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Sample records for beryllium 9 target

  1. Large-angle production of charged pions by 3 GeV/c - 12.9 GeV/c protons on beryllium, aluminium and lead targets

    CERN Document Server

    Catanesi, M G; Edgecock, R; Ellis, Malcolm; Soler, F J P; Gössling, C; Bunyatov, S; Krasnoperov, A; Popov, B; Serdiouk, V; Tereschenko, V; Di Capua, E; Vidal-Sitjes, G; Artamonov, A; Giani, S; Gilardoni, S; Gorbunov, P; Grant, A; Grossheim, A; Ivanchenko, V; Kayis-Topaksu, A; Panman, J; Papadopoulos, I; Chernyaev, E; Tsukerman, I; Veenhof, R; Wiebusch, C; Zucchelli, P; Blondel, A; Borghi, S; Morone, M C; Prior, G; Schroeter, R; Meurer, C; Gastaldi, U; Mills, G B; Graulich, J S; Grégoire, G; Bonesini, M; Ferri, F; Kirsanov, M; Bagulya, A; Grichine, V; Polukhina, N; Palladino, V; Coney, L; Schmitz, D; Barr, G; De Santo, A; Bobisut, F; Gibin, D; Guglielmi, A; Mezzetto, M; Dumarchez, J; Dore, U; Orestano, D; Pastore, F; Tonazzo, A; Tortora, L; Booth, C; Howlett, L; Bogomilov, M; Chizhov, M; Kolev, D; Tsenov, R; Piperov, Stefan; Temnikov, P; Apollonio, M; Chimenti, P; Giannini, G; Burguet-Castell, J; Cervera-Villanueva, A; Gómez-Cadenas, J J; Martín-Albo, J; Novella, P; Sorel, M; CERN. Geneva

    2008-01-01

    Measurements of the double-differential $\\pi^{\\pm}$ production cross-section in the range of momentum $100 \\MeVc \\leq p < 800 \\MeVc$ and angle $0.35 \\rad \\leq \\theta < 2.15 \\rad$ in proton--beryllium, proton--aluminium and proton--lead collisions are presented. The data were taken with the HARP detector in the T9 beam line of the CERN PS. The pions were produced by proton beams in a momentum range from 3 \\GeVc to 12.9 \\GeVc hitting a target with a thickness of 5% of a nuclear interaction length. The tracking and identification of the produced particles was performed using a small-radius cylindrical time projection chamber (TPC) placed inside a solenoidal magnet. Incident particles were identified by an elaborate system of beam detectors. Results are obtained for the double-differential cross-sections at six incident proton beam momenta (3 \\GeVc, 5 \\GeVc, 8 \\GeVc, 8.9 \\GeVc (Be only), 12 \\GeVc and 12.9 \\GeVc (Al only)) and compared to previously available data.

  2. Beryllium ignition target design for indirect drive NIF experiments

    Science.gov (United States)

    Simakov, A. N.; Wilson, D. C.; Yi, S. A.; Kline, J. L.; Salmonson, J. D.; Clark, D. S.; Milovich, J. L.; Marinak, M. M.

    2016-03-01

    Beryllium (Be) ablator offers multiple advantages over carbon based ablators for indirectly driven NIF ICF ignition targets. These are higher mass ablation rate, ablation pressure and ablation velocity, lower capsule albedo, and higher thermal conductivity at cryogenic temperatures. Such advantages can be used to improve the target robustness and performance. While previous NIF Be target designs exist, they were obtained a long time ago and do not incorporate the latest improved physical understanding and models based upon NIF experiments. Herein, we propose a new NIF Be ignition target design at 1.45 MJ, 430 TW that takes all this knowledge into account.

  3. Breakup branches of Borromean beryllium-9

    Energy Technology Data Exchange (ETDEWEB)

    Smith, R., E-mail: r.smith.3@pgr.bham.ac.uk; Freer, M.; Wheldon, C.; Curtis, N.; Ashwood, N. I.; Barr, M.; Kokalova, Tz.; Malcolm, J. D.; Ziman, V. A. [School of Physics and Astronomy, University of Birmingham, Edgbaston, Birmingham, B15 2TT (United Kingdom); Almaraz-Calderon, S.; Aprahamian, A.; Bucher, B.; Couder, M.; Fang, X.; Jung, F.; Lu, W.; Roberts, A.; Tan, W. P. [Institute for Structure and Nuclear Astrophysics, Department of Physics, University of Notre Dame, Notre Dame, IN 46556 (United States); Copp, P.; Lesher, S. R. [Department of Physics, University of Wisconsin - La Crosse, La Crosse, WI 54601 (United States); and others

    2015-10-15

    The breakup reaction {sup 9}Be({sup 4}He, 3α)n was measured using an array of four double-sided silicon strip detectors at beam energies of 22 and 26 MeV. Excited states in {sup 9}Be up to 12 MeV were populated and reconstructed through the measurement of the charged reaction products. It is proposed that limits on the spins and parities of the states can be derived from the way that they decay. Various breakup paths for excited states in {sup 9}Be have been explored including the {sup 8}Be{sub g.s.} + n, {sup 8}Be{sub 2{sup +}} + n and {sup 5}He{sub g.s.} + {sup 4}He channels. By imposing the condition that the breakup proceeded via the {sup 8}Be ground state, clean excitation spectra for {sup 9}Be were reconstructed. The remaining two breakup channels were found to possess strongly-overlapping kinematic signatures and more sophisticated methods (referenced) are required to completely disentangle these other possibilities. Emphasis is placed on the development of the experimental analysis and the usefulness of Monte-Carlo simulations for this purpose.

  4. Metallic beryllium-7 target of small diameter

    CERN Document Server

    Zyuzin, A Yu; Vincent, J S; Buckley, K R; Bateman, N P; Snover, K A; Csandjan, J M; Steiger, T D; Adelberger, E G; Swanson, H E

    1999-01-01

    The stellar sup 7 Be(p, gamma) sup 8 B reaction rate has the largest uncertainty among all nuclear reaction rates in the standard solar model. However, the solar neutrino flux predicted for the majority of proposed and existing solar neutrino detectors is directly dependent on the rate of sup 7 Be(p, gamma) sup 8 B reaction. The existing solar neutrino detectors measure rate of sup 8 B decay neutrinos that is too low. This constitutes largely the solar neutrino problem. Existing measurements of the sup 7 Be(p, gamma) sup 8 B reaction rate disagree with one another, indicating the need for more precise experiments. To provide the required targets a new procedure for sup 7 Be production, separation and target manufacturing has been developed. First, a lithium target has been designed for sup 7 Be production at TRIUMF's 13 MeV cyclotron. The lithium target has been extensively tested at 50 mu A proton beam current yielding 8.1 MBq/mu A h of sup 7 Be. An adsorption filtration technique has been developed for sup ...

  5. Estimations of neutron yield from beryllium target irradiated by SPring-8 hard synchrotron radiation

    CERN Document Server

    Gryaznykh, D A; Plokhoi, V V

    2000-01-01

    The possibility of creating a neutron source based on ''SPring-8'' synchrotron radiation interaction with beryllium targets is discussed. The possible neutron yield is estimated to be of order 10 sup 1 sup 2 s sup - sup 1 .

  6. Target organ localization of memory CD4(+) T cells in patients with chronic beryllium disease.

    Science.gov (United States)

    Fontenot, Andrew P; Canavera, Scott J; Gharavi, Laia; Newman, Lee S; Kotzin, Brian L

    2002-11-01

    Chronic beryllium disease (CBD) is caused by exposure to beryllium in the workplace, and it remains an important public health concern. Evidence suggests that CD4(+) T cells play a critical role in the development of this disease. Using intracellular cytokine staining, we found that the frequency of beryllium-specific CD4(+) T cells in the lungs (bronchoalveolar lavage) of 12 CBD patients ranged from 1.4% to 29% (mean 17.8%), and these T cells expressed a Th1-type phenotype in response to beryllium sulfate (BeSO(4)). Few, if any, beryllium-specific CD8(+) T cells were identified. In contrast, the frequency of beryllium-responsive CD4(+) T cells in the blood of these subjects ranged from undetectable to 1 in 500. No correlation was observed between the frequency of beryllium-responsive bronchoalveolar lavage (BAL) CD4(+) T cells as detected by intracellular staining and lymphocyte proliferation in culture after BeSO(4) exposure. Staining for surface marker expression showed that nearly all BAL T cells exhibit an effector memory cell phenotype. These results demonstrate a dramatically high frequency and compartmentalization of antigen-specific effector memory CD4(+) cells in the lungs of CBD patients. These studies provide insight into the phenotypic and functional characteristics of antigen-specific T cells invading other inaccessible target organs in human disease.

  7. Measurement of neutron yield by 62 MeV proton beam on a thick Beryllium target

    CERN Document Server

    Alba, R; Boccaccio, P; Celentano, A; Colonna, N; Cosentino, G; Del Zoppo, A; Di Pietro, A; Esposito, J; Figuera, P; Finocchiaro, P; Kostyukov, A; Maiolino, C; Osipenko, M; Ricco, G; Ripani, M; Viberti, C M; Santonocito, D; Schillaci, M

    2012-01-01

    In the framework of research on IVth generation reactors and high intensity neutron sources a low-power prototype neutron amplifier was recently proposed by INFN. It is based on a low-energy, high current proton cyclotron, whose beam, impinging on a thick Beryllium converter, produces a fast neutron spectrum. The world database on the neutron yield from thick Beryllium target in the 70 MeV proton energy domain is rather scarce. The new measurement was performed at LNS, covering a wide angular range from 0 to 150 degrees and an almost complete neutron energy interval. In this contribution the preliminary data are discussed together with the proposed ADS facility.

  8. The Beryllium-10(meteoric)/ Beryllium-9 ratio as a new tracer of weathering and erosion rates

    Science.gov (United States)

    von Blanckenburg, F.; Bouchez, J.; Wittmann, H.; Dannhaus, N.

    2012-04-01

    A perfect clock of the stability of the Earth surface is one that combines a first isotope the flux of which depends on the release rate during erosion, and a second isotope produced at constant rate. The ratio of the meteoric cosmogenic nuclide 10Be to stable 9Be, suggested to serve as proxy for weathering and erosion over the late Cenozoic [1], is such a system. We provide a quantitative framework for its use. In a weathering zone some of the 9Be, present typically in 2ppm concentrations in silicate minerals, is released and partitioned between a reactive phase (adsorbed to clay and hydroxide surfaces, given the high partition coefficients at intermediate pH), and into the dissolved phase. The combined mass flux of both phases is defined by the soil formation rate and a mineral dissolution rate - and is hence proportional to the chemical weathering rate and the denudation rate. At the same time, the surface of the weathering zone is continuously exposed to fallout of meteoric 10Be. This 10Be percolates into the weathering zone where it mixes with dissolved 9Be. Both isotopes may exchange with the adsorbed Be, given that equilibration rate of Be is fast relative to soil residence times. Hence a 10Be/9Be(reactive) ratio results from which the total denudation rate can be calculated. A prerequisite is that the flux of meteoric 10Be is known from field experiments or from global production models [2]. In rivers, when reactive Be and dissolved Be equilibrate, a catchment-wide denudation rate can be determined from both sediment and a sample of filtered river water. We have tested this approach in sediment-bound Be [3] and dissolved Be in water [4] of the Amazon and Orinoco basin. The reactive Be was extracted from sediment by combined hydroxylamine and HCl leaches. In the Amazon trunk stream, the Orinoco, Apure, and La Tigra river 10Be/9Be(dissolved) agrees well with 10Be/9Be(reactive), showing that in most rivers these two phases equilibrate. 10Be/9Be ratios range

  9. Conceptual design of the beryllium rotating target for the ESS-Bilbao facility

    Energy Technology Data Exchange (ETDEWEB)

    Terrón, S., E-mail: santiago.terron@essbilbao.org [ESS-Bilbao, Parque Tecnológico Bizkaia, Laida Bidea, Edificio 207 B Planta Baja. 48160 Derio (Spain); Instituto de Fusión Nuclear - UPM, ETS Ingenieros Industriales, C José Gutiérrez Abascal, 2, 28006 Madrid (Spain); Sordo, F.; Magán, M.; Ghiglino, A.; Martínez, F.; Vicente, P.J. de; Vivanco, R. [ESS-Bilbao, Parque Tecnológico Bizkaia, Laida Bidea, Edificio 207 B Planta Baja. 48160 Derio (Spain); Instituto de Fusión Nuclear - UPM, ETS Ingenieros Industriales, C José Gutiérrez Abascal, 2, 28006 Madrid (Spain); Thomsen, K. [Paul Scherrer Institut, 5232 Villigen PSI (Switzerland); Perlado, J.M. [Instituto de Fusión Nuclear - UPM, ETS Ingenieros Industriales, C José Gutiérrez Abascal, 2, 28006 Madrid (Spain); Bermejo, F.J. [Instituto de Estructura de la Materia, IEM-CSIC, Consejo Superior de Investigaciones Científicas, Serrano 123, 28006 Madrid (Spain); ESS-Bilbao, Parque Tecnológico Bizkaia, Laida Bidea, Edificio 207 B Planta Baja. 48160 Derio (Spain); Abánades, A. [Instituto de Fusión Nuclear - UPM, ETS Ingenieros Industriales, C José Gutiérrez Abascal, 2, 28006 Madrid (Spain)

    2013-10-01

    The ESS-Bilbao facility, hosted by the University of the Basque Country (UPV/EHU), envisages the operation of a high-current proton accelerator delivering beams with energies up to 50 MeV. The time-averaged proton current will be 2.25 mA, delivered by 1.5 ms proton pulses with a repetition rate of 20 Hz. This beam will feed a neutron source based upon the Be (p,n) reaction, which will enable the provision of relevant neutron experimentation capabilities. The neutron source baseline concept consists in a rotating beryllium target cooled by water. The target structure will comprise a rotatable disk made of 6061-T6 aluminium alloy holding 20 beryllium plates. Heat dissipation from the target relies upon a distribution of coolant-flow channels. The practical implementation of such a concept is here described with emphasis put on the beryllium plates thermo-mechanical optimization, the chosen coolant distribution system as well as the mechanical behavior of the assembly. -- Highlights: • The conceptual design of ESS-Bilbao neutron production target has been carried out. • This device is a rotating disk holding Be elements cooled by water. • Thermo-mechanical and lifespan behavior of the Be elements have been analyzed. • Disk structure ensures coolability and a proper mechanical behavior of the assembly.

  10. Sub-micro level monitoring of beryllium ions with a novel beryllium sensor based on 2,6-diphenyl-4-benzo-9-crown-3-pyridine.

    Science.gov (United States)

    Ganjali, Mohammad Reza; Rahimi-Nasrabadi, Mehdi; Maddah, Bozorgmehr; Moghimi, Abolghasem; Faal-Rastegar, Madjid; Borhany, Shahin; Namazian, Mansour

    2004-07-01

    The 2,6-diphenyl-4-benzo-9-crown-3-pyridine (DPCP) was used as an excellent ionophore in construction of a coated graphite poly(vinyl chloride) (PVC)-based membrane sensor. The best performance was obtained with a membrane composition of 30% poly(vinyl chloride), 60% o-nitrophenyloctyl ether (NPOE), 5% 2,6-diphenyl-4-benzo-9-crown-3-pyridine and 5% sodium tetraphenyl borate (TBP). This sensor shows very good selectivity and sensitivity towards beryllium ion over a wide variety of cations, including alkali, alkaline earth, transition and heavy metal ions. The sensor revealed a great enhancement in selectivity coefficients and sensitivity for beryllium, in comparison with the previously reported beryllium electrodes. The electrode exhibits a Nernstian behavior (with slope of 29.6mV per decade) over a very wide concentration range (1.0x10(-7) to 1.0x10(-1)) with a detection limit of 4.0x10(-8)M (360pgml(-1)). It shows relatively fast response time, in whole concentration range (beryllium in mineral ore.

  11. Comprehensive Measurement of Neutron Yield Produced by 62 MeV Protons on Beryllium Target

    CERN Document Server

    Osipenko, M; Alba, R; Ricco, G; Schillaci, M; Barbagallo, M; Boccaccio, P; Celentano, A; Colonna, N; Cosentino, L; Del Zoppo, A; Di Pietro, A; Esposito, J; Figuera, P; Finocchiaro, P; Kostyukov, A; Maiolino, C; Santonocito, D; Scuderi, V; Viberti, C M

    2013-01-01

    A low-power prototype of neutron amplifier, based on a 70 MeV, high current proton cyclotron being installed at LNL for the SPES RIB facility, was recently proposed within INFN-E project. This prototype uses a thick Beryllium converter to produce a fast neutron spectrum feeding a sub-critical reactor core. To complete the design of such facility the new measurement of neutron yield from a thick Beryllium target was performed at LNS. This measurement used liquid scintillator detectors to identify produced neutrons by Pulse Shape Discrimination and Time of Flight technique to measure neutron energy in the range 0.5-62 MeV. To extend the covered neutron energy range He3 detector was used to measure neutrons below 0.5 MeV. The obtained yields were normalized to the charge deposited by the proton beam on the metallic Beryllium target. These techniques allowed to achieve a wide angular coverage from 0 to 150 degrees and to explore almost complete neutron energy interval.

  12. Divertor performance on carbon and beryllium targets in JET

    Energy Technology Data Exchange (ETDEWEB)

    Janeschitz, G.; Koenig, R.; Lauro-Taroni, L.; Lingertat, J.; Matthews, G.; Stamp, M.; Vlases, G.; Campbell, D.; Clement, S.; De Kock, L.; Ehrenberg, J.; Gottardi, N.; Harbour, P.; Horton, L.; Jaeckel, H.; Lesourd, M.; Loarte, A.; Lowry, C.; Saibene, G.; Summers, D.; Tagle, J.A.; Thomas, P.R.; Von Hellerman, M. (JET Joint Undertaking, Abingdon (United Kingdom)); Eckstein, W.; Roth, J. (Max Planck Inst. fuer Plasmaphysik, Garching (Germany))

    1992-12-01

    The dependence of impurity production and retention on the divertor density, on the power flow into this region as well as on the X-point to target distance are investigated. Model predictions suggest a good impurity retention above a certain divertor (scrape-off) density threshold, which is dependent on heating power. In our experiments pre-programmed midplane or X-point gas puffs were used to scan the density, as well as to avoid the depletion of particles from the divertor and the scrape-off during H-models. The gas puffs reduce T[sub e] and increase N[sub e] in particular at the outer strike zone. In general the Be as well as the C influx increases with density, which is understood from the T[sub e] (T[sub i]) dependence of the sputtering yields. The impurity retention shows the expected improvement with increasing scrape-off (divertor) density as well as with increasing X-point to target distance (connection length). (orig.).

  13. Novel potentiometric sensor for monitoring beryllium based on naphto-9-crown-3.

    Science.gov (United States)

    Ganjali, Mohammad Reza; Daftari, Azadeh; Faal-Rastegar, Majid; Moghimi, Abolghasem

    2003-03-01

    A novel poly(vinyl chloride) (PVC) membrane electrode based on naphto-9-crown-3 was prepared and tested for the selective detection of beryllium ions. A suitable lipophilicity of the carrier and appropriate coordination ability were found to be essential for designing an electrode with good response characteristics. A PVC membrane with 9% naphtho-9-crown-3 carrier, 58% o-NPOE plasticizer, 3% tetraphenylborate anionic excluder and 30% poly(vinyl chloride) satisfied these requirements. The proposed sensor displayed a linear response to beryllium over a wide concentration range of 1.0 x 10(-1)-8.0 x 10(-6) M with a Nernstian slope of 29.5 mV per decade. The electrode showed very short response time (<15 s) and could be used in the pH range 3.5-9.0. The selectivity coefficient for alkali, alkaline earth, transition and heavy metal ions was smaller than 4.0 x 10(-4). The sensor was successfully used as an indicator electrode in the potentiometric titration of Be2+ with EDTA. The proposed Be(II) sensor was also used for the determination of Be2+ ions in binary mixtures.

  14. Assessment of Personal Airborne Exposures and Surface Contamination from X-ray Vaporization of Beryllium Targets at the National Ignition Facility.

    Science.gov (United States)

    Paik, Samuel Y; Epperson, Patrick M; Kasper, Kenneth M

    2017-02-28

    This study presents air and surface sampling data collected over the first two years since beryllium was introduced as a target material at the National Ignition Facility. Over this time, 101 experiments with beryllium-containing targets were executed. The data provides an assessment of current conditions in the facility and a baseline for future impacts as new, reduced regulatory limits for beryllium are being proposed by both the Occupational Safety and Health Administration and Department of Energy. This study also investigates how beryllium deposits onto exposed surfaces as a result of x-ray vaporization and the effectiveness of simple decontamination measures in reducing the amount of removable beryllium from a surface. Based on 1,961 surface wipe samples collected from entrant components (equipment directly exposed to target debris) and their surrounding work areas during routine reconfiguration activities, only one result was above the beryllium release limit of 0.2 μg/100 cm(2) and 27 results were above the analytical reporting limit of 0.01 μg/100 cm(2), for a beryllium detection rate of 1.4%. Surface wipe samples collected from the internal walls of the NIF target chamber, however, showed higher levels of beryllium, with beryllium detected on 73% and 87% of the samples during the first and second target chamber entries (performed annually), respectively, with 23% of the samples above the beryllium release limit during the second target chamber entry. The analysis of a target chamber wall panel exposed during the first 30 beryllium-containing experiments (cumulatively) indicated that 87% of the beryllium contamination remains fixed onto the surface after wet wiping the surface and 92% of the non-fixed contamination was removed by decontaminating the surface using a dry wipe followed by a wet wipe. Personal airborne exposures assessed during access to entrant components and during target chamber entry indicated that airborne beryllium was not present

  15. Target particle and heat loads in low-triangularity L-mode plasmas in JET with carbon and beryllium/tungsten walls

    NARCIS (Netherlands)

    Groth, M.; Brezinsek, S.; Belo, P.; Corrigan, G.; Harting, D.; Wiesen, S.; Beurskens, M. N. A.; Brix, M.; Clever, M.; Coenen, J. W.; Eich, T.; Flanagan, J.; Giroud, C.; Huber, A.; Jachmich, S.; Kruezi, U.; Lehnen, M.; Lowry, C.; Maggi, C. F.; Marsen, S.; Meigs, A. G.; Sergienko, G.; Sieglin, B.; Silva, C.; Sirinelli, A.; Stamp, M. F.; van Rooij, G. J.

    2013-01-01

    Divertor radiation profiles, and power and particle fluxes to the target have been measured in attached \\{JET\\} L-mode plasmas with carbon and beryllium/tungsten wall materials. In the beryllium/tungsten configuration, factors of 2–3 higher power loads and peak temperatures at the low field side tar

  16. Thick beryllium target as an epithermal neutron source for neutron capture therapy.

    Science.gov (United States)

    Wang, C K; Moore, B R

    1994-10-01

    Accelerator-based intense epithermal neutron sources for Neutron Capture Therapy (NCT) have been considered as an alternative to nuclear reactors. Lithium (Li) has generally received the widest attention for this application, since the threshold energy is low and neutron yield is high. Because of the poor thermal and chemical properties of Li and the need for heat removal in the target, the design of Li targets has been quite difficult. Beryllium (Be) has been thought of as an alternative target because of its good thermal and chemical properties and reasonable neutron yield. However, in order to have a neutron yield comparable to that of a thick Li target bombarded with 2.5 MeV protons, the proton energy required for a thick Be target must be approaching 4 MeV. Consequently, the neutrons emitted are more energetic. In addition, a significant amount of high-energy gamma rays, which is undesirable, will occur when Be is bombarded with low-energy protons. Regardless of the more energetic neutrons and additional gamma rays, in this paper it is shown that it is possible to develop a high-quality and high-intensity epithermal neutron beam based on a thick Be target for NCT treatment. For a fixed proton current, the optimal Be-target-based beam (with 4-MeV protons) can produce a neutron beam, with both quality and intensity slightly better than those produced by the optimal Li-target-based beam (with 2.5-MeV protons). The single-session NCT treatment time for the optimal Be-target-based beam is estimated to be 88 min for a proton current of 50 mA.(ABSTRACT TRUNCATED AT 250 WORDS)

  17. Measurement of the production cross-section of positive pions in the collision of 8.9 GeV/c protons on beryllium

    CERN Document Server

    Catanesi, M G; Apollonio, M; Arce, P; Artamonov, A; Bagulya, A; Barr, G; Blondel, A; Bobisut, F; Bogomilov, M; Bonesini, M; Booth, C; Borghi, S; Bunyatov, S; Burguet-Castell, J; Buttar, C; Campanelli, M; Cervera-Villanueva, A; Chelkov, G A; Chernyaev, E; Chimenti, P; Chizhov, M; Coney, L; De Min, A; De Santo, A; Dedovitch, D; Di Capua, E; Dore, U; Dumarchez, J; Edgecock, R; Ellis, M; Engel, R; Ferri, F; Gastaldi, Ugo; Giani, S; Giannini, G; Gibin, D; Gilardoni, S; Gome-Cadenas, J J; Gorbunov, P; Gostkin, M I; Grant, A; Graulich, J S; Grichine, V; Grossheim, A; Gruber, P; Grégoire, G; Guglielmi, A M; Guskov, A; Gössling, C; Hodgson, P; Howlett, L; Ivanchenko, V; Kato, I; Kayis-Topaksu, A; Khartchenko, D; Kirsanov, M; Kolev, D; Koreshev, V; Krasnoperov, A V; Krumshtein, Z; Martín-Albo, J; Meurer, C; Mezzetto, M; Mills, G B; Morone, M C; Nefedov, Y; Novella, P; Orestano, D; Paganoni, M; Paleari, F; Palladino, V; Panman, J; Papadopoulos, I; Pasternak, J; Pastore, F; Pattison, C; Piperov, S; Polukhina, N; Popov, B; Prior, G; Radicioni, E; Robbins, S; Santin, G; Schmitz, D; Schroeter, R; Semak, A; Serdiouk, V; Soler, F J P; Sorel, M; Temnikov, P; Tereshchenko, V V; Tonazzo, A; Tornero, A; Tortora, L; Tsenov, R; Tsukerman, I; Vannucci, F; Veenhof, R; Vidal-Sitjes, G; Wiebusch, C; Zaets, V; Zhemchugov, A; Zuber, K; Zucchelli, P

    2007-01-01

    The double-differential production cross-section of positive pions, $d^2\\sigma^{\\pi^{+}}/dpd\\Omega$, measured in the HARP experiment is presented. The incident particles are 8.9 \\GeVc protons directed onto a beryllium target with a nominal thickness of 5% of a nuclear interaction length. The measured cross-section has a direct impact on the prediction of neutrino fluxes for the MiniBooNE and SciBooNE experiments at Fermilab. After cuts, 13 million protons on target produced about 96,000 reconstructable secondary tracks which were used in this analysis. Cross-section results are presented in the kinematic range 0.75~${GeV}/c$ $\\leq p_{\\pi} \\leq$ 6.5 ${GeV}/c$ and 30 mrad $\\leq \\theta_{\\pi} \\leq$ 210 mrad in the laboratory frame.

  18. Antihyperlipidemic therapies targeting PCSK9.

    Science.gov (United States)

    Weinreich, Michael; Frishman, William H

    2014-01-01

    Hyperlipidemia is a major cause of cardiovascular disease despite the availability of first-line cholesterol-lowering agents such as statins. A new therapeutic approach to lowering low-density lipoprotein-cholesterol (LDL-C) acts by blocking LDL-receptor degradation by serum proprotein convertase subtilisin kexin 9 (PCSK9). Human monoclonal antibodies that target PCSK9 and its interaction with the LDL receptor are now in clinical trials (REGN727/SAR23653, AMG145, and RN316). These agents are administered by either subcutaneous or intravenous routes, and have been shown to have major LDL-C and apolipoprotein B effects when combined with statins. A phase III clinical trial program evaluating clinical endpoints is now in progress. Other PCSK9-targeted approaches are in early stages of investigation, including natural inhibitors of PCSK9, RNA interference, and antisense inhibitors.

  19. Beryllium Desorption from Sediments

    Science.gov (United States)

    Boschi, V.; Willenbring, J. K.

    2015-12-01

    Beryllium isotopes have provided a useful tool in the field of geochronology and geomorphology over the last 25 years. The amount of cosmogenic meteoric 10Be and native 9Be absorbed to soils often scales with the residence time and chemical weathering of sediments in a landscape, respectively. Thus, the concentrations in river sediment may be used to quantify the denudation of specific watersheds. When deposited in ocean sediment, these concentrations are thought to record the history of denudation on Earth over the last ~10 Ma. The use of both isotopes often relies on the premise of beryllium retention to sediment surfaces in order to preserve a landscape's erosion and weathering signature. Changes in setting, en route from the soil to fluvial system to the ocean, can cause beryllium desorption and may preclude some applications of the 10Be/9Be system. Four mechanisms were tested to determine the desorption potential of beryllium including a reduction in pH, an increase in ionic strength and complexation with soluble organic and inorganic species. These processes have the potential to mobilize beryllium into solution. For example, by both reducing the pH and increasing the ionic strength, competition for adsorption sites increases, potentially liberating beryllium from the sediment surface. In addition, organic and inorganic ligands can complex beryllium causing it to become mobilized. To determine which of these alterations influence beryllium desorption and to quantify the effect, we prepared separate solutions of beryllium bound to minerals and organic compounds and measured beryllium concentrations in solution before and after adjusting the pH, ionic strength, and changing inorganic and organic ligand concentrations. We conclude from our observations that overall, beryllium sorbed to organic compounds was more resistant to desorption relative to mineral-associated beryllium. Among the methods tested, a reduction in pH resulted in the greatest amount of

  20. Beryllium 1989

    Energy Technology Data Exchange (ETDEWEB)

    1989-01-01

    The Roskill report on beryllium gives information on the occurrence and reserves, production technology, geographic distribution, consumption and end-uses, stocks, prices and beryllium and health. There is an appendix on international trade statistics. (author).

  1. Target particle and heat loads in low-triangularity L-mode plasmas in JET with carbon and beryllium/tungsten walls

    Energy Technology Data Exchange (ETDEWEB)

    Groth, M., E-mail: mathias.groth@aalto.fi [Aalto University, Association EURATOM-Tekes, Espoo (Finland); Brezinsek, S. [Institute for Energy and Climate Research, Association EURATOM-FZJ Jülich (Germany); Belo, P. [Institute of Plasmas and Nuclear Fusion, Association EURATOM-IST, Lisbon (Portugal); Corrigan, G. [Culham Centre of Fusion Energy, EURATOM-Association, Culham Science Centre, Abingdon (United Kingdom); Harting, D.; Wiesen, S. [Institute for Energy and Climate Research, Association EURATOM-FZJ Jülich (Germany); Beurskens, M.N.A.; Brix, M. [Culham Centre of Fusion Energy, EURATOM-Association, Culham Science Centre, Abingdon (United Kingdom); Clever, M.; Coenen, J.W. [Institute for Energy and Climate Research, Association EURATOM-FZJ Jülich (Germany); Eich, T. [Max-Planck Institute for Plasma Physics, EURATOM-Association, Garching (Germany); Flanagan, J.; Giroud, C. [Culham Centre of Fusion Energy, EURATOM-Association, Culham Science Centre, Abingdon (United Kingdom); Huber, A. [Institute for Energy and Climate Research, Association EURATOM-FZJ Jülich (Germany); Jachmich, S. [Association “EURATOM Belgium State”, Laboratory for Plasma Physics, Brussels (Belgium); Kruezi, U.; Lehnen, M. [Institute for Energy and Climate Research, Association EURATOM-FZJ Jülich (Germany); Lowry, C. [EFDA Close Support Unit, Culham Science Centre, Abingdon (United Kingdom); Maggi, C.F. [Max-Planck Institute for Plasma Physics, EURATOM-Association, Garching (Germany); Marsen, S. [Max-Planck-Institut for Plasma Physics, EURATOM-Association, Greifswald (Germany); and others

    2013-07-15

    Divertor radiation profiles, and power and particle fluxes to the target have been measured in attached JET L-mode plasmas with carbon and beryllium/tungsten wall materials. In the beryllium/tungsten configuration, factors of 2–3 higher power loads and peak temperatures at the low field side target were observed in high-recycling scrape-off layer conditions, whilst in close-to-sheath-limited conditions almost identical plasmas were obtained. The 30% reduction in total radiation with the beryllium/tungsten wall is consistent with a reduction of carbon as the dominant impurity radiator; however similar ion current to the plates, emission from recycling neutrals and neutral pressures in the pumping plenum were measured. Simulations with the EDGDE2/EIRENE code of these plasmas indicate a reduction of the total divertor radiation when carbon is omitted, but significantly higher power loads in high-recycling and detached conditions are predicted than measured.

  2. Chronic Beryllium Disease

    Science.gov (United States)

    ... Science Education & Training Home Conditions Chronic Beryllium Disease Chronic Beryllium Disease Make an Appointment Find a Doctor ... MD, MSPH, FCCP (February 01, 2016) What is chronic beryllium disease (CBD)? Chronic beryllium disease (CBD) is ...

  3. Estimations and integral measurements for the spectral yield of neutrons from thick beryllium target bombarded with 16 MeV protons

    CERN Document Server

    Fenyvesi, A

    2015-01-01

    Spectral yield of p+Be neutrons emitted by thick (stopping) beryllium target bombarded by 16 MeV protons was estimated via extrapolation of literature data. The spectrum was validated via multi-foil activation method and irradiation of 2N2222 transistors. The hardness parameter (NIEL scaling factor) for displacement damage in bulk silicon was calculated and measured and kappa = 1.26 +- 0.1 was obtained.

  4. First shock tuning and backscatter measurements for large case-to-capsule ratio beryllium targets

    Science.gov (United States)

    Loomis, Eric; Yi, Austin; Kline, John; Kyrala, George; Simakov, Andrei; Wilson, Doug; Ralph, Joe; Dewald, Eduard; Strozzi, David; Celliers, Peter; Millot, Marius; Tommasini, Riccardo

    2016-10-01

    The current under performance of target implosions on the National Ignition Facility (NIF) has necessitated scaling back from high convergence ratio to access regimes of reduced physics uncertainties. These regimes, we expect, are more predictable by existing radiation hydrodynamics codes giving us a better starting point for isolating key physics questions. One key question is the lack of predictable in-flight and hot spot shape due to a complex hohlraum radiation environment. To achieve more predictable, shape tunable implosions we have designed and fielded a large 4.2 case-to-capsule ratio (CCR) target at the NIF using 6.72 mm diameter Au hohlraums and 1.6 mm diameter Cu-doped Be capsules. Simulations show that at these dimensions during a 10 ns 3-shock laser pulse reaching 270 eV hohlraum temperatures, the interaction between hohlraum and capsule plasma, which at lower CCR lead to beam propagation impedance by artificial plasma stagnation, are reduced. In this talk we will present measurements of early time drive symmetry using two-axis line-imaging velocimetry (VISAR) and streaked radiography measuring velocity of the imploding shell and their comparisons to post-shot calculations using the code HYDRA (Lawrence Livermore National Laboratory).

  5. Experimental bremsstrahlung yields for MeV proton bombardment of beryllium and carbon

    Energy Technology Data Exchange (ETDEWEB)

    Cohen, David D. [Institute for Environmental Research, Australian Nuclear Science and Technology Organisation, Private Mail Bag 1, Menai, NSW 2234 (Australia)], E-mail: dcz@ansto.gov.au; Stelcer, Eduard; Siegele, Rainer; Ionescu, Mihail; Prior, Michael [Institute for Environmental Research, Australian Nuclear Science and Technology Organisation, Private Mail Bag 1, Menai, NSW 2234 (Australia)

    2008-04-15

    Experimental bremsstrahlung yields for 2, 3 and 4 MeV protons on thin beryllium and carbon targets have been measured. The yields have been corrected for detector efficiency, self-absorption in the target and fitted to 9th order polynomials over the X-ray energy range 1-10 keV for easy comparison with theoretical calculations.

  6. Measurement of Beryllium in Biological Samples by Accelerator Mass Spectrometry: Applications for Studying Chronic Beryllium Disease

    Energy Technology Data Exchange (ETDEWEB)

    Chiarappa-Zucca, M L; Finkel, R C; Martinelli, R E; McAninch, J E; Nelson, D O; Turtletaub, K W

    2004-04-15

    A method using accelerator mass spectrometry (AMS) has been developed for quantifying attomoles of beryllium (Be) in biological samples. This method provides the sensitivity to trace Be in biological samples at very low doses with the purpose of identifying the molecular targets involved in chronic beryllium disease. Proof of the method was tested by administering 0.001, 0.05, 0.5 and 5.0 {micro}g {sup 9}Be and {sup 10}Be by intraperitoneal injection to male mice and removing spleen, liver, femurs, blood, lung, and kidneys after 24 h exposure. These samples were prepared for AMS analysis by tissue digestion in nitric acid, followed by further organic oxidation with hydrogen peroxide and ammonium persulfate and lastly, precipitation of Be with ammonium hydroxide, and conversion to beryllium oxide at 800 C. The {sup 10}Be/{sup 9}Be ratio of the extracted beryllium oxide was measured by AMS and Be in the original sample was calculated. Results indicate that Be levels were dose-dependent in all tissues and the highest levels were measured in the spleen and liver. The measured {sup 10}Be/{sup 9}Be ratios spanned 4 orders of magnitude, from 10{sup -10} to 10{sup -14}, with a detection limit of 3.0 x 10{sup -14}, which is equivalent to 0.8 attomoles of {sup 10}Be. These results show that routine quantification of nanogram levels of Be in tissues is possible and that AMS is a sensitive method that can be used in biological studies to understand the molecular dosimetry of Be and mechanisms of toxicity.

  7. Efficacy of serial medical surveillance for chronic beryllium disease in a beryllium machining plant.

    Science.gov (United States)

    Newman, L S; Mroz, M M; Maier, L A; Daniloff, E M; Balkissoon, R

    2001-03-01

    There is limited information on the use of the blood beryllium lymphocyte proliferation test (BeLPT) at regular intervals in medical surveillance. Employees of a beryllium machining plant were screened with the BeLPT biennially, and new employees were screened within 3 months of hire. Of 235 employees screened from 1995 to 1997, a total of 15 (6.4%) had confirmed abnormal BeLPT results indicating beryllium sensitization; nine of these employees were diagnosed with chronic beryllium disease. Four of the 15 cases were diagnosed within 3 months of first exposure. When 187 of the 235 employees participated in biennial screening in 1997 to 1999, seven more had developed beryllium sensitization or chronic beryllium disease, increasing the overall rate to 9.4% (22 of 235). The blood BeLPT should be used serially in beryllium disease surveillance to capture new or missed cases of sensitization and disease. Beryllium sensitization and chronic beryllium disease can occur within 50 days of first exposure in modern industry.

  8. Beryllium chemistry and processing

    CERN Document Server

    Walsh, Kenneth A

    2009-01-01

    This book introduces beryllium; its history, its chemical, mechanical, and physical properties including nuclear properties. The 29 chapters include the mineralogy of beryllium and the preferred global sources of ore bodies. The identification and specifics of the industrial metallurgical processes used to form oxide from the ore and then metal from the oxide are thoroughly described. The special features of beryllium chemistry are introduced, including analytical chemical practices. Beryllium compounds of industrial interest are identified and discussed. Alloying, casting, powder processing, forming, metal removal, joining and other manufacturing processes are covered. The effect of composition and process on the mechanical and physical properties of beryllium alloys assists the reader in material selection. The physical metallurgy chapter brings conformity between chemical and physical metallurgical processing of beryllium, metal, alloys, and compounds. The environmental degradation of beryllium and its all...

  9. An industrial risk: Beryllium

    Directory of Open Access Journals (Sweden)

    Emrah Çaylak

    2012-03-01

    Full Text Available Beryllium is a vocational disease factor and berylliumexposure can potentially lead to Chronic Beryllium Disease(CBD in 2-6 % of workers. While acute lymphocyticpneumonia occurred in individuals who were exposedto high doses of beryllium, low dose exposure to berylliumfollowed by a long subclinical period can cause CBDcharacterized with chronic granulomatosis. It has beenobserved that varying amounts of beryllium exposureare necessary to produce symptoms of CBD or berylliumsensitization (BeS. Genetic differences between patientsmay be the underlying cause of these dose-effects andfurther study of the differences in patients exposed to berylliummay lead to earlier diagnosis and the identificationof biomarkers of CBD. In this review, it is summarizedthe general properties of beryllium exposure, the immunopathogenesisand genetic differences of beryllium-induceddiseases, genotoxicity and the carcinogenic effectsof beryllium. J Clin Exp Invest 2012; 3(1: 141-148

  10. (Beryllium). Internal Report No. 137, Jan. 15, 1958; Le beryllium

    Energy Technology Data Exchange (ETDEWEB)

    Mouret, P.; Rigaud, A

    1959-07-01

    After a brief summary of the physical and chemical properties of beryllium, the various chemical treatments which can be applied to beryllium minerals either directly or after a physical enrichment are discussed. These various treatments give either the hydroxide or beryllium salts, from which either beryllium oxide or metallic beryllium can easily be obtained. The purification, analysis and uses of beryllium are also briefly discussed. (author)

  11. Beryllium: genotoxicity and carcinogenicity.

    Science.gov (United States)

    Gordon, Terry; Bowser, Darlene

    2003-12-10

    Beryllium (Be) has physical-chemical properties, including low density and high tensile strength, which make it useful in the manufacture of products ranging from space shuttles to golf clubs. Despite its utility, a number of standard setting agencies have determined that beryllium is a carcinogen. Only a limited number of studies, however, have addressed the underlying mechanisms of the carcinogenicity and mutagenicity of beryllium. Importantly, mutation and chromosomal aberration assays have yielded somewhat contradictory results for beryllium compounds and whereas bacterial tests were largely negative, mammalian test systems showed evidence of beryllium-induced mutations, chromosomal aberrations, and cell transformation. Although inter-laboratory differences may play a role in the variability observed in genotoxicity assays, it is more likely that the different chemical forms of beryllium have a significant effect on mutagenicity and carcinogenicity. Because workers are predominantly exposed to airborne particles which are generated during the machining of beryllium metal, ceramics, or alloys, testing of the mechanisms of the mutagenic and carcinogenic activity of beryllium should be performed with relevant chemical forms of beryllium.

  12. Characterization of the energy distribution of neutrons generated by 5 MeV protons on a thick beryllium target at different emission angles

    Energy Technology Data Exchange (ETDEWEB)

    Agosteo, S. [Politecnico di Milano, Dipartimento di Energia, Piazza Leonardo da Vinci 32, 20133 Milano (Italy)] [Istituto Nazionale di Fisica Nucleare, Sezione di Milano, via Celoria 16, 20133 Milano (Italy); Colautti, P., E-mail: paolo.colautti@lnl.infn.it [INFN, Laboratori Nazionali di Legnaro (LNL), Via dell' Universita, 2, I-35020 Legnaro (PD) (Italy); Esposito, J., E-mail: juan.esposito@tin.it [INFN, Laboratori Nazionali di Legnaro (LNL), Via dell' Universita, 2, I-35020 Legnaro (PD) (Italy); Fazzi, A.; Introini, M.V.; Pola, A. [Politecnico di Milano, Dipartimento di Energia, Piazza Leonardo da Vinci 32, 20133 Milano (Italy)] [Istituto Nazionale di Fisica Nucleare, Sezione di Milano, via Celoria 16, 20133 Milano (Italy)

    2011-12-15

    Neutron energy spectra at different emission angles, between 0 Degree-Sign and 120 Degree-Sign from the Be(p,xn) reaction generated by a beryllium thick-target bombarded with 5 MeV protons, have been measured at the Legnaro Laboratories (LNL) of the Italian National Institute for Nuclear Physics research (INFN). A new and quite compact recoil-proton spectrometer, based on a monolithic silicon telescope, coupled to a polyethylene converter, was efficiently used with respect to the traditional Time-of-Flight (TOF) technique. The measured distributions of recoil-protons were processed through an iterative unfolding algorithm in order to determine the neutron energy spectra at all the angles accounted for. The neutron energy spectrum measured at 0 Degree-Sign resulted to be in good agreement with the only one so far available at the requested energy and measured years ago with TOF technique. Moreover, the results obtained at different emission angles resulted to be consistent with detailed past measurements performed at 4 MeV protons at the same angles by TOF techniques.

  13. X-ray drive of beryllium capsule implosions at the National Ignition Facility

    Science.gov (United States)

    Wilson, D. C.; Yi, S. A.; Simakov, A. N.; Kline, J. L.; Kyrala, G. A.; Dewald, E. L.; Tommasini, R.; Ralph, J. E.; Olson, R. E.; Strozzi, D. J.; Celliers, P. M.; Schneider, M. B.; MacPhee, A. G.; Zylstra, A. B.; Callahan, D. A.; Hurricane, O. A.; Milovich, J. L.; Hinkel, D. E.; Rygg, J. R.; Rinderknecht, H. G.; Sio, H.; Perry, T. S.; Batha, S.

    2016-05-01

    National Ignition Facility experiments with beryllium capsules have followed a path begun with “high-foot” plastic capsule implosions. Three shock timing keyhole targets, one symmetry capsule, a streaked backlit capsule, and a 2D backlit capsule were fielded before the DT layered shot. After backscatter subtraction, laser drive degradation is needed to match observed X-ray drives. VISAR measurements determined drive degradation for the picket, trough, and second pulse. Time dependence of the total Dante flux reflects degradation of the of the third laser pulse. The same drive degradation that matches Dante data for three beryllium shots matches Dante and bangtimes for plastic shots N130501 and N130812. In the picket of both Be and CH hohlraums, calculations over-estimate the x-ray flux > 1.8 keV by ∼100X, while calculating the total flux correctly. In beryllium calculations these X-rays cause an early expansion of the beryllium/fuel interface at ∼3 km/s. VISAR measurements gave only ∼0.3 km/s. The X-ray drive on the Be DT capsule was further degraded by an unplanned decrease of 9% in the total picket flux. This small change caused the fuel adiabat to rise from 1.8 to 2.3. The first NIF beryllium DT implosion achieved 29% of calculated yield, compared to CH capsules with 68% and 21%.

  14. Performance of Beryllium Targets with Full-scale Capsules in Low-fill 6.72-mm Hohlraums on the National Ignition Facility

    Science.gov (United States)

    Simakov, A. N.; Yi, S. A.; Kline, J. L.; Kyrala, G. A.; Loomis, E. N.; Wilson, D. C.; Perry, T. S.; Batha, S. H.; Dewald, E. L.; Ralph, J. E.; Strozzi, D. J.

    2016-10-01

    When used with full-size beryllium (Be) capsules, high-fill 5.75-mm hohlraums exhibit significant drive degradation via laser backscatter and ``missing energy''. Also, hard to simulate cross-beam energy transfer (CBET) must be used to control the implosion symmetry. Low-fill (<=0.6 mg/cm3) 6.72-mm hohlraums offer improved drive efficiency and the symmetry tunability without the CBET. In FY16, we carried out an exploratory campaign to evaluate performance of full-size Be capsules in such hohlraums. Specifically, we have performed a fill-density scan with a three-shock, 9.5-ns pulse and found that an appropriate laser beam repointing and outer-quad splitting results in approximately 5% laser backscatter at fill densities <=0.3 mg/cm3, with the implosion becoming less oblate as the fill-density decreases. We also plan to perform an implosion with a lower-foot, 12.6-ns pulse, to observe a more prolate symmetry. Work supported by the US Department of Energy.

  15. Beryllium concentration in pharyngeal tonsils in children.

    Science.gov (United States)

    Nogaj, Ewa; Kwapulinski, Jerzy; Misiołek, Maciej; Golusiński, Wojciech; Kowol, Jolanta; Wiechuła, Danuta

    2014-01-01

    Power plant dust is believed to be the main source of the increased presence of the element beryllium in the environment which has been detected in the atmospheric air, surface waters, groundwater, soil, food, and cigarette smoke. In humans, beryllium absorption occurs mainly via the respiratory system. The pharyngeal tonsils are located on the roof of the nasopharynx and are in direct contact with dust particles in inhaled air. As a result, the concentration levels of beryllium in the pharyngeal tonsils are likely to be a good indicator of concentration levels in the air. The presented study had two primary aims: to investigate the beryllium concentration in pharyngeal tonsils in children living in southern Poland, and the appropriate reference range for this element in children's pharyngeal tonsils. Pharyngeal tonsils were extracted from a total of 379 children (age 2-17 years, mean 6.2 ± 2.7 years) living in southern Poland. Tonsil samples were mineralized in a closed cycle in a pressure mineralizer PDS 6, using 65% spectrally pure nitric acid. Beryllium concentration was determined using the ICP-AES method with a Perkin Elmer Optima 5300DVTM. The software Statistica v. 9 was used for the statistical analysis. It was found that girls had a significantly greater beryllium concentration in their pharyngeal tonsils than boys. Beryllium concentration varies greatly, mostly according to the place of residence. Based on the study results, the reference value for beryllium in pharyngeal tonsils of children is recommended to be determined at 0.02-0.04 µg/g.

  16. Beryllium concentration in pharyngeal tonsils in children

    Directory of Open Access Journals (Sweden)

    Ewa Nogaj

    2014-06-01

    Full Text Available Power plant dust is believed to be the main source of the increased presence of the element beryllium in the environment which has been detected in the atmospheric air, surface waters, groundwater, soil, food, and cigarette smoke. In humans, beryllium absorption occurs mainly via the respiratory system. The pharyngeal tonsils are located on the roof of the nasopharynx and are in direct contact with dust particles in inhaled air. As a result, the concentration levels of beryllium in the pharyngeal tonsils are likely to be a good indicator of concentration levels in the air. The presented study had two primary aims: to investigate the beryllium concentration in pharyngeal tonsils in children living in southern Poland, and the appropriate reference range for this element in children’s pharyngeal tonsils. Pharyngeal tonsils were extracted from a total of 379 children (age 2–17 years, mean 6.2 ± 2.7 years living in southern Poland. Tonsil samples were mineralized in a closed cycle in a pressure mineralizer PDS 6, using 65% spectrally pure nitric acid. Beryllium concentration was determined using the ICP-AES method with a Perkin Elmer Optima 5300DVTM. The software Statistica v. 9 was used for the statistical analysis. It was found that girls had a significantly greater beryllium concentration in their pharyngeal tonsils than boys. Beryllium concentration varies greatly, mostly according to the place of residence. Based on the study results, the reference value for beryllium in pharyngeal tonsils of children is recommended to be determined at 0.02–0.04 µg/g.

