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Sample records for helium 6 target

  1. 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.

  2. 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.

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

    NASA Astrophysics Data System (ADS)

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

    2012-12-01

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

  4. 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.

  5. Photoionization and photofragmentation of SF6 in helium nanodroplets.

    PubMed

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

    2006-10-12

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

  6. 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.

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

    NASA Astrophysics Data System (ADS)

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

    2017-04-01

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

  8. 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.

  9. 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.

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

    NASA Astrophysics Data System (ADS)

    Dehdashti-Jahromi, M.; Farrokhpour, H.

    2017-02-01

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

  11. 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.

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

    SciTech Connect

    Morgan, M.J.; Lohmeier, D.

    1990-01-01

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

  13. Targeting interleukin-6 for noninfectious uveitis.

    PubMed

    Lin, Phoebe

    2015-01-01

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

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

    DOE PAGES

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

    2014-12-10

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

  15. 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.

  16. 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.

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

    NASA Technical Reports Server (NTRS)

    Moore, J. A.

    1975-01-01

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

  18. 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.

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

    SciTech Connect

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

    1982-01-01

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

  20. 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.

  1. 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.

  2. 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)].

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

    SciTech Connect

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

    1992-04-01

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

  4. 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

  5. Helium diffusion in carbonates

    NASA Astrophysics Data System (ADS)

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

    2013-12-01

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

  6. 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...

  7. 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...

  8. 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...

  9. 21 CFR 582.1355 - Helium.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

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

  10. 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...

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

    PubMed Central

    Michaud-Levesque, Jonathan; Richard, Stéphane

    2009-01-01

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

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

    PubMed

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

    2017-03-07

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

  13. Helium tables.

    NASA Technical Reports Server (NTRS)

    Havill, Clinton H

    1928-01-01

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

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

    SciTech Connect

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

    1993-10-01

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

  15. E5/E6 Target Generation Study (TARGEN)

    DTIC Science & Technology

    1988-07-01

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

  16. TARGETING CDK4 AND CDK6: FROM DISCOVERY TO THERAPY

    PubMed Central

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

    2015-01-01

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

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

    NASA Astrophysics Data System (ADS)

    Hammer, Markus; Seidel, Wolfhart

    1997-10-01

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

  18. 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

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

    PubMed Central

    Yun, Hyung-Mun

    2011-01-01

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

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

    PubMed Central

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

    2013-01-01

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

  1. Helium Plants and Storage. Design Manual 24.2.

    DTIC Science & Technology

    1980-06-01

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

  2. 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.

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

    NASA Astrophysics Data System (ADS)

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

    2002-05-01

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

  4. 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

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

    PubMed Central

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

    2017-01-01

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

  6. Ras Laffan helium recovery unit 2

    NASA Astrophysics Data System (ADS)

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

    2012-06-01

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

  7. 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.

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

    NASA Astrophysics Data System (ADS)

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

    2016-05-01

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

  9. 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.

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

    SciTech Connect

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

    2016-03-10

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

  11. 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.

  12. 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.

  13. Reprogramming metabolism by targeting sirtuin 6 attenuates retinal degeneration

    PubMed Central

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

    2016-01-01

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

  14. 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.

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

    PubMed

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

    1981-03-01

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

  16. 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.

  17. Helium transport in plasma edge regions

    NASA Astrophysics Data System (ADS)

    Abou-Gabal, Hanaa Hassan

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

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

    PubMed Central

    Johnson, Benny; Mahadevan, Daruka

    2015-01-01

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

  19. Molecular dynamics study of helium bubble pressure in tungsten

    NASA Astrophysics Data System (ADS)

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

    2015-06-01

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

  20. Helium damage and helium effusion in fully stabilised zirconia

    NASA Astrophysics Data System (ADS)

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

    2002-05-01

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

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

    PubMed

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

    2003-08-15

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

  2. Noncavitating Pump For Liquid Helium

    NASA Technical Reports Server (NTRS)

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

    1996-01-01

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

  3. 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.

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2016-09-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2016-12-01

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

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

    DTIC Science & Technology

    2010-09-01

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

  9. 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.

  10. Suicide by asphyxiation due to helium inhalation.

    PubMed

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

    2011-03-01

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

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

    PubMed

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

    2017-02-15

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

  12. 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

  13. 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.

  14. Pharmacologic targeting of S6K1 in PTEN-deficient neoplasia

    PubMed Central

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

    2017-01-01

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

  15. 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.

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

    PubMed Central

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

    2012-01-01

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

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

    SciTech Connect

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

    1990-01-01

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

  18. 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.

  19. 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.

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

    PubMed Central

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

    2009-01-01

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

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

    PubMed

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

    2016-10-01

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

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

    ERIC Educational Resources Information Center

    Becker, Marla G.; Calhoun, Deane

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

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

    NASA Astrophysics Data System (ADS)

    Underwood-Lemons, Theresa Ann

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

  4. Cavitation in flowing superfluid helium

    NASA Technical Reports Server (NTRS)

    Daney, D. E.

    1988-01-01

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

  5. 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.

  6. 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.

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

    PubMed Central

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

    2016-01-01

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

  8. 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

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

    PubMed Central

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

    2016-01-01

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

  10. Thermodynamic properties of hydrogen-helium plasmas

    NASA Technical Reports Server (NTRS)

    Nelson, H. F.

    1971-01-01

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

  11. Superfluid helium-4 in one dimensional channel

    NASA Astrophysics Data System (ADS)

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

    2013-03-01

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

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

    NASA Technical Reports Server (NTRS)

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

    2001-01-01

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

  13. THE VISCOSITY OF HELIUM-CESIUM MIXTURES,

    DTIC Science & Technology

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

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

    NASA Astrophysics Data System (ADS)

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

    2015-04-01

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

  15. Helium anion formation inside helium droplets

    NASA Astrophysics Data System (ADS)

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

    2016-07-01

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

  16. 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.

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

    PubMed

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

    2016-05-01

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

  18. 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.

  19. 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

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

    PubMed

    Kalu, Nene N; Johnson, Faye M

    2017-02-01

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

  1. 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.

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

    PubMed Central

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

    2008-01-01

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

  3. Auroral helium precipitation.

    NASA Technical Reports Server (NTRS)

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

    1972-01-01

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

  4. 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

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

    PubMed

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

    2016-01-01

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

  6. 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

  7. 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.

  8. 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.

  9. Education in Helium Refrigeration

    NASA Astrophysics Data System (ADS)

    Gistau Baguer, G. M.

    2004-06-01

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

  10. 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.

  11. 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

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

    PubMed

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

    2016-11-01

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

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

    PubMed

    LeBlanc, Andrea C

    2013-06-01

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

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

    PubMed

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

    2012-02-01

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

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

    PubMed Central

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

    2012-01-01

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

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

    PubMed

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

    2012-05-03

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

  17. 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.

  18. 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.

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

    NASA Astrophysics Data System (ADS)

    Milone, A. P.

    2015-01-01

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

  20. The winter helium bulge revisited

    NASA Astrophysics Data System (ADS)

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

    2014-10-01

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

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

    PubMed

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

    2014-05-01

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

  2. 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)...

  3. 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)...

  4. 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)...

  5. Helium jet dispersion to atmosphere

    NASA Astrophysics Data System (ADS)

    Khan, Hasna J.

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

  6. 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.

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2017-02-01

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

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

    PubMed Central

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

    2017-01-01

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

  10. 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.

  11. Calcipotriol Targets LRP6 to Inhibit Wnt Signaling in Pancreatic Cancer

    PubMed Central

    Arensman, Michael D.; Nguyen, Phillip; Kershaw, Kathleen M.; Lay, Anna R.; Ostertag-Hill, Claire A.; Sherman, Mara H.; Downes, Michael; Liddle, Christopher; Evans, Ronald M.; Dawson, David W.

    2015-01-01

    Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy in need of more effective treatment approaches. One potential therapeutic target is Wnt/β-catenin signaling, which plays important roles in PDAC tumor initiation and progression. Among Wnt inhibitors with suitable in vivo biological activity is vitamin D, which is known to antagonize Wnt/β-catenin signaling in colorectal cancer and have anti-tumor activity in PDAC. For this study the relationship between vitamin D signaling, Wnt/β-catenin activity and tumor cell growth in PDAC was investigated through the use of calcipotriol, a potent non-hypercalcemic vitamin D analog. PDAC tumor cell growth inhibition by calcipotriol was positively correlated with vitamin D receptor (VDR) expression and Wnt/β-catenin activity. Furthermore, vitamin D and Wnt signaling activity were found to be reciprocally linked through feedback regulation. Calcipotriol inhibited autocrine Wnt/β-catenin signaling in PDAC cell lines in parallel with decreased protein levels of the low density lipoprotein receptor-related protein 6 (LRP6), a requisite co-receptor for ligand-dependent canonical Wnt signaling. Decrease in LRP6 protein seen with calcipotriol was mediated through a novel mechanism involving transcriptional upregulation of low-density lipoprotein receptor adaptor protein 1 (LDLRAP1). Finally, changes in LRP6 or LDLRAP1 expression directly altered Wnt reporter activity, supporting their roles as regulators of ligand-dependent Wnt/β-catenin signaling. Implications This study provides a novel biochemical target through which vitamin D signaling exerts inhibitory effects on Wnt/β-catenin signaling, as well as potential biomarkers for predicting and following tumor response to vitamin D-based therapy. PMID:26224368

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

    PubMed

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

    2016-08-19

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

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

    PubMed

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

    2017-03-01

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

  14. Rayleigh Scattering by Helium in Stellar Atmospheres

    NASA Astrophysics Data System (ADS)

    Fišák, J.; Kubát, J.; Krtička, J.

    2017-02-01

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

  15. 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

  16. Operations aspects of the Fermilab Central Helium Liquefier Facility

    SciTech Connect

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

    1995-03-01

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

  17. Helium dilution refrigeration system

    DOEpatents

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

    1988-09-13

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

  18. Helium dilution refrigeration system

    DOEpatents

    Roach, Patrick R.; Gray, Kenneth E.

    1988-01-01

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

  19. 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.

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

    NASA Astrophysics Data System (ADS)

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

    2017-02-01

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

  1. Helium isotope ratios in Ethiopian Rift basalts

    NASA Astrophysics Data System (ADS)

    Scarsi, P.; Craig, H.

    1996-11-01

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

  2. 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

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

    PubMed

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

    2009-09-01

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

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

    PubMed Central

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

    2009-01-01

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

  5. Helium segregation on surfaces of plasma-exposed tungsten

    SciTech Connect

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

    2016-01-21

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

  6. Helium segregation on surfaces of plasma-exposed tungsten

    DOE PAGES

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

    2016-01-21

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

  7. Helium segregation on surfaces of plasma-exposed tungsten

    NASA Astrophysics Data System (ADS)

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

    2016-02-01

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

  8. 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)].

  9. Characterization of gaseous helium jet dispersion to atmosphere

    NASA Astrophysics Data System (ADS)

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

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

  10. 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.

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

    SciTech Connect

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

    2016-11-15

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

  12. 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

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

    PubMed Central

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

    2017-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

    1999-11-01

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

  15. 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…

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

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... allocated among Class II acquisition date assets of target in proportion to the fair market values of such... 26 Internal Revenue 4 2011-04-01 2011-04-01 false Allocation of ADSP and AGUB among target assets... among target assets. (a) Scope—(1) In general. This section prescribes rules for allocating ADSP...

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

    NASA Astrophysics Data System (ADS)

    Lee, D. M.

    2006-03-01

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

  18. 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

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

    PubMed

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

    2016-07-18

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

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

    PubMed

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

    2013-11-14

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

  1. 48 CFR 52.208-8 - Required Sources for Helium and Helium Usage Data.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... Office's Authorized List of Federal Helium Suppliers available via the Internet at http://www.nm.blm.gov..., insert the following clause: Required Sources for Helium and Helium Usage Data (APR 2002) (a)...

  2. Perspectives on Lunar Helium-3

    NASA Astrophysics Data System (ADS)

    Schmitt, Harrison H.

    1999-01-01

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

  3. Targeted Analysis of KLF6/KLF6-SV1 Regulating Pathways in Prostate Cancer Development and Metastasis

    DTIC Science & Technology

    2011-09-01

    suppressor gene mutated in prostate cancer. Science. 294, 2563-2566. 2. Chen, C, Hyytinen, ER, Sun, X, Helin, HJ, Koivisto, PA, et al. (2003) Deletion ...transcription factor family which was first identified as a tumor suppressor gene frequently inactivated in prostate cancer (PCa). A single germline SNP...increases PCa risk and KLF6 gene alternative splicing to produce KLF6-SV1, which promotes tumor cell growth and metastasis. Since their original

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

    PubMed

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

    2016-12-01

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

  5. 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.

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

    PubMed Central

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

    2016-01-01

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

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

    NASA Technical Reports Server (NTRS)

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

    1978-01-01

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

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

    DOE PAGES

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

    2016-11-15

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

  9. The Stress Response Factors Yap6, Cin5, Phd1, and Skn7 Direct Targeting of the Conserved Co-Repressor Tup1-Ssn6 in S. cerevisiae

    PubMed Central

    Hanlon, Sean E.; Rizzo, Jason M.; Tatomer, Deirdre C.; Lieb, Jason D.; Buck, Michael J.

    2011-01-01

    Maintaining the proper expression of the transcriptome during development or in response to a changing environment requires a delicate balance between transcriptional regulators with activating and repressing functions. The budding yeast transcriptional co-repressor Tup1-Ssn6 is a model for studying similar repressor complexes in multicellular eukaryotes. Tup1-Ssn6 does not bind DNA directly, but is directed to individual promoters by one or more DNA-binding proteins, referred to as Tup1 recruiters. This functional architecture allows the Tup1-Ssn6 to modulate the expression of genes required for the response to a variety of cellular stresses. To understand the targeting or the Tup1-Ssn6 complex, we determined the genomic distribution of Tup1 and Ssn6 by ChIP-chip. We found that most loci bound by Tup1-Ssn6 could not be explained by co-occupancy with a known recruiting cofactor and that deletion of individual known Tup1 recruiters did not significantly alter the Tup1 binding profile. These observations suggest that new Tup1 recruiting proteins remain to be discovered and that Tup1 recruitment typically depends on multiple recruiting cofactors. To identify new recruiting proteins, we computationally screened for factors with binding patterns similar to the observed Tup1-Ssn6 genomic distribution. Four top candidates, Cin5, Skn7, Phd1, and Yap6, all known to be associated with stress response gene regulation, were experimentally confirmed to physically interact with Tup1 and/or Ssn6. Incorporating these new recruitment cofactors with previously characterized cofactors now explains the majority of Tup1 targeting across the genome, and expands our understanding of the mechanism by which Tup1-Ssn6 is directed to its targets. PMID:21552514

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

    NASA Astrophysics Data System (ADS)

    Brower, Michael Chadbourne

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

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

    NASA Astrophysics Data System (ADS)

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

    2003-06-01

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

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

    PubMed

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

    2015-05-01

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

  13. 26 CFR 1.338-6 - Allocation of ADSP and AGUB among target assets.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

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

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

    PubMed

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

    2017-03-24

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

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

    NASA Astrophysics Data System (ADS)

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

    2014-04-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2016-11-01

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

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

    DOE PAGES

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

    2016-11-01

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

  18. Lamb shift in the muonic helium ion

    SciTech Connect

    Martynenko, A. P.

    2007-07-15

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

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

    PubMed

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

    2016-02-23

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

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

    NASA Astrophysics Data System (ADS)

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

    2013-05-01

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

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

    SciTech Connect

    Maki, J.T.

    1987-01-01

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

  2. Rogue mantle helium and neon.

    PubMed

    Albarède, Francis

    2008-02-15

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

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

    NASA Astrophysics Data System (ADS)

    Anufriev, G. S.

    2010-10-01

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

  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. 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.

  6. 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.

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

    PubMed Central

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

    2014-01-01

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

  8. 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

  9. 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.

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

    NASA Astrophysics Data System (ADS)

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

    1992-05-01

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

  11. 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.

  12. 21 CFR 184.1355 - Helium.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 3 2012-04-01 2012-04-01 false Helium. 184.1355 Section 184.1355 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN... Substances Affirmed as GRAS § 184.1355 Helium. (a) Helium (empirical formula He, CAS Reg. No. 7440-59-7) is...

  13. 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...

  14. 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...

  15. 21 CFR 184.1355 - Helium.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 3 2013-04-01 2013-04-01 false Helium. 184.1355 Section 184.1355 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN... Substances Affirmed as GRAS § 184.1355 Helium. (a) Helium (empirical formula He, CAS Reg. No. 7440-59-7) is...

  16. 21 CFR 184.1355 - Helium.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Helium. 184.1355 Section 184.1355 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DIRECT FOOD....1355 Helium. (a) Helium (empirical formula He, CAS Reg. No. 7440-59-7) is a colorless,...

  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. 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.

  19. 21 CFR 184.1355 - Helium.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 3 2011-04-01 2011-04-01 false Helium. 184.1355 Section 184.1355 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN... Substances Affirmed as GRAS § 184.1355 Helium. (a) Helium (empirical formula He, CAS Reg. No. 7440-59-7) is...

  20. 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...

  1. 21 CFR 184.1355 - Helium.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Helium. 184.1355 Section 184.1355 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN... Substances Affirmed as GRAS § 184.1355 Helium. (a) Helium (empirical formula He, CAS Reg. No. 7440-59-7) is...

  2. 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.

  3. 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.

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

    NASA Astrophysics Data System (ADS)

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

    2014-11-01

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

  5. 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.

  6. 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".

  7. 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.

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

    PubMed Central

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

    2016-01-01

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

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

    NASA Technical Reports Server (NTRS)

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

    1975-01-01

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

  10. 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

  11. Helium embrittlement of a lamellar titanium aluminide

    NASA Astrophysics Data System (ADS)

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

    2013-03-01

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

  12. 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

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

    NASA Astrophysics Data System (ADS)

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

    2012-12-01

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

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

    NASA Astrophysics Data System (ADS)

    Krasnopolsky, Vladimir A.; Gladstone, G. Randall

    2005-08-01

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

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

    PubMed

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

    2016-01-01

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

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

    PubMed Central

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

    2016-01-01

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

  17. 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.

  18. 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.

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

    PubMed

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

    2017-01-01

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

  20. 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.

  1. 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.

  2. 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

  3. 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.

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

    SciTech Connect

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

    2011-01-01

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

  5. Design, synthesis and evaluation of novel 2,5,6-trisubstituted benzimidazoles targeting FtsZ as antitubercular agents.

    PubMed

    Park, Bora; Awasthi, Divya; Chowdhury, Soumya R; Melief, Eduard H; Kumar, Kunal; Knudson, Susan E; Slayden, Richard A; Ojima, Iwao

    2014-05-01

    Filamenting temperature-sensitive protein Z (FtsZ), an essential cell division protein, is a promising target for the drug discovery of new-generation antibacterial agents against various bacterial pathogens. As a part of SAR studies on benzimidazoles, we have synthesized a library of 376 novel 2,5,6-trisubstituted benzimidazoles, bearing ether or thioether linkage at the 6-position. In a preliminary HTP screening against Mtb H37Rv, 108 compounds were identified as hits at a cut off concentration of 5 μg/mL. Among those hits, 10 compounds exhibited MIC values in the range of 0.63-12.5 μg/mL. Light scattering assay and TEM analysis with the most potent compound 5a clearly indicate that its molecular target is Mtb-FtsZ. Also, the Kd of 5a with Mtb-FtsZ was determined to be 1.32 μM.

  6. Deciphering downstream gene targets of PI3K/mTOR/p70S6K pathway in breast cancer

    PubMed Central

    Heinonen, Henna; Nieminen, Anni; Saarela, Matti; Kallioniemi, Anne; Klefström, Juha; Hautaniemi, Sampsa; Monni, Outi

    2008-01-01

    Background The 70 kDa ribosomal protein S6 kinase (RPS6KB1), located at 17q23, is amplified and overexpressed in 10–30% of primary breast cancers and breast cancer cell lines. p70S6K is a serine/threonine kinase regulated by PI3K/mTOR pathway, which plays a crucial role in control of cell cycle, growth and survival. Our aim was to determine p70S6K and PI3K/mTOR/p70S6K pathway dependent gene expression profiles by microarrays using five breast cancer cell lines with predefined gene copy number and gene expression alterations. The p70S6K dependent profiles were determined by siRNA silencing of RPS6KB1 in two breast cancer cell lines overexpressing p70S6K. These profiles were further correlated with gene expression alterations caused by inhibition of PI3K/mTOR pathway with PI3K inhibitor Ly294002 or mTOR inhibitor rapamycin. Results Altogether, the silencing of p70S6K altered the expression of 109 and 173 genes in two breast cancer cell lines and 67 genes were altered in both cell lines in addition to RPS6KB1. Furthermore, 17 genes including VTCN1 and CDKN2B showed overlap with genes differentially expressed after PI3K or mTOR inhibition. The gene expression signatures responsive to both PI3K/mTOR pathway and p70S6K inhibitions revealed previously unidentified genes suggesting novel downstream targets for PI3K/mTOR/p70S6K pathway. Conclusion Since p70S6K overexpression is associated with aggressive disease and poor prognosis of breast cancer patients, the potential downstream targets of p70S6K and the whole PI3K/mTOR/p70S6K pathway identified in our study may have diagnostic value. PMID:18652687

  7. MicroRNA-181b regulates endotoxin tolerance by targeting IL-6 in macrophage RAW264.7 cells.

    PubMed

    Zhang, Wenjun; Shen, Xiaojun; Xie, Luyang; Chu, Maoping; Ma, Yanmei

    2015-01-01

    Interleukin 6 (IL-6) is a major pro-inflammatory cytokine and dysregulation of IL-6 is relevant to many inflammatory diseases. Endotoxin induced tolerance of IL-6 is an important mechanism to avoid the excessive immune reaction. But to date, the molecular mechanisms of endotoxin tolerance of IL-6 remain unclear. Here we reported that IL-6 secretion and microRNA-181b (miR-181b) expression were inversely correlated following LPS stimulation. We also demonstrated that miR-181b targeting the 3'-UTR of IL-6 transcripts and up-regulation of miR-181b was associated with NF-kB. We further demonstrated that up-regulation of miR-181b in response to LPS was required for inducing IL-6 tolerance in macrophage. Our results suggested that the post-transcriptional control mediated by miR-181b could be involved in fine tuning the critical level of IL-6 expression in endotoxin tolerance.

  8. IL-6 Inhibits the Targeted Modulation of PDCD4 by miR-21 in Prostate Cancer.

    PubMed

    Dong, Biao; Shi, Zhihao; Wang, Jiaping; Wu, Jing; Yang, Zhaoqing; Fang, Kewei

    2015-01-01

    Prostate cancer is the most common cancer among men in the Unites States. The cytokine IL-6 activates several prostate cancer pathways, but its upstream trans-signaling pathway remains poorly understood. In this study, we evaluated the role of IL-6 in PDCD4 gene expression and how the microRNA miR-21 regulates this process in prostate cancer cell lines PC-3 and LNCaP. The expression pattern of PDCD4 from samples from human prostate cancer, precancerous lesions, and benign prostatic hyperplasia was investigated by immunohistochemistry. PDCD4 transcription and translation were detected by quantitative real-time PCR (qRT-PCR) and Western blot analysis, respectively. The targeted modulation of PDCD4 by miR-21 was analyzed in PC-3 and LNCaP cells, and the effect of IL-6 on the expression of PDCD4 was studied in vitro. PDCD4 expression in samples from the 3 tissue types progressively increased, and the expression levels of PDCD4 and prostate-specific antigen were negatively correlated. The levels of PDCD4 mRNA and protein in PC-3 and LNCaP cells transfected with anti-miR-21 constructs were lower than those in control cells. The expression of PDCD4 was inhibited by IL-6, but this effect was weakened in cell lines with low expression of miR-21. Our study demonstrates that the regulation of PDCD4 by miR-21 is targeted and IL-6 inhibits expression of the PDCD4 gene in PC-3 and LNCaP cells through the targeted function of miR-21 on PDCD4. These findings support the feasibility of future efforts for diagnosis and gene therapy for prostate cancer that are based on IL-6, miR-21, and PDCD4.

  9. 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.

  10. 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.

  11. Blocking CD40-TRAF6 signaling is a therapeutic target in obesity-associated insulin resistance

    PubMed Central

    Chatzigeorgiou, Antonios; Seijkens, Tom; Zarzycka, Barbara; Engel, David; Poggi, Marjorie; van den Berg, Susan; van den Berg, Sjoerd; Soehnlein, Oliver; Winkels, Holger; Beckers, Linda; Lievens, Dirk; Driessen, Ann; Kusters, Pascal; Biessen, Erik; Garcia-Martin, Ruben; Klotzsche-von Ameln, Anne; Gijbels, Marion; Noelle, Randolph; Boon, Louis; Hackeng, Tilman; Schulte, Klaus-Martin; Xu, Aimin; Vriend, Gert; Nabuurs, Sander; Chung, Kyoung-Jin; Willems van Dijk, Ko; Rensen, Patrick C. N.; Gerdes, Norbert; de Winther, Menno; Block, Norman L.; Schally, Andrew V.; Weber, Christian; Bornstein, Stefan R.; Nicolaes, Gerry; Chavakis, Triantafyllos; Lutgens, Esther

    2014-01-01

    The immune system plays an instrumental role in obesity and insulin resistance. Here, we unravel the role of the costimulatory molecule CD40 and its signaling intermediates, TNF receptor-associated factors (TRAFs), in diet-induced obesity (DIO). Although not exhibiting increased weight gain, male CD40−/− mice in DIO displayed worsened insulin resistance, compared with wild-type mice. This worsening was associated with excessive inflammation of adipose tissue (AT), characterized by increased accumulation of CD8+ T cells and M1 macrophages, and enhanced hepatosteatosis. Mice with deficient CD40-TRAF2/3/5 signaling in MHCII+ cells exhibited a similar phenotype in DIO as CD40−/− mice. In contrast, mice with deficient CD40-TRAF6 signaling in MHCII+ cells displayed no insulin resistance and showed a reduction in both AT inflammation and hepatosteatosis in DIO. To prove the therapeutic potential of inhibition of CD40-TRAF6 in obesity, DIO mice were treated with a small-molecule inhibitor that we designed to specifically block CD40-TRAF6 interactions; this compound improved insulin sensitivity, reduced AT inflammation, and decreased hepatosteatosis. Our study reveals that the CD40-TRAF2/3/5 signaling pathway in MHCII+ cells protects against AT inflammation and metabolic complications associated with obesity whereas CD40-TRAF6 interactions in MHCII+ cells aggravate these complications. Inhibition of CD40-TRAF6 signaling by our compound may provide a therapeutic option in obesity-associated insulin resistance. PMID:24492375

  12. 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.

