 0.4% (SD, n=4) and mudstones 3.1 {+-} 0.8% (SD, n=4).

  19. Ceapins are a new class of unfolded protein response inhibitors, selectively targeting the ATF6α branch

    PubMed Central

    Gallagher, Ciara M; Garri, Carolina; Cain, Erica L; Ang, Kenny Kean-Hooi; Wilson, Christopher G; Chen, Steven; Hearn, Brian R; Jaishankar, Priyadarshini; Aranda-Diaz, Andres; Arkin, Michelle R; Renslo, Adam R; Walter, Peter

    2016-01-01

    The membrane-bound transcription factor ATF6α plays a cytoprotective role in the unfolded protein response (UPR), required for cells to survive ER stress. Activation of ATF6α promotes cell survival in cancer models. We used cell-based screens to discover and develop Ceapins, a class of pyrazole amides, that block ATF6α signaling in response to ER stress. Ceapins sensitize cells to ER stress without impacting viability of unstressed cells. Ceapins are highly specific inhibitors of ATF6α signaling, not affecting signaling through the other branches of the UPR, or proteolytic processing of its close homolog ATF6β or SREBP (a cholesterol-regulated transcription factor), both activated by the same proteases. Ceapins are first-in-class inhibitors that can be used to explore both the mechanism of activation of ATF6α and its role in pathological settings. The discovery of Ceapins now enables pharmacological modulation all three UPR branches either singly or in combination. DOI: http://dx.doi.org/10.7554/eLife.11878.001 PMID:27435960

  20. Ceapins are a new class of unfolded protein response inhibitors, selectively targeting the ATF6α branch.

    PubMed

    Gallagher, Ciara M; Garri, Carolina; Cain, Erica L; Ang, Kenny Kean-Hooi; Wilson, Christopher G; Chen, Steven; Hearn, Brian R; Jaishankar, Priyadarshini; Aranda-Diaz, Andres; Arkin, Michelle R; Renslo, Adam R; Walter, Peter

    2016-01-01

    The membrane-bound transcription factor ATF6α plays a cytoprotective role in the unfolded protein response (UPR), required for cells to survive ER stress. Activation of ATF6α promotes cell survival in cancer models. We used cell-based screens to discover and develop Ceapins, a class of pyrazole amides, that block ATF6α signaling in response to ER stress. Ceapins sensitize cells to ER stress without impacting viability of unstressed cells. Ceapins are highly specific inhibitors of ATF6α signaling, not affecting signaling through the other branches of the UPR, or proteolytic processing of its close homolog ATF6β or SREBP (a cholesterol-regulated transcription factor), both activated by the same proteases. Ceapins are first-in-class inhibitors that can be used to explore both the mechanism of activation of ATF6α and its role in pathological settings. The discovery of Ceapins now enables pharmacological modulation all three UPR branches either singly or in combination. PMID:27435960

  1. Transparent Helium in Stripped Envelope Supernovae

    NASA Astrophysics Data System (ADS)

    Piro, Anthony L.; Morozova, Viktoriya S.

    2014-09-01

    Using simple arguments based on photometric light curves and velocity evolution, we propose that some stripped envelope supernovae (SNe) show signs that a significant fraction of their helium is effectively transparent. The main pieces of evidence are the relatively low velocities with little velocity evolution, as are expected deep inside an exploding star, along with temperatures that are too low to ionize helium. This means that the helium should not contribute to the shaping of the main SN light curve, and thus the total helium mass may be difficult to measure from simple light curve modeling. Conversely, such modeling may be more useful for constraining the mass of the carbon/oxygen core of the SN progenitor. Other stripped envelope SNe show higher velocities and larger velocity gradients, which require an additional opacity source (perhaps the mixing of heavier elements or radioactive nickel) to prevent the helium from being transparent. We discuss ways in which similar analysis can provide insights into the differences and similarities between SNe Ib and Ic, which will lead to a better understanding of their respective formation mechanisms.

  2. TRANSPARENT HELIUM IN STRIPPED ENVELOPE SUPERNOVAE

    SciTech Connect

    Piro, Anthony L.; Morozova, Viktoriya S.

    2014-09-01

    Using simple arguments based on photometric light curves and velocity evolution, we propose that some stripped envelope supernovae (SNe) show signs that a significant fraction of their helium is effectively transparent. The main pieces of evidence are the relatively low velocities with little velocity evolution, as are expected deep inside an exploding star, along with temperatures that are too low to ionize helium. This means that the helium should not contribute to the shaping of the main SN light curve, and thus the total helium mass may be difficult to measure from simple light curve modeling. Conversely, such modeling may be more useful for constraining the mass of the carbon/oxygen core of the SN progenitor. Other stripped envelope SNe show higher velocities and larger velocity gradients, which require an additional opacity source (perhaps the mixing of heavier elements or radioactive nickel) to prevent the helium from being transparent. We discuss ways in which similar analysis can provide insights into the differences and similarities between SNe Ib and Ic, which will lead to a better understanding of their respective formation mechanisms.

  3. Helium release from radioisotope heat sources

    SciTech Connect

    Peterson, D.E.; Early, J.W.; Starzynski, J.S.; Land, C.C.

    1984-05-01

    Diffusion of helium in /sup 238/PuO/sub 2/ fuel was characterized as a function of the heating rate and the fuel microstructure. The samples were thermally ramped in an induction furnace and the helium release rates measured with an automated mass spectrometer. The diffusion constants and activation energies were obtained from the data using a simple diffusion model. The release rates of helium were correlated with the fuel microstructure by metallographic examination of fuel samples. The release mechanism consists of four regimes, which are dependent upon the temperature. Initially, the release is controlled by movement of point defects combined with trapping along grain boundaries. This regime is followed by a process dominated by formation and growth of helium bubbles along grain boundaries. The third regime involves volume diffusion controlled by movement of oxygen vacancies. Finally, the release at the highest temperatures follows the diffusion rate of intragranular bubbles. The tendency for helium to be trapped within the grain boundaries diminishes with small grain sizes, slow thermal pulses, and older fuel.

  4. BASG thermomechanical pump helium 2 transfer tests

    NASA Technical Reports Server (NTRS)

    Mills, G. L.; Newell, D. A.; Urbach, A. R.

    1990-01-01

    The purpose of the effort described was to perform experiments and calculations related to using a thermomechanical pump in the space-based resupply of the Space Infrared Telescope Facility (SIRTF) with Helium 2. Thermomechanical (fountain effect) pumps have long been suggested as a means for pumping large quantities of Helium 2. The unique properties of Helium 2 have made it useful for cooling space instruments. Several space science missions, including SIRTF, are now being planned which would benefit greatly from on-orbit resupply of Helium 2. A series of experiments were performed to demonstrate that large volumes of Helium 2 can be transferred with a thermomechanical pump at high flow rates and at high efficiency from one dewar to another through valves and lines that are similar to the plumbing arrangement that would be necessary to accomplish such a transfer on-orbit. In addition, temperature, pressure, and flow rate data taken during the tests were used to verify and refine a computer model which was developed.

  5. Commissioning of a new helium pipeline

    NASA Technical Reports Server (NTRS)

    2000-01-01

    At the commissioning of a new high-pressure helium pipeline at Kennedy Space Center, participants cut the lines to helium-filled balloons. From left, they are Center Director Roy Bridges; Michael Butchko, president, SGS; Pierre Dufour, president and CEO, Air Liquide America Corporation; David Herst, director, Delta IV Launch Sites; Pamela Gillespie, executive administrator, office of Congressman Dave Weldon; and Col. Samuel Dick, representative of the 45th Space Wing. The nine-mile-long buried pipeline will service launch needs at the new Delta IV Complex 37 at Cape Canaveral Air Force Station. It will also serve as a backup helium resource for Shuttle launches. Nearly one launch's worth of helium will be available in the pipeline to support a Shuttle pad in an emergency. The line originates at the Helium Facility on KSC and terminates in a meter station at the perimeter of the Delta IV launch pad. Others at the ceremony were Jerry Jorgensen, pipeline project manager, Space Gateway Support (SGS), and Ramon Lugo, acting executive director, JPMO.

  6. Commissioning of a new helium pipeline

    NASA Technical Reports Server (NTRS)

    2000-01-01

    At the commissioning of a new high-pressure helium pipeline at Kennedy Space Center, participants watch as helium-filled balloons take to the sky after their lines were cut. From left, they are Center Director Roy Bridges; Michael Butchko, president, SGS; Pierre Dufour, president and CEO, Air Liquide America Corporation; David Herst, director, Delta IV Launch Sites; Pamela Gillespie, executive administrator, office of Congressman Dave Weldon; and Col. Samuel Dick, representative of the 45th Space Wing. The nine-mile-long buried pipeline will service launch needs at the new Delta IV Complex 37 at Cape Canaveral Air Force Station. It will also serve as a backup helium resource for Shuttle launches. Nearly one launch's worth of helium will be available in the pipeline to support a Shuttle pad in an emergency. The line originates at the Helium Facility on KSC and terminates in a meter station at the perimeter of the Delta IV launch pad. Others at the ceremony were Jerry Jorgensen, pipeline project manager, Space Gateway Support (SGS), and Ramon Lugo, acting executive director, JPMO.

  7. Study of the amorphization of surface silicon layers implanted by low-energy helium ions

    NASA Astrophysics Data System (ADS)

    Lomov, A. A.; Myakon'kikh, A. V.; Oreshko, A. P.; Shemukhin, A. A.

    2016-03-01

    The structural changes in surface layers of Si(001) substrates subjected to plasma-immersion implantation by (2-5)-keV helium ions to a dose of D = 6 × 1015-5 × 1017 cm-2 have been studied by highresolution X-ray diffraction, Rutherford backscattering, and spectral ellipsometry. It is found that the joint application of these methods makes it possible to determine the density depth distribution ρ( z) in an implanted layer, its phase state, and elemental composition. Treatment of silicon substrates in helium plasma to doses of 6 × 1016 cm-2 leads to the formation of a 20- to 30-nm-thick amorphized surface layer with a density close to the silicon density. An increase in the helium dose causes the formation of an internal porous layer.

  8. Kinome-wide RNAi studies in human multiple myeloma identify vulnerable kinase targets, including a lymphoid-restricted kinase, GRK6

    PubMed Central

    Zhu, Yuan Xiao; Schmidt, Jessica; Yin, Hongwei; Shi, Chang-Xin; Que, Qiang; Basu, Gargi; Azorsa, David; Perkins, Louise M.; Braggio, Esteban; Fonseca, Rafael; Bergsagel, P. Leif; Mousses, Spyro; Stewart, A. Keith

    2010-01-01

    A paucity of validated kinase targets in human multiple myeloma has delayed clinical deployment of kinase inhibitors in treatment strategies. We therefore conducted a kinome-wide small interfering RNA (siRNA) lethality study in myeloma tumor lines bearing common t(4;14), t(14;16), and t(11;14) translocations to identify critically vulnerable kinases in myeloma tumor cells without regard to preconceived mechanistic notions. Fifteen kinases were repeatedly vulnerable in myeloma cells, including AKT1, AK3L1, AURKA, AURKB, CDC2L1, CDK5R2, FES, FLT4, GAK, GRK6, HK1, PKN1, PLK1, SMG1, and TNK2. Whereas several kinases (PLK1, HK1) were equally vulnerable in epithelial cells, others and particularly G protein–coupled receptor kinase, GRK6, appeared selectively vulnerable in myeloma. GRK6 inhibition was lethal to 6 of 7 myeloma tumor lines but was tolerated in 7 of 7 human cell lines. GRK6 exhibits lymphoid-restricted expression, and from coimmunoprecipitation studies we demonstrate that expression in myeloma cells is regulated via direct association with the heat shock protein 90 (HSP90) chaperone. GRK6 silencing causes suppression of signal transducer and activator of transcription 3 (STAT3) phosphorylation associated with reduction in MCL1 levels and phosphorylation, illustrating a potent mechanism for the cytotoxicity of GRK6 inhibition in multiple myeloma (MM) tumor cells. As mice that lack GRK6 are healthy, inhibition of GRK6 represents a uniquely targeted novel therapeutic strategy in human multiple myeloma. PMID:19996089

  9. The histone chaperone Spt6 is required for activation-induced cytidine deaminase target determination through H3K4me3 regulation.