  17. Characteristics of beryllium exposure to small particles at a beryllium production facility.

    Science.gov (United States)

    Virji, M Abbas; Stefaniak, Aleksandr B; Day, Gregory A; Stanton, Marcia L; Kent, Michael S; Kreiss, Kathleen; Schuler, Christine R

    2011-01-01

    Epidemiological studies have reported process-specific elevated prevalence of beryllium sensitization (BeS) and chronic beryllium disease (CBD) among workers. However, exposure-response relationships have been inconsistent, possibly due to incomplete characterization of many biologically relevant aspects of exposure, including particle size. In 1999, two surveys were conducted 3-5 months apart at a beryllium metal, oxide, and alloy production facility during which personal impactor samples (n = 198) and personal 37-mm closed-face cassette (CFC) 'total' samples (n = 4026) were collected. Among process areas, median particle mass median aerodynamic diameter ranged from 5 to 14 μm. A large fraction of the beryllium aerosol was in the nonrespirable size range. Respirable beryllium concentrations were among the highest for oxide production [geometric mean (GM) = 2.02 μg m⁻³, geometric standard deviation (GSD) = 1.3] and pebbles plant (GM = 1.05 μg m⁻³, GSD = 2.9), areas historically associated with high risk of BeS and CBD. The relationship between GM 'CFC total' and GM respirable beryllium for jobs varied by process areas; the rank order of the jobs showed high overall consistency (Spearman r = 0.84), but the overall correlation was moderate (Pearson r = 0.43). Total beryllium concentrations varied greatly within and between workers among process areas; within-worker variance was larger than between-worker variance for most processes. A review of exposure characteristics among process areas revealed variation in chemical forms and solubility. Process areas with high risk of BeS and CBD had exposure to both soluble and insoluble forms of beryllium. Consideration of biologically relevant aspects of exposure such as beryllium particle size distribution, chemical form, and solubility will likely improve exposure assessment.

  18. Target specificity of the CRISPR-Cas9 system

    OpenAIRE

    Wu, Xuebing; Kriz, Andrea J.; Sharp, Phillip A.

    2014-01-01

    The CRISPR-Cas9 system, naturally a defense mechanism in prokaryotes, has been repurposed as an RNA-guided DNA targeting platform. It has been widely used for genome editing and transcriptome modulation, and has shown great promise in correcting mutations in human genetic diseases. Off-target effects are a critical issue for all of these applications. Here we review the current status on the target specificity of the CRISPR-Cas9 system.

  19. Cooperativity in beryllium bonds.

    Science.gov (United States)

    Alkorta, Ibon; Elguero, José; Yáñez, Manuel; Mó, Otilia

    2014-03-07

    A theoretical study of the beryllium bonded clusters of the (iminomethyl)beryllium hydride and (iminomethyl)beryllium fluoride [HC(BeX)=NH, X = H, F] molecules has been carried out at the B3LYP/6-311++G(3df,2p) level of theory. Linear and cyclic clusters have been characterized up to the decamer. The geometric, energetic, electronic and NMR properties of the clusters clearly indicate positive cooperativity. The evolution of the molecular properties, as the size of the cluster increases, is similar to those reported in polymers held together by hydrogen bonds.

  20. Beryllium Manufacturing Processes

    Energy Technology Data Exchange (ETDEWEB)

    Goldberg, A

    2006-06-30

    This report is one of a number of reports that will be combined into a handbook on beryllium. Each report covers a specific topic. To-date, the following reports have been published: (1) Consolidation and Grades of Beryllium; (2) Mechanical Properties of Beryllium and the Factors Affecting these Properties; (3) Corrosion and Corrosion Protection of Beryllium; (4) Joining of Beryllium; (5) Atomic, Crystal, Elastic, Thermal, Nuclear, and other Properties of Beryllium; and (6) Beryllium Coating (Deposition) Processes and the Influence of Processing Parameters on Properties and Microstructure. The conventional method of using ingot-cast material is unsuitable for manufacturing a beryllium product. Beryllium is a highly reactive metal with a high melting point, making it susceptible to react with mold-wall materials forming beryllium compounds (BeO, etc.) that become entrapped in the solidified metal. In addition, the grain size is excessively large, being 50 to 100 {micro}m in diameter, while grain sizes of 15 {micro}m or less are required to meet acceptable strength and ductility requirements. Attempts at refining the as-cast-grain size have been unsuccessful. Because of the large grain size and limited slip systems, the casting will invariably crack during a hot-working step, which is an important step in the microstructural-refining process. The high reactivity of beryllium together with its high viscosity (even with substantial superheat) also makes it an unsuitable candidate for precision casting. In order to overcome these problems, alternative methods have been developed for the manufacturing of beryllium. The vast majority of these methods involve the use of beryllium powders. The powders are consolidated under pressure in vacuum at an elevated temperature to produce vacuum hot-pressed (VHP) blocks and vacuum hot-isostatic-pressed (HIP) forms and billets. The blocks (typically cylindrical), which are produced over a wide range of sizes (up to 183 cm dia. by 61

  1. Beryllium toxicity testing in the suspension culture of mouse fibroblasts.

    Science.gov (United States)

    Rössner, P; Bencko, V

    1980-01-01

    Suspension culture of mouse fibroblast cell line L-A 115 was used to test beryllium toxicity in the presence of magnesium ions. Beryllium added to the MEM cultivation medium was bound in a complex with sulphosalicylic acid BeSSA complex, because the use of beryllium chloride turned out to yield ineffective beryllium phosphate that formed macroscopically detectable insoluble opacities. The BeSSA complex was used in the concentration range: 10(-3)--10(-9)M, magnesium was used in 3 concentrations: 10(-1)M, 5 x 10(-2)M and 10(-2)M. Growth curve analysis revealed pronounced beryllium toxicity at the concentration of 10(-3)M, magnesium-produced toxic changes were observed only at the concentration of 10(-1)M. No competition between the beryllium and magnesium ions was recorded. It is assumed that the possible beryllium-magnesium competition was significantly modified by the use of BeSSA complex-bound beryllium.

  2. Intravascular AAV9 preferentially targets neonatal neurons and adult astrocytes.

    Science.gov (United States)

    Foust, Kevin D; Nurre, Emily; Montgomery, Chrystal L; Hernandez, Anna; Chan, Curtis M; Kaspar, Brian K

    2009-01-01

    Delivery of genes to the brain and spinal cord across the blood-brain barrier (BBB) has not yet been achieved. Here we show that adeno-associated virus (AAV) 9 injected intravenously bypasses the BBB and efficiently targets cells of the central nervous system (CNS). Injection of AAV9-GFP into neonatal mice through the facial vein results in extensive transduction of dorsal root ganglia and motor neurons throughout the spinal cord and widespread transduction of neurons throughout the brain, including the neocortex, hippocampus and cerebellum. In adult mice, tail vein injection of AAV9-GFP leads to robust transduction of astrocytes throughout the entire CNS, with limited neuronal transduction. This approach may enable the development of gene therapies for a range of neurodegenerative diseases, such as spinal muscular atrophy, through targeting of motor neurons, and amyotrophic lateral sclerosis, through targeting of astrocytes. It may also be useful for rapid postnatal genetic manipulations in basic neuroscience studies.

  3. MicroRNA-9 controls dendritic development by targeting REST

    Science.gov (United States)

    Giusti, Sebastian A; Vogl, Annette M; Brockmann, Marisa M; Vercelli, Claudia A; Rein, Martin L; Trümbach, Dietrich; Wurst, Wolfgang; Cazalla, Demian; Stein, Valentin; Deussing, Jan M; Refojo, Damian

    2014-01-01

    MicroRNAs (miRNAs) are conserved noncoding RNAs that function as posttranscriptional regulators of gene expression. miR-9 is one of the most abundant miRNAs in the brain. Although the function of miR-9 has been well characterized in neural progenitors, its role in dendritic and synaptic development remains largely unknown. In order to target miR-9 in vivo, we developed a transgenic miRNA sponge mouse line allowing conditional inactivation of the miR-9 family in a spatio-temporal-controlled manner. Using this novel approach, we found that miR-9 controls dendritic growth and synaptic transmission in vivo. Furthermore, we demonstrate that miR-9-mediated downregulation of the transcriptional repressor REST is essential for proper dendritic growth. DOI: http://dx.doi.org/10.7554/eLife.02755.001 PMID:25406064

  4. Quantum molecular dynamics simulations of beryllium at high pressures

    Science.gov (United States)

    Desjarlais, Michael; Knudson, Marcus

    2008-03-01

    The phase boundaries and high pressure melt properties of beryllium have been the subject of several recent experimental and theoretical studies. The interest is motivated in part by the use of beryllium as an ablator material in inertial confinement fusion capsule designs. In this work, the high pressure melt curve, Hugoniot crossings, sound speeds, and phase boundaries of beryllium are explored with DFT based quantum molecular dynamics calculations. The entropy differences between the various phases of beryllium are extracted in the vicinity of the melt curve and agree favorably with earlier theoretical work on normal melting. High velocity flyer plate experiments with beryllium targets on Sandia's Z machine have generated high quality data for the Hugoniot, bulk sound speeds, and longitudinal sound speeds. This data provides a tight constraint on the pressure for the onset of shock melting of beryllium and intriguing information on the solid phase prior to melt. The results of the QMD calculations and the experimental results will be compared, and implications for the HCP and BCC phase boundaries of beryllium will be presented.

  5. CRISPR/Cas9-mediated targeted mutagenesis in Nicotiana tabacum.

    Science.gov (United States)

    Gao, Junping; Wang, Genhong; Ma, Sanyuan; Xie, Xiaodong; Wu, Xiangwei; Zhang, Xingtan; Wu, Yuqian; Zhao, Ping; Xia, Qingyou

    2015-01-01

    Genome editing is one of the most powerful tools for revealing gene function and improving crop plants. Recently, RNA-guided genome editing using the type II clustered regularly interspaced short palindromic repeats (CRISPR)-associated protein (Cas) system has been used as a powerful and efficient tool for genome editing in various organisms. Here, we report genome editing in tobacco (Nicotiana tabacum) mediated by the CRISPR/Cas9 system. Two genes, NtPDS and NtPDR6, were used for targeted mutagenesis. First, we examined the transient genome editing activity of this system in tobacco protoplasts, insertion and deletion (indel) mutations were observed with frequencies of 16.2-20.3% after transfecting guide RNA (gRNA) and the nuclease Cas9 in tobacco protoplasts. The two genes were also mutated using multiplexing gRNA at a time. Additionally, targeted deletions and inversions of a 1.8-kb fragment between two target sites in the NtPDS locus were demonstrated, while indel mutations were also detected at both the sites. Second, we obtained transgenic tobacco plants with NtPDS and NtPDR6 mutations induced by Cas9/gRNA. The mutation percentage was 81.8% for NtPDS gRNA4 and 87.5% for NtPDR6 gRNA2. Obvious phenotypes were observed, etiolated leaves for the psd mutant and more branches for the pdr6 mutant, indicating that highly efficient biallelic mutations occurred in both transgenic lines. No significant off-target mutations were obtained. Our results show that the CRISPR/Cas9 system is a useful tool for targeted mutagenesis of the tobacco genome.

  6. Reprocessing technology development for irradiated beryllium

    Energy Technology Data Exchange (ETDEWEB)

    Kawamura, H.; Sakamoto, N. [Oarai Research Establishment, Ibaraki-ken (Japan); Tatenuma, K. [KAKEN Co., Ibaraki-ken (Japan)] [and others

    1995-09-01

    At present, beryllium is under consideration as a main candidate material for neutron multiplier and plasma facing material in a fusion reactor. Therefore, it is necessary to develop the beryllium reprocessing technology for effective resource use. And, we have proposed reprocessing technology development on irradiated beryllium used in a fusion reactor. The preliminary reprocessing tests were performed using un-irradiated and irradiated beryllium. At first, we performed beryllium separation tests using un-irradiated beryllium specimens. Un-irradiated beryllium with beryllium oxide which is a main impurity and some other impurities were heat-treated under chlorine gas flow diluted with Ar gas. As the results high purity beryllium chloride was obtained in high yield. And it appeared that beryllium oxide and some other impurities were removed as the unreactive matter, and the other chloride impurities were separated by the difference of sublimation temperature on beryllium chloride. Next, we performed some kinds of beryllium purification tests from beryllium chloride. And, metallic beryllium could be recovered from beryllium chloride by the reduction with dry process. In addition, as the results of separation and purification tests using irradiated beryllium specimens, it appeared that separation efficiency of Co-60 from beryllium was above 96%. It is considered that about 4% Co-60 was carried from irradiated beryllium specimen in the form of cobalt chloride. And removal efficiency of tritium from irradiated beryllium was above 95%.

  7. Aerosols generated during beryllium machining.

    Science.gov (United States)

    Martyny, J W; Hoover, M D; Mroz, M M; Ellis, K; Maier, L A; Sheff, K L; Newman, L S

    2000-01-01

    Some beryllium processes, especially machining, are associated with an increased risk of beryllium sensitization and disease. Little is known about exposure characteristics contributing to risk, such as particle size. This study examined the characteristics of beryllium machining exposures under actual working conditions. Stationary samples, using eight-stage Lovelace Multijet Cascade Impactors, were taken at the process point of operation and at the closest point that the worker would routinely approach. Paired samples were collected at the operator's breathing zone by using a Marple Personal Cascade Impactor and a 35-mm closed-faced cassette. More than 50% of the beryllium machining particles in the breathing zone were less than 10 microns in aerodynamic diameter. This small particle size may result in beryllium deposition into the deepest portion of the lung and may explain elevated rates of sensitization among beryllium machinists.

  8. T cell recognition of beryllium.

    Science.gov (United States)

    Dai, Shaodong; Falta, Michael T; Bowerman, Natalie A; McKee, Amy S; Fontenot, Andrew P

    2013-12-01

    Chronic beryllium disease (CBD) is a granulomatous lung disorder caused by a hypersensitivity to beryllium and characterized by the accumulation of beryllium-specific CD4(+) T cells in the lung. Genetic susceptibility to beryllium-induced disease is strongly associated with HLA-DP alleles possessing a glutamic acid at the 69th position of the β-chain (βGlu69). The structure of HLA-DP2, the most prevalent βGlu69-containing molecule, revealed a unique solvent-exposed acidic pocket that includes βGlu69 and represents the putative beryllium-binding site. The delineation of mimotopes and endogenous self-peptides that complete the αβTCR ligand for beryllium-specific CD4(+) T cells suggests a unique role of these peptides in metal ion coordination and the generation of altered self-peptides, blurring the distinction between hypersensitivity and autoimmunity.

  9. Targeted genome modifications in soybean with CRISPR/Cas9

    OpenAIRE

    Jacobs, Thomas; LaFayette, Peter R.; Schmitz, Robert J.; Parrott, Wayne A.

    2015-01-01

    Background The ability to selectively alter genomic DNA sequences in vivo is a powerful tool for basic and applied research. The CRISPR/Cas9 system precisely mutates DNA sequences in a number of organisms. Here, the CRISPR/Cas9 system is shown to be effective in soybean by knocking-out a green fluorescent protein (GFP) transgene and modifying nine endogenous loci. Results Targeted DNA mutations were detected in 95% of 88 hairy-root transgenic events analyzed. Bi-allelic mutations were detecte...

  10. Characterization of shocked beryllium

    Directory of Open Access Journals (Sweden)

    Papin P.A.

    2012-08-01

    Full Text Available While numerous studies have investigated the low-strain-rate constitutive response of beryllium, the combined influence of high strain rate and temperature on the mechanical behavior and microstructure of beryllium has received limited attention over the last 40 years. In the current work, high strain rate tests were conducted using both explosive drive and a gas gun to accelerate the material. Prior studies have focused on tensile loading behavior, or limited conditions of dynamic strain rate and/or temperature. Two constitutive strength (plasticity models, the Preston-Tonks-Wallace (PTW and Mechanical Threshold Stress (MTS models, were calibrated using common quasi-static and Hopkinson bar data. However, simulations with the two models give noticeably different results when compared with the measured experimental wave profiles. The experimental results indicate that, even if fractured by the initial shock loading, the Be remains sufficiently intact to support a shear stress following partial release and subsequent shock re-loading. Additional “arrested” drive shots were designed and tested to minimize the reflected tensile pulse in the sample. These tests were done to both validate the model and to put large shock induced compressive loads into the beryllium sample.

  11. Large-angle production of charged pions with 3-12.9 GeV/c incident protons on nuclear targets

    CERN Document Server

    Catanesi, M G; Edgecock, R; Ellis, M; Soler, F J P; Goling, C; Bunyatov, S; Krasnoperov, A; Popov, B; Serdiouk, V; Tereschenko, V; Di Capua, E; Vidal-Sitjes, G; Artamonov, A; Giani, S; Gilardoni, S; Gorbunov, P; Grant, A; Grossheim, A; Ivanchenko, A; Ivanchenko, V; Kayis-Topaksu, A; Panman, J; Papadopoulos, I; Chernyaev, E; Tsukerman, I; Veenhof, R; Wiebusch, C; Zucchelli, P; Blondel, A; Borghi, S; Morone, M C; Prior, G; Schroeter, R; Meurer, C; Gastaldi, Ugo; Mills, G B; Graulich, J S; Grégoire, G; Bonesini, M; Ferri, F; Kirsanov, M; Bagulya, A; Grichine, V; Polukhina, N; Palladino, V; Coney, L; Schmitz, D; Barr, G; De Santo, A; Bobisuta, F; Gibina, D; Guglielmib, A; Mezzettob, M; Dumarchez, J; Dore, U; Orestanoc, D; Pastorec, F; Tonazzoc, A; Tortorad, L; Booth, C; Howlett, L; Skoro, G; Bogomilov, M; Chizhov, M; Kolev, D; Tsenov, R; Piperov, S; Temnikov, P; Apollonio, M; Chimenti, P; Giannini, G; Burguet-Castell, J; Cervera-Villanueva, Anselmo; Gómez-Cadenas, J J; Martn Albo, J; Novella, P; Sorel, M; Tornero, A

    2008-01-01

    Measurements of the double-differential charged pion production cross-section in the range of momentum 100 MeV/c < p < 800 MeV/c and angle 0.35 < \\theta < 2.15 rad in proton-beryllium, proton-carbon, proton-aluminium, proton-copper, proton-tin, proton-tantalum and proton-lead collisions are presented. The data were taken with the large acceptance HARP detector in the T9 beam line of the CERN PS. The pions were produced by proton beams in a momentum range from 3 GeV/c to 12.9 GeV/c hitting a target with a thickness of 5% of a nuclear interaction length.

  12. Joining of Beryllium

    Energy Technology Data Exchange (ETDEWEB)

    Goldberg, A

    2006-02-01

    A handbook dealing with the many aspects of beryllium that would be important for the users of this metal is currently being prepared. With an introduction on the applications, advantages and limitations in the use of this metal the following topics will be discussed in this handbook: physical, thermal, and nuclear properties; extraction from the ores; purification and casting of ingots; production and types of beryllium powders; consolidation methods, grades, and properties; mechanical properties with emphasis on the various factors affecting these properties; forming and mechanical working; welding, brazing, bonding, and fastening; machining; powder deposition; corrosion; health aspects; and examples of production of components. This report consists of ''Section X--Joining'' from the handbook. The prefix X is maintained here for the figures, tables and references. In this section the different methods used for joining beryllium and the advantages, disadvantages and limitations of each are presented. The methods discussed are fusion welding, brazing, solid state bonding (diffusion bonding and deformation bonding), soldering, and mechanical fastening. Since beryllium has a high affinity for oxygen and nitrogen with the formation of oxides and nitrides, considerable care must be taken on heating the metal, to protect it from the ambient atmosphere. In addition, mating surfaces must be cleaned and joints must be designed to minimize residual stresses as well as locations for stress concentration (notch effects). In joining any two metals the danger exists of having galvanic corrosion if the part is subjected to moisture or to any type of corroding environment. This becomes a problem if the less noble (anodic) metal has a significantly smaller area than the more noble (cathodic) metal since the ions (positive charges) from the anodic (corroding) metal must correspond to the number of electrons (negative charges) involved at the cathode. Beryllium

  13. Emerging innovative therapeutic approaches targeting PCSK9 to lower lipids.

    Science.gov (United States)

    Shantha, G P S; Robinson, J G

    2016-01-01

    Statins are established therapies for cardiovascular disease prevention and ezetimibe has recently been shown to modestly reduce cardiovascular events when added to background statin therapy. Yet here remains a clear unmet need for additional therapies aimed at lowering low density lipoprotein cholesterol (LDL-C) to further reduce cardiovascular risk. Multiple strategies targeting proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition have emerged as effective modalities for LDL-C lowering. PCSK9 monoclonal antibodies are the farthest along in clinical development and alirocumab and evolocumab were approved for clinical use by regulatory agencies in 2015. In addition to robust LDL-C lowering (nearly 50-65% from baseline), they improve other lipid parameters as well. Adverse events associated with these medications are minimal. Importantly, they improve clinical cardiovascular disease outcomes, although long-term study results are awaited. Cost may be an important limiting factor in their use and we propose two possible solutions which can potentially curtail cost.

  14. Annexin A9 (ANXA9) biomarker and therapeutic target in epithelial cancer

    Science.gov (United States)

    Hu, Zhi [El Cerrito, CA; Kuo, Wen-Lin [San Ramon, CA; Neve, Richard M [San Mateo, CA; Gray, Joe W [San Francisco, CA

    2012-06-12

    Amplification of the ANXA9 gene in human chromosomal region 1q21 in epithelial cancers indicates a likelihood of both in vivo drug resistance and metastasis, and serves as a biomarker indicating these aspects of the disease. ANXA9 can also serve as a therapeutic target. Interfering RNAs (iRNAs) (such as siRNA and miRNA) and shRNA adapted to inhibit ANXA9 expression, when formulated in a therapeutic composition, and delivered to cells of the tumor, function to treat the epithelial cancer.

  15. Technical Basis for PNNL Beryllium Inventory

    Energy Technology Data Exchange (ETDEWEB)

    Johnson, Michelle Lynn

    2014-07-09

    The Department of Energy (DOE) issued Title 10 of the Code of Federal Regulations Part 850, “Chronic Beryllium Disease Prevention Program” (the Beryllium Rule) in 1999 and required full compliance by no later than January 7, 2002. The Beryllium Rule requires the development of a baseline beryllium inventory of the locations of beryllium operations and other locations of potential beryllium contamination at DOE facilities. The baseline beryllium inventory is also required to identify workers exposed or potentially exposed to beryllium at those locations. Prior to DOE issuing 10 CFR 850, Pacific Northwest Nuclear Laboratory (PNNL) had documented the beryllium characterization and worker exposure potential for multiple facilities in compliance with DOE’s 1997 Notice 440.1, “Interim Chronic Beryllium Disease.” After DOE’s issuance of 10 CFR 850, PNNL developed an implementation plan to be compliant by 2002. In 2014, an internal self-assessment (ITS #E-00748) of PNNL’s Chronic Beryllium Disease Prevention Program (CBDPP) identified several deficiencies. One deficiency is that the technical basis for establishing the baseline beryllium inventory when the Beryllium Rule was implemented was either not documented or not retrievable. In addition, the beryllium inventory itself had not been adequately documented and maintained since PNNL established its own CBDPP, separate from Hanford Site’s program. This document reconstructs PNNL’s baseline beryllium inventory as it would have existed when it achieved compliance with the Beryllium Rule in 2001 and provides the technical basis for the baseline beryllium inventory.

  16. Beryllium coating produced by evaporation-condensation method and some their properties

    Energy Technology Data Exchange (ETDEWEB)

    Pepekin, G.I.; Anisimov, A.B.; Chernikov, A.S.; Mozherinn, S.I.; Pirogov, A.A. [SRI SIA Lutch., Podolsk (Russian Federation)

    1998-01-01

    The method of vacuum evaporation-condensation for deposition of beryllium coatings on metal substrates, considered in the paper, side by side with a plasma-spray method is attractive fon ITER application. In particular this technique may be useful for repair the surface of eroded tiles which is operated in a strong magnetic field. The possibility of deposition of beryllium coatings with the rate of layer growth 0.1-0.2 mm/h is shown. The compatibility of beryllium coating with copper or stainless steel substrate is provided due to intermediate barrier. The results of examination of microstructure, microhardness, porosity, thermal and physical properties and stability under thermal cycling of beryllium materials are presented. The value of thermal expansion coefficient and thermal conductivity of condensed beryllium are approximately the same as for industrial grade material produced by powder mettalurgy technique. However, the condensed beryllium has higher purity (up to 99.9-99.99 % wt.). (author)

  17. Determination of beryllium by using X-ray fluorescence spectrometry.

    Science.gov (United States)

    Zawisza, Beata

    2008-03-01

    X-ray fluorescence spectrometry method is subject to certain difficulties and inconveniences for the elements having the atomic number 9 or less. These difficulties become progressively more severe as the atomic number decreases, and are quite serious for beryllium, which is practically indeterminable directly by XRF. Therefore, an indirect determination of beryllium that is based on the evaluation of cobalt in the precipitate is taken into consideration. In the thesis below, there is a description of a new, simple, and precise method by selective precipitation using hexamminecobalt(III) chloride and ammonium carbonate-EDTA solution as a complexing agent for the determining of a trace amount of beryllium using X-ray fluorescence spectrometry. The optimum conditions for [Co(NH(3))(6)][Be(2)(OH)(3)(CO(3))(2)(H(2)O)(2)].(3)H(2)O complex formation were studied. The complex was collected on the membrane filter, and the Co Kalpha line was measured by XRF. The method presents the advantages of the sample preparation and the elimination of the matrix effects due to the thin film obtained. The detection limit of the proposed method is 0.2 mg of beryllium. The method was successfully applied to beryllium determination in copper/ beryllium/cobalt alloys.

  18. PIGE analysis of magnesium and beryllium

    Science.gov (United States)

    Fonseca, M.; Jesus, A. P.; Luís, H.; Mateus, R.; Cruz, J.; Gasques, L.; Galaviz, D.; Ribeiro, J. P.

    2010-06-01

    In this work, we present an alternative method for PIGE analysis of magnesium and beryllium in thick samples. This method is based on the ERYA - Emitted Radiation Yield Analysis - code, which integrates the nuclear reaction excitation function along the depth of the sample. For this purpose, the excitations functions of the 25Mg(p,p'γ) 25Mg ( Eγ = 585 keV) and 9Be(p,γ) 10B ( Eγ = 718 keV) reactions were employed. Calculated gamma-ray yields were compared, at several proton energy values, with experimental yields for thick samples made of inorganic compounds containing magnesium or beryllium. The agreement is better than 5%. Taking into consideration the experimental uncertainty of the measured yields and the errors related to the stopping power values, this agreement shows that effects as the beam energy straggling, ignored in the calculation, seem to play a minor role.

  19. Beryllium induces premature senescence in human fibroblasts.

    Science.gov (United States)

    Coates, Shannon S A; Lehnert, Bruce E; Sharma, Sunil; Kindell, Susan M; Gary, Ronald K

    2007-07-01

    After cells have completed a sufficient number of cell divisions, they exit the cell cycle and enter replicative senescence. Here, we report that beryllium causes proliferation arrest with premature expression of the principal markers of senescence. After young presenescent human fibroblasts were treated with 3 microM BeSO(4) for 24 h, p21 cyclin-dependent kinase inhibitor mRNA increased by >200%. Longer periods of exposure caused mRNA and protein levels to increase for both p21 and p16(Ink4a), a senescence regulator that prevents pRb-mediated cell cycle progression. BeSO(4) also caused dose-dependent induction of senescence-associated beta-galactosidase activity (SA-beta-gal). Untreated cells had 48 relative fluorescence units (RFU)/microg/h of SA-beta-gal, whereas 3 microM BeSO(4) caused activity to increase to 84 RFU/microg/h. In chromatin immunoprecipitation experiments, BeSO(4) caused p53 protein to associate with its DNA binding site in the promoter region of the p21 gene, indicating that p53 transcriptional activity is responsible for the large increase in p21 mRNA elicited by beryllium. Forced expression of human telomerase reverse transcriptase (hTERT) rendered HFL-1 cells incapable of normal replicative senescence. However, there was no difference in the responsiveness of normal HFL-1 fibroblasts (IC(50) = 1.9 microM) and hTERT-immortalized cells (IC(50) = 1.7 microM) to BeSO(4) in a 9-day proliferation assay. The effects of beryllium resemble those of histone deacetylase-inhibiting drugs, which also cause large increases in p21. However, beryllium produced no changes in histone acetylation, suggesting that Be(2+) acts as a novel and potent pharmacological inducer of premature senescence.

  20. Thermal fatigue of beryllium

    Energy Technology Data Exchange (ETDEWEB)

    Deksnis, E.; Ciric, D.; Falter, H. [JET Joint undertaking, Abingdon (United Kingdom)] [and others

    1995-09-01

    Thermal fatigue life of S65c beryllium castellated to a geometry 6 x 6 x (8-10)mm deep has been tested for steady heat fluxes of 3 MW/m{sup 2} to 5 MW/m{sup 2} and under pulsed heat fluxes (10-20 MW/m{sup 2}) for which the time averaged heat flux is 5 MW/m{sup 2}. These tests were carried out in the JET neutral beam test facility A test sequence with peak surface temperatures {le} 600{degrees}C produced no visible fatigue cracks. In the second series of tests, with T{sub max} {le} 750{degrees}C evidence for fatigue appeared after a minimum of 1350 stress cycles. These fatigue data are discussed in view of the observed lack of thermal fatigue in JET plasma operations with beryllium PFC. JET experience with S65b and S65c is reviewed; recent operations with {Phi} = 25 MW/m{sup 2} and sustained melting/resolidification are also presented. The need for a failure criterion for finite element analyses of Be PFC lifetimes is discussed.

  1. Neutron counter based on beryllium activation

    Energy Technology Data Exchange (ETDEWEB)

    Bienkowska, B.; Prokopowicz, R.; Kaczmarczyk, J.; Paducha, M. [Institute of Plasma Physics and Laser Microfusion (IPPLM), Hery 23, 01-497 Warsaw (Poland); Scholz, M.; Igielski, A. [Institute of Nuclear Physics PAS (IFJPAN), Radzikowskiego 152, 31-342 Krakow (Poland); Karpinski, L. [Faculty of Electrical Engineering, Rzeszow University of Technology, Pola 2, 35-959 Rzeszow (Poland); Pytel, K. [National Centre for Nuclear Research (NCBJ), Soltana 7, 05-400 Otwock - Swierk (Poland)

    2014-08-21

    The fusion reaction occurring in DD plasma is followed by emission of 2.45 MeV neutrons, which carry out information about fusion reaction rate and plasma parameters and properties as well. Neutron activation of beryllium has been chosen for detection of DD fusion neutrons. The cross-section for reaction {sup 9}Be(n, α){sup 6}He has a useful threshold near 1 MeV, which means that undesirable multiple-scattered neutrons do not undergo that reaction and therefore are not recorded. The product of the reaction, {sup 6}He, decays with half-life T{sub 1/2} = 0.807 s emitting β{sup −} particles which are easy to detect. Large area gas sealed proportional detector has been chosen as a counter of β–particles leaving activated beryllium plate. The plate with optimized dimensions adjoins the proportional counter entrance window. Such set-up is also equipped with appropriate electronic components and forms beryllium neutron activation counter. The neutron flux density on beryllium plate can be determined from the number of counts. The proper calibration procedure needs to be performed, therefore, to establish such relation. The measurements with the use of known β–source have been done. In order to determine the detector response function such experiment have been modeled by means of MCNP5–the Monte Carlo transport code. It allowed proper application of the results of transport calculations of β{sup −} particles emitted from radioactive {sup 6}He and reaching proportional detector active volume. In order to test the counter system and measuring procedure a number of experiments have been performed on PF devices. The experimental conditions have been simulated by means of MCNP5. The correctness of simulation outcome have been proved by measurements with known radioactive neutron source. The results of the DD fusion neutron measurements have been compared with other neutron diagnostics.

  2. Neutron counter based on beryllium activation

    Science.gov (United States)

    Bienkowska, B.; Prokopowicz, R.; Scholz, M.; Kaczmarczyk, J.; Igielski, A.; Karpinski, L.; Paducha, M.; Pytel, K.

    2014-08-01

    The fusion reaction occurring in DD plasma is followed by emission of 2.45 MeV neutrons, which carry out information about fusion reaction rate and plasma parameters and properties as well. Neutron activation of beryllium has been chosen for detection of DD fusion neutrons. The cross-section for reaction 9Be(n, α)6He has a useful threshold near 1 MeV, which means that undesirable multiple-scattered neutrons do not undergo that reaction and therefore are not recorded. The product of the reaction, 6He, decays with half-life T1/2 = 0.807 s emitting β- particles which are easy to detect. Large area gas sealed proportional detector has been chosen as a counter of β-particles leaving activated beryllium plate. The plate with optimized dimensions adjoins the proportional counter entrance window. Such set-up is also equipped with appropriate electronic components and forms beryllium neutron activation counter. The neutron flux density on beryllium plate can be determined from the number of counts. The proper calibration procedure needs to be performed, therefore, to establish such relation. The measurements with the use of known β-source have been done. In order to determine the detector response function such experiment have been modeled by means of MCNP5-the Monte Carlo transport code. It allowed proper application of the results of transport calculations of β- particles emitted from radioactive 6He and reaching proportional detector active volume. In order to test the counter system and measuring procedure a number of experiments have been performed on PF devices. The experimental conditions have been simulated by means of MCNP5. The correctness of simulation outcome have been proved by measurements with known radioactive neutron source. The results of the DD fusion neutron measurements have been compared with other neutron diagnostics.

  3. Proton irradiation effects on beryllium - A macroscopic assessment

    Science.gov (United States)

    Simos, Nikolaos; Elbakhshwan, Mohamed; Zhong, Zhong; Camino, Fernando

    2016-10-01

    Beryllium, due to its excellent neutron multiplication and moderation properties, in conjunction with its good thermal properties, is under consideration for use as plasma facing material in fusion reactors and as a very effective neutron reflector in fission reactors. While it is characterized by unique combination of structural, chemical, atomic number, and neutron absorption cross section it suffers, however, from irradiation generated transmutation gases such as helium and tritium which exhibit low solubility leading to supersaturation of the Be matrix and tend to precipitate into bubbles that coalesce and induce swelling and embrittlement thus degrading the metal and limiting its lifetime. Utilization of beryllium as a pion production low-Z target in high power proton accelerators has been sought both for its low Z and good thermal properties in an effort to mitigate thermos-mechanical shock that is expected to be induced under the multi-MW power demand. To assess irradiation-induced changes in the thermal and mechanical properties of Beryllium, a study focusing on proton irradiation damage effects has been undertaken using 200 MeV protons from the Brookhaven National Laboratory Linac and followed by a multi-faceted post-irradiation analysis that included the thermal and volumetric stability of irradiated beryllium, the stress-strain behavior and its ductility loss as a function of proton fluence and the effects of proton irradiation on the microstructure using synchrotron X-ray diffraction. The mimicking of high temperature irradiation of Beryllium via high temperature annealing schemes has been conducted as part of the post-irradiation study. This paper focuses on the thermal stability and mechanical property changes of the proton irradiated beryllium and presents results of the macroscopic property changes of Beryllium deduced from thermal and mechanical tests.

  4. Neutron beams from protons on beryllium.

    Science.gov (United States)

    Bewley, D K; Meulders, J P; Octave-Prignot, M; Page, B C

    1980-09-01

    Measurements of dose rate and penetration in water have been made for neutron beams produced by 30--75 MeV protons on beryllium. The effects of Polythene filters added on the target side of the collimator have also been studied. A neutron beam comparable with a photon beam from a 4--8 MeV linear accelerator can be produced with p/Be neutrons plus 5 cm Polythene filtrations, with protons in the range 50--75 MeV. This is a more economical method than use of the d/Be reaction.

  5. Study of beryllium redeposition under bombardment by high intensity -low energy- hydrogen ion beams

    Energy Technology Data Exchange (ETDEWEB)

    Gureev, V.M.; Guseva, M.I.; Danelyan, L.S. [Russian Research Centre Kurchatov Inst., Moscow (Russian Federation)] [and others

    1998-01-01

    The results of studying the erosion of beryllium under an effect of intense ion fluxes with the energy of 250 eV, at the fluences {approx}10{sup 2}1 cm{sup -2}, at the MAGRAS-stand are given. The operating conditions under which a practically-complete redeposition of the sputtered beryllium upon the target surface were experimentally-realized. A change in the microstructure of a beryllium target under sputtering and redeposition is analyzed. Some technological applications are considered. (author)

  6. Measurement of Pion and Kaon Fluxes Below 60 GeV/c Produced by 450~GeV/c Protons on a Beryllium Target The SPY Collaboration

    CERN Multimedia

    2002-01-01

    % NA56 \\\\ \\\\ We propose to perform a measurement of the production rates of $\\pi$'s and K's and their ratio below 60~GeV/c from 450~GeV/c protons hitting a Be target. These data are of great importance for the correct evaluation of the neutrino flux at the present and future SPS neutrino experiments. The apparatus of the NA52 experiment has the capability of performing the measurement, using about two weeks of proton beam time and a target closely resembling the one used in the current SPS neutrino beam line.

  7. Beryllium Related Matter

    Energy Technology Data Exchange (ETDEWEB)

    Gaylord, R F

    2008-12-23

    In recent months, LLNL has identified, commenced, and implemented a series of interim controls, compensatory measures, and initiatives to ensure worker safety, and improve safety processes with regards to potential worker exposure to beryllium. Many of these actions have been undertaken in response to the NNSA Independent Review (COR-TS-5/15/2008-8550) received by LLNL in November of 2008. Others are the result of recent discoveries, events or incidents, and lessons learned, or were scheduled corrective actions from earlier commitments. Many of these actions are very recent in nature, or are still in progress, and vary in the formality of implementation. Actions are being reviewed for effectiveness as they progress. The documentation of implementation, and review of effectiveness, when appropriate, of these actions will be addressed as part of the formal Corrective Action Plan addressing the Independent Review. The mitigating actions taken fall into the following categories: (1) Responses to specific events/concerns; (2) Development of interim controls; (3) Review of ongoing activities; and (4) Performance improvement measures.

  8. Coolant choice for the central beryllium pipe of the BESIII beam pipe

    Science.gov (United States)

    Zheng, Li-Fang; Wang, Li; Wu, Ping; Ji, Quan; Li, Xun-Feng; Liu, Jian-Ping

    2010-07-01

    In order to take away much more heat on the BESIII beam pipe to guarantee the normal particle detection, EDM-1 (oil No.1 for electric discharge machining), with good thermal and flow properties was selected as the candidate coolant for the central beryllium pipe of the BESIII beam pipe. Its cooling character was studied and dynamic corrosion experiment was undertaken to examine its corrosion on beryllium. The experiment results show that EDM-1 would corrode the beryllium 19.9 μm in the depth in 10 years, which is weak and can be neglected. Finite element simulation and experiment research were taken to check the cooling capacity of EDM-1. The results show that EDM-1 can meet the cooling requirement of the central beryllium pipe. Now EDM-1 is being used to cool the central beryllium pipe of the BESIII beam pipe.

  9. On-line separation of short-lived beryllium isotopes

    CERN Document Server

    Köster, U; Catherall, R; Fedosseev, V; Georg, U; Huber, G; Jading, Y; Jonsson, O; Koizumi, M; Kratz, K L; Kugler, E; Lettry, Jacques; Mishin, V I; Ravn, H L; Sebastian, V; Tamburella, C; Wöhr, A

    1998-01-01

    With the development of a new laser ionization scheme, it became possible to ionize beryllium efficiently in the hot cavity of the ISOLDE laser ion source. The high target and ion source temperatures enable the release of short-lived beryllium isotopes. Thus all particle-stable beryllium isotopes could be extracted from a standard uranium carbide/graphite target. For the first time the short-lived isotopes /sup 12/Be and /sup 14/Be could be identified at an ISOL facility, /sup 14/Be being among the most short-lived isotopes separated so far at ISOLDE. The release time from the UC/graphite target was studied with several beryllium isotopes. Profiting from the element selectivity of laser ionization, the strong and isotopically pure beam of /sup 12/Be allowed to determine the half- life to T/sub 1/2 /=21.34(23) ms and the probability of beta-delayed neutron emission to P/sub n/=0.48/sub -0.10//sup +0.12/(23 refs).

  10. Proceedings of the third IEA international workshop on beryllium technology for fusion

    Energy Technology Data Exchange (ETDEWEB)

    Kawamura, Hiroshi; Okamoto, Makoto [eds.

    1998-01-01

    This report is the Proceedings of the Third International Energy Agency International Workshop on Beryllium Technology for Fusion. The workshop was held on October 22-24, 1997, at the Sangyou Kaikan in Mito City with 68 participants who attended from the Europe, the Russian Federation, the Kazakstan, the United States and Japan. The topics for papers were arranged into 9 sessions; beryllium applications for ITER, production and characterization, chemical compatibility and corrosion, forming and joining, plasma/tritium interactions, beryllium coating, first wall applications, neutron irradiation effects, health and safety. To utilize beryllium in the pebble type blanket, a series of discussions were intensified in multiple view points such as the swelling, He/T release from beryllium pebble irradiated up to high He content, effective thermal conductivity, tritium permeation and coating, and fabrication cost, and so on. As the plasma facing material, life time of beryllium and coated beryllium, dust and particle production, joining, waste treatment, mechanical properties and deformation by swelling were discussed as important issues. Especially, it was recognized throughout the discussions that the comparative study by the different researchers should be carried out to establish the reliability of the data reported in the workshop and in others. To enhance the comparative study, the world wide collaboration for the relative evaluation of the beryllium was proposed by the International Organization Committee and the proposal was approved by all of the participants. The 45 of the presented papers are indexed individually. (J.P.N.)

  11. Mineral resource of the month: beryllium

    Science.gov (United States)

    ,

    2013-01-01

    The article discusses information about Beryllium. It notes that Beryllium is a light metal that has a gray color. The metal is used in the production of parts and devices including bearings, computer-chip heat sinks, and output windows of X-ray tubes. The article mentions Beryllium's discovery in 1798 by French chemist, Louis-Nicolas Vanquelin. It cites that bertrandite and beryl are the principal mineral components for the commercial production of beryllium.

  12. Beryllium--important for national defense

    Science.gov (United States)

    Boland, M.A.

    2012-01-01

    Beryllium is one of the lightest and stiffest metals, but there was little industrial demand for it until the 1930s and 1940s when the aerospace, defense, and nuclear sectors began using beryllium and its compounds. Beryllium is now classified by the U.S. Department of Defense as a strategic and critical material because it is used in products that are vital to national security. The oxide form of beryllium was identified in 1797, and scientists first isolated metallic beryllium in 1828. The United States is the world's leading source of beryllium. A single mine at Spor Mountain, Utah, produced more than 85 percent of the beryllium mined worldwide in 2010. China produced most of the remainder, and less than 2 percent came from Mozambique and other countries. National stockpiles also provide significant amounts of beryllium for processing. To help predict where future beryllium supplies might be located, U.S.Geological Survey (USGS) scientists study how and where beryllium resources are concentrated in Earth's crust and use that knowledge to assess the likelihood that undiscovered beryllium resources may exist. Techniques to assess mineral resources have been developed by the USGS to support the stewardship of Federal lands and to better evaluate mineral resource availability in a global context. The USGS also compiles statistics and information on the worldwide supply of, demand for, and flow of beryllium. These data are used to inform U.S. national policymaking.

  13. 10 CFR 850.33 - Beryllium emergencies.

    Science.gov (United States)

    2010-01-01

    ... 10 Energy 4 2010-01-01 2010-01-01 false Beryllium emergencies. 850.33 Section 850.33 Energy DEPARTMENT OF ENERGY CHRONIC BERYLLIUM DISEASE PREVENTION PROGRAM Specific Program Requirements § 850.33 Beryllium emergencies. (a) The responsible employer must comply with 29 CFR 1910.120(l) for...

  14. Electronic structure of alkali-metal/alkaline-earth-metal fluorine beryllium borate NaSr3Be3B3O9F4 single crystal: DFT approach

    Science.gov (United States)

    Reshak, A. H.; Kamarudin, H.; Auluck, S.

    2015-10-01

    The electronic band structure, total and angular momentum resolved projected density of states for NaSr3Be3B3O9F4 are calculated using the all-electron full potential linearized augmented plane wave plus local orbitals (FP-LAPW + lo) method. The calculations are performed within four exchange correlations namely; local density approximation (LDA), general gradient approximation (PBE-GGA), Engel-Vosko generalized gradient approximation (EVGGA) and the recently modified Becke-Johnson potential (mBJ). Calculations suggest that NaSr3Be3B3O9F4 is a direct wide band gap semiconductor. The exchange correlations potentials exhibit significant influence on the value of the energy gap being about 4.82 eV (LDA), 5.16 eV (GGA), 6.20 (EVGGA) and 7.20 eV (mBJ). The mBJ approach succeed by large amount in bringing the calculated energy gap closer to the experimental one (7.28 eV). The angular momentum resolved projected density of states shows the existence of a strong hybridization between the various orbitals. In additional we have calculated the electronic charge density distribution in two crystallographic planes namely (1 0 1) and (0 0 -1) to visualized the chemical bonding characters.

  15. Neutron irradiation of beryllium pebbles

    Energy Technology Data Exchange (ETDEWEB)

    Gelles, D.S.; Ermi, R.M. [Pacific Northwest National Lab., Richland, WA (United States); Tsai, H. [Argonne National Lab., IL (United States)

    1998-03-01

    Seven subcapsules from the FFTF/MOTA 2B irradiation experiment containing 97 or 100% dense sintered beryllium cylindrical specimens in depleted lithium have been opened and the specimens retrieved for postirradiation examination. Irradiation conditions included 370 C to 1.6 {times} 10{sup 22} n/cm{sup 2}, 425 C to 4.8 {times} 10{sup 22} n/cm{sup 2}, and 550 C to 5.0 {times} 10{sup 22} n/cm{sup 2}. TEM specimens contained in these capsules were also retrieved, but many were broken. Density measurements of the cylindrical specimens showed as much as 1.59% swelling following irradiation at 500 C in 100% dense beryllium. Beryllium at 97% density generally gave slightly lower swelling values.

  16. Beryllium strain under dynamic loading

    Directory of Open Access Journals (Sweden)

    Pushkov Victor

    2015-01-01

    Full Text Available There are some data (not much on dynamic characteristics of beryllium that are important, for example, when estimating construction performance at NPP emergencies. A number of data on stress-strain curves, spall strength, shear strength, fracture and structure responses of shock loaded beryllium have obtained in US and Russian laboratories. For today the model description of this complex metal behavior does not have a reasonable agreement with the experimental data, thus a wider spectrum of experimental data is required. This work presents data on dynamic compression-test diagrams of Russian beryllium. Experiments are performed using Hopkinson bar method (SHPB. Strain rates were ε ∼ 103 s−1.

  17. Extraction of beryllium sulfate by a long chain amine; Extraction du sulfate de beryllium par une amine a longue chaine

    Energy Technology Data Exchange (ETDEWEB)

    Etaix, E.S. [Commissariat a l' Energie Atomique, Fontenay-Aux-Roses (France). Centre d' Etudes Nucleaires

    1968-06-01

    The extraction of sulfuric acid in aqueous solution by a primary amine in benzene solution, 3-9 (diethyl) - 6-amino tri-decane (D.E.T. ) - i.e., with American nomenclature 1-3 (ethyl-pentyl) - 4-ethyl-octyl amine (E.P.O.) - has made it possible to calculate the formation constants of alkyl-ammonium sulfate and acid sulfate. The formula of the beryllium and alkyl-ammonium sulfate complex formed in benzene has next been determined, for various initial acidity of the aqueous solution. Lastly, evidence has been given of negatively charged complexes of beryllium and sulfate in aqueous solution, through the dependence of the aqueous sulfate ions concentration upon beryllium extraction. The formation constant of these anionic complexes has been evaluated. (author) [French] L'etude de l'extraction de l'acide sulfurique en solution aqueuse par une amine primaire en solution dans le benzene, le diethyl-3,9 amino-6 tridecane (D.E.T.) - autre nom americain 1-3 (ethylpentyl) - 4-ethyloctylamine (E.P.O.) a permis de calculer les constantes de formation du sulfate et de l'hydrogenosulfate d'alkyl-ammonium. La formule du complexe de sulfate de beryllium et d'alkyl-ammonium forme en solution benzenique a ete ensuite determinee pour diverses acidites initiales de la solution aqueuse. Enfin, l'influence de la concentration des ions sulfate de la phase aqueuse sur l'extraction du beryllium a mis en evidence la formation en solution aqueuse de complexes anioniques de sulfate et de beryllium dont la constante de formation a ete evaluee. (auteur)

  18. CRISPR/Cas9系统的脱靶效应%Off-target of CRISPR/Cas9 System

    Institute of Scientific and Technical Information of China (English)

    尹珅; 贺桂芳; 赖方秾; 谢凤云; 马俊宇

    2016-01-01

    在细菌中发现的免疫系统CRISPR/Cas9,已经成为最有效的基因工程编辑工具,甚至大有希望可以治疗人类遗传性疾病。但是CRISPR/Cas9系统在使用时会产生严重的脱靶问题,导致假表型和错误的解释。提高与靶点结合的高效率,同时减少脱靶效应,将是今后CRISPR/Cas9技术的挑战。综述关注与CRISPR/Cas9脱靶效应相关的内容,总结了影响其靶点专一性的因素,减少CRISPR/Cas9脱靶效应的可行性方法和设计工具等,供大家学习讨论。%As an adaptive immune system discovered in bacteria,clustered regularly interspaced short palindromic repeats(CRISPR)/CRISPR-associated protein 9(Cas9)technology has been used as the most effective genome-editing tool. By now,CRISPR/Cas9 has shown a great promise in healing human genetic diseases,however,off-target is a critical issue while applying it. The off-target of CRISPR/Cas9 leads to the false phenotype and wrong interpretation. Optimization of on-target activity and minimizing off-target activity will be challenges while CRISPR/Cas9 is applied in the future. In this review,we focused on the off-target related issues,including factors involved in the target specificity,strategies and tools of minimizing the off-target of CRISPR/Cas9.