  13. Profiling Global Kinome Signatures of the Radioresistant MCF-7/C6 Breast Cancer Cells Using MRM-based Targeted Proteomics

    PubMed Central

    2015-01-01

    Ionizing radiation is widely used in cancer therapy; however, cancer cells often develop radioresistance, which compromises the efficacy of cancer radiation therapy. Quantitative assessment of the alteration of the entire kinome in radioresistant cancer cells relative to their radiosensitive counterparts may provide important knowledge to define the mechanism(s) underlying tumor adaptive radioresistance and uncover novel target(s) for effective prevention and treatment of tumor radioresistance. By employing a scheduled multiple-reaction monitoring analysis in conjunction with isotope-coded ATP affinity probes, we assessed the global kinome of radioresistant MCF-7/C6 cells and their parental MCF-7 human breast cancer cells. We rigorously quantified 120 kinases, of which 1/3 exhibited significant differences in expression levels or ATP binding affinities. Several kinases involved in cell cycle progression and DNA damage response were found to be overexpressed or hyperactivated, including checkpoint kinase 1 (CHK1), cyclin-dependent kinases 1 and 2 (CDK1 and CDK2), and the catalytic subunit of DNA-dependent protein kinase. The elevated expression of CHK1, CDK1, and CDK2 in MCF-7/C6 cells was further validated by Western blot analysis. Thus, the altered kinome profile of radioresistant MCF-7/C6 cells suggests the involvement of kinases on cell cycle progression and DNA repair in tumor adaptive radioresistance. The unique kinome profiling results also afforded potential effective targets for resensitizing radioresistant cancer cells and counteracting deleterious effects of ionizing radiation exposure. PMID:25341124

  14. Toolkit for Professional Developers: Training Targets 3?6 Grade Teachers

    ERIC Educational Resources Information Center

    McMunn, Nancy; Dunnivant, Michael; Williamson, Jan; Reagan, Hope

    2004-01-01

    The professional development CAR Toolkit is focused on the assessment of reading process at the text level, rather than at the word level. Most students in grades 3-6 generally need support in comprehending text, not just decoding words. While the assessment of reading methods in the CAR Toolkit will help teachers pinpoint difficulties at the word…

  15. Superfluid helium leak sealant study

    NASA Technical Reports Server (NTRS)

    Vorreiter, J. W.

    1981-01-01

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

  16. 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.

  17. 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.

  18. Superfluid Helium Tanker (SFHT) study

    NASA Technical Reports Server (NTRS)

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

    1988-01-01

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

  19. Hypoxia-induced miR-181b enhances angiogenesis of retinoblastoma cells by targeting PDCD10 and GATA6.

    PubMed

    Xu, Xiaofang; Ge, Shengfang; Jia, Renbing; Zhou, Yixiong; Song, Xin; Zhang, He; Fan, Xianqun

    2015-06-01

    Previous findings showed that miR-181b is upregulated under hypoxic conditions in retinoblastoma cells. Since hypoxia is a common feature of retinoblastoma that affects tumor progression as well as tumor therapy, in the present study, we investigated the regulatory mechanism of miR-181b under hypoxic conditions, and examined the role of miR-181b in retinoblastoma responses to hypoxia (chemoresistance and angiogenesis) and possible downstream genes. The level of hypoxia-inducible factor-1α (HIF-1α) and miR-181b was detected to examine the link between them. Tube formation and cell cytotoxicity assays were used to clarify the effects of miR-181b on hypoxic responses of retinoblastoma cells. Bioinformatics analysis was performed to predict potential targets of miR-181b and western blotting was used to verify these targets. The results showed a significantly increased expression of HIF-1α in hypoxia-treated retinoblastoma cells. Downregulation of HIF-1α using a small-interfering RNA (siRNA) knockdown technology did not decrease the expression of miR-181b. Through gain- and loss-of-function studies, miR-181b was demonstrated to significantly stimulate the ability of capillary tube formation of endothelial cells. Programmed cell death-10 (PDCD10) and GATA binding protein 6 (GATA6) were identified as the target genes of miR‑181b. To the best of our knowledge, results of the present study provide the first evidence that miR-181b was upregulated by hypoxia in retinoblastoma in an HIF-1α-independent manner. miR-181b increased tumor angiogenesis of retinoblastoma cells. Additionally, miR-181b exerts its angiogenic function, at least in part, by inhibiting PDCD10 and GATA6. Thus, it is a new potentially useful therapeutic target for retinoblastoma.

  20. 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

  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. Destabilization of ERBB2 transcripts by targeting 3' untranslated region messenger RNA associated HuR and histone deacetylase-6.

    PubMed

    Scott, Gary K; Marx, Corina; Berger, Crystal E; Saunders, Laura R; Verdin, Eric; Schäfer, Stefan; Jung, Manfred; Benz, Christopher C

    2008-07-01

    In addition to repressing ERBB2 promoter function, histone deacetylase (HDAC) inhibitors induce the accelerated decay of mature ERBB2 transcripts; the mechanism mediating this transcript destabilization is unknown but depends on the 3' untranslated region (UTR) of ERBB2 mRNA. Using ERBB2-overexpressing human breast cancer cells (SKBR3), the mRNA stability factor HuR was shown to support ERBB2 transcript integrity, bind and endogenously associate with a conserved U-rich element within the ERBB2 transcript 3' UTR, coimmunoprecipitate with RNA-associated HDAC activity, and colocalize with HDAC6. HDAC6 also coimmunoprecipitates with HuR in an RNA-dependent manner and within 6 hours of exposure to a pan-HDAC inhibitor dose, that does not significantly alter cytosolic HuR levels or HuR binding to ERBB2 mRNA. Cellular ERBB2 transcript levels decline while remaining physically associated with HDAC6. Knockdown of HDAC6 protein by small interfering RNA partially suppressed the ERBB2 transcript decay induced by either pan-HDAC or HDAC6-selective enzymatic inhibitors. Three novel hydroxamates, ST71, ST17, and ST80 were synthesized and shown to inhibit HDAC6 with 14-fold to 31-fold greater selectivity over their binding and inhibition of HDAC1. Unlike more potent pan-HDAC inhibitors, these HDAC6-selective inhibitors produced dose-dependent growth arrest of ERBB2-overexpressing breast cancer cells by accelerating the decay of mature ERBB2 mRNA without repressing ERBB2 promoter function. In sum, these findings point to the therapeutic potential of HuR and HDAC6-selective inhibitors, contrasting ERBB2 stability effects induced by HDAC6 enzymatic inhibition and HDAC6 protein knockdown, and show that ERBB2 transcript stability mechanisms include exploitable targets for the development of novel anticancer therapies.

  3. 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.

  4. 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

  5. Ig-like domain 6 of VCAM-1 is a potential therapeutic target in TNFα-induced angiogenesis

    PubMed Central

    Kim, Taek-Keun; Park, Chang Sik; Na, Hee-Jun; Lee, Kangseung; Yoon, Aerin; Chung, Junho; Lee, Sukmook

    2017-01-01

    Tumor necrosis factor alpha (TNFα)-induced angiogenesis plays important roles in the progression of various diseases, including cancer, wet age-related macular degeneration, and rheumatoid arthritis. However, the relevance and role of vascular cell adhesion molecule-1 (VCAM-1) in angiogenesis have not yet been clearly elucidated. In this study, VCAM-1 knockdown shows VCAM-1 involvement in TNFα-induced angiogenesis. Through competitive blocking experiments with VCAM-1 Ig-like domain 6 (VCAM-1-D6) protein, we identified VCAM-1-D6 as a key domain regulating TNFα-induced vascular tube formation. We demonstrated that a monoclonal antibody specific to VCAM-1-D6 suppressed TNFα-induced endothelial cell migration and tube formation and TNFα-induced vessel sprouting in rat aortas. We also found that the antibody insignificantly affected endothelial cell viability, morphology and activation. Finally, the antibody specifically blocked VCAM-1-mediated cell–cell contacts by directly inhibiting VCAM-1-D6-mediated interaction between VCAM-1 molecules. These findings suggest that VCAM-1-D6 may be a potential novel therapeutic target in TNFα-induced angiogenesis and that antibody-based modulation of VCAM-1-D6 may be an effective strategy to suppress TNFα-induced angiogenesis. PMID:28209985

  6. Ig-like domain 6 of VCAM-1 is a potential therapeutic target in TNFα-induced angiogenesis.

    PubMed

    Kim, Taek-Keun; Park, Chang Sik; Na, Hee-Jun; Lee, Kangseung; Yoon, Aerin; Chung, Junho; Lee, Sukmook

    2017-02-17

    Tumor necrosis factor alpha (TNFα)-induced angiogenesis plays important roles in the progression of various diseases, including cancer, wet age-related macular degeneration, and rheumatoid arthritis. However, the relevance and role of vascular cell adhesion molecule-1 (VCAM-1) in angiogenesis have not yet been clearly elucidated. In this study, VCAM-1 knockdown shows VCAM-1 involvement in TNFα-induced angiogenesis. Through competitive blocking experiments with VCAM-1 Ig-like domain 6 (VCAM-1-D6) protein, we identified VCAM-1-D6 as a key domain regulating TNFα-induced vascular tube formation. We demonstrated that a monoclonal antibody specific to VCAM-1-D6 suppressed TNFα-induced endothelial cell migration and tube formation and TNFα-induced vessel sprouting in rat aortas. We also found that the antibody insignificantly affected endothelial cell viability, morphology and activation. Finally, the antibody specifically blocked VCAM-1-mediated cell-cell contacts by directly inhibiting VCAM-1-D6-mediated interaction between VCAM-1 molecules. These findings suggest that VCAM-1-D6 may be a potential novel therapeutic target in TNFα-induced angiogenesis and that antibody-based modulation of VCAM-1-D6 may be an effective strategy to suppress TNFα-induced angiogenesis.

  7. 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.

  8. 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.

  9. CerS6 Is a Novel Transcriptional Target of p53 Protein Activated by Non-genotoxic Stress.

    PubMed

    Fekry, Baharan; Jeffries, Kristen A; Esmaeilniakooshkghazi, Amin; Ogretmen, Besim; Krupenko, Sergey A; Krupenko, Natalia I

    2016-08-05

    Our previous study suggested that ceramide synthase 6 (CerS6), an enzyme in sphingolipid biosynthesis, is regulated by p53: CerS6 was elevated in several cell lines in response to transient expression of p53 or in response to folate stress, which is known to activate p53. It was not clear, however, whether CerS6 gene is a direct transcriptional target of p53 or whether this was an indirect effect through additional regulatory factors. In the present study, we have shown that the CerS6 promoter is activated by p53 in luciferase assays, whereas transcriptionally inactive R175H p53 mutant failed to induce the luciferase expression from this promoter. In vitro immunoprecipitation assays and gel shift analyses have further demonstrated that purified p53 binds within the CerS6 promoter sequence spanning 91 bp upstream and 60 bp downstream of the transcription start site. The Promo 3.0.2 online tool for the prediction of transcription factor binding sites indicated the presence of numerous putative non-canonical p53 binding motifs in the CerS6 promoter. Luciferase assays and gel shift analysis have identified a single motif upstream of the transcription start as a key p53 response element. Treatment of cells with Nutlin-3 or low concentrations of actinomycin D resulted in a strong elevation of CerS6 mRNA and protein, thus demonstrating that CerS6 is a component of the non-genotoxic p53-dependent cellular stress response. This study has shown that by direct transcriptional activation of CerS6, p53 can regulate specific ceramide biosynthesis, which contributes to the pro-apoptotic cellular response.

  10. Helium Ionization in the Diffuse Ionized Gas Surrounding UCH ii Regions

    NASA Astrophysics Data System (ADS)

    Anish Roshi, D.; Churchwell, E.; Anderson, L. D.

    2017-04-01

    We present measurements of the singly ionized helium-to-hydrogen ratio ({n}{{He}+}/{n}{{{H}}+}) toward diffuse gas surrounding three ultracompact H ii (UCH ii) regions: G10.15-0.34, G23.46-0.20, and G29.96-0.02. We observe radio recombination lines of hydrogen and helium near 5 GHz using the GBT to measure the {n}{{He}+}/{n}{{{H}}+} ratio. The measurements are motivated by the low helium ionization observed in the warm ionized medium and in the inner Galaxy diffuse ionized regions. Our data indicate that the helium is not uniformly ionized in the three observed sources. Helium lines are not detected toward a few observed positions in sources G10.15-0.34 and G23.46-0.20, and the upper limits of the {n}{{He}+}/{n}{{{H}}+} ratio obtained are 0.03 and 0.05, respectively. The selected sources harbor stars of type O6 or hotter as indicated by helium line detection toward the bright radio continuum emission from the sources with mean {n}{{He}+}/{n}{{{H}}+} value 0.06 ± 0.02. Our data thus show that helium in diffuse gas located a few parsecs away from the young massive stars embedded in the observed regions is not fully ionized. We investigate the origin of the nonuniform helium ionization and rule out the possibilities (a) that the helium is doubly ionized in the observed regions and (b) that the low {n}{{He}+}/{n}{{{H}}+} values are due to additional hydrogen ionizing radiation produced by accreting low-mass stars. We find that selective absorption of ionizing photons by dust can result in low helium ionization but needs further investigation to develop a self-consistent model for dust in H ii regions.

  11. Mutation of miR-21 targets endogenous lipoprotein receptor-related protein 6 and nonalcoholic fatty liver disease.

    PubMed

    Li, Chang-Ping; Li, Hong-Jue; Nie, Jiao; Chen, Xia; Zhou, Xian

    2017-01-01

    Nonalcoholic fatty liver disease (NAFLD) is a chronic disorder characterized by hepatic fat accumulation and abnormal lipid metabolism. Although miR-21 has been implicated in nonalcoholic fatty liver disease, it is unknown whether miR-21 could function as a therapeutic target. Here, we perform transfection analysis of miR-21 mimic or control mimic to evaluate the effects of miR-21 expression levels on human HepG2 nonalcoholic fatty liver cells. We used siRNA techniques to knock down miR-21 in HepG2 and control 293T cell lines, and then monitored lipid production and the expression levels of genes involved in lipid metabolism. The effects of miR-21 expression levels on LDL receptor-related protein 6 (LRP6) expression were evaluated using qRT-PCR and western blot analyses. Luciferase reporter assays were conducted to confirm the effects of miR-21 expression levels on LRP6. The results indicated that transfection of miR-21 mimic induced changes in the expression levels of lipogenic enzymes, including acetyl-CoA carboxylase 1 (ACC1), stearoyl CoA desaturase (1SCD1), sterol regulatory element-binding protein 1 (SREBP1), and liver X receptor alpha (LXRα). Transfection of miR-21 mimic suppressed the transcription and translation of LRP6 at the mRNA and protein levels, whereas miR-21 knockdown increased the expression levels of LRP6. Transfection of miR-21 mimic in HepG2 cells also induced lipid production and triggered the expression of critical lipid metabolic enzymes. These data suggest that mutation of miR-21 may be a new therapeutic strategy to treat nonalcoholic fatty liver diseases by targeting endogenous LRP6.

  12. Mutation of miR-21 targets endogenous lipoprotein receptor-related protein 6 and nonalcoholic fatty liver disease

    PubMed Central

    Li, Chang-Ping; Li, Hong-Jue; Nie, Jiao; Chen, Xia; Zhou, Xian

    2017-01-01

    Nonalcoholic fatty liver disease (NAFLD) is a chronic disorder characterized by hepatic fat accumulation and abnormal lipid metabolism. Although miR-21 has been implicated in nonalcoholic fatty liver disease, it is unknown whether miR-21 could function as a therapeutic target. Here, we perform transfection analysis of miR-21 mimic or control mimic to evaluate the effects of miR-21 expression levels on human HepG2 nonalcoholic fatty liver cells. We used siRNA techniques to knock down miR-21 in HepG2 and control 293T cell lines, and then monitored lipid production and the expression levels of genes involved in lipid metabolism. The effects of miR-21 expression levels on LDL receptor-related protein 6 (LRP6) expression were evaluated using qRT-PCR and western blot analyses. Luciferase reporter assays were conducted to confirm the effects of miR-21 expression levels on LRP6. The results indicated that transfection of miR-21 mimic induced changes in the expression levels of lipogenic enzymes, including acetyl-CoA carboxylase 1 (ACC1), stearoyl CoA desaturase (1SCD1), sterol regulatory element-binding protein 1 (SREBP1), and liver X receptor alpha (LXRα). Transfection of miR-21 mimic suppressed the transcription and translation of LRP6 at the mRNA and protein levels, whereas miR-21 knockdown increased the expression levels of LRP6. Transfection of miR-21 mimic in HepG2 cells also induced lipid production and triggered the expression of critical lipid metabolic enzymes. These data suggest that mutation of miR-21 may be a new therapeutic strategy to treat nonalcoholic fatty liver diseases by targeting endogenous LRP6. PMID:28337300

  13. 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,...

  14. 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,...

  15. 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,...

  16. 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,...

  17. 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,...

  18. Helium recovery and purification at CHMFL

    NASA Astrophysics Data System (ADS)

    Li, J.; Meng, Q.; Ouyang, Z.; Shi, L.; Ai, X.; Chen, X.

    2017-02-01

    Currently, rising demand and declining reserves of helium have led to dramatic increases in the helium price. The High Magnetic Field Laboratory of Chinese Academy of Sciences (CHMFL) has made efforts since its foundation to increase the percentage of helium recovered. The piping network connects all the helium experimental facilities to the recovery system, and even exhaust ports of pressure relief valves and vacuum pumps are also connected. In each year, about 30,000 cubic meters helium gas is recovered. The recovery gas is purified, liquefied and supplied to the users again. This paper will provide details about the helium recovery and purification system at CHMFL, including system flowchart, components, problems and solutions.

  19. Thermodynamic properties of hydrogen-helium plasmas.

    NASA Technical Reports Server (NTRS)

    Nelson, H. F.

    1972-01-01

    Calculation of the thermodynamic properties of an atomic hydrogen-helium plasma for postulated conditions present in a stagnation shock layer of a spacecraft entering the atmosphere of Jupiter. These properties can be used to evaluate transport properties, to calculate convective heating, and to investigate nonequilibrium behavior. The calculations have been made for temperatures from 10,000 to 100,000 K, densities of 10 to the minus 7th and .00001 g cu cm, and three plasma compositions: pure hydrogen, 50% hydrogen/50% helium, and pure helium. The shock layer plasma consists of electrons, protons, atomic hydrogen, atomic helium, singly ionized helium, and doubly atomized helium. The thermodynamic properties which have been investigated are: pressure, average molecular weight, internal energy, enthalpy, entropy, specific heat, and isentropic speed of sound. A consistent model was used for the reduction of the ionization potential in the calculation of the partition functions.

  20. Advanced polymer targets for TNSA regime producing 6 MeV protons at 1016 W/cm2 laser intensity

    NASA Astrophysics Data System (ADS)

    Torrisi, L.

    2017-02-01

    High intensity laser pulses, at an intensity of the order of 1016 W/cm2, are employed to irradiate in vacuum polyethylene terephthalate thin foils in the target normal sheath acceleration (TNSA) regime. The plasma obtained in the forward emission is investigated using ion collectors and semiconductor detectors connected in a time-of-flight configuration, Thomson parabola spectrometer, and X-ray streak camera. The results indicate that the foil thickness of 1 micron is optimal to accelerate protons of up to 6.5 MeV. The high ion acceleration can be due to different effects such as the high absorption in the advanced semicrystalline polymer containing spherulite centers, the high resonant absorption in gold nanoparticles embedded in the polymer, the optimal thickness of the used polymer to enhance the electron density in the forward plasma, and the self-focusing effect induced by preplasma created in front of the irradiated target.

  1. 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.

  2. 48 CFR 52.208-8 - Required Sources for Helium and Helium Usage Data.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... pressure and 70 degrees Fahrenheit temperature) of gaseous helium or 7510 liters of liquid helium delivered... provide to the Contracting Officer the following data within 10 days after the Contractor or...

  3. 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

  4. 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

  5. The C1 and C2 domains target human type 6 adenylyl cyclase to lipid rafts and caveolae.

    PubMed

    Thangavel, Muthusamy; Liu, Xiaoqiu; Sun, Shu Qiang; Kaminsky, Joseph; Ostrom, Rennolds S

    2009-02-01

    Previous data has shown that adenylyl cyclase type 6 (AC6) is expressed principally in lipid rafts or caveolae of cardiac myocytes and other cell types while certain other isoforms of AC are excluded from these microdomains. The mechanism by which AC6 is localized to lipid rafts or caveolae is unknown. In this study, we show AC6 is localized in lipid rafts of COS-7 cells (expressing caveolin-1) and in HEK-293 cells or cardiac fibroblasts isolated from caveolin-1 knock-out mice (both of which lack prototypical caveolins). To determine the region of AC6 that confers raft localization, we independently expressed each of the major intracellular domains, the N-terminus, C1 and C2 domains, and examined their localization with various approaches. The N-terminus did not associate with lipid rafts or caveolae of either COS-7 or HEK-293 cells nor did it immunoprecipitate with caveolin-1 when expressed in COS-7 cells. By contrast, the C1 and C2 domains each associated with lipid rafts to varying degrees and were present in caveolin-1 immunoprecipitates. There were no differences in the pattern of localization of either the C1 or C2 domains between COS-7 and HEK-293 cells. Further dissection of the C1 domain into four individual proteins indicated that the N-terminal half of this domain is responsible for its raft localization. To probe for a role of a putative palmitoylation motif in the C-terminal portion of the C2 domain, we expressed various truncated forms of AC6 lacking most or all of the C-terminal 41 amino acids. These truncated AC6 proteins were not altered in terms of their localization in lipid rafts or their catalytic activity, implying that this C-terminal region is not required for lipid raft targeting of AC6. We conclude that while the C1 domain may be most important, both the C1 and C2 domains of AC6 play a role in targeting AC6 to lipid rafts.

  6. 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.

  7. Helium cyclotron resonance within the earth's magnetosphere

    SciTech Connect

    Mauk, B.H.; McIlwain, C.E.; McPherron, R.L.

    1981-01-01

    A histogram of electromagnetic Alfven/ion cyclotron wave frequencies, sampled within the geostationary enviroment and normalized by the equatorial proton cyclotron frequency, shows a dramatic gap centered near the helium (He/sup +/) cyclotron frequency. Also, strongly cyclotron phase bunched helium ions (20--200 eV) have been observed directly within the vicinity of wave environments. These observations are interpreted as resulting from the absorption of the waves through cyclotron resonance by cool ambient populations of helium ions.

  8. 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.

  9. Gluten T cell epitope targeting by TG3 and TG6; implications for dermatitis herpetiformis and gluten ataxia.

    PubMed

    Stamnaes, Jorunn; Dorum, Siri; Fleckenstein, Burkhard; Aeschlimann, Daniel; Sollid, Ludvig M

    2010-11-01

    Transglutaminase 2 (TG2) is well characterized as the main autoantigen of celiac disease. The ability of TG2 to deamidate and crosslink gluten peptides is essential for the gluten-dependent production of TG2 specific autoantibodies. In patients with primarily extraintestinal manifestation of gluten sensitivity the repertoire of autoantibodies may be different. In dermatitis herpetiformis (DH), TG3 appears to be the target autoantigen whereas in gluten ataxia (GA) autoantibodies reactive with TG6 are present. A functional role for TG3 and TG6 in these diseases has yet to be described. It is also not known whether these enzymes can use gluten peptides implicated in the pathology as substrates. We here report that similar to TG2, TG3 and TG6 can specifically deamidate gluten T cell epitopes. However, the fine specificities of the enzymes were found to differ. TG2 can form covalent complexes with gluten by iso-peptide and thioester bonds. We found that both TG3 and TG6 were able to complex with gluten peptides through thioester linkage although less efficiently than TG2, whereas TG6 but not TG3 was able to form iso-peptide linked complexes. Our findings lend credence to the notion that TG3 and TG6 are involved in the gluten-induced autoimmune responses of DH and GA.

  10. Gas6/Axl pathway is activated in chronic liver disease and its targeting reduces fibrosis via hepatic stellate cell inactivation

    PubMed Central

    Bárcena, Cristina; Stefanovic, Milica; Tutusaus, Anna; Joannas, Leonel; Menéndez, Anghara; García-Ruiz, Carmen; Sancho-Bru, Pau; Marí, Montserrat; Caballeria, Joan; Rothlin, Carla V.; Fernández-Checa, José C.; de Frutos, Pablo García; Morales, Albert

    2015-01-01

    Background & Aims Liver fibrosis, an important health concern associated to chronic liver injury that provides a permissive environment for cancer development, is characterized by accumulation of extracellular matrix components mainly derived from activated hepatic stellate cells (HSCs). Axl, a receptor tyrosine kinase, and its ligand Gas6 are involved in cell differentiation, immune response and carcinogenesis. Methods HSCs were obtained from wild type and Axl−/− mice, treated with recombinant Gas6 protein (rGas6), Axl siRNAs or the Axl inhibitor BGB324, and analyzed by western blot and real-time PCR. Experimental fibrosis was studied in CCl4-treated wild type and Axl−/− mice, and in combination with Axl inhibitor. Gas6 and Axl serum levels were measured in alcoholic liver disease (ALD) and hepatitis C virus (HCV) patients. Results In primary mouse HSCs, Gas6 and Axl levels paralleled HSC activation. rGas6 phosphorylated Axl and AKT prior to HSC phenotypic changes, while Axl siRNA silencing reduced HSC activation. Moreover, BGB324 blocked Axl/AKT phosphorylation and diminished HSC activation. In addition, Axl KO mice displayed decreased HSC activation in vitro and liver fibrogenesis after chronic damage by CCl4 administration. Similarly, BGB324 reduced collagen deposition and CCl4-induced liver fibrosis in mice. Importantly, Gas6 and Axl serum levels increased in ALD and HCV patients, inversely correlating with liver functionality. Conclusions: The Gas6/Axl axis is required for full HSC activation. Gas6 and Axl serum levels increase in parallel to chronic liver disease progression. Axl targeting may be a therapeutic strategy for liver fibrosis management. PMID:25908269

  11. 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.

  12. 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.

  13. 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.

  14. Targeting of HPV-16+ epithelial cancer cells by TCR gene engineered T cells directed against E6

    PubMed Central

    Draper, Lindsey M.; Kwong, Mei Li; Gros, Alena; Stevanović, Sanja; Tran, Eric; Kerkar, Sid; Raffeld, Mark; Rosenberg, Steven A.; Hinrichs, Christian S.