    PubMed

    Begum, Nasim A; Stanlie, Andre; Nakata, Mikiyo; Akiyama, Hideo; Honjo, Tasuku

    2012-09-21

    H3K4me3 plays a critical role in the activation-induced cytidine deaminase (AID)-induced DNA cleavage of switch (S) regions in the immunoglobulin heavy chain (IgH) locus during class-switch recombination (CSR). The histone chaperone complex facilitates chromatin transcription (FACT) is responsible for forming H3K4me3 at AID target loci. Here we show that the histone chaperone suppressor of Ty6 (Spt6) also participates in regulating H3K4me3 for CSR and for somatic hypermutation in AID target loci. We found that H3K4me3 loss was correlated with defects in AID-induced DNA breakage and reduced mutation frequencies in IgH loci in both S and variable regions and in non-IgH loci such as metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) and small nucleolar RNA host gene 3 (SNHG3). Global gene expression analysis revealed that Spt6 can act as both a positive and negative transcriptional regulator in B cells, affecting ∼5% of the genes that includes suppressor of Ty4 (Spt4) and AID. Interestingly, Spt6 regulates CSR and AID expression through two distinct histone modification pathways, H3K4me3 and H3K36me3, respectively. Tandem SH2 domain of Spt6 plays a critical role in CSR and H3K4me3 regulation involving Set1 histone methyltransferase. We conclude that Spt6 is a unique histone chaperone capable of regulating the histone epigenetic state of both AID targets and the AID locus.

  10. The histone chaperone Spt6 is required for activation-induced cytidine deaminase target determination through H3K4me3 regulation.

    PubMed

    Begum, Nasim A; Stanlie, Andre; Nakata, Mikiyo; Akiyama, Hideo; Honjo, Tasuku

    2012-09-21

    H3K4me3 plays a critical role in the activation-induced cytidine deaminase (AID)-induced DNA cleavage of switch (S) regions in the immunoglobulin heavy chain (IgH) locus during class-switch recombination (CSR). The histone chaperone complex facilitates chromatin transcription (FACT) is responsible for forming H3K4me3 at AID target loci. Here we show that the histone chaperone suppressor of Ty6 (Spt6) also participates in regulating H3K4me3 for CSR and for somatic hypermutation in AID target loci. We found that H3K4me3 loss was correlated with defects in AID-induced DNA breakage and reduced mutation frequencies in IgH loci in both S and variable regions and in non-IgH loci such as metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) and small nucleolar RNA host gene 3 (SNHG3). Global gene expression analysis revealed that Spt6 can act as both a positive and negative transcriptional regulator in B cells, affecting ∼5% of the genes that includes suppressor of Ty4 (Spt4) and AID. Interestingly, Spt6 regulates CSR and AID expression through two distinct histone modification pathways, H3K4me3 and H3K36me3, respectively. Tandem SH2 domain of Spt6 plays a critical role in CSR and H3K4me3 regulation involving Set1 histone methyltransferase. We conclude that Spt6 is a unique histone chaperone capable of regulating the histone epigenetic state of both AID targets and the AID locus. PMID:22843687

  11. Single ionization of helium by 730-eV electrons

    SciTech Connect

    Stevenson, M. A.; Lohmann, B.; Bray, I.; Fursa, D. V.; Stelbovics, A. T.

    2007-03-15

    We present fully differential measurements of 730-eV electron-impact single ionization of the ground state of helium with 205- or 100-eV outgoing electrons. Internormalized data are obtained for coplanar geometries with the fast electron detected at {theta}{sub A}=6 degree sign , 9 degree sign , and 12 degree sign . The data are compared, where possible, with the corresponding data of Catoire et al. [J. Phys. B 39, 2827 (2006)] and the convergent close-coupling theory. An improved agreement is found between the present measurements and the theory.

  12. Analysis of 6-pyruvyl tetrahydropterin synthase, a target gene product of su(s) suppressor in Drosophila

    SciTech Connect

    Yim, J.J.; Park, Y.S.; Kim, J.H.; Jacobson, K.B. . Dept. of Microbiology; Oak Ridge National Lab., TN )

    1989-01-01

    Of the 20 suppressor mutants listed in Drosophila, su(s){sup 2} has been studied for the biochemical characterization of the suppression. In su(s){sup 2} suppression, some mutants at vermilion (v, 1-33.0), sable (s, 1-43.0), speck (sp, 2-107.0), and purple (pr, 2-54.5) are suppressible by mutants at the suppressor of sable (su(s)) locus. There have been many reports of suppression mechanism studies in purple led to purple loci. The biochemical studies in purple led to in vitro demonstration of a su(s){sup +} gene product as a negative effector against suppressed purple PPH{sub 4} synthase, which has been also demonstrated in the gene product of vermilion more recently. Both studies led to a proposal for a posttranslational mechanism in which the su(s){sup +} gene produces a substance that interferes with the function of the target enzymes from the purple and vermilion mutant. In contrast to the transcriptional regulation of the su(s) locus the posttranslational mechanism is based on qualitative differences between wild and suppressed enzyme. Therefore this investigation was to determine if any quantitative or qualitative differences exist between the mutant and wild type target enzymes. 7 refs., 4 figs.

  13. The thick-target sup 9 Be(d,n) neutron spectra for deuteron energies between 2. 6 and 7. 0-MeV

    SciTech Connect

    Meadows, J.W.

    1991-11-01

    The measurement of the zero deg. neutron spectra and yields from deuterons incident on thick beryllium metal targets is described. {sup 235}U and {sup 238}U fission ion chambers were used as neutron detectors to span the neutron energy range above 0.05-MeV with a time resolution of {le} 3 nanosec. Measurements were made for incident deuteron energies from 2.6 to 7.0-MeV, at 0.4-MeV intervals, using time-of-flight techniques with flight paths of 2.7 and 6.8 meters. The results are presented in graphical form and in tables.

  14. The thick-target {sup 9}Be(d,n) neutron spectra for deuteron energies between 2.6 and 7.0-MeV

    SciTech Connect

    Meadows, J.W.

    1991-11-01

    The measurement of the zero deg. neutron spectra and yields from deuterons incident on thick beryllium metal targets is described. {sup 235}U and {sup 238}U fission ion chambers were used as neutron detectors to span the neutron energy range above 0.05-MeV with a time resolution of {le} 3 nanosec. Measurements were made for incident deuteron energies from 2.6 to 7.0-MeV, at 0.4-MeV intervals, using time-of-flight techniques with flight paths of 2.7 and 6.8 meters. The results are presented in graphical form and in tables.

  15. Targeted disruption of the M(r) 46,000 mannose 6-phosphate receptor gene in mice results in misrouting of lysosomal proteins.

    PubMed Central

    Köster, A; Saftig, P; Matzner, U; von Figura, K; Peters, C; Pohlmann, R

    1993-01-01

    Lysosomal enzymes containing mannose 6-phosphate recognition markers are sorted to lysosomes by mannose 6-phosphate receptors (MPRs). The physiological importance of this targeting mechanism is illustrated by I-cell disease, a fatal lysosomal storage disorder caused by the absence of mannose 6-phosphate residues in lysosomal enzymes. Most mammalian cells express two MPRs. Although the binding specificities, subcellular distribution and expression pattern of the two receptors can be differentiated, their coexpression is not understood. The larger of the two receptors with an M(r) of approximately 300,000 (MPR300), which also binds IGFII, appears to have a dominant role in lysosomal enzyme targeting, while the function of the smaller receptor with an M(r) of 46,000 (MPR46) is less clear. To investigate the in vivo function of the MPR46, we generated MPR46-deficient mice using gene targeting in embryonic stem cells. Reduced intracellular retention of newly synthesized lysosomal proteins in cells from MPR46 -/- mice demonstrated an essential sorting function of MPR46. The phenotype of MPR46 -/- mice was normal, indicating mechanisms that compensate the MPR46 deficiency in vivo. Images PMID:8262064

  16. MiR-506 suppresses proliferation and induces senescence by directly targeting the CDK4/6-FOXM1 axis in ovarian cancer.

    PubMed

    Liu, Guoyan; Sun, Yan; Ji, Ping; Li, Xia; Cogdell, David; Yang, Da; Parker Kerrigan, Brittany C; Shmulevich, Ilya; Chen, Kexin; Sood, Anil K; Xue, Fengxia; Zhang, Wei

    2014-07-01

    Ovarian carcinoma is the most lethal gynaecological malignancy. Better understanding of the molecular pathogenesis of this disease and effective targeted therapies are needed to improve patient outcomes. MicroRNAs play important roles in cancer progression and have the potential for use as either therapeutic agents or targets. Studies in other cancers have suggested that miR-506 has anti-tumour activity, but its function has yet to be elucidated. We found that deregulation of miR-506 in ovarian carcinoma promotes an aggressive phenotype. Ectopic over-expression of miR-506 in ovarian cancer cells was sufficient to inhibit proliferation and to promote senescence. We also demonstrated that CDK4 and CDK6 are direct targets of miR-506, and that miR-506 can inhibit CDK4/6-FOXM1 signalling, which is activated in the majority of serous ovarian carcinomas. This newly recognized miR-506-CDK4/6-FOXM1 axis provides further insight into the pathogenesis of ovarian carcinoma and identifies a potential novel therapeutic agent.

  17. MiR-506 Suppresses Proliferation and Induces Senescence by Directly Targeting the CDK4/6-FOXM1 Axis in Ovarian Cancer

    PubMed Central

    Liu, Guoyan; Sun, Yan; Ji, Ping; Li, Xia; Cogdell, David; Yang, Da; Parker Kerrigan, Brittany C.; Shmulevich, Ilya; Chen, Kexin; Sood, Anil K.; Xue, Fengxia; Zhang, Wei

    2014-01-01

    Ovarian carcinoma is the most lethal gynecological malignancy. Better understanding of the molecular pathogenesis of this disease and effective targeted therapies are needed to improve patient outcomes. MicroRNAs play important roles in cancer progression and have the potential for use as either therapeutic agents or targets. Studies in other cancers have suggested that miR-506 has antitumor activity, but its function has yet to be elucidated. We found that deregulation of miR-506 in ovarian carcinoma promotes an aggressive phenotype. Ectopic overexpression of miR-506 in ovarian cancer cells was sufficient to inhibit proliferation and to promote senescence. We also demonstrated that CDK4 and CDK6 are direct targets of miR-506, and that miR-506 can inhibit CDK4/6-FOXM1 signaling, which is activated in the majority of serous ovarian carcinomas. This newly recognized miR-506/CDK4/6-FOXM1 axis provides further insight into the pathogenesis of ovarian carcinoma and identifies a potential novel therapeutic agent. PMID:24604117

  18. Three-finger snake neurotoxins and Ly6 proteins targeting nicotinic acetylcholine receptors: pharmacological tools and endogenous modulators.

    PubMed

    Tsetlin, Victor I

    2015-02-01

    Snake venom neurotoxins and lymphocyte antigen 6 (Ly6) proteins, most of the latter being membrane tethered by a glycosylphosphatidylinositol (GPI) anchor, have a variety of biological activities, but their three-finger (3F) folding combines them in one Ly6/neurotoxin family. Subsets of two groups, represented by α-neurotoxins and Lynx1, respectively, interact with nicotinic acetylcholine receptors (nAChR) and, hence, are of therapeutic interest for the treatment of neurodegenerative diseases, pain, and cancer. Information on the mechanisms of action and 3D structure of the binding sites, which is required for drug design, is available from the 3D structure of α-neurotoxin complexes with nAChR models. Here, I compare the structural and functional features of α-neurotoxins versus Lynx1 and its homologs to get a clearer picture of Lynx1-nAChR interactions that is necessary for fundamental science and practical applications.