  19. Codeposition of deuterium ions with beryllium oxide at elevated temperatures

    CERN Document Server

    Markin, A V; Gorodetsky, A E; Negodaev, M A; Rozhanskii, N V; Scaffidi-Argentina, F; Werle, H; Wu, C H; Zalavutdinov, R K; Zakharov, A P

    2000-01-01

    Deuterium-loaded BeO films were produced by sputtering the beryllium target with 10 keV Ne ions in D sub 2 gas at a pressure of approximately 1 Pa. The sputtered beryllium reacts - on the substrate surface - with the residual oxygen, thus forming a beryllium oxide layer. Biasing the substrate negatively with respect to the target provides the simultaneous bombardment of the growing film surface with D ions formed by Ne-D sub 2 collisions. Substrate potential governs the maximum energy of ions striking the growing film surface while its size governs the flux density. According to X-ray photoelectron spectroscopy (XPS), electron probe microanalysis (EPMA) and reflection high energy electron diffraction (RHEED) data, the beryllium is deposited in the form of polycrystalline hcp-BeO layers with negligible (about 1 at.%) carbon and neon retention. Thermal desorption spectroscopy (TDS) data shows a strong deuterium bonding, with a desorption peak at 950 K, in the films deposited at -50 and -400 V substrate potentia...

  20. Reactivity test between beryllium and copper

    Energy Technology Data Exchange (ETDEWEB)

    Kawamura, H. [Japan Atomic Energy Research Institute, Ibaraki-ken (Japan); Kato, M. [NGK Insulators, Ltd., Aichi-ken (Japan)

    1995-09-01

    Beryllium has been expected for using as plasma facing material on ITER. And, copper alloy has been proposed as heat sink material behind plasma facing components. Therefore, both materials must be joined. However, the elementary process of reaction between beryllium and copper alloy does not clear in detail. For example, other authors reported that beryllium reacted with copper at high temperature, but it was not obvious about the generation of reaction products and increasing of the reaction layer. In the present work, from this point, for clarifying the elementary process of reaction between beryllium and copper, the out-of-pile compatibility tests were conducted with diffusion couples of beryllium and copper which were inserted in the capsule filled with high purity helium gas (6N). Annealing temperatures were 300, 400, 500, 600 and 700{degrees}C, and annealing periods were 100, 300 and 1000h. Beryllium specimens were hot pressed beryllium, and copper specimens were OFC (Oxygen Free Copper).

  1. Development of radiation resistant grades of beryllium for nuclear and fusion facilities

    Energy Technology Data Exchange (ETDEWEB)

    Kupriyanov, I.B.; Gorokhov, V.A.; Nikolaev, G.N. [Russia Research Institute of Inorganic Materials, Moscow (Russian Federation)

    1995-09-01

    R&D results on beryllium with high radiation resistance obtained recently are described in this report. The data are presented on nine different grades of isotropic beryllium manufactured by VNIINM and distinguished by both initial powder characteristics and properties of billets, made of these powders. The average grain size of the investigated beryllium grades varied from 8 to 26 {mu}m, the content of beryllium oxide was 0.9 - 3.9 wt.%, the dispersity of beryllium oxide - 0.04 - 0.5 {mu}m, tensile strength -- 250 - 650 MPa. All materials were irradiated in SM - 2 reactor over the temperature range 550 - 780{degrees}C. The results of the investigation showed, that HIP beryllium grades are less susceptible to swelling at higher temperatures in comparison with hot pressed and extruded grades. Beryllium samples, having the smallest grain size, demonstrated minimal swelling, which was less than 0.8 % at 750{degrees}C and Fs = 3.7 {center_dot}10{sup 21} cm{sup -2} (E>0.1 MeV). The mechanical properties, creep and microstructure parameters, measured before and after irradiation, are presented.

  2. Machining risk of beryllium disease and sensitization with median exposures below 2 micrograms/m3.

    Science.gov (United States)

    Kreiss, K; Mroz, M M; Newman, L S; Martyny, J; Zhen, B

    1996-07-01

    We examined the prevalence of beryllium sensitization in relation to work process and beryllium exposure measurements in a beryllia ceramics plant that had operated since 1980. We interviewed 136 employees (97.8% of the workforce), ascertained beryllium sensitization with the beryllium lymphocyte proliferation blood test, and reviewed historical industrial hygiene measurements. Of eight beryllium-sensitized employees (5.9%), six (4.4% of participating employees) had granulomatous disease on transbronchial lung biopsy. Machinists had a sensitization rate of 14.3% compared to a rate of 1.2% among other employees. Machining had significantly higher general area and breathing zone measurements than did other processes in the time period in which most beryllium-sensitized cases had started machining work. Daily weighted average (DWA) estimates of exposure for matching processes also exceeded estimates for other work processes in that time period, with a median DWA of 0.9 microgram/m3. Machining process DWAs accounted for the majority of DWAs exceeding the 2.0 micrograms/m3 OSHA standard, with 8.1% of machining DWAs above the standard. We conclude that lowering machining process-related exposures may be important to lowering risk of beryllium disease.

  3. Rewiring Cas9 to Target New PAM Sequences.

    Science.gov (United States)

    Siksnys, Virginijus; Gasiunas, Giedrius

    2016-03-17

    Papers by Anders et al. (2016) and Hirano et al. (2016b), published in this issue of Molecular Cell, show that SpCas9 uses an induced fit mechanism to recognize altered protospacer adjacent motif (PAM) sequences.

  4. Progress of application and off-target effects of CRISPR/Cas9.

    Science.gov (United States)

    Wu, Zheng; Feng, Gu

    2015-10-01

    The clustered regulatory interspaced short palindromic repeat/Cas9 (CRISPR/Cas9) system mediates genome editing and is revolutionizing genetic researches. Scientists are able to manipulate the gene of interest from any organism with CRISPR/Cas9. Compared with zinc finger nucleases (ZFNs) and transcription activator-like effector nucleases (TALENs) technologies, the CRISPR/Cas9 technology provides an easy and efficient approach to manipulate the genome. In this system, sgRNA (Single guide RNA), a short RNA matching the targeted DNA fragment, guides the CRISPR/Cas9 to interrogate the genome. Because sgRNA can tolerate certain mismatches to the DNA targets and thereby promote undesired off-target mutagenesis, the key limit of this technology is off-target effects. To eliminate the off-target effects, different strategies have been adopted. In this review, we summarize the application of CRISPR/Cas9 and different strategies for addressing off-target effects.

  5. Worker Environment Beryllium Characterization Study

    Energy Technology Data Exchange (ETDEWEB)

    NSTec Environment, Safety, Health & Quality

    2009-12-28

    This report summarizes the conclusion of regular monitoring of occupied buildings at the Nevada Test Site and North Las Vegas facility to determine the extent of beryllium (Be) contamination in accordance with Judgment of Needs 6 of the August 14, 2003, “Minnema Report.”

  6. CRISPR/Cas9-mediated target validation of the Splicing Inhibitor Pladienolide B

    KAUST Repository

    Aouida, Mustapha

    2016-02-24

    CRISPR/Cas9 system confers molecular immunity in archeal and bacterial species against invading foreign nucleic acids. CRISPR/Cas9 system is used for genome engineering applications across diverse eukaryotic species. In this study, we demonstrate the utility of the CRISPR/Cas9 genome engineering system for drug target validation in human cells. Pladienolide B is a natural macrolide with antitumor activities mediated through the inhibition of pre-mRNA splicing. To validate the spliceosomal target of Pladienolide B, we employed the CRSIPR/Cas9 system to introduce targeted mutations in the subunits of the SF3B complex in the HEK293T cells. Our data reveal that targeted mutagenesis of the SF3b1 subunit exhibited higher levels of resistance to Pladienolide B. Therefore, our data validate the spliceosomal target of Pladienolide B and provide a proof of concept on using the CRISPR/Cas9 system for drug target identification and validation.

  7. OVERVIEW OF BERYLLIUM SAMPLING AND ANALYSIS

    Energy Technology Data Exchange (ETDEWEB)

    Brisson, M

    2009-04-01

    Because of its unique properties as a lightweight metal with high tensile strength, beryllium is widely used in applications including cell phones, golf clubs, aerospace, and nuclear weapons. Beryllium is also encountered in industries such as aluminium manufacturing, and in environmental remediation projects. Workplace exposure to beryllium particulates is a growing concern, as exposure to minute quantities of anthropogenic forms of beryllium may lead to sensitization and to chronic beryllium disease, which can be fatal and for which no cure is currently known. Furthermore, there is no known exposure-response relationship with which to establish a 'safe' maximum level of beryllium exposure. As a result, the current trend is toward ever lower occupational exposure limits, which in turn make exposure assessment, both in terms of sampling and analysis, more challenging. The problems are exacerbated by difficulties in sample preparation for refractory forms of beryllium, such as beryllium oxide, and by indications that some beryllium forms may be more toxic than others. This chapter provides an overview of sources and uses of beryllium, health risks, and occupational exposure limits. It also provides a general overview of sampling, analysis, and data evaluation issues that will be explored in greater depth in the remaining chapters. The goal of this book is to provide a comprehensive resource to aid personnel in a wide variety of disciplines in selecting sampling and analysis methods that will facilitate informed decision-making in workplace and environmental settings.

  8. Sampling and analysis plan for assessment of beryllium in soils surrounding TA-40 building 15

    Energy Technology Data Exchange (ETDEWEB)

    Ruedig, Elizabeth [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2016-12-19

    Technical Area (TA) 40 Building 15 (40-15) is an active firing site at Los Alamos National Laboratory. The weapons facility operations (WFO) group plans to build an enclosure over the site in 2017, so that test shots may be conducted year-round. The enclosure project is described in PRID 16P-0209. 40-15 is listed on LANL OSH-ISH’s beryllium inventory, which reflects the potential for beryllium in/on soils and building surfaces at 40-15. Some areas in and around 40-15 have previously been sampled for beryllium, but past sampling efforts did not achieve complete spatial coverage of the area. This Sampling and Analysis Plan (SAP) investigates the area surrounding 40-15 via 9 deep (≥1-ft.) soil samples and 11 shallow (6-in.) soil samples. These samples will fill the spatial data gaps for beryllium at 40-15, and will be used to support OSH-ISH’s final determination of 40-15’s beryllium registry status. This SAP has been prepared by the Environmental Health Physics program in consultation with the Industrial Hygiene program. Industrial Hygiene is the owner of LANL’s beryllium program, and will make a final determination with regard to the regulatory status of beryllium at 40-15.

  9. The uses and adverse effects of beryllium on health

    Directory of Open Access Journals (Sweden)

    Cooper Ross

    2009-01-01

    Full Text Available Context: This review describes the health effects of beryllium exposure in the workplace and the environment. Aim: To collate information on the consequences of occupational and environmental exposure to beryllium on physiological function and well being. Materials and Methods: The criteria used in the current review for selecting articles were adopted from proposed criteria in The International Classification of Functioning, Disability, and Health. Articles were classified based on acute and chronic exposure and toxicity of beryllium. Results: The proportions of utilized and nonutilized articles were tabulated. Years 2001-10 gave the greatest match (45.9% for methodological parameters, followed by 27.71% for 1991-2000. Years 1971-80 and 1981-90 were not significantly different in the information published and available whereas years 1951-1960 showed a lack of suitable articles. Some articles were published in sources unobtainable through requests at the British Library, and some had no impact factor and were excluded. Conclusion: Beryllium has some useful but undoubtedly harmful effects on health and well-being. Measures need to be taken to prevent hazardous exposure to this element, making its biological monitoring in the workplace essential.

  10. Biological exposure metrics of beryllium-exposed dental technicians.

    Science.gov (United States)

    Stark, Moshe; Lerman, Yehuda; Kapel, Arik; Pardo, Asher; Schwarz, Yehuda; Newman, Lee; Maier, Lisa; Fireman, Elizabeth

    2014-01-01

    Beryllium is commonly used in the dental industry. This study investigates the association between particle size and shape in induced sputum (IS) with beryllium exposure and oxidative stress in 83 dental technicians. Particle size and shape were defined by laser and video, whereas beryllium exposure data came from self-reports and beryllium lymphocyte proliferation test (BeLPT) results. Heme oxygenase-1 (HO1) gene expression in IS was evaluated by quantitative polymerase chain reaction. A high content of particles (92%) in IS >5 μ in size is correlated to a positive BeLPT risk (odds ratio [OR] = 3.4, 95% confidence interval [CI]: 0.9-13). Use of masks, hoods, and type of exposure yielded differences in the transparency of IS particles (gray level) and modulate HO1 levels. These results indicate that parameters of size and shape of particles in IS are sensitive to workplace hygiene, affect the level of oxidative stress, and may be potential markers for monitoring hazardous dust exposures.

  11. CRISPR/Cas9 technology for targeted genome editing

    Directory of Open Access Journals (Sweden)

    Lomov N. A.

    2015-08-01

    Full Text Available CRISPRs (Clustered Regularly Interspaced Short Palindromic Repeats are the segments of prokaryotic DNA containing short repeats in its nucleotide sequence. Today we know that this is a bacterial protection system against viral DNA. The molecular components of CRISPR/Cas9 system have been used for a gene editing in eukaryotes since 2013. But as any other method it also has the limitations and drawbacks. Here we are going to review the history of CRISPR biology and to discuss the possibilities that this new technology provides to researchers as well as the prospects for its use in the medical research and treatment.

  12. Defense programs beryllium good practice guide

    Energy Technology Data Exchange (ETDEWEB)

    Herr, M.

    1997-07-01

    Within the DOE, it has recently become apparent that some contractor employees who have worked (or are currently working) with and around beryllium have developed chronic beryllium disease (CBD), an occupational granulomatous lung disorder. Respiratory exposure to aerosolized beryllium, in susceptible individuals, causes an immunological reaction that can result in granulomatous scarring of the lung parenchyma, shortness of breath, cough, fatigue, weight loss, and, ultimately, respiratory failure. Beryllium disease was originally identified in the 1940s, largely in the fluorescent light industry. In 1950, the Atomic Energy Commission (AEC) introduced strict exposure standards that generally curtailed both the acute and chronic forms of the disease. Beginning in 1984, with the identification of a CBD case in a DOE contractor worker, there was increased scrutiny of both industrial hygiene practices and individuals in this workforce. To date, over 100 additional cases of beryllium-specific sensitization and/or CBD have been identified. Thus, a disease previously thought to be largely eliminated by the adoption of permissible exposure standards 45 years ago is still a health risk in certain workforces. This good practice guide forms the basis of an acceptable program for controlling workplace exposure to beryllium. It provides (1) Guidance for minimizing worker exposure to beryllium in Defense Programs facilities during all phases of beryllium-related work, including the decontamination and decommissioning (D&D) of facilities. (2) Recommended controls to be applied to the handling of metallic beryllium and beryllium alloys, beryllium oxide, and other beryllium compounds. (3) Recommendations for medical monitoring and surveillance of workers exposed (or potentially exposed) to beryllium, based on the best current understanding of beryllium disease and medical diagnostic tests available. (4) Site-specific safety procedures for all processes of beryllium that is likely to

  13. Beryllium Lymphocyte Proliferation Test Surveillance Identifies Clinically Significant Beryllium Disease

    Science.gov (United States)

    Mroz, Margaret M.; Maier, Lisa A.; Strand, Matthew; Silviera, Lori; Newman, Lee S.

    2011-01-01

    Background Workplace surveillance identifies chronic beryllium disease (CBD) but it remains unknown over what time frame mild CBD will progress to a more severe form. Methods We examined physiology and treatment in 229 beryllium sensitization (BeS) and 171 CBD surveillance-identified cases diagnosed from 1982 to 2002. Never smoking CBD cases (81) were compared to never smoking BeS patients (83) to assess disease progression. We compared CBD machinists to non-machinists to examine effects of exposure. Results At baseline, CBD and BeS cases did not differ significantly in exposure time or physiology. CBD patients were more likely to have machined beryllium. Of CBD cases, 19.3% went on to require oral immunosuppressive therapy. At 30 years from first exposure, measures of gas exchange were significantly worse and total lung capacity was lower for CBD subjects. Machinists had faster disease progression as measured by pulmonary function testing and gas exchange. Conclusions Medical surveillance for CBD identifies individuals at significant risk of disease progression and impairment with sufficient time since first exposure. PMID:19681064

  14. Mutagenicity, carcinogenicity and teratogenicity of beryllium.

    Science.gov (United States)

    Léonard, A; Lauwerys, R

    1987-07-01

    The carcinogenicity of a number of beryllium compounds has been confirmed in experiments on laboratory animals and this metal has to be treated as a possible carcinogenic threat to man. These carcinogenic properties are associated with mutagenic activity as shown by the results of short-term tests performed in vitro with beryllium chloride and beryllium sulfate. These soluble beryllium compounds can produce some infidelity of in vitro synthesis, forward gene mutations in microorganisms and in mammalian cells. They are also able to induce cell transformation. In addition to the positive results obtained in several short-term assays beryllium compounds have been found to bind to nucleoproteins, to inhibit certain enzymes needed for DNA synthesis, to bind nucleic acids to cell membranes and to inhibit microtubule polymerization. The teratogenicity of beryllium salts is relatively unknown and needs additional investigation.

  15. Advances in identifying beryllium sensitization and disease.

    Science.gov (United States)

    Middleton, Dan; Kowalski, Peter

    2010-01-01

    Beryllium is a lightweight metal with unique qualities related to stiffness, corrosion resistance, and conductivity. While there are many useful applications, researchers in the 1930s and 1940s linked beryllium exposure to a progressive occupational lung disease. Acute beryllium disease is a pulmonary irritant response to high exposure levels, whereas chronic beryllium disease (CBD) typically results from a hypersensitivity response to lower exposure levels. A blood test, the beryllium lymphocyte proliferation test (BeLPT), was an important advance in identifying individuals who are sensitized to beryllium (BeS) and thus at risk for developing CBD. While there is no true "gold standard" for BeS, basic epidemiologic concepts have been used to advance our understanding of the different screening algorithms.

  16. Preparation of Beryllium Targets by Vacuum Evaporation

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    The apparatus is shown in Fig.1, which is mounted within a conventional metal bell jar 45 cm in diameter and 70 cm high. The boat source could be seen through the windows of the appratus and the bell jar.There was no straight-line exit from the apparatus to the interor of the bell jar for Be vapor originating at the boat.Tantalum boat, 13 mm wide, 28 mm long, and 0.1 mm thick, was used as evaporation source. The distance from the boat to the substrate was 15 cm. Microscope glass slide coated with betaine as substrate.The Be foils produced by resistance heating were removed from the glass by dissolving the

  17. Targeted RP9 ablation and mutagenesis in mouse photoreceptor cells by CRISPR-Cas9

    Science.gov (United States)

    Lv, Ji-Neng; Zhou, Gao-Hui; Chen, Xuejiao; Chen, Hui; Wu, Kun-Chao; Xiang, Lue; Lei, Xin-Lan; Zhang, Xiao; Wu, Rong-Han; Jin, Zi-Bing

    2017-01-01

    Precursor messenger RNA (Pre-mRNA) splicing is an essential biological process in eukaryotic cells. Genetic mutations in many spliceosome genes confer human eye diseases. Mutations in the pre-mRNA splicing factor, RP9 (also known as PAP1), predispose autosomal dominant retinitis pigmentosa (adRP) with an early onset and severe vision loss. However, underlying molecular mechanisms of the RP9 mutation causing photoreceptor degeneration remains fully unknown. Here, we utilize the CRISPR/Cas9 system to generate both the Rp9 gene knockout (KO) and point mutation knock in (KI) (Rp9, c.A386T, P.H129L) which is analogous to the reported one in the retinitis pigmentosa patients (RP9, c.A410T, P.H137L) in 661 W retinal photoreceptor cells in vitro. We found that proliferation and migration were significantly decreased in the mutated cells. Gene expression profiling by RNA-Seq demonstrated that RP associated genes, Fscn2 and Bbs2, were down-regulated in the mutated cells. Furthermore, pre-mRNA splicing of the Fscn2 gene was markedly affected. Our findings reveal a functional relationship between the ubiquitously expressing RP9 and the disease-specific gene, thereafter provide a new insight of disease mechanism in RP9-related retinitis pigmentosa. PMID:28216641

  18. Inhibited solid propellant composition containing beryllium hydride

    Science.gov (United States)

    Thompson, W. W. (Inventor)

    1978-01-01

    An object of this invention is to provide a composition of beryllium hydride and carboxy-terminated polybutadiene which is stable. Another object of this invention is to provide a method for inhibiting the reactivity of beryllium hydride toward carboxy-terminated polybutadiene. It was found that a small amount of lecithin inhibits the reaction of beryllium hydride with the acid groups in carboxy terminated polybutadiene.

  19. MEASUREMENTS OF THE PROPERTIES OF BERYLLIUM FOIL

    Energy Technology Data Exchange (ETDEWEB)

    ZHAO,Y.; WANG,H.

    2000-03-31

    The electrical conductivity of beryllium at radio frequency (800 MHz) and liquid nitrogen temperature were investigated and measured. This summary addresses a collection of beryllium properties in the literature, an analysis of the anomalous skin effect, the test model, the experimental setup and improvements, MAFIA simulations, the measurement results and data analyses. The final results show that the conductivity of beryllium is not as good as indicated by the handbook, yet very close to copper at liquid nitrogen temperature.

  20. CRISPR-Cas9 nuclear dynamics and target recognition in living cells.

    Science.gov (United States)

    Ma, Hanhui; Tu, Li-Chun; Naseri, Ardalan; Huisman, Maximiliaan; Zhang, Shaojie; Grunwald, David; Pederson, Thoru

    2016-08-29

    The bacterial CRISPR-Cas9 system has been repurposed for genome engineering, transcription modulation, and chromosome imaging in eukaryotic cells. However, the nuclear dynamics of clustered regularly interspaced short palindromic repeats (CRISPR)-associated protein 9 (Cas9) guide RNAs and target interrogation are not well defined in living cells. Here, we deployed a dual-color CRISPR system to directly measure the stability of both Cas9 and guide RNA. We found that Cas9 is essential for guide RNA stability and that the nuclear Cas9-guide RNA complex levels limit the targeting efficiency. Fluorescence recovery after photobleaching measurements revealed that single mismatches in the guide RNA seed sequence reduce the target residence time from >3 h to as low as CRISPR discriminates between genuine versus mismatched targets for genome editing via radical alterations in residence time.

  1. Targeted Germline Modifications in Rats Using CRISPR/Cas9 and Spermatogonial Stem Cells

    Directory of Open Access Journals (Sweden)

    Karen M. Chapman

    2015-03-01

    Full Text Available Organisms with targeted genomic modifications are efficiently produced by gene editing in embryos using CRISPR/Cas9 RNA-guided DNA endonuclease. Here, to facilitate germline editing in rats, we used CRISPR/Cas9 to catalyze targeted genomic mutations in rat spermatogonial stem cell cultures. CRISPR/Cas9-modified spermatogonia regenerated spermatogenesis and displayed long-term sperm-forming potential following transplantation into rat testes. Targeted germline mutations in Epsti1 and Erbb3 were vertically transmitted from recipients to exclusively generate “pure,” non-mosaic mutant progeny. Epsti1 mutant rats were produced with or without genetic selection of donor spermatogonia. Monoclonal enrichment of Erbb3 null germlines unmasked recessive spermatogenesis defects in culture that were buffered in recipients, yielding mutant progeny isogenic at targeted alleles. Thus, spermatogonial gene editing with CRISPR/Cas9 provided a platform for generating targeted germline mutations in rats and for studying spermatogenesis.

  2. Post irradiation characterization of beryllium and beryllides after high temperature irradiation up to 3000 appm helium production in HIDOBE-01

    Energy Technology Data Exchange (ETDEWEB)

    Fedorov, A.V., E-mail: fedorov@nrg.eu [Nuclear Research and Consultancy Group, Westerduinweg 3, Postbus 25, Petten, 1755 ZG (Netherlands); Til, S. van; Stijkel, M.P. [Nuclear Research and Consultancy Group, Westerduinweg 3, Postbus 25, Petten, 1755 ZG (Netherlands); Nakamichi, M. [Japan Atomic Energy Agency, Rokkasho (Japan); Zmitko, M. [The European Joint Undertaking for ITER and the Development of Fusion Energy, c/ Josep Pla, n° 2, Torres Diagonal Litoral, Edificio B3, Barcelona 08019 (Spain)

    2016-01-15

    Titanium beryllides are considered as advanced candidate material for neutron multiplier for the helium cooled pebble bed (HCPB) and/or the water cooled ceramic breeder (WCCB) breeder blankets. In the HIDOBE-01 (HIgh DOse irradiation of BEryllium) experiment, beryllium and beryllide pellets with 5 at% and 7 at% Ti are irradiated at four different target temperatures (T{sub irr}): 425 °C, 525 °C, 650 °C and 750 °C up to the dose corresponding to 3000 appm He production in beryllium. The pellets were supplied by JAEA. During post irradiation examinations the critical properties of volumetric swelling and tritium retention were studied. Both titanium beryllide grades show significantly less swelling than the beryllium grade, with the difference increasing with the irradiation temperature. The irradiation induced swelling was studied by using direct dimensions. Both beryllide grades showed much less swelling as compare to the reference beryllium grade. Densities of the grades were studied by Archimedean immersion and by He-pycnometry, giving indications of porosity formation. While both beryllide grades show no significant reduction in density at all irradiation temperatures, the beryllium density falls steeply at higher T{sub irr}. Finally, the tritium release and retention were studied by temperature programmed desorption (TPD). Beryllium shows the same strong tritium retention as earlier observed in studies on beryllium pebbles, while the tritium inventory of the beryllides is significantly less, already at the lowest T{sub irr} of 425 °C.

  3. Beryllium Exposure Control Program at the Cardiff Atomic Weapons Establishment in the United Kingdom.

    Science.gov (United States)

    Johnson, J S; Foote, K; McClean, M; Cogbill, G

    2001-05-01

    The Cardiff Atomic Weapons Establishment (AWE) plant, located in Cardiff, Wales, United Kingdom, used metallic beryllium in their beryllium facility during the years of operation 1961-1997. The beryllium production processes included melting and casting, powder production, pressing, machining, and heat and surface treatments. As part of Cardiff's industrial hygiene program, extensive area measurements and personal lapel measurements of airborne beryllium concentrations were collected for Cardiff workers over the 36-year period of operation. In addition to extensive air monitoring, the beryllium control program also utilized surface contamination controls, building design, engineering controls, worker controls, material controls, and medical surveillance. The electronic database includes 367,757 area sampling records at 101 locations and 217,681 personal lapel sampling records collected from 194 employees over the period 1981-1997. Similar workplace samples were collected from 1961 to 1980, but they were not analyzed because they were not available electronically. Annual personal mean sampling concentrations for all workers ranged from 0.11 to 0.72 micrograms per cubic meter (microg/m3) with 95th percentiles ranging from 0.22 to 1.89 microg/m3; foundry workers worked in the highest concentration areas with a mean of 0.87 microg/m3 and a 95th percentile of 2.9 microg/m3. Area sampling concentrations, as expected, were lower than personal sampling concentrations. Mean annual area sample concentrations for all locations ranged from 0.02 to 0.32 microg/m3. The area sample 95th percentile concentrations for all years were below 0.5 microg/m3. For the overwhelming majority of samples, airborne beryllium concentrations were below the 2.0 microg/m3 standard. Although blood lymphocyte testing for beryllium sensitization has not been routinely conducted among these workers, this metal beryllium processing facility is the only large scale beryllium facility of its kind to have

  4. Beryllium particulate exposure and disease relations in a beryllium machining plant.

    Science.gov (United States)

    Kelleher, P C; Martyny, J W; Mroz, M M; Maier, L A; Ruttenber, A J; Young, D A; Newman, L S

    2001-03-01

    We examined the relationship between exposure to beryllium and the presence of beryllium sensitization (BeS) and chronic beryllium disease (CBD) in a cohort of workers in a beryllium precision machining facility. Twenty workers with BeS or CBD (cases) were compared with 206 worker-controls in a case-control study. Exposure for each job title was measured using cascade impactors placed in the workers' breathing zone to measure total beryllium exposure and exposure to particles 0.20. In conclusion, increased cumulative and LTW exposure to total and respirable beryllium was observed in workers with CBD or BeS compared with the controls. These results support efforts to control beryllium exposure in the workplace.

  5. Beryllium Drive Disc Characterization for Laboratory Astrophysics Experiments

    Science.gov (United States)

    Ditmar, J. R.; Drake, R. P.; Kuranz, C. C.; Grosskopf, M. J.

    2009-11-01

    Laboratory Astrophysics scales large-scale phenomena, such as core-collapse supernovae shocks, down to the sub-millimeter scale for investigation in a laboratory setting. In some experiments, targets are constructed with a 20μm thick beryllium disc attached to a polyimide tube. A shockwave is created by irradiating the Be disc with ˜ 4kJ of energy from the Omega Laser. The Be material is rolled into a 20μm sheet and then machined to a 2.5mm diameter. Characterizing the roughness and knowing if there are any major features on the initial surface could affect interpretations of data taken during experiments. Structure in the Beryllium discs could become an important parameter in future high-fidelity computer simulations. Surfaces were characterized with a Scanning Electron Microscope and an Atomic Force Microscope.

  6. Broadening Staphylococcus aureus Cas9 Targeting Range by Modifying PAM Recognition

    Science.gov (United States)

    Kleinstiver, Benjamin P.; Prew, Michelle S.; Tsai, Shengdar Q.; Nguyen, Nhu T.; Topkar, Ved V.; Zheng, Zongli; Joung, J. Keith

    2015-01-01

    CRISPR-Cas9 nucleases are primarily guided by RNA-DNA interactions but also require Cas9-mediated recognition of a protospacer adjacent motif (PAM). While potentially advantageous for specificity, extended PAM sequences limit the targeting range of Cas9 orthologues for genome editing. One possible strategy to relieve this restriction is to relax specificities for certain positions within the PAM. Here we used molecular evolution to modify the NNGRRT PAM specificity of Staphylococcus aureus Cas9 (SaCas9). One variant we identified, referred to as KKH SaCas9, shows robust genome editing activities at endogenous human target sites with NNNRRT PAMs. Importantly, using GUIDE-seq, we show that both wild-type and KKH SaCas9 induce comparable numbers of off-target effects in human cells. KKH SaCas9 increased the targeting range of SaCas9 by nearly two- to four-fold. Our molecular evolution strategy does not require structural information and therefore should be applicable to a wide range of Cas9 orthologues. PMID:26524662

  7. Discovery of cancer drug targets by CRISPR-Cas9 screening of protein domains.

    Science.gov (United States)

    Shi, Junwei; Wang, Eric; Milazzo, Joseph P; Wang, Zihua; Kinney, Justin B; Vakoc, Christopher R

    2015-06-01

    CRISPR-Cas9 genome editing technology holds great promise for discovering therapeutic targets in cancer and other diseases. Current screening strategies target CRISPR-Cas9-induced mutations to the 5' exons of candidate genes, but this approach often produces in-frame variants that retain functionality, which can obscure even strong genetic dependencies. Here we overcome this limitation by targeting CRISPR-Cas9 mutagenesis to exons encoding functional protein domains. This generates a higher proportion of null mutations and substantially increases the potency of negative selection. We also show that the magnitude of negative selection can be used to infer the functional importance of individual protein domains of interest. A screen of 192 chromatin regulatory domains in murine acute myeloid leukemia cells identifies six known drug targets and 19 additional dependencies. A broader application of this approach may allow comprehensive identification of protein domains that sustain cancer cells and are suitable for drug targeting.

  8. Modeling of hydrogen interactions with beryllium

    Energy Technology Data Exchange (ETDEWEB)

    Longhurst, G.R. [Lockheed Martin Idaho Technologies Co., Idaho Falls, ID (United States)

    1998-01-01

    In this paper, improved mathematical models are developed for hydrogen interactions with beryllium. This includes the saturation effect observed for high-flux implantation of ions from plasmas and retention of tritium produced from neutronic transmutations in beryllium. Use of the models developed is justified by showing how they can replicated experimental data using the TMAP4 tritium transport code. (author)

  9. Investigation of beryllium/steam interaction

    Energy Technology Data Exchange (ETDEWEB)

    Chekhonadskikh, A.M.; Vurim, A.D.; Vasilyev, Yu.S.; Pivovarov, O.S. [Inst. of Atomic Energy National Nuclear Center of the Republic of Kazakstan Semipalatinsk (Kazakhstan); Shestakov, V.P.; Tazhibayeva, I.L.

    1998-01-01

    In this report program on investigations of beryllium emissivity and transient processes on overheated beryllium surface attacked by water steam to be carried out in IAE NNC RK within Task S81 TT 2096-07-16 FR. The experimental facility design is elaborated in this Report. (author)

  10. Benchmark Experiment for Beryllium Slab Samples

    Institute of Scientific and Technical Information of China (English)

    NIE; Yang-bo; BAO; Jie; HAN; Rui; RUAN; Xi-chao; REN; Jie; HUANG; Han-xiong; ZHOU; Zu-ying

    2015-01-01

    In order to validate the evaluated nuclear data on beryllium,a benchmark experiment has been performed at China Institution of Atomic Energy(CIAE).Neutron leakage spectra from pure beryllium slab samples(10cm×10cm×11cm)were measured at 61°and 121°using timeof-

  11. Diffusion-bonded beryllium aluminum optical structures

    Science.gov (United States)

    Grapes, Thomas F.

    2003-12-01

    Beryllium aluminum material can present significant advantages for optical support structures. A likely advantage of beryllium aluminum compared to aluminum or titanium for such structures is its higher specific stiffness. However, beryllium aluminum material is significantly more expensive than most competing materials. The cost problem with beryllium aluminum is exacerbated if fabrication methods that result in near net shape parts are not used. Near net shape methods result in the least amount of material "thrown away" in the fabrication process. Casting is a primary example of near net shape manufacturing that is appropriate for some optical support structures. Casting aluminum, and other materials as well, is common. Casting of beryllium aluminum is very difficult, however, and has not had significant success. Diffusion bonding - a different approach for achieving near net shape beryllium aluminum optical support structures, was pursued and accomplished. Diffusion bonding is a term used to describe the joining of solid metal pieces under high temperature and pressure, but without melting. Three different optical support structures were designed and built of beryllium aluminum using diffusion bonding. Relatively small solid beryllium aluminum pieces were arranged together and then joined under hot isostatic pressure conditions. The resulting relatively large pressure bonded part was then machined to achieve the final product. Significant cost savings as compared to machining the part from a solid block were realized. Difficulties achieving diffusion bonds in complex joints were experienced and addressed.

  12. BERYLLIUM MEASUREMENT IN COMMERCIALLY AVAILABLE WET WIPES

    Energy Technology Data Exchange (ETDEWEB)

    Youmans-Mcdonald, L.

    2011-02-18

    Analysis for beryllium by fluorescence is now an established method which is used in many government-run laboratories and commercial facilities. This study investigates the use of this technique using commercially available wet wipes. The fluorescence method is widely documented and has been approved as a standard test method by ASTM International and the National Institute for Occupational Safety and Health (NIOSH). The procedure involves dissolution of samples in aqueous ammonium bifluoride solution and then adding a small aliquot to a basic hydroxybenzoquinoline sulfonate fluorescent dye (Berylliant{trademark} Inc. Detection Solution Part No. CH-2) , and measuring the fluorescence. This method is specific to beryllium. This work explores the use of three different commercial wipes spiked with beryllium, as beryllium acetate or as beryllium oxide and subsequent analysis by optical fluorescence. The effect of possible interfering metals such as Fe, Ti and Pu in the wipe medium is also examined.

  13. Some characteristics of fine beryllium particle combustion

    Science.gov (United States)

    Davydov, D. A.; Kholopova, O. V.; Kolbasov, B. N.

    2007-08-01

    Beryllium dust will be produced under plasma interaction with beryllium armor of the first wall in ITER. Exothermal reaction of this dust with water steam or air, which can leak into the reactor vacuum chamber in some accidents, gives concern in respect to reactor safety. Results of studies devoted to combustion of fine beryllium particles are reviewed in the paper. A chemically active medium and elevated temperature are prerequisite to the combustion of beryllium particles. Their ignition is hampered by oxide films, which form a diffusion barrier on the particle surface as a result of pre-flame oxidation. The temperature to initiate combustion of particles depends on flame temperature, particle size, composition of combustible mixture, heating rate and other factors. In mixtures enriched with combustible, the flame temperature necessary to ignite individual particles approaches the beryllium boiling temperature.

  14. Lowering serum lipids via PCSK9-targeting drugs: current advances and future perspectives

    Science.gov (United States)

    He, Ni-ya; Li, Qing; Wu, Chun-yan; Ren, Zhong; Gao, Ya; Pan, Li-hong; Wang, Mei-mei; Wen, Hong-yan; Jiang, Zhi-sheng; Tang, Zhi-han; Liu, Lu-shan

    2017-01-01

    Proprotein convertase subtilisin/kexin type 9 (PCSK9), also known as neural apoptosis regulated convertase (NARC1), is a key modulator of cholesterol metabolism. PCSK9 increases the serum concentration of low-density lipoprotein cholesterol by escorting low-density lipoprotein receptors (LDLRs) from the membrane of hepatic cells into lysosomes, where the LDLRs are degraded. Owing to the importance of PCSK9 in lipid metabolism, considerable effort has been made over the past decade in developing drugs targeting PCSK9 to lower serum lipid levels. Nevertheless, some problems and challenges remain. In this review we first describes the structure and function of PCSK9 and its gene polymorphisms. We then discuss the various designs of pharmacological targets of PCSK9, including those that block the binding of PCSK9 to hepatic LDLRs (mimetic peptides, adnectins, and monoclonal antibodies), inhibit PCSK9 expression (the clustered regularly interspaced short palindromic repeats/Cas9 platform, small molecules, antisense oligonucleotides, and small interfering RNAs), and interfere with PCSK9 secretion. Finally, this review highlights future challenges in this field, including safety concerns associated with PCSK9 monoclonal antibodies, the limited utility of PCSK9 inhibitors in the central nervous system, and the cost-effectiveness of PCSK9 inhibitors. PMID:28112180

  15. Discovery of cancer drug targets by CRISPR-Cas9 screening of protein domains

    OpenAIRE

    Shi, Junwei; Wang, Eric; Milazzo, Joseph P.; Wang, Zhihua; Kinney, Justin B.; Vakoc, Christopher R.

    2015-01-01

    CRISPR-Cas9 genome editing technology holds great promise for discovering therapeutic targets in cancer and other diseases. Current screening strategies target CRISPR-induced mutations to the 5’ exons of candidate genes 1–5 , but this approach often produces in-frame variants that retain functionality, which can obscure even strong genetic dependencies. Here we overcome this limitation by targeting CRISPR mutagenesis to exons encoding functional protein domains. This generates a higher propor...

  16. Beryllium coating on Inconel tiles

    Energy Technology Data Exchange (ETDEWEB)

    Bailescu, V.; Burcea, G.; Lungu, C.P.; Mustata, I.; Lungu, A.M. [Association EURATOM-MEC Romania, National Institute of Laser, Plasma and Radiation Physics, Bucharest (Romania); Rubel, M. [Alfven Laboratory, Royal Institute of Technology, Stockholm (Sweden); Coad, J.P. [Culham Science Centre, EURATOM-UKAEA Fusion Association, Abingdon, OX, Oxon (United Kingdom); Matthews, G.; Pedrick, L.; Handley, R. [UKAEA Fusion, Association Euratom-UKAEA, Culham Science and Engineering Centre, OX 3DB ABINGDON, Oxon (United Kingdom)

    2007-07-01

    Full text of publication follows: The Joint European Torus (JET) is a large experimental nuclear fusion device. Its aim is to confine and study the behaviour of plasma in conditions and dimensions approaching those required for a fusion reactor. The plasma is created in the toroidal shaped vacuum vessel of the machine in which it is confined by magnetic fields. In preparation for ITER a new ITER-like Wall (ILW) will be installed on Joint European Torus (JET), a wall not having any carbon facing the plasma [1]. In places Inconel tiles are to be installed, these tiles shall be coated with Beryllium. MEdC represented by the National Institute for Laser, Plasma and Radiation Physics, Magurele, Bucharest and in direct cooperation with Nuclear Fuel Plant Pitesti started to coat Inconel tiles with 8 {mu}m of Beryllium in accordance with the requirements of technical specification and fit for installation in the JET machine. This contribution provides an overview of the principles of manufacturing processes using thermal evaporation method in vacuum and the properties of the prepared coatings. The optimization of the manufacturing process (layer thickness, structure and purity) has been carried out on Inconel substrates (polished and sand blasted) The results of the optimization process and analysis (SEM, TEM, XRD, Auger, RBS, AFM) of the coatings will be presented. Reference [1] Takeshi Hirai, H. Maier, M. Rubel, Ph. Mertens, R. Neu, O. Neubauer, E. Gauthier, J. Likonen, C. Lungu, G. Maddaluno, G. F. Matthews, R. Mitteau, G. Piazza, V. Philipps, B. Riccardi, C. Ruset, I. Uytdenhouwen, R and D on full tungsten divertor and beryllium wall for JET TIER-like Wall Project, 24. Symposium on Fusion Technology - 11-15 September 2006 -Warsaw, Poland. (authors)

  17. Targeting cellular mRNAs translation by CRISPR-Cas9.

    Science.gov (United States)

    Liu, Yuchen; Chen, Zhicong; He, Anbang; Zhan, Yonghao; Li, Jianfa; Liu, Li; Wu, Hanwei; Zhuang, Chengle; Lin, Junhao; Zhang, Qiaoxia; Huang, Weiren

    2016-07-13

    Recently CRISPR-Cas9 system has been reported to be capable of targeting a viral RNA, and this phenomenon thus raises an interesting question of whether Cas9 can also influence translation of cellular mRNAs. Here, we show that both natural and catalytically dead Cas9 can repress mRNA translation of cellular genes, and that only the first 14 nt in the 5' end of sgRNA is essential for this process. CRISPR-Cas9 can suppress the protein expression of an unintended target gene without affecting its DNA sequence and causes unexpected phenotypic changes. Using the designed RNA aptamer-ligand complexes which physically obstruct translation machinery, we indicate that roadblock mechanism is responsible for this phenomenon. Our work suggests that studies on Cas9 should avoid the potential off-target effects by detecting the alteration of genes at both the DNA and protein levels.

  18. Postirradiation examination of beryllium pebbles

    Energy Technology Data Exchange (ETDEWEB)

    Gelles, D.S. [Pacific Northwest National Lab., Richland, WA (United States)

    1998-03-01

    Postirradiation examinations of COBRA-1A beryllium pebbles irradiated in the EBR-II fast reactor at neutron fluences which generated 2700--3700 appm helium have been performed. Measurements included density change, optical microscopy, scanning electron microscopy, and transmission electron microscopy. The major change in microstructure is development of unusually shaped helium bubbles forming as highly non-equiaxed thin platelet-like cavities on the basal plane. Measurement of the swelling due to cavity formation was in good agreement with density change measurements.

  19. 40 CFR 421.150 - Applicability: Description of the primary beryllium subcategory.

    Science.gov (United States)

    2010-07-01

    ... primary beryllium subcategory. 421.150 Section 421.150 Protection of Environment ENVIRONMENTAL PROTECTION... CATEGORY Primary Beryllium Subcategory § 421.150 Applicability: Description of the primary beryllium... beryllium by primary beryllium facilities processing beryllium ore concentrates or beryllium hydroxide...

  20. CRISPR/Cas9-mediated targeted mutagenesis in the liverwort Marchantia polymorpha L.

    Science.gov (United States)

    Sugano, Shigeo S; Shirakawa, Makoto; Takagi, Junpei; Matsuda, Yoriko; Shimada, Tomoo; Hara-Nishimura, Ikuko; Kohchi, Takayuki

    2014-03-01

    Targeted genome modification technologies are key tools for functional genomics. The clustered regularly interspaced short palindromic repeats (CRISPR)-associated endonuclease Cas9 system (CRISPR/Cas9) is an emerging technology for targeted genome modification. The CRISPR/Cas9 system consists of a short guide RNA (gRNA), which specifies the target genome sequence, and the Cas9 protein, which has endonuclease activity. The CRISPR/Cas9 system has been applied to model animals and flowering plants, including rice, sorghum, wheat, tobacco and Arabidopsis. Here, we report the application of CRISPR/Cas9 to targeted mutagenesis in the liverwort Marchantia polymorpha L., which has emerged as a model species for studying land plant evolution. The U6 promoter of M. polymorpha was identified and cloned to express the gRNA. The target sequence of the gRNA was designed to disrupt the gene encoding auxin response factor 1 (ARF1) in M. polymorpha. Using Agrobacterium-mediated transformation, we isolated stable mutants in the gametophyte generation of M. polymorpha. CRISPR/Cas9-based site-directed mutagenesis in vivo was achieved using either the Cauliflower mosaic virus 35S or M. polymorpha EF1α promoter to express Cas9. Isolated mutant individuals showing an auxin-resistant phenotype were not chimeric. Moreover, stable mutants were produced by asexual reproduction of T1 plants. Multiple arf1 alleles were easily established using CRIPSR/Cas9-based targeted mutagenesis. Our results provide a rapid and simple approach for molecular genetics in M. polymorpha, and raise the possibility that CRISPR/Cas9 may be applied to a wide variety of plant species.

  1. Conditional targeting of Ispd using paired Cas9 nickase and a single DNA template in mice

    Directory of Open Access Journals (Sweden)

    Angus Yiu-fai Lee

    2014-01-01

    Full Text Available CRISPR/Cas9 technology is a highly promising genome editing tool in the mouse, potentially overcoming the costs and time required for more traditional gene targeting methods in embryonic stem (ES cells. Recently, compared to the wildtype nuclease, paired Cas9 nickase (Cas9n combined with single guide RNA (sgRNA molecules has been found to enhance the specificity of genome editing while reducing off-target effects. Paired Cas9n has been shown to be as efficient as Cas9 for generating insertion and deletion (indel mutations by non-homologous end joining and targeted deletion in the genome. However, an efficient and reliable approach to the insertion of loxP sites flanking critical exon(s to create a conditional allele of a target gene remains an elusive goal. In this study, we microinjected Cas9n RNA with sgRNAs together with a single DNA template encoding two loxP sites flanking (floxing exon 2 of the isoprenoid synthase containing domain (Ispd into the pronucleus and cytoplasm of C57BL/6NCr one-cell stage zygotes. After surgical transfer, one F0 mouse expressing a conditional allele was produced (at a frequency of ∼8% of live pups born. The floxed allele was transmitted through the germline to F1 progeny, and could be successfully recombined using Cre recombinase. This study indicates that conditional targeting can be accomplished effectively using paired Cas9n and a single DNA template.

  2. Selecting Pharmacological Targets of PCSK9%PCSK9的药理学筛选靶点

    Institute of Scientific and Technical Information of China (English)

    武春艳; 唐志晗; 刘录山; 姜志胜

    2009-01-01

    Hypercholesterolemia is a major risk factor for atherosclerosis and heart disease. Current cholesterol-limiting therapies fail in some patients, where additional therapeutic targets are needed. PCSK9 encodes a pro-protein convertase subtilisin/kexin type 9a that plays an important role in cholesterol metabolism by the modulation of LDL receptor levels in the liver. Gain-of-function mutations of PCSK9 resulted in elevated levels of LDL-cholesterol in the plasma. Loss-of-function mutations led to high levels of the LDL receptor and low LDL-cholesterol. This review focuses on the structure, functions and pharmacological targets of PCSK9.%前蛋白转化酶枯草溶菌素9(PCSK9)基因编码神经凋亡调节转化酶即NARC1,通过影响肝LDLR水平,在胆固醇代谢中发挥了重要的作用.其功能获得型突变使血浆胆固醇水平增高,而功能缺失型突变降低胆固醇水平.流行病学调查显示,高胆固醇血症是动脉粥样硬化和心脏病的主要危险因素.一些患者运用当前的降胆固醇药物治疗仍不能达到推荐的目标LDL水平,PCSK9作为新的降脂靶点引起了广泛的关注.本文将对PCSK9的结构、功能和药理学靶点进行综述.

  3. Technical issues for beryllium use in fusion blanket applications

    Energy Technology Data Exchange (ETDEWEB)

    McCarville, T.J.; Berwald, D.H.; Wolfer, W.; Fulton, F.J.; Lee, J.D.; Maninger, R.C.; Moir, R.W.; Beeston, J.M.; Miller, L.G.

    1985-01-01

    Beryllium is an excellent non-fissioning neutron multiplier for fusion breeder and fusion electric blanket applications. This report is a compilation of information related to the use of beryllium with primary emphasis on the fusion breeder application. Beryllium resources, production, fabrication, properties, radiation damage and activation are discussed. A new theoretical model for beryllium swelling is presented.

  4. Exposure-response analysis for beryllium sensitization and chronic beryllium disease among workers in a beryllium metal machining plant.