    2015-01-01

    Purpose The E6 and E7 oncoproteins of HPV-associated epithelial cancers are in principle ideal immunotherapeutic targets, but evidence that T cells specific for these antigens can recognize and kill HPV+ tumor cells is limited. We sought to determine if TCR gene engineered T cells directed against an HPV oncoprotein can successfully target HPV+ tumor cells. Experimental design T cell responses against the HPV-16 oncoproteins were investigated in a patient with an ongoing 22-month disease-free interval after her second resection of distant metastatic anal cancer. T cells genetically engineered to express an oncoprotein-specific TCR from this patient’s tumor-infiltrating T cells were tested for specific reactivity against HPV+ epithelial tumor cells. Results We identified, from an excised metastatic anal cancer tumor, T cells that recognized an HLA-A*02:01-restricted epitope of HPV-16 E6. The frequency of the dominant T cell clonotype from these cells was approximately 400-fold greater in the patient’s tumor than in her peripheral blood. T cells genetically engineered to express the TCR from this clonotype displayed high avidity for an HLA-A*02:01-restricted epitope of HPV-16, and they showed specific recognition and killing of HPV-16+ cervical, and head and neck cancer cell lines. Conclusion These findings demonstrate that HPV-16+ tumors can be targeted by E6-specific TCR gene engineered T cells, and they provide the foundation for a novel cellular therapy directed against HPV-16+ malignancies including cervical, oropharyngeal, anal, vulvar, vaginal, and penile cancers. PMID:26429982

  15. 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...

  16. 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...

  17. 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...

  18. 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...

  19. Solvation of Na+, K+, and their dimers in helium.

    PubMed

    An der Lan, Lukas; Bartl, Peter; Leidlmair, Christian; Jochum, Roland; Denifl, Stephan; Echt, Olof; Scheier, Paul

    2012-04-02

    Helium atoms bind strongly to alkali cations which, when embedded in liquid helium, form so-called snowballs. Calculations suggest that helium atoms in the first solvation layer of these snowballs form rigid structures and that their number (n) is well defined, especially for the lighter alkalis. However, experiments have so far failed to accurately determine values of n. We present high-resolution mass spectra of Na(+)He(n), K(+)He(n), Na(2)(+)He(n) and K(2)(+)He(n), formed by electron ionization of doped helium droplets; the data allow for a critical comparison with several theoretical studies. For sodium and potassium monomers the spectra indicate that the value of n is slightly smaller than calculated. Na(2)(+)He(n) displays two distinct anomalies at n=2 and n=6, in agreement with theory; dissociation energies derived from experiment closely track theoretical values. K(2)(+)He(n) distributions are fairly featureless, which also agrees with predictions.

  20. Highly Excited States of cs Atoms on Helium Nanodroplets

    NASA Astrophysics Data System (ADS)

    Lackner, F.; Theisen, M.; Koch, M.; Ernst, W. E.

    2011-06-01

    Cs atoms on the surface of helium nanodroplets have been excited to high lying nS (n = 8-11), nP (n = 8-11), and nD (n = 6-10) levels. A two-step excitation scheme via the 62P1/2(2Π1/2) state using two cw lasers was applied. This intermediate state has the advantage that a large fraction of the excited Cs atoms does not desorb from the helium nanodroplets. An absorption spectrum was recorded by detecting laser induced fluorescence light from the 62P3/2→62S1/2 transition. The pseudo-diatomic model for helium nanodroplets doped with single alkali-metal atoms holds for the observed spectrum. An investigation of spectral trends shows that the n'2P(Π)←62P1/2(2Π1/2) and n'2D(Δ)←62P1/2(2Π1/2) (n' > 9) transitions are lower in energy than the corresponding free-atom transitions. This indicates that the Cs*--HeN potential becomes attractive for these highly excited states. Our results suggest a possibility of generating an artificial super-atom with a positive ion core inside a helium nanodroplet and the electron outside, which will be subject to future experiments. M. Theisen, F. Lackner, F. Ancilotto, C. Callegari, and W.E. Ernst, Eur. Phys. J. D 61, 403-408 (2011)

  1. The left lung is preferentially targeted during experimental paracoccidioidomycosis in C57BL/6 mice

    PubMed Central

    Tristão, F.S.M.; Rocha, F.A.; Dias, F.C.; Rossi, M.A.; Silva, J.S.

    2013-01-01

    Paracoccidioidomycosis (PCM) is a chronic systemic mycosis caused by the inhalation of the thermally dimorphic fungus Paracoccidioides brasiliensis as well as the recently described P. lutzii. Because the primary infection occurs in the lungs, we investigated the differential involvement of the right and left lungs in experimental P. brasiliensis infection. Lungs were collected from C57BL/6 mice at 70 days after intravenous infection with 1×106 yeast cells of a virulent strain of P. brasiliensis (Pb18). The left lung, which in mice is smaller and has fewer lobes than the right lung, yielded increased fungal recovery associated with a predominant interleukin-4 response and diminished synthesis of interferon-γ and nitric oxide compared with the right lung. Our data indicate differential involvement of the right and left lungs during experimental PCM. This knowledge emphasizes the need for an accurate, standardized protocol for tissue collection during studies of experimental P. brasiliensis infection, since experiments using the same lungs favor the collection of comparable data among different mice. PMID:24141611

  2. 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.

  3. 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...

  4. 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...

  5. 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...

  6. 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...

  7. Methyl 6-Amino-6-deoxy-d-pyranoside-Conjugated Platinum(II) Complexes for Glucose Transporter (GLUT)-Mediated Tumor Targeting: Synthesis, Cytotoxicity, and Cellular Uptake Mechanism.

    PubMed

    Li, Taoli; Gao, Xiangqian; Yang, Liu; Shi, Yunli; Gao, Qingzhi

    2016-05-19

    Methyl 6-aminodeoxy-d-pyranoside-derived platinum(II) glycoconjugates were designed and synthesized based on the clinical drug oxaliplatin for glucose transporter (GLUT)-mediated tumor targeting. In addition to a substantial improvement in water solubility, the conjugates exhibited cytotoxicity similar to or higher than that of oxaliplatin in six different human cancer cell lines. GLUT-mediated transport of the complexes was investigated with a cell-based fluorescence competition assay and GLUT-inhibitor-mediated cytotoxicity analysis in a GLUT-overexpressing human colorectal adenocarcinoma (HT29) cell line. The antitumor effect of the aminodeoxypyranoside-conjugated platinum(II) complexes was found to depend significantly on the GLUT inhibitor, and the cellular uptake of the molecules was regulated by GLUT-mediated transport. The results from this study demonstrate the potential advantages of aminodeoxypyranosides as sugar motifs for glycoconjugation for Warburg-effect-targeted drug design. These fundamental results also support the potential of aminodeoxypyranoside-conjugated platinum(II) complexes as lead compounds for further preclinical evaluation.

  8. Remote operation of the GOLEM tokamak with hydrogen and helium plasmas

    NASA Astrophysics Data System (ADS)

    Svoboda, V.; Dvornova, A.; Dejarnac, R.; Prochazka, M.; Zaprianov, S.; Akhmethanov, R.; Bogdanova, M.; Dimitrova, M.; Dimitrov, Zh; Grover, O.; Hlavata, L.; Ivanov, K.; Kruglov, K.; Marinova, P.; Masherov, P.; Mogulkin, A.; Mlynar, J.; Stockel, J.; Volynets, A.

    2016-10-01

    The GOLEM tokamak was operated remotely via Internet connection during the 6th International Workshop and Summer School on Plasma Physics. Performances of hydrogen and helium discharges are compared in this paper. It is found, at similar vacuum conditions, that helium discharges are shorter but the breakdown of the working gas can be quite easily achieved at almost the same loop voltage. The plasma current in helium discharges is slightly lower than in the case of hydrogen. Turbulent fluctuations of the floating potential measured by means of an array of Langmuir probes reveal a noticeably different character in the two discharges.

  9. A small and light weight heat exchanger for on-board helium refrigerator

    NASA Technical Reports Server (NTRS)

    Koizumi, T.; Takahashi, M.; Uchida, T.; Kanazawa, Y.; Suzuki, M.

    1983-01-01

    A small and light weight heat exchanger used for small helium refrigerator has been developed by Sumitomo Heavy Industries, Ltd. This heat exchanger is a laminated metal heat exchanger which consists of perforated aluminum metal plates and glassfiber reinforced plastic separators. The size is from 100 mm to 28 mm in diameter and about 300 mm in length. The weight is from 2.5 kg to 0.6 kg. Also it can be used between room temperature and liquid helium temperature. The thermal efficiency obtained has been more than 96%. The heat exchanger has been practically used for on-board helium refrigerator in Japanese National Railways' superconducting magnetic levitated trains.

  10. p90 ribosomal S6 kinase: a potential therapeutic target in lung cancer.

    PubMed

    Poomakkoth, Noufira; Issa, Aya; Abdulrahman, Nabeel; Abdelaziz, Somaia Gamal; Mraiche, Fatima

    2016-01-14

    A global survey of cancer has shown that lung cancer is the most common cause of the new cancer cases and cancer deaths in men worldwide. The mortality from lung cancer is more than the combined mortality from breast, prostate and colorectal cancers. The two major histological types of lung cancer are non-small cell lung cancer (NSCLC) accounting for about 85 % of cases and small cell lung cancer accounting for 15 % of cases. NSCLC, the more prevalent form of lung cancer, is often diagnosed at an advanced stage and has a very poor prognosis. Many factors have been shown to contribute to the development of lung cancer in humans including tobacco smoking, exposure to environmental carcinogens (asbestos, or radon) and genetic factors. Despite the advances in treatment, lung cancer remains one of the leading causes of cancer death worldwide. Interestingly, the overall 5 year survival from lung cancer has not changed appreciably in the past 25 years. For this reason, novel and more effective treatments and strategies for NSCLC are critically needed. p90 ribosomal S6 kinase (RSK), a serine threonine kinase that lies downstream of the Ras-MAPK (mitogen activated protein kinase) cascade, has been demonstrated to be involved in the regulation of cell proliferation in various malignancies through indirect (e.g., modulation of transcription factors) or direct effects on the cell-cycle machinery. Increased expression of RSK has been demonstrated in various cancers, including lung cancer. This review focuses on the role of RSK in lung cancer and its potential therapeutic application.

  11. 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

  12. Downregulation of microRNA-23a suppresses prostate cancer metastasis by targeting the PAK6-LIMK1 signaling pathway

    PubMed Central

    Li, Xiaojuan; Cai, Yi; Ye, Zhiqiang; Li, Shigeng; Li, Jun; Huang, Huaiqiu; Peng, Shubin; Wang, Jun; Tao, Yiran; Huang, Hongxing; Wen, Xinglai; Mo, Jianfeng; Deng, Zhupeng; Wang, Jian; Zhang, Yangfan; Gao, Xin; Wen, Xingqiao

    2015-01-01

    Here we found that levels of miR-23a were decreased in prostate cancer cell lines and tumor tissues. These low levels were associated with poor patients' prognosis. MiR-23a inhibited migration and invasion of prostate cancer in vivo and in orthotopic prostate cancer mice model. MiR-23a decreased levels of p21-activated kinase 6 (PAK6). Expression of miR-23a inhibited phosphorylation of LIM kinase 1 (LIMK1) and cofilin, in turn suppressing formation of stress fibers and actin filaments, which was required for cell motility and invasion. PAK6 bound to LIMK1 and activated it via phosphorylation at Thr-508. Also, PAK6 and LIMK1 were colocalized in the cytoplasma. Thus, miR-23a regulated cytoskeleton by affecting LIMK1 and cofilin. In summary, we have identified the miR-23a-PAK6-LIMK1 pathway of prostate cancer metastasis. Potential therapeutic approach by targeting miR-23 is suggested. PMID:25714010

  13. Interleukin-11 is the dominant IL-6 family cytokine during gastrointestinal tumorigenesis and can be targeted therapeutically.

    PubMed

    Putoczki, Tracy L; Thiem, Stefan; Loving, Andrea; Busuttil, Rita A; Wilson, Nicholas J; Ziegler, Paul K; Nguyen, Paul M; Preaudet, Adele; Farid, Ryan; Edwards, Kirsten M; Boglev, Yeliz; Luwor, Rodney B; Jarnicki, Andrew; Horst, David; Boussioutas, Alex; Heath, Joan K; Sieber, Oliver M; Pleines, Irina; Kile, Benjamin T; Nash, Andrew; Greten, Florian R; McKenzie, Brent S; Ernst, Matthias

    2013-08-12

    Among the cytokines linked to inflammation-associated cancer, interleukin (IL)-6 drives many of the cancer "hallmarks" through downstream activation of the gp130/STAT3 signaling pathway. However, we show that the related cytokine IL-11 has a stronger correlation with elevated STAT3 activation in human gastrointestinal cancers. Using genetic mouse models, we reveal that IL-11 has a more prominent role compared to IL-6 during the progression of sporadic and inflammation-associated colon and gastric cancers. Accordingly, in these models and in human tumor cell line xenograft models, pharmacologic inhibition of IL-11 signaling alleviated STAT3 activation, suppressed tumor cell proliferation, and reduced the invasive capacity and growth of tumors. Our results identify IL-11 signaling as a potential therapeutic target for the treatment of gastrointestinal cancers.

  14. Helium II level measurement techniques

    NASA Astrophysics Data System (ADS)

    Celik, D.; Hilton, D. K.; Zhang, T.; Van Sciver, S. W.

    2001-05-01

    In this paper, a survey of cryogenic liquid level measurement techniques applicable to superfluid helium (He II) is given. The survey includes both continuous and discrete measurement techniques. A number of different probes and controlling circuits for this purpose have been described in the literature. They fall into one of the following categories: capacitive liquid level gauges, superconducting wire liquid level gauges, thermodynamic (heat transfer-based) liquid level gauges, resistive gauges, ultrasound and transmission line-based level detectors. The present paper reviews these techniques and their suitability for He II service. In addition to these methods, techniques for measuring the total liquid volume and mass gauging are also discussed.

  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 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.

  17. Quantum Dynamics of Helium Clusters

    DTIC Science & Technology

    1993-03-01

    helium clusters [10-12]. (10) DMC starts with the time - dependent Schr ~ dinger equation in imaginary time and has been employed most- The approximate...bound. (For example, the binding values may be computed by the Metropolis approach . energy of He 3 is five times greater than that of 1l1lie I We first...or four times for computational effort. If this is also the case with the the larger clusters) its original size. If the maximum en- DMC approach

  18. Investigation of Cellular Interactions of Nanoparticles by Helium Ion Microscopy

    SciTech Connect

    Arey, Bruce W.; Shutthanandan, V.; Xie, Yumei; Tolic, Ana; Williams, Nolann G.; Orr, Galya

    2011-06-01

    The helium ion mircroscope (HIM) probes light elements (e.g. C, N, O, P) with high contrast due to the large variation in secondary electron yield, which minimizes the necessity of specimen staining. A defining characteristic of HIM is its remarkable capability to neutralize charge by the implementation of an electron flood gun, which eliminates the need for coating non-conductive specimens for imaging at high resolution. In addition, the small convergence angle in HeIM offers a large depth of field (~5x FE-SEM), enabling tall structures to be viewed in focus within a single image. Taking advantage of these capabilities, we investigate the interactions of engineered nanoparticles (NPs) at the surface of alveolar type II epithelial cells grown at the air-liquid interface (ALI). The increasing use of nanomaterials in a wide range of commercial applications has the potential to increase human exposure to these materials, but the impact of such exposure on human health is still unclear. One of the main routs of exposure is the respiratory tract, where alveolar epithelial cells present a vulnerable target at the interface with ambient air. Since the cellular interactions of NPs govern the cellular response and ultimately determine the impact on human health, our studies will help delineating relationships between particle properties and cellular interactions and response to better evaluate NP toxicity or biocompatibility. The Rutherford backscattered ion (RBI) is a helium ions imaging mode, which backscatters helium ions from every element except hydrogen, with a backscatter yield that depends on the atomic number of the target. Energy-sensitive backscatter analysis is being developed, which when combined with RBI image information, supports elemental identification at helium ion nanometer resolution. This capability will enable distinguishing NPs from cell surface structures with nanometer resolution.

  19. Investigation of cellular interactions of nanoparticles by helium ion microscopy

    NASA Astrophysics Data System (ADS)

    Arey, B. W.; Shutthanandan, V.; Xie, Y.; Tolic, A.; Williams, N.; Orr, G.

    2011-06-01

    The helium ion microscope (HIM) probes light elements (e.g. C, N, O, P) with high contrast due to the large variation in secondary electron yield, which minimizes the necessity of specimen staining. A defining characteristic of HIM is its remarkable capability to neutralize charge by the implementation of an electron flood gun, which eliminates the need for coating non-conductive specimens for imaging at high resolution. In addition, the small convergence angle in HeIM offers a large depth of field (~5× FE-SEM), enabling tall structures to be viewed in focus within a single image. Taking advantage of these capabilities, we investigate the interactions of engineered nanoparticles (NPs) at the surface of alveolar type II epithelial cells grown at the airliquid interface (ALI). The increasing use of nanomaterials in a wide range of commercial applications has the potential to increase human exposure to these materials, but the impact of such exposure on human health is still unclear. One of the main routs of exposure is the respiratory tract, where alveolar epithelial cells present a vulnerable target at the interface with ambient air. Since the cellular interactions of NPs govern the cellular response and ultimately determine the impact on human health, our studies will help delineating relationships between particle properties and cellular interactions and response to better evaluate NP toxicity or biocompatibility. The Rutherford backscattered ion (RBI) is a helium ions imaging mode, which backscatters helium ions from every element except hydrogen, with a backscatter yield that depends on the atomic number of the target. Energy-sensitive backscatter analysis is being developed, which when combined with RBI image information, supports elemental identification at helium ion nanometer resolution. This capability will enable distinguishing NPs from cell surface structures with nanometer resolution.

  20. 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. 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.

  2. 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.

  3. Design of subcooled helium II refrigerator with helium-3 cold compressor

    SciTech Connect

    Kato, D.; Saji, N.; Ohya, H.; Asakura, H.; Kubota, M.; Kaneko, Y.; Nagai, S.

    1994-12-31

    This paper will study the possibility of a He II refrigerator made up of three cold compressors by making use of helium-3 characteristics. This system is compact enough to fit inside a small cold box, so it can be easily connected with an existing helium-4 refrigerator. The authors designed the compressors, calculated the He II cooling capacity, 4.4 K refrigeration load, required inventory of helium-3, and Carnot efficiency. Though helium-3 is expensive, the required inventory of helium-3 to be filled inside this He II refrigerator was calculated to be small enough to prove practicality of constructing this refrigerator.

  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. MicroRNA-29a suppresses the growth, migration, and invasion of lung adenocarcinoma cells by targeting carcinoembryonic antigen-related cell adhesion molecule 6.

    PubMed

    Han, Hye Sook; Son, Seung-Myoung; Yun, Jieun; Jo, Yeong Nang; Lee, Ok-Jun

    2014-10-16

    Carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6) is an important regulator of cell adhesion, invasion, and metastasis. The aim of this study was to evaluate the functional roles of CEACAM6 in lung adenocarcinoma and to identify miRNAs that inhibit the growth, migration, and invasion of lung adenocarcinoma cells by targeting CEACAM6. CEACAM6 expression is associated with poor prognosis of patients with lung adenocarcinoma, and CEACAM6 has important functional roles in controlling the growth, migration, and invasion of lung adenocarcinoma cells in vitro and in vivo. Furthermore, miR-29a can suppress the growth, migration, and invasion of lung adenocarcinoma cells by targeting CEACAM6. Therefore, miR-29a/CEACAM6 axis represents a potential therapeutic target for treatment of lung adenocarcinoma.

  6. 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…

  7. 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.

  8. Theoretical model of the helium pinhole microscope

    NASA Astrophysics Data System (ADS)

    Palau, Adrià Salvador; Bracco, Gianangelo; Holst, Bodil

    2016-12-01

    In recent years, the development of neutral helium microscopes has gained increasing interest. The low energy, charge neutrality, and inertness of the helium atoms makes helium microscopy an attractive candidate for the imaging of a range of samples. The simplest neutral helium microscope is the so-called pinhole microscope. It consists of a supersonic expansion helium beam collimated by two consecutive apertures (skimmer and pinhole), which together determine the beam spot size and hence the resolution at a given working distance to the sample. Due to the high ionization potential of neutral helium atoms, it is difficult to build efficient helium detectors. Therefore, it is crucial to optimize the microscope design to maximize the intensity for a given resolution and working distance. Here we present an optimization model for the helium pinhole microscope system. We show that for a given resolution and working distance, there is a single intensity maximum. Further we show that with present-day state-of-the-art detector technology (ionization efficiency 1 ×10-3 ), a resolution of the order of 600 nm at a working distance of 3 mm is possible. In order to make this quantification, we have assumed a Lambertian reflecting surface and calculated the beam spot size that gives a signal 100 cts/s within a solid angle of 0.02 π sr, following an existing design. Reducing the working distance to the micron range leads to an improved resolution of around 40 nm.

  9. 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).

  10. Neutral atom lithography with metastable helium

    NASA Astrophysics Data System (ADS)

    Allred, Claire Shean

    In this dissertation we describe our performance of resist assisted neutral atom lithography using a bright beam of metastable 23S1 Helium (He*). Metastable Helium atoms have 20 eV of internal energy making them easy to detect and able to destroy a resist. The He* is produced by a reverse flow DC discharge source and then collimated with the bichromatic force, followed by three optical molasses velocity compression stages. The atoms in the resulting beam have a mean longitudinal velocity of 1125 m/s and a divergence of 1.1 mrad. The typical beam flux is 2 x 109 atoms/mm2s through a 0.1mm diameter aperture 70 cm away from the source. The internal energy of the atoms damages the molecules of a self assembled monolayer (SAM) of nonanethiol. The undisturbed SAM protects a 200 A layer of gold that has been evaporated onto a prepared Silicon wafer from a wet chemical etch. Two methods are used to pattern the He* atoms before they destroy the SAM. First, a Nickel micro mesh was used to protect the SAM. These experiments established an appropriate dosage and etch time for patterning. The samples were analyzed with an atomic force microscope and found to have an edge resolution of 63 nm. Then, patterning was accomplished using the dipole force the atoms experience while traversing a standing wave of lambda = 1083nm light tuned 500MHz below the 23S 1 → 23P2 transition. Depending on the intensity of the light, the He* atoms are focused or channeled into lines separated by lambda/2. The lines cover the entire exposed length of the substrate, about 3 mm. They are about 3 mm long, corresponding to about twice the beam waist of the laser standing wave. Thus there are 6 x 10 3 lines of length 5500lambda. These results agree with our numerical simulations of the experiment.

  11. 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

  12. In silico-guided target identification of a scaffold-focused library: 1,3,5-triazepan-2,6-diones as novel phospholipase A2 inhibitors.

    PubMed

    Muller, Pascal; Lena, Gersande; Boilard, Eric; Bezzine, Sofiane; Lambeau, Gérard; Guichard, Gilles; Rognan, Didier

    2006-11-16

    A collection of 2150 druggable active sites from the Protein Data Bank was screened by high-throughput docking to identify putative targets for five representative molecules of a combinatorial library sharing a 1,3,5-triazepan-2,6-dione scaffold. Five targets were prioritized for experimental evaluation by computing enrichment in individual protein entries among the top 2% scoring targets. Out of the five proposed proteins, secreted phospholipase A2 (sPLA2) was shown to be a true target for a panel of 1,3,5-triazepan-2,6-diones which exhibited micromolar affinities toward two human sPLA2 members.

  13. Cellular effects of helium in different organs.

    PubMed

    Oei, Gezina T M L; Weber, Nina C; Hollmann, Markus W; Preckel, Benedikt

    2010-06-01

    Experimental research in cardiac and neuronal tissue has shown that besides volatile anesthetics and xenon, the nonanesthetic noble gas helium also reduces ischemia-reperfusion damage. Even though the distinct mechanisms of helium-induced organ protection are not completely unraveled, several signaling pathways have been identified. Beside the protective effects on heart and brain that are mainly obtained by different pre- and postconditioning protocols, helium also exerts effects in the lungs, the immune system, and the blood vessels. Obviously, this noble gas is biochemically not inert and exerts biologic effects, although until today the question remains open on how these changes are mediated. Because of its favorable characteristics and the lack of hemodynamic side effects, helium is suitable for use also in critically ill patients. This review covers the cellular effects of helium, which may lead to new clinical strategies of tissue salvage in ischemia-reperfusion situations, both within and outside the perioperative setting.

  14. Cryogenic helium 2 systems for space applications

    NASA Technical Reports Server (NTRS)

    Urban, E.; Katz, L.; Hendricks, J.; Karr, G.

    1978-01-01

    Two cryogenic systems are described which will provide cooling for experiments to be flown on Spacelab 2 in the early 1980's. The first system cools a scanning infrared telescope by the transfer of cold helium gas from a separate superfluid helium storage dewar. The flexible design permits the helium storage dewar and transfer assembly to be designed independent of the infrared experiment. Where possible, modified commerical apparatus is used. The second cryogenic system utilizes a specially designed superfluid dewar in which a superfluid helium experiment chamber is immersed. Each dewar system employs a porous plug as a phase separator to hold the liquid helium within the dewar and provide cold gas to a vent line. To maintain the low vapor pressure of the superfluid, each system requires nearly continuous prelaunch vacuum pump service, and each will vent to space during the Spacelab 2 flight.

  15. Double differential cross sections for electron impact ionization of helium

    NASA Astrophysics Data System (ADS)

    Yun-fei, Yao; Zhang-jin, Chen

    1999-03-01

    The double differential cross sections for electron impact ionization of helium at incident energies of 200 eV, 100 eV and 64.6 eV have been calculated in the BBK model. The present results are found to be in generally good agreement with the latest measurements of Röder et al. and the theoretical results of the convergent close-coupling method although some quantitative discrepancy remains.