  19. Laser spectroscopic measurement of helium isotope ratios.

    SciTech Connect

    Wang, L.-B.; Mueller, P.; Holt, R. J.; Lu, Z.-T.; O'Connor, T. P.; Sano, Y.; Sturchio, N.; Univ. of Illinois; Univ. of Tokyo; Univ. of Illinois at Chicago

    2003-06-13

    A sensitive laser spectroscopic method has been applied to the quantitative determination of the isotope ratio of helium at the level of {sup 3}He/{sup 4}He = 10{sup -7}--10{sup -5}. The resonant absorption of 1083 nm laser light by the metastable {sup 3}He atoms in a discharge cell was measured with the frequency modulation saturation spectroscopy technique while the abundance of {sup 4}He was measured by a direct absorption technique. The results on three different samples extracted from the atmosphere and commercial helium gas were in good agreement with values obtained with mass spectrometry. The achieved 3{sigma} detection limit of {sup 3}He in helium is 4 x 10{sup -9}. This demonstration required a 200 {mu}L STP sample of He. The sensitivity can be further improved, and the required sample size reduced, by several orders of magnitude with the addition of cavity enhanced spectroscopy.

  20. Ages of globular clusters and helium diffusion

    NASA Technical Reports Server (NTRS)

    Chaboyer, Brian; Sarajedini, Ata; Demarque, Pierre

    1992-01-01

    Evolutionary tracks have been calculated with alpha-enhanced compositions which cover the entire globular cluster metallicity range and have constructed isochrones which include the effects of microscopic diffusion of helium. The turnoff magnitudes from the isochrones were combined with the theoretical RR Lyrae magnitudes from Lee to determine the ages of 32 Galactic globular clusters using the magnitude difference between the turnoff and horizontal branch. It is found that including the effects of helium diffusion has a negligible effect on the derived ages of globular clusters. Regardless of the inclusion of helium diffusion, a significant age spread of 5 Gyr among the globular clusters is found. The oldest globular clusters studied here are 17 +/- 2 Gyr old.

  1. SCREW COMPRESSOR CHARACTERISTICS FOR HELIUM REFRIGERATION SYSTEMS

    SciTech Connect

    Ganni, Venkatarao; Knudsen, Peter; Creel, Jonathan; Arenius, Dana; Casagrande, Fabio; Howell, Matt

    2008-03-01

    The oil injected screw compressors have practically replaced all other types of compressors in modern helium refrigeration systems due to their large displacement capacity, minimal vibration, reliability and capability of handling helium's high heat of compression.At the present state of compressor system designs for helium systems, typically two-thirds of the lost input power is due to the compression system. Therefore it is important to understand the isothermal and volumetric efficiencies of these machines to help properly design these compression systems to match the refrigeration process. This presentation summarizes separate tests that have been conducted on Sullair compressors at the Superconducting Super-Collider Laboratory (SSCL) in 1993, Howden compressors at Jefferson Lab (JLab) in 2006 and Howden compressors at the Spallation Neutron Source (SNS) in 2006. This work is part of an ongoing study at JLab to understand the theoretical basis for these efficiencies and their loss

  2. Helium Speech: An Application of Standing Waves

    NASA Astrophysics Data System (ADS)

    Wentworth, Christopher D.

    2011-04-01

    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 phenomenon requires that we distinguish between the frequencies of sound produced by the larynx and the filtering of those frequencies by the vocal tract. We will describe here an experiment done by introductory physics students that uses helium speech as a context for learning about the human vocal system and as an application of the standing sound-wave concept. Modern acoustic analysis software easily obtained by instructors for student use allows data to be obtained and analyzed quickly.

  3. Helium corona-assisted air discharge

    SciTech Connect

    Jiang Nan; Gao Lei; Ji Ailing; Cao Zexian

    2011-10-15

    Operation of atmospheric discharge of electronegative gases including air at low voltages yet without consuming any inert gas will enormously promote the application of non-thermal plasmas. By taking advantage of the low onset voltage for helium corona, air discharge was successfully launched at much reduced voltages with a needle-plate system partly contained in a helium-filled glass bulb--for a needle-plate distance of 12 mm, 1.0 kV suffices. Ultraviolet emission from helium corona facilitates the discharging of air, and the discharge current manifests distinct features such as relatively broad Trichel pulses in both half periods. This design allows safe and economic implementation of atmospheric discharge of electronegative gases, which will find a broad palette of applications in surface modification, plasma medicine and gas treatment, etc.

  4. Targeting Inhibitor of κB Kinase β Prevents Inflammation-Induced Preterm Delivery by Inhibiting IL-6 Production from Amniotic Cells.

    PubMed

    Toda, Aska; Sawada, Kenjiro; Fujikawa, Tomoyuki; Wakabayashi, Atsuko; Nakamura, Koji; Sawada, Ikuko; Yoshimura, Akihiko; Nakatsuka, Erika; Kinose, Yasuto; Hashimoto, Kae; Mabuchi, Seiji; Tokuhira, Atsushi; Nakayama, Masahiro; Itai, Akiko; Kurachi, Hirohisa; Kimura, Tadashi

    2016-03-01

    Preterm delivery (PTD) remains a serious challenge in perinatology. Intrauterine infection and/or inflammation, followed by increased inflammatory cytokines, represented by IL-6, are involved in this pathology. Our aim was to identify IL-6-producing cells in the placenta and to analyze the potential of targeting IκB kinase β (IKKβ) signaling to suppress IL-6 production for the treatment of PTD. Immunohistochemical analyses using placentas complicated with severe chorioamnionitis revealed that IL-6 is mainly expressed in human amniotic mesenchymal stromal cells (hAMSCs). Primary hAMSCs were collected, and strong IL-6 expression was confirmed. In hAMSCs, the treatment of tumor necrosis factor-α or IL-1β drastically induced IL-6 production, followed by the phosphorylation of IKKs. A novel IKKβ inhibitor, IMD-0560, almost completely inhibited IL-6 production from hAMSCs. Using an experimental lipopolysaccharide-induced PTD mouse model, the therapeutic potential of IMD-0560 was examined. IMD-0560 was delivered vaginally 4 hours before lipopolysaccharide administration. Mice in the IMD-0560 (30 mg/kg, twice a day) group had a significantly lower rate of PTD [10 of 22 (45%)] without any apparent adverse events on the mice and their pups. In uteri collected from mice, IMD-0560 inhibited not only IL-6 production but also production of related cytokines, such as keratinocyte-derived protein chemokine/CXCL1, macrophage inflammatory protein-2/CXCL2, and monocyte chemoattractant protein-1/chemokine ligand 2. Targeting IKKβ signaling shows promising effects through the suppression of these cytokines and can be explored as a future option for the prevention of PTD. PMID:26796146

  5. The Effect of Bi-Terminal PEGylation of an Integrin αvβ6Targeted 18F Peptide on Pharmacokinetics and Tumor Uptake

    PubMed Central

    Hausner, Sven H.; Bauer, Nadine; Hu, Lina Y.; Knight, Leah M.; Sutcliffe, Julie L.

    2015-01-01

    Radiotracers based on the peptide A20FMDV2 selectively target the cell surface receptor integrin αvβ6. This integrin has been identified as a prognostic indicator correlating with the severity of disease for several challenging malignancies. In previous studies of A20FMDV2 peptides labeled with 4-18F-fluorobenzoic acid (18F-FBA), we have shown that the introduction of poly(ethylene glycol) (PEG) improves pharmacokinetics, including increased uptake in αvβ6-expressing tumors. The present study evaluated the effect of site-specific C-terminal or dual (N- and C-terminal) PEGylation, yielding 18F-FBAA20FMDV2-PEG28 (4) and 18F-FBA-PEG28-A20FMDV2-PEG28 (5), on αvβ6-targeted tumor uptake and pharmacokinetics. The results are compared with 18F-FBA–labeled A20FMDV2 radiotracers (1–3) bearing either no PEG or different PEG units at the N terminus. Methods The radiotracers were prepared and radiolabeled on solid phase. Using 3 cell lines, DX3puroβ6 (αvβ6 +), DX3puro (αvβ6 −), and BxPC-3 (αvβ6 +), we evaluated the radiotracers in vitro (serum stability; cell binding and internalization) and in vivo in mouse models bearing paired DX3puroβ6–DX3puro and, for 5, BxPC-3 xenografts. Results The size and location of the PEG units significantly affected αvβ6 targeting and pharmacokinetics. Although the C-terminally PEGylated 4 showed some improvements over the un-PEGylated 18F-FBA-A20FMDV2 (1), it was the bi-terminally PEGylated 5 that displayed the more favorable combination of high αvβ6 affinity, selectivity, and pharmacokinetic profile. In vitro, 5 bound to αvβ6-expressing DX3puroβ6 and BxPC-3 cells with 60.5% ± 3.3% and 48.8% ± 8.3%, respectively, with a significant fraction of internalization (37.2% ± 4.0% and 37.6% ± 4.1% of total radioactivity, respectively). By comparison, in the DX3puro control 5 showed only 3.0% ± 0.5% binding and 0.9% ± 0.2% internalization. In vivo, 5 maintained high, αvβ6-directed binding in the paired DX3puroβ6– DX

  6. D0 Silicon Upgrade: Commissioning Test Results for D-Zero's Helium Refrigerator

    SciTech Connect

    Rucinski, Russ; /Fermilab

    1997-06-30

    The test objectives are: (1) Make liquid helium and measure refrigerator capacity; (2) Measure liquid helium dewar heat leak, transfer line heat leak, and liquid nitrogen consumption rates; (3) Operate all cryogenic transfer lines; (4) Get some running time on all components; (5) Debug mechanical components, instrumentation, DMACs user interface, tune loops, and otherwise shake out any problems; (6) Get some operating time in to get familiar with system behavior; (7) Revise and/or improve operating procedures to actual practice; and (8) Identify areas for future improvement. D-Zero's stand alone helium refrigerator (STAR) liquified helium at a rate of 114 L/hr. This is consistent with other STAR installations. Refrigeration capacity was not measured due to lack of a calibrated heat load. Measured heat leaks were within design values. The helium dewar loss was measured at 2 to 4 watts or 9% per day, the solenoid and VLPC helium transfer lines had a heat leak of about 20 watts each. The liquid nitrogen consumption rates of the mobile purifier, STAR, and LN2 subcooler were measured at 20 gph, 20 to 64 gph, and 3 gph respectively. All cryogenic transfer lines including the solenoid and visible light photon counter (VLPC) transfer lines were cooled to their cryogenic operating temperatures. This included independent cooling of nitrogen shields and liquid helium components. No major problems were observed. The system ran quite well. Many problems were identified and corrected as they came up. Areas for improvement were noted and will be implemented in the future. The instrumentation and control system operated commendably during the test. The commissioning test run was a worthwhile and successful venture.

  7. AM Canum Venaticorum Progenitors with Helium Star Donors and the Resultant Explosions

    NASA Astrophysics Data System (ADS)

    Brooks, Jared; Bildsten, Lars; Marchant, Pablo; Paxton, Bill

    2015-07-01

    We explore the outcome of mass transfer via Roche lobe overflow of {M}{He}≲ 0.51{M}⊙ pure helium burning stars in close binaries with WDs. The evolution is driven by the loss of angular momentum through gravitational wave radiation (GWR), and both stars are modeled using Modules for Experiments in Stellar Astrophysics (MESA). The donors have masses of {M}{He}=0.35,0.4,{and}0.51{M}⊙ and accrete onto WDs of mass MWD from 0.6{M}⊙ to 1.26{M}⊙ . The initial orbital periods (Porb) span 20-80 minutes. For all cases, the accretion rate onto the WD is below the stable helium burning range, leading to accumulation of helium followed by unstable ignition. The mass of the convective core in the donors is small enough so that the WD accretes enough helium-rich matter to undergo a thermonuclear runaway in the helium shell before any carbon-oxygen enriched matter is transferred. The mass of the accumulated helium shell depends on MWD and the accretion rate. We show that for {M}{He}≳ 0.4{M}⊙ and {M}{WD}≳ 0.8{M}⊙ , the first flash is likely vigorous enough to trigger a detonation in the helium layer. These thermonuclear runaways may be observed as either faint and fast Ia SNe or, if the carbon in the core is also detonated, Type Ia SNe. Those that survive the first flash and eject mass will have a temporary increase in orbital separation, but GWR drives the donor back into contact, resuming mass transfer and triggering several subsequent weaker flashes.