    Science.gov (United States)

    Madl, Amy K; Unice, Ken; Brown, Jay L; Kolanz, Marc E; Kent, Michael S

    2007-06-01

    The current occupational exposure limit (OEL) for beryllium has been in place for more than 50 years and was believed to be protective against chronic beryllium disease (CBD) until studies in the 1990s identified beryllium sensitization (BeS) and subclinical CBD in the absence of physical symptoms. Inconsistent sampling and exposure assessment methodologies have often prevented the characterization of a clear exposure-response relationship for BeS and CBD. Industrial hygiene (3831 personal lapel and 616 general area samples) and health surveillance data from a beryllium machining facility provided an opportunity to reconstruct worker exposures prior to the ascertainment of BeS or the diagnosis of CBD. Airborne beryllium concentrations for different job titles were evaluated, historical trends of beryllium levels were compared for pre- and postengineering control measures, and mean and upper bound exposure estimates were developed for workers identified as beryllium sensitized or diagnosed with subclinical or clinical CBD. Five approaches were used to reconstruct historical exposures of each worker: industrial hygiene data were pooled by year, job title, era of engineering controls, and the complete work history (lifetime weighted average) prior to diagnosis. Results showed that exposure metrics based on shorter averaging times (i.e., year vs. complete work history) better represented the upper bound worker exposures that could have contributed to the development of BeS or CBD. Results showed that beryllium-sensitized and CBD workers were exposed to beryllium concentrations greater than 0.2 microg/m3 (95th percentile), and 90% were exposed to concentrations greater than 0.4 microg/m3 (95th percentile) within a given year of their work history. Based on this analysis, BeS and CBD generally occurred as a result of exposures greater than 0.4 microg/m3 and maintaining exposures below 0.2 microg/m3 95% of the time may prevent BeS and CBD in the workplace.

  5. Targeted genome editing of sweet orange using Cas9/sgRNA.

    Directory of Open Access Journals (Sweden)

    Hongge Jia

    Full Text Available Genetic modification, including plant breeding, has been widely used to improve crop yield and quality, as well as to increase disease resistance. Targeted genome engineering is expected to contribute significantly to future varietal improvement, and genome editing technologies using zinc finger nucleases (ZFNs, transcription activator-like effector nucleases (TALENs, and clustered regularly interspaced short palindromic repeat (CRISPR/Cas9/single guide RNA (sgRNA have already been successfully used to genetically modify plants. However, to date, there has been no reported use of any of the current genome editing approaches in sweet orange, an important fruit crop. In this study, we first developed a novel tool, Xcc-facilitated agroinfiltration, for enhancing transient protein expression in sweet orange leaves. We then successfully employed Xcc-facilitated agroinfiltration to deliver Cas9, along with a synthetic sgRNA targeting the CsPDS gene, into sweet orange. DNA sequencing confirmed that the CsPDS gene was mutated at the target site in treated sweet orange leaves. The mutation rate using the Cas9/sgRNA system was approximately 3.2 to 3.9%. Off-target mutagenesis was not detected for CsPDS-related DNA sequences in our study. This is the first report of targeted genome modification in citrus using the Cas9/sgRNA system-a system that holds significant promise for the study of citrus gene function and for targeted genetic modification.

  6. Targeted genome editing of sweet orange using Cas9/sgRNA.

    Science.gov (United States)

    Jia, Hongge; Wang, Nian

    2014-01-01

    Genetic modification, including plant breeding, has been widely used to improve crop yield and quality, as well as to increase disease resistance. Targeted genome engineering is expected to contribute significantly to future varietal improvement, and genome editing technologies using zinc finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), and clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9/single guide RNA (sgRNA) have already been successfully used to genetically modify plants. However, to date, there has been no reported use of any of the current genome editing approaches in sweet orange, an important fruit crop. In this study, we first developed a novel tool, Xcc-facilitated agroinfiltration, for enhancing transient protein expression in sweet orange leaves. We then successfully employed Xcc-facilitated agroinfiltration to deliver Cas9, along with a synthetic sgRNA targeting the CsPDS gene, into sweet orange. DNA sequencing confirmed that the CsPDS gene was mutated at the target site in treated sweet orange leaves. The mutation rate using the Cas9/sgRNA system was approximately 3.2 to 3.9%. Off-target mutagenesis was not detected for CsPDS-related DNA sequences in our study. This is the first report of targeted genome modification in citrus using the Cas9/sgRNA system-a system that holds significant promise for the study of citrus gene function and for targeted genetic modification.

  7. Targeted mutagenesis in soybean using the CRISPR-Cas9 system

    OpenAIRE

    Sun, Xianjun; Hu, Zheng; Chen, Rui; Jiang, Qiyang; Song, Guohua; Zhang, Hui; Xi, Yajun

    2015-01-01

    Genome editing is a valuable technique for gene function analysis and crop improvement. Over the past two years, the CRISPR-Cas9 system has emerged as a powerful tool for precisely targeted gene editing. In this study, we predicted 11 U6 genes in soybean (Glycine max L.). We then constructed two vectors (pCas9-GmU6-sgRNA and pCas9-AtU6-sgRNA) using the soybean U6-10 and Arabidopsis U6-26 promoters, respectively, to produce synthetic guide RNAs (sgRNAs) for targeted gene mutagenesis. Three gen...

  8. Measuring and Reducing Off-Target Activities of Programmable Nucleases Including CRISPR-Cas9.

    Science.gov (United States)

    Koo, Taeyoung; Lee, Jungjoon; Kim, Jin-Soo

    2015-06-01

    Programmable nucleases, which include zinc-finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), and RNA-guided engineered nucleases (RGENs) repurposed from the type II clustered, regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein 9 (Cas9) system are now widely used for genome editing in higher eukaryotic cells and whole organisms, revolutionising almost every discipline in biological research, medicine, and biotechnology. All of these nucleases, however, induce off-target mutations at sites homologous in sequence with on-target sites, limiting their utility in many applications including gene or cell therapy. In this review, we compare methods for detecting nuclease off-target mutations. We also review methods for profiling genome-wide off-target effects and discuss how to reduce or avoid off-target mutations.

  9. Targeted mutagenesis in soybean using the CRISPR-Cas9 system.

    Science.gov (United States)

    Sun, Xianjun; Hu, Zheng; Chen, Rui; Jiang, Qiyang; Song, Guohua; Zhang, Hui; Xi, Yajun

    2015-05-29

    Genome editing is a valuable technique for gene function analysis and crop improvement. Over the past two years, the CRISPR-Cas9 system has emerged as a powerful tool for precisely targeted gene editing. In this study, we predicted 11 U6 genes in soybean (Glycine max L.). We then constructed two vectors (pCas9-GmU6-sgRNA and pCas9-AtU6-sgRNA) using the soybean U6-10 and Arabidopsis U6-26 promoters, respectively, to produce synthetic guide RNAs (sgRNAs) for targeted gene mutagenesis. Three genes, Glyma06g14180, Glyma08g02290 and Glyma12g37050, were selected as targets. Mutations of these three genes were detected in soybean protoplasts. The vectors were then transformed into soybean hairy roots by Agrobacterium rhizogenes infection, resulting in efficient target gene editing. Mutation efficiencies ranged from 3.2-9.7% using the pCas9-AtU6-sgRNA vector and 14.7-20.2% with the pCas9-GmU6-sgRNA vector. Biallelic mutations in Glyma06g14180 and Glyma08g02290 were detected in transgenic hairy roots. Off-target activities associated with Glyma06g14180 and Glyma12g37050 were also detected. Off-target activity would improve mutation efficiency for the construction of a saturated gene mutation library in soybean. Targeted mutagenesis using the CRISPR-Cas9 system should advance soybean functional genomic research, especially that of genes involved in the roots and nodules.

  10. Calculations for electron-impact excitation and ionization of beryllium

    Science.gov (United States)

    Zatsarinny, Oleg; Bartschat, Klaus; Fursa, Dmitry V.; Bray, Igor

    2016-12-01

    The B-spline R-matrix and the convergent close-coupling methods are used to study electron collisions with neutral beryllium over an energy range from threshold to 100 eV. Coupling to the target continuum significantly affects the results for transitions from the ground state, but to a lesser extent the strong transitions between excited states. Cross sections are presented for selected transitions between low-lying physical bound states of beryllium, as well as for elastic scattering, momentum transfer, and ionization. The present cross sections for transitions from the ground state from the two methods are in excellent agreement with each other, and also with other available results based on nonperturbative convergent pseudostate and time-dependent close-coupling models. The elastic cross section at low energies is dominated by a prominent shape resonance. The ionization from the {(2s2p)}3P and {(2s2p)}1P states strongly depends on the respective term. The current predictions represent an extensive set of electron scattering data for neutral beryllium, which should be sufficient for most modeling applications.

  11. Recommended design correlations for S-65 beryllium

    Energy Technology Data Exchange (ETDEWEB)

    Billone, M.C. [Argonne National Lab., IL (United States)

    1995-09-01

    The properties of tritium and helium behavior in irradiated beryllium are reviewed, along with the thermal-mechanical properties needed for ITER design analysis. Correlations are developed to describe the performance of beryllium in a fusion reactor environment. While this paper focuses on the use of beryllium as a plasma-facing component (PFC) material, the correlations presented here can also be used to describe the performance of beryllium as a neutron multiplier for a tritium breeding blanket. The performance properties for beryllium are subdivided into two categories: properties which do not change with irradiation damage to the bulk of the material; and properties which are degraded by neutron irradiation. The irradiation-independent properties described within are: thermal conductivity, specific heat capacity, thermal expansion, and elastic constants. Irradiation-dependent properties include: yield strength, ultimate tensile strength, plastic tangent modulus, uniform and total tensile elongation, thermal and irradiation-induced creep strength, He-induced swelling and tritium retention/release. The approach taken in developing properties correlations is to describe the behavior of dense, pressed S-65 beryllium -- the material chosen for ITER PFC application -- as a function of temperature. As there are essentially no data on the performance of porous and/or irradiated S-65 beryllium, the degradation of properties with as-fabricated porosity and irradiation are determined from the broad data base on S-200F, as well as other types and grades, and applied to S-65 beryllium by scaling factors. The resulting correlations can be used for Be produced by vacuum hot pressing (VHP) and cold-pressing (CP)/sintering(S)/hot-isostatic-pressing (HIP). The performance of plasma-sprayed beryllium is discussed but not quantified.

  12. CCTop: An Intuitive, Flexible and Reliable CRISPR/Cas9 Target Prediction Tool.

    Directory of Open Access Journals (Sweden)

    Manuel Stemmer

    Full Text Available Engineering of the CRISPR/Cas9 system has opened a plethora of new opportunities for site-directed mutagenesis and targeted genome modification. Fundamental to this is a stretch of twenty nucleotides at the 5' end of a guide RNA that provides specificity to the bound Cas9 endonuclease. Since a sequence of twenty nucleotides can occur multiple times in a given genome and some mismatches seem to be accepted by the CRISPR/Cas9 complex, an efficient and reliable in silico selection and evaluation of the targeting site is key prerequisite for the experimental success. Here we present the CRISPR/Cas9 target online predictor (CCTop, http://crispr.cos.uni-heidelberg.de to overcome limitations of already available tools. CCTop provides an intuitive user interface with reasonable default parameters that can easily be tuned by the user. From a given query sequence, CCTop identifies and ranks all candidate sgRNA target sites according to their off-target quality and displays full documentation. CCTop was experimentally validated for gene inactivation, non-homologous end-joining as well as homology directed repair. Thus, CCTop provides the bench biologist with a tool for the rapid and efficient identification of high quality target sites.

  13. Targeted mutagenesis in cotton (Gossypium hirsutum L.) using the CRISPR/Cas9 system

    Science.gov (United States)

    Chen, Xiugui; Lu, Xuke; Shu, Na; Wang, Shuai; Wang, Junjuan; Wang, Delong; Guo, Lixue; Ye, Wuwei

    2017-01-01

    The CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats)/Cas9 system has been widely used for genome editing in various plants because of its simplicity, high efficiency and design flexibility. However, to our knowledge, there is no report on the application of CRISPR/Cas9-mediated targeted mutagenesis in cotton. Here, we report the genome editing and targeted mutagenesis in upland cotton (Gossypium hirsutum L., hereafter cotton) using the CRISPR/Cas9 system. We designed two guide RNAs to target distinct sites of the cotton Cloroplastos alterados 1 (GhCLA1) and vacuolar H+-pyrophosphatase (GhVP) genes. Mutations in these two genes were detected in cotton protoplasts. Most of the mutations were nucleotide substitutions, with one nucleotide insertion and one substitution found in GhCLA1 and one deletion found in GhVP in cotton protoplasts. Subsequently, the two vectors were transformed into cotton shoot apexes through Agrobacterium-mediated transformation, resulting in efficient target gene editing. Most of the mutations were nucleotide deletions, and the mutation efficiencies were 47.6–81.8% in transgenic cotton plants. Evaluation using restriction-enzyme-PCR assay and sequence analysis detected no off-target mutations. Our results indicated that the CRISPR/Cas9 system was an efficient and specific tool for targeted mutagenesis of the cotton genome. PMID:28287154

  14. Efficient gene targeting in golden Syrian hamsters by the CRISPR/Cas9 system.

    Directory of Open Access Journals (Sweden)

    Zhiqiang Fan

    Full Text Available The golden Syrian hamster is the model of choice or the only rodent model for studying many human diseases. However, the lack of gene targeting tools in hamsters severely limits their use in biomedical research. Here, we report the first successful application of the CRISPR/Cas9 system to efficiently conduct gene targeting in hamsters. We designed five synthetic single-guide RNAs (sgRNAs--three for targeting the coding sequences for different functional domains of the hamster STAT2 protein, one for KCNQ1, and one for PPP1R12C--and demonstrated that the CRISPR/Cas9 system is highly efficient in introducing site-specific mutations in hamster somatic cells. We then developed unique pronuclear (PN and cytoplasmic injection protocols in hamsters and produced STAT2 knockout (KO hamsters by injecting the sgRNA/Cas9, either in the form of plasmid or mRNA, targeting exon 4 of hamster STAT2. Among the produced hamsters, 14.3% and 88.9% harbored germline-transmitted STAT2 mutations from plasmid and mRNA injection, respectively. Notably, 10.4% of the animals produced from mRNA injection were biallelically targeted. This is the first success in conducting site-specific gene targeting in hamsters and can serve as the foundation for developing other genetically engineered hamster models for human disease.

  15. Efficiency and Inheritance of Targeted Mutagenesis in Maize Using CRISPR-Cas9.

    Science.gov (United States)

    Zhu, Jinjie; Song, Ning; Sun, Silong; Yang, Weilong; Zhao, Haiming; Song, Weibin; Lai, Jinsheng

    2016-01-20

    CRISPR/Cas (clustered regularly interspaced short palindromic repeats/CRISPR-associated proteins) is an adaptive immune system in bacteria and archaea to defend against invasion from foreign DNA fragments. Recently, it has been developed as a powerful targeted genome editing tool for a wide variety of species. However, its application in maize has only been tested with transiently expressed somatic cells or with a limited number of stable transgenic T0 plants. The exact efficiency and specificity of the CRISPR/Cas system in the highly complex maize genome has not been documented yet. Here we report an extensive study of the well-studied type II CRISPR-Cas9 system for targeted genome editing in maize, with the codon-optimized Cas9 protein and the short non-coding guide RNA generated through a functional maize U6 snRNA promoter. Targeted gene mutagenesis was detected for 90 loci by maize protoplast assay, with an average cleavage efficiency of 10.67%. Stable knockout transformants for maize phytoene synthase gene (PSY1) were obtained. Mutations occurred in germ cells can be stably inherited to the next generation. Moreover, no off-target effect was detected at the computationally predicted putative off-target loci. No significant difference between the transcriptomes of the Cas9 expressed and non-expressed lines was detected. Our results confirmed that the CRISPR-Cas9 could be successfully applied as a robust targeted genome editing system in maize.

  16. Examination of Beryllium Under Intense High Energy Proton Beam at CERN's HiRadMat Facility

    CERN Document Server

    Ammigan, K; Hurh, P; Zwaska, R; Atherton, A; Caretta, O; Davenne, t; Densham, C; Fitton, M; Loveridge, P; O'Dell, J; Roberts, S; Kuksenko, v; Butcher, M; Calviani, M; Guinchard, M; Losito, R

    2015-01-01

    Beryllium is extensively used in various accelerator beam lines and target facilities as material for beam win- dows, and to a lesser extent, as secondary particle produc- tion targets. With increasing beam intensities of future ac- celerator facilities, it is critical to understand the response of beryllium under extreme conditions to avoid compro- mising particle production efficiency by limiting beam pa- rameters. As a result, the planned experiment at CERN’s HiRadMat facility will take advantage of the test facility’s tunable high intensity proton beam to probe and investigate the damage mechanisms of several grades of beryllium. The test matrix will consist of multiple arrays of thin discs of varying thicknesses as well as cylinders, each exposed to increasing beam intensities. Online instrumentations will acquire real time temperature, strain, and vibration data of the cylinders, while Post-Irradiation-Examination (PIE) of the discs will exploit advanced microstructural characteri- zation and imagin...

  17. Enhancing Targeted Genomic DNA Editing in Chicken Cells Using the CRISPR/Cas9 System

    Science.gov (United States)

    Wang, Ling; Yang, Likai; Guo, Yijie; Du, Weili; Yin, Yajun; Zhang, Tao; Lu, Hongzhao

    2017-01-01

    The CRISPR/Cas9 system has enabled highly efficient genome targeted editing for various organisms. However, few studies have focused on CRISPR/Cas9 nuclease-mediated chicken genome editing compared with mammalian genomes. The current study combined CRISPR with yeast Rad52 (yRad52) to enhance targeted genomic DNA editing in chicken DF-1 cells. The efficiency of CRISPR/Cas9 nuclease-induced targeted mutations in the chicken genome was increased to 41.9% via the enrichment of the dual-reporter surrogate system. In addition, the combined effect of CRISPR nuclease and yRad52 dramatically increased the efficiency of the targeted substitution in the myostatin gene using 50-mer oligodeoxynucleotides (ssODN) as the donor DNA, resulting in a 36.7% editing efficiency after puromycin selection. Furthermore, based on the effect of yRad52, the frequency of exogenous gene integration in the chicken genome was more than 3-fold higher than that without yRad52. Collectively, these results suggest that ssODN is an ideal donor DNA for targeted substitution and that CRISPR/Cas9 combined with yRad52 significantly enhances chicken genome editing. These findings could be extensively applied in other organisms. PMID:28068387

  18. Metallurgical viewpoints on the brittleness of beryllium

    Energy Technology Data Exchange (ETDEWEB)

    Lagerberg, G.

    1960-02-15

    At present the development and use of beryllium metal for structural applications is severely hampered by its brittleness. Reasons for this lack of ductility are reviewed in discussing the deformation behaviour of beryllium in relation to other hexagonal metals. The ease of fracturing in beryllium is assumed to be a consequence of a limited number of deformation modes in combination with high deformation resistance. Models for the nucleation of fracture are suggested. The relation of ductility to elastic constants as well as to grain size, texture and alloying additions is discussed.

  19. THE IDAHO NATIONAL LABORATORY BERYLLIUM TECHNOLOGY UPDATE

    Energy Technology Data Exchange (ETDEWEB)

    Glen R. Longhurst

    2007-12-01

    A Beryllium Technology Update meeting was held at the Idaho National Laboratory on July 18, 2007. Participants came from the U.S., Japan, and Russia. There were two main objectives of this meeting. One was a discussion of current technologies for beryllium in fission reactors, particularly the Advanced Test Reactor and the Japan Materials Test Reactor, and prospects for material availability in the coming years. The second objective of the meeting was a discussion of a project of the International Science and Technology Center regarding treatment of irradiated beryllium for disposal. This paper highlights discussions held during that meeting and major conclusions reached

  20. RAC-tagging: Recombineering And Cas9-assisted targeting for protein tagging and conditional analyses.

    Science.gov (United States)

    Baker, Oliver; Gupta, Ashish; Obst, Mandy; Zhang, Youming; Anastassiadis, Konstantinos; Fu, Jun; Stewart, A Francis

    2016-05-24

    A fluent method for gene targeting to establish protein tagged and ligand inducible conditional loss-of-function alleles is described. We couple new recombineering applications for one-step cloning of gRNA oligonucleotides and rapid generation of short-arm (~1 kb) targeting constructs with the power of Cas9-assisted targeting to establish protein tagged alleles in embryonic stem cells at high efficiency. RAC (Recombineering And Cas9)-tagging with Venus, BirM, APEX2 and the auxin degron is facilitated by a recombineering-ready plasmid series that permits the reuse of gene-specific reagents to insert different tags. Here we focus on protein tagging with the auxin degron because it is a ligand-regulated loss-of-function strategy that is rapid and reversible. Furthermore it includes the additional challenge of biallelic targeting. Despite high frequencies of monoallelic RAC-targeting, we found that simultaneous biallelic targeting benefits from long-arm (>4 kb) targeting constructs. Consequently an updated recombineering pipeline for fluent generation of long arm targeting constructs is also presented.

  1. Efficient targeted mutagenesis in soybean by TALENs and CRISPR/Cas9.

    Science.gov (United States)

    Du, Hongyang; Zeng, Xuanrui; Zhao, Meng; Cui, Xiaopei; Wang, Qing; Yang, Hui; Cheng, Hao; Yu, Deyue

    2016-01-10

    Gene targeting (GT) is of great significance for advancing basic plant research and crop improvement. Both TALENs (transcription activator-like effectors nucleases) and CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/CRISPR-associated 9) systems have been developed for genome editing in eukaryotes, including crop plants. In this work, we present the comparative analysis of these two technologies for two soybean genome editing targets, GmPDS11 and GmPDS18. We found GT in soybean hairy roots with a single targeting efficiency range of 17.5-21.1% by TALENs, 11.7-18.1% by CRISPR/Cas9 using the AtU6-26 promoter, and 43.4-48.1% by CRISPR/Cas9 using the GmU6-16g-1 promoter, suggesting that the CRISPR/Cas9 using the GmU6-16g-1 promoter is probably a much more efficient tool compared to the other technologies. Similarly, our double mutation GT efficiency experiment with these three technologies displayed a targeting efficiency of 6.25% by TALENs, 12.5% by CRISPR/Cas9 using the AtU6-26 promoter, and 43.4-48.1% by CRISPR/Cas9 using the GmU6-16g-1 promoter, suggesting that CRISPR/Cas9 is still a better choice for simultaneous editing of multiple homoeoalleles. Furthermore, we observed albino and dwarf buds (PDS knock-out) by soybean transformation in cotyledon nodes. Our results demonstrated that both TALENs and CRISPR/Cas9 systems are powerful tools for soybean genome editing.

  2. Targeting PCSK9 as a promising new mechanism for lowering low-density lipoprotein cholesterol.

    Science.gov (United States)

    Della Badia, Laura A; Elshourbagy, Nabil A; Mousa, Shaker A

    2016-08-01

    Statins and other lipid-lowering drugs have dominated the market for many years for achievement of recommended levels of low-density lipoprotein cholesterol (LDL-C). However, a substantial number of high-risk patients are unable to achieve the LDL-C goal. Proprotein convertase subtilisin/kexin 9 (PCSK9) has recently emerged as a new, promising key therapeutic target for hypercholesterolemia. PCSK9 is a protease involved in chaperoning the low-density lipoprotein receptor to the process of degradation. PCSK9 inhibitors and statins effectively lower LDL-C. The PCSK9 inhibitors decrease the degradation of the LDL receptors, whereas statins mainly interfere with the synthetic machinery of cholesterol by inhibiting the key rate limiting enzyme, the HMG CoA reductase. PCSK9 inhibitors are currently being developed as monoclonal antibodies for their primary use in lowering LDL-C. They may be especially useful for patients with homozygous familial hypercholesterolemia, who at present receive minimal benefit from traditional statin therapy. The monoclonal antibody PCSK9 inhibitors, recently granted FDA approval, show the most promising safety and efficacy profile compared to other, newer LDL-C lowering therapies. This review will primarily focus on the safety and efficacy of monoclonal antibody PCSK9 inhibitors in comparison to statins. The review will also address new, alternative PCSK9 targeting drug classes such as small molecules, gene silencing agents, apolipoprotein B antisense oligonucleotides, and microsomal triglyceride transfer protein inhibitors.

  3. Hydrogen release from reactor-irradiated beryllium

    Energy Technology Data Exchange (ETDEWEB)

    Klepikov, A.Kh. [Kazakh State Univ., Alma-Ata (Kazakstan); Tazhibaeva, I.L. [Kazakh State Univ., Alma-Ata (Kazakstan); Shestakov, V.P. [Kazakh State Univ., Alma-Ata (Kazakstan); Romanenko, O.G. [Kazakh State Univ., Alma-Ata (Kazakstan); Chikhray, Y.V. [Kazakh State Univ., Alma-Ata (Kazakstan); Kenzhin, E.A. [IAE NNC RK, Semipalatinsk-21 (Russian Federation); Cherepnin, Yu.S. [IAE NNC RK, Semipalatinsk-21 (Russian Federation); Tikhomirov, L.N. [IAE NNC RK, Semipalatinsk-21 (Russian Federation)

    1996-10-01

    Experiments on gas release of reactor-irradiated beryllium samples were carried out and compared to control samples. The simultaneous influence of reactor irradiation and exposure to hydrogen results in more hydrogen retention in beryllium, than if beryllium is initially irradiated and then exposed to hydrogen. Appearance of low temperature peaks at 460 K and 540 K with 0.71 eV/atom and 0.84 eV/atom desorption activation energies, respectively, assessed in a frame of a second order desorption model, is mainly responsible for the increase in hydrogen content. These peaks can be attributed to chemical hydrogen bonds with surface oxide. The simultaneous influence of hydrogen and nuclear reactor irradiation at a temperature of 1150 K was assumed to increase significantly microcrack formation near the surface of beryllium samples, resulting in an increase in low temperature peak intensities. (orig.).

  4. Chronic Beryllium Disease Prevention Program Report

    Energy Technology Data Exchange (ETDEWEB)

    Lee, S

    2012-03-29

    This document describes how Lawrence Livermore National Laboratory (LLNL) meets the requirements and management practices of federal regulation 10 CFR 850, 'Chronic Beryllium Disease Prevention Program (CBDPP).' This revision of the LLNL CBDPP incorporates clarification and editorial changes based on lessons learned from employee discussions, observations and reviews of Department of Energy (DOE) Complex and commercial industry beryllium (Be) safety programs. The information is used to strengthen beryllium safety practices at LLNL, particularly in the areas of: (1) Management of small parts and components; and (2) Communication of program status to employees. Future changes to LLNL beryllium activities and on-going operating experience will be incorporated into the program as described in Section S, 'Performance Feedback.'

  5. Synthesis and ceramization of polycarbosilane containing beryllium

    Institute of Scientific and Technical Information of China (English)

    黄小忠; 周珊; 程勇; 杜作娟; 段曦东; 王超英

    2014-01-01

    Polycarbosilane containing beryllium (BPCS) precursors was prepared by the reaction of polycarbosilane (PCS) with beryllium acetylacetone (Be (acac)2). The analysis of structures and components of BPCS demonstrates that their main structures are basically the same as PCS. Ceramization of BPCS precursors shows that BPCS precursors are organic below 600 °C and inorganic at 800 °C. At 1400 °C, BPCS precursors convert into silicon carbide ceramics. The ceramization of different beryllium content precursors were studied, which show that beryllium plays an important role in the inhibition of crystalline grain growth ofβ-SiC at high temperature and it can adjust the dielectric constant of silicon carbide ceramics.

  6. Efficient and Heritable Targeted Mutagenesis in Mosses Using the CRISPR/Cas9 System.

    Science.gov (United States)

    Nomura, Toshihisa; Sakurai, Tetsuya; Osakabe, Yuriko; Osakabe, Keishi; Sakakibara, Hitoshi

    2016-12-01

    Targeted genome modification by RNA-guided nucleases derived from the clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated nuclease 9 (Cas9) system has seen rapid development in many organisms, including several plant species. In the present study, we succeeded in introducing the CRISPR/Cas9 system into the non-model organism Scopelophila cataractae, a moss that exhibits heavy metal tolerance, and the model organism Physcomitrella patens Utilizing the process by which moss plants regenerate from protoplasts, we conducted targeted mutagenesis by expression of single-chain guide RNA (sgRNA) and Cas9 in protoplasts. Using this method, the acquisition rate of strains exhibiting phenotypic changes associated with the target genes was approximately 45-69%, and strains with phenotypic changes exhibited various insertion and deletion mutations. In addition, we report that our method is capable of multiplex targeted mutagenesis (two independent genes) and also permits the efficient introduction of large deletions (∼3 kbp). These results demonstrate that the CRISPR/Cas9 system can be used to accelerate investigations of bryology and land plant evolution.

  7. Targeted plant genome editing via the CRISPR/Cas9 technology.

    Science.gov (United States)

    Li, Jian-Feng; Zhang, Dandan; Sheen, Jen

    2015-01-01

    Targeted modification of plant genome is key for elucidating and manipulating gene functions in basic and applied plant research. The CRISPR (clustered regularly interspaced short palindromic repeats)/CRISPR-associated protein (Cas) technology is emerging as a powerful genome editing tool in diverse organisms. This technology utilizes an easily reprogrammable guide RNA (gRNA) to guide Streptococcus pyogenes Cas9 endonuclease to generate a DNA double-strand break (DSB) within an intended genomic sequence and subsequently stimulate chromosomal mutagenesis or homologous recombination near the DSB site through cellular DNA repair machineries. In this chapter, we describe the detailed procedure to design, construct, and evaluate dual gRNAs for plant codon-optimized Cas9 (pcoCas9)-mediated genome editing using Arabidopsis thaliana and Nicotiana benthamiana protoplasts as model cellular systems. We also discuss strategies to apply the CRISPR/Cas9 system to generating targeted genome modifications in whole plants.

  8. Benchmark Experiment for Beryllium Slab Samples

    Institute of Scientific and Technical Information of China (English)

    NIE; Yang-bo; BAO; Jie; HAN; Rui; RUAN; Xi-chao; REN; Jie; HUANG; Han-xiong; ZHOU; Zu-ying

    2013-01-01

    The neutron leakage spectra were measured at 60°from pure beryllium slab samples(10 cm×10 cm×5 cm and 10 cm×10 cm×11 cm)by TOF method.The experimental results were compared with the calculated ones by MCNP5 simulation,using the evaluated data of beryllium from CENDL3.1,

  9. Hydrogen release from deposited beryllium layers

    Energy Technology Data Exchange (ETDEWEB)

    Shestakov, V.P.; Klepikov, A.Kh.; Chikhray, Y.V.; Tazhibaeva, I.L. [NIIETF of Al Farabi Kazakh State Univ., Almaty (Kazakhstan)

    2000-04-01

    The analysis of hydrogen retained in deposited beryllium layers deposited by magnetron sputtering was carried out by means of thermodesorption (TDS) technique. Two hydrogen release peaks were clearly seen on the thermodesorption curves at the temperatures 760-800 K and 920-970 K. Hydrogen concentrations in the deposited beryllium layers were calculated from the gas release curves corresponding to the number of Be atoms in the beryllium layer of 100% theoretical density. Average hydrogen concentration in the beryllium samples loaded in the process of magnetron sputtering was equal to 3800{+-}200 appm. The experiments with beryllium layers, enriched with carbon, revealed the increase of retained hydrogen concentration up to 9600{+-}200 appm. Assuming that gas release can be described within the framework of model of diffusion from layer system BeO-Be-BeO, hydrogen diffusion coefficient in BeO and the trapping and detrapping constants for the traps appearing in beryllium in the process of deposition were evaluated. (orig.)

  10. Tritium release from neutron irradiated beryllium pebbles

    Energy Technology Data Exchange (ETDEWEB)

    Scaffidi-Argentina, F.; Werle, H. [Forschungszentrum Karlsruhe GmbH Technik und Umwelt (Germany). Inst. fuer Neutronenphysik und Reactortechnik

    1998-01-01

    One of the most important open issues related to beryllium for fusion applications refers to the kinetics of the tritium release as a function of neutron fluence and temperature. The EXOTIC-7 as well as the `Beryllium` experiments carried out in the HFR reactor in Petten are considered as the most detailed and significant tests for investigating the beryllium response under neutron irradiation. This paper reviews the present status of beryllium post-irradiation examinations performed at the Forschungszentrum Karlsruhe with samples from the above mentioned irradiation experiments, trying to elucidate the tritium release controlling processes. In agreement with previous studies it has been found that release starts at about 500-550degC and achieves a maximum at about 700-750degC. The observed release at about 500-550degC is probably due to tritium escaping from chemical traps, while the maximum release at about 700-750degC is due to tritium escaping from physical traps. The consequences of a direct contact between beryllium and ceramics during irradiation, causing tritium implanting in a surface layer of beryllium up to a depth of about 40 mm and leading to an additional inventory which is usually several times larger than the neutron-produced one, are also presented and the effects on the tritium release are discussed. (author)

  11. Characteristics of beryllium bonds; a QTAIM study.

    Science.gov (United States)

    Eskandari, K

    2012-08-01

    The nature of beryllium bonds formed between BeX2 (X is H, F and Cl) and some Lewis bases have been investigated. The distribution of the Laplacian of electron density shows that there is a region of charge depletion around the Be atom, which, according to Laplacian complementary principal, can interact with a region of charge concentration of an atom in the base and form a beryllium bond. The molecular graphs of the investigated complexes indicate that beryllium in BeH2 and BeF2 can form “beryllium bonds” with O, N and P atoms but not with halogens. In addition, eight criteria based on QTAIM properties, including the values of electron density and its Laplacian at the BCP, penetration of beryllium and acceptor atom, charge, energy, volume and first atomic moment of beryllium atom, have been considered and compared with the corresponding ones in conventional hydrogen bonds. These bonds share many common features with very strong hydrogen bonds, however,some differences have also been observed.

  12. Occupational Exposure to Beryllium. Final rule.

    Science.gov (United States)

    2017-01-09

    The Occupational Safety and Health Administration (OSHA) is amending its existing standards for occupational exposure to beryllium and beryllium compounds. OSHA has determined that employees exposed to beryllium at the previous permissible exposure limits face a significant risk of material impairment to their health. The evidence in the record for this rulemaking indicates that workers exposed to beryllium are at increased risk of developing chronic beryllium disease and lung cancer. This final rule establishes new permissible exposure limits of 0.2 micrograms of beryllium per cubic meter of air (0.2 [mu]g/m\\3\\) as an 8-hour time-weighted average and 2.0 [mu]g/m\\3\\ as a short-term exposure limit determined over a sampling period of 15 minutes. It also includes other provisions to protect employees, such as requirements for exposure assessment, methods for controlling exposure, respiratory protection, personal protective clothing and equipment, housekeeping, medical surveillance, hazard communication, and recordkeeping. OSHA is issuing three separate standards--for general industry, for shipyards, and for construction--in order to tailor requirements to the circumstances found in these sectors.

  13. Heritable CRISPR/Cas9-mediated targeted integration in Xenopus tropicalis.

    Science.gov (United States)

    Shi, Zhaoying; Wang, Fengqin; Cui, Yan; Liu, Zhongzhen; Guo, Xiaogang; Zhang, Yanqi; Deng, Yi; Zhao, Hui; Chen, Yonglong

    2015-12-01

    Xenopus tropicalis is an emerging vertebrate genetic model. A gene knock-in method has not yet been reported in this species. Here, we report that heritable targeted integration can be achieved in this diploid frog using a concurrent cleavage strategy mediated by the clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated protein 9 (CRISPR/Cas9) system. The key point of the strategy is the addition of a Cas9/guide RNA cleavage site in the donor vector, allowing simultaneous cutting of the chromosomal target site and circular donor DNA in vivo. For the 3 distinct loci tested, all showed efficient targeted integration that was verified by both germ-line transmission and Southern blot analyses. By designing the target sites in introns, we were able to get precise editing of the tyrosinase coding sequence and green fluorescent protein expression from endogenous n-tubulin promoter and enhancers. We were unable to detect off-target effects with the T7 endonuclease I assay. Precise editing of protein coding sequences in X. tropicalis expands the utility of this diploid frog, such as for establishing models to study human inherited diseases.

  14. Sanitary-hygienic and ecological aspects of beryllium production

    Energy Technology Data Exchange (ETDEWEB)

    Dvinskykh, E.M.; Savchuk, V.V.; Sidorov, V.L.; Slobodin, D.B.; Tuzov, Y.V. [Ulba Metallurgical Plant, Ust-Kamenogorsk (Kazakhstan)

    1998-01-01

    The Report describes An organization of sanitary-hygienic and ecological control of beryllium production at Ulba metallurgical plant. It involves: (1) the consideration of main methods for protection of beryllium production personnel from unhealthy effect of beryllium, (2) main kinds of filters, used in gas purification systems at different process areas, (3) data on beryllium monitoring in water, soil, on equipment. This Report also outlines problems connected with designing devices for a rapid analysis of beryllium in air as well as problems of beryllium production on ecological situation in the town. (author)

  15. Protein lysine methyltransferase G9a acts on non-histone targets

    Science.gov (United States)

    Rathert, Philipp; Dhayalan, Arunkumar; Murakami, Marie; Zhang, Xing; Tamas, Raluca; Jurkowska, Renata; Komatsu, Yasuhiko; Shinkai, Yoichi; Cheng, Xiaodong; Jeltsch, Albert

    2009-01-01

    By methylation of peptide arrays, we determined the specificity profile of the protein methyltransferase G9a. We show that it mostly recognizes an Arg-Lys sequence and that its activity is inhibited by methylation of the arginine residue. Using the specificity profile, we identified new non-histone protein targets of G9a, including CDYL1, WIZ, ACINUS and G9a (automethylation), as well as peptides derived from CSB. We demonstrate potential downstream signaling pathways for methylation of non-histone proteins. PMID:18438403

  16. Targeting ABCB1-mediated tumor multidrug resistance by CRISPR/Cas9-based genome editing

    Science.gov (United States)

    Yang, Yang; Qiu, Jian-Ge; Li, Yong; Di, Jin-Ming; Zhang, Wen-Ji; Jiang, Qi-Wei; Zheng, Di-Wei; Chen, Yao; Wei, Meng-Ning; Huang, Jia-Rong; Wang, Kun; Shi, Zhi

    2016-01-01

    The RNA-guided clustered regularly interspaced short palindromic (CRISPR) in combination with a CRISPR-associated nuclease 9 (Cas9) nuclease system is a new rapid and precise technology for genome editing. In the present study, we applied the CRISPR/Cas9 system to target ABCB1 (also named MDR1) gene which encodes a 170 kDa transmembrane glycoprotein (P-glycoprotein/P-gp) transporting multiple types of chemotherapeutic drugs including taxanes, epipodophyllotoxins, vinca alkaloids and anthracyclines out of cells to contribute multidrug resistance (MDR) in cancer cells. Our data showed that knockout of ABCB1 by CRISPR/Cas9 system was succesfully archieved with two target sgRNAs in two MDR cancer cells due to the alteration of genome sequences. Knockout of ABCB1 by CRISPR/Cas9 system significantly enhances the sensitivity of ABCB1 substrate chemotherapeutic agents and the intracellular accumulation of rhodamine 123 and doxorubicin in MDR cancer cells. Although now there are lots of limitations to the application of CRISPR/Cas9 for editing cancer genes in human patients, our study provides valuable clues for the use of the CRISPR/Cas9 technology in the investigation and conquest of cancer MDR. PMID:27725879

  17. Generation of CRISPR/Cas9-mediated gene-targeted pigs via somatic cell nuclear transfer.

    Science.gov (United States)

    Zhou, Xiaoqing; Xin, Jige; Fan, Nana; Zou, Qingjian; Huang, Jiao; Ouyang, Zhen; Zhao, Yu; Zhao, Bentian; Liu, Zhaoming; Lai, Sisi; Yi, Xiaoling; Guo, Lin; Esteban, Miguel A; Zeng, Yangzhi; Yang, Huaqiang; Lai, Liangxue

    2015-03-01

    The domestic pig has been widely used as an important large animal model. Precise and efficient genetic modification in pig provides a great promise in biomedical research. Recently, clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated (Cas) system has been successfully used to produce many gene-targeted animals. However, these animals have been generated by co-injection of Cas9 mRNA and single-guide RNA (sgRNA) into one-cell stage embryos, which mostly resulted in mosaicism of the modification. One or two rounds of further breeding should be performed to obtain homozygotes with identical genotype and phenotype. To address this issue, gene-targeted somatic cells can be used as donor for somatic cell nuclear transfer (SCNT) to produce gene-targeted animals with single and identical mutations. In this study, we applied Cas9/sgRNAs to effectively direct gene editing in porcine fetal fibroblasts and then mutant cell colonies were used as donor to generate homozygous gene-targeted pigs through single round of SCNT. As a result, we successfully obtained 15 tyrosinase (TYR) biallelic mutant pigs and 20 PARK2 and PINK1 double-gene knockout (KO) pigs. They were all homozygous and no off-target mutagenesis was detected by comprehensive analysis. TYR (-/-) pigs showed typical albinism and the expression of parkin and PINK1 were depleted in PARK2 (-/-)/PINK1 (-/-) pigs. The results demonstrated that single- or double-gene targeted pigs can be effectively achieved by using the CRISPR/Cas9 system combined with SCNT without mosaic mutation and detectable off-target effects. This gene-editing system provides an efficient, rapid, and less costly manner to generate genetically modified pigs or other large animals.

  18. Study the effect of beryllium reflector poisoning on the Syrian MNSR.

    Science.gov (United States)

    Omar, H; Ghazi, N; Haddad, Kh; Ezzuddin, H

    2012-06-01

    Neutron interactions with beryllium lead to formation of (3)H and strong neutron absorbers (3)He and (6)Li in the reflector (so called beryllium poisoning). After the reactor shutdown, the concentration of (3)He increases in time due to tritium decay. This paper illustrates the impact of poisoning accumulation in the beryllium reflectors on reactivity for the Syrian MNSR research reactor. The prediction of (6)Li and (3)He poison concentrations, initiated by the 9Be(n,α) reaction, in the beryllium reflectors of the MNSR was also presented. The results were based on MCNP Monte Carlo calculations and solutions to the differential equations which describe the time dependent poison concentrations as a function of reactor operation time and shutdown periods. The whole reactor history was taken into account to predict reliable values of parasitic isotope concentrations. It was found that the (3)He and (6)Li accumulations in the beryllium reflectors during the actual working history decreased the excess reactivity by about 28%. While, the effect became more significant at the reactor life's end and the reactor became subcritical after 25,000 h operation. The results contained in this paper could be used in assess the safety analysis of the MNSR reactor.

  19. All-solid-state continuous-wave laser systems for ionization, cooling and quantum state manipulation of beryllium ions

    CERN Document Server

    Lo, H -Y; Kienzler, D; Keitch, B C; de Clercq, L E; Negnevitsky, V; Home, J P

    2013-01-01

    We describe laser systems for photoionization, Doppler cooling and quantum state manipulation of beryllium ions. For photoionization of neutral beryllium, we have developed a continuous-wave 235 nm source obtained by two stages of frequency doubling from a diode laser at 940 nm. The system delivers up to 400 mW at 470 nm and 28 mW at 235 nm. For control of the beryllium ion, three laser wavelengths at 313 nm are produced by sum-frequency generation and second-harmonic generation from four infrared fiber lasers. Up to 7.2 W at 626 nm and 1.9 W at 313 nm are obtained using two pump beams at 1051 and 1551 nm. Intensity fluctuations below 0.5 % per hour (during 8 hours of operation) have been measured at a 313 nm power of 1 W. These systems are used to load beryllium ions into a segmented ion trap.

  20. Cas9 specifies functional viral targets during CRISPR-Cas adaptation.

    Science.gov (United States)

    Heler, Robert; Samai, Poulami; Modell, Joshua W; Weiner, Catherine; Goldberg, Gregory W; Bikard, David; Marraffini, Luciano A

    2015-03-12

    Clustered regularly interspaced short palindromic repeat (CRISPR) loci and their associated (Cas) proteins provide adaptive immunity against viral infection in prokaryotes. Upon infection, short phage sequences known as spacers integrate between CRISPR repeats and are transcribed into small RNA molecules that guide the Cas9 nuclease to the viral targets (protospacers). Streptococcus pyogenes Cas9 cleavage of the viral genome requires the presence of a 5'-NGG-3' protospacer adjacent motif (PAM) sequence immediately downstream of the viral target. It is not known whether and how viral sequences flanked by the correct PAM are chosen as new spacers. Here we show that Cas9 selects functional spacers by recognizing their PAM during spacer acquisition. The replacement of cas9 with alleles that lack the PAM recognition motif or recognize an NGGNG PAM eliminated or changed PAM specificity during spacer acquisition, respectively. Cas9 associates with other proteins of the acquisition machinery (Cas1, Cas2 and Csn2), presumably to provide PAM-specificity to this process. These results establish a new function for Cas9 in the genesis of prokaryotic immunological memory.

  1. Targeted HIV-1 Latency Reversal Using CRISPR/Cas9-Derived Transcriptional Activator Systems.

    Directory of Open Access Journals (Sweden)

    Julia K Bialek

    Full Text Available CRISPR/Cas9 technology is currently considered the most advanced tool for targeted genome engineering. Its sequence-dependent specificity has been explored for locus-directed transcriptional modulation. Such modulation, in particular transcriptional activation, has been proposed as key approach to overcome silencing of dormant HIV provirus in latently infected cellular reservoirs. Currently available agents for provirus activation, so-called latency reversing agents (LRAs, act indirectly through cellular pathways to induce viral transcription. However, their clinical performance remains suboptimal, possibly because reservoirs have diverse cellular identities and/or proviral DNA is intractable to the induced pathways. We have explored two CRISPR/Cas9-derived activator systems as targeted approaches to induce dormant HIV-1 proviral DNA. These systems recruit multiple transcriptional activation domains to the HIV 5' long terminal repeat (LTR, for which we have identified an optimal target region within the LTR U3 sequence. Using this target region, we demonstrate transcriptional activation of proviral genomes via the synergistic activation mediator complex in various in culture model systems for HIV latency. Observed levels of induction are comparable or indeed higher than treatment with established LRAs. Importantly, activation is complete, leading to production of infective viral particles. Our data demonstrate that CRISPR/Cas9-derived technologies can be applied to counteract HIV latency and may therefore represent promising novel approaches in the quest for HIV elimination.

  2. Mechanical performance of irradiated beryllium pebbles

    Energy Technology Data Exchange (ETDEWEB)

    Scaffidi-Argentina, F.; Dalle-Donne, M.; Werle, H. [Forschungszentrum Karlsruhe GmbH Technik und Umwelt (Germany). Inst. fuer Neutronenphysik und Reaktortechnik

    1998-01-01

    For the Helium Cooled Pebble Bed (HCPB) Blanket, which is one of the two reference concepts studied within the European Fusion Technology Programme, the neutron multiplier consists of a mixed bed of about 2 and 0.1-0.2 mm diameter beryllium pebbles. Beryllium has no structural function in the blanket, however microstructural and mechanical properties are important, as they might influence the material behavior under neutron irradiation. The EXOTIC-7 as well as the `Beryllium` experiments carried out in the HFR reactor in Petten are considered as the most detailed and significant tests for investigating it. This paper reviews the present status of beryllium post-irradiation examinations performed at the Forschungszentrum Karlsruhe with samples from these irradiation experiments, emphasizing the effects of irradiation of essential material properties and trying to elucidate the processes controlling the property changes. The microstructure, the porosity distribution, the impurity content, the behavior under compression loads and the compatibility of the beryllium pebbles with lithium orthosilicate (Li{sub 4}SiO{sub 4}) during the in-pile irradiation are presented and critically discussed. Qualitative information on ductility and creep obtained by hardness-type measurements are also supplied. (author)

  3. Illness Absences Among Beryllium Sensitized Workers

    Science.gov (United States)

    Watkins, Janice P.; Ellis, Elizabeth D.; Girardi, David J.; Cragle, Donna L.

    2014-01-01

    Objectives. This study examined absence rates among US Department of Energy workers who had beryllium sensitization (BeS) or were diagnosed with chronic beryllium disease (CBD) compared with those of other workers. Methods. We used the lymphocyte proliferation test to determine beryllium sensitivity. In addition, we applied multivariable logistic regression to compare absences from 2002 to 2011 between workers with BeS or CBD to those without, and survival analysis to compare time to first absence by beryllium sensitization status. Finally, we examined beryllium status by occupational group. Results. Fewer than 3% of the 19 305 workers were BeS, and workers with BeS or CBD had more total absences (odds ratio [OR] = 1.31; 95% confidence interval [CI] = 1.18, 1.46) and respiratory absences (OR = 1.51; 95% CI = 1.24, 1.84) than did other workers. Time to first absence for all causes and for respiratory conditions occurred earlier for workers with BeS or CBD than for other workers. Line operators and crafts personnel were at increased risk for BeS or CBD. Conclusions. Although not considered “diseased,” workers with BeS have higher absenteeism compared with nonsensitized workers. PMID:25211750

  4. High-fidelity CRISPR-Cas9 nucleases with no detectable genome-wide off-target effects.

    Science.gov (United States)

    Kleinstiver, Benjamin P; Pattanayak, Vikram; Prew, Michelle S; Tsai, Shengdar Q; Nguyen, Nhu T; Zheng, Zongli; Joung, J Keith

    2016-01-28

    CRISPR-Cas9 nucleases are widely used for genome editing but can induce unwanted off-target mutations. Existing strategies for reducing genome-wide off-target effects of the widely used Streptococcus pyogenes Cas9 (SpCas9) are imperfect, possessing only partial or unproven efficacies and other limitations that constrain their use. Here we describe SpCas9-HF1, a high-fidelity variant harbouring alterations designed to reduce non-specific DNA contacts. SpCas9-HF1 retains on-target activities comparable to wild-type SpCas9 with >85% of single-guide RNAs (sgRNAs) tested in human cells. Notably, with sgRNAs targeted to standard non-repetitive sequences, SpCas9-HF1 rendered all or nearly all off-target events undetectable by genome-wide break capture and targeted sequencing methods. Even for atypical, repetitive target sites, the vast majority of off-target mutations induced by wild-type SpCas9 were not detected with SpCas9-HF1. With its exceptional precision, SpCas9-HF1 provides an alternative to wild-type SpCas9 for research and therapeutic applications. More broadly, our results suggest a general strategy for optimizing genome-wide specificities of other CRISPR-RNA-guided nucleases.