  16. Hsp72 is targeted to the mitotic spindle by Nek6 to promote K-fiber assembly and mitotic progression.

    PubMed

    O'Regan, Laura; Sampson, Josephina; Richards, Mark W; Knebel, Axel; Roth, Daniel; Hood, Fiona E; Straube, Anne; Royle, Stephen J; Bayliss, Richard; Fry, Andrew M

    2015-05-11

    Hsp70 proteins represent a family of chaperones that regulate cellular homeostasis and are required for cancer cell survival. However, their function and regulation in mitosis remain unknown. In this paper, we show that the major inducible cytoplasmic Hsp70 isoform, Hsp72, is required for assembly of a robust bipolar spindle capable of efficient chromosome congression. Mechanistically, Hsp72 associates with the K-fiber-stabilizing proteins, ch-TOG and TACC3, and promotes their interaction with each other and recruitment to spindle microtubules (MTs). Targeting of Hsp72 to the mitotic spindle is dependent on phosphorylation at Thr-66 within its nucleotide-binding domain by the Nek6 kinase. Phosphorylated Hsp72 concentrates on spindle poles and sites of MT-kinetochore attachment. A phosphomimetic Hsp72 mutant rescued defects in K-fiber assembly, ch-TOG/TACC3 recruitment and mitotic progression that also resulted from Nek6 depletion. We therefore propose that Nek6 facilitates association of Hsp72 with the mitotic spindle, where it promotes stable K-fiber assembly through recruitment of the ch-TOG-TACC3 complex.

  17. 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.

  18. PCAF-mediated acetylation of transcriptional factor HOXB9 suppresses lung adenocarcinoma progression by targeting oncogenic protein JMJD6

    PubMed Central

    Wan, Junhu; Xu, Weizhi; Zhan, Jun; Ma, Ji; Li, Xueying; Xie, Yuping; Wang, Jiadong; Zhu, Wei-guo; Luo, Jianyuan; Zhang, Hongquan

    2016-01-01

    HOXB9 is a homeobox domain-containing transcription factor, playing an important role in embryonic development and cancer progression. However, the precise post-translational modifications (PTMs) of HOXB9 and the corresponding roles are unclear. Here, we report that acetyltransferase p300/CBP-associated factor (PCAF) interacts with and acetylates HOXB9 both in vivo and in vitro. Conversely, the acetylation of HOXB9 can be reversed by deacetylase SIRT1. Furthermore, we found that HOXB9 is acetylated at lysine 27 (AcK27). Functionally, in contrast to the wild type HOXB9, AcK27-HOXB9 decreased its capacity in promoting lung cancer cell migration and tumor growth in mice. Mechanistically, AcK27-HOXB9 suppresses the transcription of its target gene Jumonji domain-containing protein 6 (JMJD6) by direct occupying the promoter of JMJD6 gene. For clinical relevance, elevated HOXB9 acetylation at K27 predicts a better prognosis in lung adenocarcinoma patients. Taken together, we identified the first PTM of HOXB9 by demonstrating that HOXB9 can be acetylated and AcK27-HOXB9 counteracts the role of the wild-type HOXB9 in regulating lung adenocarcinoma progression. PMID:27613418

  19. 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

  20. Sensitivity of KRAS-Mutant Colorectal Cancers to Combination Therapy that Co-Targets MEK and CDK4/6

    PubMed Central

    Ziemke, Elizabeth K.; Dosch, Joseph S.; Maust, Joel D.; Shettigar, Amrith; Sen, Ananda; Welling, Theodore H.; Hardiman, Karin M.; Sebolt-Leopold, Judith S.

    2015-01-01

    Purpose The emerging need for rational combination treatment approaches led us to test the concept that co-targeting MEK and CDK4/6 would prove efficacious in KRAS mutant (KRASmt) colorectal cancers, where upregulated CDK4 and hyperphosphorylated retinoblastoma (RB) typify the vast majority of tumors. Experimental Design Initial testing was carried out in the HCT-116 tumor model, which is known to harbor a KRAS mutation. Efficacy studies were then performed with five RB+ patient-derived colorectal xenograft models, genomically diverse with respect to KRAS, BRAF, and PIK3CA mutational status. Tolerance, efficacy, and pharmacodynamic evaluation of target modulation were evaluated in response to daily dosing with either agent alone or concurrent co-administration. Results Synergy was observed in vitro when HCT-116 cells were treated over a broad range of doses of trametinib and palbociclib. Subsequent in vivo evaluation of this model showed a higher degree of antitumor activity resulting from the combination compared to that achievable with single agent treatment. Testing of colorectal patient-derived xenograft (PDX) models further showed that combination of trametinib and palbociclib was well tolerated and resulted in objective responses in all KRASmt models tested. Stasis was observed in a KRAS/BRAF wild type and a BRAFmt model. Conclusions Combination of trametinib and palbociclib was well tolerated and highly efficacious in all three KRAS mutant CRC PDX models tested. Promising preclinical activity seen here supports clinical evaluation of this treatment approach to improve therapeutic outcome for metastatic colorectal cancer patients. PMID:26369631

  1. 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

  2. PAK6 targets to cell–cell adhesions through its N-terminus in a Cdc42-dependent manner to drive epithelial colony escape

    PubMed Central

    Morse, Elizabeth M.; Sun, Xiaowen; Olberding, Jordan R.; Ha, Byung Hak; Boggon, Titus J.; Calderwood, David A.

    2016-01-01

    ABSTRACT The six serine/threonine kinases in the p21-activated kinase (PAK) family are important regulators of cell adhesion, motility and survival. PAK6, which is overexpressed in prostate cancer, was recently reported to localize to cell–cell adhesions and to drive epithelial cell colony escape. Here we report that PAK6 targeting to cell–cell adhesions occurs through its N-terminus, requiring both its Cdc42/Rac interactive binding (CRIB) domain and an adjacent polybasic region for maximal targeting efficiency. We find PAK6 localization to cell–cell adhesions is Cdc42-dependent, as Cdc42 knockdown inhibits PAK6 targeting to cell–cell adhesions. We further find the ability of PAK6 to drive epithelial cell colony escape requires kinase activity and is disrupted by mutations that perturb PAK6 cell–cell adhesion targeting. Finally, we demonstrate that all type II PAKs (PAK4, PAK5 and PAK6) target to cell–cell adhesions, albeit to differing extents, but PAK1 (a type I PAK) does not. Notably, the ability of a PAK isoform to drive epithelial colony escape correlates with its targeting to cell–cell adhesions. We conclude that PAKs have a broader role in the regulation of cell–cell adhesions than previously appreciated. PMID:26598554

  3. Electric response in superfluid helium

    NASA Astrophysics Data System (ADS)

    Chagovets, Tymofiy V.

    2016-05-01

    We report an experimental investigation of the electric response of superfluid helium that arises in the presence of a second sound standing wave. It was found that the signal of the electric response is observed in a narrow range of second sound excitation power. The linear dependence of the signal amplitude has been derived at low excitation power, however, above some critical power, the amplitude of the signal is considerably decreased. It was established that the rapid change of the electric response is not associated with a turbulent regime generated by the second sound wave. A model of the appearance of the electric response as a result of the oscillation of electron bubbles in the normal fluid velocity field in the second sound wave is presented. Possible explanation for the decrease of the electric response are presented.

  4. Nondipole effects in helium photoionization

    NASA Astrophysics Data System (ADS)

    Argenti, Luca; Moccia, Roberto

    2010-12-01

    An accurate calculation of the nondipole anisotropy parameter γ in the photoionization of helium below the N = 2 threshold is presented. The calculated results are in fairly good agreement with the experimental results of Krässig et al (2002 Phys. Rev. Lett. 88 203002), but not as good as the accuracy of the calculation should have warranted. A careful examination of the possible causes for the observed discrepancies between theory and experiment seems to rule out any role either of the multipolar terms higher than the electric quadrupole, or of the singlet-triplet spin-orbit mixing. It is argued that such discrepancies might have an instrumental origin, due to the difficulty of measuring vanishingly small total cross sections σtot with the required accuracy. In such eventuality, it might be more appropriate to use a parameter other than γ, such as for instance the drag current, to measure the nondipole anisotropy of the photoelectron angular distribution.

  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. 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.

  7. Nitro and amino substitution in the D-ring of 5-(2-dimethylaminoethyl)- 2,3-methylenedioxy-5H-dibenzo[c,h][1,6]naphthyridin-6-ones: effect on topoisomerase-I targeting activity and cytotoxicity.

    PubMed

    Singh, Sudhir K; Ruchelman, Alexander L; Li, Tsai-Kun; Liu, Angela; Liu, Leroy F; LaVoie, Edmond J

    2003-05-22

    5H-8,9-dimethoxy-5-(2-N,N-dimethylaminoethyl)-2,3-methylenedioxydibenzo[c,h][1,6]naphthyridin-6-one exhibits potent TOP1-targeting activity and pronounced antitumor activity. It was hypothesized that replacement of the two methoxyl groups with a nitro substituent would allow for retention of similar activity. In this study 8-, 9-, and 10-nitro-5H-2,3-methylenedioxy-5-(2-N,N-dimethylaminoethyl)dibenzo[c,h][1,6]naphthyridin-6-one and their amino derivatives were synthesized and assessed for their relative TOP1-targeting activity and cytotoxicity. In the case of both the 8- and 9-nitro analogues, their TOP1-targeting activity and cytotoxicity are greater than that of camptothecin and comparable to that of 5H-8,9-dimethoxy-5-(2-N,N-dimethylaminoethyl)-2,3-methylenedioxydibenzo[c,h][1,6]naphthyridin-6-one.

  8. 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

  9. 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.

  10. 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.

  11. 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...

  12. 21 CFR 868.1640 - Helium gas analyzer.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Helium gas analyzer. 868.1640 Section 868.1640...) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Diagnostic Devices § 868.1640 Helium gas analyzer. (a) Identification. A helium gas analyzer is a device intended to measure the concentration of helium in a...

  13. 21 CFR 868.1640 - Helium gas analyzer.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Helium gas analyzer. 868.1640 Section 868.1640...) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Diagnostic Devices § 868.1640 Helium gas analyzer. (a) Identification. A helium gas analyzer is a device intended to measure the concentration of helium in a...

  14. 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...

  15. 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...

  16. Helium-Rich Bursters Reveal the NS Interiors

    NASA Astrophysics Data System (ADS)

    Misanovic, Zdenka

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

  17. Contrasting pressure-support ventilation and helium-oxygen during exercise in severe COPD.

    PubMed

    Hussain, Omar; Collins, Eileen G; Adiguzel, Nalan; Langbein, W Edwin; Tobin, Martin J; Laghi, Franco

    2011-03-01

    Helium-oxygen mixtures and pressure-support ventilation have been used to unload the respiratory muscles and increase exercise tolerance in COPD. Considering the different characteristics of these techniques, we hypothesized that helium-oxygen would be more effective in reducing exercise-induced dynamic hyperinflation than pressure-support. We also hypothesized that patients would experience greater increases in respiratory rate and minute ventilation with helium-oxygen than with pressure-support. The hypotheses were tested in ten patients with severe COPD (FEV(1) = 28 ± 3% predicted [mean ± SE]) during constant-load cycling (80% maximal workrate) while breathing 30% oxygen-alone, helium-oxygen, and pressure-support in randomized order. As hypothesized, helium-oxygen had greater impact on dynamic hyperinflation than did pressure-support (end-exercise; p = 0.03). For the most part of exercise, respiratory rate and minute ventilation were greater with helium-oxygen than with pressure-support (p ≤ 0.008). During the initial phases of exercise, helium-oxygen caused less rib-cage muscle recruitment than did pressure-support (p < 0.03), and after the start of exercise it caused greater reduction in inspiratory reserve volume (p ≤ 0.02). Despite these different responses, helium-oxygen and pressure-support caused similar increases in exercise duration (oxygen-alone: 6.9 ± 0.8 min; helium-oxygen: 10.7 ± 1.4 min; pressure-support: 11.2 ± 1.6 min; p = 0.003) and similar decreases in inspiratory effort (esophageal pressure-time product), respiratory drive, pulmonary resistance, dyspnea and leg effort (p < 0.03). In conclusion, helium-oxygen reduced exercise-induced dynamic hyperinflation by improving the relationship between hyperinflation and minute ventilation. In contrast, pressure-support reduced hyperinflation solely as a result of lowering ventilation. Helium-oxygen was more effective in reducing exercise-induced dynamic hyperinflation in severe COPD, and was

  18. Helium resources of the United States, 1987. Information Circular/1988

    SciTech Connect

    Miller, R.D.

    1987-01-01

    The helium-resources base of the United States was estimated by the Bureau of Mines to be 1040 Bcf as of January 1, 1987. These resources are divided into four categories in decreasing degree of assurance of their existence: (1) helium in storage and in proved natural gas reserves, 265 Bcf, (2) helium in probable natural gas resources, 228 Bcf, (3) helium in possible natural gas resources, 320 Bcf, and (4) helium in speculative natural gas resources, 227 Bcf. These helium resources are further divided into depleting and nondepleting, with the helium in storage being in a separate classification.

  19. 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.

  20. 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.

  1. Development of a transferline connecting a helium liquefier coldbox and a liquid helium Dewar

    NASA Astrophysics Data System (ADS)

    Menon, Rajendran S.; Rane, Tejas; Chakravarty, Anindya; Joemon, V.

    2017-02-01

    A helium liquefier with demonstrated capacity of 32 1/hr has been developed by BARC. Mumbai. A transferline for two way flow of helium between the helium liquefier coldbox and receiver Dewar has been developed in-house at BARC. Further, a functionally similar, but structurally improved transferline has been developed through a local fabricator. This paper describes and discusses issues related to the development of these cryogenic transferlines. The developed transferlines have been tested with a flow of liquid nitrogen and successfully utilised later in the helium liquefier plant.

  2. 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.

  3. Primary helium heater for propellant pressurization systems

    NASA Technical Reports Server (NTRS)

    Reichmuth, D. M.; Nguyen, T. V.; Pieper, J. L.

    1991-01-01

    The primary helium heater is a unique design that provides direct heating of pressurant gas for large pressure fed propulsion systems. It has been conceptually designed to supply a heated (800-1000 R) pressurization gas to both a liquid oxygen and an RP-1 propellant tank. This pressurization gas is generated within the heater by mixing super critical helium (40-300 R and 3000-1600 psi) with an appropriate amount of combustion products from a 4:1 throttling stoichiometric LO2/LH2 combustor. This simple, low cost and reliable mixer utilizes the large quantity of helium to provide stoichiometric combustor cooling, extend the throttling limits and enhance the combustion stability margin. Preliminary combustion, thermal, and CFD analyses confirm that this low-pressure-drop direct helium heater can provide the constant-temperature pressurant suitable for tank pressurization of both fuel and oxidizer tanks of large pressure fed vehicles.

  4. 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.

  5. 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)

  6. 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...

  7. Loss of tumor suppressor KDM6A amplifies PRC2-regulated transcriptional repression in bladder cancer and can be targeted through inhibition of EZH2.

    PubMed

    Ler, Lian Dee; Ghosh, Sujoy; Chai, Xiaoran; Thike, Aye Aye; Heng, Hong Lee; Siew, Ee Yan; Dey, Sucharita; Koh, Liang Kai; Lim, Jing Quan; Lim, Weng Khong; Myint, Swe Swe; Loh, Jia Liang; Ong, Pauline; Sam, Xin Xiu; Huang, Dachuan; Lim, Tony; Tan, Puay Hoon; Nagarajan, Sanjanaa; Cheng, Christopher Wai Sam; Ho, Henry; Ng, Lay Guat; Yuen, John; Lin, Po-Hung; Chuang, Cheng-Keng; Chang, Ying-Hsu; Weng, Wen-Hui; Rozen, Steven G; Tan, Patrick; Creasy, Caretha L; Pang, See-Tong; McCabe, Michael T; Poon, Song Ling; Teh, Bin Tean

    2017-02-22

    Trithorax-like group complex containing KDM6A acts antagonistically to Polycomb-repressive complex 2 (PRC2) containing EZH2 in maintaining the dynamics of the repression and activation of gene expression through H3K27 methylation. In urothelial bladder carcinoma, KDM6A (a H3K27 demethylase) is frequently mutated, but its functional consequences and therapeutic targetability remain unknown. About 70% of KDM6A mutations resulted in a total loss of expression and a consequent loss of demethylase function in this cancer type. Further transcriptome analysis found multiple deregulated pathways, especially PRC2/EZH2, in KDM6A-mutated urothelial bladder carcinoma. Chromatin immunoprecipitation sequencing analysis revealed enrichment of H3K27me3 at specific loci in KDM6A-null cells, including PRC2/EZH2 and their downstream targets. Consequently, we targeted EZH2 (an H3K27 methylase) and demonstrated that KDM6A-null urothelial bladder carcinoma cell lines were sensitive to EZH2 inhibition. Loss- and gain-of-function assays confirmed that cells with loss of KDM6A are vulnerable to EZH2. IGFBP3, a direct KDM6A/EZH2/H3K27me3 target, was up-regulated by EZH2 inhibition and contributed to the observed EZH2-dependent growth suppression in KDM6A-null cell lines. EZH2 inhibition delayed tumor onset in KDM6A-null cells and caused regression of KDM6A-null bladder tumors in both patient-derived and cell line xenograft models. In summary, our study demonstrates that inactivating mutations of KDM6A, which are common in urothelial bladder carcinoma, are potentially targetable by inhibiting EZH2.

  8. CHARACTERIZING TRITIUM WASTE USING HELIUM RATIOS

    SciTech Connect

    Ovink, R.W.; McMahon, W.J.; Borghese, J.V.; Olsen, K.B.

    2003-02-27

    When routine sampling revealed greatly elevated tritium levels (3.14 x 105 Bq/L [8.5-million pCi/liter]) in the groundwater near a solid waste landfill at the Hanford Site, an innovative technique was used to assess the extent of the plume. Helium-3/helium-4 ratios, relative to ambient air-in-soil gas samples, were used to identify the tritium source and initially delineate the extent of the groundwater tritium plume. This approach is a modification of a technique developed in the late 1960s to age-date deep ocean water as part of the GEOSECS ocean monitoring program. Poreda, et al. (1) and Schlosser, et al. (2) applied this modified technique to shallow aquifers. A study was also conducted to demonstrate the concept of using helium-3 as a tool to locate vadose zone sources of tritium and tracking groundwater tritium plumes at Hanford (3). Seventy sampling points were installed around the perimeter and along four transects downgradient of the burial ground. Soil gas samples were collected, analyzed for helium isotopes, and helium-3/helium-4 ratios were calculated for these 70 points. The helium ratios indicated a vadose zone source of tritium along the northern edge of the burial ground that is likely the source of tritium in the groundwater. The helium ratios also indicate the groundwater plume is traveling east-northeast from the burial ground and that no up-gradient tritium sources are affecting the burial ground. Based on the helium ratio results, six downgradient groundwater sampling locations were identified to verify the tritium plume extent and groundwater tritium concentrations. The tritium results from the initial groundwater samples confirmed that elevated helium ratios were indicative of tritium contamination in the local groundwater. The measurement of helium isotopes in soil gas provided a rapid and cost- effective technique to define the shape and extent of tritium contamination from the burial ground. Using this soil gas sampling approach, the

  9. 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.

  10. Properties of vanadium-base alloys irradiated in the dynamic helium charging experiment

    SciTech Connect

    Chung, H.M.; Loomis, B.A.; Smith, D.L.

    1996-02-01

    One property of vanadium-base alloys that is not well understood in terms of their potential use as fusion reactor structural materials is the effect of simultaneous generation of helium and neutron damage. In the present Dynamic Helium Charging Experiment (DHCE), helium was produced uniformly in the specimen at linear rates of {approx} 0.4 to 4.2 appm helium/dpa by the decay of tritium during irradiation to 18--31 dpa at 425--600 C in Li-filled capsules in a sodium-cooled fast reactor. This paper presents results of postirradiation examination and tests of microstructure and mechanical properties of V-5Ti, V-3Ti-1Si, V-8Cr-6Ti, and V-4Cr-4Ti (the latter alloy has been identified as the most promising candidate vanadium alloy). Effects of helium on tensile strength and ductility were insignificant after irradiation and testing at > 420 C. However, postirradiation ductilities at < 250 C were higher than those of the non-DHCE specimens (< 0.1 appm helium), whereas strengths were lower, indicating that different types of hardening centers are produced during DHCE and non-DHCE irradiation. Ductile-brittle transition behavior of the DHCE specimens was also determined from bend tests and fracture appearance of transmission electron microscopy (TEM) disks and broken tensile specimens. No brittle behavior was observed at temperatures > {minus}150 C in DHCE specimens. Predominantly brittle-cleavage fracture morphologies were observed only at {minus}196 C in some specimens that were irradiated to 31 dpa at 425 C during the DHCE. For the helium generation rates in this experiment ({approx} 0.4--4.2 appm He/dpa), grain-boundary coalescence of helium microcavities was negligible and intergranular fracture was not observed.

  11. 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.

  12. Bronchomotor response to cold air or helium-oxygen at normal and high ambient pressures.

    PubMed

    Jammes, Y; Burnet, H; Cosson, P; Lucciano, M

    1988-05-01

    Effects of inhalation of cold air or helium-oxygen mixture on lung resistance (RL) were studied in anesthetized and tracheotomized rabbits under normal ambient pressure and in human volunteers under normo- and hyperbaric conditions. In artificially ventilated rabbits, an increase in RL occurred when the tracheal temperature fell to 10 degrees C. This effect was more than double with helium breathing compared to air, despite a lower respiratory heat loss by convection (Hc) with helium. In 3 normal humans, inhalation of cold air (mouth temperature = 8 degrees C) at sea level had no effect on RL value. However, with a helium-nitrogen-oxygen mixture, a weak but significant increase in RL due to cold gas breathing was measured in 1 subject at 2 ATA and in 2 individuals at 3.5 ATA. The density of inhaled gas mixture (air or He-N2-O2) was near the same in the three circumstances (1, 2, and 3.5 ATA) but Hc value increased with helium. At 8 ATA a 30-55% increase in RL occurred in the 3 divers during inhalation of cold gas (Hc was multiplied by 6 compared to air at sea level) and at 25 ATA the cold-induced bronchospasm ranged between 38 and 95% (Hc multiplied by 27). Thus, in rabbits and humans helium breathing enhanced the cold-induced increase in RL at normal or elevated ambient pressure, and this effect was interpreted as resulting from different mechanisms in the two circumstances.

  13. 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.

  14. Radioactive Ions and Atoms in Superfluid Helium

    NASA Astrophysics Data System (ADS)

    Dendooven, P.; Purushothaman, S.; Gloos, K.; ńystö, J.; Takahashi, N.; Huang, W. X.

    2006-04-01

    We are investigating the use of superfluid helium as a medium to handle and manipulate radioactive ions and atoms. Preliminary results on the extraction of positive ions from superfluid helium at temperatures close to 1 K are described. Increasing the electric field up to 1.2 kV/cm did not improve the extraction. Evaporating a thin surface layer of the liquid using second-sound pulses gave an extraction efficiency of 7.2 %.

  15. Helium Reionization in From New Sightlines

    NASA Astrophysics Data System (ADS)

    Syphers, David

    2017-01-01

    A very small number of sightlines to z~3 quasars have been studied in detail to show the progress of helium reionization. Although studying the same sightlines with each new UV spectrograph lead to a better understanding of them, the sightline variance is very strong during this patchy and extended process. We discuss detailed R>10,000 COS data from new sightlines, and what they reveal about the progress and end of helium reionization.

  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. 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.

  18. Rydberg States of Na-doped Helium Nanodroplets

    NASA Astrophysics Data System (ADS)

    Drabbels, Marcel

    2008-03-01

    The dynamics of excited states of Na atoms deposited on the surface of helium nanodroplets has been investigated with velocity map ion imaging, photoelectron spectroscopy and time-of-flight mass-spectroscopy. For the first time, the excitation spectra of Na-doped helium nanodroplets corresponding to Rydberg states of Na atoms have been measured from the lowest excited 3p state up to the ionization threshold. All lines in the excitation spectra are shifted and broadened with respect to the corresponding atomic lines. In addition to bare Na* atoms also Na*HeN (N = 1-6) exciplexes are detected upon excitation. Photoelectron spectroscopy reveals the desorption of Na* not only in the initially excited states but also in lower lying states, indicating that relaxation plays an important role. The recorded velocity distributions show interesting characteristics: for the lowest states the mean kinetic energy of Na* increases linearly with excitation energy. The velocity distributions of Na*HeN exciplexes do not manifest such remarkable properties. The observations can be largely explained by assuming that the interaction of Na* with the helium nanodroplet can be described by the sum of Na*-He pair potentials.

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. Positive ion extraction across the superfluid-vapor helium interface

    NASA Astrophysics Data System (ADS)

    Purushothaman, S.; Peräjärvi, K.; Ranjan, M.; Saastamoinen, A.; Gloos, K.; Takahashi, N.; Dendooven, P.

    2009-02-01

    The extraction efficiency of positive Rn ions across the superfluid-vapor helium interface above ~1.3 K indicates that extraction results from thermal activation across a barrier of about 20 K. Below ~1.3 K, the extraction efficiency is constant at about 0.7%. The evaporation of the superfluid surface by second sound pulses has a negative impact on the ion extraction, but not on the ions themselves. It takes 3.2(6) s at 1.60 K and 15(6) s at 1.15 K for the extraction process to recover from a disturbed state of yet unknown nature.

  4. Helium Ion Imaging and Milling at the Nanometer Dimensions

    NASA Astrophysics Data System (ADS)

    Ming, Bin

    2009-03-01

    The helium ion microscope (HeIM) is a new, powerful instrument for nano-metrology and nanotechnology. As an emerging imaging and measurement tool it offers several advantages over the traditional scanning electron microscope (SEM) currently in use in research and manufacturing facilities across the world. First, resolution 2 to 4 times better than that from comparable SEMs is theoretically possible, due to the very high source brightness and the short wavelength of the helium ions. Ion images with unprecedented resolution have been routinely collected on a wide range of samples with sub-nanometer features. More importantly, the interaction volume of the helium ion beam in the sample is substantially different in its size and shape from that of the electron beam in an SEM. As a consequence, the signals generated, especially secondary electrons, reveal more surface details. Imaging by the HeIM can further benefit from the superb depth of field and the fact that He ion imaging is less susceptible to sample charging. In addition, it is possible to compensate for charging by the use of an electron flood gun. Scattered He ions produced as a result of Rutherford scattering of the incident ions on the target nuclei can provide material contrast information that can be used for quantitative compositional analysis. Beyond imaging, the HeIM is a potent tool for milling and modifying surface structures at the nanometer scale, due to the relatively low mass of the helium ion, the narrow ion beam, and especially the low beam currents. It is possible to drill close to 10 nm diameter holes and mill other nanoscale structures that cannot be fabricated with any other method. It is expected that, as with the electron beam, it is feasible to expose resist and deposit various materials with He ion beam irradiation. The work is at its exploratory stage, and likely soon will yield more exciting results. This presentation will report on some of the newest research work on the NIST helium

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. Measurement of Helium-3/Helium-4 Ratios in Soil Gas at the 618-11 Burial Ground

    SciTech Connect

    Olsen, Khris B.; Dresel, P Evan; Evans, John C.