  8. Development and testing of a pulsed helium ion source for probing materials and warm dense matter studies.

    PubMed

    Ji, Q; Seidl, P A; Waldron, W L; Takakuwa, J H; Friedman, A; Grote, D P; Persaud, A; Barnard, J J; Schenkel, T

    2016-02-01

    The neutralized drift compression experiment was designed and commissioned as a pulsed, linear induction accelerator to drive thin targets to warm dense matter (WDM) states with peak temperatures of ∼1 eV using intense, short pulses (∼1 ns) of 1.2 MeV lithium ions. At that kinetic energy, heating a thin target foil near the Bragg peak energy using He(+) ions leads to more uniform energy deposition of the target material than Li(+) ions. Experiments show that a higher current density of helium ions can be delivered from a plasma source compared to Li(+) ions from a hot plate type ion source. He(+) beam pulses as high as 200 mA at the peak and 4 μs long were measured from a multi-aperture 7-cm-diameter emission area. Within ±5% variation, the uniform beam area is approximately 6 cm across. The accelerated and compressed pulsed ion beams can be used for materials studies and isochoric heating of target materials for high energy density physics experiments and WDM studies. PMID:26932070

  9. Development and testing of a pulsed helium ion source for probing materials and warm dense matter studies

    NASA Astrophysics Data System (ADS)

    Ji, Q.; Seidl, P. A.; Waldron, W. L.; Takakuwa, J. H.; Friedman, A.; Grote, D. P.; Persaud, A.; Barnard, J. J.; Schenkel, T.

    2016-02-01

    The neutralized drift compression experiment was designed and commissioned as a pulsed, linear induction accelerator to drive thin targets to warm dense matter (WDM) states with peak temperatures of ˜1 eV using intense, short pulses (˜1 ns) of 1.2 MeV lithium ions. At that kinetic energy, heating a thin target foil near the Bragg peak energy using He+ ions leads to more uniform energy deposition of the target material than Li+ ions. Experiments show that a higher current density of helium ions can be delivered from a plasma source compared to Li+ ions from a hot plate type ion source. He+ beam pulses as high as 200 mA at the peak and 4 μs long were measured from a multi-aperture 7-cm-diameter emission area. Within ±5% variation, the uniform beam area is approximately 6 cm across. The accelerated and compressed pulsed ion beams can be used for materials studies and isochoric heating of target materials for high energy density physics experiments and WDM studies.

  10. Resistance to UV-induced apoptosis by β-HPV5 E6 involves targeting of activated BAK for proteolysis by recruitment of the HERC1 ubiquitin ligase.

    PubMed

    Holloway, Amy; Simmonds, Mark; Azad, Abul; Fox, Joanna L; Storey, Alan

    2015-06-15

    UV exposure is the main etiological agent in the development of non-melanoma skin cancer (NMSC), but mounting evidence suggests a co-factorial role for β-genus HPV types early in tumor initiation or progression. UV damage initiates an apoptotic response, driven at the mitochondrial level by BCL-2 family proteins, that eliminates damaged cells that may accumulate deleterious mutations and acquire tumorigenic properties. BAK is a pro-apoptotic BCL-2 protein that functions ultimately to form pores that permeabilize the mitochondrial outer membrane, thereby committing a cell to death, a process involving changes in BAK phosphorylation and conformation. The E6 protein of β-type HPV5 signals BAK for proteasomal degradation, a function that confers protection from UV-induced apoptosis. We find that HPV5 E6 does not constitutively target BAK for proteolysis, but targets the latter stages of BAK activation, following changes in phosphorylation and conformation. A mutational analysis identified the lysine residue on BAK required for proteolysis, and a functional siRNA screen identified the HECT domain E3 ubiquitin ligase HERC1 as being required for E6-mediated BAK degradation. We show that HERC1 interacts with BAK in E6-expressing cells that have been damaged by UV, and provide evidence that the interaction of HERC1 with BAK requires access to a hydrophobic surface on BAK that binds BH3 domains of BCL-2 proteins. We also show that HERC1 contains a putative BH3 domain that can bind to BAK. These findings reveal a specific and unique mechanism used by the HPV5 E6 protein to target BAK.

  11. Observation of the antimatter helium-4 nucleus.

    PubMed

    2011-05-19

    High-energy nuclear collisions create an energy density similar to that of the Universe microseconds after the Big Bang; in both cases, matter and antimatter are formed with comparable abundance. However, the relatively short-lived expansion in nuclear collisions allows antimatter to decouple quickly from matter, and avoid annihilation. Thus, a high-energy accelerator of heavy nuclei provides an efficient means of producing and studying antimatter. The antimatter helium-4 nucleus (4He), also known as the anti-α (α), consists of two antiprotons and two antineutrons (baryon number B = -4). It has not been observed previously, although the α-particle was identified a century ago by Rutherford and is present in cosmic radiation at the ten per cent level. Antimatter nuclei with B < -1 have been observed only as rare products of interactions at particle accelerators, where the rate of antinucleus production in high-energy collisions decreases by a factor of about 1,000 with each additional antinucleon. Here we report the observation of 4He, the heaviest observed antinucleus to date. In total, 18 4He counts were detected at the STAR experiment at the Relativistic Heavy Ion Collider (RHIC; ref. 6) in 10(9) recorded gold-on-gold (Au+Au) collisions at centre-of-mass energies of 200 GeV and 62 GeV per nucleon-nucleon pair. The yield is consistent with expectations from thermodynamic and coalescent nucleosynthesis models, providing an indication of the production rate of even heavier antimatter nuclei and a benchmark for possible future observations of 4He in cosmic radiation.

  12. Observation of the antimatter helium-4 nucleus.

    PubMed

    2011-05-19

    High-energy nuclear collisions create an energy density similar to that of the Universe microseconds after the Big Bang; in both cases, matter and antimatter are formed with comparable abundance. However, the relatively short-lived expansion in nuclear collisions allows antimatter to decouple quickly from matter, and avoid annihilation. Thus, a high-energy accelerator of heavy nuclei provides an efficient means of producing and studying antimatter. The antimatter helium-4 nucleus (4He), also known as the anti-α (α), consists of two antiprotons and two antineutrons (baryon number B = -4). It has not been observed previously, although the α-particle was identified a century ago by Rutherford and is present in cosmic radiation at the ten per cent level. Antimatter nuclei with B < -1 have been observed only as rare products of interactions at particle accelerators, where the rate of antinucleus production in high-energy collisions decreases by a factor of about 1,000 with each additional antinucleon. Here we report the observation of 4He, the heaviest observed antinucleus to date. In total, 18 4He counts were detected at the STAR experiment at the Relativistic Heavy Ion Collider (RHIC; ref. 6) in 10(9) recorded gold-on-gold (Au+Au) collisions at centre-of-mass energies of 200 GeV and 62 GeV per nucleon-nucleon pair. The yield is consistent with expectations from thermodynamic and coalescent nucleosynthesis models, providing an indication of the production rate of even heavier antimatter nuclei and a benchmark for possible future observations of 4He in cosmic radiation. PMID:21516103

  13. Ab Initio Simulations of Dense Helium Plasmas

    SciTech Connect

    Wang Cong; He Xiantu; Zhang Ping

    2011-04-08

    We study the thermophysical properties of dense helium plasmas by using quantum molecular dynamics and orbital-free molecular dynamics simulations, where densities are considered from 400 to 800 g/cm{sup 3} and temperatures up to 800 eV. Results are presented for the equation of state. From the Kubo-Greenwood formula, we derive the electrical conductivity and electronic thermal conductivity. In particular, with the increase in temperature, we discuss the change in the Lorenz number, which indicates a transition from strong coupling and degenerate state to moderate coupling and partial degeneracy regime for dense helium.

  14. Experiments with single electrons in liquid helium

    SciTech Connect

    Guo, W.; Jin, D.; Seidel, G. M.; Maris, H. J.

    2009-02-01

    We describe experiments we have performed in which we are able to image the motion of individual electrons moving in liquid helium 4. Electrons in helium form bubbles of radius {approx}19 A. We use the negative pressure produced by a sound wave to expand these bubbles to a radius of about 10 {mu}m. The bubbles are then illuminated with light from a flash lamp and their position recorded. We report on several interesting phenomena that have been observed in these experiments. It appears that the majority of the electrons that we detect result from cosmic rays passing through the experimental cell. We discuss this mechanism for electron production.

  15. Helium building no. 2 west and south sides. Looking 70 ...

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

    Helium building no. 2 west and south sides. Looking 70 ENE. - Marine Corps Air Station Tustin, Helium Tank Building No. 1, Near intersection of Meffett Avenue & Maxfield Street, Tustin, Orange County, CA

  16. 8. ORIGINAL HELIUM COMPRESSOR, CIRCA 1957, BY HASKELL ENGINEERING, GLENDALE, ...

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

    8. ORIGINAL HELIUM COMPRESSOR, CIRCA 1957, BY HASKELL ENGINEERING, GLENDALE, CALIFORNIA. Looking north. - Edwards Air Force Base, Air Force Rocket Propulsion Laboratory, Helium Compression Plant, Test Area 1-115, intersection of Altair & Saturn Boulevards, Boron, Kern County, CA

  17. Helium building no. 2 east and north sides. Looking 270 ...

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

    Helium building no. 2 east and north sides. Looking 270 W. - Marine Corps Air Station Tustin, Helium Tank Building No. 1, Near intersection of Meffett Avenue & Maxfield Street, Tustin, Orange County, CA

  18. 5. INTERIOR, LOOKING PAST HELIUM COMPRESSORS NO. 3 AND NO. ...

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

    5. INTERIOR, LOOKING PAST HELIUM COMPRESSORS NO. 3 AND NO. 2, TO NORTHEAST FRONT. - Edwards Air Force Base, Air Force Rocket Propulsion Laboratory, Helium Compression Plant, Test Area 1-115, intersection of Altair & Saturn Boulevards, Boron, Kern County, CA

  19. Adsorption of Helium Atoms on Two-Dimensional Substrates

    NASA Astrophysics Data System (ADS)

    Burganova, Regina; Lysogorskiy, Yury; Nedopekin, Oleg; Tayurskii, Dmitrii

    2016-01-01

    The study of the adsorption phenomenon of helium began many decades ago with the discovery of graphite as a homogeneous substrate for the investigation of physically adsorbed monolayer films. In particular, helium monoatomic layers on graphite were found to exhibit a very rich phase diagram. In the present work we have investigated the adsorption phenomenon of helium atoms on graphene and silicene substrates by means of density functional theory with Born-Oppenheimer approximation. Helium-substrate and helium-helium interactions were considered from first principles. Vibrational properties of adsorbed monolayers have been used to explore the stability of the system. This approach reproduces results describing the stability of a helium monolayer on graphene calculated by quantum Monte Carlo (QMC) simulations for low and high coverage cases. However, for the moderate coverage value there is a discrepancy with QMC results due to the lack of helium zero point motion.

  20. A helium liquefier using three 4 k pulse tube cryocoolers

    NASA Astrophysics Data System (ADS)

    Wang, Chao; Oviedo, Abner

    2012-06-01

    We have developed a helium liquefier which can be used for recondensing/reliquefying helium vapor in a helium cryostat or liquefying helium gas in a storage dewar. The helium liquefier employs three 4 K pulse tube cryocoolers, Cryomech model PT415. Each PT415 has remote motor/rotary valve assembly to minimize vibration, providing ≥ 1.5W at 4.2K. The liquefier can liquefy room temperature helium gas with a liquefaction rate of 62 Liter/day. When installing it in the cryostat, it can recondense and reliquefy helium vapor with a rate of 78 L/day. The liquefier will be installed in a gravitational wave detector in Brazil to recondense/reliquefy the helium boil off from the cryostat.

  1. An efficient helium circulation system with small GM cryocoolers

    NASA Astrophysics Data System (ADS)

    Takeda, Tsunehiro; Okamoto, Masayoshi; Atsuda, Kazuhiro; Kobayashi, Akihiro; Owaki, Takashi; Katagiri, Keishi

    2008-01-01

    We developed a helium circulating system that re-liquefies all the evaporating helium gas and consumes far less power than conventional systems, because warm helium gas at about 40 K collected high above the surface of the liquid helium in the Dewar is used to keep the Dewar cold, and because cold helium gas just above the liquid helium surface is collected and re-liquefied while still cold. A special transfer tube with multi-concentric pipes was developed to make the system operate efficiently. The system can produce up to 35.5 l/D of liquid helium from the evaporated helium using two 1.5 W@4.2 K GM cryocoolers.