  5. Multigene knockout utilizing off-target mutations of the CRISPR/Cas9 system in rice.

    Science.gov (United States)

    Endo, Masaki; Mikami, Masafumi; Toki, Seiichi

    2015-01-01

    The clustered regularly interspaced short palindromic repeat (CRISPR)-associated endonuclease 9 (CRISPR/Cas9) system has been demonstrated to be a robust genome engineering tool in a variety of organisms including plants. However, it has been shown that the CRISPR/Cas9 system cleaves genomic DNA sequences containing mismatches to the guide RNA strand. We expected that this low specificity could be exploited to induce multihomeologous and multiparalogous gene knockouts. In the case of polyploid plants, simultaneous modification of multiple homeologous genes, i.e. genes with similar but not identical DNA sequences, is often needed to obtain a desired phenotype. Even in diploid plants, disruption of multiparalogous genes, which have functional redundancy, is often needed. To validate the applicability of the CRISPR/Cas9 system to target mutagenesis of paralogous genes in rice, we designed a single-guide RNA (sgRNA) that recognized 20 bp sequences of cyclin-dependent kinase B2 (CDKB2) as an on-target locus. These 20 bp possess similarity to other rice CDK genes (CDKA1, CDKA2 and CDKB1) with different numbers of mismatches. We analyzed mutations in these four CDK genes in plants regenerated from Cas9/sgRNA-transformed calli and revealed that single, double and triple mutants of CDKA2, CDKB1 and CDKB2 can be created by a single sgRNA.

  6. Modeling Human Severe Combined Immunodeficiency and Correction by CRISPR/Cas9-Enhanced Gene Targeting.

    Science.gov (United States)

    Chang, Chia-Wei; Lai, Yi-Shin; Westin, Erik; Khodadadi-Jamayran, Alireza; Pawlik, Kevin M; Lamb, Lawrence S; Goldman, Frederick D; Townes, Tim M

    2015-09-08

    Mutations of the Janus family kinase JAK3 gene cause severe combined immunodeficiency (SCID). JAK3 deficiency in humans is characterized by the absence of circulating T cells and natural killer (NK) cells with normal numbers of poorly functioning B cells (T(-)B(+)NK(-)). Using SCID patient-specific induced pluripotent stem cells (iPSCs) and a T cell in vitro differentiation system, we demonstrate a complete block in early T cell development of JAK3-deficient cells. Correction of the JAK3 mutation by CRISPR/Cas9-enhanced gene targeting restores normal T cell development, including the production of mature T cell populations with a broad T cell receptor (TCR) repertoire. Whole-genome sequencing of corrected cells demonstrates no CRISPR/Cas9 off-target modifications. These studies describe an approach for the study of human lymphopoiesis and provide a foundation for gene correction therapy in humans with immunodeficiencies.

  7. 75 FR 80734 - Chronic Beryllium Disease Prevention Program

    Science.gov (United States)

    2010-12-23

    ... CFR Part 850 RIN 1992-AA39 Chronic Beryllium Disease Prevention Program AGENCY: Office of Health... beryllium disease prevention program. The Department solicits comment and information on the permissible... course of action regarding its chronic beryllium disease prevention program. DATES: All comments on...

  8. Occupational and non-occupational allergic contact dermatitis from beryllium.

    Science.gov (United States)

    Vilaplana, J; Romaguera, C; Grimalt, F

    1992-05-01

    There are various references to sensitization to beryllium in the literature. Since introducing a patch testing series for patients with suspected sensitization to metals, we have found 3 cases of sensitization to beryllium. Of these 3 cases, we regard the first 2 as having relevant sensitization. Beryllium chloride (1% pet.) was positive in 3 patients and negative in 150 controls.

  9. 20 CFR 30.508 - What is beryllium sensitivity monitoring?

    Science.gov (United States)

    2010-04-01

    ... 20 Employees' Benefits 1 2010-04-01 2010-04-01 false What is beryllium sensitivity monitoring? 30... and Offsets; Overpayments Payment of Claims and Offset for Certain Payments § 30.508 What is beryllium sensitivity monitoring? Beryllium sensitivity monitoring shall consist of medical examinations to confirm...

  10. A novel peptide targeting Clec9a on dendritic cell for cancer immunotherapy

    Science.gov (United States)

    Yan, Zhongyi; Wu, Yahong; Du, Jiangfeng; Li, Guodong; Wang, Shengdian; Cao, Wenpeng; Zhou, Xiuman; Wu, Chunjing; Zhang, Dan; Jing, Xueli; Li, Yifan; Wang, Hongfei; Gao, Yanfeng; Qi, Yuanming

    2016-01-01

    Dendritic cells (DCs) are professional antigen-presenting cells with antigen recognition molecules on the surface. Clec9a is selectively expressed on mouse CD8a+ DCs and CD103+ DCs subsets, which are functionally similar to human BDCA3+ DCs. It is reported that Clec9a is responsible for the antigen cross-presentation of these DC subsets. In the present study, by using phage display technique, we discovered a novel peptide WH, which can selectively bind to mouse Flt3L induced Clec9a+ DCs or Clec9a over-expressed HEK-293T cells. Furthermore, by using computer-aided docking model and mutation assay, we observed that Asp248 and Trp250 are two key residues for Clec9a to bind with peptide WH. When coupled with OVA257-264 epitope, peptide WH can significantly enhance the ability of Clec9a+ DCs to activate OVA-specific CD8+ T cells, which elicit strong ability to secret IFN-γ, express perforin and granzyme B mRNA. In B16-OVA lung metastasis mouse model, WH-OVA257-264 fusion peptide can also enhance the activation of CD8+ T cells and decrease the lung metastasis loci. All these results suggested that peptide WH could be considered as an antigen delivery carrier targeting Clec9a+ DCs for cancer immunotherapy. PMID:27250027

  11. In vivo genome editing via CRISPR/Cas9 mediated homology-independent targeted integration

    KAUST Repository

    Suzuki, Keiichiro

    2016-11-15

    Targeted genome editing via engineered nucleases is an exciting area of biomedical research and holds potential for clinical applications. Despite rapid advances in the field, in vivo targeted transgene integration is still infeasible because current tools are inefficient1, especially for non-dividing cells, which compose most adult tissues. This poses a barrier for uncovering fundamental biological principles and developing treatments for a broad range of genetic disorders2. Based on clustered regularly interspaced short palindromic repeat/Cas9 (CRISPR/Cas9)3, 4 technology, here we devise a homology-independent targeted integration (HITI) strategy, which allows for robust DNA knock-in in both dividing and non-dividing cells in vitro and, more importantly, in vivo (for example, in neurons of postnatal mammals). As a proof of concept of its therapeutic potential, we demonstrate the efficacy of HITI in improving visual function using a rat model of the retinal degeneration condition retinitis pigmentosa. The HITI method presented here establishes new avenues for basic research and targeted gene therapies.

  12. In vivo genome editing via CRISPR/Cas9 mediated homology-independent targeted integration

    Science.gov (United States)

    Suzuki, Keiichiro; Tsunekawa, Yuji; Hernandez-Benitez, Reyna; Wu, Jun; Zhu, Jie; Kim, Euiseok J.; Hatanaka, Fumiyuki; Yamamoto, Mako; Araoka, Toshikazu; Li, Zhe; Kurita, Masakazu; Hishida, Tomoaki; Li, Mo; Aizawa, Emi; Guo, Shicheng; Chen, Song; Goebl, April; Soligalla, Rupa Devi; Qu, Jing; Jiang, Tingshuai; Fu, Xin; Jafari, Maryam; Esteban, Concepcion Rodriguez; Berggren, W. Travis; Lajara, Jeronimo; Nuñez-Delicado, Estrella; Guillen, Pedro; Campistol, Josep M.; Matsuzaki, Fumio; Liu, Guang-Hui; Magistretti, Pierre; Zhang, Kun; Callaway, Edward M.; Zhang, Kang; Belmonte, Juan Carlos Izpisua

    2017-01-01

    Targeted genome editing via engineered nucleases is an exciting area of biomedical research and holds potential for clinical applications. Despite rapid advances in the field, in vivo targeted transgene integration is still infeasible because current tools are inefficient1, especially for non-dividing cells, which compose most adult tissues. This poses a barrier for uncovering fundamental biological principles and developing treatments for a broad range of genetic disorders2. Based on clustered regularly interspaced short palindromic repeat/Cas9 (CRISPR/Cas9)3,4 technology, here we devise a homology-independent targeted integration (HITI) strategy, which allows for robust DNA knock-in in both dividing and non-dividing cells in vitro and, more importantly, in vivo (for example, in neurons of postnatal mammals). As a proof of concept of its therapeutic potential, we demonstrate the efficacy of HITI in improving visual function using a rat model of the retinal degeneration condition retinitis pigmentosa. The HITI method presented here establishes new avenues for basic research and targeted gene therapies. PMID:27851729

  13. [Effects of beryllium chloride on cultured cells].

    Science.gov (United States)

    Sakaguchi, T; Sakaguchi, S; Nakamura, I; Kagami, M

    1984-05-01

    The effects of beryllium on cultured cells were investigated. Three cell-lines (HeLa-S3, Vero, HEL-R66) were used in these experiments and they were cultured in Eagle's MEM plus 5 or 10% FBS (Fetal Bovine Serum) containing beryllium in various concentrations. HeLa cells or Vero cells were able to grow in the medium with 10 micrograms Be/ml (1.1 mM). On the other hand, the growth of HEL cells were strongly inhibited, even when cultured in the medium with 1 microgram Be/ml (1.1 X 10(-1) mM) and the number of living cells showed markedly low level as compared to that of the control samples cultured in the medium without beryllium. The cytotoxic effects of beryllium on these cells, which were cultured for three days in the medium with beryllium, were observed. None of cytotoxic effects were found on HeLa cells cultured with 0.5 micrograms/ml (5.5 X 10(-2) mM) and on Vero cells cultured with 0.05 micrograms Be/ml (5.5 X 10(-3) mM), while HEL cells received cytotoxic effects even when cultured in the medium containing 0.05 micrograms Be/ml (5.5 X 10(-3) mM), and these effects on the cells appeared strong when cultured in the medium without FBS. It was revealed from these experiments that HEL cells are very sensitive in terms of toxic effects of beryllium. Therefore, there cells can be used for the toxicological study on low level concentrations of the metal.

  14. Targeting CDK11 in osteosarcoma cells using the CRISPR-Cas9 system.

    Science.gov (United States)

    Feng, Yong; Sassi, Slim; Shen, Jacson K; Yang, Xiaoqian; Gao, Yan; Osaka, Eiji; Zhang, Jianming; Yang, Shuhua; Yang, Cao; Mankin, Henry J; Hornicek, Francis J; Duan, Zhenfeng

    2015-02-01

    Osteosarcoma is the most common type primary malignant tumor of bone. Patients with regional osteosarcoma are routinely treated with surgery and chemotherapy. In addition, many patients with metastatic or recurrent osteosarcoma show poor prognosis with current chemotherapy agents. Therefore, it is important to improve the general condition and the overall survival rate of patients with osteosarcoma by identifying novel therapeutic strategies. Recent studies have revealed that CDK11 is essential in osteosarcoma cell growth and survival by inhibiting CDK11 mRNA expression with RNAi. Here, we apply the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-Cas9 system, a robust and highly efficient novel genome editing tool, to determine the effect of targeting endogenous CDK11 gene at the DNA level in osteosarcoma cell lines. We show that CDK11 can be efficiently silenced by CRISPR-Cas9. Inhibition of CDK11 is associated with decreased cell proliferation and viability, and induces cell death in osteosarcoma cell lines KHOS and U-2OS. Furthermore, the migration and invasion activities are also markedly reduced by CDK11 knockout. These results demonstrate that CRISPR-Cas9 system is a useful tool for the modification of endogenous CDK11 gene expression, and CRISPR-Cas9 targeted CDK11 knockout may be a promising therapeutic regimen for the treatment of osteosarcoma.

  15. Simple and Efficient Targeting of Multiple Genes Through CRISPR-Cas9 in Physcomitrella patens

    Directory of Open Access Journals (Sweden)

    Mauricio Lopez-Obando

    2016-11-01

    Full Text Available Powerful genome editing technologies are needed for efficient gene function analysis. The CRISPR-Cas9 system has been adapted as an efficient gene-knock-out technology in a variety of species. However, in a number of situations, knocking out or modifying a single gene is not sufficient; this is particularly true for genes belonging to a common family, or for genes showing redundant functions. Like many plants, the model organism Physcomitrella patens has experienced multiple events of polyploidization during evolution that has resulted in a number of families of duplicated genes. Here, we report a robust CRISPR-Cas9 system, based on the codelivery of a CAS9 expressing cassette, multiple sgRNA vectors, and a cassette for transient transformation selection, for gene knock-out in multiple gene families. We demonstrate that CRISPR-Cas9-mediated targeting of five different genes allows the selection of a quintuple mutant, and all possible subcombinations of mutants, in one experiment, with no mutations detected in potential off-target sequences. Furthermore, we confirmed the observation that the presence of repeats in the vicinity of the cutting region favors deletion due to the alternative end joining pathway, for which induced frameshift mutations can be potentially predicted. Because the number of multiple gene families in Physcomitrella is substantial, this tool opens new perspectives to study the role of expanded gene families in the colonization of land by plants.

  16. Mineral resource of the month: beryllium

    Science.gov (United States)

    Shedd, Kim B.

    2006-01-01

    Beryllium metal is lighter than aluminum and stiffer than steel. These and other properties, including its strength, dimensional stability, thermal properties and reflectivity, make it useful for aerospace and defense applications, such as satellite and space-vehicle structural components. Beryllium’s nuclear properties, combined with its low density, make it useful as a neutron reflector and moderator in nuclear reactors. Because it is transparent to most X rays, beryllium is used as X-ray windows in medical, industrial and analytical equipment.

  17. Detection of beryllium treatment of natural sapphires by NRA

    Science.gov (United States)

    Gutiérrez, P. C.; Ynsa, M.-D.; Climent-Font, A.; Calligaro, T.

    2010-06-01

    Since the 1990's, artificial treatment of natural sapphires (Al 2O 3 crystals coloured by impurities) by diffusion of beryllium at high temperature has become a growing practice. This process permits to enhance the colour of these gemstones, and thus to increase their value. Detection of such a treatment - diffusion of tens of μg/g of beryllium in Al 2O 3 crystals - is usually achieved using high sensitivity techniques like laser-ablation inductively coupled plasma mass spectrometry (LA-ICP/MS) or laser-induced breakdown spectrometry (LIBS) which are unfortunately micro-destructive (leaving 50-100-μm diameter craters on the gems). The simple and non-destructive alternative method proposed in this work is based on the nuclear reaction 9Be(α, nγ) 12C with an external helium ion beam impinging on the gem directly placed in air. The 4439 keV prompt γ-ray tagging Be atoms are detected with a high efficiency bismuth germanate scintillator. Beam dose is monitored using the 2235 keV prompt γ-ray produced during irradiation by the aluminium of the sapphire matrix through the 27Al(α, pγ) 30Si nuclear reaction. The method is tested on a series of Be-treated sapphires previously analyzed by LA-ICP/MS to determine the optimal conditions to obtain a peak to background appropriate to reach the required μg/g sensitivity. Using a 2.8-MeV external He beam and a beam dose of 200 μC, beryllium concentrations from 5 to 16 μg/g have been measured in the samples, with a detection limit of 1 μg/g.

  18. Detection of beryllium treatment of natural sapphires by NRA

    Energy Technology Data Exchange (ETDEWEB)

    Gutierrez, P.C., E-mail: carolina.gutierrez@uam.e [Centro de Micro-Analisis de Materiales (CMAM), Universidad Autonoma de Madrid, Campus de Cantoblanco, 28049 Madrid (Spain); Ynsa, M.-D.; Climent-Font, A. [Centro de Micro-Analisis de Materiales (CMAM), Universidad Autonoma de Madrid, Campus de Cantoblanco, 28049 Madrid (Spain); Dpto. Fisica Aplicada C-12, Universidad Autonoma de Madrid, Campus de Cantoblanco, 28049 Madrid (Spain); Calligaro, T. [Centre de Recherche et de Restauration des musees de France C2RMF, CNRS-UMR171, 14 quai Francois Mitterrand, 75001 Paris (France)

    2010-06-15

    Since the 1990's, artificial treatment of natural sapphires (Al{sub 2}O{sub 3} crystals coloured by impurities) by diffusion of beryllium at high temperature has become a growing practice. This process permits to enhance the colour of these gemstones, and thus to increase their value. Detection of such a treatment - diffusion of tens of {mu}g/g of beryllium in Al{sub 2}O{sub 3} crystals - is usually achieved using high sensitivity techniques like laser-ablation inductively coupled plasma mass spectrometry (LA-ICP/MS) or laser-induced breakdown spectrometry (LIBS) which are unfortunately micro-destructive (leaving 50-100-{mu}m diameter craters on the gems). The simple and non-destructive alternative method proposed in this work is based on the nuclear reaction {sup 9}Be({alpha}, n{gamma}){sup 12}C with an external helium ion beam impinging on the gem directly placed in air. The 4439 keV prompt {gamma}-ray tagging Be atoms are detected with a high efficiency bismuth germanate scintillator. Beam dose is monitored using the 2235 keV prompt {gamma}-ray produced during irradiation by the aluminium of the sapphire matrix through the {sup 27}Al({alpha}, p{gamma}){sup 30}Si nuclear reaction. The method is tested on a series of Be-treated sapphires previously analyzed by LA-ICP/MS to determine the optimal conditions to obtain a peak to background appropriate to reach the required {mu}g/g sensitivity. Using a 2.8-MeV external He beam and a beam dose of 200 {mu}C, beryllium concentrations from 5 to 16 {mu}g/g have been measured in the samples, with a detection limit of 1 {mu}g/g.

  19. Preliminary results for explosion bonding of beryllium to copper

    Energy Technology Data Exchange (ETDEWEB)

    Butler, D.J. [Northwest Technical Industries, Inc., Sequim, WA (United States); Dombrowski, D.E. [Brush Wellman, Inc., Cleveland, OH (United States)

    1995-09-01

    This program was undertaken to determine if explosive bonding is a viable technique for joining beryllium to copper substrates. The effort was a cursory attempt at trying to solve some of the problems associated with explosive bonding beryllium and should not be considered a comprehensive research effort. There are two issues that this program addressed. Can beryllium be explosive bonded to copper substrates and can the bonding take place without shattering the beryllium? Thirteen different explosive bonding iterations were completed using various thicknesses of beryllium that were manufactured with three different techniques.

  20. Analysis of mice with targeted deletion of AQP9 gene provides conclusive evidence for expression of AQP9 in neurons

    DEFF Research Database (Denmark)

    Mylonakou, Maria N; Petersen, Petur H; Rinvik, Eric;

    2009-01-01

    AQP9 is an aquaglyceroporin that serves important functions in peripheral organs, including the liver. Reflecting the lack of AQP9 knockout mice, uncertainties still prevail regarding the localization and roles of AQP9 in the central nervous system. Here we present a comprehensive analysis of AQP9...... and mouse liver, the organ with the highest level of AQP9. By blue native gel analysis it could be demonstrated that the brain contains tetrameric AQP9, corresponding to the functional form of AQP9. The band corresponding to the AQP9 tetramer was absent in AQP9 knockout brain and liver. Immunocytochemistry...... and in situ hybridization analyses with AQP9 knockout controls show that subpopulations of nigral neurons express AQP9 both at the mRNA and at the protein levels and that populations of cortical cells (including hilar neurons in the hippocampus) contain AQP9 mRNA but no detectable AQP9 immunosignal...

  1. Calculations for electron-impact excitation and ionization of beryllium

    CERN Document Server

    Zatsarinny, Oleg; Fursa, Dmitry V; Bray, Igor

    2016-01-01

    The B-spline R-matrix and the convergent close-coupling methods are used to study electron collisions with neutral beryllium over an energy range from threshold to 100 eV. Coupling to the target continuum significantly affects the results for transitions from the ground state, but to a lesser extent the strong transitions between excited states. Cross sections are presented for selected transitions between low-lying physical bound states of beryllium, as well as for elastic scattering, momentum transfer, and ionization. The present cross sections for transitions from the ground state from the two methods are in excellent agreement with each other, and also with other available results based on nonperturbative convergent pseudo-state and time-dependent close-coupling models. The elastic cross section at low energies is dominated by a prominent shape resonance. The ionization from the $(2s2p)^3P$ and $(2s2p)^1P$ states strongly depends on the respective term. The current predictions represent an extensive set o...

  2. Highly Efficient Targeted Mutagenesis of Drosophila with the CRISPR/Cas9 System

    Directory of Open Access Journals (Sweden)

    Andrew R. Bassett

    2013-07-01

    Full Text Available Here, we present a simple and highly efficient method for generating and detecting mutations of any gene in Drosophila melanogaster through the use of the CRISPR/Cas9 system (clustered regularly interspaced palindromic repeats/CRISPR-associated. We show that injection of RNA into the Drosophila embryo can induce highly efficient mutagenesis of desired target genes in up to 88% of injected flies. These mutations can be transmitted through the germline to make stable lines. Our system provides at least a 10-fold improvement in efficiency over previously published reports, enabling wider application of this technique. We also describe a simple and highly sensitive method of detecting mutations in the target gene by high-resolution melt analysis and discuss how the new technology enables the study of gene function.

  3. Status of beryllium development for fusion applications

    Energy Technology Data Exchange (ETDEWEB)

    Billone, M.C. [Argonne National Lab., IL (United States); Donne, M.D. [Kernforschungszentrum Karlsruhe GmbH (Germany). Institut fuer Neutronphysik and Reaktortechnik; Macaulay-Newcombe, R.G. [McMaster Univ., Ontario, CA (United States). Dept. of Engineering Physics

    1994-05-01

    Beryllium is a leading candidate material for the neutron multiplier of tritium breeding blankets and the plasma facing component of first wall and divertor systems. Depending on the application, the fabrication methods proposed include hot-pressing, hot-isostatic-pressing, cold isostatic pressing/sintering, rotary electrode processing and plasma spraying. Product forms include blocks, tubes, pebbles, tiles and coatings. While, in general, beryllium is not a leading structural material candidate, its mechanical performance, as well its performance with regard to sputtering, heat transport, tritium retention/release, helium-induced swelling and chemical compatibility, is an important consideration in first-wall/blanket design. Differential expansion within the beryllium causes internal stresses which may result in cracking, thereby affecting the heat transport and barrier performance of the material. Overall deformation can result in loading of neighboring structural material. Thus, in assessing the performance of beryllium for fusion applications, it is important to have a good database in all of these performance areas, as well as a set of properties correlations and models for the purpose of interpolation/extrapolation.

  4. The knockout reaction of 15C on a 9Be target at intermediate energies

    Science.gov (United States)

    Sadeghi, H.; Fereidonnejad, R.; Ghambari, M.

    2016-05-01

    In this work, neutron knockout reactions of 15C on a 9Be target at energy 103 and 250 MeV/nucleon are studied. Using the Eikonal approximation of the Glauber model, total neutron removal cross sections, the stripping and diffractive cross sections as well as 14C longitudinal momentum distributions are determined in both 15C ground state and exited states of the wave function. We compared the results of our calculations with the available experimental data obtained recently. The calculated cross sections of 15C and 14C reactions, as well as the momentum distribution are in relatively good agreement with available data.

  5. Breakup of 33.4 MeV/u 17N on a 9Be Target

    Institute of Scientific and Technical Information of China (English)

    HUA Hui; GUO Zhong-Yan; LI Zu-Yu; WANG Hong-Wei; WANG Su-Fang; JIANG Dong-Xing; LI Xiang-Qing; QIAN Tao; WU He-Yu; JIN Gen-Ming; ZHAN Wen-Long; DUAN Li-Min; XIAO Zhi-Guang

    2000-01-01

    Correlation measurements of neutrons and fragments have been performed in a reaction of 33.4 MeV/u 17 N on a 9Be target. Energy spectra of n and nitrogen fragments were obtained at different angles. Based on the nuclear diffraction dissociation model, the measured energy spectra and the neutron angular distributions werereproduced quite well assuming that 1 7 N was composed of 16 N and n or 15 N and 2n interacting with the nonlocal separable potential. The satisfactory agreement between the heoretical calculations and the experimental data shows that the contribution of Coulomb dissociation is negligible in the reaction concerned.

  6. sup 1 sup 2 sup 9 I targets for studies of nuclear waste transmutation

    CERN Document Server

    Ingelbrecht, C; Raptis, K; Altzitzoglou, T; Noguere, G

    2002-01-01

    Nuclear incineration of long-lived fission products and minor actinides is being investigated as an alternative means of reactor waste disposal. sup 1 sup 2 sup 9 I is of particular interest because of its long half-life and high mobility in the environment. Lead iodide targets of sup 1 sup 2 sup 9 I for neutron capture cross-section measurements were prepared from 210 l fuel reprocessing waste solution containing 1.3 g l sup - sup 1 iodine and other fission products. The iodine was separated by oxidation to I sub 2 and extraction into chloroform, reduction to iodide by sodium sulphite and re-extraction into an aqueous phase. Iodide was precipitated using lead nitrate and dried. The chemistry was carried out batch-wise using 400 ml starting solution each time and recycling the chloroform. An extraction efficiency of about 90%, determined by gamma-ray spectrometry, was achieved.

  7. Biased and Unbiased Methods for the Detection of Off-Target Cleavage by CRISPR/Cas9: An Overview

    OpenAIRE

    Francisco Martin; Sabina Sánchez-Hernández; Alejandra Gutiérrez-Guerrero; Javier Pinedo-Gomez; Karim Benabdellah

    2016-01-01

    The clustered regularly interspaced short palindromic repeat (CRISPR)-associated protein 9 endonuclease (Cas9) derived from bacterial adaptive immune systems is a revolutionary tool used in both basic and applied science. It is a versatile system that enables the genome of different species to be modified by generating double strand breaks (DSBs) at specific locations. However, all of the CRISPR/Cas9 systems can also produce DSBs at off-target sites that differ substantially from on-target si...

  8. CRISPR/Cas9-based tools for targeted genome editing and replication control of HBV

    Institute of Scientific and Technical Information of China (English)

    Cheng; Peng; Mengji; Lu; Dongliang; Yang

    2015-01-01

    Hepatitis B virus(HBV) infection remains a major global health problem because current therapies rarely eliminate HBV infections to achieve a complete cure. A different treatment paradigm to effectively clear HBV infection and eradicate latent viral reservoirs is urgently required. In recent years, the development of a new RNA-guided gene-editing tool, the CRISPR/Cas9(clustered regularly interspaced short palindromic repeats/CRISPR-associated nuclease 9) system, has greatly facilitated site-specific mutagenesis and represents a very promising potential therapeutic tool for diseases, including for eradication of invasive pathogens such as HBV. Here, we review recent advances in the use of CRISPR/Cas9, which is designed to target HBV specific DNA sequences to inhibit HBV replication and to induce viral genome mutation, in cell lines or animal models. Advantages, limitations and possible solutions, and proposed directions for future research are discussed to highlight the opportunities and challenges of CRISPR/Cas9 as a new, potentially curative therapy for chronic hepatitis B infection.

  9. The PCSK9 Inhibitors: A Novel Therapeutic Target Enters Clinical Practice

    Science.gov (United States)

    Lepor, Norman E.; Kereiakes, Dean J.

    2015-01-01

    There is a critical need for alternative, potent agents that can reduce low-density lipoprotein cholesterol (LDL-C) levels in patients with heterozygous familial hyperlipidemia and statin intolerance and those not reaching lipid-lowering treatment goals who are at high risk for cardiovascular (CV) events. The first proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor was approved in July 2015 by the US Food and Drug Administration as an adjunct to diet and maximally tolerated statin therapy for treatment of adults with heterozygous familial hyperlipidemia or clinical atherosclerotic CV disease, who require additional lowering of LDL-C levels. In clinical trials, PCSK9 inhibitors have been shown to reduce LDL-C levels by as much as 60% to 70% when administered as monotherapy or as an add-on treatment to statins and other lipid-lowering therapies. In studies of PCSK9 genetic mutations, loss of function in the PCSK9 allele was associated with a relative decrease of 88% in the risk for atherosclerotic CV events during 15 years of patient follow-up. The use of PCSK9 inhibitors may eventually support the LDL-C hypothesis that the lower the LDL-C level, the lower the CV risk. Although some recent clinical practice guidelines have deemphasized the importance of numeric LDL-C targets, many clinicians are reluctant to discard them, and this position is supported by recent clinical evidence. We eagerly await the results of the ODYSSEY, FOURIER, and SPIRE clinical outcome trials, which we anticipate will provide further validation that “lower is better” with respect to reducing LDL-C levels and improving clinical outcomes. PMID:26834934

  10. Historical analysis of airborne beryllium concentrations at a copper beryllium machining facility (1964-2000).

    Science.gov (United States)

    McAtee, B L; Donovan, E P; Gaffney, S H; Frede, W; Knutsen, J S; Paustenbach, D J

    2009-06-01

    Copper beryllium alloys are the most commonly used form of beryllium; however, there have been few studies assessing occupational exposure in facilities that worked exclusively with this alloy versus those where pure metal or beryllium oxide may also have been present. In this paper, we evaluated the airborne beryllium concentrations at a machining plant using historical industrial hygiene samples collected between 1964 and 2000. With the exception of a few projects conducted in the 1960s, it is believed that >95% of the operations used copper beryllium alloy exclusively. Long-term (>120 min) and short-term (machining of copper beryllium-containing parts, as well as finishing operations (e.g., deburring and polishing) and decontamination of machinery. A total of 580 beryllium air samples were analyzed (311 personal and 269 area samples). The average concentration based on area samples (1964-2000) was 0.021 microg m(-3) (SD 0.17 microg m(-3); range 0.00012-2.5 microg m(-3)); 68.8% were below the analytical limit of detection (LOD). The average airborne beryllium concentration, based on all personal samples available from 1964 through the end of 2000 (n = 311), was 0.026 microg m(-3) (SD 0.059 microg m(-3); range 0.019-0.8 microg m(-3)); 97.4% were below the LOD. Personal samples collected from machinists (n = 78) had an average airborne concentration of 0.021 microg m(-3) (SD 0.014 microg m(-3); range 0.019-0.14 microg m(-3)); 97.4% were below the LOD. Airborne concentrations were consistently below the Occupational Safety and Health Administration permissible exposure limit for beryllium (2 microg m(-3)). Overall, the data indicate that for machining operations involving copper beryllium, the airborne concentrations for >95% of the samples were below the contemporaneous occupational exposure limits or the 1999 Department of Energy action level of 0.2 microg m(-3) and, in most cases, were below the LOD.

  11. Modeling Human Severe Combined Immunodeficiency and Correction by CRISPR/Cas9-Enhanced Gene Targeting

    Directory of Open Access Journals (Sweden)

    Chia-Wei Chang

    2015-09-01

    Full Text Available Mutations of the Janus family kinase JAK3 gene cause severe combined immunodeficiency (SCID. JAK3 deficiency in humans is characterized by the absence of circulating T cells and natural killer (NK cells with normal numbers of poorly functioning B cells (T–B+NK–. Using SCID patient-specific induced pluripotent stem cells (iPSCs and a T cell in vitro differentiation system, we demonstrate a complete block in early T cell development of JAK3-deficient cells. Correction of the JAK3 mutation by CRISPR/Cas9-enhanced gene targeting restores normal T cell development, including the production of mature T cell populations with a broad T cell receptor (TCR repertoire. Whole-genome sequencing of corrected cells demonstrates no CRISPR/Cas9 off-target modifications. These studies describe an approach for the study of human lymphopoiesis and provide a foundation for gene correction therapy in humans with immunodeficiencies.

  12. The CRISPR-Cas9 technology: Closer to the ultimate toolkit for targeted genome editing.

    Science.gov (United States)

    Quétier, Francis

    2016-01-01

    The first period of plant genome editing was based on Agrobacterium; chemical mutagenesis by EMS (ethyl methanesulfonate) and ionizing radiations; each of these technologies led to randomly distributed genome modifications. The second period is associated with the discoveries of homing and meganuclease enzymes during the 80s and 90s, which were then engineered to provide efficient tools for targeted editing. From 2006 to 2012, a few crop plants were successfully and precisely modified using zinc-finger nucleases. A third wave of improvement in genome editing, which led to a dramatic decrease in off-target events, was achieved in 2009-2011 with the TALEN technology. The latest revolution surfaced in 2013 with the CRISPR-Cas9 system, whose high efficiency and technical ease of use is really impressive; scientists can use in-house kits or commercially available kits; the only two requirements are to carefully choose the location of the DNA double strand breaks to be induced and then to order an oligonucleotide. While this close-to- ultimate toolkit for targeted editing of genomes represents dramatic scientific progress which allows the development of more complex useful agronomic traits through synthetic biology, the social acceptance of genome editing remains regularly questioned by anti-GMO citizens and organizations.

  13. First beryllium capsule implosions on the National Ignition Facility

    Science.gov (United States)

    Kline, J. L.; Yi, S. A.; Simakov, A. N.; Olson, R. E.; Wilson, D. C.; Kyrala, G. A.; Perry, T. S.; Batha, S. H.; Zylstra, A. B.; Dewald, E. L.; Tommasini, R.; Ralph, J. E.; Strozzi, D. J.; MacPhee, A. G.; Callahan, D. A.; Hinkel, D. E.; Hurricane, O. A.; Milovich, J. L.; Rygg, J. R.; Khan, S. F.; Haan, S. W.; Celliers, P. M.; Clark, D. S.; Hammel, B. A.; Kozioziemski, B.; Schneider, M. B.; Marinak, M. M.; Rinderknecht, H. G.; Robey, H. F.; Salmonson, J. D.; Patel, P. K.; Ma, T.; Edwards, M. J.; Stadermann, M.; Baxamusa, S.; Alford, C.; Wang, M.; Nikroo, A.; Rice, N.; Hoover, D.; Youngblood, K. P.; Xu, H.; Huang, H.; Sio, H.

    2016-05-01

    The first indirect drive implosion experiments using Beryllium (Be) capsules at the National Ignition Facility confirm the superior ablation properties and elucidate possible Be-ablator issues such as hohlraum filling by ablator material. Since the 1990s, Be has been the preferred Inertial Confinement Fusion (ICF) ablator because of its higher mass ablation rate compared to that of carbon-based ablators. This enables ICF target designs with higher implosion velocities at lower radiation temperatures and improved hydrodynamic stability through greater ablative stabilization. Recent experiments to demonstrate the viability of Be ablator target designs measured the backscattered laser energy, capsule implosion velocity, core implosion shape from self-emission, and in-flight capsule shape from backlit imaging. The laser backscatter is similar to that from comparable plastic (CH) targets under the same hohlraum conditions. Implosion velocity measurements from backlit streaked radiography show that laser energy coupling to the hohlraum wall is comparable to plastic ablators. The measured implosion shape indicates no significant reduction of laser energy from the inner laser cone beams reaching the hohlraum wall as compared with plastic and high-density carbon ablators. These results indicate that the high mass ablation rate for beryllium capsules does not significantly alter hohlraum energetics. In addition, these data, together with data for low fill-density hohlraum performance, indicate that laser power multipliers, required to reconcile simulations with experimental observations, are likely due to our limited understanding of the hohlraum rather than the capsule physics since similar multipliers are needed for both Be and CH capsules as seen in experiments.

  14. Digenome-seq: genome-wide profiling of CRISPR-Cas9 off-target effects in human cells.

    Science.gov (United States)

    Kim, Daesik; Bae, Sangsu; Park, Jeongbin; Kim, Eunji; Kim, Seokjoong; Yu, Hye Ryeong; Hwang, Jinha; Kim, Jong-Il; Kim, Jin-Soo

    2015-03-01

    Although RNA-guided genome editing via the CRISPR-Cas9 system is now widely used in biomedical research, genome-wide target specificities of Cas9 nucleases remain controversial. Here we present Digenome-seq, in vitro Cas9-digested whole-genome sequencing, to profile genome-wide Cas9 off-target effects in human cells. This in vitro digest yields sequence reads with the same 5' ends at cleavage sites that can be computationally identified. We validated off-target sites at which insertions or deletions were induced with frequencies below 0.1%, near the detection limit of targeted deep sequencing. We also showed that Cas9 nucleases can be highly specific, inducing off-target mutations at merely several, rather than thousands of, sites in the entire genome and that Cas9 off-target effects can be avoided by replacing 'promiscuous' single guide RNAs (sgRNAs) with modified sgRNAs. Digenome-seq is a robust, sensitive, unbiased and cost-effective method for profiling genome-wide off-target effects of programmable nucleases including Cas9.

  15. Genomic Access to Monarch Migration Using TALEN and CRISPR/Cas9-Mediated Targeted Mutagenesis

    Directory of Open Access Journals (Sweden)

    Matthew J. Markert

    2016-04-01

    Full Text Available The eastern North American monarch butterfly, Danaus plexippus, is an emerging model system to study the neural, molecular, and genetic basis of animal long-distance migration and animal clockwork mechanisms. While genomic studies have provided new insight into migration-associated and circadian clock genes, the general lack of simple and versatile reverse-genetic methods has limited in vivo functional analysis of candidate genes in this species. Here, we report the establishment of highly efficient and heritable gene mutagenesis methods in the monarch butterfly using transcriptional activator-like effector nucleases (TALENs and CRISPR-associated RNA-guided nuclease Cas9 (CRISPR/Cas9. Using two clock gene loci, cryptochrome 2 and clock (clk, as candidates, we show that both TALENs and CRISPR/Cas9 generate high-frequency nonhomologous end-joining (NHEJ-mediated mutations at targeted sites (up to 100%, and that injecting fewer than 100 eggs is sufficient to recover mutant progeny and generate monarch knockout lines in about 3 months. Our study also genetically defines monarch CLK as an essential component of the transcriptional activation complex of the circadian clock. The methods presented should not only greatly accelerate functional analyses of many aspects of monarch biology, but are also anticipated to facilitate the development of these tools in other nontraditional insect species as well as the development of homology-directed knock-ins.

  16. Characterization of plasma sprayed beryllium ITER first wall mockups

    Energy Technology Data Exchange (ETDEWEB)

    Castro, R.G.; Vaidya, R.U.; Hollis, K.J. [Los Alamos National Lab., NM (United States). Material Science and Technology Div.

    1998-01-01

    ITER first wall beryllium mockups, which were fabricated by vacuum plasma spraying the beryllium armor, have survived 3000 thermal fatigue cycles at 1 MW/m{sup 2} without damage during high heat flux testing at the Plasma Materials Test Facility at Sandia National Laboratory in New Mexico. The thermal and mechanical properties of the plasma sprayed beryllium armor have been characterized. Results are reported on the chemical composition of the beryllium armor in the as-deposited condition, the through thickness and normal to the through thickness thermal conductivity and thermal expansion, the four-point bend flexure strength and edge-notch fracture toughness of the beryllium armor, the bond strength between the beryllium armor and the underlying heat sink material, and ultrasonic C-scans of the Be/heat sink interface. (author)

  17. Mechanisms of hydrogen retention in metallic beryllium and beryllium oxide and properties of ion-induced beryllium nitride; Rueckhaltemechanismen fuer Wasserstoff in metallischem Beryllium und Berylliumoxid sowie Eigenschaften von ioneninduziertem Berylliumnitrid

    Energy Technology Data Exchange (ETDEWEB)

    Oberkofler, Martin

    2011-09-22

    In the framework of this thesis laboratory experiments on atomically clean beryllium surfaces were performed. They aim at a basic understanding of the mechanisms occurring upon interaction of a fusion plasma with a beryllium first wall. The retention and the temperature dependent release of implanted deuterium ions are investigated. An atomistic description is developed through simulations and through the comparison with calculations based on density functional theory. The results of these investigations are compared to the behaviour of hydrogen upon implantation into thermally grown beryllium oxide layers. Furthermore, beryllium nitride is produced by implantation of nitrogen into metallic beryllium and its properties are investigated. The results are interpreted with regard to the use of beryllium in a fusion reactor. (orig.)

  18. Plasma cleaning of beryllium coated mirrors

    Science.gov (United States)

    Moser, L.; Marot, L.; Steiner, R.; Newman, M.; Widdowson, A.; Ivanova, D.; Likonen, J.; Petersson, P.; Pintsuk, G.; Rubel, M.; Meyer, E.; Contributors, JET

    2016-02-01

    Cleaning systems of metallic first mirrors are needed in more than 20 optical diagnostic systems from ITER to avoid reflectivity losses. Currently, plasma sputtering is considered as one of the most promising techniques to remove deposits coming from the main wall (mainly beryllium and tungsten). This work presents the results of plasma cleaning of rhodium and molybdenum mirrors exposed in JET-ILW and contaminated with typical tokamak elements (including beryllium and tungsten). Using radio frequency (13.56 MHz) argon or helium plasma, the removal of mixed layers was demonstrated and mirror reflectivity improved towards initial values. The cleaning was evaluated by performing reflectivity measurements, scanning electron microscopy, x-ray photoelectron spectroscopy and ion beam analysis.

  19. Electronic bistability in linear beryllium chains.

    Science.gov (United States)

    Helal, Wissam; Monari, Antonio; Evangelisti, Stefano; Leininger, Thierry

    2009-04-30

    A theoretical investigation on the mixed-valence behavior (bistability) of a series of cationic linear chains composed of beryllium atoms, Be(N)(+) (with N = 6,..., 12), is presented. The calculations were performed at CAS-SCF and MR-CI levels by using an ANO basis set containing 6s4p3d2f orbitals for each atom. Our results show a consistent gradual shift between different classes of mixed-valence compounds as the number of beryllium atoms increases, from class III strong coupling toward class II valence trapped. Indeed, in the largest cases (N > 10), the cationic chains were found to be closer to class I, where the coupling vanishes. The intramolecular electron transfer parameters V(ab), E(a), and E(opt) were calculated for each atomic chain. It is shown that the decrease of V(ab) with increasing N follows an exponential pattern.

  20. Highly efficient targeted mutagenesis in axolotl using Cas9 RNA-guided nuclease.

    Science.gov (United States)

    Flowers, G Parker; Timberlake, Andrew T; McLean, Kaitlin C; Monaghan, James R; Crews, Craig M

    2014-05-01

    Among tetrapods, only urodele salamanders, such as the axolotl Ambystoma mexicanum, can completely regenerate limbs as adults. The mystery of why salamanders, but not other animals, possess this ability has for generations captivated scientists seeking to induce this phenomenon in other vertebrates. Although many recent advances in molecular biology have allowed limb regeneration and tissue repair in the axolotl to be investigated in increasing detail, the molecular toolkit for the study of this process has been limited. Here, we report that the CRISPR-Cas9 RNA-guided nuclease system can efficiently create mutations at targeted sites within the axolotl genome. We identify individual animals treated with RNA-guided nucleases that have mutation frequencies close to 100% at targeted sites. We employ this technique to completely functionally ablate EGFP expression in transgenic animals and recapitulate developmental phenotypes produced by loss of the conserved gene brachyury. Thus, this advance allows a reverse genetic approach in the axolotl and will undoubtedly provide invaluable insight into the mechanisms of salamanders' unique regenerative ability.

  1. Quantitative method of determining beryllium or a compound thereof in a sample

    Energy Technology Data Exchange (ETDEWEB)

    McCleskey, T. Mark (Los Alamos, NM); Ehler, Deborah S. (Los Alamos, NM); John, Kevin D. (Santa Fe, NM); Burrell, Anthony K. (Los Alamos, NM); Collis, Gavin E. (Los Alamos, NM); Minogue, Edel M. (Los Alamos, NM); Warner, Benjamin P. (Los Alamos, NM)

    2010-08-24

    A method of determining beryllium or a beryllium compound thereof in a sample, includes providing a sample suspected of comprising beryllium or a compound thereof, extracting beryllium or a compound thereof from the sample by dissolving in a solution, adding a fluorescent indicator to the solution to thereby bind any beryllium or a compound thereof to the fluorescent indicator, and determining the presence or amount of any beryllium or a compound thereof in the sample by measuring fluorescence.

  2. Quantitative method of determining beryllium or a compound thereof in a sample

    Energy Technology Data Exchange (ETDEWEB)

    McCleskey, T. Mark; Ehler, Deborah S.; John, Kevin D.; Burrell, Anthony K.; Collis, Gavin E.; Minogue, Edel M.; Warner, Benjamin P.

    2006-10-31

    A method of determining beryllium or a beryllium compound thereof in a sample, includes providing a sample suspected of comprising beryllium or a compound thereof, extracting beryllium or a compound thereof from the sample by dissolving in a solution, adding a fluorescent indicator to the solution to thereby bind any beryllium or a compound thereof to the fluorescent indicator, and determining the presence or amount of any beryllium or a compound thereof in the sample by measuring fluorescence.

  3. Computer simulation of electronic excitations in beryllium

    CERN Document Server

    Popov, A V

    2016-01-01

    An effective method for the quantitative description of the electronic excited states of polyatomic systems is developed by using computer technology. The proposed method allows calculating various properties of matter at the atomic level within the uniform scheme. A special attention is paid to the description of beryllium atoms interactions with the external fields, comparable by power to the fields in atoms, molecules and clusters.

  4. Possible health risks from low level exposure to beryllium.

    Science.gov (United States)

    Stange, A W; Hilmas, D E; Furman, F J

    1996-07-17

    The first case of chronic beryllium disease (CBD) at the Rocky Flats Environmental Technology Site (Rocky Flats) was diagnosed in a machinist in 1984. Rocky Flats, located 16 miles northwest of Denver, Colorado, is part of the United States Department of Energy (DOE) nuclear weapons complex. Research and development operations using beryllium began at Rocky Flats in 1953, and beryllium production operations began in 1957. Exposures could have occurred during foundry operations, casting, shearing, rolling, cutting, welding, machining, sanding, polishing, assembly, and chemical analysis operations. The Beryllium Health Surveillance Program (BHSP) was established in June 1991 at Rocky Flats to provide health surveillance for beryllium exposed employees using the Lymphocyte Proliferation Test (LPT) to identify sensitized individuals. Of the 29 cases of CBD and 76 cases of beryllium sensitization identified since 1991, several cases appear to have had only minimal opportunistic exposures to beryllium, since they were employed in administrative functions rather than primary beryllium operations. In conjunction with other health surveillance programs, a questionnaire and interview are administered to obtain detailed work and health histories. These histories, along with other data, are utilized to estimate the extent of an individual's exposure. Additional surveillance is in progress to attempt to characterize the possible risks from intermittent or brief exposures to beryllium in the workplace.

  5. Behavior of beryllium pebbles under irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Dalle-Donne, M.; Scaffidi-Argentina, F. [Forschungszentrum Karlsruhe GmbH Technik und Umwelt (Germany). Inst. fuer Neutronenphysik und Reactortechnik; Baldwin, D.L.; Gelles, D.S.; Greenwood, L.R.; Kawamura, H.; Oliver, B.M.

    1998-01-01

    Beryllium pebbles are being considered in fusion reactor blanket designs as neutron multiplier. An example is the European `Helium Cooled Pebble Bed Blanket.` Several forms of beryllium pebbles are commercially available but little is known about these forms in response to fast neutron irradiation. Commercially available beryllium pebbles have been irradiated to approximately 1.3 x 10{sup 22} n/cm{sup 2} (E>1 MeV) at 390degC. Pebbles 1-mm in diameter manufactured by Brush Wellman, USA and by Nippon Gaishi Company, Japan, and 3-mm pebbles manufactured by Brush Wellman were included. All were irradiated in the below-core area of the Experimental Breeder Reactor-II in Idaho Falls, USA, in molybdenum alloy capsules containing helium. Post-irradiation results are presented on density change measurements, tritium release by assay, stepped-temperature anneal, and thermal ramp desorption tests, and helium release by assay and stepped-temperature anneal measurements, for Be pebbles from two manufacturing methods, and with two specimen diameters. The experimental results on density change and tritium and helium release are compared with the predictions of the code ANFIBE. (author)

  6. Disposal of beryllium and cadmium from research reactors; Entsorgung von Beryllium und Cadmium aus Forschungsreaktoren

    Energy Technology Data Exchange (ETDEWEB)

    Lierse von Gostomski, C.; Remmert, A.; Stoewer, W. [Inst. fuer Radiochemie, Technische Univ. Muenchen, Garching (Germany); Bach, F.W.; Wilk, P.; Kutlu, I. [Inst. fuer Werkstoffkunde, Univ. Hannover, Hannover (Germany); Blenski, H.J.; Berthold, M. [Gesellschaft fuer Nuklear-Service mbH, Essen (Germany); Nerlich, K.D.; Plank, W. [TUeV Sueddeutschland Bau und Betrieb GmbH, Muenchen (Germany)

    2003-07-01

    Beryllium and cadmium mostly occur in metal form as radioactive special materials during the deconstruction of research reactors. Beryllium is usually used in these reactors as a neutron reflector and moderator, while cadmium is used above all as a neutron absorber. Both metals together have a high chemotoxicity as well as an inventory of radionuclides which has not been more closely characterised up to now. A high tritium content is to be expected, particularly in the case of beryllium; this tritium is due to the reaction of the metal with thermal reactor neutrons in particular. However, other nuclides which may be formed by neutron capture from impurities also contribute to the activity inventory. Up to now there is no qualified process for proper treatment, conditioning and intermediate and final repository in Germany. (orig.)