    2001-10-31

    Seventy soil gas-sampling points were installed around the perimeter of the 618-11 Burial Ground, approximately 400 feet downgradient of well 699-13-3A, and in four transects downgradient of the burial ground to a maximum distance of 3,100 feet. Soil gas samples were collected and analyzed for helium-3/helium-4 ratios from these 70 points. Helium-3/helium-4 ratios determined from the soil gas sampling points showed significant enrichments, relative to ambient air helium-3 concentrations. The highest concentrations were located along the northern perimeter of the burial ground. Helium-3/helium-4 ratios (normalized to the abundances in ambient air) ranged from 1.0 to 62 around the burial ground. The helium-3/helium-4 ratios from the 4 transect downgradient of the burial ground ranged from 0.988 to 1.68. The helium-3/helium-4 ratios from around the burial ground suggest there is a vadose zone source of tritium along the north side of the burial ground. This vadose zone source is likely the source of tritium in the groundwater. The helium-3/helium-4 ratios also suggest the groundwater plume is traveling east-northeast from the burial ground and the highest groundwater tritium value may be to the north of well 699-13-3A. Finally, there appears to be no immediately upgradient sources of tritium impacting the burial ground since all the upgradient helium-3/helium-4 ratios are approximately 1.0.

  10. 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.

  11. 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

  12. 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.

  13. Effect of dislocations on helium retention in deformed pure iron

    NASA Astrophysics Data System (ADS)

    Gong, Y. H.; Cao, X. Z.; Jin, S. X.; Lu, E. Y.; Hu, Y. C.; Zhu, T.; Kuang, P.; Xu, Q.; Wang, B. Y.

    2016-12-01

    The effects of dislocations created by deformation on helium retention in pure iron, including the helium atoms diffusion along the dislocation line and desorption from dislocation trapping sites, were investigated. The dislocation defect was introduced in specimens by cold-rolling, and then 5 keV helium ions were implanted into the deformed specimens. Slow positron beam technology and thermal desorption spectroscopy were used to investigate the evolution of dislocation defects and the desorption behavior of helium atoms under influence of dislocation. The behaviors of S-E, W-E and S-W plots indicate clearly that lots of helium atoms remain in the deformed specimen and helium atoms combining with dislocation change the distribution of electron density. The helium desorption plot indicates that dislocation accelerates helium desorption at 293 K-600 K and facilitates helium dissociation from HenVm (n/m = 1.8) cluster.

  14. Knowledge based and interactive control for the Superfluid Helium On-orbit Transfer Project

    NASA Technical Reports Server (NTRS)

    Castellano, Timothy P.; Raymond, Eric A.; Shapiro, Jeff C.; Robinson, Frank A.; Rosenthal, Donald A.

    1989-01-01

    NASA's Superfluid Helium On-Orbit Transfer (SHOOT) project is a Shuttle-based experiment designed to acquire data on the properties of superfluid helium in micro-gravity. Aft Flight Deck Computer Software for the SHOOT experiment is comprised of several monitoring programs which give the astronaut crew visibility into SHOOT systems and a rule based system which will provide process control, diagnosis and error recovery for a helium transfer without ground intervention. Given present Shuttle manifests, this software will become the first expert system to be used in space. The SHOOT Command and Monitoring System (CMS) software will provide a near real time highly interactive interface for the SHOOT principal investigator to control the experiment and to analyze and display its telemetry. The CMS software is targeted for all phases of the SHOOT project: hardware development, pre-flight pad servicing, in-flight operations, and post-flight data analysis.

  15. Interactions of satellite-speed helium atoms with satellite surfaces. 3: Drag coefficients from spatial and energy distributions of reflected helium atoms

    NASA Technical Reports Server (NTRS)

    Sharma, P. K.; Knuth, E. L.

    1977-01-01

    Spatial and energy distributions of helium atoms scattered from an anodized 1235-0 aluminum surface as well as the tangential and normal momentum accommodation coefficients calculated from these distributions are reported. A procedure for calculating drag coefficients from measured values of spatial and energy distributions is given. The drag coefficient calculated for a 6061 T-6 aluminum sphere is included.

  16. AAV-Mediated Transduction and Targeting of Retinal Bipolar Cells with Improved mGluR6 Promoters in Rodents and Primates

    PubMed Central

    Lu, Q; Ganjawala, TH; Ivanova, E; Cheng, JG; Troilo, D; Pan, Z-H

    2016-01-01

    Adeno-associated virus (AAV) vectors have been a powerful gene delivery vehicle to the retina for basic research and gene therapy. For many of these applications, achieving cell-type specific targeting and high transduction efficiency is desired. Recently, there has been increasing interest in AAV-mediated gene targeting to specific retinal bipolar cell types. A 200-bp enhancer in combination with a basal SV40 promoter has been commonly used to target transgenes into ON-type bipolar cells. In the current study, we searched for additional cis-regulatory elements in the mGluR6 gene for improving AAV-mediated transduction efficiency into retinal bipolar cells. Our results showed that the combination of the endogenous mGluR6 promoter with additional enhancers in the introns of the mGluR6 gene markedly enhanced AAV transduction efficiency as well as made the targeting more selective for rod bipolar cells in mice. Furthermore, the AAV vectors with the improved promoter could target to ON bipolar cells with robust transduction efficiency in the para-fovea and the far peripheral retina of marmoset monkeys. The improved mGluR6 promoter constructs could provide a valuable tool for genetic manipulation in rod bipolar cells in mice and facilitate clinical applications for ON bipolar cell-based gene therapies. PMID:27115727

  17. AAV-mediated transduction and targeting of retinal bipolar cells with improved mGluR6 promoters in rodents and primates.

    PubMed

    Lu, Q; Ganjawala, T H; Ivanova, E; Cheng, J G; Troilo, D; Pan, Z-H

    2016-08-01

    Adeno-associated virus (AAV) vectors have been a powerful gene delivery vehicle to the retina for basic research and gene therapy. For many of these applications, achieving cell type-specific targeting and high transduction efficiency is desired. Recently, there has been increasing interest in AAV-mediated gene targeting to specific retinal bipolar cell types. A 200-bp enhancer in combination with a basal SV40 promoter has been commonly used to target transgenes into ON-type bipolar cells. In the current study, we searched for additional cis-regulatory elements in the mGluR6 gene for improving AAV-mediated transduction efficiency into retinal bipolar cells. Our results showed that the combination of the endogenous mGluR6 promoter with additional enhancers in the introns of the mGluR6 gene markedly enhanced AAV transduction efficiency as well as made the targeting more selective for rod bipolar cells in mice. Furthermore, the AAV vectors with the improved promoter could target to ON bipolar cells with robust transduction efficiency in the parafovea and the far peripheral retina of marmoset monkeys. The improved mGluR6 promoter constructs could provide a valuable tool for genetic manipulation in rod bipolar cells in mice and facilitate clinical applications for ON bipolar cell-based gene therapies.

  18. 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.

  19. 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.

  20. 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 Central

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

    2016-01-01

    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. PMID:26865405

  1. 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.

  2. Hydrodynamic simulations of the core helium flash

    NASA Astrophysics Data System (ADS)

    Mocák, Miroslav; Müller, Ewald; Weiss, Achim; Kifonidis, Konstantinos

    2008-10-01

    We desribe and discuss hydrodynamic simulations of the core helium flash using an initial model of a 1.25 M⊙ star with a metallicity of 0.02 near at its peak. Past research concerned with the dynamics of the core helium flash is inconclusive. Its results range from a confirmation of the standard picture, where the star remains in hydrostatic equilibrium during the flash (Deupree 1996), to a disruption or a significant mass loss of the star (Edwards 1969; Cole & Deupree 1980). However, the most recent multidimensional hydrodynamic study (Dearborn et al. 2006) suggests a quiescent behavior of the core helium flash and seems to rule out an explosive scenario. Here we present partial results of a new comprehensive study of the core helium flash, which seem to confirm this qualitative behavior and give a better insight into operation of the convection zone powered by helium burning during the flash. The hydrodynamic evolution is followed on a computational grid in spherical coordinates using our new version of the multi-dimensional hydrodynamic code HERAKLES, which is based on a direct Eulerian implementation of the piecewise parabolic method.

  3. 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.

  4. 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).

  5. Neutron-scattering investigation of the excitation spectrum of liquid helium

    SciTech Connect

    Kalinin, I. V. Lauter, H.; Puchkov, A. V.

    2007-07-15

    The results of the investigation of the temperature evolution of the scattering law S(Q, {omega}) of superfluid helium measured in the wave-vector range 0.3 < Q < 0.8 A{sup -1} and helium temperatures from 1.0 to 2.2 K are reported. The investigations have been performed on the high-flux reactor at the Institut Laue-Langevin (France) with the IN6 neutron inelastic-scattering spectrometer. The deviation of the experimental scattering law of liquid helium from the damping harmonic oscillator model, which was previously observed independently in the experiments with the IN6 spectrometer and with the DIN-2PI spectrometer (at the IBR-2 reactor, Dubna, Russia) and were more recently called extrapeak, has been corroborated. The temperature dependence of the extrapeak parameters has been determined. This dependence makes it possible to propose hypotheses on the nature of the extrapeak.

  6. Performance of all-metal demountable cryogenic seals at superfluid helium temperatures

    NASA Technical Reports Server (NTRS)

    Salerno, L. J.; Kittel, P. L.; Spivak, A. L.

    1991-01-01

    Two all-metal demountable cryogenic seals with an outside diameter of 36.6 mm, inside diameter of 27.2 mm and thickness of 0.51 mm were leak-tested at room temperature (300 K), liquid nitrogen temperature (21 cycles at 77 K), liquid helium temperature (nine cycles at 4.2K) and superfluid helium temperature (four cycles at 1.6 K). Each seal was mounted and demounted for 13 cycles. Thickness measurements at 90 deg intervals along the circumference showed a maximum seal compression of 0.038 mm. Leak rate measurements at all temperatures showed no detectable leak above the helium background level, typically 0.1 x 10 exp -9 std cu cm/s, during testing.

  7. Performance of all-metal demountable cryogenic seals at superfluid helium temperatures

    NASA Technical Reports Server (NTRS)

    Salerno, Louis J.; Kittel, Peter; Spivak, Alan L.

    1989-01-01

    Two all-metal demountable cryogenic seals with an outside diameter of 36.6 mm, inside diameter of 27.2 mm, and thickness of 0.51 mm were leak-tested at room temperature (300 K), liquid nitrogen temperature (21 cycles at 77 K), liquid helium temperature (9 cycles at 4.2 K), and superfluid helium temperature (4 cycles at 1.6 K). Each seal was mounted and demounted for 13 cycles. Thickness measurements at 90 deg intervals along the circumference showed a maximum seal compression of 0.038 mm. Leak-rate measurements at all temperatures showed no detectable leak above the helium background level, typically 0.1 x 10(-9) std-cc/sec, during testing.

  8. Performance of all-metal demountable cryogenic seals at superfluid helium temperatures

    NASA Technical Reports Server (NTRS)

    Salerno, Louis J.; Spivak, Alan L.; Kittel, Peter

    1989-01-01

    Two all-metal demountable cryogenic seals with an outside diameter of 36.6 mm, inside diameter of 27.2 mm, and thickness of 0.51 mm were leak-tested at room temperature (300 K), liquid nitrogen temperature (21 cycles at 77 K), liquid helium temperature (9 cycles at 4.2 K), and susperfluid helium temperature (4 cycles at 1.6 K). Each seal was mounted and demounted for 13 cycles. Thickness measurements at 90 deg intervals along the circumference showed a maximum seal compression of 0.038 mm. Leak-rate measurements at all temperatures showed no detectable leak above the helium background level, typically 0.1 x 10(-9) std-cc/sec, during testing.

  9. Moments of dipole oscillator-strength distribution for the helium sequence

    NASA Technical Reports Server (NTRS)

    Khan, F.; Khandelwal, G. S.; Wilson, J. W.

    1990-01-01

    The moments S(mu) for mu at least -6 but no more than 2 and L(mu) for mu = 0, 1, and 2 are calculated for the helium sequence for atomic numbers (Z) up to 30 under a screened hydrogenic model. The model describes the atom by single-particle hydrogenic wave functions and treats the initial and the final state as characterized by two different effective charge parameters Zi and Zf, respectively. The differential oscillator strength of the screened hydrogenic model is asymptotically expanded. Assuming the value of 287.6 for the coefficient of the term epsilon to the -7/2 for helium atoms, the parameter Zf is determined for the helium sequence.

  10. Moments of dipole oscillator-strength distribution for the helium sequence.

    PubMed

    Khan, F; Khandelwal, G S; Wilson, J W

    1990-08-28

    The moments S(mu) for -6 < or = mu < or = 2 and L(mu) for mu = 0, 1 and 2 are calculated for the helium sequence for atomic numbers Z up to 30 under a screened hydrogenic model. In this model, one describes the atom by single-particle hydrogenic wavefunctions and treats the initial and the final state as characterised by two different effective charge parameters Zi and Zf, respectively. An asymptotic expansion is made of the differential oscillator strength of the screened hydrogenic model. Assuming the value 287.6 for the coefficient of the term epsilon -7/2 for helium atom as given by Salpeter and Zaidi, the parameter Zf is determined for the helium sequence. This approach has resulted in values which are in reasonable agreement with the various moment values of other authors.

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

    PubMed

    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.

  12. High resolution helium ion scanning microscopy of the rat kidney.

    PubMed

    Rice, William L; Van Hoek, Alfred N; Păunescu, Teodor G; Huynh, Chuong; Goetze, Bernhard; Singh, Bipin; Scipioni, Larry; Stern, Lewis A; Brown, Dennis

    2013-01-01

    Helium ion scanning microscopy is a novel imaging technology with the potential to provide sub-nanometer resolution images of uncoated biological tissues. So far, however, it has been used mainly in materials science applications. Here, we took advantage of helium ion microscopy to explore the epithelium of the rat kidney with unsurpassed image quality and detail. In addition, we evaluated different tissue preparation methods for their ability to preserve tissue architecture. We found that high contrast, high resolution imaging of the renal tubule surface is possible with a relatively simple processing procedure that consists of transcardial perfusion with aldehyde fixatives, vibratome tissue sectioning, tissue dehydration with graded methanol solutions and careful critical point drying. Coupled with the helium ion system, fine details such as membrane texture and membranous nanoprojections on the glomerular podocytes were visualized, and pores within the filtration slit diaphragm could be seen in much greater detail than in previous scanning EM studies. In the collecting duct, the extensive and striking apical microplicae of the intercalated cells were imaged without the shrunken or distorted appearance that is typical with conventional sample processing and scanning electron microscopy. Membrane depressions visible on principal cells suggest possible endo- or exocytotic events, and central cilia on these cells were imaged with remarkable preservation and clarity. We also demonstrate the use of colloidal gold probes for highlighting specific cell-surface proteins and find that 15 nm gold labels are practical and easily distinguishable, indicating that external labels of various sizes can be used to detect multiple targets in the same tissue. We conclude that this technology represents a technical breakthrough in imaging the topographical ultrastructure of animal tissues. Its use in future studies should allow the study of fine cellular details and provide

  13. 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

  14. Targeting the IL-6 pathway in multiple myeloma and its implications in cancer-associated gene hypermethylation.

    PubMed

    Ingersoll, Susan Blaydes; Ahmad, Sarfraz; Thoni, Natalie D; Ahmed, Farhana H; Monahan, Kimberly A; Edwards, John R

    2011-09-01

    Aberrant methylation of tumor suppressor genes (TSG) is an important epigenetic event in cancer, including multiple myeloma (MM). Interleukin-6 (IL-6), which plays a significant role in the pathogenesis of MM, also regulates DNA methylation. However, attempts to bring IL-6 blockade to the clinic have had limited success. We hypothesize that IL-6 regulation of hypermethylation may be an important pathway leading to rational chemotherapeutic/anti-IL-6 combinations. We first studied the correlation of IL-6 expression and dependence in MM cell lines: U266B1, RPMI8226, and KAS6/1. We confirmed that KAS6/1 is IL-6-dependent whereas U266B1 and RPMI8226 cells are IL-6-independent and that blocking IL-6 inhibited the growth of U266B1 (36% inhibition; p<0.05) and KAS6/1 (68% inhibition; p<0.01), but not the RPMI8226 cells. Using RT-PCR, we showed that U266B1 cells express IL-6, but RPMI8226 and KAS6/1 cells do not. This IL-6 expression pattern correlates with the anti-IL-6 inhibition findings. To correlate IL-6 sensitivity with hypermethylation of TSG, we investigated promoter methylation of CDH1 and DcR1. We found that the promoter of DcR1 and CDH1 is methylated in U266B1 cells and un-methylated in RPMI8226 cells. Furthermore, the DcR1 promoter was un-methylated in KAS6/1 cells. These data support our hypothesis that an IL-6-dependent pathway may regulate hypermethylation of TSG in MM. Newer chemotherapeutic agents that affect methylation are being studied in combination with IL-6 blockade.

  15. Soft or hard ionization of molecules in helium nanodroplets? An electron impact investigation of alcohols and ethers.

    PubMed

    Yang, Shengfu; Brereton, Scott M; Wheeler, Martyn D; Ellis, Andrew M

    2005-12-21

    Electron impact (70 eV) mass spectra of a series of C1-C6 alcohols encased in large superfluid liquid helium nanodroplets (approximately 60,000 helium atoms) have been recorded. 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, most notably cleavage of the C(alpha)-H bond in the parent ion to form the corresponding oxonium ion. Parent ion intensities are also enhanced by the helium, 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. To demonstrate that these findings are not unique to alcohols, we have also investigated several ethers. The results obtained for both alcohols and ethers 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. The set of molecules explored in this work suggest that electron impact ionization of doped helium nanodroplets does not provide a sufficiently large softening effect to be useful in analytical mass spectrometry.

  16. Transcriptome-wide identification of NMD-targeted human mRNAs reveals extensive redundancy between SMG6- and SMG7-mediated degradation pathways

    PubMed Central

    Colombo, Martino; Karousis, Evangelos D.; Bourquin, Joël; Bruggmann, Rémy; Mühlemann, Oliver

    2017-01-01

    Besides degrading aberrant mRNAs that harbor a premature translation termination codon (PTC), nonsense-mediated mRNA decay (NMD) also targets many seemingly “normal” mRNAs that encode for full-length proteins. To identify a bona fide set of such endogenous NMD targets in human cells, we applied a meta-analysis approach in which we combined transcriptome profiling of knockdowns and rescues of the three NMD factors UPF1, SMG6, and SMG7. We provide evidence that this combinatorial approach identifies NMD-targeted transcripts more reliably than previous attempts that focused on inactivation of single NMD factors. Our data revealed that SMG6 and SMG7 act on essentially the same transcripts, indicating extensive redundancy between the endo- and exonucleolytic decay routes. Besides mRNAs, we also identified as NMD targets many long noncoding RNAs as well as miRNA and snoRNA host genes. The NMD target feature with the most predictive value is an intron in the 3′ UTR, followed by the presence of upstream open reading frames (uORFs) and long 3′ UTRs. Furthermore, the 3′ UTRs of NMD-targeted transcripts tend to have an increased GC content and to be phylogenetically less conserved when compared to 3′ UTRs of NMD insensitive transcripts. PMID:27864472

  17. 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.

  18. Quantum Halo States in Helium Tetramers.

    PubMed

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

    2017-01-12

    The universality of quantum halo states enables a comparison of systems from different fields of physics, as demonstrated in two- and three-body clusters. In the present work, we studied weakly bound helium tetramers in order to test whether some of these four-body realistic systems qualify as halos. Their ground-state binding energies and structural properties were thoroughly estimated using the diffusion Monte Carlo method with pure estimators. Helium tetramer properties proved to be less sensitive on the potential model than previously evaluated trimer properties. We predict the existence of realistic four-body halo (4)He2(3)He2, whereas (4)He4 and (4)He3(3)He are close to the border and thus can be used as prototypes of quasi-halo systems. Our results could be tested by the experimental determination of the tetramers' structural properties using a setup similar to the one developed for the study of helium trimers.

  19. 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.

  20. 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.

  1. 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.

  2. Helium irradiation effects in single crystals of MgAl 2O 4

    NASA Astrophysics Data System (ADS)

    Neeft, E. A. C.; Schram, R. P. C.; van Veen, A.; Labohm, F.; Fedorov, A. V.

    2000-05-01

    Magnesium aluminate spinel, (MgAl2O4), is a promising material as a uranium free matrix for the transmutation of americium. Fission products and α-particles are produced during the transmutation. The impact of α-particles is simulated by 30 keV 3He ion implantations at room temperature (RT) with the doses 6.2, 16, 20 and 53×1015 cm-2. In another set of experiments a single crystal MgAl2O4 (1 0 0) sample is irradiated with α-particles (4.5 MeV) from a 241Am source at RT to a dose of 1.3×1012 cm-2. Helium release from the implanted samples was studied by thermal desorption spectrometry (TDS). The numerical analysis of the experimental thermal desorption results of α-implanted samples to a very low helium concentration (0.0288 appm in the irradiation zone of 12.4 μm) show that helium release is dominated by helium interstitial diffusion with an activation energy of 1.8 eV. In the case of high dose implantation to 1.74 at.% in the implantation zone approximately of 100 nm, helium is released from He-vacancy clusters with the activation energy of 2.35 eV. The evolution of the helium concentration profile in the temperature range from RT to 1483 K is monitored by neutron depth profiling (NDP). It confirms that the release of helium is governed by dissociation from vacancy clusters.

  3. Component separation of oceanic helium

    NASA Astrophysics Data System (ADS)

    Roether, Wolfgang; Well, Roland; Putzka, Alfred; Rüth, Christine

    1998-11-01

    A new procedure to quantify the components of oceanic helium ("terrigenic" 3He and 4He released from the ocean floor and "tritiugenic" 3He from tritium decay) is described. Terrigenic He and nonatmospheric 3He (i.e., terrigenic and tritiugenic combined) are obtained in terms of measured concentrations of the He isotopes and also of neon (Ne) (which improves the separation considerably), assuming terrigenic He to vanish in the mixed layer. For the subsequent separation of terrigenic and tritiugenic 3He, additional information is required and 3He due to natural tritium represents a complication. The procedure is applied to data from a hydrographic section in the South Atlantic (19°S, 1991) and one in the Eastern Mediterranean (1987). The 1σ data precisions and a systematic error accounting for uncertainties in mixed-layer He are approximately 0.3%. Sections of the new representations of oceanic He and 3He and comparisons to the nearest classical quantities (i.e., 3He, He) are presented. In the South Atlantic the 3He distribution reflects the hydrographic structure. East of 20°W the average 3He/4He ratio of terrigenic He below 800 m is 4.5±0.8 times the atmospheric ratio, which implies a substantial contribution of crustal He. In the upper waters, tritiugenic 3He (0.5 tritium units, ±20%) is separated from terrigenic 3He. In the Eastern Mediterranean, tritiugenic 3He is quantified throughout the water column in the presence of substantial levels of terrigenic He; the release rate of terrigenic He from the sea floor is found to be 3.1±1.2 1010 atoms m-2 s-1, similar to the rate for continental crust, with a mantle He contribution of 5±1.2% only. Recommendations for future work are to reduce the mentioned systematic error and the uncertainty margins of the He and Ne solubilities and of 3He due to natural tritium.

  4. Targeting of heme oxygenase-1 attenuates the negative impact of Ikaros isoform 6 in adult BCR-ABL1-positive B-ALL.

    PubMed

    Lin, Xiaojing; Zou, Xingli; Wang, Ziming; Fang, Qin; Chen, Shuya; Huang, Jun; Zhe, Nana; Yu, Meisheng; Zhang, Yaming; Wang, Jishi

    2016-08-16

    The correlation between Heme oxygenase-1 (HO-1) and dominant-negative Ikaros isoform 6 (IK6) is unclear. Firstly, we detected that IK6 existed in 20 of 42 (47.6%) adult BCR-ABL1-positive B-lineage acute lymphoblastic leukemia (BCR-ABL1-positive B-ALL) by using reverse transcribed polymerase chain reaction (PCR) and nucleotide sequencing. IK6-positive patients had an unfavorable outcome compared with IK6-negative ones. Further study showed that the level of HO-1 expression was higher in IK6-positive patients' samples than that in IK6-negative ones. And there was a strong correlation between the expression of IK6 and HO-1. The growth of primary CD34+ leukemic cells derived from our IK6-positive patients' pool was prohibited by silencing HO-1, further promoting their apoptosis. Furthermore, primary CD34+ leukemic cells derived from IK6-positive patients shown poor responses to imatinib in comparison with wild-type (IK1) patients, suggesting that the expression of IK6 resisted to imatinib in adult BCR-ABL1-positive B-ALL. Importantly, inhibition of HO-1 also increased their sensitivity to tyrosine kinase inhibitors (TKIs). Finally, we found that IK6 activated downstream STAT5, and HO-1 was one of the downstream target genes of STAT5. In conclusion, HO-1 is an essential survival factor in BCR-ABL1-positive B-ALL with IK6, and targeting HO-1 can attenuate the negative impact of IK6.

  5. Pump performance requirement for the liquid helium orbital resupply tanker

    NASA Technical Reports Server (NTRS)

    Lee, J. H.; Ng, Y. S.

    1988-01-01

    The Liquid Helium Orbital Resupply Tanker (currently renamed to Superfluid Helium Tanker) will greatly enhance the lifetime of the space missions which require superfluid helium. The Superfluid Helium Tanker pump performance requirement is driven by the superfluid helium replenishment needs of the Space Infrared Telescope Facility (SIRTF). SIRTF is one of the space missions which will require on-orbit superfluid helium resupply in the 1990s. The Superfluid Helium Tanker will carry at least 10,000 L of superfluid helium and provide a minimum pump head of 170 torr (0 to 200 L/h) to cool SIRTF from 150 to 2 K. When the SIRTF tank starts to collect liquid, a minimum flow rate of 300 L/h with a pump head of 60 torr is required to fill the 4000-liter tank.

  6. 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

  7. 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

  8. 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

  9. 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

  10. 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

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

    NASA Astrophysics Data System (ADS)

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

    2012-08-01

    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/cm3) and stainless steel foil-lined cavity targets (steel thickness 1-5 μm). 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 Te=2 to 3 keV, ne=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 Te˜ 2 keV, ne˜ 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.