  2. 2. SOUTHEAST SIDE. HIGH PRESSURE HELIUM STORAGE TANKS AT LEFT. ...

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

    2. SOUTHEAST SIDE. HIGH PRESSURE HELIUM STORAGE TANKS AT LEFT. - Edwards Air Force Base, Air Force Rocket Propulsion Laboratory, Helium Compression Plant, Test Area 1-115, intersection of Altair & Saturn Boulevards, Boron, Kern County, CA

  3. The dynamics and helium distribution in hydrogen-helium fluid planets

    NASA Technical Reports Server (NTRS)

    Stevenson, D. J.; Salpeter, E. E.

    1977-01-01

    The simple case of a homogeneous planet without first-order phase transitions is considered and an investigation is conducted concerning a pure hydrogen planet in which a first-order phase transition takes place from fluid molecular hydrogen to fluid metallic hydrogen. Attention is also given to convection in the presence of a compositional gradient, the effects of helium insolubility in a cooling hydrogen-helium planet, a hydrogen-helium planet in its early evolution, and the case in which influence of phase transition occurs much later in the evolution of the planet.

  4. Exocyclic carbons adjacent to the N6 of adenine are targets for oxidation by the Escherichia coli adaptive response protein AlkB.

    PubMed

    Li, Deyu; Delaney, James C; Page, Charlotte M; Yang, Xuedong; Chen, Alvin S; Wong, Cintyu; Drennan, Catherine L; Essigmann, John M

    2012-05-30

    The DNA and RNA repair protein AlkB removes alkyl groups from nucleic acids by a unique iron- and α-ketoglutarate-dependent oxidation strategy. When alkylated adenines are used as AlkB targets, earlier work suggests that the initial target of oxidation can be the alkyl carbon adjacent to N1. Such may be the case with ethano-adenine (EA), a DNA adduct formed by an important anticancer drug, BCNU, whereby an initial oxidation would occur at the carbon adjacent to N1. In a previous study, several intermediates were observed suggesting a pathway involving adduct restructuring to a form that would not hinder replication, which would match biological data showing that AlkB almost completely reverses EA toxicity in vivo. The present study uses more sensitive spectroscopic methodology to reveal the complete conversion of EA to adenine; the nature of observed additional putative intermediates indicates that AlkB conducts a second oxidation event in order to release the two-carbon unit completely. The second oxidation event occurs at the exocyclic carbon adjacent to the N(6) atom of adenine. The observation of oxidation of a carbon at N(6) in EA prompted us to evaluate N(6)-methyladenine (m6A), an important epigenetic signal for DNA replication and many other cellular processes, as an AlkB substrate in DNA. Here we show that m6A is indeed a substrate for AlkB and that it is converted to adenine via its 6-hydroxymethyl derivative. The observation that AlkB can demethylate m6A in vitro suggests a role for AlkB in regulation of important cellular functions in vivo. PMID:22512456

  5. Cancer-testis antigen lymphocyte antigen 6 complex locus K is a serologic biomarker and a therapeutic target for lung and esophageal carcinomas.

    PubMed

    Ishikawa, Nobuhisa; Takano, Atsushi; Yasui, Wataru; Inai, Kouki; Nishimura, Hitoshi; Ito, Hiroyuki; Miyagi, Yohei; Nakayama, Haruhiko; Fujita, Masahiro; Hosokawa, Masao; Tsuchiya, Eiju; Kohno, Nobuoki; Nakamura, Yusuke; Daigo, Yataro

    2007-12-15

    Gene expression profile analyses of non-small cell lung carcinomas (NSCLC) and esophageal squamous cell carcinomas (ESCC) revealed that lymphocyte antigen 6 complex locus K (LY6K) was specifically expressed in testis and transactivated in a majority of NSCLCs and ESCCs. Immunohistochemical staining using 406 NSCLC and 265 ESCC specimens confirmed that LY6K overexpression was associated with poor prognosis for patients with NSCLC (P = 0.0003), as well as ESCC (P = 0.0278), and multivariate analysis confirmed its independent prognostic value for NSCLC (P = 0.0035). We established an ELISA to measure serum LY6K and found that the proportion of the serum LY6K-positive cases was 38 of 112 (33.9%) NSCLC and 26 of 81 (32.1%) ESCC, whereas only 3 of 74 (4.1%) healthy volunteers were falsely diagnosed. In most cases, there was no correlation between serum LY6K and conventional tumor markers of carcinoembryonic antigen (CEA) and cytokeratin 19-fragment (CYFRA 21-1) values. A combined ELISA for both LY6K and CEA classified 64.7% of lung adenocarcinoma patients as positive, and the use of both LY6K and CYFRA 21-1 increased sensitivity in the detection of lung squamous cell carcinomas and ESCCs up to 70.4% and 52.5%, respectively, whereas the false positive rate was 6.8% to 9.5%. In addition, knocked down of LY6K expression with small interfering RNAs resulted in growth suppression of the lung and esophageal cancer cells. Our data imply that a cancer-testis antigen, LY6K, should be useful as a new type of tumor biomarker and probably as a target for the development of new molecular therapies for cancer treatment.

  6. Advanced helium purge seals for Liquid Oxygen (LOX) turbopumps

    NASA Technical Reports Server (NTRS)

    Shapiro, Wilbur; Lee, Chester C.

    1989-01-01

    Program objectives were to determine three advanced configurations of helium buffer seals capable of providing improved performance in a space shuttle main engine (SSME), high-pressure liquid oxygen (LOX) turbopump environment, and to provide NASA with the analytical tools to determine performance of a variety of seal configurations. The three seal designs included solid-ring fluid-film seals often referred to as floating ring seals, back-to-back fluid-film face seals, and a circumferential sectored seal that incorporated inherent clearance adjustment capabilities. Of the three seals designed, the sectored seal is favored because the self-adjusting clearance features accommodate the variations in clearance that will occur because of thermal and centrifugal distortions without compromising performance. Moreover, leakage can be contained well below the maximum target values; minimizing leakage is important on the SSME since helium is provided by an external tank. A reduction in tank size translates to an increase in payload that can be carried on board the shuttle. The computer codes supplied under this program included a code for analyzing a variety of gas-lubricated, floating ring, and sector seals; a code for analyzing gas-lubricated face seals; a code for optimizing and analyzing gas-lubricated spiral-groove face seals; and a code for determining fluid-film face seal response to runner excitations in as many as five degrees of freedom. These codes proved invaluable for optimizing designs and estimating final performance of the seals described.

  7. Targeting Atp6v1c1 Prevents Inflammation and Bone Erosion Caused by Periodontitis and Reveals Its Critical Function in Osteoimmunology

    PubMed Central

    Wang, Lin; Lu, Yun; Li, Qian; Zhu, Zheng; Shao, Jian-Zhong; Chen, Wei

    2015-01-01

    Periodontal disease (Periodontitis) is a serious disease that affects a majority of adult Americans and is associated with other systemic diseases, including diabetes, rheumatoid arthritis, and other inflammatory diseases. While great efforts have been devoted toward understanding the pathogenesis of periodontitis, there remains a pressing need for developing potent therapeutic strategies for targeting this pervasive and destructive disease. In this study, we utilized novel adeno-associated virus (AAV)-mediated Atp6v1c1 knockdown gene therapy to treat bone erosion and inflammatory caused by periodontitis in mouse model. Atp6v1c1 is a subunit of the V-ATPase complex and regulator of the assembly of the V0 and V1 domains of the V-ATPase complex. We demonstrated previously that Atp6v1c1 has an essential function in osteoclast mediated bone resorption. We hypothesized that Atp6v1c1 may be an ideal target to prevent the bone erosion and inflammation caused by periodontitis. To test the hypothesis, we employed AAV RNAi knockdown of Atp6v1c1 gene expression to prevent bone erosion and gingival inflammation simultaneously. We found that lesion-specific injection of AAV-shRNA-Atp6v1c1 into the periodontal disease lesions protected against bone erosion (>85%) and gingival inflammation caused by P. gingivalis W50 infection. AAV-mediated Atp6v1c1 knockdown dramatically reduced osteoclast numbers and inhibited the infiltration of dendritic cells and macrophages in the bacteria-induced inflammatory lesions in periodontitis. Silencing of Atp6v1c1 expression also prevented the expressions of osteoclast-related genes and pro-inflammatory cytokine genes. Our data suggests that AAV-shRNA-Atp6v1c1 treatment can significantly attenuate the bone erosion and inflammation caused by periodontitis, indicating the dual function of AAV-shRNA-Atp6v1c1 as an inhibitor of bone erosion mediated by osteoclasts, and as an inhibitor of inflammation through down-regulation of pro

  8. Tacrolimus (FK506) prevents early stages of ethanol induced hepatic fibrosis by targeting LARP6 dependent mechanism of collagen synthesis.

    PubMed

    Manojlovic, Zarko; Blackmon, John; Stefanovic, Branko

    2013-01-01

    Tacrolimus (FK506) is a widely used immunosuppressive drug. Its effects on hepatic fibrosis have been controversial and attributed to immunosuppression. We show that in vitro FK506, inhibited synthesis of type I collagen polypeptides, without affecting expression of collagen mRNAs. In vivo, administration of FK506 at a dose of 4 mg/kg completely prevented development of alcohol/carbon tetrachloride induced liver fibrosis in rats. Activation of hepatic stellate cells (HSCs) was absent in the FK506 treated livers and expression of collagen α2(I) mRNA was at normal levels. Collagen α1(I) mRNA was increased in the FK506 treated livers, but this mRNA was not translated into α1(I) polypeptide. No significant inflammation was associated with the fibrosis model used. FK506 binding protein 3 (FKBP3) is one of cellular proteins which binds FK506 with high affinity. We discovered that FKBP3 interacts with LARP6 and LARP6 is the major regulator of translation and stability of collagen mRNAs. In the presence of FK506 the interaction between FKBP3 and LARP6 is weakened and so is the pull down of collagen mRNAs with FKBP3. We postulate that FK506 inactivates FKBP3 and that lack of interaction of LARP6 and FKBP3 results in aberrant translation of collagen mRNAs and prevention of fibrosis. This is the first report of such activity of FK506 and may renew the interest in using this drug to alleviate hepatic fibrosis.

  9. Tacrolimus (FK506) Prevents Early Stages of Ethanol Induced Hepatic Fibrosis by Targeting LARP6 Dependent Mechanism of Collagen Synthesis

    PubMed Central

    Manojlovic, Zarko; Blackmon, John; Stefanovic, Branko

    2013-01-01

    Tacrolimus (FK506) is a widely used immunosuppressive drug. Its effects on hepatic fibrosis have been controversial and attributed to immunosuppression. We show that in vitro FK506, inhibited synthesis of type I collagen polypeptides, without affecting expression of collagen mRNAs. In vivo, administration of FK506 at a dose of 4 mg/kg completely prevented development of alcohol/carbon tetrachloride induced liver fibrosis in rats. Activation of hepatic stellate cells (HSCs) was absent in the FK506 treated livers and expression of collagen α2(I) mRNA was at normal levels. Collagen α1(I) mRNA was increased in the FK506 treated livers, but this mRNA was not translated into α1(I) polypeptide. No significant inflammation was associated with the fibrosis model used. FK506 binding protein 3 (FKBP3) is one of cellular proteins which binds FK506 with high affinity. We discovered that FKBP3 interacts with LARP6 and LARP6 is the major regulator of translation and stability of collagen mRNAs. In the presence of FK506 the interaction between FKBP3 and LARP6 is weakened and so is the pull down of collagen mRNAs with FKBP3. We postulate that FK506 inactivates FKBP3 and that lack of interaction of LARP6 and FKBP3 results in aberrant translation of collagen mRNAs and prevention of fibrosis. This is the first report of such activity of FK506 and may renew the interest in using this drug to alleviate hepatic fibrosis. PMID:23755290

  10. Dynamics of vortex assisted metal condensation in superfluid helium

    NASA Astrophysics Data System (ADS)