  7. RNA-guided Cas9 as an in vivo desired-target mutator in maize.

    Science.gov (United States)

    Li, Chuxi; Liu, Changlin; Qi, Xiantao; Wu, Yongchun; Fei, Xiaohong; Mao, Long; Chen, Beijiu; Li, Xinhai; Xie, Chuanxiao

    2017-04-05

    The RNA-guided Cas9 system is a versatile tool for genome editing. Here, we established a RNA-guided endonuclease (RGEN) system as an in vivo desired-target mutator (DTM) in maize to reduce the linkage drag during breeding procedure, using the LIGULELESS1 (LG1) locus as a proof-of-concept. Our system showed 51.5% to 91.2% mutation frequency in T0 transgenic plants. We then crossed the T1 plants stably expressing DTM with six diverse recipient maize lines and found that 11.79% to 28.71% of the plants tested were mutants induced by the DTM effect. Analysis of successive F2 plants indicated that the mutations induced by the DTM effect were largely heritable. Moreover, DTM-generated hybrids had significantly smaller leaf angles that were reduced more than 50% when compared with that of the wild type. Planting experiments showed that DTM generated maize plants can be grown with significantly higher density and hence greater yield potential. Our work demonstrate that stably expressed RGEN could be implemented as an in vivo DTM to rapidly generate and spread desired mutations in maize through hybridization and subsequent backcrossing, and hence bypassing the linkage drag effect in convention introgression methodology. This proof-of-concept experiment can be a potentially much more efficient breeding strategy in crops employing the RNA-guided Cas9 genome editing. This article is protected by copyright. All rights reserved.

  8. Tritium release from neutron irradiated beryllium: Kinetics, long-time annealing and effect or crack formation

    Energy Technology Data Exchange (ETDEWEB)

    Scaffidi-Argentina, F.; Werle, H. [Forschungszentrum Karlsruhe, (Germany)

    1995-09-01

    Since beryllium is considered as one of the best neutron multiplier materials in the blanket of the next generation fusion reactors, several studies have been started to evaluate its behaviour under irradiation during both operating and accidental conditions. Based on safety considerations, tritium produced in beryllium during neutron irradiation represents one important issue, therefore it is necessary to investigate tritium transport processes by using a comprehensive mathematical model and comparing its predictions with well characterized experimental tests. Because of the difficulties in extrapolating the short-time tritium release tests to a longer time scale, also long-time annealing experiments with beryllium samples from the SIBELIUS irradiation. have been carried out at the Forschungszentrum Karlsruhe. Samples were annealed up to 12 months at temperatures up to 650{degrees}C. The inventory after annealing was determined by heating the samples up to 1050{degrees}C with a He+0.1 vo1% H{sub 2} purge gas. Furthermore, in order to investigate the likely effects of cracks formation eventually causing a faster tritium release from beryllium, the behaviour of samples irradiated at low temperature (40-50{degrees}C) but up to very high fast neutron fluences (0.8-3.9{center_dot}10{sup 22} cm{sup -2}, E{sub n}{ge}1 MeV) in the BR2 reactor has been investigated. Tritium was released by heating the beryllium samples up to 1050{degrees}C and purging them with He+0.1 vo1% H{sub 2}. Tritium release from high-irradiated beryllium samples showed a much faster kinetics than from the low-irradiated ones, probably because of crack formation caused by thermal stresses in the brittle material and/or by helium bubbles migration. The obtained experimental data have been compared with predictions of the code ANFIBE with the goal to better understand the physical mechanisms governing tritium behaviour in beryllium and to assess the prediction capabilities of the code.

  9. Nuclear charge radius measurements of radioactive beryllium isotopes

    CERN Multimedia

    2002-01-01

    We propose to measure the nuclear charge radii of the beryllium isotopes $^{7,9,10}$Be and the one-neutron halo isotope $^{11}$Be using laser spectroscopy of trapped ions. Ions produced at ISOLDE and ionized with the laser ion source will be cooled and bunched in the radio-frequency buncher of the ISOLTRAP experiment and then transferred into a specially designed Paul trap. Here, they will be cooled to temperatures in the mK range employing sympathetic and direct laser cooling. Precision laser spectroscopy of the isotope shift on the cooled ensemble in combination with accurate atomic structure calculations will provide nuclear charge radii with a precision of better than 3%. This will be the first model-independent determination of a one-neutron halo nuclear charge radius.

  10. Functionally Graded Nanophase Beryllium/Carbon Composites

    Science.gov (United States)

    Choi, Michael K.

    2003-01-01

    Beryllium, beryllium alloys, beryllium carbide, and carbon are the ingredients of a class of nanophase Be/Be2C/C composite materials that can be formulated and functionally graded to suit a variety of applications. In a typical case, such a composite consists of a first layer of either pure beryllium or a beryllium alloy, a second layer of B2C, and a third layer of nanophase sintered carbon derived from fullerenes and nanotubes. The three layers are interconnected through interpenetrating spongelike structures. These Be/Be2C/C composite materials are similar to Co/WC/diamond functionally graded composite materials, except that (1) W and Co are replaced by Be and alloys thereof and (2) diamond is replaced by sintered carbon derived from fullerenes and nanotubes. (Optionally, one could form a Be/Be2C/diamond composite.) Because Be is lighter than W and Co, the present Be/Be2C/C composites weigh less than do the corresponding Co/WC/diamond composites. The nanophase carbon is almost as hard as diamond. WC/Co is the toughest material. It is widely used for drilling, digging, and machining. However, the fact that W is a heavy element (that is, has high atomic mass and mass density) makes W unattractive for applications in which weight is a severe disadvantage. Be is the lightest tough element, but its toughness is less than that of WC/Co alloy. Be strengthened by nanophase carbon is much tougher than pure or alloy Be. The nanophase carbon has an unsurpassed strength-to-weight ratio. The Be/Be2C/C composite materials are especially attractive for terrestrial and aerospace applications in which there are requirements for light weight along with the high strength and toughness of the denser Co/WC/diamond materials. These materials could be incorporated into diverse components, including cutting tools, bearings, rocket nozzles, and shields. Moreover, because Be and C are effective as neutron moderators, Be/Be2C/C composites could be attractive for some nuclear applications.

  11. Targeted Resequencing of 9p in Acute Lymphoblastic Leukemia Yields Concordant Results with Array CGH and Reveals Novel Genomic Alterations

    NARCIS (Netherlands)

    Sarhadi, V.K.; Lahti, L.M.; Scheinin, I.; Tyybäkinoja, A.; Savola, S.; Usvasalo, A.; Räty, R.; Elonen, E.; Saarinen-Pihkala, U.M.; Knuutila, S.

    2013-01-01

    Genetic alterations of the short arm of chromosome 9 are frequent in acute lymphoblastic leukemia. We performed targeted sequencing of 9p region in 35 adolescent and adult acute lymphoblastic leukemia patients and sought to investigate the sensitivity of detecting copy number alterations in comparis

  12. Systematic analysis of CRISPR-Cas9 mismatch tolerance reveals low levels of off-target activity.

    Science.gov (United States)

    Anderson, Emily M; Haupt, Amanda; Schiel, John A; Chou, Eldon; Machado, Hidevaldo B; Strezoska, Žaklina; Lenger, Steve; McClelland, Shawn; Birmingham, Amanda; Vermeulen, Annaleen; Smith, Anja van Brabant

    2015-10-10

    The discovery that the bacterial clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein 9 (Cas9) acquired immune system can be utilized to create double-strand breaks (DSBs) in eukaryotic genomes has resulted in the ability to create genomic changes more easily than with other genome engineering techniques. While there is significant potential for the CRISPR-Cas9 system to advance basic and applied research, several unknowns remain, including the specificity of the RNA-directed DNA cleavage by the small targeting RNA, the CRISPR RNA (crRNA). Here we describe a novel synthetic RNA approach that allows for high-throughput gene editing experiments. This was used with a functional assay for protein disruption to perform high-throughput analysis of crRNA activity and specificity. We performed a comprehensive test of target cleavage using crRNAs that contain one and two nucleotide mismatches to the DNA target in the 20mer targeting region of the crRNA, allowing for the evaluation of hundreds of potential mismatched target sites without the requirement for the off-target sequences and their adjacent PAMs to be present in the genome. Our results demonstrate that while many crRNAs are functional, less than 5% of crRNAs with two mismatches to their target are effective in gene editing; this suggests an overall high level of functionality but low level of off-targeting.

  13. Beryllium metal II. a review of the available toxicity data.

    Science.gov (United States)

    Strupp, Christian

    2011-01-01

    Beryllium metal was classified in Europe collectively with beryllium compounds, e.g. soluble salts. Toxicological equivalence was assumed despite greatly differing physicochemical properties. Following introduction of the Registration, Evaluation, Authorization and Restriction of Chemicals (REACH) regulation, beryllium metal was classified as individual substance and more investigational efforts to appropriately characterize beryllium metal as a specific substance apart from soluble beryllium compounds was required. A literature search on toxicity of beryllium metal was conducted, and the resulting literature compiled together with the results of a recently performed study package into a comprehensive data set. Testing performed under Organisation for Economic Co-Operation and Development guidelines and Good Laboratory Practice concluded that beryllium metal was neither a skin irritant, an eye irritant, a skin sensitizer nor evoked any clinical signs of acute oral toxicity; discrepancies between the current legal classification of beryllium metal in the European Union (EU) and the experimental results were identified. Furthermore, genotoxicity and carcinogenicity were discussed in the context of the literature data and the new experimental data. It was concluded that beryllium metal is unlikely to be a classical nonthreshold mutagen. Effects on DNA repair and morphological cell transformation were observed but need further investigation to evaluate their relevance in vivo. Animal carcinogenicity studies deliver evidence of carcinogenicity in the rat; however, lung overload may be a species-specific confounding factor in the existing studies, and studies in other species do not give convincing evidence of carcinogenicity. Epidemiology has been intensively discussed over the last years and has the problem that the studies base on the same US beryllium production population and do not distinguish between metal and soluble compounds. It is noted that the correlation

  14. Targeting CD9 produces stimulus-independent antiangiogenic effects predominantly in activated endothelial cells during angiogenesis: A novel antiangiogenic therapy

    Energy Technology Data Exchange (ETDEWEB)

    Kamisasanuki, Taro [Department of Gene Therapy and Regenerative Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8544 (Japan); Department of Ophthalmology, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8544 (Japan); Tokushige, Saori [Department of Gene Therapy and Regenerative Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8544 (Japan); Terasaki, Hiroto [Department of Gene Therapy and Regenerative Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8544 (Japan); Department of Ophthalmology, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8544 (Japan); Khai, Ngin Cin; Wang, Yuqing [Department of Gene Therapy and Regenerative Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8544 (Japan); Sakamoto, Taiji [Department of Ophthalmology, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8544 (Japan); Kosai, Ken-ichiro, E-mail: kosai@m2.kufm.kagoshima-u.ac.jp [Department of Gene Therapy and Regenerative Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8544 (Japan)

    2011-09-16

    Highlights: {yields} CD9 plays stimulus-independent roles in angiogenesis in vitro and in vivo. {yields} Targeting CD9 expression is effective in an angiogenic disease model. {yields} Targeting CD9 expression predominantly affects activated endothelial cells. {yields} CD9 is involved in endothelial cell proliferation, but not survival. {yields} CD9 is part of angiogenic machinery in endothelial cells during angiogenesis. -- Abstract: The precise roles of tetraspanin CD9 are unclear. Here we show that CD9 plays a stimulus-independent role in angiogenesis and that inhibiting CD9 expression or function is a potential antiangiogenic therapy. Knocking down CD9 expression significantly inhibited in vitro endothelial cell migration and invasion induced by vascular endothelial growth factor (VEGF) or hepatocyte growth factor (HGF). Injecting CD9-specific small interfering RNA (siRNA-CD9) markedly inhibited HGF- or VEGF-induced subconjunctival angiogenesis in vivo. Both results revealed potent and stimulus-independent antiangiogenic effects of targeting CD9. Furthermore, intravitreous injections of siRNA-CD9 or anti-CD9 antibodies were therapeutically effective for laser-induced retinal and choroidal neovascularization in mice, a representative ocular angiogenic disease model. In terms of the mechanism, growth factor receptor and downstream signaling activation were not affected, whereas abnormal localization of integrins and membrane type-1 matrix metalloproteinase was observed during angiogenesis, by knocking down CD9 expression. Notably, knocking down CD9 expression did not induce death and mildly inhibited proliferation of quiescent endothelial cells under conditions without an angiogenic stimulus. Thus, CD9 does not directly affect growth factor-induced signal transduction, which is required in angiogenesis and normal vasculature, but is part of the angiogenesis machinery in endothelial cells during angiogenesis. In conclusion, targeting CD9 produced stimulus

  15. Experimental results of beryllium exposed to intense high energy proton beam pulses

    Energy Technology Data Exchange (ETDEWEB)

    Ammigan, K. [Fermilab; Hartsell, B. [Fermilab; Hurh, P. [Fermilab; Zwaska, R. [Fermilab; Butcher, M. [CERN; Guinchard, M. [CERN; Calviani, M. [CERN; Losito, R. [CERN; Roberts, S. [Culham Lab; Kuksenko, V. [Oxford U.; Atherton, A. [Rutherford; Caretta, O. [Rutherford; Davenne, T. [Rutherford; Densham, C. [Rutherford; Fitton, M. [Rutherford; Loveridge, J. [Rutherford; O' Dell, J. [Rutherford

    2017-02-10

    Beryllium is extensively used in various accelerator beam lines and target facilities as a material for beam windows, and to a lesser extent, as secondary particle production targets. With increasing beam intensities of future accelerator facilities, it is critical to understand the response of beryllium under extreme conditions to reliably operate these components as well as avoid compromising particle production efficiency by limiting beam parameters. As a result, an exploratory experiment at CERN’s HiRadMat facility was carried out to take advantage of the test facility’s tunable high intensity proton beam to probe and investigate the damage mechanisms of several beryllium grades. The test matrix consisted of multiple arrays of thin discs of varying thicknesses as well as cylinders, each exposed to increasing beam intensities. This paper outlines the experimental measurements, as well as findings from Post-Irradiation-Examination (PIE) work where different imaging techniques were used to analyze and compare surface evolution and microstructural response of the test matrix specimens.

  16. Efficient CRISPR-Cas9-Mediated Generation of Knockin Human Pluripotent Stem Cells Lacking Undesired Mutations at the Targeted Locus

    Directory of Open Access Journals (Sweden)

    Florian T. Merkle

    2015-05-01

    Full Text Available The CRISPR-Cas9 system has the potential to revolutionize genome editing in human pluripotent stem cells (hPSCs, but its advantages and pitfalls are still poorly understood. We systematically tested the ability of CRISPR-Cas9 to mediate reporter gene knockin at 16 distinct genomic sites in hPSCs. We observed efficient gene targeting but found that targeted clones carried an unexpectedly high frequency of insertion and deletion (indel mutations at both alleles of the targeted gene. These indels were induced by Cas9 nuclease, as well as Cas9-D10A single or dual nickases, and often disrupted gene function. To overcome this problem, we designed strategies to physically destroy or separate CRISPR target sites at the targeted allele and developed a bioinformatic pipeline to identify and eliminate clones harboring deleterious indels at the other allele. This two-pronged approach enables the reliable generation of knockin hPSC reporter cell lines free of unwanted mutations at the targeted locus.

  17. 10 CFR 850.20 - Baseline beryllium inventory.

    Science.gov (United States)

    2010-01-01

    ... 10 Energy 4 2010-01-01 2010-01-01 false Baseline beryllium inventory. 850.20 Section 850.20 Energy... Baseline beryllium inventory. (a) The responsible employer must develop a baseline inventory of the... inventory, the responsible employer must: (1) Review current and historical records; (2) Interview...

  18. Joining of beryllium by braze welding technique: preliminary results

    Energy Technology Data Exchange (ETDEWEB)

    Banaim, P.; Abramov, E. [Ben-Gurion Univ. of the Negev, Beersheba (Israel); Zalkind, S.; Eden, S.

    1998-01-01

    Within the framework of some applications, there is a need to join beryllium parts to each other. Gas Tungsten Arc Braze Welds were made in beryllium using 0.3 mm commercially Aluminum (1100) shim preplaced at the joint. The welds exhibited a tendency to form microcracks in the Fusion Zone and Heat Affected Zone. All the microcracks were backfilled with Aluminum. (author)

  19. Ionization energies of beryllium in strong magnetic fields

    Institute of Scientific and Technical Information of China (English)

    GUANXiao-xu; ZHANGYue-xia

    2004-01-01

    We have develop an effective frozen core approximation to calculate energy levels and ionization enegies of the beryllium atom in magnetic field strengths up to 2.35 × 105T. Systematic improvement over the Hartree-Fock results for the beryllium low-lying states has been accomplished.

  20. Ionization energies of beryllium in strong magnetic fields

    Institute of Scientific and Technical Information of China (English)

    GUAN Xiao-xu; ZHANG Yue-xia

    2004-01-01

    We have develop an effective frozen core approximation to calculate energy levels and ionization enegies of the beryllium atom in magnetic field strengths up to 2.35×105T. Systematic improvement over the Hartree-Fock results for the beryllium low-lying states has been accomplished.

  1. Dissolution of beryllium in artificial lung alveolar macrophage phagolysosomal fluid.

    Science.gov (United States)

    Stefaniak, Aleksandr B; Virji, M Abbas; Day, Gregory A

    2011-05-01

    Dissolution of a lung burden of poorly soluble beryllium particles is hypothesized to be necessary for development of chronic beryllium lung disease (CBD) in humans. As such, particle dissolution rate must be sufficient to activate the lung immune response and dissolution lifetime sufficient to maintain chronic inflammation for months to years to support development of disease. The purpose of this research was to investigate the hypothesis that poorly soluble beryllium compounds release ions via dissolution in lung fluid. Dissolution kinetics of 17 poorly soluble particulate beryllium materials that span extraction through ceramics machining (ores, hydroxide, metal, copper-beryllium [CuBe] fume, oxides) and three CuBe alloy reference materials (chips, solid block) were measured over 31 d using artificial lung alveolar macrophage phagolysosomal fluid (pH 4.5). Differences in beryllium-containing particle physicochemical properties translated into differences in dissolution rates and lifetimes in artificial phagolysosomal fluid. Among all materials, dissolution rate constant values ranged from 10(-5) to 10(-10)gcm(-2)d(-1) and half-times ranged from tens to thousands of days. The presence of magnesium trisilicate in some beryllium oxide materials may have slowed dissolution rates. Materials associated with elevated prevalence of CBD had faster beryllium dissolution rates [10(-7)-10(-8)gcm(-2)d(-1)] than materials not associated with elevated prevalence (p<0.05).

  2. IRIS TOXICOLOGICAL REVIEW AND SUMMARY DOCUMENTS FOR BERYLLIUM AND COMPOUNDS

    Science.gov (United States)

    EPA's assessment of the noncancer health effects and carcinogenic potential of Beryllium was added to the IRIS database in 1998. The IRIS program is updating the IRIS assessment for Beryllium. This update will incorporate health effects information published since the last assess...

  3. Biased and Unbiased Methods for the Detection of Off-Target Cleavage by CRISPR/Cas9: An Overview

    Directory of Open Access Journals (Sweden)

    Francisco Martin

    2016-09-01

    Full Text Available The clustered regularly interspaced short palindromic repeat (CRISPR-associated protein 9 endonuclease (Cas9 derived from bacterial adaptive immune systems is a revolutionary tool used in both basic and applied science. It is a versatile system that enables the genome of different species to be modified by generating double strand breaks (DSBs at specific locations. However, all of the CRISPR/Cas9 systems can also produce DSBs at off-target sites that differ substantially from on-target sites. The generation of DSBs in locations outside the intended site can produce mutations that need to be carefully monitored, especially when using these tools for therapeutic purposes. However, off-target analyses of the CRISPR/Cas9 system have been very challenging, particularly when performed directly in cells. In this manuscript, we review the different strategies developed to identify off-targets generated by CRISPR/cas9 systems and other specific nucleases (ZFNs, TALENs in real target cells.

  4. [CRISPR/Cas9-based genome editing systems and the analysis of targeted genome mutations in plants].

    Science.gov (United States)

    Xingliang, Ma; Yaoguang, Liu

    2016-02-01

    Targeted genomic editing technologies use programmable DNA nucleases to cleave genomic target sites, thus inducing targeted mutations in the genomes. The newly prevailed clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9 (CRISPR/Cas9) system that consists of the Cas9 nuclease and single guide RNA (sgRNA) has the advantages of simplicity and high efficiency as compared to other programmable DNA nuclease systems such as zinc finger nucleases (ZFNs) and transcription activator like effector nucleases (TALENs). Currently, a number of cases have been reported on the application of the CRISPR/Cas9 genomic editing technology in plants. In this review, we summarize the strategies for preparing the Cas9 and sgRNA expression constructs, the transformation method for obtaining targeted mutations, the efficiency and features of the resulting mutations and the methods for detecting or genotyping of the mutation sites. We also discuss the existing problems and perspectives of CRISPR/Cas9-based genomic editing in plants.

  5. Protection of air in premises and environment against beryllium aerosols

    Energy Technology Data Exchange (ETDEWEB)

    Bitkolov, N.Z.; Vishnevsky, E.P.; Krupkin, A.V. [Research Inst. of Industrial and Marine Medicine, St. Petersburg (Russian Federation)

    1998-01-01

    First and foremost, the danger of beryllium aerosols concerns a possibility of their inhalation. The situation is aggravated with high biological activity of the beryllium in a human lung. The small allowable beryllium aerosols` concentration in air poses a rather complex and expensive problem of the pollution prevention and clearing up of air. The delivery and transportation of beryllium aerosols from sites of their formation are defined by the circuit of ventilation, that forms aerodynamics of air flows in premises, and aerodynamic links between premises. The causes of aerosols release in air of premises from hoods, isolated and hermetically sealed vessels can be vibrations, as well as pulses of temperature and pressure. Furthermore, it is possible the redispersion of aerosols from dirty surfaces. The effective protection of air against beryllium aerosols at industrial plants is provided by a complex of hygienic measures: from individual means of breath protection up to collective means of the prevention of air pollution. (J.P.N.)

  6. Estimating occupational beryllium exposure from compliance monitoring data.

    Science.gov (United States)

    Hamm, Michele P; Burstyn, Igor

    2011-01-01

    Occupational exposure to beryllium is widespread and is a health risk. The objectives of this study were to develop plausible models to estimate occupational airborne beryllium exposure. Compliance monitoring data were obtained from the Occupational Safety and Health Administration for 12,148 personal measurements of beryllium exposure from 1979 to 2005. Industry codes were maintained as reported or collapsed based on the number of measurements per cell of a job-exposure matrix (JEM). Probability of exposure was predicted based on year, industry, job, and sampling duration. In these models, probability of exposure decreased over time, was highest in full-shift personal samples, and varied with industry and job. The probability of exposure was calculated using 6 JEMs, each providing similar rankings of the likelihood of non-negligible exposure to beryllium. These statistical models, with expert appraisal, are suitable for the assessment of the probability of elevated occupational exposure to beryllium.

  7. Toxicological effects of beryllium on platelets and vascular endothelium.

    Science.gov (United States)

    Togna, G; Togna, A R; Russo, P; Caprino, L

    1997-06-01

    Although ample research has described the toxic effects of the metal beryllium on the respiratory apparatus, less is known about its effects on the vascular apparatus, including pulmonary blood vessels. We investigated the in vitro effects of beryllium on endothelial vascular adenosine diphosphatase activity and prostacyclin production in bovine aortic endothelium, and on nitric oxide release in isolated rabbit arteries. Rabbit and human platelet responsiveness was also evaluated. Beryllium inhibited vascular endothelial adenosine diphosphatase activity, prostacyclin production, and nitric oxide release, thus inducing functional alterations in vascular endothelial cells. It also induced platelet hyperreactivity to arachidonic acid, as shown by a lowering of the threshold of aggregating concentration and by concurrently increasing thromboxane production. In contrast, beryllium left the response to aggregating and nonaggregating concentrations of ADP and collagen unchanged. These findings show that beryllium may impair some vascular endothelial functions and alter the interaction between platelet and endothelial mediators.

  8. Release of beryllium into artificial airway epithelial lining fluid.

    Science.gov (United States)

    Stefaniak, Aleksandr B; Virji, M Abbas; Day, Gregory A

    2012-01-01

    Inhaled beryllium particles that deposit in the lung airway lining fluid may dissolve and interact with immune-competent cells resulting in sensitization. As such, solubilization of 17 beryllium-containing materials (ore, hydroxide, metal, oxide, alloys, and process intermediates) was investigated using artificial human airway epithelial lining fluid. The maximum beryllium release in 7 days was 11.78% (from a beryl ore melter dust), although release from most materials was beryllium ions may be released in the respiratory tract via dissolution in airway lining fluid. Beryllium-containing particles that deposit in the respiratory tract dissolve in artificial lung epithelial lining fluid, thereby providing ions for absorption in the lung and interaction with immune-competent cells in the respiratory tract.

  9. ZIRCONIUM-TITANIUM-BERYLLIUM BRAZING ALLOY

    Science.gov (United States)

    Gilliland, R.G.; Patriarca, P.; Slaughter, G.M.; Williams, L.C.

    1962-06-12

    A new and improved ternary alloy is described which is of particular utility in braze-bonding parts made of a refractory metal selected from Group IV, V, and VI of the periodic table and alloys containing said metal as a predominating alloying ingredient. The brazing alloy contains, by weight, 40 to 50 per cent zirconium, 40 to 50 per cent titanium, and the balance beryllium in amounts ranging from 1 to 20 per cent, said alloy having a melting point in the range 950 to 1400 deg C. (AEC)

  10. Alkali-metal/alkaline-earth-metal fluorine beryllium borate NaSr{sub 3}Be{sub 3}B{sub 3}O{sub 9}F{sub 4} with large nonlinear optical properties in the deep-ultraviolet region

    Energy Technology Data Exchange (ETDEWEB)

    Reshak, A. H., E-mail: maalidph@yahoo.com [New Technologies—Research Centre, University of West Bohemia, Univerzitni 8, 306 14 Pilsen (Czech Republic); Center of Excellence Geopolymer and Green Technology, School of Material Engineering, University Malaysia Perlis, 01007 Kangar, Perlis (Malaysia); Huang, Hongwei [School of Materials Science and Technology, China University of Geosciences, Beijing 100083 (China); Kamarudin, H. [Center of Excellence Geopolymer and Green Technology, School of Material Engineering, University Malaysia Perlis, 01007 Kangar, Perlis (Malaysia); Auluck, S. [Council of Scientific and Industrial Research—National Physical Laboratory, Dr. K S Krishnan Marg, New Delhi 110012, India and Physics Department, Indian Institute of Technology - Delhi, Hauz Khas, New Delhi 110016 (India)

    2015-02-28

    The linear optical response and second harmonic generation (SHG) in alkali-metal/alkaline-earth-metal fluorine beryllium borate NaSr{sub 3}Be{sub 3}B{sub 3}O{sub 9}F{sub 4} are investigated by means of density functional theory. Calculations are performed using four types of exchange correlations: Ceperley-Alder local density approximation, Perdew Burke and Ernzerhof general gradient approximation, Engel-Vosko generalized gradient approximation, and the recently modified Becke-Johnson potential (mBJ). The mBJ approach brings the calculated band gap (7.20 eV) in excellent agreement with the experimental one (7.28 eV). The calculated values of the uniaxial anisotropy δε=−0.076 and the birefringence Δn(0)=0.052 indicate considerable anisotropy in the linear optical properties, which makes it favorable for the second harmonic generation. The dominant component of the second harmonic generation is χ{sub 111}{sup (2)}(ω). The value of |χ{sub 111}{sup (2)}(ω)| is about 1.2 pm/V at λ = 1064 nm in agreement with previous calculations. To analyze the origin of the high SHG of NaSr{sub 3}Be{sub 3}B{sub 3}O{sub 9}F{sub 4} single crystals, we have correlated the features of |χ{sub 111}{sup (2)}(ω)| spectra with the features of ε{sub 2}(ω) spectra as a function of ω/2 and ω. From the calculated dominant component |χ{sub 111}{sup (2)}(ω)|, we find that the microscopic first hyperpolarizability, β{sub 111}, the vector components along the dipole moment direction is 0.5 × 10{sup −30} esu at static limit and 0.6 × 10{sup −30} esu at λ = 1064 nm.

  11. Integrative Analysis of CRISPR/Cas9 Target Sites in the Human HBB Gene

    Directory of Open Access Journals (Sweden)

    Yumei Luo

    2015-01-01

    Full Text Available Recently, the clustered regularly interspaced short palindromic repeats (CRISPR system has emerged as a powerful customizable artificial nuclease to facilitate precise genetic correction for tissue regeneration and isogenic disease modeling. However, previous studies reported substantial off-target activities of CRISPR system in human cells, and the enormous putative off-target sites are labor-intensive to be validated experimentally, thus motivating bioinformatics methods for rational design of CRISPR system and prediction of its potential off-target effects. Here, we describe an integrative analytical process to identify specific CRISPR target sites in the human β-globin gene (HBB and predict their off-target effects. Our method includes off-target analysis in both coding and noncoding regions, which was neglected by previous studies. It was found that the CRISPR target sites in the introns have fewer off-target sites in the coding regions than those in the exons. Remarkably, target sites containing certain transcriptional factor motif have enriched binding sites of relevant transcriptional factor in their off-target sets. We also found that the intron sites have fewer SNPs, which leads to less variation of CRISPR efficiency in different individuals during clinical applications. Our studies provide a standard analytical procedure to select specific CRISPR targets for genetic correction.

  12. Integrative Analysis of CRISPR/Cas9 Target Sites in the Human HBB Gene.

    Science.gov (United States)

    Luo, Yumei; Zhu, Detu; Zhang, Zhizhuo; Chen, Yaoyong; Sun, Xiaofang

    2015-01-01

    Recently, the clustered regularly interspaced short palindromic repeats (CRISPR) system has emerged as a powerful customizable artificial nuclease to facilitate precise genetic correction for tissue regeneration and isogenic disease modeling. However, previous studies reported substantial off-target activities of CRISPR system in human cells, and the enormous putative off-target sites are labor-intensive to be validated experimentally, thus motivating bioinformatics methods for rational design of CRISPR system and prediction of its potential off-target effects. Here, we describe an integrative analytical process to identify specific CRISPR target sites in the human β-globin gene (HBB) and predict their off-target effects. Our method includes off-target analysis in both coding and noncoding regions, which was neglected by previous studies. It was found that the CRISPR target sites in the introns have fewer off-target sites in the coding regions than those in the exons. Remarkably, target sites containing certain transcriptional factor motif have enriched binding sites of relevant transcriptional factor in their off-target sets. We also found that the intron sites have fewer SNPs, which leads to less variation of CRISPR efficiency in different individuals during clinical applications. Our studies provide a standard analytical procedure to select specific CRISPR targets for genetic correction.

  13. CD9 monoclonal antibody-conjugated PEGylated liposomes for targeted delivery of rapamycin in the treatment of cellular senescence

    Science.gov (United States)

    Thuy Nguyen, Hanh; Thapa, Raj Kumar; Shin, Beom Soo; Jeong, Jee-Heon; Kim, Jae-Ryong; Yong, Chul Soon; Kim, Jong Oh

    2017-03-01

    Premature cellular senescence refers to the state of irreversible cell cycle arrest due to DNA damage or other stresses. In this study, CD9 monoclonal antibody (CD9mAb) was successfully conjugated to the surface of PEGylated liposomes for targeted delivery of rapamycin (LR-CD9mAb) to overcome senescence of CD9 receptor-overexpressing cells. LR-CD9mAb has a small particle size (143.3 ± 2.4 nm), narrow size distribution (polydispersity index: 0.220 ± 0.036), and negative zeta potential (‑14.6 ± 1.2 mV). The uptake of CD9-targeted liposomes by premature senescent human dermal fibroblasts (HDFs) was higher than that by young HDFs, as displayed by confocal microscopic images. The senescence might not be reversed by treatment with rapamycin; however, the drug promoted cell proliferation and reduced the number of cells that expressed the senescence-associated-β-galactosidase (SA-β-gal). These effects were further confirmed by cell viability, cell cycle, and Western blotting analyses. Moreover, CD9-targeted liposomes showed better anti-senescence activity, in comparison with free rapamycin or the conventional liposomal formulation, suggesting the potential application of this system in further in vivo studies.

  14. 40 CFR 63.11166 - What General Provisions apply to primary beryllium production facilities?

    Science.gov (United States)

    2010-07-01

    ... primary beryllium production facilities? 63.11166 Section 63.11166 Protection of Environment ENVIRONMENTAL... Primary Nonferrous Metals Area Sources-Zinc, Cadmium, and Beryllium Primary Beryllium Production Facilities § 63.11166 What General Provisions apply to primary beryllium production facilities? (a) You...

  15. CA19-9 as a Potential Target for Radiolabeled Antibody-Based Positron Emission Tomography of Pancreas Cancer

    Directory of Open Access Journals (Sweden)

    Mark D. Girgis

    2011-01-01

    Full Text Available Introduction. Sensitive and specific imaging of pancreas cancer are necessary for accurate diagnosis, staging, and treatment. The vast majority of pancreas cancers express the carbohydrate tumor antigen CA19-9. The goal of this study was to determine the potential to target CA19-9 with a radiolabeled anti-CA19-9 antibody for imaging pancreas cancer. Methods. CA19-9 was quantified using flow cytometry on human pancreas cancer cell lines. An intact murine anti-CA19-9 monoclonal antibody was labeled with a positron emitting radionuclide (Iodine-124 and injected into mice harboring antigen positive and negative xenografts. MicroPET/CT were performed at successive time intervals (72 hours, 96 hours, 120 hours after injection. Radioactivity was measured in blood and tumor to provide objective confirmation of the images. Results. Antigen expression by flow cytometry revealed approximately 1.3×106 CA19-9 antigens for the positive cell line and no expression in the negative cell line. Pancreas xenograft imaging with Iodine-124-labeled anti-CA19-9 mAb demonstrated an average tumor to blood ratio of 5 and positive to negative tumor ratio of 20. Conclusion. We show in vivo targeting of our antigen positive xenograft with a radiolabeled anti-CA19-9 antibody. These data demonstrate the potential to achieve anti-CA19-9 antibody based positron emission tomography of pancreas cancer.

  16. "Autophagy suite": Atg9 cycling in the cytoplasm to vacuole targeting pathway.

    Science.gov (United States)

    Munakata, Nobuo; Klionsky, Daniel J

    2010-08-01

    Macroautophagy continues to gather increasing attention because it is connected with a wide range of human pathophysiologies, developmental processes and life span extension. It is also an interesting process from a basic cellular biology standpoint, as it involves dynamic membrane rearrangements and multiple protein-protein interactions. Although macroautophagy can be nonspecific, there are many examples of selective sequestration including pexophagy, mitophagy and the cytoplasm to vacuole targeting (Cvt) pathway. At present, the Cvt pathway is unique in that it is the only example of a biosynthetic use of macroautophagy. Most of the autophagy-related (Atg) proteins are involved in the Cvt pathway, and various types of analyses have placed these proteins at particular stages of the process. For example, Atg9 is the only characterized transmembrane protein that is absolutely required for Cvt vesicle formation, and it is proposed to carry membrane from peripheral donor sites to the phagophore assembly site where the vesicle forms. Additional proteins, including Atg11, Atg23 and Atg27 are involved in this anterograde movement, whereas Atg1-Atg13 and Atg2-Atg18 are required for the retrograde return to the peripheral sites. Even when we illustrate our understanding of these events in a schematic model, however, they are by necessity flat two-dimensional representations, lacking movement and sound. Yet the cell is a living entity that is not well served by this sole method of information display. Accordingly, we decided to present the Cvt pathway as a vibrant, dynamic process by combining science, music and illustration.

  17. Isotopic distributions of the sup 1 sup 8 N fragmentation products in coincidence with neutrons on targets sup 1 sup 9 sup 7 Au and sup 9 Be

    CERN Document Server

    Li Xiang Qing; Ye Yan Lin; Hua Hui; Chen Tao; Li Zhi Huan; Ge Yuch Eng; Wang Quan Jin; Wu He Yu; Jin Ge; Duan Li Min; Xiao Zhi Gang; Wang Hong Wei; Li Zhu Yu; Wang Su Fang

    2002-01-01

    The authors present the experimental isotopic distributions of the sup 1 sup 8 N projectile fragmentation products Li, Be, B and C in coincidence with neutrons, as well as the inclusive ones on sup 1 sup 9 sup 7 Au and sup 9 Be targets. In the framework of the abrasion-ablation model, these distributions are calculated for various nucleon density distributions of the projectile. The comparison with experimental isotopic distributions of the projectile-like fragments in coincidence with neutrons shows that the information on the nucleon density distribution of the sup 1 sup 8 N projectile can be extracted

  18. The Multi MegaWatt target station of EURISOL facility and its performance (SATIF9)

    CERN Document Server

    Kharoua, C

    This presentation summarises the work carried out for the Multi Megawatt target station of the EURISOL Design Study with a special attention to the coupled neutronics of the liquid converter and fission target (MAFF/PIAFE design like) and the overall performance of the facility, which will sustain fast neutron fluxes of the order of 1014 n/cm2/s. The production of radionuclides in the actinide targets as well as in the liquid metal are also evaluated, showing that the targeted 1015 fissions/s can be achieved.

  19. High-throughput profiling of off-target DNA cleavage reveals RNA-programmed Cas9 nuclease specificity.

    Science.gov (United States)

    Pattanayak, Vikram; Lin, Steven; Guilinger, John P; Ma, Enbo; Doudna, Jennifer A; Liu, David R

    2013-09-01

    The RNA-programmable Cas9 endonuclease cleaves double-stranded DNA at sites complementary to a 20-base-pair guide RNA. The Cas9 system has been used to modify genomes in multiple cells and organisms, demonstrating its potential as a facile genome-engineering tool. We used in vitro selection and high-throughput sequencing to determine the propensity of eight guide-RNA:Cas9 complexes to cleave each of 10(12) potential off-target DNA sequences. The selection results predicted five off-target sites in the human genome that were confirmed to undergo genome cleavage in HEK293T cells upon expression of one of two guide-RNA:Cas9 complexes. In contrast to previous models, our results show that guide-RNA:Cas9 specificity extends past a 7- to 12-base-pair seed sequence. Our results also suggest a tradeoff between activity and specificity both in vitro and in cells as a shorter, less-active guide RNA is more specific than a longer, more-active guide RNA. High concentrations of guide-RNA:Cas9 complexes can cleave off-target sites containing mutations near or within the PAM that are not cleaved when enzyme concentrations are limiting.

  20. Benchmark calculations for electron-impact excitation and ionization of beryllium

    Science.gov (United States)

    Zatsarinny, Oleg; Bartschat, Klaus; Fursa, Dmitry V.; Bray, Igor

    2016-09-01

    The B-spline R-matrix and the convergent close-coupling methods are used to study electron collisions with neutral beryllium for energies from threshold to 100 eV. Coupling to the target continuum significantly affects the results for transitions from the ground state, but to a lesser extent the strong transitions between excited states. Cross sections are presented for selected transitions between low-lying physical bound states of beryllium, as well as for elastic scattering, momentum transfer, and ionization. The present cross sections for transitions from the ground state from the two methods are in excellent agreement with each other, and also with previous results based on nonperturbative convergent pseudostate and time-dependent close-coupling models. The elastic cross section at low energies is dominated by a shape resonance. The ionization from the (2 s 2 p) 3 P and (2 s 2 p) 1 P states strongly depends on the respective term. The current predictions represent an extensive set of electron scattering data for neutral beryllium, which should be sufficient for most modeling applications. This work was supported by the United States National Science Foundation (OZ and KB) and the Australian Research Council (DVF and IB).

  1. Liposomal Tumor Targeting in Drug Delivery Utilizing MMP-2- and MMP-9-Binding Ligands

    Directory of Open Access Journals (Sweden)

    Oula Penate Medina

    2011-01-01

    Full Text Available Nanotechnology offers an alternative to conventional treatment options by enabling different drug delivery and controlled-release delivery strategies. Liposomes being especially biodegradable and in most cases essentially nontoxic offer a versatile platform for several different delivery approaches that can potentially enhance the delivery and targeting of therapies to tumors. Liposomes penetrate tumors spontaneously as a result of fenestrated blood vessels within tumors, leading to known enhanced permeability and subsequent drug retention effects. In addition, liposomes can be used to carry radioactive moieties, such as radiotracers, which can be bound at multiple locations within liposomes, making them attractive carriers for molecular imaging applications. Phage display is a technique that can deliver various high-affinity and selectivity peptides to different targets. In this study, gelatinase-binding peptides, found by phage display, were attached to liposomes by covalent peptide-PEG-PE anchor creating a targeted drug delivery vehicle. Gelatinases as extracellular targets for tumor targeting offer a viable alternative for tumor targeting. Our findings show that targeted drug delivery is more efficient than non-targeted drug delivery.

  2. Beryllium nitrate inhibits fibroblast migration to disrupt epimorphic regeneration.

    Science.gov (United States)

    Cook, Adam B; Seifert, Ashley W

    2016-10-01

    Epimorphic regeneration proceeds with or without formation of a blastema, as observed for the limb and skin, respectively. Inhibition of epimorphic regeneration provides a means to interrogate the cellular and molecular mechanisms that regulate it. In this study, we show that exposing amputated limbs to beryllium nitrate disrupts blastema formation and causes severe patterning defects in limb regeneration. In contrast, exposing full-thickness skin wounds to beryllium only causes a delay in skin regeneration. By transplanting full-thickness skin from ubiquitous GFP-expressing axolotls to wild-type hosts, we demonstrate that beryllium inhibits fibroblast migration during limb and skin regeneration in vivo Moreover, we show that beryllium also inhibits cell migration in vitro using axolotl and human fibroblasts. Interestingly, beryllium did not act as an immunostimulatory agent as it does in Anurans and mammals, nor did it affect keratinocyte migration, proliferation or re-epithelialization, suggesting that the effect of beryllium is cell type-specific. While we did not detect an increase in cell death during regeneration in response to beryllium, it did disrupt cell proliferation in mesenchymal cells. Taken together, our data show that normal blastema organogenesis cannot occur without timely infiltration of local fibroblasts and highlights the importance of positional information to instruct pattern formation during regeneration. In contrast, non-blastemal-based skin regeneration can occur despite early inhibition of fibroblast migration and cell proliferation.

  3. Fluorimetric method for determination of Beryllium; Determinazione fluorimetrica del berillio

    Energy Technology Data Exchange (ETDEWEB)

    Sparacino, N.; Sabbioneda, S. [ENEA, Centro Ricerche Saluggia, Vercelli (Italy). Dip. Energia

    1996-10-01

    The old fluorimetric method for the determination of Beryllium, based essentially on the fluorescence of the Beryllium-Morine complex in a strongly alkaline solution, is still competitive and stands the comparison with more modern methods or at least three reasons: in the presence of solid or gaseous samples (powders), the times necessary to finalize an analytic determination are comparable since the stage of the process which lasts the longest is the mineralization of the solid particles containing Beryllium, the cost of a good fluorimeter is by far Inferior to the cost, e. g., of an Emission Spectrophotometer provided with ICP torch and magnets for exploiting the Zeeman effect and of an Atomic absorption Spectrophotometer provided with Graphite furnace; it is possible to determine, fluorimetrically, rather small Beryllium levels (about 30 ng of Beryllium/sample), this potentiality is more than sufficient to guarantee the respect of all the work safety and hygiene rules now in force. The study which is the subject of this publication is designed to the analysis procedure which allows one to reach good results in the determination of Beryllium, chiefly through the control and measurement of the interference effect due to the presence of some metals which might accompany the environmental samples of workshops and laboratories where Beryllium is handled, either at the pure state or in its alloys. The results obtained satisfactorily point out the merits and limits of this analytic procedure.

  4. Sarcoidosis and chronic beryllium disease: similarities and differences.

    Science.gov (United States)

    Mayer, Annyce S; Hamzeh, Nabeel; Maier, Lisa A

    2014-06-01

    Chronic beryllium disease (CBD) is a granulomatous lung disease that may be pathologically and clinically indistinguishable from pulmonary sarcoidosis, except through use of immunologic testing, such as the beryllium lymphocyte proliferation test (BeLPT). Similar to sarcoidosis, the pulmonary manifestations of CBD are variable and overlap with other respiratory diseases. Definitive diagnosis of CBD is established by evidence of immune sensitization to beryllium and diagnostic bronchoscopy with bronchoalveolar lavage and transbronchial biopsy. However, the diagnosis of CBD can also be established on a medically probable basis in beryllium-exposed patients with consistent radiographic imaging and clinical course. Beryllium workers exposed too much higher levels of beryllium in the past demonstrated a much more fulminant disease than is usually seen today. Some extrapulmonary manifestations similar to sarcoidosis were noted in these historic cohorts, although with a narrower spectrum. Extrapulmonary manifestations of CBD are rare today. Since lung-predominant sarcoidosis can very closely resemble CBD, CBD is still misdiagnosed as sarcoidosis when current or past exposure to beryllium is not recognized and no BeLPT is obtained. This article describes the similarities and differences between CBD and sarcoidosis, including clinical and diagnostic features that can help physicians consider CBD in patients with apparent lung-predominant sarcoidosis.

  5. The Size, Shape, and Albedo of Deep Impact Target 9P/Tempel 1

    Science.gov (United States)

    A'Hearn, Michael; Lisse, Carey; Lisse, C.; Fernandez, Y.; Belton, M.; Groussin, O.; Meech, K.; van Cleve, J.

    2004-02-01

    The Deep Impact mission, the eighth mission in NASA's Discovery Program, will launch on 30 Dec 2004 and will impact the nucleus of comet 9P/Tempel 1 on 4 July 2005. Delivering an impactor to a cometary nucleus and observing the results of the impact is a challenging task. Mission success depends critically on the ability of the DI spacecraft to navigate to the comet. Despite robust targeting algorithms, large uncertainties in size, shape, albedo distribution, and rotational state significantly degrade the probability that the impactor will land in a sunlit portion of the surface that is observable from the flyby. The uncertainties in the size, axial ratio, and rotational state further jeopardize the ability of the flyby spacecraft to point its High Resolution Instrument at the actual impact site with sufficient precision to ensure it is in the field of view. Current estimate of the comet's size using Keck LWS observations are uncertain by 50% and they have provided no information on the distribution of albedo. Although uncertainty in the phasing of the optical lightcurve represents a large part of that error, there is also a significant uncertainty due to the combination of low SNR in the data from Keck and the limited spectral range over which data could be obtained. In order to improve our estimate of the size and shape of the nucleus of Tempel 1, we must obtain data with much higher SNR and with one-hour time resolution over a significant portion of the rotation light curve when the comet is inactive. We must determine whether or not there are large variations in albedo across the surface to order to ensure that the rotational lightcurve from optical data can be used to predict the convex hull of the actual shape. Tempel 1 is available in only one Spitzer viewing widow before it is expected to be close enough to the sun to become active, namely the window from 27 Feb through 29 April 2004, before the first GO observing period, at 3.7 AU from the Sun. The expect

  6. Angiotensin-1 converting enzyme polymorphisms in chronic beryllium disease.

    Science.gov (United States)

    Maier, L A; Raynolds, M V; Young, D A; Barker, E A; Newman, L S

    1999-04-01

    To test the hypothesis that the angiotensin converting enzyme (ACE) genotype is associated with chronic beryllium disease (CBD) and disease severity, we studied 50 cases of CBD and compared their ACE genotype to that of two different control groups, consisting of: (1) 50 participants from a beryllium machining facility; and (2) 50 participants from a non-beryllium-associated workplace. We found no statistically significant difference in the frequency of the I or D allele or of the DD genotype among cases of CBD and either control group. The odds ratio (OR) for the CBD DD genotype as compared with the non-DD genotype was 1.58 (95% confidence interval [CI]: 0.68 to 3.66, p = 0.12) for the beryllium-exposed control group, and 1.09 (95% CI: 0.48 to 2.46, p = 0.56) for the non-beryllium-exposed controls. We found an association between serum ACE activity and the ACE genotype, with DD cases having the highest median serum ACE activity (p = 0.005). We evaluated the beryllium lymphocyte proliferation test (BeLPT), bronchoalveolar lavage (BAL) cell components, chest radiography, pulmonary function test results, and exercise physiology in our CBD cases. No statistically significant associations with these disease markers were found for the CBD cases with the DD genotype. Although the difference was not statistically significant, the DD cases had a shorter median duration of exposure to beryllium before diagnosis of CBD, and tended to have a weaker response in their blood and BAL BeLPT than did the non-DD cases. These findings may indicate that the ACE genotype is important in the immune response to beryllium and in progression to beryllium disease.

  7. A novel 9 × 9 map-based solvent selection strategy for targeted counter-current chromatography isolation of natural products.

    Science.gov (United States)

    Liang, Junling; Meng, Jie; Wu, Dingfang; Guo, Mengzhe; Wu, Shihua

    2015-06-26

    Counter-current chromatography (CCC) is an efficient liquid-liquid chromatography technique for separation and purification of complex mixtures like natural products extracts and synthetic chemicals. However, CCC is still a challenging process requiring some special technical knowledge especially in the selection of appropriated solvent systems. In this work, we introduced a new 9 × 9 map-based solvent selection strategy for CCC isolation of targets, which permit more than 60 hexane-ethyl acetate-methanol-water (HEMWat) solvent systems as the start candidates for the selection of solvent systems. Among these solvent systems, there are clear linear correlations between partition coefficient (K) and the system numbers. Thus, an appropriate CCC solvent system (i.e., sweet spot for K = 1) may be hit by measurement of k values of the target only in two random solvent systems. Besides this, surprisingly, we found that through two sweet spots, we could get a line ("Sweet line") where there are infinite sweet solvent systems being suitable for CCC separation. In these sweet solvent systems, the target has the same partition coefficient (K) but different solubilities. Thus, the better sweet solvent system with higher sample solubility can be obtained for high capacity CCC preparation. Furthermore, we found that there is a zone ("Sweet zone") where all solvent systems have their own sweet partition coefficients values for the target in range of 0.4 natural products as standards and further confirmed by isolation of several targets including honokiol and magnolol from the extracts of Magnolia officinalis Rehd. Et Wils and tanshinone IIA from Salvia miltiorrhiza Bunge. In practice, it is much easier to get a suitable solvent system only by making a simple screening two to four HEMWat two-phase solvent systems to obtain the sweet line or sweet zone without special knowledge or comprehensive standards as references. This is an important advancement for solvent system selection

  8. Beryllium Health and Safety Committee Data Reporting Task Force

    Energy Technology Data Exchange (ETDEWEB)

    MacQueen, D H

    2007-02-21

    On December 8, 1999, the Department of Energy (DOE) published Title 10 CFR 850 (hereafter referred to as the Rule) to establish a chronic beryllium disease prevention program (CBDPP) to: {sm_bullet} reduce the number of workers currently exposed to beryllium in the course of their work at DOE facilities managed by DOE or its contractors, {sm_bullet} minimize the levels of, and potential for, expos exposure to beryllium, and {sm_bullet} establish medical surveillance requirements to ensure early detection of the disease.