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

    SciTech Connect

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

    2012-08-01

    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/cm36-16 mg/cm3) and stainless steel foil-lined cavity targets (steel thickness 1-5 μm1-5 μm). 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%<5% of the incident laser light backscattered by the resulting plasma in all cases (typically <2.5%<2.5%). The aerogel targets produced Te=2Te=2 to 3 keV, ne=0.12-0.2ne=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 Te~2 keV, Te~2 keV, ne~0.15ne~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.

  13. 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.

  14. 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.

  15. 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.

  16. Pharmaceutical container/closure integrity. III: Validation of the helium leak rate method for rigid pharmaceutical containers.

    PubMed

    Kirsch, L E; Nguyen, L; Gerth, R

    1997-01-01

    Validation of a helium leak rate method for pharmaceutical container/closure integrity quality assurance required the demonstration that this physical testing method was as good or better than microbial immersion challenge testing in detecting potential integrity failures. One lot of rubber-stoppered, broth-filled glass vials also containing defective vials with known leaks were subjected to both helium leak rate and microbial challenge testing. The defective vials were prepared by affixing glass micropipettes (0.1 to 10 microns) into the vial side walls. The validation lot included a 10% seeded defect rate of which about 50% contained leaks with a predicted probability of failing a microbial challenge (> 10%). Helium tracer was placed in the test units by charging them for 4 hours under a 40 psi helium pressure. The critical leak rate after charging was determined to be 10(-7) standard cc/second, and test units with measured leak rates greater than this value were considered helium leak rate failures. Microbial immersion challenge was conducted by exposing the test units in a bath inoculated with 10(9-10) viable E. coli and B. diminuta organisms for 24 hours followed by a 13 day (35 degrees C) incubation. Microbial failures were determined visually. The helium and microbial leak test methods were compared statistically using mean failure rates. The mean helium failure rate was 6.9%, whereas the mean microbial failure rate was 2.8%. The difference between helium and microbial failure rates was significantly greater than zero. Thus, helium leak rate testing was demonstrated to be a suitable pharmaceutical container/closure integrity method for microbial quality assurance of rigid containers.

  17. 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.

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

    SciTech Connect

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

    2016-02-15

    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{sup +} ions leads to more uniform energy deposition of the target material than Li{sup +} ions. Experiments show that a higher current density of helium ions can be delivered from a plasma source compared to Li{sup +} ions from a hot plate type ion source. He{sup +} 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.

  19. 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.

  20. Effect of helium on structure and compression behavior of SiO2 glass

    PubMed Central

    Shen, Guoyin; Mei, Qiang; Prakapenka, Vitali B.; Lazor, Peter; Sinogeikin, Stanislav; Meng, Yue; Park, Changyong

    2011-01-01

    The behavior of volatiles is crucial for understanding the evolution of the Earth’s interior, hydrosphere, and atmosphere. Noble gases as neutral species can serve as probes and be used for examining gas solubility in silicate melts and structural responses to any gas inclusion. Here, we report experimental results that reveal a strong effect of helium on the intermediate range structural order of SiO2 glass and an unusually rigid behavior of the glass. The structure factor data show that the first sharp diffraction peak position of SiO2 glass in helium medium remains essentially the same under pressures up to 18.6 GPa, suggesting that helium may have entered in the voids in SiO2 glass under pressure. The dissolved helium makes the SiO2 glass much less compressible at high pressures. GeO2 glass and SiO2 glass with H2 as pressure medium do not display this effect. These observations suggest that the effect of helium on the structure and compression of SiO2 glass is unique. PMID:21444785

  1. 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.

  2. Predicted vacancy cluster structures in MgO and their interaction with helium

    NASA Astrophysics Data System (ADS)

    Busker, G.; van Huis, M. A.; Grimes, R. W.; van Veen, A.

    2000-12-01

    Atomistic simulation calculations were performed to predict defect energies of vacancy clusters and dissociation energies of clusters with helium. The computation technique was based on pair potentials and the Mott-Littleton methodology was used as implemented in the CASCADE code. Both the full charge and the partial charge model were employed. The partial charge model shows better agreement with experimental data reported in the literature. The energetically most favourable spatial configurations for clusters composed of up to eight vacancies were determined and the associated formation energies calculated. The results indicate that the three-dimensional growth of vacancy clusters in MgO is energetically favourable. Next, the activation energies for dissociation of helium atoms from these vacancy clusters were calculated. The activation energy for dissociation of a helium atom from vacancy clusters larger than a monovacancy is approximately 3.6 eV for the partial charge model. Remarkably, the activation energy for dissociation of a helium atom from a monovacancy was found to be higher, 3.9 eV for the partial charge model. This last energy is enhanced by lattice relaxation around the monovacancy. The dissociation energies from large vacancy clusters is in good agreement with the permeation energy of 3.3 ± 0.3 eV obtained experimentally with a permeation experiment in which helium release was monitored with neutron depth profiling (NDP).

  3. Mantle-derived helium in foreland basins in Xinjiang, Northwest China

    NASA Astrophysics Data System (ADS)

    Xu, Sheng; Zheng, Guodong; Zheng, Jianjing; Zhou, Shixin; Shi, Pilong

    2017-01-01

    Hydrocarbon-rich natural gases from the Tarim, Junggar, Turpan-Hami and Santanghu basins in Xinjiang, Northwest China have measured 3He/4He ratios from 0.01 to 0.6 times higher than the atmospheric value, indicating 0-7% helium derived from the mantle. The mantle-derived helium is high in foreland basins associated with the Tianshan, Kunlun and Zhayier-Halalate orogenic mountains, but low towards the center of basins. This spatial distribution suggests that the mantle-derived helium originates either from fluids or small scale melts in the upper asthenospheric or lithospheric mantle which have found pathways into the root zones of the major faults defining these mountains, but do not significantly move into the basins themselves. During upward transport to near the surface, the mantle-derived helium is significantly diluted by radiogenic helium produced in the crust. Despite the lack of recent magmatic activity or extensional tectonics within the basins, this pattern shows strong evidence that the major faults play an important role in mantle-derived components degassing from the mantle to the surface.

  4. 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

  5. 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.

  6. Thermodynamics of dense molecular hydrogen-helium mixtures at high pressure

    NASA Technical Reports Server (NTRS)

    Marley, Mark S.; Hubbard, William B.

    1988-01-01

    Effective intermolecular pair potentials derived from liquid hydrogen and helium shock wave experiments are presently used in Monte Carlo simulations of mixtures of hydrogen and helium, at densities of up to 1.2 g/cu cm. The model interaction Helmholtz free energy derived accurately reproduces both the Monte Carlo calculation results and the experimental data obtained for densities of up to about 0.6 g/cu cm. An equation of state is derived from the free energy expression that could be useful in interior models of such Jovian planets as Saturn.

  7. 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.

  8. Cross-talk between sirtuin and mammalian target of rapamycin complex 1 (mTORC1) signaling in the regulation of S6 kinase 1 (S6K1) phosphorylation.

    PubMed

    Hong, Sungki; Zhao, Bin; Lombard, David B; Fingar, Diane C; Inoki, Ken

    2014-05-09

    p70 ribosomal S6 kinase (S6K1), a major substrate of the mammalian target of rapamycin (mTOR) kinase, regulates diverse cellular processes including protein synthesis, cell growth, and survival. Although it is well known that the activity of S6K1 is tightly coupled to its phosphorylation status, the regulation of S6K1 activity by other post-translational modifications such as acetylation has not been well understood. Here we show that the acetylation of the C-terminal region (CTR) of S6K1 blocks mTORC1-dependent Thr-389 phosphorylation, an essential phosphorylation site for S6K1 activity. The acetylation of the CTR of S6K1 is inhibited by the class III histone deacetylases, SIRT1 and SIRT2. An S6K1 mutant lacking acetylation sites in its CTR shows enhanced Thr-389 phosphorylation and kinase activity, whereas the acetylation-mimetic S6K1 mutant exhibits decreased Thr-389 phosphorylation and kinase activity. Interestingly, relative to the acetylation-mimetic S6K1 mutant, the acetylation-defective mutant displays higher affinity toward Raptor, an essential scaffolding component of mTORC1 that recruits mTORC1 substrates. These observations indicate that sirtuin-mediated regulation of S6K1 acetylation is an additional important regulatory modification that impinges on the mechanisms underlying mTORC1-dependent S6K1 activation.

  9. 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.

  10. 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

  11. Clinical potential of novel therapeutic targets in breast cancer: CDK4/6, Src, JAK/STAT, PARP, HDAC, and PI3K/AKT/mTOR pathways

    PubMed Central

    Hosford, Sarah R; Miller, Todd W

    2014-01-01

    Breast cancers expressing estrogen receptor α, progesterone receptor, or the human epidermal growth factor receptor 2 (HER2) proto-oncogene account for approximately 90% of cases, and treatment with antiestrogens and HER2-targeted agents has resulted in drastically improved survival in many of these patients. However, de novo or acquired resistance to antiestrogen and HER2-targeted therapies is common, and many tumors will recur or progress despite these treatments. Additionally, the remaining 10% of breast tumors are negative for estrogen receptor α, progesterone receptor, and HER2 (“triple-negative”), and a clinically proven tumor-specific drug target for this group has not yet been identified. Therefore, the identification of new therapeutic targets in breast cancer is of vital clinical importance. Preclinical studies elucidating the mechanisms driving resistance to standard therapies have identified promising targets including cyclin-dependent kinase 4/6, phosphoinositide 3-kinase, poly adenosine diphosphate–ribose polymerase, Src, and histone deacetylase. Herein, we discuss the clinical potential and status of new therapeutic targets in breast cancer. PMID:25206307

  12. Electrons on helium — The ``polaron'' transition

    NASA Astrophysics Data System (ADS)

    Andrei, E. Y.; Grimes, C. C.; Adams, G.

    1984-07-01

    We describe the observation of the polaronic transition of a system of electrons supported above a helium film. The electron mobility drops sharply by more than four orders of magnitude as the film thickness is reduced below ≈ 1000 Å. The transition was observed in the temperature range 0.4 ⩽ T ⩽ 1 K.

  13. 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.

  14. 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.

  15. 30 CFR 256.11 - Helium.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 30 Mineral Resources 2 2011-07-01 2011-07-01 false Helium. 256.11 Section 256.11 Mineral Resources BUREAU OF OCEAN ENERGY MANAGEMENT, REGULATION, AND ENFORCEMENT, DEPARTMENT OF THE INTERIOR OFFSHORE LEASING OF SULPHUR OR OIL AND GAS IN THE OUTER CONTINENTAL SHELF Outer Continental Shelf Oil, Gas,...

  16. Thermal flickers: A semianalytical approach. [helium stars

    NASA Technical Reports Server (NTRS)

    Perdang, J.; Buchler, J. R.

    1980-01-01

    In order to enhance physical insight into the nature of thermal oscillations arising from a thin helium burning shell, the behavior in its phase plane of a simple two zone model which, however, contains all the relevant physics is analyzed. This simple model very naturally reproduces thermal flickers and is relatively insensitive to all but two parameters.

  17. Atmospheric helium and geomagnetic field reversals.

    NASA Technical Reports Server (NTRS)

    Sheldon, W. R.; Kern, J. W.

    1972-01-01

    The problem of the earth's helium budget is examined in the light of recent work on the interaction of the solar wind with nonmagnetic planets. It is proposed that the dominant mode of helium (He4) loss is ion pumping by the solar wind during geomagnetic field reversals, when the earth's magnetic field is very small. The interaction of the solar wind with the earth's upper atmosphere during such a period is found to involve the formation of a bow shock. The penetration altitude of the shock-heated solar plasma is calculated to be about 700 km, and ionization rates above this level are estimated for a cascade ionization (electron avalanche) process to average 10 to the 9th power ions/sq cm/sec. The calculated ionization rates and the capacity of the solar wind to remove ionized helium (He4) from the upper atmosphere during geomagnetic dipole reversals are sufficient to yield a secular equilibrium over geologic time scales. The upward transport of helium from the lower atmosphere under these conditions is found to be adequate to sustain the proposed loss rate.

  18. 30 CFR 556.11 - Helium.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... BUREAU OF OCEAN ENERGY MANAGEMENT, DEPARTMENT OF THE INTERIOR OFFSHORE LEASING OF SULPHUR OR OIL AND GAS IN THE OUTER CONTINENTAL SHELF Outer Continental Shelf Oil, Gas, and Sulphur Management, General... helium from all gas produced from the leased area. (b) In case the United States elects to take...

  19. 30 CFR 556.11 - Helium.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... BUREAU OF OCEAN ENERGY MANAGEMENT, DEPARTMENT OF THE INTERIOR OFFSHORE LEASING OF SULPHUR OR OIL AND GAS IN THE OUTER CONTINENTAL SHELF Outer Continental Shelf Oil, Gas, and Sulphur Management, General... 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

    ... BUREAU OF OCEAN ENERGY MANAGEMENT, DEPARTMENT OF THE INTERIOR OFFSHORE LEASING OF SULPHUR OR OIL AND GAS IN THE OUTER CONTINENTAL SHELF Outer Continental Shelf Oil, Gas, and Sulphur Management, General... helium from all gas produced from the leased area. (b) In case the United States elects to take...

  1. Helium and Sulfur Hexafluoride in Musical Instruments

    ERIC Educational Resources Information Center

    Forinash, Kyle; Dixon, Cory L.

    2014-01-01

    The effects of inhaled helium on the human voice were investigated in a recent article in "The Physics Teacher." As mentioned in that article, demonstrations of the effect are a popular classroom activity. If the number of YouTube videos is any indication, the effects of sulfur hexafluoride on the human voice are equally popular.…

  2. PC1/3, PC2 and PC5/6A are targeted to dense core secretory granules by a common mechanism.

    PubMed

    Dikeakos, Jimmy D; Mercure, Chantal; Lacombe, Marie-Josée; Seidah, Nabil G; Reudelhuber, Timothy L

    2007-08-01

    There are seven members of the proprotein convertase (PC) family of secreted serine proteases that cleave their substrates at basic amino acids, thereby activating a variety of hormones, growth factors, and viruses. PC1/3, PC2 and PC5/6A are the only members of the PC family that are targeted to dense core secretory granules, where they carry out the processing of proteins that are secreted from the cell in a regulated manner. Previous studies have identified alpha-helices in the C-termini of the PC1/3 and PC2 proteases that are required for this subcellular targeting. In the current study, we demonstrate that a predicted alpha-helix in the C-terminus of PC5/6A is also critical for the ability of this domain to target a heterologous protein to the regulated secretory pathway of mouse endocrine AtT-20 cells. Analysis of the subcellular distribution of fusion proteins containing the C-terminal domains of PC1/3, PC2 and PC5/6A confirmed that all three domains have the capacity to redirect a constitutively secreted protein to the granule-containing cytoplasmic extensions. Analysis of the predicted structures formed by these three granule-sorting helices shows a correlation between their granule-sorting efficiency and the clustering of hydrophobic amino acids in their granule-targeting helices.

  3. Q6, a novel hypoxia-targeted drug, regulates hypoxia-inducible factor signaling via an autophagy-dependent mechanism in hepatocellular carcinoma.

    PubMed

    Liu, Xiao-Wen; Cai, Tian-Yu; Zhu, Hong; Cao, Ji; Su, Yi; Hu, Yong-Zhou; He, Qiao-Jun; Yang, Bo

    2014-01-01

    Tumor hypoxia underlies treatment failure and yields more aggressive and metastatic cancer phenotypes. Although therapeutically targeting these hypoxic environments has been proposed for many years, to date no approaches have shown the therapeutic value to gain regulatory approval. Here, we demonstrated that a novel hypoxia-activated prodrug, Q6, exhibits potent antiproliferative efficacy under hypoxic conditions and induces caspase-dependent apoptosis in 2 hepatocellular carcinoma (HCC) cell lines, with no obvious toxicity being detected in 2 normal liver cell lines. Treatment with Q6 markedly downregulated HIF1A [hypoxia inducible factor 1, α subunit (basic helix-loop-helix transcription factor)] expression and transcription of the downstream target gene, VEGFA (vascular endothelial growth factor A). This dual hypoxia-targeted modulation mechanism leads to high potency in suppressing tumor growth and vascularization in 2 in vivo models. Intriguingly, it is the autophagy-dependent degradation pathway that plays a crucial role in Q6-induced attenuation of HIF1A expression, rather than the proteasome-dependent pathway, which is normally regarded as the predominant mechanism underlying posttranslational regulation of HIF1A. Inhibition of autophagy, either by short interfering RNA (siRNA) or by chemical inhibitors, blocked Q6-induced HIF1A degradation. Autophagic degradation of HIF1A was further confirmed by the observation that HIF1A coimmunoprecipitated with the ubiquitin-binding adaptor protein, SQSTM1, which is degraded through autophagy. Additionally, silencing of SQSTM1 inhibited Q6-induced HIF1A degradation. These findings suggest that the novel hypoxia-targeted agent, Q6, has potential clinical value in the therapy of HCC. Furthermore, the identification of autophagy as a crucial regulator of HIF1A provides new insights into hypoxia-related treatments.

  4. 43 CFR 3195.24 - What must I do before contacting a non-Federal helium supplier for my helium needs?

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ...-Federal helium supplier for my helium needs? 3195.24 Section 3195.24 Public Lands: Interior Regulations... MANAGEMENT (3000) HELIUM CONTRACTS Federal Agency Requirements § 3195.24 What must I do before contacting a non-Federal helium supplier for my helium needs? You must make an initial determination about...

  5. 43 CFR 3195.24 - What must I do before contacting a non-Federal helium supplier for my helium needs?

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ...-Federal helium supplier for my helium needs? 3195.24 Section 3195.24 Public Lands: Interior Regulations... MANAGEMENT (3000) HELIUM CONTRACTS Federal Agency Requirements § 3195.24 What must I do before contacting a non-Federal helium supplier for my helium needs? You must make an initial determination about...

  6. 43 CFR 3195.24 - What must I do before contacting a non-Federal helium supplier for my helium needs?

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ...-Federal helium supplier for my helium needs? 3195.24 Section 3195.24 Public Lands: Interior Regulations... MANAGEMENT (3000) HELIUM CONTRACTS Federal Agency Requirements § 3195.24 What must I do before contacting a non-Federal helium supplier for my helium needs? You must make an initial determination about...

  7. 43 CFR 3195.24 - What must I do before contacting a non-Federal helium supplier for my helium needs?

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ...-Federal helium supplier for my helium needs? 3195.24 Section 3195.24 Public Lands: Interior Regulations... MANAGEMENT (3000) HELIUM CONTRACTS Federal Agency Requirements § 3195.24 What must I do before contacting a non-Federal helium supplier for my helium needs? You must make an initial determination about...

  8. Prolonged helium postconditioning protocols during early reperfusion do not induce cardioprotection in the rat heart in vivo: role of inflammatory cytokines.

    PubMed

    Oei, Gezina Tanya Mei Ling; Aslami, Hamid; Kerindongo, Raphaela Priscilla; Steenstra, Renske Johanna; Beurskens, Charlotte Jacqueline Peter; Tuip-de Boer, Anita Maria; Juffermans, Nicole Petra; Hollmann, Markus Werner; Preckel, Benedikt; Weber, Nina Claudia

    2015-01-01

    Postconditioning of myocardial tissue employs short cycles of ischemia or pharmacologic agents during early reperfusion. Effects of helium postconditioning protocols on infarct size and the ischemia/reperfusion-induced immune response were investigated by measurement of protein and mRNA levels of proinflammatory cytokines. Rats were anesthetized with S-ketamine (150 mg/kg) and diazepam (1.5 mg/kg). Regional myocardial ischemia/reperfusion was induced; additional groups inhaled 15, 30, or 60 min of 70% helium during reperfusion. Fifteen minutes of helium reduced infarct size from 43% in control to 21%, whereas 30 and 60 minutes of helium inhalation led to an infarct size of 47% and 39%, respectively. Increased protein levels of cytokine-induced neutrophil chemoattractant (CINC-3) and interleukin-1 beta (IL-1β) were found after 30 or 60 min of helium inhalation, in comparison to control. 30 min of helium increased mRNA levels of CINC-3, IL-1β, interleukin 6 (IL-6), and tumor necrosis factor alpha (TNF-α) in myocardial tissue not directly subjected to ischemia/reperfusion. These results suggest that the effectiveness of the helium postconditioning protocol is very sensitive to duration of noble gas application. Additionally, helium was associated with higher levels of inflammatory cytokines; however, it is not clear whether this is causative of nature or part of an epiphenomenon.

  9. The effectiveness of an anti-human IL-6 receptor monoclonal antibody combined with chemotherapy to target colon cancer stem-like cells.

    PubMed

    Ying, Jin; Tsujii, Masahiko; Kondo, Jumpei; Hayashi, Yoshito; Kato, Motohiko; Akasaka, Tomofumi; Inoue, Takuta; Shiraishi, Eri; Inoue, Tahahiro; Hiyama, Satoshi; Tsujii, Yoshiki; Maekawa, Akira; Kawai, Shoichiro; Fujinaga, Tetsuji; Araki, Maekawa; Shinzaki, Shinichiro; Watabe, Kenji; Nishida, Tsutomu; Iijima, Hideki; Takehara, Tetsuo

    2015-04-01

    Recent studies have demonstrated that cancer stem cells (CSCs) can initiate and sustain tumor growth and exhibit resistance to clinical cytotoxic therapies. Therefore, CSCs represent the main target of anticancer therapy. Interleukin-6 (IL-6) promotes cellular proliferation and drug resistance in colorectal cancer, and its serum levels correlate with patient survival. Therefore, IL-6 and its downstream signaling molecule the signal transducer and activator of transcription-3 (STAT3) represent potential molecular targets. In the present study, we investigated the effects of IL-6 and its downstream signaling components on stem cell biology, particularly the chemoresistance of CSCs, to explore potential molecular targets for cancer therapy. The colon cancer cell line WiDr was cultured in serum-free, non-adherent, and three-dimensional spheroid-forming conditions to enrich the stem cell-like population. Spheroid-forming cells slowly proliferated and expressed high levels of Oct-4, Klf4, Bmi-1, Lgr5, IL-6, and Notch 3 compared with adherent cells. Treatment with an anti-human IL-6 receptor monoclonal antibody reduced spheroid formation, stem cell-related gene expression, and 5-fluorouracil (5-FU) resistance. In addition, IL-6 treatment enhanced the levels of p-STAT3 (Tyr705), the expression of Oct-4, Klf4, Lgr5, and Notch 3, and chemoresistance to 5-FU. siRNA targeting Notch 3 suppressed spheroid formation, Oct-4 and Lgr5 expression, and 5-FU chemoresistance, whereas STAT3 inhibition enhanced Oct-4, Klf4, Lgr5, and Notch 3 expression and 5-FU chemoresistance along with reduced spheroid growth. Taken together, these results indicate that IL-6 functions in dichotomous pathways involving Notch 3 induction and STAT3 activation. The former pathway is involved in cancer stem-like cell biology and enhanced chemoresistance, and the latter pathway leads to accelerated proliferation and reduced chemoresistance. Thus, an anti-human IL-6 receptor monoclonal antibody or Notch 3

  10. 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.

  11. Generation of a stable anti-human CD44v6 scFv and analysis of its cancer-targeting ability in vitro.

    PubMed

    Chen, Yinting; Huang, Kaihong; Li, Xuexian; Lin, Xiangan; Zhu, Zhaohua; Wu, Ying

    2010-06-01

    CD44v6 is a cancer-associated antigen that mainly expresses in a subset of adenocarcinomas. Therefore, in this study, anti-human CD44v6 single-chain variable fragment (scFv) has been selected and characterized because it is the first step of primary importance towards the construction of a novel cancer-targeted agent for cancer diagnosis and therapy. In our study, anti-human CD44v6 scFv was selected from a human phage-displayed scFv library based on its ability to bind in vitro to CD44v6 antigen. Subsequently, immunofluorescent staining and Western blot analyses were performed to measure the binding characteristics of this scFv. In addition, flow cytometric analysis was done to verify its cancer-targeting ability in vitro. And a flow cytometry-based assay was used to determine its equilibrium dissociation constant (K (D)). Finally, one functional anti-CD44v6 scFv was selected and characterized. Nucleotide sequencing verified that it was an incomplete scFv gene but had a variable heavy chain (V(H)) alone. However, anti-CD44v6 scFv demonstrated cell-binding and antigen-binding activities by immunofluorescent staining and Western blot analyses. Furthermore, flow cytometric analysis proved that this scFv specifically targeted CD44v6-expressing cancer cells other than CD44v6 non-expressing normal cells or tumor cells in vitro. The K (D) of this scFv was calculated to be 7.85 +/- 0.93 x 10(-8) M. In summary, the selected human scFv against CD44v6 has specific binding activity and favorable binding affinity despite lacking a variable light chain (V(L)). Moreover, it can effectively and specifically target CD44v6-expressing cancer cells. All these characteristics make anti-CD44v6 scFv a promising agent for cancer detection and anti-cancer therapy.

  12. Helium induced fine structure in the electronic spectra of anthracene derivatives doped into superfluid helium nanodroplets

    SciTech Connect

    Pentlehner, D.; Slenczka, A.

    2015-01-07

    Electronic spectra of organic molecules doped into superfluid helium nanodroplets show characteristic features induced by the helium environment. Besides a solvent induced shift of the electronic transition frequency, in many cases, a spectral fine structure can be resolved for electronic and vibronic transitions which goes beyond the expected feature of a zero phonon line accompanied by a phonon wing as known from matrix isolation spectroscopy. The spectral shape of the zero phonon line and the helium induced phonon wing depends strongly on the dopant species. Phonon wings, for example, are reported ranging from single or multiple sharp transitions to broad (Δν > 100 cm{sup −1}) diffuse signals. Despite the large number of example spectra in the literature, a quantitative understanding of the helium induced fine structure of the zero phonon line and the phonon wing is missing. Our approach is a systematic investigation of related molecular compounds, which may help to shed light on this key feature of microsolvation in superfluid helium droplets. This paper is part of a comparative study of the helium induced fine structure observed in electronic spectra of anthracene derivatives with particular emphasis on a spectrally sharp multiplet splitting at the electronic origin. In addition to previously discussed species, 9-cyanoanthracene and 9-chloroanthracene will be presented in this study for the first time.