    Popov, Evgeny; Mammetkuliyev, Muhammet; Eloranta, Jussi

    2013-05-01

    Laser ablation of copper and silver targets immersed in bulk normal and superfluid 4He was studied through time-resolved shadowgraph photography. In normal fluid, only a sub-millimeter cavitation bubble is created and immediate formation of metal clusters is observed within a few hundred microseconds. The metal clusters remain spatially tightly focused up to 15 ms, and it is proposed that this observation may find applications in particle image velocimetry. In superfluid helium, the cavitation bubble formation process is distinctly different from the normal fluid. Due to the high thermal conductivity and an apparent lag in the breakdown of superfluidity, about 20% of the laser pulse energy was transferred directly into the liquid and a large gas bubble, up to several millimeters depending on laser pulse energy, is created. The internal temperature of the gas bubble is estimated to exceed 9 K and the following bubble cool down period therefore includes two separate phase transitions: gas-normal liquid and normal liquid-superfluid. The last stage of the cool down process was assigned to the superfluid lambda transition where a sudden formation of large metal clusters is observed. This is attributed to high vorticity created in the volume where the gas bubble previously resided. As shown by theoretical bosonic density functional theory calculations, quantized vortices can trap atoms and dimers efficiently, exhibiting static binding energies up to 22 K. This, combined with hydrodynamic Bernoulli attraction, yields total binding energies as high as 35 K. For larger clusters, the static binding energy increases as a function of the volume occupied in the liquid to minimize the surface tension energy. For heliophobic species an energy barrier develops as a function of the cluster size, whereas heliophilics show barrierless entry into vortices. The present theoretical and experimental observations are used to rationalize the previously reported metal nanowire assembly in

  11. Targeting the sugar metabolism of tumors with a first-in-class 6-phosphofructo-2-kinase (PFKFB4) inhibitor

    PubMed Central

    Chesney, Jason; Clark, Jennifer; Lanceta, Lilibeth; Trent, John O.; Telang, Sucheta

    2015-01-01

    Human tumors exhibit increased glucose uptake and metabolism as a result of high demand for ATP and anabolic substrates and this metabolotype is a negative prognostic indicator for survival. Recent studies have demonstrated that cancer cells from several tissue origins and genetic backgrounds require the expression of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 4 (PFKFB4), a regulatory enzyme that synthesizes an allosteric activator of glycolysis, fructose-2,6-bisphosphate. We report the discovery of a first-in-class PFKFB4 inhibitor, 5-(n-(8-methoxy-4-quinolyl)amino)pentyl nitrate (5MPN), using structure-based virtual computational screening. We find that 5MPN is a selective inhibitor of PFKFB4 that suppresses the glycolysis and proliferation of multiple human cancer cell lines but not non-transformed epithelial cells in vitro. Importantly, 5MPN has high oral bioavailability and per os administration of a non-toxic dose of 5MPN suppresses the glucose metabolism and growth of tumors in mice. PMID:26221874

  12. Targeting the sugar metabolism of tumors with a first-in-class 6-phosphofructo-2-kinase (PFKFB4) inhibitor.

    PubMed

    Chesney, Jason; Clark, Jennifer; Lanceta, Lilibeth; Trent, John O; Telang, Sucheta

    2015-07-20

    Human tumors exhibit increased glucose uptake and metabolism as a result of high demand for ATP and anabolic substrates and this metabolotype is a negative prognostic indicator for survival. Recent studies have demonstrated that cancer cells from several tissue origins and genetic backgrounds require the expression of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 4 (PFKFB4), a regulatory enzyme that synthesizes an allosteric activator of glycolysis, fructose-2,6-bisphosphate. We report the discovery of a first-in-class PFKFB4 inhibitor, 5-(n-(8-methoxy-4-quinolyl)amino)pentyl nitrate (5MPN), using structure-based virtual computational screening. We find that 5MPN is a selective inhibitor of PFKFB4 that suppresses the glycolysis and proliferation of multiple human cancer cell lines but not non-transformed epithelial cells in vitro. Importantly, 5MPN has high oral bioavailability and per os administration of a non-toxic dose of 5MPN suppresses the glucose metabolism and growth of tumors in mice.

  13. Identification of Sc-type ILV6 as a target to reduce diacetyl formation in lager brewers' yeast.

    PubMed

    Duong, C T; Strack, L; Futschik, M; Katou, Y; Nakao, Y; Fujimura, T; Shirahige, K; Kodama, Y; Nevoigt, E

    2011-11-01

    Diacetyl causes an unwanted buttery off-flavor in lager beer. It is spontaneously generated from α-acetolactate, an intermediate of yeast's valine biosynthesis released during the main beer fermentation. Green lager beer has to undergo a maturation process lasting two to three weeks in order to reduce the diacetyl level below its taste-threshold. Therefore, a reduction of yeast's α-acetolactate/diacetyl formation without negatively affecting other brewing relevant traits has been a long-term demand of brewing industry. Previous attempts to reduce diacetyl production by either traditional approaches or rational genetic engineering had different shortcomings. Here, three lager yeast strains with marked differences in diacetyl production were studied with regard to gene copy numbers as well as mRNA abundances under conditions relevant to industrial brewing. Evaluation of data for the genes directly involved in the valine biosynthetic pathway revealed a low expression level of Sc-ILV6 as a potential molecular determinant for low diacetyl formation. This hypothesis was verified by disrupting the two copies of Sc-ILV6 in a commercially used lager brewers' yeast strain, which resulted in 65% reduction of diacetyl concentration in green beer. The Sc-ILV6 deletions did not have any perceptible impact on beer taste. To our knowledge, this has been the first study exploiting natural diversity of lager brewers' yeast strains for strain optimization.

  14. ASK1 (MAP3K5) as a potential therapeutic target in malignant fibrous histiocytomas with 12q14-q15 and 6q23 amplifications.

    PubMed

    Chibon, Frédéric; Mariani, Odette; Derré, Josette; Mairal, Aline; Coindre, Jean-Michel; Guillou, Louis; Sastre, Xavier; Pédeutour, Florence; Aurias, Alain

    2004-05-01

    Malignant fibrous histiocytomas (MFHs) are aggressive tumors without any definable line of differentiation. We recently demonstrated that about 20% of them are characterized by high-level amplifications of the 12q14-q15 chromosome region, associated with either 1p32 or 6q23 band amplification. This genetic finding, very similar to that in well-differentiated liposarcomas, strongly suggests that these tumors actually correspond to undifferentiated liposarcomas. It also suggests that the lack of differentiation could be the consequence of amplification of target genes localized in the 1p32 or 6q23 bands. We report here the characterization by array CGH of the 6q23 minimal region of amplification. Our findings demonstrate that amplification and overexpression of ASK1 (MAP3K5), a gene localized in the 6q23 band and encoding a mitogen-activated protein kinase kinase kinase of the JNK-MAPK signaling pathway, could inhibit the adipocytic differentiation process of the tumor cells. Treatment of a cell line with specific inhibitors of ASK1 protein resulted in the bypass of the differentiation block and induction of a strong adipocytic differentiation. These observations indicate that ASK1 is a target for new therapeutic management of these aggressive tumors. PMID:15034865

  15. The SCF-FBXW5 E3-ubiquitin ligase is regulated by PLK4 and targets HsSAS-6 to control centrosome duplication.

    PubMed

    Puklowski, Anja; Homsi, Yahya; Keller, Debora; May, Martin; Chauhan, Sangeeta; Kossatz, Uta; Grünwald, Viktor; Kubicka, Stefan; Pich, Andreas; Manns, Michael P; Hoffmann, Ingrid; Gönczy, Pierre; Malek, Nisar P

    2011-08-01

    Deregulated centrosome duplication can result in genetic instability and contribute to tumorigenesis. Here, we show that centrosome duplication is regulated by the activity of an E3-ubiquitin ligase that employs the F-box protein FBXW5 (ref. 3) as its targeting subunit. Depletion of endogenous FBXW5 or overexpression of an F-box-deleted mutant version results in centrosome overduplication and formation of multipolar spindles. We identify the centriolar protein HsSAS-6 (refs 4,5) as a critical substrate of the SCF-FBXW5 complex. FBXW5 binds HsSAS-6 and promotes its ubiquitylation in vivo. The activity of SCF-FBXW5 is in turn negatively regulated by Polo-like kinase 4 (PLK4), which phosphorylates FBXW5 at Ser 151 to suppress its ability to ubiquitylate HsSAS-6. FBXW5 is a cell-cycle-regulated protein with expression levels peaking at the G1/S transition. We show that FBXW5 levels are controlled by the anaphase-promoting (APC/C) complex, which targets FBXW5 for degradation during mitosis and G1, thereby helping to reset the centrosome duplication machinery. In summary, we show that a cell-cycle-regulated SCF complex is regulated by the kinase PLK4, and that this in turn restricts centrosome re-duplication through degradation of the centriolar protein HsSAS-6. PMID:21725316

  16. miR-155 targets histone deacetylase 4 (HDAC4) and impairs transcriptional activity of B-cell lymphoma 6 (BCL6) in the Eµ-miR-155 transgenic mouse model

    PubMed Central

    Sandhu, Sukhinder K.; Volinia, Stefano; Costinean, Stefan; Galasso, Marco; Neinast, Reid; Santhanam, Ramasamy; Parthun, Mark R.; Perrotti, Danilo; Marcucci, Guido; Garzon, Ramiro; Croce, Carlo M.

    2012-01-01

    Multiple studies have established that microRNAs (miRNAs) are involved in the initiation and progression of cancer. Notably, miR-155 is one of the most overexpressed miRNAs in several solid and hematological malignancies. Ectopic miR-155 expression in mice B cells (Eμ-miR-155 transgenic mice) has been shown to induce pre–B-cell proliferation followed by high-grade lymphoma/leukemia. Loss of miR-155 in mice resulted in impaired immunity due to defective T-cell–mediated immune response. Here we provide a mechanistic insight into miR-155–induced leukemogenesis in the Eμ-miR-155 mouse model through genome-wide transcriptome analysis of naïve B cells and target studies. We found that a key transcriptional repressor and proto-oncogene, Bcl6 is significantly down-regulated in Eμ-miR-155 mice. The reduction of Bcl6 subsequently leads to de-repression of some of the known Bcl6 targets like inhibitor of differentiation (Id2), interleukin-6 (IL6), cMyc, Cyclin D1, and Mip1α/ccl3, all of which promote cell survival and proliferation. We show that Bcl6 is indirectly regulated by miR-155 through Mxd1/Mad1 up-regulation. Interestingly, we found that miR-155 directly targets HDAC4, a corepressor partner of BCL6. Furthermore, ectopic expression of HDAC4 in human-activated B-cell–type diffuse large B-cell lymphoma (DLBCL) cells results in reduced miR-155–induced proliferation, clonogenic potential, and increased apoptosis. Meta-analysis of the diffuse large B-cell lymphoma patient microarray data showed that miR-155 expression is inversely correlated with Bcl6 and Hdac4. Hence this study provides a better understanding of how miR-155 causes disruption of the BCL6 transcriptional machinery that leads to up-regulation of the survival and proliferation genes in miR-155–induced leukemias. PMID:23169640

  17. Phophatidylinositol-3 kinase/mammalian target of rapamycin/p70S6K regulates contractile protein accumulation in airway myocyte differentiation.