  9. Inhibitory effects of beryllium chloride on rat liver microsomal enzymes.

    Science.gov (United States)

    Teixeira, C F; Yasaka, W J; Silva, L F; Oshiro, T T; Oga, S

    1990-04-30

    A single i.v. dose (0.1 mmol Be2+/kg) of beryllium chloride prolonged the duration of pentobarbital-induced sleep and zoxazolamine-induced paralysis, in rats. The effects are correlated with changes of the pharmacokinetic parameters and with the in vitro inhibition of both aliphatic and aromatic hydroxylation of pentobarbital and zoxazolamine. In vitro N-demethylation of meperidine and aminopyrine was partially inhibited while O-demethylation of quinidine was unaffected by liver microsomes of rats pretreated with beryllium salt. The findings give clues that beryllium chloride inhibits some forms of cytochrome P-450, especially those responsible for hydroxylation of substrates, like pentobarbital and zoxazolamine.

  10. Development of Beryllium Vacuum Chamber Technology for the LHC

    CERN Document Server

    Veness, R; Dorn, C

    2011-01-01

    Beryllium is the material of choice for the beam vacuum chambers around collision points in particle colliders due to a combination of transparency to particles, high specific stiffness and compatibility with ultra-high vacuum. New requirements for these chambers in the LHC experiments have driven the development of new methods for the manufacture of beryllium chambers. This paper reviews the requirements for experimental vacuum chambers. It describes the new beryllium technology adopted for the LHC and experience gained in the manufacture and installation.

  11. A high-efficiency CRISPR/Cas9 system for targeted mutagenesis in Cotton (Gossypium hirsutum L.)

    Science.gov (United States)

    Li, Chao; Unver, Turgay; Zhang, Baohong

    2017-01-01

    The complex allotetraploid genome is one of major challenges in cotton for repressing gene expression. Developing site-specific DNA mutation is the long-term dream for cotton breeding scientists. The clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9 (CRISPR/Cas9) system is emerging as a robust biotechnology for targeted-DNA mutation. In this study, two sgRNAs, GhMYB25-like-sgRNA1 and GhMYB25-like-sgRNA2, were designed in the identical genomic regions of GhMYB25-like A and GhMYB25-like D, which were encoded by cotton A subgenome and the D subgenome, respectively, was assembled to direct Cas9-mediated allotetraploid cotton genome editing. High proportion (14.2–21.4%) CRISPR/Cas9-induced specific truncation events, either from GhMYB25-like A DNA site or from GhMYB25-like D DNA site, were detected in 50% examined transgenic cotton through PCR amplification assay and sequencing analyses. Sequencing results also demonstrated that 100% and 98.8% mutation frequency were occurred on GhMYB25-like-sgRNA1 and GhMYB25-like-sgRNA2 target site respectively. The off-target effect was evaluated by sequencing two putative off-target sites, which have 3 and 1 mismatched nucleotides with GhMYB25-like-sgRNA1 and GhMYB25-like-sgRNA2, respectively; all the examined samples were not detected any off-target-caused mutation events. Thus, these results demonstrated that CRISPR/Cas9 is qualified for generating DNA level mutations on allotetraploid cotton genome with high-efficiency and high-specificity. PMID:28256588

  12. Low incidence of off-target mutations in individual CRISPR-Cas9 and TALEN targeted human stem cell clones detected by whole-genome sequencing.

    Science.gov (United States)

    Veres, Adrian; Gosis, Bridget S; Ding, Qiurong; Collins, Ryan; Ragavendran, Ashok; Brand, Harrison; Erdin, Serkan; Cowan, Chad A; Talkowski, Michael E; Musunuru, Kiran

    2014-07-03

    Genome editing has attracted wide interest for the generation of cellular models of disease using human pluripotent stem cells and other cell types. CRISPR-Cas systems and TALENs can target desired genomic sites with high efficiency in human cells, but recent publications have led to concern about the extent to which these tools may cause off-target mutagenic effects that could potentially confound disease-modeling studies. Using CRISPR-Cas9 and TALEN targeted human pluripotent stem cell clones, we performed whole-genome sequencing at high coverage in order to assess the degree of mutagenesis across the entire genome. In both types of clones, we found that off-target mutations attributable to the nucleases were very rare. From this analysis, we suggest that, although some cell types may be at risk for off-target mutations, the incidence of such effects in human pluripotent stem cells may be sufficiently low and thus not a significant concern for disease modeling and other applications.

  13. Experimental investigation of the energy and temperature dependence of beryllium self sputtering

    Energy Technology Data Exchange (ETDEWEB)

    Korshunov, S.N.; Guseva, M.I.; Stolijarova, V.G. [RRC Kurchatov Institute, Moscow (Russian Federation)

    1995-09-01

    The low-Z metal beryllium is considered as plasma facing material (PFM) for the ITER. It is expected that operation temperature range of beryllium PFM will be (670 - 1070) K. While experimental Be-sputtering data bases exist for H{sup +}, D{sup +} and He{sup +}-ions, the self-sputtering yields of Be have only been estimated by computer simulation. In this paper we report the experimental results on the energy and temperature dependence of the beryllium self-sputtering yield (S). The energy dependence of S{sup s} in the energy range (0.5 - 10.0) keV was measured at 670 K. The self-sputtering yield of Be attains its maximal value at the ion energy of 1.5 keV, being equal to 0.32 {+-} at./ion. Comparison of the experimental results and theoretical prediction shows a good agreement for energy dependence of S{sup s}. The temperature dependence of S{sup s} in the temperature range (370-1070)K was obtained for 0.9keV Be{sup +}-ions. The value of S{sup s} is not changed up to 870 K. It sharply increases at the temperatures above 870 attaining the value of 0.75 at./ion at 1070 K.

  14. Development of spectrophotometric determination of beryllium in beryl minerals using chrome Azurol S

    Directory of Open Access Journals (Sweden)

    Hisham K. Fouad

    2016-09-01

    Full Text Available A developed, direct, rapid, and sensitive spectrophotometric determination of beryllium in beryl minerals with Chrome Azurol S (CAS as a chromogenic reagent was developed in the present article. The determination was performed without either solvent extraction or ion exchange separation of beryllium from its matrix. The stable 1:1 Be-CAS complex was formed instantly with duration time of at least 24 h with constant absorbance. Different parameters such as wavelengths, pH, EDTA concentration and dye concentration were studied for the optimum determination of beryllium. Interference due to presence of high aluminum concentrations was overcome by adding 5% EDTA disodium salt solution. Maximum absorbance for Be-CAS complex was performed at λmax 568 NM using acetate buffer at pH 4.6. Beer’s law was obeyed in the range from 0.02 to 9 ppm with molar absorptivity ε = 0.22 × 104 mol−1 cm−1 and an average standard deviation of 0.7. The R.S.D for 10 replicate measurements of 1 ppm Be was 1.2%.

  15. Extraction of beryllium from refractory beryllium oxide with dilute ammonium bifluoride and determination by fluorescence: a multiparameter performance evaluation.

    Science.gov (United States)

    Goldcamp, Michael J; Goldcamp, Diane M; Ashley, Kevin; Fernback, Joseph E; Agrawal, Anoop; Millson, Mark; Marlow, David; Harrison, Kenneth

    2009-12-01

    Beryllium exposure can cause a number of deleterious health effects, including beryllium sensitization and the potentially fatal chronic beryllium disease. Efficient methods for monitoring beryllium contamination in workplaces are valuable to help prevent dangerous exposures to this element. In this work, performance data on the extraction of beryllium from various size fractions of high-fired beryllium oxide (BeO) particles (from Beryllium concentrations were determined by fluorescence using a hydroxybenzoquinoline fluorophore. The effects of ABF concentration and volume, extraction temperature, sample tube types, and presence of filter or wipe media were examined. Three percent ABF extracts beryllium nearly twice as quickly as 1% ABF; extraction solution volume has minimal influence. Elevated temperatures increase the rate of extraction dramatically compared with room temperature extraction. Sample tubes with constricted tips yield poor extraction rates owing to the inability of the extraction medium to access the undissolved particles. The relative rates of extraction of Be from BeO of varying particle sizes were examined. Beryllium from BeO particles in fractions ranging from less than 32 microm up to 212 microm were subjected to various extraction schemes. The smallest BeO particles are extracted more quickly than the largest particles, although at 90 degrees C even the largest BeO particles reach nearly quantitative extraction within 4 hr in 3% ABF. Extraction from mixed cellulosic-ester filters, cellulosic surface-sampling filters, wetted cellulosic dust wipes, and cotton gloves yielded 90% or greater recoveries. Scanning electron microscopy of BeO particles, including partially dissolved particles, shows that dissolution in dilute ABF occurs not just on the exterior surface but also via accessing particles' interiors due to porosity of the BeO material. Comparison of dissolution kinetics data shows that as particle diameter approximately doubles, extraction

  16. CRISPRseek: a bioconductor package to identify target-specific guide RNAs for CRISPR-Cas9 genome-editing systems.

    Directory of Open Access Journals (Sweden)

    Lihua J Zhu

    Full Text Available CRISPR-Cas systems are a diverse family of RNA-protein complexes in bacteria that target foreign DNA sequences for cleavage. Derivatives of these complexes have been engineered to cleave specific target sequences depending on the sequence of a CRISPR-derived guide RNA (gRNA and the source of the Cas9 protein. Important considerations for the design of gRNAs are to maximize aimed activity at the desired target site while minimizing off-target cleavage. Because of the rapid advances in the understanding of existing CRISPR-Cas9-derived RNA-guided nucleases and the development of novel RNA-guided nuclease systems, it is critical to have computational tools that can accommodate a wide range of different parameters for the design of target-specific RNA-guided nuclease systems. We have developed CRISPRseek, a highly flexible, open source software package to identify gRNAs that target a given input sequence while minimizing off-target cleavage at other sites within any selected genome. CRISPRseek will identify potential gRNAs that target a sequence of interest for CRISPR-Cas9 systems from different bacterial species and generate a cleavage score for potential off-target sequences utilizing published or user-supplied weight matrices with position-specific mismatch penalty scores. Identified gRNAs may be further filtered to only include those that occur in paired orientations for increased specificity and/or those that overlap restriction enzyme sites. For applications where gRNAs are desired to discriminate between two related sequences, CRISPRseek can rank gRNAs based on the difference between predicted cleavage scores in each input sequence. CRISPRseek is implemented as a Bioconductor package within the R statistical programming environment, allowing it to be incorporated into computational pipelines to automate the design of gRNAs for target sequences identified in a wide variety of genome-wide analyses. CRISPRseek is available under the GNU General

  17. High efficiency of targeted mutagenesis in arabidopsis via meiotic promoter-driven expression of Cas9 endonuclease

    KAUST Repository

    Eid, Ayman

    2016-05-28

    Key message: The use of a meiosis I-specific promoter increased the efficiency of targeted mutagenesis and will facilitate the manipulation of homologous recombination. Abstract: The CRISPR/Cas9 system has been harnessed for targeted engineering of eukaryotic genomes, including plants; however, CRISPR/Cas9 efficiency varies considerably in different plant tissues and species. In Arabidopsis, the generation of homozygous or bi-allelic mutants in the first (T1) generation is inefficient. Here, we used specific promoters to drive the expression of Cas9 during meiosis to maximize the efficiency of recovering heritable mutants in T1 plants. Our data reveal that the use of a promoter active in meiosis I resulted in high-efficiency (28 %) recovery of targeted mutants in the T1 generation. Moreover, this method enabled efficient simultaneous targeting of three genes for mutagenesis. Taken together, our results show that the use of meiosis-specific promoters will improve methods for functional genomic analysis and studying the molecular underpinnings of homologous recombination. © 2016, Springer-Verlag Berlin Heidelberg.

  18. CRISPR/Cas9 Targets Chicken Embryonic Somatic Cells In Vitro and In Vivo and generates Phenotypic Abnormalities

    Science.gov (United States)

    Abu-Bonsrah, Kwaku Dad; Zhang, Dongcheng; Newgreen, Donald F.

    2016-01-01

    Chickens are an invaluable model for studying human diseases, physiology and especially development, but have lagged in genetic applications. With the advent of Programmable Engineered Nucleases, genetic manipulation has become efficient, specific and rapid. Here, we show that the CRISPR/Cas9 system can precisely edit the chicken genome. We generated HIRA, TYRP1, DICER, MBD3, EZH2, and 6 other gene knockouts in two chicken cell lines using the CRISPR/Cas9 system, with no off-target effects detected. We also showed that very large deletions (>75 kb) could be achieved. We also achieved targeted modification by homology-directed repair (HDR), producing MEN2A and MEN2B mutations of the RET gene. We also targeted DGCR8 in neural cells of the chicken embryo by in vivo electroporation. After FACS isolation of transfected cells, we observed appropriate sequence changes in DGCR8. Wholemount and frozen section antibody labelling showed reduction of DGCR8 levels in transfected cells. In addition, there was reduced expression levels of DGCR8-associated genes DROSHA, YPEL1 and NGN2. We also observed morphological differences in neural tissue and cardiac-related tissues of transfected embryos. These findings demonstrate that precisely targeted genetic manipulation of the genome using the CRISPR/Cas9 system can be extended to the highly adaptable in vivo chicken embryo model. PMID:27694906

  19. A CRISPR-Cas9 gene drive system targeting female reproduction in the malaria mosquito vector Anopheles gambiae.

    Science.gov (United States)

    Hammond, Andrew; Galizi, Roberto; Kyrou, Kyros; Simoni, Alekos; Siniscalchi, Carla; Katsanos, Dimitris; Gribble, Matthew; Baker, Dean; Marois, Eric; Russell, Steven; Burt, Austin; Windbichler, Nikolai; Crisanti, Andrea; Nolan, Tony

    2016-01-01

    Gene drive systems that enable super-Mendelian inheritance of a transgene have the potential to modify insect populations over a timeframe of a few years. We describe CRISPR-Cas9 endonuclease constructs that function as gene drive systems in Anopheles gambiae, the main vector for malaria. We identified three genes (AGAP005958, AGAP011377 and AGAP007280) that confer a recessive female-sterility phenotype upon disruption, and inserted into each locus CRISPR-Cas9 gene drive constructs designed to target and edit each gene. For each targeted locus we observed a strong gene drive at the molecular level, with transmission rates to progeny of 91.4 to 99.6%. Population modeling and cage experiments indicate that a CRISPR-Cas9 construct targeting one of these loci, AGAP007280, meets the minimum requirement for a gene drive targeting female reproduction in an insect population. These findings could expedite the development of gene drives to suppress mosquito populations to levels that do not support malaria transmission.

  20. Investigation of the ion beryllium surface interaction

    Energy Technology Data Exchange (ETDEWEB)

    Guseva, M.I.; Birukov, A.Yu.; Gureev, V.M. [RRC Kurchatov Institute, Moscow (Russian Federation)] [and others

    1995-09-01

    The self -sputtering yield of the Be was measured. The energy dependence of the Be self-sputtering yield agrees well with that calculated by W. Eckstein et. al. Below 770 K the self-sputtering yield is temperature independent; at T{sub irr}.> 870 K it increases sharply. Hot-pressed samples at 370 K were implanted with monoenergetic 5 keV hydrogen ions and with a stationary plasma (flux power {approximately} 5 MW/m{sup 2}). The investigation of hydrogen behavior in beryllium shows that at low doses hydrogen is solved, but at doses {ge} 5x10{sup 22} m{sup -2} the bubbles and channels are formed. It results in hydrogen profile shift to the surface and decrease of its concentration. The sputtering results in further concentration decrease at doses > 10{sup 25}m{sup -2}.

  1. Primordial beryllium as a big bang calorimeter.

    Science.gov (United States)

    Pospelov, Maxim; Pradler, Josef

    2011-03-25

    Many models of new physics including variants of supersymmetry predict metastable long-lived particles that can decay during or after primordial nucleosynthesis, releasing significant amounts of nonthermal energy. The hadronic energy injection in these decays leads to the formation of ⁹Be via the chain of nonequilibrium transformations: Energy(h)→T, ³He→⁶He, ⁶Li→⁹Be. We calculate the efficiency of this transformation and show that if the injection happens at cosmic times of a few hours the release of O(10 MeV) per baryon can be sufficient for obtaining a sizable ⁹Be abundance. The absence of a plateau structure in the ⁹Be/H abundance down to a O(10⁻¹⁴) level allows one to use beryllium as a robust constraint on new physics models with decaying or annihilating particles.

  2. Photodesorption from copper, beryllium, and thin films

    Science.gov (United States)

    Foerster, C. L.; Halama, H. J.; Korn, G.

    Ever increasing circulating currents in electron-positron colliders and light sources demand lower and lower photodesportion (PSD) from the surfaces of their vacuum chambers and their photon absorbers. This is particularly important in compact electron storage rings and B meson factories where photon power of several kw cm(exp -1) is deposited on the surfaces. Given the above factors, we have measured PSD from 1 m long bars of solid copper and solid beryllium, and TiN, Au and C thin films deposited on solid copper bars. Each sample was exposed to about 10(exp 23) photons/m with a critical energy of 500 eV at the VUV ring of the NSLS. PSD was recorded for two conditions: after a 200 C bake-out and after an Ar glow discharge cleaning. In addition, we also measured reflected photons, photoelectrons and desorption as functions of normal, 75 mrad, 100 mrad, and 125 mrad incident photons.

  3. New facility for post irradiation examination of neutron irradiated beryllium

    Energy Technology Data Exchange (ETDEWEB)

    Ishitsuka, Etsuo; Kawamura, Hiroshi [Oarai Research Establishment, Ibaraki-Ken (Japan)

    1995-09-01

    Beryllium is expected as a neutron multiplier and plasma facing materials in the fusion reactor, and the neutron irradiation data on properties of beryllium up to 800{degrees}C need for the engineering design. The acquisition of data on the tritium behavior, swelling, thermal and mechanical properties are first priority in ITER design. Facility for the post irradiation examination of neutron irradiated beryllium was constructed in the hot laboratory of Japan Materials Testing Reactor to get the engineering design data mentioned above. This facility consist of the four glove boxes, dry air supplier, tritium monitoring and removal system, storage box of neutron irradiated samples. Beryllium handling are restricted by the amount of tritium;7.4 GBq/day and {sup 60}Co;7.4 MBq/day.

  4. The uses and adverse effects of beryllium on health

    DEFF Research Database (Denmark)

    Cooper, Ross G.; Harrison, Adrian Paul

    2009-01-01

    Context: This review describes the health effects of beryllium exposure in the workplace and the environment. Aim: To collate information on the consequences of occupational and environmental exposure to beryllium on physiological function and well being. Materials and Methods: The criteria used...... in the current review for selecting articles were adopted from proposed criteria in The International Classification of Functioning, Disability, and Health. Articles were classified based on acute and chronic exposure and toxicity of beryllium. Results: The proportions of utilized and nonutilized articles were...... published in sources unobtainable through requests at the British Library, and some had no impact factor and were excluded. Conclusion: Beryllium has some useful but undoubtedly harmful effects on health and well-being. Measures needed to be taken to prevent hazardous exposure to this element, making its...

  5. Effect of microRNA-101 on apoptosis of rabbit condylar cartilage cells by inhibiting target gene SOX9

    Institute of Scientific and Technical Information of China (English)

    Xin Li; Zi-Xin Wang; Zi-Sheng Wang; Quan-Fang Li

    2015-01-01

    Objective:To explore the effect of microRNA-101 on apoptosis of condylar cartilage cells and the specific mechanism of molecular biology. Methods: IL-1 was used to stimulate and establish the model of apoptosis of condylar cartilage cells. The expression change of miR-101 in control group was compared with that in IL-1 stimulation group by qRT-PCR. Overexpression and down-regulation models of miR-101 were established by transfecting Mimics and Inhibitor and verified by qRT-PCR. Flow cytometry was used to detect the effect of miR-101 overexpression and down-regulation on apoptosis. Target gene of miR-101 was analyzed and calculated through bioinformatics. Western blot and Luciferase report assay were used to detect whether Sox9 could become the target gene of miR-101. Results:qRT-PCR results showed that IL-1 stimulation could cause the increase of miR-101 expression. After the transfection of rabbit condylar cartilage cells by Mimics and Inhibitor, qRT-PCR results confirmed the significant effect of miR-101 overexpression and down-regulation. It was confirmed by flow cytometry that overexpression of miR-101 could promote the apoptosis of condylar cartilage cells, and down-regulation of miR-101 could reduce the apoptosis. It was confirmed by Western blot and Luciferase report assay that Sox9 was the target gene of miR-101, and miR-101 inhibited SOX9 expression through complementary pairing with 3’UTR of Sox9 mRNA. Conclusions:miR-101 can promote the apoptosis of condylar cartilage cells through inhibiting the protein level of target gene SOX9.

  6. Development of Biomarkers for Chronic Beryllium Disease in Mice

    Energy Technology Data Exchange (ETDEWEB)

    Gordon, Terry

    2013-01-25

    Beryllium is a strategic metal, indispensable for national defense programs in aerospace, telecommunications, electronics, and weaponry. Exposure to beryllium is an extensively documented occupational hazard that causes irreversible, debilitating granulomatous lung disease in as much as 3 - 5% of exposed workers. Mechanistic research on beryllium exposure-disease relationships has been severely limited by a general lack of a sufficient CBD animal model. We have now developed and tested an animal model which can be used for dissecting dose-response relationships and pathogenic mechanisms and for testing new diagnostic and treatment paradigms. We have created 3 strains of transgenic mice in which the human antigen-presenting moiety, HLA-DP, was inserted into the mouse genome. Each mouse strain contains HLA-DPB1 alleles that confer different magnitude of risk for chronic beryllium disease (CBD): HLA-DPB1*0401 (odds ratio = 0.2), HLA-DPB1*0201 (odds ratio = 15), HLA-DPB1*1701 (odds ratio = 240). Our preliminary work has demonstrated that the *1701 allele, as predicted by human studies, results in the greatest degree of sensitization in a mouse ear swelling test. We have also completed dose-response experiments examining beryllium-induced lung granulomas and identified susceptible and resistant inbred strains of mice (without the human transgenes) as well as quantitative trait loci that may contain gene(s) that modify the immune response to beryllium. In this grant application, we propose to use the transgenic and normal inbred strains of mice to identify biomarkers for the progression of beryllium sensitization and CBD. To achieve this goal, we propose to compare the sensitivity and accuracy of the lymphocyte proliferation test (blood and bronchoalveolar lavage fluid) with the ELISPOT test in the three HLA-DP transgenic mice strains throughout a 6 month treatment with beryllium particles. Because of the availability of high-throughput proteomics, we will also identify

  7. The beryllium production at Ulba metallurgical plant (Ust-Kamenogrsk, Kazakhstan)

    Energy Technology Data Exchange (ETDEWEB)

    Dvinskykh, E.M.; Savchuk, V.V.; Tuzov, Y.V. [Ulba Metallurgical Plant (Zavod), Ust-Kamenogorsk, Abay prospect 102 (Kazakhstan)

    1998-01-01

    The Report includes data on beryllium production of Ulba metallurgical plant, located in Ust-Kamenogorsk (Kazakhstan). Beryllium production is showed to have extended technological opportunities in manufacturing semi-products (beryllium ingots, master alloys, metallic beryllium powders, beryllium oxide) and in production of structural beryllium and its parts. Ulba metallurgical plant owns a unique technology of beryllium vacuum distillation, which allows to produce reactor grades of beryllium with a low content of metallic impurities. At present Ulba plant does not depend on raw materials suppliers. The quantity of stored raw materials and semi-products will allow to provide a 25-years work of beryllium production at a full capacity. The plant has a satisfactory experience in solving ecological problems, which could be useful in ITER program. (author)

  8. Nanostructured Alloys as an Alternative to Copper-Beryllium

    Science.gov (United States)

    2014-11-19

    bushing applications;  2) Nanometal/composite for high specific strength/stiffness components; and  3) Nanometal cobalt / copper enabled...performance of Integran’s Nanovate cobalt -based and nickel- cobalt metals is superior to copper beryllium (peak hardness); Mechanical Property Summary...Nanostructured Cobalt Alloy 285 ksi (1967 MPa) 225 ksi (1550 MPa) 290 ksi (2000 MPa) 18855 ksi (130 GPa) Copper Beryllium (C17200-TH04) 142 ksi

  9. Actinide/beryllium neutron sources with reduced dispersion characteristics

    Science.gov (United States)

    Schulte, Louis D.

    2012-08-14

    Neutron source comprising a composite, said composite comprising crystals comprising BeO and AmBe.sub.13, and an excess of beryllium, wherein the crystals have an average size of less than 2 microns; the size distribution of the crystals is less than 2 microns; and the beryllium is present in a 7-fold to a 75-fold excess by weight of the amount of AmBe.sub.13; and methods of making thereof.

  10. Beryllium contamination and exposure monitoring in an inhalation laboratory setting.

    Science.gov (United States)

    Muller, Caroline; Audusseau, Séverine; Salehi, Fariba; Truchon, Ginette; Chevalier, Gaston; Mazer, Bruce; Kennedy, Greg; Zayed, Joseph

    2010-02-01

    Beryllium (Be) is used in several forms: pure metal, beryllium oxide, and as an alloy with copper, aluminum, or nickel. Beryllium oxide, beryllium metal, and beryllium alloys are the main forms present in the workplace, with inhalation being the primary route of exposure. Cases of workers with sensitization or chronic beryllium disease challenge the scientific community for a better understanding of Be toxicity. Therefore, a toxicological inhalation study using a murine model was performed in our laboratory in order to identify the toxic effects related to different particle sizes and chemical forms of Be. This article attempts to provide information regarding the relative effectiveness of the environmental monitoring and exposure protection program that was enacted to protect staff (students and researchers) in this controlled animal beryllium inhalation exposure experiment. This includes specific attention to particle migration control through intensive housekeeping and systematic airborne and surface monitoring. Results show that the protective measures applied during this research have been effective. The highest airborne Be concentration in the laboratory was less than one-tenth of the Quebec OEL (occupational exposure limit) of 0.15 microg/m(3). Considering the protection factor of 10(3) of the powered air-purifying respirator used in this research, the average exposure level would be 0.03 x 10(- 4) microg/m(3), which is extremely low. Moreover, with the exception of one value, all average Be concentrations on surfaces were below the Quebec Standard guideline level of 3 microg/100 cm(2) for Be contamination. Finally, all beryllium lymphocyte proliferation tests for the staff were not higher than controls.

  11. Potential of PCSK9 as a new target for the management of LDL cholesterol

    Directory of Open Access Journals (Sweden)

    Mombelli G

    2015-07-01

    Full Text Available Guiliana Mombelli, Samuela Castelnuovo, Chiara PavanelloCardiovascular Department, Dyslipidemia Center, Azienda Ospedaliera Niguarda Cà Granda, Milan, ItalyAbstract: A large proportion of patients at high risk for cardiovascular disease continue to suffer from cardiovascular events despite current therapies. The need for additional therapies to lower the residual risk has led to research on new pharmacological approaches. The discovery of proteins regulating the activity of the low-density lipoprotein receptor has been a major breakthrough in the development of new cholesterol-lowering drugs. This review describes inhibition of proprotein convertase subtilisin/kexin type 9 (PCSK9 as a promising treatment for familial hypercholesterolemia, especially the relatively good short-term safety of PCSK9 inhibitors. In particular, we focus on its additive effect with statins and its advantage as a monotherapy in statin-intolerant patients. The additional low-density lipoprotein cholesterol lowering obtained with PCSK9 inhibition will be able to reduce the additional risk, but its effect on cardiovascular events has to be evaluated in future studies.Keywords: proprotein convertase subtilisin/kexin type 9, PCSK9, additional or replacement therapy to statins, statin intolerance, residual cardiovascular risk

  12. Inelastic Collisions of Positrons with Beryllium and Magnesium Ions

    Science.gov (United States)

    El-Bakry, Salah-Yaseen

    The collision of positrons with beryllium and magnesium positive ions is treated for the first time as a three-channel problem with the assumption that the elastic, ground-positronium and excited-positronium formation channels are open. A one-valence-electron model for the targets, based on the Clementi-Roetti Slater basis functions, as well as an improved coupled-static approach allowing for the polarization of the excited positronium, are used for calculating the partial cross-sections of eight partial waves (corresponding to 0≤ℓ≤7, where ℓ is the total angular momentum of the scattering problem considered). The calculations are carried out, in each case, at 19 values of the incident energy lying above the excited positronium formation threshold (i.e. above 16.42 eV in e+-Be+ scattering and above 13.02 eV in e+-Mg+ scattering). The total elastic cross-sections of e+-Mg+ scattering show a peak around the ionization threshold of Mg+ (at 14.723 eV) but for e+-Be+ scattering, display a peak at 90 eV (remember that the ionization threshold of Be+ is 18.2 eV). Although the resulting total collisional positronium formation cross-sections are smaller than the elastic ones, their relatively large values should draw the attention of experimental and theoretical physicists to the field of positron-ion collisions.

  13. Impurities effect on the swelling of neutron irradiated beryllium

    Energy Technology Data Exchange (ETDEWEB)

    Donne, M.D.; Scaffidi-Argentina, F. [Institut fuer Neutronenphysik und Reaktortechnik, Karlsruhe (Germany)

    1995-09-01

    An important factor controlling the swelling behaviour of fast neutron irradiated beryllium is the impurity content which can strongly affect both the surface tension and the creep strength of this material. Being the volume swelling of the old beryllium (early sixties) systematically higher than that of the more modem one (end of the seventies), a sensitivity analysis with the aid of the computer code ANFIBE (ANalysis of Fusion Irradiated BEryllium) to investigate the effect of these material properties on the swelling behaviour of neutron irradiated beryllium has been performed. Two sets of experimental data have been selected: the first one named Western refers to quite recently produced Western beryllium, whilst the second one, named Russian refers to relatively old (early sixties) Russian beryllium containing a higher impurity rate than the Western one. The results obtained with the ANFIBE Code were assessed by comparison with experimental data and the used material properties were compared with the data available in the literature. Good agreement between calculated and measured values has been found.

  14. Genomic Copy Number Dictates a Gene-Independent Cell Response to CRISPR/Cas9 Targeting | Office of Cancer Genomics

    Science.gov (United States)

    The CRISPR/Cas9 system enables genome editing and somatic cell genetic screens in mammalian cells. We performed genome-scale loss-of-function screens in 33 cancer cell lines to identify genes essential for proliferation/survival and found a strong correlation between increased gene copy number and decreased cell viability after genome editing. Within regions of copy-number gain, CRISPR/Cas9 targeting of both expressed and unexpressed genes, as well as intergenic loci, led to significantly decreased cell proliferation through induction of a G2 cell-cycle arrest.

  15. CRISPR/Cas9 Targets Chicken Embryonic Somatic Cells In Vitro and In Vivo and generates Phenotypic Abnormalities

    OpenAIRE

    Kwaku Dad Abu-Bonsrah; Dongcheng Zhang; Newgreen, Donald F

    2016-01-01

    Chickens are an invaluable model for studying human diseases, physiology and especially development, but have lagged in genetic applications. With the advent of Programmable Engineered Nucleases, genetic manipulation has become efficient, specific and rapid. Here, we show that the CRISPR/Cas9 system can precisely edit the chicken genome. We generated HIRA, TYRP1, DICER, MBD3, EZH2, and 6 other gene knockouts in two chicken cell lines using the CRISPR/Cas9 system, with no off-target effects de...

  16. Generation of CRISPR/Cas9-mediated lactoferrin-targeted mice by pronuclear injection of plasmid pX330

    Directory of Open Access Journals (Sweden)

    Mengxu GE,Fei LIU,Fei CHANG,Zhaolin SUN,Jing FEI,Ying GUO,Yunping DAI,Zhengquan YU,Yaofeng ZHAO,Ning LI,Qingyong MENG

    2015-09-01

    Full Text Available Lactoferrin is a member of the transferrin family of multifunctional iron binding glycoproteins. While numerous physiological functions have been described for lactoferrin, the mechanisms underlying these functions are not clear. To further study the functions and mechanisms of lactoferrin, we modified the lactoferrin promoter of mice using the CRISPR/Cas9 system to reduce or eliminate lactoferrin expression. Seven mice with lactoferrin promoter mutations were obtained with an efficiency of 24% (7/29 by injecting the plasmid pX330, expressing a small guide RNA and human codon-optimized SpCas9, into fertilized eggs of mice. Plasmid integration and off-targeting of pX330 were not detected. These results confirmed that pronuclear injection of a circular plasmid is a feasible and efficient method for targeted mutagenesis in mice.

  17. Toxic PR Poly-Dipeptides Encoded by the C9orf72 Repeat Expansion Target LC Domain Polymers.

    Science.gov (United States)

    Lin, Yi; Mori, Eiichiro; Kato, Masato; Xiang, Siheng; Wu, Leeju; Kwon, Ilmin; McKnight, Steven L

    2016-10-20

    Two complementary approaches were used in search of the intracellular targets of the toxic PR poly-dipeptide encoded by the repeat sequences expanded in the C9orf72 form of amyotrophic lateral sclerosis. The top categories of PRn-bound proteins include constituents of non-membrane invested cellular organelles and intermediate filaments. PRn targets are enriched for the inclusion of low complexity (LC) sequences. Evidence is presented indicating that LC sequences represent the direct target of PRn binding and that interaction between the PRn poly-dipeptide and LC domains is polymer-dependent. These studies indicate that PRn-mediated toxicity may result from broad impediments to the dynamics of cell structure and information flow from gene to message to protein.

  18. Toxic PR poly-dipeptides encoded by the C9orf72 repeat expansion target LC domain polymers

    Science.gov (United States)

    Lin, Yi; Mori, Eiichiro; Kato, Masato; Xiang, Siheng; Wu, Leeju; Kwon, Ilmin; McKnight, Steven L.

    2016-01-01

    Summary Two complementary approaches were used in search of the intracellular targets of the toxic PR poly-dipeptide encoded by the repeat sequences expanded in the C9orf72 form of amyotrophic lateral sclerosis. The top categories of PRn-bound proteins include constituents of non-membrane invested cellular organelles and intermediate filaments. PRn targets are enriched for the inclusion of low complexity (LC) sequences. Evidence is presented indicating that LC sequences represent the direct target of PRn binding, and that interaction between the PRn poly-dipeptide and LC domains is polymer-dependent. These studies indicate that PRn-mediated toxicity may result from broad impediments to the dynamics of cell structure and information flow from gene to message to protein. PMID:27768897

  19. Pion yield from 450 GeV/c protons on beryllium

    CERN Document Server

    Ambrosini, G; Bernier, K; Biino, C; Bonesini, M; Bonivento, W; Borer, K; Brooijmans, G; Catanesi, M G; Collazuol, G; Daniels, D C; Dittus, F B; Elsener, K; Godley, A; Grant, A; Grégoire, G; Guglielmi, A M; Kabana, S; Klingenberg, R; Lehmann, G; Lindén, T; Linssen, Lucie; Marchionni, A; Mishra, S R; Moffitt, L; Moser, U; Palladino, Vittorio; Pietropaolo, F; Pretzl, Klaus P; Pullia, Antonio; Radicioni, E; Ragazzi, S; Schacher, J; Sergiampietri, F; Soler, F J P; Stoffel, F; Tabarelli de Fatis, T; Terranova, F; Tovey, Stuart N; Tsesmelis, E; Weber, M

    1998-01-01

    This paper reports on the charged pion production yields measured by the SPY/NA56 experiment for 450 GeV/c proton interactions on beryllium targets. The present data cover a secondary momentum range from 7 GeV/c to 135 GeV/c in the forward direction. An experimental accuracy ranging from 5 to 10\\%, depending on the beam momentum, has been achieved, limited mainly by the knowledge of the beam acceptance. These results will be relevant in the calculation of neutrino fluxes in present and future neutrino beams.

  20. K/π production ratios from 450 GeV/c protons on beryllium

    Science.gov (United States)

    Spy Collaboration; Ambrosini, G.; Arsenescu, R.; Bernier, K.; Biino, C.; Bonesini, M.; Bonivento, W.; Borer, K.; Brooijmans, G.; Catanesi, M. G.; Collazuol, G.; Daniels, D.; Dittus, F.; Elsener, K.; Godley, A.; Grant, A.; Gregoire, G.; Guglielmi, A.; Kabana, S.; Klingenberg, R.; Lehmann, G.; Lindén, T.; Linssen, L.; Marchionni, A.; Mishra, S. R.; Moffitt, L.; Moser, U.; Palladino, V.; Pietropaolo, F.; Pretzl, K.; Pullia, A.; Radicioni, E.; Ragazzi, S.; Schacher, J.; Sergiampietri, F.; Soler, F. J. P.; Stoffel, F.; Tabarelli de Fatis, T.; Terranova, F.; Tovey, S. N.; Tsesmelis, E.; Weber, M.

    1998-02-01

    This paper reports on the charged K/π production ratios and on the shape of the pT distributions of π fluxes measured by the SPY/NA56 experiment for 450 GeV/c proton interactions on beryllium targets. The present data cover a secondary momentum range from 7 GeV/c to 135 GeV/c in the forward direction and with pT values up to 600 MeV/c. An experimental accuracy of about 3% has been achieved. These results will reduce the uncertainty on the estimation of the νe component of neutrino beams.

  1. Pion yield from 450 GeV/c protons on beryllium

    Science.gov (United States)

    Spy Collaboration; Ambrosini, G.; Arsenescu, R.; Bernier, K.; Biino, C.; Bonesini, M.; Bonivento, W.; Borer, K.; Brooijmans, G.; Catanesi, M. G.; Collazuol, G.; Daniels, D.; Dittus, F.; Elsener, K.; Godley, A.; Grant, A.; Gregoire, G.; Guglielmi, A.; Kabana, S.; Klingenberg, R.; Lehmann, G.; Lindén, T.; Linssen, L.; Marchionni, A.; Mishra, S. R.; Moffitt, L.; Moser, U.; Palladino, V.; Pietropaolo, F.; Pretzl, K.; Pullia, A.; Radicioni, E.; Ragazzi, S.; Schacher, J.; Sergiampietri, F.; Soler, F. J. P.; Stoffel, F.; Tabarelli de Fatis, T.; Terranova, F.; Tovey, S. N.; Tsesmelis, E.; Weber, M.

    1998-04-01

    This paper reports on the charged pion production yields measured by the SPY/NA56 experiment for 450 GeV/c proton interactions on beryllium targets. The present data cover a secondary momentum range from 7 GeV/c to 135 GeV/c in the forward direction. An experimental accuracy ranging from 5 to 10%, depending on the beam momentum, has been achieved, limited mainly by the knowledge of the beam acceptance. These results will be relevant in the calculation of neutrino fluxes in present and future neutrino beams.

  2. Accelerating genome editing in CHO cells using CRISPR Cas9 and CRISPy, a web-based target finding tool.

    Science.gov (United States)

    Ronda, Carlotta; Pedersen, Lasse Ebdrup; Hansen, Henning Gram; Kallehauge, Thomas Beuchert; Betenbaugh, Michael J; Nielsen, Alex Toftgaard; Kildegaard, Helene Faustrup

    2014-08-01

    Chinese hamster ovary (CHO) cells are widely used in the biopharmaceutical industry as a host for the production of complex pharmaceutical proteins. Thus genome engineering of CHO cells for improved product quality and yield is of great interest. Here, we demonstrate for the first time the efficacy of the CRISPR Cas9 technology in CHO cells by generating site-specific gene disruptions in COSMC and FUT8, both of which encode proteins involved in glycosylation. The tested single guide RNAs (sgRNAs) created an indel frequency up to 47.3% in COSMC, while an indel frequency up to 99.7% in FUT8 was achieved by applying lectin selection. All eight sgRNAs examined in this study resulted in relatively high indel frequencies, demonstrating that the Cas9 system is a robust and efficient genome-editing methodology in CHO cells. Deep sequencing revealed that 85% of the indels created by Cas9 resulted in frameshift mutations at the target sites, with a strong preference for single base indels. Finally, we have developed a user-friendly bioinformatics tool, named "CRISPy" for rapid identification of sgRNA target sequences in the CHO-K1 genome. The CRISPy tool identified 1,970,449 CRISPR targets divided into 27,553 genes and lists the number of off-target sites in the genome. In conclusion, the proven functionality of Cas9 to edit CHO genomes combined with our CRISPy database have the potential to accelerate genome editing and synthetic biology efforts in CHO cells.

  3. Targeting of miR9/NOTCH1 interaction reduces metastatic behavior in triple-negative breast cancer.

    Science.gov (United States)

    Mohammadi-Yeganeh, Samira; Mansouri, Ardalan; Paryan, Mahdi

    2015-11-01

    Many reports have indicated deregulation of a variety of microRNAs (miRNAs) in human cancers. In this study, we appraised miR-9 correlation with NOTCH1 involved in Notch signaling in metastatic breast cancer. The Notch signaling pathway has been approved to be associated with the development and progression of many human cancers, including breast cancer, but the precise mechanism has remained unknown. To the best of our knowledge, this is the first study that introduces miR-9 and NOTCH1 correlation as an effective factor in breast cancer. We found that miR-9 expression was decreased in MDA-MB-231 breast cancer cells compared with MCF-10A normal breast cell line. However, NOTCH1 was upregulated in the metastatic breast cancer cells. Furthermore, luciferase assay revealed a significant inverse correlation between miR-9 and NOTCH1. Overexpression of Notch signaling via Notch1 intracellular domain in MDA-MB-231 cell line was suppressed by lentiviruses expressing miR-9. Taken together, the results obtained by MTT, flow cytometry, migration, and wound healing assays showed that it is possible to inhibit metastasis and induce pro-apoptotic state by induction of miR-9 expression in MDA-MB-231 cells but with no effect on cell proliferation. These results shows that miR-9, by direct targeting of NOTCH1, can reveal a suppressor-like activity in metastatic breast cancer cells.

  4. Simple and efficient CRISPR/Cas9-mediated targeted mutagenesis in Xenopus tropicalis.

    Science.gov (United States)

    Nakayama, Takuya; Fish, Margaret B; Fisher, Marilyn; Oomen-Hajagos, Jamina; Thomsen, Gerald H; Grainger, Robert M

    2013-12-01

    We have assessed the efficacy of the recently developed CRISPR/Cas (clustered regularly interspaced short palindromic repeats/CRISPR-associated) system for genome modification in the amphibian Xenopus tropicalis. As a model experiment, targeted mutations of the tyrosinase gene were verified, showing the expected albinism phenotype in injected embryos. We further tested this technology by interrupting the six3 gene, which is required for proper eye and brain formation. Expected eye and brain phenotypes were observed when inducing mutations in the six3 coding regions, as well as when deleting the gene promoter by dual targeting. We describe here a standardized protocol for genome editing using this system. This simple and fast method to edit the genome provides a powerful new reverse genetics tool for Xenopus researchers.

  5. Differential Killing of Salmonella enterica Serovar Typhi by Antibodies Targeting Vi and Lipopolysaccharide O:9 Antigen.

    Directory of Open Access Journals (Sweden)

    Peter J Hart

    Full Text Available Salmonella enterica serovar Typhi expresses a capsule of Vi polysaccharide, while most Salmonella serovars, including S. Enteritidis and S. Typhimurium, do not. Both S. Typhi and S. Enteritidis express the lipopolysaccharide O:9 antigen, yet there is little evidence of cross-protection from anti-O:9 antibodies. Vaccines based on Vi polysaccharide have efficacy against typhoid fever, indicating that antibodies against Vi confer protection. Here we investigate the role of Vi capsule and antibodies against Vi and O:9 in antibody-dependent complement- and phagocyte-mediated killing of Salmonella. Using isogenic Vi-expressing and non-Vi-expressing derivatives of S. Typhi and S. Typhimurium, we show that S. Typhi is inherently more sensitive to serum and blood than S. Typhimurium. Vi expression confers increased resistance to both complement- and phagocyte-mediated modalities of antibody-dependent killing in human blood. The Vi capsule is associated with reduced C3 and C5b-9 deposition, and decreased overall antibody binding to S. Typhi. However, purified human anti-Vi antibodies in the presence of complement are able to kill Vi-expressing Salmonella, while killing by anti-O:9 antibodies is inversely related to Vi expression. Human serum depleted of antibodies to antigens other than Vi retains the ability to kill Vi-expressing bacteria. Our findings support a protective role for Vi capsule in preventing complement and phagocyte killing of Salmonella that can be overcome by specific anti-Vi antibodies, but only to a limited extent by anti-O:9 antibodies.

  6. Differential Killing of Salmonella enterica Serovar Typhi by Antibodies Targeting Vi and Lipopolysaccharide O:9 Antigen.

    Science.gov (United States)

    Hart, Peter J; O'Shaughnessy, Colette M; Siggins, Matthew K; Bobat, Saeeda; Kingsley, Robert A; Goulding, David A; Crump, John A; Reyburn, Hugh; Micoli, Francesca; Dougan, Gordon; Cunningham, Adam F; MacLennan, Calman A

    2016-01-01

    Salmonella enterica serovar Typhi expresses a capsule of Vi polysaccharide, while most Salmonella serovars, including S. Enteritidis and S. Typhimurium, do not. Both S. Typhi and S. Enteritidis express the lipopolysaccharide O:9 antigen, yet there is little evidence of cross-protection from anti-O:9 antibodies. Vaccines based on Vi polysaccharide have efficacy against typhoid fever, indicating that antibodies against Vi confer protection. Here we investigate the role of Vi capsule and antibodies against Vi and O:9 in antibody-dependent complement- and phagocyte-mediated killing of Salmonella. Using isogenic Vi-expressing and non-Vi-expressing derivatives of S. Typhi and S. Typhimurium, we show that S. Typhi is inherently more sensitive to serum and blood than S. Typhimurium. Vi expression confers increased resistance to both complement- and phagocyte-mediated modalities of antibody-dependent killing in human blood. The Vi capsule is associated with reduced C3 and C5b-9 deposition, and decreased overall antibody binding to S. Typhi. However, purified human anti-Vi antibodies in the presence of complement are able to kill Vi-expressing Salmonella, while killing by anti-O:9 antibodies is inversely related to Vi expression. Human serum depleted of antibodies to antigens other than Vi retains the ability to kill Vi-expressing bacteria. Our findings support a protective role for Vi capsule in preventing complement and phagocyte killing of Salmonella that can be overcome by specific anti-Vi antibodies, but only to a limited extent by anti-O:9 antibodies.

  7. Computational Predictions of the Beryllium Analogue of Borole, Cp(+), and the Fluorenyl Cation: Highly Stabilized, non-Lewis Acidic Antiaromatic Ring Systems.

    Science.gov (United States)

    Field-Theodore, Terri E; Wilson, David J D; Dutton, Jason L

    2015-08-17

    A computational study of a set of synthetically unknown beryllium-containing rings, anionic analogues of antiaromatic boroles, has been carried out to investigate their structure, stability, and potential reactivity. The results indicate that these compounds should be electronically viable (as assessed from HOMO-LUMO and singlet-triplet gaps) and therefore potential targets for synthesis. In strong contrast with boroles, these beryllium species are predicted to be not Lewis acidic but rather Lewis basic, with reactivity centered on the endocyclic Be-C bond.

  8. The SPS Target Station for CHORUS and NOMAD Neutrino Experiments

    CERN Document Server

    Péraire, S; Zazula, J M

    1996-01-01

    A new SPS target station, T9, has been constructed for the CHORUS and NOMAD neutrino experiments at CERN. The heart of the station is the target box : 11 beryllium rods are aligned in a cast aluminium box ; they are cooled by a closed circuit helium gas with adjusted flow to each rod. The box is motorised horizontally and vertically at both ends, to remotely optimise the secondary particle production by aligning the target with the incident proton beam. Radiation protection around the station is guaranteed by more than 100 tons of shielding material (iron, copper, marble). This presentation describes briefly the various components of the target station ; it emphasises particularly the thermal and mechanical calculations which define a safe maximum beam intensity on the beryllium rods. Over the first two years of successful operation, the station has received more than 2€1019 protons at 450 GeV/c, with intensity peaks of 2.8€1013 protons per machine cycle.

  9. K4, K9 and K18 in human histone H3 are targets for biotinylation by biotinidase.

    Science.gov (United States)

    Kobza, Keyna; Camporeale, Gabriela; Rueckert, Brian; Kueh, Alice; Griffin, Jacob B; Sarath, Gautam; Zempleni, Janos

    2005-08-01

    Histones are modified post-translationally, e.g. by methylation of lysine and arginine residues, and by phosphorylation of serine residues. These modifications regulate processes such as gene expression, DNA repair, and mitosis and meiosis. Recently, evidence has been provided that histones are also modified by covalent binding of the vitamin biotin. The aims of this study were to identify biotinylation sites in histone H3, and to investigate the crosstalk among histone biotinylation, methylation and phosphorylation. Synthetic peptides based on the sequence of human histone H3 were used as substrates for enzymatic biotinylation by biotinidase; biotin in peptides was probed using streptavidin peroxidase. These studies provided evidence that K4, K9 and K18 in histone H3 are good targets for biotinylation; K14 and K23 are relatively poor targets. Antibodies were generated to histone H3, biotinylated either at K4, K9 or K18. These antibodies localized to nuclei in human placental cells in immunocytochemistry and immunoblotting experiments, suggesting that lysines in histone H3 are biotinylated in vivo. Dimethylation of R2, R8 and R17 increased biotinylation of K4, K9 and K18, respectively, by biotinidase; phosphorylation of S10 abolished biotinylation of K9. These observations are consistent with crosstalk between biotinylation of histones and other known modifications of histones. We speculate that this crosstalk provides a link to known roles for biotin in gene expression and cell proliferation.