  13. Developmental competence and gene expression of immature oocytes following liquid helium vitrification in bovine.

    PubMed

    Chen, Jun-Yi; Li, Xiao-Xia; Xu, Ya-Kun; Wu, Hua; Zheng, Jun-Jun; Yu, Xue-Li

    2014-12-01

    The objective of this study was to develop an effective ultra-rapid vitrification method and evaluate its effect on maturation, developmental competence and development-related gene expression in bovine immature oocytes. Bovine cumulus oocyte complexes were randomly allocated into three groups: (1) controls, (2) liquid nitrogen vitrification, and (3) liquid helium vitrification. Oocytes were vitrified and then warmed, the percentage of morphologically normal oocytes in liquid helium group (89.0%) was significantly higher (P<0.05) than that of the liquid nitrogen group (81.1%). When the vitrified-thawed oocytes were matured in vitro for 24h, the maturation rate in liquid helium group (50.6%) was higher (P<0.05) than liquid nitrogen group (42.6%). Oocytes of liquid helium vitrification had higher cleavage and blastocyst rates (41.1% and 10.0%) than that of liquid nitrogen vitrification (33.0% and 4.5%; P<0.05) after in vitro fertilization. Moreover, the expression of GDF9 (growth/differentiation factor-9), BAX (apoptosis factor) and ZAR1 (zygote arrest 1) was analyzed by quantitative real-time polymerase chain reaction (qRT-PCR) when the vitrified-thawed oocytes were matured 24h. The expression of these genes was altered after vitrification. Expression of GDF9 and BAX in the liquid helium vitrification group was not significantly different from that of the control, however there were significant differences between the liquid nitrogen vitrification group and control. In conclusion, it was feasible to use liquid helium for vitrifying bovine immature oocytes. There existed an association between the compromised developmental competence and the altered expression levels of these genes for the vitrified oocytes.

  14. 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.

  15. Evaluation of helium cooling for fusion divertors

    SciTech Connect

    Baxi, C.B.

    1993-09-01

    The divertors of future fusion reactors will have a power throughput of several hundred MW. The peak heat flux on the diverter surface is estimated to be 5 to 15 MW/m{sup 2} at an average heat flux of 2 MW/m{sup 2}. The divertors have a requirement of both minimum temperature (100{degrees}C) and maximum temperature. The minimum temperature is dictated by the requirement to reduce the absorption of plasma, and the maximum temperature is determined by the thermo-mechanical properties of the plasma facing materials. Coolants that have been considered for fusion reactors are water, liquid metals and helium. Helium cooling has been shown to be very attractive from safety and other considerations. Helium is chemically and neutronically inert and is suitable for power conversion. The challenges associated with helium cooling are: (1) Manifold sizes; (2) Pumping power; and (3) Leak prevention. In this paper the first two of the above design issues are addressed. A variety of heat transfer enhancement techniques are considered to demonstrate that the manifold sizes and the pumping power can be reduced to acceptable levels. A helium-cooled diverter module was designed and fabricated by GA for steady-state heat flux of 10 MW/m{sup 2}. This module was recently tested at Sandia National Laboratories. At an inlet pressure of 4 MPa, the module was tested at a steady-state heat flux of 10 MW/m{sup 2}. The pumping power required was less than 1% of the power removed. These results verified the design prediction.

  16. Optimization of Helium Vessel Design for ILC Cavities

    SciTech Connect

    Fratangelo, Enrico

    2009-01-01

    the compliance of the Helium vessel and the cavity to the ASME code standard. After briefly recalling to the main contents of the the ASME Code (Sections II and Vlll - Division ll), the procedure used for finding all relevant stresses and comparing the obtained results with the maximum values allowed are explained. This part also includes the buckling verification of the cavity. In Chapter 5 the manufacturing process of the cavity end-caps, whose function is to link the Helium vessel with the cavity, is studied. The present configuration of the dies is described and the manufacturing process is simulated in order to explain the origin of some defects fol.llld on real parts. Finally a new design of the dies is proposed and the resulting deformed piece is compared with the design requirements. Chapter 6 describes a finite elements analysis to assess the efficiency and the stiffness of the Helium vessel. Furthermore the results of the optimization of the Helium vessel (in order to increase the value of the efficiency) are reported. The same stiffness analysis is used in Chapter 7 for the Blade-Tuner study. After a description of this tuner and of its function, the preliminary analyses done to confirm the results provided by the vendor are described and then its limiting load conditions are found. Chapter 8 shows a study of the resistance of all the welds present in between the cavity and the end-cap and between the end-caps and the He vessel for a smaller superconducting cavity operating at 3.9 GHz. Finally Chapter 9 briefly describes some R&D activities in progress at INFN (Section of Pisa) and Fermilab that could produce significant cost reductions of the Helium vessel design. All the finite elements analyses contained and described in this thesis made possible the certification of the whole superconducting cavity-Helium vessel assembly at Fermilab. Furthermore they gave several useful indications to the Fermilab staff to improve the performance of the Helium vessel by

  17. Survey of helium in soil gases of Long Valley, Califorina

    SciTech Connect

    Hinkle, M.E.; Kilburn, J.E.

    1980-01-01

    Soil and water samples in and around the Long Valley geothermal area, Mono County, California, were collected and analyzed for helium by means of a modified mass spectrometer leak detector to see what relationship helium concentrations might have to geothermal features of the area, and to previously studied mercury anomalies in the area. Anomalously high concentrations of helium occurred over part of a major Sierra Nevada frontal fault and over other faults outside of the caldera. Anomalously low concentrations of helium occurred in several areas of high mercury concentrations, which were also areas of hydrothermal alteration. Quantities of helium exsolved from water samples did not fit any pattern.

  18. Method to control the amount of helium during leak testing

    SciTech Connect

    Frank E. Jurvic, Jr.

    2002-03-29

    The purpose of this paper is to demonstrate a method for limiting the amount of helium administered during leak testing and provide a method for keeping the atmospheric helium in a location to a minimum to eliminate backstreaming into the system. This method utilizes the permeability of a balloon. The transporting of helium to the leak check area is also safer by not requiring a cylinder in the leak check location. Utilizing the many shapes of balloons and partially filling of the balloon, any configuration can deliver helium to the leak location. The balloon I filled for the test fell to the floor with the amount of helium I put into the balloon.

  19. The effects of convective overshooting on naked helium stars

    NASA Astrophysics Data System (ADS)

    Yan, Jing-Zhi; Zhu, Chun-Hua; Wang, Zhao-Jun; Lü, Guo-Liang

    2016-09-01

    Using stellar evolutionary models, we investigate the effects of convective overshooting on naked helium stars. We find that a larger value of overshooting parameter δov results in a larger convective core, which prolongs the lifetimes of naked helium stars on the helium main sequence and leads to higher effective temperatures and luminosities. For naked helium stars with masses lower than about 0.8 M⊙, they hardly become giant stars as a result of a weak burning shell. However, naked helium stars with masses between about 0.8 M⊙ and 1.1 M⊙ can evolve into giant branch phases, and finally become carbon oxygen white dwarfs.

  20. Examining Helium Line Intensities and Ratios in a Linear Helium Plasma to Identify Te and ne

    NASA Astrophysics Data System (ADS)

    Ray, H.; Biewer, T. M.; Unterberg, E. A.; Fehling, D. T.; Isler, R. C.

    2015-11-01

    Oak Ridge National Laboratory's prototype Material Plasma Exposure eXperiment (Proto-MPEX) is a linear plasma device dedicated to the understanding of plasma material interaction physics. A photomultiplier tube (PMT) based diagnostic system called a filterscope examines the visible light emission from Proto-MPEX. The filterscope is a non-invasive, high sensitivity, and high temporal resolution compact system with multiple PMT channels. Three PMTs contain He I narrow bandpass filters of wavelengths 667.9, 723.6, and 706.7 nm for line ratio analysis. Helium line intensities and ratios have been widely applied on astrophysical plasmas and machines such as JET and NSTX to determine profiles of electron temperatures, Te, and densities, ne. Ratios of the He I intensities measured by the filterscope are compared to calculated intensity ratios determined through a collisional radiative model (CRM) as follows: An excited He atom in state P will de-excite to a lower energy level Q by emitting a photon of a specific wavelength. A CRM uses the interactions P has with Q and other energy levels to calculate the population density of P. The calculated population density is used to determine the spectral line intensity of the wavelength analyzed. The aforementioned process is performed for each of the He I bandpass filters, and ratios dependent on Te and ne are calculated and compared to the filterscopes measured ratios. This work was supported by the US. D.O.E. contract DE-AC05-00OR22725.

  1. Determination of 6-thioguanosine diphosphate and triphosphate and nucleoside diphosphate kinase activity in erythrocytes: novel targets for thiopurine therapy?

    PubMed

    Karner, Susanne; Shi, Shaojun; Fischer, Christine; Schaeffeler, Elke; Neurath, Markus F; Herrlinger, Klaus R; Hofmann, Ute; Schwab, Matthias

    2010-04-01

    6-Thioguanine nucleotides are the sum of 6-thioguanosine 5'-monophosphate (TGMP), -diphosphate (TGDP), and -triphosphate (TGTP) representing essential metabolites involved in drug action of thiopurines. Elevated levels of TGDP have been associated with poor response to azathioprine therapy in patients with inflammatory bowel disease. The conversion of TGDP to TGTP is supposed to be catalyzed by nucleoside diphosphate kinase (NDPK). The aim of this work was to investigate simultaneously individual 6-thioguanosine phosphate levels and NDPK activity in red blood cells (RBCs) of patients on azathioprine therapy. Ion-pair high-performance liquid chromatography methods with fluorescence and ultraviolet detection were applied to quantify individual levels of 6-thioguanosine 5'-phosphates and NDPK activity, respectively, in RBCs. Recombinantly expressed NDPK isoforms A and B were unequivocally identified to catalyze the formation of TGTP (30.6 +/- 3.88 nmol x min x mg for NDPK A versus 41.2 +/- 1.05 nmol x min x mg for NDPK B). Comprehensive analyses on the stability of TGMP, TGDP, and TGTP and the reproducibility of NDPK activity in RBCs were performed to provide a reliable sampling protocol for clinical practice. Of note, isolation of RBCs within 6 hours followed by immediate storage at -80 degrees C is crucial for prevention of degradation of 5'-phosphates. In a clinical study of 37 patients on azathioprine, TGTP was the predominant 6-thioguanosine phosphate in RBCs. In contrast, three patients showed TGTP/(TGDP + TGTP) ratios of 57.2%, 64.3%, and 66% corresponding to elevated TGDP levels. NDPK activity ranged from 4.1 to 11.3 nmol x min x mg hemoglobin. No correlation between NDPK activity and the 6-thioguanosine phosphate levels was found. The question whether interindividual variability of NDPK activity may explain differences in 6-thioguanosine 5'-phosphates levels has to be investigated in a prospective large-scale study.

  2. Review of Membranes for Helium Separation and Purification.

    PubMed

    Scholes, Colin A; Ghosh, Ujjal K

    2017-02-17

    Membrane gas separation has potential for the recovery and purification of helium, because the majority of membranes have selectivity for helium. This review reports on the current state of the research and patent literature for membranes undertaking helium separation. This includes direct recovery from natural gas, as an ancillary stage in natural gas processing, as well as niche applications where helium recycling has potential. A review of the available polymeric and inorganic membranes for helium separation is provided. Commercial gas separation membranes in comparable gas industries are discussed in terms of their potential in helium separation. Also presented are the various membrane process designs patented for the recovery and purification of helium from various sources, as these demonstrate that it is viable to separate helium through currently available polymeric membranes. This review places a particular focus on those processes where membranes are combined in series with another separation technology, commonly pressure swing adsorption. These combined processes have the most potential for membranes to produce a high purity helium product. The review demonstrates that membrane gas separation is technically feasible for helium recovery and purification, though membranes are currently only applied in niche applications focused on reusing helium rather than separation from natural sources.

  3. Review of Membranes for Helium Separation and Purification

    PubMed Central

    Scholes, Colin A.; Ghosh, Ujjal K.

    2017-01-01

    Membrane gas separation has potential for the recovery and purification of helium, because the majority of membranes have selectivity for helium. This review reports on the current state of the research and patent literature for membranes undertaking helium separation. This includes direct recovery from natural gas, as an ancillary stage in natural gas processing, as well as niche applications where helium recycling has potential. A review of the available polymeric and inorganic membranes for helium separation is provided. Commercial gas separation membranes in comparable gas industries are discussed in terms of their potential in helium separation. Also presented are the various membrane process designs patented for the recovery and purification of helium from various sources, as these demonstrate that it is viable to separate helium through currently available polymeric membranes. This review places a particular focus on those processes where membranes are combined in series with another separation technology, commonly pressure swing adsorption. These combined processes have the most potential for membranes to produce a high purity helium product. The review demonstrates that membrane gas separation is technically feasible for helium recovery and purification, though membranes are currently only applied in niche applications focused on reusing helium rather than separation from natural sources. PMID:28218644

  4. Helium Accumulation Behavior in Iron Based Model Alloys

    SciTech Connect

    Sugano, R.; Morishita, K.; Kimura, A.

    2003-09-15

    Helium desorption from Fe-based model alloys irradiated by energetic helium ions was measured during post-irradiation annealing to investigate the energetics and kinetics of formation and annihilation of helium-related defects. Desorption temperatures were observed to be widely ranged from 450 to 1500 K, indicating that helium is bound to a wide variety of trapping sites such as vacancies and dislocations at various binding states. Such a feature is also observed in fusion ferritic steel. A comparison of helium desorption spectra obtained using Fe, Fe-Cr and Fe-Cr-Ni alloys showed that helium is more strongly trapped in bcc Fe than fcc Fe. It indicates that the long distance migration of helium takes place less frequently in bcc matrix, which may reduce the probability of helium clustering. Fusion ferric steel has a lot of trapping sites for helium such as dislocations, solute atoms, the interface of precipitates, impurities and lath boundaries, and so on, and in addition, it has bct matrix, indicating that most of helium atoms must be dispersed in the matrix and therefore it is difficult for them to cluster as a bubble. This may be a reason for higher helium resistance of the steel.

  5. Thermal desorption behavior of helium in aged titanium tritide films

    NASA Astrophysics Data System (ADS)

    Cheng, G. J.; Shi, L. Q.; Zhou, X. S.; Liang, J. H.; Wang, W. D.; Long, X. G.; Yang, B. F.; Peng, S. M.

    2015-11-01

    The desorption behavior of helium in TiT(1.5∼1.8)-x3Hex film samples (x = 0.0022-0.22) was investigated by thermal desorption technique in vacuum condition in this paper. The thermal helium desorption spectrometry (THDS) of aging titanium tritide films prepared by electron beam evaporation revealed that, depending on the decayed 3He concentration in the samples, there are more than four states of helium existing in the films. The divided four zones in THDS based on helium states represent respectively: (1) the mobile single helium atoms with low activation energy in all aging samples resulted from the interstitial sites or dissociated from interstitial clusters, loops and dislocations, (2) helium bubbles inside the grain lattices, (3) helium bubbles in the grain boundaries and interconnected networks of dislocations in the helium concentration of 3Hegen/Ti > 0.0094, and (4) helium bubbles near or linked to the film surface by interconnected channel for later aging stage with 3Hegen/Ti > 0.18. The proportion of helium desorption in each zone was estimated, and dissociated energies of helium for different trapping states were given.

  6. Helium-3 from the mantle - Primordial signal or cosmic dust?

    NASA Technical Reports Server (NTRS)

    Anderson, Don L.

    1993-01-01

    Helium-3 in hotspot magmas has been used as unambiguous evidence for the existence of a primordial, undegassed reservoir deep in the Earth's mantle. However, a large amount of helium-3 is delivered to the Earth's surface by interplanetary dust particles (IDPs). Recycling of deep-sea sediments containing these particles to the mantle, and eventual incorporation in magma, can explain the high helium-3/helium-4 ratios of hotspot magmas. Basalts with high helium-3/helium-4 ratios may represent degassing of helium introduced by ancient (probably 1.5 to 2.0 billion years old) pelagic sediments rather than degassing of primordial lower mantle material brought to the surface in plumes. Influx of IDPs can also explain the neon and siderophile compositions of mantle samples.

  7. A superfluid helium system for an LST IR experiment

    NASA Technical Reports Server (NTRS)

    Breckenridge, R. W., Jr.; Moore, R. W., Jr.

    1975-01-01

    The results are presented of a study program directed toward evaluating the problems associated with cooling an LST instrument to 2 K for a year by using superfluid helium as the cooling means. The results include the parametric analysis of systems using helium only, and systems using helium plus a shield cryogen. A baseline system, using helium only is described. The baseline system is sized for an instrument heat leak of 50 mw. It contains 71 Kg of superfluid helium and has a total, filled weight of 217 Kg. A brief assessment of the technical problems associated with a long life, spaceborne superfluid helium storage system is also made. It is concluded that a one year life, superfluid helium cooling system is feasible, pending experimental verification of a suitable low g vent system.

  8. A pencil beam algorithm for helium ion beam therapy

    SciTech Connect

    Fuchs, Hermann; Stroebele, Julia; Schreiner, Thomas; Hirtl, Albert; Georg, Dietmar

    2012-11-15

    Purpose: To develop a flexible pencil beam algorithm for helium ion beam therapy. Dose distributions were calculated using the newly developed pencil beam algorithm and validated using Monte Carlo (MC) methods. Methods: The algorithm was based on the established theory of fluence weighted elemental pencil beam (PB) kernels. Using a new real-time splitting approach, a minimization routine selects the optimal shape for each sub-beam. Dose depositions along the beam path were determined using a look-up table (LUT). Data for LUT generation were derived from MC simulations in water using GATE 6.1. For materials other than water, dose depositions were calculated by the algorithm using water-equivalent depth scaling. Lateral beam spreading caused by multiple scattering has been accounted for by implementing a non-local scattering formula developed by Gottschalk. A new nuclear correction was modelled using a Voigt function and implemented by a LUT approach. Validation simulations have been performed using a phantom filled with homogeneous materials or heterogeneous slabs of up to 3 cm. The beams were incident perpendicular to the phantoms surface with initial particle energies ranging from 50 to 250 MeV/A with a total number of 10{sup 7} ions per beam. For comparison a special evaluation software was developed calculating the gamma indices for dose distributions. Results: In homogeneous phantoms, maximum range deviations between PB and MC of less than 1.1% and differences in the width of the distal energy falloff of the Bragg-Peak from 80% to 20% of less than 0.1 mm were found. Heterogeneous phantoms using layered slabs satisfied a {gamma}-index criterion of 2%/2mm of the local value except for some single voxels. For more complex phantoms using laterally arranged bone-air slabs, the {gamma}-index criterion was exceeded in some areas giving a maximum {gamma}-index of 1.75 and 4.9% of the voxels showed {gamma}-index values larger than one. The calculation precision of the

  9. 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...

  10. 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...

  11. 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

    2016-07-20

    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.

  12. 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

  13. Asymmetric partitioning of metals among cluster anions and cations generated via laser ablation of mixed aluminum/Group 6 transition metal targets.

    PubMed

    Waller, Sarah E; Mann, Jennifer E; Jarrold, Caroline Chick

    2013-02-28

    While high-power laser ablation of metal alloys indiscriminately produces gas-phase atomic ions in proportion to the abundance of the various metals in the alloy, gas-phase ions produced by moderate-power laser ablation sources coupled with molecular beams are formed by more complicated mechanisms. A mass spectrometric study that directly compares the mass distributions of cluster anions and cations generated from laser ablation of pure aluminum, an aluminum/molybdenum mixed target, and an aluminum/tungsten mixed target is detailed. Mass spectra of anionic species generated from the mixed targets showed that both tungsten and molybdenum were in higher abundance in the negatively charged species than in the target material. Mass spectra of the cationic species showed primarily Al(+) and aluminum oxide and hydroxide cluster cations. No molybdenum- or tungsten-containing cluster cations were definitively assigned. The asymmetric distribution of aluminum and Group 6 transition metals in cation and anion cluster composition is attributed to the low ionization energy of atomic aluminum and aluminum suboxide clusters. In addition, the propensity of both molybdenum and tungsten to form metal oxide cluster anions under the same conditions that favor metallic aluminum cluster anions is attributed to differences in the optical properties of the surface oxide that is present in the metal powders used to prepare the ablation targets. Mechanisms of mixed metal oxide clusters are considered.

  14. miR-1 inhibits progression of high-risk papillomavirus-associated human cervical cancer by targeting G6PD.

    PubMed

    Hu, Tao; Chang, Ye-Fei; Xiao, Zhangang; Mao, Rui; Tong, Jun; Chen, Bo; Liu, Guang-Cai; Hong, Ying; Chen, Hong-Lan; Kong, Shu-Yi; Huang, Yan-Mei; Xiyang, Yan-Bin; Jin, Hua

    2016-12-27

    Ectopic glucose-6-phosphate dehydrogenase (G6PD) expression may contribute to tumorigenesis in cervical cancer associated with high-risk human papillomavirus (HR-HPV 16 and 18) infections. Here, we demonstrate that microRNA-1 (miR-1) in association with AGO proteins targets G6PD in HR-HPV-infected human cervical cancer cells. miR-1 inhibited expression of a reporter construct containing a putative G6PD 3'-UTR seed region and suppressed endogenous G6PD expression. Down-regulation of miR-1 increased G6PD expression in cervical cancer cells. Regression analysis revealed that miR-1 levels correlate negatively with the clinicopathologic features in HR-HPV 16/18-infected cervical cancer patients. miR-1 overexpression inhibited proliferation and promoted apoptosis in cervical cancer cells and reduced xenograft tumor growth in nude mice. Conversely, sponge-mediated miR-1 knockdown markedly increased viability and reduced apoptosis in cervical cancer cells and supported neoplasm growth. Restoration of G6PD expression partially reversed the effects of miR-1 overexpression both in vitro and in vivo. In addition, co-transfection of G6PD siRNA and miR-1 sponge partially reversed miR-1 sponge-induced reductions in cell viability and neoplasm growth. These results suggest that miR-1 suppresses the development and progression of HR-HPV 16/18-infected cervical cancer by targeting G6PD and may be a promising novel therapeutic candidate.

  15. miR-1 inhibits progression of high-risk papillomavirus-associated human cervical cancer by targeting G6PD

    PubMed Central

    Liu, Guang-Cai; Hong, Ying; Chen, Hong-Lan; Kong, Shu-Yi; Huang, Yan-Mei; Xiyang, Yan-Bin; Jin, Hua

    2016-01-01

    Ectopic glucose-6-phosphate dehydrogenase (G6PD) expression may contribute to tumorigenesis in cervical cancer associated with high-risk human papillomavirus (HR-HPV 16 and 18) infections. Here, we demonstrate that microRNA-1 (miR-1) in association with AGO proteins targets G6PD in HR-HPV-infected human cervical cancer cells. miR-1 inhibited expression of a reporter construct containing a putative G6PD 3′-UTR seed region and suppressed endogenous G6PD expression. Down-regulation of miR-1 increased G6PD expression in cervical cancer cells. Regression analysis revealed that miR-1 levels correlate negatively with the clinicopathologic features in HR-HPV 16/18-infected cervical cancer patients. miR-1 overexpression inhibited proliferation and promoted apoptosis in cervical cancer cells and reduced xenograft tumor growth in nude mice. Conversely, sponge-mediated miR-1 knockdown markedly increased viability and reduced apoptosis in cervical cancer cells and supported neoplasm growth. Restoration of G6PD expression partially reversed the effects of miR-1 overexpression both in vitro and in vivo. In addition, co-transfection of G6PD siRNA and miR-1 sponge partially reversed miR-1 sponge-induced reductions in cell viability and neoplasm growth. These results suggest that miR-1 suppresses the development and progression of HR-HPV 16/18-infected cervical cancer by targeting G6PD and may be a promising novel therapeutic candidate. PMID:27861141

  16. Mitochondrial calcium uptake capacity as a therapeutic target in the R6/2 mouse model of Huntington's disease

    PubMed Central

    Perry, Giselle M.; Tallaksen-Greene, Sara; Kumar, Ashish; Heng, Mary Y.; Kneynsberg, Andrew; van Groen, Thomas; Detloff, Peter J.; Albin, Roger L.; Lesort, Mathieu

    2010-01-01

    Huntington's disease (HD) is an incurable autosomal-dominant neurodegenerative disorder initiated by an abnormally expanded polyglutamine domain in the huntingtin protein. It is proposed that abnormal mitochondrial Ca2+ capacity results in an increased susceptibility to mitochondrial permeability transition (MPT) induction that may contribute significantly to HD pathogenesis. The in vivo contribution of these hypothesized defects remains to be elucidated. In this proof-of-principle study, we examined whether increasing mitochondrial Ca2+ capacity could ameliorate the well-characterized phenotype of the R6/2 transgenic mouse model. Mouse models lacking cyclophilin D demonstrate convincingly that cyclophilin D is an essential component and a key regulator of MPT induction. Mitochondria of cyclophilin D knockout mice are particularly resistant to Ca2+ overload. We generated R6/2 mice with normal, reduced or absent cyclophilin D expression and examined the effect of increasing mitochondrial Ca2+ capacity on the behavioral and neuropathological features of the R6/2 model. A predicted outcome of this approach was the finding that cyclophilin D deletion enhanced the R6/2 brain mitochondria Ca2+ capacity significantly. Increased neuronal mitochondrial Ca2+ capacity failed to ameliorate either the behavioral and neuropathological features of R6/2 mice. We found no alterations in body weight changes, lifespan, RotaRod performances, grip strength, overall activity and no significant effect on the neuropathological features of R6/2 mice. The results of this study demonstrate that increasing neuronal mitochondrial Ca2+-buffering capacity is not beneficial in the R6/2 mouse model of HD. PMID:20558522

  17. Direct evidence of mismatching effect on H emission in laser-induced atmospheric helium gas plasma

    SciTech Connect

    Zener Sukra Lie; Koo Hendrik Kurniawan; May On Tjia; Rinda, Hedwig; Suliyanti, Maria Margaretha; Syahrun Nur Abdulmadjid; Nasrullah Idris; Alion Mangasi Marpaung; Marincan Pardede; Jobiliong, Eric; Muliadi Ramli; Heri Suyanto; Fukumoto, Kenichi; Kagawa, Kiichiro

    2013-02-07

    A time-resolved orthogonal double pulse laser-induced breakdown spectroscopy (LIBS) with helium surrounding gas is developed for the explicit demonstration of time mismatch between the passage of fast moving impurity hydrogen atoms and the formation of thermal shock wave plasma generated by the relatively slow moving major host atoms of much greater masses ablated from the same sample. Although this so-called 'mismatching effect' has been consistently shown to be responsible for the gas pressure induced intensity diminution of hydrogen emission in a number of LIBS measurements using different ambient gases, its explicit demonstration has yet to be reported. The previously reported helium assisted excitation process has made possible the use of surrounding helium gas in our experimental set-up for showing that the ablated hydrogen atoms indeed move faster than the simultaneously ablated much heavier major host atoms as signaled by the earlier H emission in the helium plasma generated by a separate laser prior to the laser ablation. This conclusion is further substantiated by the observed dominant distribution of H atoms in the forward cone-shaped target plasma.