    PubMed

    Halayko, Andrew J; Kartha, Sreedharan; Stelmack, Gerald L; McConville, John; Tam, John; Camoretti-Mercado, Blanca; Forsythe, Sean M; Hershenson, Marc B; Solway, Julian

    2004-09-01

    Increased airway smooth muscle in airway remodeling results from myocyte proliferation and hypertrophy. Skeletal and vascular smooth muscle hypertrophy is induced by phosphatidylinositide-3 kinase (PI(3) kinase) via mammalian target of rapamycin (mTOR) and p70S6 kinase (p70S6K). We tested the hypothesis that this pathway regulates contractile protein accumulation in cultured canine airway myocytes acquiring an elongated contractile phenotype in serum-free culture. In vitro assays revealed a sustained activation of PI(3) kinase and p70S6K during serum deprivation up to 12 d, with concomitant accumulation of SM22 and smooth muscle myosin heavy chain (smMHC) proteins. Immunocytochemistry revealed that activation of PI3K/mTOR/p70S6K occurred almost exclusively in myocytes that acquire the contractile phenotype. Inhibition of PI(3) kinase or mTOR with LY294002 or rapamycin blocked p70S6K activation, prevented formation of large elongated contractile phenotype myocytes, and blocked accumulation of SM22 and smMHC. Inhibition of MEK had no effect. Steady-state mRNA abundance for SM22 and smMHC was unaffected by blocking p70S6K activation. These studies provide primary evidence that PI(3) kinase and mTOR activate p70S6K in airway myocytes leading to the accumulation of contractile apparatus proteins, differentiation, and growth of large, elongated contractile phenotype airway smooth muscle cells. PMID:15105162

  18. The effect of MC and MN stabilizer additions on the creep rupture properties of helium implanted Fe-25% Ni-15% Cr austenitic alloy

    NASA Astrophysics Data System (ADS)

    Yamamoto, Norikazu; Nagakawa, Johsei; Shiraishi, Haruki

    1995-10-01

    Helium embrittlement resistance of Fe-25% Ni-15% Cr austenitic alloys with various MX (M = V, Ti, Nb, Zr; X = C, N) stabilizers was compared through post helium implantation creep testing at 923 K. While significant deterioration by helium in terms of creep rupture time and elongation occurred for all materials investigated, the suppression of the deterioration, especially in rupture time, was discerned for the materials in which semi-coherent MC (M = Ti, Ti + Nb, V + Ti) particles were distributed at high density. The material which contains the incoherent M 23C 6 as predominant precipitates seems to be less degraded by helium than those containing the MXs (M = Zr, V; X = C, N), if compared at the same number density of precipitates. Therefore, it is suggested that the high density dispersion of incoherent M 23C 6 as well as semi-coherent Ti containing MC particles would be beneficial in reducing the detrimental helium influences on mechanical properties.

  19. Excitation of target Auger-electron emission by the impact of highly charged ions: N sup 6+ , O sup 7+ , and Ne sup 9+ on Pt(110)

    SciTech Connect

    Schippers, S.; Hustedt, S.; Heiland, W. ); Koehrbrueck, R. ); Bleck-Neuhaus, J. ); Kemmler, J. ); Lecler, D.; Stolterfoht, N. )

    1992-10-01

    We studied the interaction of highly charged ions on metal surfaces leading to the emission of electrons from the projectile and from the target. The target electrons are due to potential emission, kinetic emission, and Auger-electron emission. In our electron spectra two types of target Auger electrons are distinguished. Electrons near 135 and 220 eV are ascribed to Pt {ital N}{sub 45}{ital O1}{ital O23} and {ital N}{sub 45}{ital N67}{ital V} Auger transitions. They are caused by {ital K}-vacancy transfer into the Pt {ital N} shell and are only emitted under bombardment with N{sup 6+} and O{sup 7+}. The other type of electrons near 40 and 60 eV are ascribed to Pt {ital O}{sub 23}{ital VV} and {ital N}{sub 67}{ital VV} Auger transitions. They are due to direct ionization and are emitted under bombardment with each projectile used. According to our analysis, the initial projectile {ital K}-shell vacancy survives the transport to and at least 8{times}10{sup {minus}16} s within the target surface.

  20. Anti-tumoral, anti-angiogenic and anti-metastatic efficacy of a tetravalent bispecific antibody (TAvi6) targeting VEGF-A and angiopoietin-2.

    PubMed

    Scheuer, Werner; Thomas, Markus; Hanke, Petra; Sam, Johannes; Osl, Franz; Weininger, Diana; Baehner, Monika; Seeber, Stefan; Kettenberger, Hubert; Schanzer, Jürgen; Brinkmann, Ulrich; Weidner, K Michael; Regula, Jörg; Klein, Christian

    2016-01-01

    Vascular endothelial growth factor (VEGF)-A blockade has been validated clinically as a treatment for human cancers. Angiopoietin-2 (Ang-2) is a key regulator of blood vessel remodeling and maturation. In tumors, Ang-2 is up-regulated and an unfavorable prognostic factor. Recent data demonstrated that Ang-2 inhibition mediates anti-tumoral effects. We generated a tetravalent bispecific antibody (Ang-2-VEGF-TAvi6) targeting VEGF-A with 2 arms based on bevacizumab (Avastin®), and targeting Ang-2 with 2 arms based on a novel anti-Ang-2 antibody (LC06). The two Ang-2-targeting single-chain variable fragments are disulfide-stabilized and fused to the C-terminus of the heavy chain of bevacizumab. Treatment with Ang-2-VEGF-A-TAvi6 led to a complete abrogation of angiogenesis in the cornea micropocket assay. Metastatic spread and tumor growth of subcutaneous, orthotopic and anti-VEGF-A resistant tumors were also efficiently inhibited. These data further establish Ang-2-VEGF bispecific antibodies as a promising anti-angiogenic, anti-metastatic and anti-tumor agent for the treatment of cancer. PMID:26864324

  1. Anti-tumoral, anti-angiogenic and anti-metastatic efficacy of a tetravalent bispecific antibody (TAvi6) targeting VEGF-A and angiopoietin-2

    PubMed Central

    Scheuer, Werner; Thomas, Markus; Hanke, Petra; Sam, Johannes; Osl, Franz; Weininger, Diana; Baehner, Monika; Seeber, Stefan; Kettenberger, Hubert; Schanzer, Jürgen; Brinkmann, Ulrich; Weidner, K. Michael; Regula, Jörg; Klein, Christian

    2016-01-01

    ABSTRACT Vascular endothelial growth factor (VEGF)-A blockade has been validated clinically as a treatment for human cancers. Angiopoietin-2 (Ang-2) is a key regulator of blood vessel remodeling and maturation. In tumors, Ang-2 is up-regulated and an unfavorable prognostic factor. Recent data demonstrated that Ang-2 inhibition mediates anti-tumoral effects. We generated a tetravalent bispecific antibody (Ang-2-VEGF-TAvi6) targeting VEGF-A with 2 arms based on bevacizumab (Avastin®), and targeting Ang-2 with 2 arms based on a novel anti-Ang-2 antibody (LC06). The two Ang-2-targeting single-chain variable fragments are disulfide-stabilized and fused to the C-terminus of the heavy chain of bevacizumab. Treatment with Ang-2-VEGF-A-TAvi6 led to a complete abrogation of angiogenesis in the cornea micropocket assay. Metastatic spread and tumor growth of subcutaneous, orthotopic and anti-VEGF-A resistant tumors were also efficiently inhibited. These data further establish Ang-2-VEGF bispecific antibodies as a promising anti-angiogenic, anti-metastatic and anti-tumor agent for the treatment of cancer. PMID:26864324

  2. Rogue Mantle Helium and Neon

    NASA Astrophysics Data System (ADS)

    Albarede, F.

    2007-12-01

    mid- ocean ridges, the characteristic times of melt extraction in each of these two environments are 10,000 y and 1 My, respectively, and the maximum thickness of refractory layers contributing their He to the magmas are 10 m and 100 m, respectively. The difference in 3He/4He ratios of ocean-island and mid-ocean ridge basalts and the preservation of solar neon are ascribed to the reservoirs rocks being stretched to a different extent during melting. Old fragments of oceanic lithosphere, and possibly cumulates from the magma ocean, rather than primordial mantle 'nuggets', should host most of the primordial He and Ne presently observed in oceanic basalts. Helium with high 3He/4He ratios may contain a component of primordial origin, but not necessarily reflect the reservoir in which it has been residing for most of the Earth's history.

  3. Superfluid Onset and 2D phase transitions of Helium-4 on Lithium and Sodium

    NASA Astrophysics Data System (ADS)

    Velasco, Angel; Huisman, Fawn; van Cleve, Eli; Taborek, Peter

    2012-02-01

    We have fabricated lithium and sodium films on quartz crystal microbalances (QCM) using in situ low temperature pulsed laser deposition. The frequency shift and dissipation of the QCM was measured as a function of helium pressure and chemical potential and used to construct the phase diagram of helium films on these substrates. Pressure measurement techniques based on an RGA mass spectrometer, which provides accurate measurement below 10-8 Torr will be described. Lithium and sodium are predicted to be intermediate strength substrates which are strong enough to be wetted by He-4 but weak enough that solid-like layers do not form, so they are candidates for observing sub-monolayer superfluidity in direct contact with a metallic surface. Helium adsorption isotherms and quenches between 0.5K and 1.6K on both lithium and sodium indicated continuous, sub-monolayer helium film growth and superfluid onsets in sub-monolayer films. Features below 1K indicate a collision between a classical 2D liquid/vapor phase transition and the Kosterlitz-Thouless superfluid phase transition. We see no evidence for the pre-wetting step instability predicted for helium on sodium.

  4. Flow visualization in superfluid helium-4 using He2 molecular tracers

    NASA Astrophysics Data System (ADS)

    Guo, Wei

    Flow visualization in superfluid helium is challenging, yet crucial for attaining a detailed understanding of quantum turbulence. Two problems have impeded progress: finding and introducing suitable tracers that are small yet visible; and unambiguous interpretation of the tracer motion. We show that metastable He2 triplet molecules are outstanding tracers compared with other particles used in helium. These molecular tracers have small size and relatively simple behavior in superfluid helium: they follow the normal fluid motion at above 1 K and will bind to quantized vortex lines below about 0.6 K. A laser-induced fluorescence technique has been developed for imaging the He2 tracers. We will present our recent experimental work on studying the normal-fluid motion by tracking thin lines of He2 tracers created via femtosecond laser-field ionization in helium. We will also discuss a newly launched experiment on visualizing vortex lines in a magnetically levitated superfluid helium drop by imaging the He2 tracers trapped on the vortex cores. This experiment will enable unprecedented insight into the behavior of a rotating superfluid drop and will untangle several key issues in quantum turbulence research. We acknowledge the support from the National Science Foundation under Grant No. DMR-1507386 and the US Department of Energy under Grant No. DE-FG02 96ER40952.

  5. Synthesis and evaluation of a radioiodinated peptide probe targeting αvβ6 integrin for the detection of pancreatic ductal adenocarcinoma

    SciTech Connect

    Ueda, Masashi; Fukushima, Takahiro; Ogawa, Kei; Kimura, Hiroyuki; Ono, Masahiro; Yamaguchi, Takashi; Ikehara, Yuzuru; Saji, Hideo

    2014-03-14

    Highlights: • We developed a radioiodinated peptide probe targeting αvβ6 integrin ({sup 123}I-IFMDV2). • {sup 123}I-IFMDV2 had a high affinity and selectivity for αvβ6 integrin. • {sup 123}I-IFMDV2 showed a specific binding to αvβ6 integrin in vivo. • {sup 123}I-IFMDV2 enabled clear visualization of the αvβ6-integrin-positive tumor. - Abstract: Introduction: Pancreatic ductal adenocarcinoma (PDAC) remains a major cause of cancer-related death. Since significant upregulation of αvβ6 integrin has been reported in PDAC, this integrin is a promising target for PDAC detection. In this study, we aimed to develop a radioiodinated probe for the imaging of αvβ6 integrin-positive PDAC with single-photon emission computed tomography (SPECT). Methods: Four peptide probes were synthesized and screened by competitive and saturation binding assays using 2 PDAC cell lines (AsPC-1, αvβ6 integrin-positive; MIA PaCa-2, αvβ6 integrin-negative). The probe showing the best affinity was used to study the biodistribution assay, an in vivo blocking study, and SPECT imaging using tumor bearing mice. Autoradiography and immunohistochemical analysis were also performed. Results: Among the 4 probes examined in this study, {sup 125}I-IFMDV2 showed the highest affinity for αvβ6 integrin expressed in AsPC-1 cells and no affinity for MIA PaCa-2 cells. The accumulation of {sup 125}I-IFMDV2 in the AsPC-1 xenograft was 3–5 times greater than that in the MIA PaCa-2 xenograft, consistent with the expression of αvβ6 integrin in each xenograft, and confirmed by immunohistochemistry. Pretreatment with excess amounts of A20FMDV2 significantly blocked the accumulation of {sup 125}I-IFMDV2 in the AsPC-1 xenograft, but not in the MIA PaCa-2 xenograft. Furthermore, {sup 123}I-IFMDV2 enabled clear visualization of the AsPC-1 xenograft. Conclusion: {sup 123}I-IFMDV2 is a potential SPECT probe for the imaging of αvβ6 integrin in PDAC.

  6. The effects of tritium and decay helium on the fracture toughness properties of stainless steels

    SciTech Connect

    Morgan, M.J.

    1991-01-01

    J-integral fracture mechanics techniques and scanning electron microscopy observations were used to investigate the effects of tritium and its decay product, helium-3, on Types 304L, 316L, 21-6-9, A286, and JBK-75 (Modified A286) stainless steels. Tritium-exposed samples of each steel had lower fracture toughness values and less resistance to stable crack growth than control samples. Type 316L stainless steel was more resistant to the embrittling effects of tritium and decay helium than the other steels.

  7. The effects of tritium and decay helium on the fracture toughness properties of stainless steels

    SciTech Connect

    Morgan, M.J.

    1991-12-31

    J-integral fracture mechanics techniques and scanning electron microscopy observations were used to investigate the effects of tritium and its decay product, helium-3, on Types 304L, 316L, 21-6-9, A286, and JBK-75 (Modified A286) stainless steels. Tritium-exposed samples of each steel had lower fracture toughness values and less resistance to stable crack growth than control samples. Type 316L stainless steel was more resistant to the embrittling effects of tritium and decay helium than the other steels.

  8. Relative abundance of the helium isotopes He-3 and He-4 in the cosmic radiation

    NASA Technical Reports Server (NTRS)

    Jordan, S. P.; Meyer, P.

    1984-01-01

    The geomagnetic field near the equator is used to measure the He-3/He-4 abundance ratio near 6 GeV/nucleon. This ratio is found to be 0.24 + or - 0.05, under the assumption that the helium rigidity spectrum has the form dI/dR = about R exp(-2.65). If all He-3 is of secondary origin, this implies an interstellar mean escape-path length of about 15 g/sq cm, a value considerably larger than that determined from observations of heavier elements but compatible with measurements of the helium isotopic ratio at lower energies.

  9. Flow properties in expansion tube with helium, argon, air, and CO2

    NASA Technical Reports Server (NTRS)

    Miller, C. G.

    1974-01-01

    Test flow velocities from 5 to 7 km/sec were generated in a 6-in. expansion tube using helium, argon, air, and CO2 test gases. Pitot pressure profiles across the flow at the test section are presented for the four test gases, and measured flow quantities are compared to computer predicted values. Comparison of predicted and measured flow quantities suggests the expansion to be near thermochemical equilibrium for all test gases and implies the existence of a totally reflected shock at the secondary diaphragm. Argon, air, and CO2 flows were observed to attenuate while traversing the acceleration section, whereas no attenuation was observed for helium.

  10. Antroquinonol Targets FAK-Signaling Pathway Suppressed Cell Migration, Invasion, and Tumor Growth of C6 Glioma.

    PubMed

    Thiyagarajan, Varadharajan; Tsai, May-Jywan; Weng, Ching-Feng

    2015-01-01

    Focal adhesion kinase (FAK) is a non-receptor protein tyrosine that is overexpressed in many types of tumors and plays a pivotal role in multiple cell signaling pathways involved in cell survival, migration, and proliferation. This study attempts to determine the effect of synthesized antroquinonol on the modulation of FAK signaling pathways and explore their underlying mechanisms. Antroquinonol significantly inhibits cell viability with an MTT assay in both N18 neuroblastoma and C6 glioma cell lines, which exhibits sub G1 phase cell cycle, and further induction of apoptosis is confirmed by a TUNEL assay. Antroquinonol decreases anti-apoptotic proteins, whereas it increases p53 and pro-apoptotic proteins. Alterations of cell morphology are observed after treatment by atomic force microscopy. Molecular docking results reveal that antroquinonol has an H-bond with the Arg 86 residue of FAK. The protein levels of Src, pSrc, FAK, pFAK, Rac1, and cdc42 are decreased after antroquinonol treatment. Additionally, antroquinonol also regulates the expression of epithelial to mesenchymal transition (EMT) proteins. Furthermore, antroquinonol suppresses the C6 glioma growth in xenograft studies. Together, these results suggest that antroquinonol is a potential anti-tumorigenesis and anti-metastasis inhibitor of FAK. PMID:26517117

  11. Dynamics of the Galapagos hotspot from helium isotope geochemistry

    SciTech Connect

    Kurz, M.D.; Geist, D.

    1999-12-01

    The authors have measured the isotopes of He, Sr, Nd and Pb in a number of lava flows from the Galapagos Archipelago; the main goal is to use magmatic helium as a tracer of plume influence in the western volcanoes. Because the Galapagos lava flows are so well preserved, it is also possible to measure surface exposure ages using in situ cosmic-ray-produced {sup 3}He. The exposure ages range from {lt}0.1 to 580 Ka, are consistent with other chronological constrains, and provide the first direct dating of these lava flows. The new age data demonstrate the utility of the technique in this important age range and show that the western Galapagos volcanoes have been erupting distance compositions simultaneously for the last {approximately}10 Ka. The magmatic {sup 3}He/{sup 4}He ratios range from 6.0 to 27 times atmospheric (R{sub a}), with the highest values found on the islands of Isabella (16.8 R{sub a} for Vulcan Sierra Negra) and Fernandina (23 to 27 R{sub a}). Values from Santa Cruz are close to typical mid-ocean ridge basalt values (MORB, of {approximately}9 R{sub 2}) and Pinta has a {sup 3}He/{sup 4}He ratio lower than MORB (6.9 R{sub a}). These data confirm that the plume is centered beneath Fernandina which is the most active volcano in the archipelago and is at the leading edge of plate motion. The data are consistent with previous isotopic studies, confirming extensive contributions from depleted asthenospheric or lithospheric mantle sources, especially to the central islands. The most striking aspect of the helium isotopic data is that the {sup 3}He/{sup 4}He ratios decrease systematically in all directions from Fernandina. This spatial variability is assumed to reflect the contribution of the purest plume component to Fernandina magmatism, and shows that helium is a sensitive indicator of plume influence. The highest {sup 3}He/{sup 4}He ratios are found in volcanoes with lowest Na{sub 2}O(8) and FeO(8), which may relate to source composition as well as degree

  12. A configurational study of helium clusters doped with He(∗-) and He2(∗-).

    PubMed

    Rodríguez-Cantano, Rocío; González-Lezana, Tomás; Villarreal, Pablo; Gianturco, Franco A

    2015-03-14

    Helium clusters doped with electronically excited atomic and molecular helium anions He(∗-) and He2(∗-) at T = 0.4 K are studied by means of path integral Monte Carlo calculations. Geometry and energetics of the systems with up to 32 solvating He atoms are characterised. The interactions between the anions and the neutral He atoms have been described by fitting previously reported ab initio points to analytical expressions. The HeN-He(∗-) clusters with N > 6 display a structure defined by a bipyramid which completely solvates the atomic anion, whereas the rest of surrounding He atoms form a dimple around that initial cage. On the contrary, the structures observed for the HeN-He2(∗-) clusters clearly show the dopant located outside the helium droplet, thereby confirming the heliophobic character of He2(∗-). PMID:25770536

  13. A three-stage Stirling pulse tube cryocooler operating below the critical point of helium-4

    NASA Astrophysics Data System (ADS)

    Qiu, L. M.; Cao, Q.; Zhi, X. Q.; Gan, Z. H.; Yu, Y. B.; Liu, Y.

    2011-10-01

    Precooled phase shifters can significantly enhance the phase shift effect and further improve the performance of pulse tube cryocoolers. A separate three-stage Stirling pulse tube cryocooler (SPTC) with a cold inertance tube was designed and fabricated. Helium-4 instead of the rare helium-3 was used as the working fluid. The cryocooler reached a bottom temperature of 4.97 K with a net cooling power of 25 mW at 6.0 K. The operating frequency was 29.9 Hz and the charging pressure was 0.91 MPa. It is the first time a refrigeration temperature below the critical point of helium-4 was obtained in a three-stage Stirling pulse tube cryocooler.

  14. Density decrease in vanadium-base alloys irradiated in the dynamic helium charging experiment

    SciTech Connect

    Chung, H.M.; Galvin, T.M.; Smith, D.L.

    1996-04-01

    Combined effects of dynamically charged helium and neutron damage on density decrease (swelling) of V-4Cr-4Ti, V-5Ti, V-3Ti-1Si, and V-8Cr-6Ti alloys have been determined after irradiation to 18-31 dpa at 425-600{degrees}C in the Dynamic helium Charging Experiment (DHCE). To ensure better accuracy in density measurement, broken pieces of tensile specimens {approx} 10 times heavier than a transmission electron microscopy (TEM) disk were used. Density increases of the four alloys irradiated in the DHCE were <0.5%. This small change seems to be consistent with the negligible number density of microcavities characterized by TEM. Most of the dynamically produced helium atoms seem to have been trapped in the grain matrix without significant cavity nucleation or growth.

  15. A Study on the Heat Transfer Properties of Pressurized Helium II through Fine Channels

    SciTech Connect

    Kimura, N.; Nakai, H.; Yamamoto, A.; Murakami, M.; Shintomi, T.

    2006-04-27

    An experimental study was carried out on the heat transfer properties of pressurized superfluid helium in the Gorter-Mellink heat transfer region. By using channels of hydraulic diameter from 5.6 x 10- through 4.81 x 10-3 m, the heat transfer properties of pressurized superfluid helium were measured in the experiment. The temperature dependence of Gorter-Mellink parameter, AGM, is revealed from the experimental results. It is also proven that AGM depend only on temperature, and not on the channel size and shape. The effect of quantized vortices on heat transfer of pressurized superfluid helium is discussed in comparison of the channel diameter with the mean vortex line spacing.

  16. NUCLEAR CONDENSATE AND HELIUM WHITE DWARFS

    SciTech Connect

    Bedaque, Paulo F.; Berkowitz, Evan; Cherman, Aleksey E-mail: evanb@umd.edu

    2012-04-10

    We consider a high-density region of the helium phase diagram, where the nuclei form a Bose-Einstein condensate rather than a classical plasma or a crystal. Helium in this phase may be present in helium-core white dwarfs. We show that in this regime there is a new gapless quasiparticle not previously noticed, arising when the constraints imposed by gauge symmetry are taken into account. The contribution of this quasiparticle to the specific heat of a white dwarf core turns out to be comparable in a range of temperatures to the contribution from the particle-hole excitations of the degenerate electrons. The specific heat in the condensed phase is two orders of magnitude smaller than in the uncondensed plasma phase, which is the ground state at higher temperatures, and four orders of magnitude smaller than the specific heat that an ion lattice would provide, if formed. Since the specific heat of the core is an important input for setting the rate of cooling of a white dwarf star, it may turn out that such a change in the thermal properties of the cores of helium white dwarfs has observable implications.

  17. Diffusion of cyclooctane (1); helium (2)

    NASA Astrophysics Data System (ADS)

    Winkelmann, J.

    This document is part of Subvolume A `Gases in Gases, Liquids and their Mixtures' of Volume 15 `Diffusion in Gases, Liquids and Electrolytes' of Landolt-Börnstein Group IV `Physical Chemistry'. It is part of the chapter of the chapter `Diffusion in Pure Gases' and contains data on diffusion of (1) cyclooctane; (2) helium

  18. The Weakest Link: Bonding between Helium Atoms

    ERIC Educational Resources Information Center

    Lohr, Lawrence L.; Blinder, S. M.

    2007-01-01

    A highly simplified model for helium dimers that reproduces their essential features without the need for elaborate computation is presented. The He-He potential is predicted to have minimum of 10.9 K at a nuclear separation of 5.61 bohrs.

  19. Excitation of helium ion by positron impact

    SciTech Connect

    Khan, P.; Ghosh, A.S.

    1986-01-01

    Three (1s,2s,2p) and five (1s,2s,2p,3s-bar,3p-bar) -state close-coupling methods have been employed to calculate the n = 2 excitation cross sections of helium ion by positron impact. The effect of pseudostate is found to be very pronounced in the case of 1s-2s excitation.

  20. Helium-Shell Nucleosynthesis and Extinct Radioactivities

    NASA Astrophysics Data System (ADS)

    Meyer, B. S.; The, L.-S.; Clayton, D. D.; El Eid, M. F.

    2004-03-01

    We present details of explosive nucleosynthesis in the helium-burning shell of a 25 solar mass star. We describe the production of short-lived radioactivities in this environment. We finally describe how to access the details of our calculations over the world-wide web.