  18. Targeted delivery of vitamin D3-loaded nanoparticles to C6 glioma cell line increased resistance to doxorubicin, epirubicin, and docetaxel in vitro.

    PubMed

    Maleklou, Nargess; Allameh, Abdolamir; Kazemi, Bahram

    2016-12-01

    In recent years, targeted delivery systems have been used along with combinatorial therapy to decrease drug resistance and increase cancer therapy efficacy. The anti-proliferative effects of vitamin D3 (VD3) on cancerous cells, such as C6 glioma, with active hedgehog pathways raised the question as to whether pre-targeting C6 glioma cells with VD3-loaded nanoparticles (VD3NPs) can enhance the anti-tumor effects of doxorubicin, epirobicin, and docetaxel on this drug-resistant cell line. Here, studying at cellular, nuclear, protein, and gene levels we demonstrated that VD3NP-doxorubicin and VD3NP-epirobicin combinations increased the probability of chemotherapy/radiotherapy resistance and cancer stem cell (CSC) properties in C6 glioma significantly (P < 0.05), compared to doxorubicin and epirobicin alone. However, VD3NP-docetaxel combination may have the potential in sensitizing C6 cells to ionizing irradiation, but this combination also increased the CSC properties and the probability of drug resistance significantly (P < 0.05), compared to docetaxel alone. Although our previous study showed that targeted delivery of VD3 reduced the rate of proliferation significantly (P < 0.05) in C6 glioma cells (a drug-resistant cell line), here we concluded that combinatorial therapy of exogenous VD3 with doxorubicin, epirobicin, and docetaxel not only did not lead to the enhancement of cytotoxic effects of the aforementioned drugs but also increased the cancerous characteristics in C6 glioma, in vitro.

  19. Evaluation of a new biocompatible poly(N-(morpholino ethyl methacrylate)-based copolymer for the delivery of ruthenium oligonucleotides, targeting HPV16 E6 oncogene.

    PubMed

    Reschner, Anca; Shim, Yong Ho; Dubois, Philippe; Delvenne, Philippe; Evrard, Brigitte; Marcélis, Lionel; Moucheron, Cécile; Kirsch-De Mesmaeker, Andrée; Defrancq, Eric; Raes, Martine; Piette, Jacques; Collard, Laurence; Piel, Géraldine

    2013-08-01

    This study investigates the use of a new biocompatible block copolymer poly(2-(dimethylamino)ethyl methacrylate-N-(morpholino)ethyl methacrylate (PDMAEMA-b-PMEMA) for the delivery of a particular antisense oligonucleotide targeting E6 gene from human papilloma virus. This antisense oligonucleotide was derivatized with a polyazaaromatic Ru(II) complex which, under visible illumination, is able to produce an irreversible crosslink with the complementary targeted sequence. The purpose of this study is to determine whether by the use of a suitable transfection agent, it is possible to increase the efficiency of the antisense oligonucleotide targeting E6 gene, named Ru-P-4. In a recent study, we showed that Oligofectamine transfected Ru-P-4 antisense oligonucleotide failed to inhibit efficiently the growth of cervical cancer cell line SiHa, contrarily to the Ru-P-6 antisense oligonucleotide, another sequence also targeting the E6 gene. The ability of PDMAEMA-b-PMEMA to form polyplexes with optimal physicochemical characteristics was investigated first. Then the ability of the PDMAEMA-b-PMEMA/Ru-P-4 antisense oligonucleotide polyplexes to transfect two keratinocyte cell lines (SiHa and HaCat) and the capacity of polyplexes to inhibit HPV16+ cervical cancer cell growth was evaluated. PDMAEMA-b-PMEMA base polyplexes at the optimal molar ratio of polymer nitrogen atoms to DNA phosphates (N/P), were able to deliver Ru-P-4 antisense oligonucleotide and to induce a higher growth inhibition in human cervical cancer SiHa cells, compared to other formulations based on Oligofectamine.

  20. Measurement of Helium-3/Helium-4 Ratios in Soil Gas at the 618-11 Burial Ground

    SciTech Connect

    Olsen, Khris B; Dresel, P Evan; Evans, John C

    2001-10-31

    Seventy soil gas-sampling points were installed around the perimeter of the 618-11 Burial Ground, approximately 400 feet downgradient of well 699-13-3A, and in four transects downgradient of the burial ground to a maximum distance of 3,100 feet. Soil gas samples were collected and analyzed for helium-3/helium-4 ratios from these 70 points. Helium-3/helium-4 ratios determined from the soil gas sampling points showed significant enrichments, relative to ambient air helium-3 concentrations. The highest concentrations were located along the northern perimeter of the burial ground. Helium-3/helium-4 ratios (normalized to the abundances in ambient air) ranged from 1.0 to 62 around the burial ground. The helium-3/helium-4 ratios from the 4 transect downgradient of the burial ground ranged from 0.988 to 1.68. The helium-3/helium-4 ratios from around the burial ground suggest there is a vadose zone source of tritium along the north side of the burial ground.

  1. Development and Dissemination of a Nationwide Helium Database for a National Assessment of Helium Resources.

    NASA Astrophysics Data System (ADS)

    Brennan, S. T.; East, J. A., II; Garrity, C. P.

    2015-12-01

    In 2013, Congress passed the Helium Stewardship Act requiring the U.S. Geological Survey (USGS) to undertake a national helium gas resource assessment to determine the nation's helium resources. An important initial component necessary to complete this assessment was the development of a comprehensive database of Helium (He) concentrations from petroleum exploration wells. Because Helium is often used as the carrier gas for compositional analyses for commercial and exploratory oil and gas wells, this limits the available helium concentration data. A literature search in peer-reviewed publications, state geologic survey databases, USGS energy geochemical databases, and the Bureau of Land Management databases provided approximately 16,000 data points from wells that had measurable He concentrations in the gas composition analyses. The data from these wells includes, date of sample collection, American Petroleum Institute well number, formation name, field name, depth of sample collection, and location. The gas compositional analyses, some performed as far back as 1934, do not all have the same level of precision and accuracy, therefore the date of the analysis is critical to the assessment as it indicates the relative amount of uncertainty in the analytical results. Non-proprietary data was used to create a GIS based interactive web interface that allows users to visualize, inspect, interact, and download our most current He data. The user can click on individual locations to see the available data at that location, as well as zoom in and out on a data density map. Concentrations on the map range from .04 mol% (lowest concentration of economic value) to 12% (highest naturally occurring values). This visual interface will allow users to develop a rapid appreciation of the areas with the highest potential for high helium concentrations within oil and gas fields.

  2. Helium (3) Rich Solar Flares

    DOE R&D Accomplishments Database

    Colgate, S. A.; Audouze, J.; Fowler, W. A.

    1977-05-03

    The extreme enrichment of {sup 3} He {sup 4} He greater than or equal to 1 in some solar flares as due to spallation and the subsequent confinement of the products in a high temperature, kT approx. = 200 keV, high density, n{sub e} approx. = 3 x 10{sup 15} cm {sup -3} plasma associated with the magnetic instability producing the flare is interpreted. The pinch or filament is a current of high energy protons that creates the spallation and maintains the temperature that produces the high energy x-ray spectrum and depletes other isotopes D, Li, Be, and B as observed. Finally the high temperature plasma is a uniquely efficient spallation target that is powered by the interaction of stellar convection and self generated magnetic field.

  3. Effects of helium on inflammatory and oxidative stress-induced endothelial cell damage.

    PubMed

    Smit, Kirsten F; Kerindongo, Raphaela P; Böing, Anita; Nieuwland, Rienk; Hollmann, Markus W; Preckel, Benedikt; Weber, Nina C

    2015-09-10

    Helium induces preconditioning in human endothelium protecting against postischemic endothelial dysfunction. Circulating endothelial microparticles are markers of endothelial dysfunction derived in response to injury. Another noble gas, xenon, protected human umbilical vein endothelial cells (HUVEC) against inflammatory stress in vitro. We hypothesised that helium protects the endothelium in vitro against inflammatory and oxidative stress. HUVEC were isolated from fresh umbilical cords and grown upon confluence. Cells were subjected to starving medium for 12h before the experiment and treated for either 3 × 5 min or 1 × 30 min with helium (5% CO2, 25% O2, 70% He) or control gas (5% CO2, 25% O2, 70% N2) in a specialised gas chamber. Subsequently, cells were stimulated with TNF-α (40 ng/ml for 24h or 10 ng/ml for 2h) or H2O2 (500 μM for 2h) or left untreated. Adhesion molecule expression was analysed using real-time quantitative polymerase chain reaction. Caspase-3 expression and viability of the cells was measured by flowcytometry. Microparticles were investigated by nanoparticle tracking analysis. Helium had no effect on adhesion molecule expression after TNF-α stimulation but in combination with oxidative stress decreased cell viability (68.9 ± 1.3% and 58 ± 1.9%) compared to control. Helium further increased TNF-α induced release of caspase-3 containing particles compared to TNF-α alone (6.4 × 10(6) ± 1.1 × 10(6) and 2.9 × 10(6) ± 0.7 × 10(6), respectively). Prolonged exposure of helium increased microparticle formation (2.4 × 10(9) ± 0.5 × 10(9)) compared to control (1.7 × 10(9) ± 0.2 × 10(9)). Summarized, helium increases inflammatory and oxidative stress-induced endothelial damage and is thus not biologically inert. A possible noxious effects on the cellular level causing alterations in microparticle formation both in number and content should be acknowledged.

  4. Helium-Cooled Refractory Alloys First Wall and Blanket Evaluation

    SciTech Connect

    Wong, C.P.C.; Nygren, R.E.; Baxi, C.B.; Fogarty, P.; Ghoniem, N.; Khater, H.; McCarthy, K.; Merrill, B.; Nelson, B.; Reis, E.E.; Sharafat, S.; Schleicher, R.; Sze, D.K.; Ulrickson, M.; Willms, S.; Youssef, M.; Zinkel, S.

    1999-08-01

    Under the APEX program the He-cooled system design task is to evaluate and recommend high power density refractory alloy first wall and blanket designs and to recommend and initiate tests to address critical issues. We completed the preliminary design of a helium-cooled, W-5Re alloy, lithium breeder design and the results are reported in this paper. Many areas of the design were assessed, including material selection, helium impurity control, and mechanical, nuclear and thermal hydraulics design, and waste disposal, tritium and safety design. System study results show that at a closed cycle gas turbine (CCGT) gross thermal efficiency of 57.5%, a superconducting coil tokamak reactor, with an aspect ratio of 4, and an output power of 2 GWe, can be projected to have a cost of electricity at 54.6 mill/kWh. Critical issues were identified and we plan to continue the design on some of the critical issues during the next phase of the APEX design study.

  5. Partial cross sections of helium satellites at medium photon energies

    SciTech Connect

    Wehlitz, R.; Sellin, I.A.; Hemmers, O.

    1997-04-01

    Still of current interest is the important role of single ionization with excitation compared to single ionization alone. The coupling between the electrons and the incoming photon is a single-particle operator. Thus, an excitation in addition to an ionization, leading to a so-called satellite line in a photoelectron spectrum, is entirely due to electron-electron interaction and probes the electron correlation in the ground and final state. Therefore the authors have undertaken the study of the intensity of helium satellites He{sup +}nl (n = 2 - 6) relative to the main photoline (n = 1) as a function of photon energy at photon energies well above threshold up to 900 eV. From these results they could calculate the partial cross-sections of the helium satellites. In order to test the consistency of their satellite-to-1s ratios with published double-to-single photoionization ratios, the authors calculated the double-to-single photoionization ratio from their measured ratios using the theoretical energy-distribution curves of Chang and Poe and Le Rouzo and Dal Cappello which proved to be valid for photon energies below 120 eV. These calculated double-to-single ionization ratios agree fairly well with recent ion measurements. In the lower photon energy range the authors ratios agree better with the ratios of Doerner et al. while for higher photon energies the agreement is better with the values of Levin et al.

  6. Helium-neon laser treatment transforms fibroblasts into myofibroblasts.

    PubMed Central

    Pourreau-Schneider, N.; Ahmed, A.; Soudry, M.; Jacquemier, J.; Kopp, F.; Franquin, J. C.; Martin, P. M.

    1990-01-01

    The differentiation of myofibroblastic cells from normal human gingival fibroblasts in vitro has been established by transmission electron microscopy and quantitated by immunohistochemistry, using antigelsolin monoclonal antibodies. Untreated control cultures were compared to cultures exposed to Helium-Neon (He-Ne) laser irradiation. A direct and massive transformation of the cultured fibroblasts into myofibroblasts was observed as early as 24 hours after laser treatment, whereas control cultures were comprised of only resting fibroblasts and active fibroblasts. This in vitro induction of myofibroblasts may be analogous to that which occurs in vivo. Therefore we undertook a similar study using biopsies from gingival tissues after wisdom tooth extraction. Myofibroblasts were present in the connective tissue of laser-treated gums 48 hours after irradiation, but not in untreated contralateral control tissues. These data provide evidence that the primary biologic effect of the Helium-Neon laser on connective tissue is the rapid generation of myofibroblasts from fibroblasts. The induction of a phenotype with contractile properties may have clinical significance in the acceleration of the wound-healing process. Images Figure 6 Figure 7 Figure 8 Figure 9 Figure 10 Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 PMID:2372040

  7. A conserved RAD6-MDM2 ubiquitin ligase machinery targets histone chaperone ASF1A in tumorigenesis.

    PubMed

    Wang, Chen; Chang, Jian-Feng; Yan, Hongli; Wang, Da-Liang; Liu, Yan; Jing, Yuanya; Zhang, Meng; Men, Yu-Long; Lu, Dongdong; Yang, Xiao-Mei; Chen, Su; Sun, Fang-Lin

    2015-10-06

    Chromatin is a highly organized and dynamic structure in eukaryotic cells. The change of chromatin structure is essential in many cellular processes, such as gene transcription, DNA damage repair and others. Anti-silencing function 1 (ASF1) is a histone chaperone that participates in chromatin higher-order organization and is required for appropriate chromatin assembly. In this study, we identified the E2 ubiquitin-conjugating enzyme RAD6 as an evolutionary conserved interacting protein of ASF1 in D. melanogaster and H. sapiens that promotes the turnover of ASF1A by cooperating with a well-known E3 ligase, MDM2, via ubiquitin-proteasome pathway in H. sapiens. Further functional analyses indicated that the interplay between RAD6 and ASF1A associates with tumorigenesis. Together, these data suggest that the RAD6-MDM2 ubiquitin ligase machinery is critical for the degradation of chromatin-related proteins.

  8. Physiological response of rats to delivery of helium and xenon: implications for hyperpolarized noble gas imaging

    NASA Technical Reports Server (NTRS)

    Ramirez, M. P.; Sigaloff, K. C.; Kubatina, L. V.; Donahue, M. A.; Venkatesh, A. K.; Albert, M. S.; ALbert, M. S. (Principal Investigator)

    2000-01-01

    The physiological effects of various hyperpolarized helium and xenon MRI-compatible breathing protocols were investigated in 17 Sprague-Dawley rats, by continuous monitoring of blood oxygen saturation, heart rate, EKG, temperature and endotracheal pressure. The protocols included alternating breaths of pure noble gas and oxygen, continuous breaths of pure noble gas, breath-holds of pure noble gas for varying durations, and helium breath-holds preceded by two helium rinses. Alternate-breath protocols up to 128 breaths caused a decrease in oxygen saturation level of less than 5% for either helium or xenon, whereas 16 continuous-breaths caused a 31.5% +/- 2.3% decrease in oxygen saturation for helium and a 30.7% +/- 1. 3% decrease for xenon. Breath-hold protocols up to 25 s did not cause the oxygen saturation to fall below 90% for either of the noble gases. Oxygen saturation values below 90% are considered pathological. At 30 s of breath-hold, the blood oxygen saturation dropped precipitously to 82% +/- 0.6% for helium, and to 76.5% +/- 7. 4% for xenon. Breath-holds longer than 10 s preceded by pre-rinses caused oxygen saturation to drop below 90%. These findings demonstrate the need for standardized noble gas inhalation procedures that have been carefully tested, and for continuous physiological monitoring to ensure the safety of the subject. We find short breath-hold and alternate-breath protocols to be safe procedures for use in hyperpolarized noble gas MRI experiments. Copyright 2000 John Wiley & Sons, Ltd.

  9. Thermal conductance of pressed brass contacts at liquid helium temperatures

    NASA Technical Reports Server (NTRS)

    Salerno, L. J.; Kittel, P.; Brooks, W. F.; Spivak, A. L.; Marks, W. G., Jr.

    1986-01-01

    An apparatus has been designed and fabricated which will measure the thermal conductance of pressed contacts at liquid helium temperatures as a function of applied force, with surface finish as a parameter. The apparatus is automated and was used to measure thermal conductance at temperatures from 1.5 to 6.5 K at applied forces up to 700 N for brass sample pairs having surface finishes from 0.1 to 1.6 micron rms. The experimental data were found to fit a simple power law where the thermal conductance is given by k = alpha T exp n, where k is the thermal conductance, T is the absolute temperature, and alpha and n are empirically determined constants.

  10. The effect of bi-terminal PEGylation of an integrin  αvβ6-targeted 18F peptide on pharmacokinetics and tumor uptake

    DOE PAGES

    Hausner, Sven H.; Bauer, Nadine; Hu, Lina Y.; ...

    2015-03-26

    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-FBA-A20FMDV2-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 eithermore » no PEG or different PEG units at the N terminus. 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. Here, 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–DX3puro

  11. Electron-helium scattering in Debye plasmas

    SciTech Connect

    Zammit, Mark C.; Fursa, Dmitry V.; Bray, Igor; Janev, R. K.

    2011-11-15

    Electron-helium scattering in weakly coupled hot-dense (Debye) plasma has been investigated using the convergent close-coupling method. The Yukawa-type Debye-Hueckel potential has been used to describe plasma Coulomb screening effects. Benchmark results are presented for momentum transfer cross sections, excitation, ionization, and total cross sections for scattering from the ground and metastable states of helium. Calculations cover the entire energy range up to 1000 eV for the no screening case and various Debye lengths (5-100 a{sub 0}). We find that as the screening interaction increases, the excitation and total cross sections decrease, while the total ionization cross sections increase.

  12. Helium-ion-induced human cataractogenesis

    NASA Technical Reports Server (NTRS)

    Blakely, E. A.; Daftari, I. K.; Meecham, W. J.; Alonso, L. C.; Collier, J. M.; Kroll, S. M.; Gillette, E. L.; Lee, A. C.; Lett, J. T.; Cox, A. B.

    1994-01-01

    Retrospective and ongoing analyses of clinical records from 347 primary intraocular melanoman patients treated with helium ions at Lawrence Berkeley Laboratory (LBL) will allow examination of the exposure-response data for human cataract; which is a complication of the therapy from incidental exposure of the lens. Direct particle beam traversal of at least a portion of the lens usually is unavoidable in treatment of posterior intraocular tumors. The precise treatment planned for each patient permits quantitative assessment of the lenticular dose and its radiation quality. We are reporting our preliminary results on the development of helium-ion-induced lens opacifications and cataracts in 54 of these patients who had 10% or less of their lens in the treatment field. We believe these studies will be relevant to estimating the human risk for cataract in space flight.

  13. Quantum model of the Thomson helium atom

    NASA Astrophysics Data System (ADS)

    Kazaryan, E. M.; Shakhnazaryan, V. A.; Sarkisyan, H. A.; Gusev, A. A.

    2014-03-01

    A quantum model of the Thomson helium atom is considered within the framework of stationary perturbation theory. It is shown that from a formal point of view this problem is similar to that of two-electron states in a parabolic quantum dot. The ground state energy of the quantum Thomson helium atom is estimated on the basis of Heisenberg's uncertainty principle. The ground state energies obtained in the first order of perturbation theory and qualitative estimate provide, respectively, upper and lower estimates of eigenvalues derived by numerically solving the problem for a quantum model. The conditions under which the Kohn theorem holds in this system, when the values of resonance absorption frequencies are independent of the Coulomb interaction between electrons, are discussed.

  14. Three Dimensional Particle Tracking in Superfluid Helium

    NASA Astrophysics Data System (ADS)

    Megson, Peter

    2016-11-01

    Superfluid helium is a macroscopic quantum state which exhibits exotic physical properties, such as flow without friction and ballistic heat transport. Superfluid flow is irrotational except about line-like topological phase defects with quantized circulation, known as quatized vortices. The presence of these vortices and their dynamics is the dominating factor of turbulence in superfluid flows. One commonly studied regime of superfluid turbulence is thermal counterflow, where a local heat flux drives the formation and growth of a tangle of vortices. This talk will present experimental studies of counterflow turbulence performed using a multi-camera three-dimensional imaging apparatus with micron-sized ice tracer particles as well as fluorescent nanoparticles. In particular, we will discuss the measurement of three-dimensional velocties and their autocorrelations. Additionally, we are developing new techniques for optical studies of bulk superfluid helium, with particular focus on characterizing tracer particles and particle dispersal mechanisms. Funding from NSF DMR-1407472.

  15. The mitochondria-targeted anti-oxidant MitoQ reduces aspects of mitochondrial fission in the 6-OHDA cell model of Parkinson's disease.

    PubMed

    Solesio, María E; Prime, Tracy A; Logan, Angela; Murphy, Michael P; Del Mar Arroyo-Jimenez, María; Jordán, Joaquín; Galindo, María F

    2013-01-01

    Parkinson's disease (PD) is a neurodegenerative disorder for which available treatments provide symptom relief but do not stop disease progression. Mitochondria, and in particular mitochondrial dynamics, have been postulated as plausible pharmacological targets. Mitochondria-targeted antioxidants have been developed to prevent mitochondrial oxidative damage, and to alter the involvement of reactive oxygen species (ROS) in signaling pathways. In this study, we have dissected the effect of MitoQ, which is produced by covalent attachment of ubiquinone to a triphenylphosphonium lipophilic cation by a ten carbon alkyl chain. MitoQ was tested in an in vitro PD model which involves addition of 6-hydroxydopamine (6-OHDA) to SH-SY5Y cell cultures. At sublethal concentrations of 50μM, 6-OHDA did not induce increases in protein carbonyl, mitochondrial lipid peroxidation or mitochondrial DNA damage. However, after 3h of treatment, 6-OHDA disrupts the mitochondrial morphology and activates the machinery of mitochondrial fission, but not fusion. Addition of 6-OHDA did not increase the levels of fission 1, mitofusins 1 and 2 or optic atrophy 1 proteins, but does lead to the translocation of dynamin related protein 1 from the cytosol to the mitochondria. Pre-treatment with MitoQ (50nM, 30min) results in the inhibition of the mitochondrial translocation of Drp1. Furthermore, MitoQ also inhibited the translocation of the pro-apoptotic protein Bax to the mitochondria. These findings provide mechanistic evidence for a role for redox events contributing to mitochondrial fission and suggest the potential of mitochondria-targeted therapeutics in diseases that involve mitochondrial fragmentation due to oxidative stress.

  16. Particle-Vortex Interaction in Superfluid Helium

    NASA Astrophysics Data System (ADS)

    Barenghi, Carlo F.

    2008-11-01

    The application of the classical Particle Image Velocimetry (PIV) technique in liquid helium has opened the way to better visualization of superfluid turbulence. To interpret the data, it is necessary to understand the interaction between micron-size tracer particles and vortex lines. This talk summarizes current understanding of this interaction resulting from theoretical and numerical calculations. In collaboration with Yuri A. Sergeev, Newcastle University.

  17. Helium synthesis, neutrino flavors, and cosmological implications

    NASA Technical Reports Server (NTRS)

    Stecker, F. W.

    1979-01-01

    The problem of the production of helium in big bang cosmology is re-examined in the light of several recent astrophysical observations. These data, and theoretical particle physics considerations, lead to some important inconsistencies in the standard big bang model and suggest that a more complicated picture is needed. Thus, recent constraints on the number of neutrino flavors, as well as constraints on the mean density (openness) of the universe, need not be valid.

  18. Test program, helium II orbital resupply coupling

    NASA Technical Reports Server (NTRS)

    Hyatt, William S.

    1991-01-01

    The full scope of this program was to have included development tests, design and production of custom test equipment and acceptance and qualification testing of prototype and protoflight coupling hardware. This program was performed by Ball Aerospace Systems Division, Boulder, Colorado until its premature termination in May 1991. Development tests were performed on cryogenic face seals and flow control devices at superfluid helium (He II) conditions. Special equipment was developed to allow quantified leak detection at large leak rates up to 8.4 x 10(exp -4) SCCS. Two major fixtures were developed and characterized: The Cryogenic Test Fixture (CTF) and the Thermal Mismatch Fixture (Glovebox). The CTF allows the coupling hardware to be filled with liquid nitrogen (LN2), liquid helium (LHe) or sub-cooled liquid helium when hardware flow control valves are either open or closed. Heat leak measurements, internal and external helium leakage measurements, cryogenic proof pressure tests and external load applications are performed in this fixture. Special reusable MLI closures were developed to provide repeatable installations in the CTF. The Thermal Mismatch Fixture allows all design configurations of coupling hardware to be engaged and disengaged while measuring applied forces and torques. Any two hardware components may be individually thermally preconditioned within the range of 117 deg K to 350 deg K prior to engage/disengage cycling. This verifies dimensional compatibility and operation when thermally mismatched. A clean, dry GN2 atmosphere is maintained in the fixture at all times. The first shipset of hardware was received, inspected and cycled at room temperature just prior to program termination.

  19. Combined cold compressor/ejector helium refrigerator

    DOEpatents

    Brown, Donald P.

    1985-01-01

    A refrigeration apparatus having an ejector operatively connected with a cold compressor to form a two-stage pumping system. This pumping system is used to lower the pressure, and thereby the temperature of a bath of boiling refrigerant (helium). The apparatus as thus arranged and operated has substantially improved operating efficiency when compared to other processes or arrangements for achieving a similar low pressure.

  20. Combined cold compressor/ejector helium refrigerator

    DOEpatents

    Brown, D.P.

    1984-06-05

    A refrigeration apparatus having an ejector operatively connected with a cold compressor to form a two-stage pumping system. This pumping system is used to lower the pressure, and thereby the temperature of a bath of boiling refrigerant (helium). The apparatus as thus arranged and operated has substantially improved operating efficiency when compared to other processes or arrangements for achieving a similar low pressure.