  10. Production of projectile and target K-vacancy in near-symmetric collisions of 60-100 MeV Cu9+ ions with thin Zn target

    Science.gov (United States)

    Yipan, Guo; Zhihu, Yang; Shubin, Du; Hongwei, Chang; Qingliang, Xia; Qiumei, Xu

    2016-03-01

    We report studies on both target and projectile K-shell ionization by collisions of Cu9+ ions on the thin Zn target in the energy range of 60-100 MeV. In this work, the relative ratio for the production of the target to projectile K-vacancy is measured. The result shows that it almost remains stable over this energy range and has good consistency with the predictions by vacancy transfer via the 2pσ-1sσ rotational coupling, which gives experimental evidence for K-vacancy sharing between two partners. Furthermore, the discussion for comparisons between the experimental ionization cross sections and the possible theoretical estimations is presented. These comparisons suggest that the experimental data agree well with those predicted by the Binary-Encounter approximation (BEA) model but are not in good agreement with the modified BEA calculations. It allows us to infer that the direct ionization (and/or excitation) is of importance to initial K-vacancy production before 2pσ-1sσ transitions in the present collision condition. Project supported by the Joint Funds of the National Natural Science Foundation of China (Grant No. U1332122).

  11. Targeting of Ly9 (CD229) Disrupts Marginal Zone and B1 B Cell Homeostasis and Antibody Responses.

    Science.gov (United States)

    Cuenca, Marta; Romero, Xavier; Sintes, Jordi; Terhorst, Cox; Engel, Pablo

    2016-01-15

    Marginal zone (MZ) and B1 B cells have the capacity to respond to foreign Ags more rapidly than conventional B cells, providing early immune responses to blood-borne pathogens. Ly9 (CD229, SLAMF3), a member of the signaling lymphocytic activation molecule family receptors, has been implicated in the development and function of innate T lymphocytes. In this article, we provide evidence that in Ly9-deficient mice splenic transitional 1, MZ, and B1a B cells are markedly expanded, whereas development of B lymphocytes in bone marrow is unaltered. Consistent with an increased number of these B cell subsets, we detected elevated levels of IgG3 natural Abs and a striking increase of T-independent type II Abs after immunization with 2,4,6-trinitrophenyl-Ficoll in the serum of Ly9-deficient mice. The notion that Ly9 could be a negative regulator of innate-like B cell responses was supported by the observation that administering an mAb directed against Ly9 to wild-type mice selectively eliminated splenic MZ B cells and significantly reduced the numbers of B1 and transitional 1 B cells. In addition, Ly9 mAb dramatically diminished in vivo humoral responses and caused a selective downregulation of the CD19/CD21/CD81 complex on B cells and concomitantly an impaired B cell survival and activation in an Fc-independent manner. We conclude that altered signaling caused by the absence of Ly9 or induced by anti-Ly9 may negatively regulate development and function of innate-like B cells by modulating B cell activation thresholds. The results suggest that Ly9 could serve as a novel target for the treatment of B cell-related diseases.

  12. SU-E-T-602: Beryllium Seeds Implant for Photo-Neutron Yield Using External Beam Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Koren, S [St. Lukes Roosevelt Hospital, NY, NY (United States); Veltchev, I [Fox Chase Cancer Center, Philadelphia, PA (United States); Furhang, E [Beth Israel Medical Center, Staten Island, NY (Israel)

    2014-06-01

    Purpose: To evaluate the Neutron yield obtained during prostate external beam irradiation. Methods: Neutrons, that are commonly a radiation safety concern for photon beams with energy above 10 MV, are induced inside a PTV from Beryllium implemented seeds. A high megavoltage photon beam delivered to a prostate will yield neutrons via the reaction Be-9(γ,n)2?. Beryllium was chosen for its low gamma,n reaction cross-section threshold (1.67 MeV) to be combined with a high feasible 25 MV photon beam. This beam spectra has a most probable photon energy of 2.5 to 3.0 MeV and an average photon energy of about 5.8 MeV. For this feasibility study we simulated a Beryllium-made common seed dimension (0.1 cm diameter and 0.5 cm height) without taking into account encapsulation. We created a 0.5 cm grid loading pattern excluding the Urethra, using Variseed (Varian inc.) A total of 156 seeds were exported to a 4cm diameter prostate sphere, created in Fluka, a particle transport Monte Carlo Code. Two opposed 25 MV beams were simulated. The evaluation of the neutron dose was done by adjusting the simulated photon dose to a common prostate delivery (e.g. 7560 cGy in 42 fractions) and finding the corresponding neutron dose yield from the simulation. A variance reduction technique was conducted for the neutrons yield and transported. Results: An effective dose of 3.65 cGy due to neutrons was found in the prostate volume. The dose to central areas of the prostate was found to be about 10 cGy. Conclusion: The neutron dose yielded does not justify a clinical implant of Beryllium seeds. Nevertheless, one should investigate the Neutron dose obtained when a larger Beryllium loading is combined with commercially available 40 MeV Linacs.

  13. ABCC9/SUR2 in the brain: Implications for hippocampal sclerosis of aging and a potential therapeutic target.

    Science.gov (United States)

    Nelson, Peter T; Jicha, Gregory A; Wang, Wang-Xia; Ighodaro, Eseosa; Artiushin, Sergey; Nichols, Colin G; Fardo, David W

    2015-11-01

    The ABCC9 gene and its polypeptide product, SUR2, are increasingly implicated in human neurologic disease, including prevalent diseases of the aged brain. SUR2 proteins are a component of the ATP-sensitive potassium ("KATP") channel, a metabolic sensor for stress and/or hypoxia that has been shown to change in aging. The KATP channel also helps regulate the neurovascular unit. Most brain cell types express SUR2, including neurons, astrocytes, oligodendrocytes, microglia, vascular smooth muscle, pericytes, and endothelial cells. Thus it is not surprising that ABCC9 gene variants are associated with risk for human brain diseases. For example, Cantu syndrome is a result of ABCC9 mutations; we discuss neurologic manifestations of this genetic syndrome. More common brain disorders linked to ABCC9 gene variants include hippocampal sclerosis of aging (HS-Aging), sleep disorders, and depression. HS-Aging is a prevalent neurological disease with pathologic features of both neurodegenerative (aberrant TDP-43) and cerebrovascular (arteriolosclerosis) disease. As to potential therapeutic intervention, the human pharmacopeia features both SUR2 agonists and antagonists, so ABCC9/SUR2 may provide a "druggable target", relevant perhaps to both HS-Aging and Alzheimer's disease. We conclude that more work is required to better understand the roles of ABCC9/SUR2 in the human brain during health and disease conditions.

  14. Striking Plasticity of CRISPR-Cas9 and Key Role of Non-target DNA, as Revealed by Molecular Simulations

    Science.gov (United States)

    2016-01-01

    The CRISPR (clustered regularly interspaced short palindromic repeats)-Cas9 system recently emerged as a transformative genome-editing technology that is innovating basic bioscience and applied medicine and biotechnology. The endonuclease Cas9 associates with a guide RNA to match and cleave complementary sequences in double stranded DNA, forming an RNA:DNA hybrid and a displaced non-target DNA strand. Although extensive structural studies are ongoing, the conformational dynamics of Cas9 and its interplay with the nucleic acids during association and DNA cleavage are largely unclear. Here, by employing multi-microsecond time scale molecular dynamics, we reveal the conformational plasticity of Cas9 and identify key determinants that allow its large-scale conformational changes during nucleic acid binding and processing. We show how the “closure” of the protein, which accompanies nucleic acid binding, fundamentally relies on highly coupled and specific motions of the protein domains, collectively initiating the prominent conformational changes needed for nucleic acid association. We further reveal a key role of the non-target DNA during the process of activation of the nuclease HNH domain, showing how the nontarget DNA positioning triggers local conformational changes that favor the formation of a catalytically competent Cas9. Finally, a remarkable conformational plasticity is identified as an intrinsic property of the HNH domain, constituting a necessary element that allows for the HNH repositioning. These novel findings constitute a reference for future experimental studies aimed at a full characterization of the dynamic features of the CRISPR-Cas9 system, and—more importantly—call for novel structure engineering efforts that are of fundamental importance for the rational design of new genome-engineering applications. PMID:27800559

  15. Competition between dihydrogen bond and beryllium bond in complexes between HBeH and HArF: a huge blue shift of distant H-Ar stretch.

    Science.gov (United States)

    Li, Qingzhong; Liu, Xiaofeng; Li, Ran; Cheng, Jianbo; Li, Wenzuo

    2012-05-01

    A novel interaction mechanism between HArF and BeH(2) has been validated and characterized with quantum chemical calculations at the MP2/aug-cc-pVQZ level. They can interact through beryllium bonding formed between the positively charged Be atom in BeH(2) and the negatively charged F atom in HArF, besides through dihydrogen bonding. The former (61.3 kcal/mol) is much stronger than the latter (5.9 kcal/mol). The red shift is found for the associated H-Ar stretch in the dihydrogen bonding, whereas the big blue shift is observed for the distant H-Ar stretch in the beryllium bonding. The blue shift of the distant H-Ar stretch is affected greatly by computational methods. It is calculated to be 712 cm(-1) at the CCSD(T)/6-311++G(3df,2p) level, which appears to be the largest blue shift validated for any weakly bound complex yet. The substitution effect on the beryllium bond is similar to that on hydrogen bonds. The Kr atom makes the beryllium bond weaken and the distant blue shift decrease. The nature and properties of beryllium bond have been analyzed with natural bond orbital (NBO), atoms in molecules (AIM), and energy decomposition.

  16. Analysis of HLA-DP association with beryllium disease susceptibility in pooled exposed populations

    Energy Technology Data Exchange (ETDEWEB)

    Cesare Saltini, Massimo Amicosante

    2009-12-19

    in each immunogenetic study. In this context, the populations of the study already performed in this field by the University of Modena and Rome (by Prof. C. Saltini) and the University of Pennsylvania (by Prof. M. Rossman) have been evaluated by using similar HLA molecular typing methodologies and that both populations have now been followed up for a period of 4 to 7 years. The general objective of this study has to generate a larger data base comprising the two population with which analyze gene disease association with greater statistical power and ascertain the effect of lesser common gener variants which may be missed when analyzing associations on small populations. In particular addressing the role suggested in previous study such as: (1) the role of HLA-DP rare alleles and polymorphisms, and (2) the role of the HLA markers in disease progression from sensitization. The two populations from the already published studies (Saltini et al Eur Respir J. 2001 18:677-84; Rossman et al Am J Respir Crit Care Med. 2002 165:788-94) present similar aspects about: ethnicity, type and length of exposure to Be dust, a broadly similar association between beryllium related abnormalities and HLA. The two population have been pooled and evaluated using common criteria of diagnosis (Sensitized subject: at least 2 positive BeLPT tests each with 2 positive wells; CBD-affected subject: identification of well formed non-caseating granulomas on biopsy), follow up and HLA typing technique (complete HLA-DRB, DQB, DPB high resolution typing using amplification with sequence specific primers or sequence based typing). The two populations included 137 subjects with Beryllium hypersensitized (BH) and 155 Be-exposed controls. Inclusion criteria were met by one hundred and six subjects with Be-hypersensitivity of whom 55 were affected by CBD (age 52 {+-} 11 years; 50 caucasians, 2 African-Americans 2 Hispanics and 1 Asian; 46 males and 9 females; mean duration of Be-exposure 15 {+-} 9 years

  17. Spectrophotometric determination of micro amounts of beryllium in waste water with chromeazurol S (CAS) and cetylpyridinium chloride (CPC) after separation by dynamic adsorption on activated carbon

    Energy Technology Data Exchange (ETDEWEB)

    Qiu Xingchu; Chen Jun (Environmental Science Research Inst. of Ganzhou Prefecture, Jiangxi (China)); Zhu Yingquan

    1992-01-01

    A spectrophotometric method for the determination of microamounts of beryllium in waste water has been developed using CAS and CPC. The interference of foreign ions can be eliminated by separation with dynamic adsorption on activated carbon. Beer's law is obeyed for 0 to 0.7 {mu}g of Be in 25 ml of solution. The apparent molar absorptivity is 7.9x10{sup 4} l mol{sup -1} cm {sup -1} at 605 nm. The method has been used to determine beryllium in several industrial waste waters. (orig.).

  18. Beryllium processing technology review for applications in plasma-facing components

    Energy Technology Data Exchange (ETDEWEB)

    Castro, R.G.; Jacobson, L.A.; Stanek, P.W.

    1993-07-01

    Materials research and development activities for the International Thermonuclear Experimental Reactor (ITER), i.e., the next generation fusion reactor, are investigating beryllium as the first-wall containment material for the reactor. Important in the selection of beryllium is the ability to process, fabricate and repair beryllium first-wall components using existing technologies. Two issues that will need to be addressed during the engineering design activity will be the bonding of beryllium tiles in high-heat-flux areas of the reactor, and the in situ repair of damaged beryllium tiles. The following review summarizes the current technology associated with welding and joining of beryllium to itself and other materials, and the state-of-the-art in plasma-spray technology as an in situ repair technique for damaged beryllium tiles. In addition, a review of the current status of beryllium technology in the former Soviet Union is also included.

  19. The structure, properties and performance of plasma-sprayed beryllium for fusion applications

    Energy Technology Data Exchange (ETDEWEB)

    Castro, R.G.; Stanek, P.W.; Elliott, K.E. [and others

    1995-09-01

    Plasma-spray technology is under investigation as a method for producing high thermal conductivity beryllium coatings for use in magnetic fusion applications. Recent investigations have focused on optimizing the plasma-spray process for depositing beryllium coatings on damaged beryllium surfaces. Of particular interest has been optimizing the processing parameters to maximize the through-thickness thermal conductivity of the beryllium coatings. Experimental results will be reported on the use of secondary H{sub 2} gas additions to improve the melting of the beryllium powder and transferred-arc cleaning to improve the bonding between the beryllium coatings and the underlying surface. Information will also be presented on thermal fatigue tests which were done on beryllium coated ISX-B beryllium limiter tiles using 10 sec cycle times with 60 sec cooldowns and an International Thermonuclear Experimental Reactor (ITER) relevant divertor heat flux slightly in excess of 5 MW/m{sup 2}.

  20. Controlling Beryllium Contaminated Material And Equipment For The Building 9201-5 Legacy Material Disposition Project

    Energy Technology Data Exchange (ETDEWEB)

    Reynolds, T. D.; Easterling, S. D.

    2010-10-01

    This position paper addresses the management of beryllium contamination on legacy waste. The goal of the beryllium management program is to protect human health and the environment by preventing the release of beryllium through controlling surface contamination. Studies have shown by controlling beryllium surface contamination, potential airborne contamination is reduced or eliminated. Although there are areas in Building 9201-5 that are contaminated with radioactive materials and mercury, only beryllium contamination is addressed in this management plan. The overall goal of this initiative is the compliant packaging and disposal of beryllium waste from the 9201-5 Legacy Material Removal (LMR) Project to ensure that beryllium surface contamination and any potential airborne release of beryllium is controlled to levels as low as practicable in accordance with 10 CFR 850.25.

  1. 40 CFR 468.20 - Applicability; description of the beryllium copper forming subcategory.

    Science.gov (United States)

    2010-07-01

    ... of pollutants into publicly owned treatment works from the forming of beryllium copper alloys. ... beryllium copper forming subcategory. 468.20 Section 468.20 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS COPPER FORMING POINT SOURCE...

  2. Validation of cleaning method for various parts fabricated at a Beryllium facility

    Energy Technology Data Exchange (ETDEWEB)

    Davis, Cynthia M. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2015-12-15

    This study evaluated and documented a cleaning process that is used to clean parts that are fabricated at a beryllium facility at Los Alamos National Laboratory. The purpose of evaluating this cleaning process was to validate and approve it for future use to assure beryllium surface levels are below the Department of Energy’s release limits without the need to sample all parts leaving the facility. Inhaling or coming in contact with beryllium can cause an immune response that can result in an individual becoming sensitized to beryllium, which can then lead to a disease of the lungs called chronic beryllium disease, and possibly lung cancer. Thirty aluminum and thirty stainless steel parts were fabricated on a lathe in the beryllium facility, as well as thirty-two beryllium parts, for the purpose of testing a parts cleaning method that involved the use of ultrasonic cleaners. A cleaning method was created, documented, validated, and approved, to reduce beryllium contamination.

  3. Steam-chemical reactivity for irradiated beryllium

    Energy Technology Data Exchange (ETDEWEB)

    Anderl, R.A.; McCarthy, K.A.; Oates, M.A.; Petti, D.A.; Pawelko, R.J.; Smolik, G.R. [Idaho National Engineering and Environmental Lab., Idaho Falls, ID (United States)

    1998-01-01

    This paper reports the results of an experimental investigation to determine the influence of neutron irradiation effects and annealing on the chemical reactivity of beryllium exposed to steam. The work entailed measurements of the H{sub 2} generation rates for unirradiated and irradiated Be and for irradiated Be that had been previously annealed at different temperatures ranging from 450degC to 1200degC. H{sub 2} generation rates were similar for irradiated and unirradiated Be in steam-chemical reactivity experiments at temperatures between 450degC and 600degC. For irradiated Be exposed to steam at 700degC, the chemical reactivity accelerated rapidly and the specimen experienced a temperature excursion. Enhanced chemical reactivity at temperatures between 400degC and 600degC was observed for irradiated Be annealed at temperatures of 700degC and higher. This reactivity enhancement could be accounted for by the increased specific surface area resulting from development of a surface-connected porosity in the irradiated-annealed Be. (author)

  4. Beryllium abundances in stars hosting giant planets

    CERN Document Server

    Santos, N C; Israelian, G; Mayor, M; Rebolo, R; García-Gíl, A; Pérez de Taoro, M R; Randich, S

    2002-01-01

    We have derived beryllium abundances in a wide sample of stars hosting planets, with spectral types in the range F7V-K0V, aimed at studying in detail the effects of the presence of planets on the structure and evolution of the associated stars. Predictions from current models are compared with the derived abundances and suggestions are provided to explain the observed inconsistencies. We show that while still not clear, the results suggest that theoretical models may have to be revised for stars with Teff<5500K. On the other hand, a comparison between planet host and non-planet host stars shows no clear difference between both populations. Although preliminary, this result favors a ``primordial'' origin for the metallicity ``excess'' observed for the planetary host stars. Under this assumption, i.e. that there would be no differences between stars with and without giant planets, the light element depletion pattern of our sample of stars may also be used to further investigate and constraint Li and Be deple...

  5. miR-31 Links Lipid Metabolism and Cell Apoptosis in Bacteria-Challenged Apostichopus japonicus via Targeting CTRP9

    Science.gov (United States)

    Shao, Yina; Li, Chenghua; Xu, Wei; Zhang, Pengjuan; Zhang, Weiwei; Zhao, Xuelin

    2017-01-01

    The biological functions of microRNAs (miRNAs) have been studied in a number of eukaryotic species. Recent studies on vertebrate animals have demonstrated critical roles of miRNA in immune and metabolic activities. However, studies on the functions of miRNA in invertebrates are very limited. Here, we demonstrated that miR-31 from Apostichopus japonicus disrupts the balance of lipid metabolism, thus resulting in cell apoptosis by targeting complement C1q tumor necrosis factor-related protein 9 (AjCTRP9), a novel adipokine with pleiotropic functions in immunity and metabolism. Lipidomic analysis suggested that the intercellular lipid metabolites were markedly altered, and three ceramide (Cer) species synchronously increased in the AjCTRP9-silenced coelomocytes. Moreover, exogenous Cer exposure significantly induced apoptosis in the coelomocytes in vivo, in agreement with findings from miR-31 mimic- or AjCTRP9 small-interfering RNA-transfected coelomocytes. Furthermore, we found that the imbalance in sphingolipid metabolism triggered by the overproduction of Cers ultimately resulted in the activation of the apoptosis initiator caspase-8 and executioner caspase-3. Our findings provide the first direct evidence that miR-31 negatively modulates the expression of AjCTRP9 and disturbance of Cer channels, thus leading to caspase-3- and caspase-8-dependent apoptosis, during the interactions between pathogens and host.

  6. Efficient CRISPR/Cas9-assisted gene targeting enables rapid and precise genetic manipulation of mammalian neural stem cells

    Science.gov (United States)

    Bressan, Raul Bardini; Dewari, Pooran Singh; Kalantzaki, Maria; Gangoso, Ester; Matjusaitis, Mantas; Garcia-Diaz, Claudia; Blin, Carla; Grant, Vivien; Bulstrode, Harry; Gogolok, Sabine; Skarnes, William C.

    2017-01-01

    Mammalian neural stem cell (NSC) lines provide a tractable model for discovery across stem cell and developmental biology, regenerative medicine and neuroscience. They can be derived from foetal or adult germinal tissues and continuously propagated in vitro as adherent monolayers. NSCs are clonally expandable, genetically stable, and easily transfectable – experimental attributes compatible with targeted genetic manipulations. However, gene targeting, which is crucial for functional studies of embryonic stem cells, has not been exploited to date in NSC lines. Here, we deploy CRISPR/Cas9 technology to demonstrate a variety of sophisticated genetic modifications via gene targeting in both mouse and human NSC lines, including: (1) efficient targeted transgene insertion at safe harbour loci (Rosa26 and AAVS1); (2) biallelic knockout of neurodevelopmental transcription factor genes; (3) simple knock-in of epitope tags and fluorescent reporters (e.g. Sox2-V5 and Sox2-mCherry); and (4) engineering of glioma mutations (TP53 deletion; H3F3A point mutations). These resources and optimised methods enable facile and scalable genome editing in mammalian NSCs, providing significant new opportunities for functional genetic analysis. PMID:28096221

  7. Erosion of beryllium under ITER – Relevant transient plasma loads

    Energy Technology Data Exchange (ETDEWEB)

    Kupriyanov, I.B., E-mail: igkupr@gmail.com [A.A. Bochvar High Technology Research Institute of Inorganic Materials, Rogova St. 5a, 123060 Moscow (Russian Federation); Nikolaev, G.N.; Kurbatova, L.A.; Porezanov, N.P. [A.A. Bochvar High Technology Research Institute of Inorganic Materials, Rogova St. 5a, 123060 Moscow (Russian Federation); Podkovyrov, V.L.; Muzichenko, A.D.; Zhitlukhin, A.M. [TRINITI, Troitsk, Moscow reg. (Russian Federation); Gervash, A.A. [Efremov Research Institute, S-Peterburg (Russian Federation); Safronov, V.M. [Project Center of ITER, Moscow (Russian Federation)

    2015-08-15

    Highlights: • We study the erosion, mass loss/gain and surface structure evolution of Be/CuCrZr mock-ups, armored with beryllium of TGP-56FW grade after irradiation by deuterium plasma heat load of 0.5 MJ/m{sup 2} at 250 °C and 500 °C. • Beryllium mass loss/erosion under plasma heat load at 250 °C is rather small (no more than 0.2 g/m{sup 2} shot and 0.11 μm/shot, correspondingly, after 40 shots) and tends to decrease with increasing number of shots. • Beryllium mass loss/erosion under plasma heat load at 500 °C is much higher (∼2.3 g/m{sup 2} shot and 1.2 μm/shot, correspondingly, after 10 shot) and tends to decrease with increasing the number of shots (∼0.26 g/m{sup 2} pulse and 0.14 μm/shot, correspondingly, after 100 shot). • Beryllium erosion value derived from the measurements of profile of irradiated surface is much higher than erosion value derived from mass loss data. - Abstract: Beryllium will be used as a armor material for the ITER first wall. It is expected that erosion of beryllium under transient plasma loads such as the edge-localized modes (ELMs) and disruptions will mainly determine a lifetime of the ITER first wall. This paper presents the results of recent experiments with the Russian beryllium of TGP-56FW ITER grade on QSPA-Be plasma gun facility. The Be/CuCrZr mock-ups were exposed to up to 100 shots by deuterium plasma streams (5 cm in diameter) with pulse duration of 0.5 ms and heat loads range of 0.2–0.5 MJ/m{sup 2} at different temperature of beryllium tiles. The temperature of Be tiles has been maintained about 250 and 500 °C during the experiments. After 10, 40 and 100 shots, the beryllium mass loss/gain under erosion process were investigated as well as evolution of surface microstructure and cracks morphology.

  8. A Report on the Validation of Beryllium Strength Models

    Energy Technology Data Exchange (ETDEWEB)

    Armstrong, Derek Elswick [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2016-02-05

    This report discusses work on validating beryllium strength models with flyer plate and Taylor rod experimental data. Strength models are calibrated with Hopkinson bar and quasi-static data. The Hopkinson bar data for beryllium provides strain rates up to about 4000 per second. A limitation of the Hopkinson bar data for beryllium is that it only provides information on strain up to about 0.15. The lack of high strain data at high strain rates makes it difficult to distinguish between various strength model settings. The PTW model has been calibrated many different times over the last 12 years. The lack of high strain data for high strain rates has resulted in these calibrated PTW models for beryllium exhibiting significantly different behavior when extrapolated to high strain. For beryllium, the α parameter of PTW has recently been calibrated to high precision shear modulus data. In the past the α value for beryllium was set based on expert judgment. The new α value for beryllium was used in a calibration of the beryllium PTW model by Sky Sjue. The calibration by Sjue used EOS table information to model the temperature dependence of the heat capacity. Also, the calibration by Sjue used EOS table information to model the density changes of the beryllium sample during the Hopkinson bar and quasi-static experiments. In this paper, the calibrated PTW model by Sjue is compared against experimental data and other strength models. The other strength models being considered are a PTW model calibrated by Shuh- Rong Chen and a Steinberg-Guinan type model by John Pedicini. The three strength models are used in a comparison against flyer plate and Taylor rod data. The results show that the Chen PTW model provides better agreement to this data. The Chen PTW model settings have been previously adjusted to provide a better fit to flyer plate data, whereas the Sjue PTW model has not been changed based on flyer plate data. However, the Sjue model provides a reasonable fit to

  9. Genetic determinants of sensitivity to beryllium in mice.

    Science.gov (United States)

    Tarantino-Hutchison, Lauren M; Sorrentino, Claudio; Nadas, Arthur; Zhu, Yiwen; Rubin, Edward M; Tinkle, Sally S; Weston, Ainsley; Gordon, Terry

    2009-06-01

    Chronic beryllium disease (CBD), an irreversible, debilitating granulomatous lung disease is caused by exposure to beryllium. This occupational hazard occurs in primary production and machining of Be-metal, BeO, beryllium - containing alloys, and other beryllium products. CBD begins as an MHC Class II-restricted, T(H)1 hypersensitivity, and the Human Leukocyte Antigen, HLA-DPB1E(69), is associated with risk of developing CBD. Because inbred strains of mice have not provided good models of CBD to date, three strains of HLA-DPB1 transgenic mice in an FVB/N background were developed; each contains a single allele of HLA-DPB1 that confers a different magnitude of risk for chronic beryllium disease: HLA-DPB1*0401 (OR approximately 0.2), HLA-DPB1*0201 (OR approximately 3), and HLA-DPB1*1701 (OR approximately 46). The mouse ear swelling test (MEST) was employed to determine if these different alleles would support a hypersensitivity response to beryllium. Mice were first sensitized on the back and subsequently challenged on the ear. In separate experiments, mice were placed into one of three groups (sensitization/challenge): C/C, C/Be, and Be/Be. In the HLA-DPB1*1701 mice, the strain with the highest risk transgene, the Be/Be group was the only group that displayed significant maximum increased ear thickness of 19.6% +/- 3.0% over the baseline measurement (p beryllium in seven inbred strains were investigated through use of the MEST, these included: FVB/N, AKR, Balb/c, C3H/HeJ, C57/BL6, DBA/2, and SJL/J. The FVB/N strain was least responsive, while the SJL/J and C57/BL6 strains were the highest responders. Our results suggest that the HLA-DPB1*1701 transgene product is an important risk factor for induction of the beryllium-sensitive phenotype. This model should be a useful tool for investigating beryllium sensitization.

  10. Report of a technical evaluation panel on the use of beryllium for ITER plasma facing material and blanket breeder material

    Energy Technology Data Exchange (ETDEWEB)

    Ulrickson, M.A. [ed.] [Sandia National Labs., Albuquerque, NM (United States); Manly, W.D. [Oak Ridge National Lab., TN (United States); Dombrowski, D.E. [Brush Wellman, Inc., Cleveland, OH (United States)] [and others

    1995-08-01

    Beryllium because of its low atomic number and high thermal conductivity, is a candidate for both ITER first wall and divertor surfaces. This study addresses the following: why beryllium; design requirements for the ITER divertor; beryllium supply and unirradiated physical/mechanical property database; effects of irradiation on beryllium properties; tritium issues; beryllium health and safety; beryllium-coolant interactions and safety; thermal and mechanical tests; plasma erosion of beryllium; recommended beryllium grades for ITER plasma facing components; proposed manufacturing methods to produce beryllium parts for ITER; emerging beryllium materials; proposed inspection and maintenance techniques for beryllium components and coatings; time table and costs; and the importance of integrating materials and manufacturing personnel with designers.

  11. Identification of beryllium-dependent peptides recognized by CD4+ T cells in chronic beryllium disease.

    Science.gov (United States)

    Falta, Michael T; Pinilla, Clemencia; Mack, Douglas G; Tinega, Alex N; Crawford, Frances; Giulianotti, Marc; Santos, Radleigh; Clayton, Gina M; Wang, Yuxiao; Zhang, Xuewu; Maier, Lisa A; Marrack, Philippa; Kappler, John W; Fontenot, Andrew P

    2013-07-01

    Chronic beryllium disease (CBD) is a granulomatous disorder characterized by an influx of beryllium (Be)-specific CD4⁺ T cells into the lung. The vast majority of these T cells recognize Be in an HLA-DP–restricted manner, and peptide is required for T cell recognition. However, the peptides that stimulate Be-specific T cells are unknown. Using positional scanning libraries and fibroblasts expressing HLA-DP2, the most prevalent HLA-DP molecule linked to disease, we identified mimotopes and endogenous self-peptides that bind to MHCII and Be, forming a complex recognized by pathogenic CD4⁺ T cells in CBD. These peptides possess aspartic and glutamic acid residues at p4 and p7, respectively, that surround the putative Be-binding site and cooperate with HLA-DP2 in Be coordination. Endogenous plexin A peptides and proteins, which share the core motif and are expressed in lung, also stimulate these TCRs. Be-loaded HLA-DP2–mimotope and HLA-DP2–plexin A4 tetramers detected high frequencies of CD4⁺ T cells specific for these ligands in all HLADP2+ CBD patients tested. Thus, our findings identify the first ligand for a CD4⁺ T cell involved in metal-induced hypersensitivity and suggest a unique role of these peptides in metal ion coordination and the generation of a common antigen specificity in CBD.

  12. Targeted viral-mediated plant genome editing using crispr/cas9

    KAUST Repository

    Mahfouz, Magdy M.

    2015-12-17

    The present disclosure provides a viral-mediated genome-editing platform that facilitates multiplexing, obviates stable transformation, and is applicable across plant species. The RNA2 genome of the tobacco rattle virus (TRV) was engineered to carry and systemically deliver a guide RNA molecules into plants overexpressing Cas9 endonuclease. High genomic modification frequencies were observed in inoculated as well as systemic leaves including the plant growing points. This system facilitates multiplexing and can lead to germinal transmission of the genomic modifications in the progeny, thereby obviating the requirements of repeated transformations and tissue culture. The editing platform of the disclosure is useful in plant genome engineering and applicable across plant species amenable to viral infections for agricultural biotechnology applications.

  13. Behavior of carboxylic acids upon complexation with beryllium compounds.

    Science.gov (United States)

    Mykolayivna-Lemishko, Kateryna; Montero-Campillo, M Merced; Mó, Otilia; Yáñez, Manuel

    2014-07-31

    A significant acidity enhancement and changes on aromaticity were previously observed in squaric acid and its derivatives when beryllium bonds are present in those systems. In order to know if these changes on the chemical properties could be considered a general behavior of carboxylic acids upon complexation with beryllium compounds, complexes between a set of representative carboxylic acids RCOOH (formic acid, acetic acid, propanoic acid, benzoic acid, and oxalic acid) and beryllium compounds BeX2 (X = H, F, Cl) were studied by means of density functional theory calculations. Complexes that contain a dihydrogen bond or a OH···X interaction are the most stable in comparison with other possible BeX2 complexation patterns in which no other weak interactions are involved apart from the beryllium bond. Formic, acetic, propanoic, benzoic, and oxalic acid complexes with BeX2 are much stronger acids than their related free forms. The analysis of the topology of the electron density helps to clarify the reasons behind this acidity enhancement. Importantly, when the halogen atom is replaced by hydrogen in the beryllium compound, the dihydrogen bond complex spontaneously generates a new neutral complex [RCOO:BeH] in which a hydrogen molecule is lost. This seems to be a trend for carboxylic acids on complexing BeX2 compounds.

  14. Design and cooling of BESIII beryllium beam pipe

    Science.gov (United States)

    Li, Xunfeng; Ji, Quan; Wang, Li; Zheng, Lifang

    2008-01-01

    The beryllium beam pipe was restructured according to the requirements of the upgraded BESIII (Beijing Spectrometer) experiment. SMO-1 (sparking machining oil no. 1) was selected as the coolant for the central beryllium beam pipe. The cooling gap width of the beryllium beam pipe was calculated, the influence of concentrated heat load on the wall temperature of the beryllium beam pipe was studied, and the optimal velocity of the SMO-1 in the gap was determined at the maximum heat load. A cooling system for the beam pipe was developed to control the outer wall temperature of the beam pipe. The cooling system is reported in this paper with regard to the following two aspects: the layouts and the automation. The performance of the cooling system was tested on the beam pipe model with trim size. The test results show that the design of the beryllium beam pipe is reasonable and that the cooling system achieves the BESIII experimental aim. The cooling system has already passed the acceptance test and has been installed in position. It will be put into practice for the BESIII experiment in 2008.

  15. Experimental studies and modeling of processes of hydrogen isotopes interaction with beryllium

    Energy Technology Data Exchange (ETDEWEB)

    Tazhibaeva, I.L.; Chikhray, Y.V.; Romanenko, O.G.; Klepikov, A.Kh.; Shestakov, V.P.; Kulsartov, T.V. [Science Research Inst. of Experimental and Theoretical Physics of Kazakh State Univ., Almaty (Kazakhstan); Kenzhin, E.A.

    1998-01-01

    The objective of this work was to clarify the surface beryllium oxide influence on hydrogen-beryllium interaction characteristics. Analysis of experimental data and modeling of processes of hydrogen isotopes accumulation, diffusion and release from neutron irradiated beryllium was used to achieve this purpose as well as the investigations of the changes of beryllium surface element composition being treated by H{sup +} and Ar{sup +} plasma glowing discharge. (author)

  16. Estrogen induced metastatic modulators MMP-2 and MMP-9 are targets of 3,3'-diindolylmethane in thyroid cancer.

    Directory of Open Access Journals (Sweden)

    Shilpi Rajoria

    Full Text Available BACKGROUND: Thyroid cancer is the most common endocrine related cancer with increasing incidences during the past five years. Current treatments for thyroid cancer, such as surgery or radioactive iodine therapy, often require patients to be on lifelong thyroid hormone replacement therapy and given the significant recurrence rates of thyroid cancer, new preventive modalities are needed. The present study investigates the property of a natural dietary compound found in cruciferous vegetables, 3,3'-diindolylmethane (DIM, to target the metastatic phenotype of thyroid cancer cells through a functional estrogen receptor. METHODOLOGY/PRINCIPAL FINDINGS: Thyroid cancer cell lines were treated with estrogen and/or DIM and subjected to in vitro adhesion, migration and invasion assays to investigate the anti-metastatic and anti-estrogenic effects of DIM. We observed that DIM inhibits estrogen mediated increase in thyroid cell migration, adhesion and invasion, which is also supported by ER-α downregulation (siRNA studies. Western blot and zymography analyses provided direct evidence for this DIM mediated inhibition of E(2 enhanced metastasis associated events by virtue of targeting essential proteolytic enzymes, namely MMP-2 and MMP-9. CONCLUSION/SIGNIFICANCE: Our data reports for the first time that DIM displays anti-estrogenic like activity by inhibiting estradiol enhanced thyroid cancer cell proliferation and in vitro metastasis associated events, namely adhesion, migration and invasion. Most significantly, MMP-2 and MMP-9, which are known to promote and enhance metastasis, were determined to be targets of DIM. This anti-estrogen like property of DIM may lead to the development of a novel preventive and/or therapeutic dietary supplement for thyroid cancer patients by targeting progression of the disease.

  17. Beryllium Chelation by Dicarboxylic Acids in Aqueous Solution.

    Science.gov (United States)

    Schmidt, Michael; Bauer, Andreas; Schmidbaur, Hubert

    1997-05-07

    Maleic and phthalic acids are found to react with Be(OH)(2), generated in situ from BeSO(4)(aq) and Ba(OH)(2)(aq), in aqueous solution at pH 3.0 or 4.4, respectively (25 degrees C), to give solutions containing the complexes (H(2)O)(2)Be[(OOCCH)(2)] (1) and (H(2)O)(2)Be[(OOC)(2)C(6)H(4)] (3). The products can be isolated in high yield and identified by microanalytical data. With 2 equiv of the dicarboxylic acids and the pH adjusted to 5.5 and 5.9, respectively, by addition of ammonia, the bis-chelate complexes [(NH(4))(+)](2){[Be[(OOCCH)(2)](2)}(2)(-) (2) and [(NH(4))(+)](2){Be[(OOC)(2)C(6)H(4)](2)}(2)(-) (4) are obtained, which can also be isolated. The compounds show distinct (9)Be, (1)H, and (13)C resonances in their NMR spectra in aqueous solutions. Layering of an aqueous solution of compound 4 with acetone at ambient temperature leads to the precipitation of single crystals suitable for an X-ray structure determination. This salt (5) was found to contain the bis-chelated dianion {Be[(OOC)(2)C(6)H(4)](2)}(2)(-) with the beryllium atom in the spiro center of two seven-membered rings and an overall geometry approaching closely C(2) symmetry. These anions are associated with two crystallographically independent but structurally similar counterions [MeC(O)CH(2)CMe(2)NH(3)](+), which are the product of a condensation reaction of the ammonium cation with the acetone solvent. In the crystal the ammonium hydrogen atoms of the cations form N-H.O hydrogen bonds with the oxo functions of the dianion.

  18. Isotopic Distributions of the l8N Fragmentation Products in Coincidence with Neutrons on Targets 197Au and 9Be

    Institute of Scientific and Technical Information of China (English)

    李湘庆; 江栋兴; 叶沿林; 华辉; 陈陶; 李智焕; 葛愉成; 王全进; 吴和宇; 靳根明; 段利敏; 肖志刚; 王宏伟; 李祖玉; 王素芳

    2002-01-01

    We present the experimental isotopic distributions of the 18 N projectile fragmentation products Li, Be,B and Cin coincidence with neutrons, as well as the inclusive ones on 197 Au and 9Be targets. In the framework of theabrasion-ablation model, these distributions are calculated for various nucleon density distributions of the projec-tile. The comparison with experimental isotopic distributions of the projectile-like fragments in coincidence withneutrons shows that the information on the nucleon density distribution of the 18N projectile can be extracted.

  19. Targeting triple negative breast cancer cells by N3-substituted 9,10-Phenanthrenequinone thiosemicarbazones and their metal complexes

    Science.gov (United States)

    Afrasiabi, Zahra; Stovall, Preston; Finley, Kristen; Choudhury, Amitava; Barnes, Charles; Ahmad, Aamir; Sarkar, Fazlul; Vyas, Alok; Padhye, Subhash

    2013-10-01

    Novel N3-substituted 9,10-Phenanthrenequinone thiosemicarbazones and their copper, nickel and palladium complexes are structurally characterized and reported along with the single crystal X-ray structures of three ligands and one nickel complex. All compounds were evaluated for their antiproliferative potential against Triple Negative Breast Cancer (TNBC) cells which have poor prognosis and no effective drugs to treat with. All compounds exhibited antiproliferative activity against these cells. Among the metal complexes evaluated, redox active copper complexes were found to be more potent. The possible mechanism for such enhanced activity can be attributed to the generation of oxidative stress, which was amenable for targeting through metal complexation.

  20. Developing a 1D ``like'' performance basecamp for beryllium capsule implosions

    Science.gov (United States)

    Kline, John; Yi, Austin; Loomis, Eric; Simakov, Andrei; Kyrala, George; Wilson, Doub; Dewald, Eddie; Ralph, Joe; Strozzi, David

    2016-10-01

    Experiments with Beryllium capsules in high density gas filled targets showed little difference in performance with respect to CH or HDC capsules. The hypothesis for the lack of performance difference is attributed to poor control of symmetry based on work by Clark et al. Going forward, the goal is to develop a target design that enables better comparisons between the performance of Be capsules and other ablators, as well as with simulations. To develop a platform in which Be capsules maximize performance with respect to 1D calculations, we have increased the case-to-capsule ratio and reduced the hohlraum drive. The stability properties of beryllium are expected to be accentuated at lower radiation temperature drives compared with other ablators. Experiments have been carried out with case-to-capasule ratio of 3.1 and 4.3. Results from these experiments are being used to develop an optimized case-to-capsule ratio to achieve controllable symmetric implosions with maximum 1D like performance. This presentation will focus on how results of the experiments are used to design the next series of optimized experiments..

  1. 10 CFR Appendix A to Part 850 - Chronic Beryllium Disease Prevention Program Informed Consent Form

    Science.gov (United States)

    2010-01-01

    ... 10 Energy 4 2010-01-01 2010-01-01 false Chronic Beryllium Disease Prevention Program Informed Consent Form A Appendix A to Part 850 Energy DEPARTMENT OF ENERGY CHRONIC BERYLLIUM DISEASE PREVENTION PROGRAM Pt. 850, App. A Appendix A to Part 850—Chronic Beryllium Disease Prevention Program...

  2. 10 CFR 71.23 - General license: Plutonium-beryllium special form material.

    Science.gov (United States)

    2010-01-01

    ... 10 Energy 2 2010-01-01 2010-01-01 false General license: Plutonium-beryllium special form material... RADIOACTIVE MATERIAL General Licenses § 71.23 General license: Plutonium-beryllium special form material. (a... form of plutonium-beryllium (Pu-Be) special form sealed sources, or to deliver Pu-Be sealed sources...

  3. Beryllium is an inhibitor of cellular GSK-3β that is 1,000-fold more potent than lithium.

    Science.gov (United States)

    Mudireddy, Swapna R; Abdul, Ataur Rahman Mohammed; Gorjala, Priyatham; Gary, Ronald K

    2014-12-01

    Glycogen synthase kinase 3β (GSK-3β) is a key regulator in signaling networks that control cell proliferation, metabolism, development, and other processes. Lithium chloride is a GSK-3 family inhibitor that has been a mainstay of in vitro and in vivo studies for many years. Beryllium salt has the potential to act as a lithium-like inhibitor of GSK-3, but it is not known whether this agent is effective under physiologically relevant conditions. Here we show that BeSO4 inhibits endogenous GSK-3β in cultured human cells. Exposure to 10 µM Be(2+) produced a decrease in GSK-3β kinase activity that was comparable to that produced by 10 mM Li(+), indicating that beryllium is about 1,000-fold more potent than the classical inhibitor when treating intact cells. There was a statistically significant dose-dependent reduction in specific activity of GSK-3β immunoprecipitated from cells that had been treated with either agent. Lithium inhibited GSK-3β kinase activity directly, and it also caused GSK-3β in cells to become phosphorylated at serine-9 (Ser-9), a post-translational modification that occurs as part of a well-known positive feedback loop that suppresses the kinase activity. Beryllium also inhibited the kinase directly, but unlike lithium it had little effect on Ser-9 phosphorylation in the cell types tested, suggesting that alternative modes of feedback inhibition may be elicited by this agent. These results indicate that beryllium, like lithium, can induce perturbations in the GSK-3β signaling network of treated cells.

  4. Targeted deletion of the 9p21 noncoding coronary artery disease risk interval in mice

    Energy Technology Data Exchange (ETDEWEB)

    Visel, Axel; Zhu, Yiwen; May, Dalit; Afzal, Veena; Gong, Elaine; Attanasio, Catia; Blow, Matthew J.; Cohen, Jonathan C.; Rubin, Edward M.; Pennacchio, Len A.

    2010-01-01

    Sequence polymorphisms in a 58kb interval on chromosome 9p21 confer a markedly increased risk for coronary artery disease (CAD), the leading cause of death worldwide 1,2. The variants have a substantial impact on the epidemiology of CAD and other life?threatening vascular conditions since nearly a quarter of Caucasians are homozygous for risk alleles. However, the risk interval is devoid of protein?coding genes and the mechanism linking the region to CAD risk has remained enigmatic. Here we show that deletion of the orthologous 70kb noncoding interval on mouse chromosome 4 affects cardiac expression of neighboring genes, as well as proliferation properties of vascular cells. Chr4delta70kb/delta70kb mice are viable, but show increased mortality both during development and as adults. Cardiac expression of two genes near the noncoding interval, Cdkn2a and Cdkn2b, is severely reduced in chr4delta70kb/delta70kb mice, indicating that distant-acting gene regulatory functions are located in the noncoding CAD risk interval. Allelespecific expression of Cdkn2b transcripts in heterozygous mice revealed that the deletion affects expression through a cis-acting mechanism. Primary cultures of chr4delta70kb/delta70kb aortic smooth muscle cells exhibited excessive proliferation and diminished senescence, a cellular phenotype consistent with accelerated CAD pathogenesis. Taken together, our results provide direct evidence that the CAD risk interval plays a pivotal role in regulation of cardiac Cdkn2a/b expression and suggest that this region affects CAD progression by altering the dynamics of vascular cell proliferation.

  5. Estimation of beryllium ground state energy by Monte Carlo simulation

    Energy Technology Data Exchange (ETDEWEB)

    Kabir, K. M. Ariful [Department of Physical Sciences, School of Engineering and Computer Science, Independent University, Bangladesh (IUB) Dhaka (Bangladesh); Halder, Amal [Department of Mathematics, University of Dhaka Dhaka (Bangladesh)

    2015-05-15

    Quantum Monte Carlo method represent a powerful and broadly applicable computational tool for finding very accurate solution of the stationary Schrödinger equation for atoms, molecules, solids and a variety of model systems. Using variational Monte Carlo method we have calculated the ground state energy of the Beryllium atom. Our calculation are based on using a modified four parameters trial wave function which leads to good result comparing with the few parameters trial wave functions presented before. Based on random Numbers we can generate a large sample of electron locations to estimate the ground state energy of Beryllium. Our calculation gives good estimation for the ground state energy of the Beryllium atom comparing with the corresponding exact data.

  6. Field-emission spectroscopy of beryllium atoms adsorbed on tungsten

    Energy Technology Data Exchange (ETDEWEB)

    Czyzewski, J.J.; Grzesiak, W.; Krajniak, J. (Politechnika Wroclawska (Poland))

    1981-01-01

    Field emission energy distributions (FEED) have been measured for the beryllium-tungsten (023) adsorption system over the 78-450 K temperature range. A temperature dependence of the normalized half-width, ..delta../d, of FEED peaks changed significantly due to beryllium adsorption; and the curve, ..delta../d vs p, for the Be/W adsorption system was identical in character to the calculated curve based on the free electron model in contrast to the curve for the clean tungsten surface. In the last part of this paper Gadzuk's theory of the resonance-tunneling effect is applied to the beryllium atom on tungsten. Experimental and theoretical curves of the enhancement factor as a function of energy have been discussed.

  7. Monte Carlo uncertainty analyses for integral beryllium experiments

    CERN Document Server

    Fischer, U; Tsige-Tamirat, H

    2000-01-01

    The novel Monte Carlo technique for calculating point detector sensitivities has been applied to two representative beryllium transmission experiments with the objective to investigate the sensitivity of important responses such as the neutron multiplication and to assess the related uncertainties due to the underlying cross-section data uncertainties. As an important result, it has been revealed that the neutron multiplication power of beryllium can be predicted with good accuracy using state-of-the-art nuclear data evaluations. Severe discrepancies do exist for the spectral neutron flux distribution that would transmit into significant uncertainties of the calculated neutron spectra and of the nuclear blanket performance in blanket design calculations. With regard to this, it is suggested to re-analyse the secondary energy and angle distribution data of beryllium by means of Monte Carlo based sensitivity and uncertainty calculations. Related code development work is underway.

  8. Color Enhancement by Diffusion of Beryllium in Dark Blue Sapphire

    Institute of Scientific and Technical Information of China (English)

    Kyungj in Kim; Yongkil Ahn

    2016-01-01

    Diffusion of beryllium was performed on dark blue sapphire from China and Australia.The samples were heated with beryllium as a dopant in a furnace at 1 600 ℃ for 42 h in air.After beryllium diffusion,sam-ples were analyzed by UV-Vis,FTIR,and WD-XRF spectroscopy.After heat-treatment with Be as a catalyst, the irons of the ferrous state were changed to the ferric state.Therefore,reaction of Fe2+/Ti4+ IVCT was de-creased.The absorption peaks at 3 309 cm-1 attributed to OH radical were disappeared completely due to carry out heat treatment.Consequently,the intensity of absorption band was decreased in the visible region.Espe-cially,decreased absorption band in the vicinity of 570 nm was responsible for the lighter blue color.There-fore,we confirmed that the dark blue sapphires from China and Australia were changed to vivid blue.

  9. Neutron irradiation behavior of ITER candidate beryllium grades

    Energy Technology Data Exchange (ETDEWEB)

    Kupriyanov, I.B.; Gorokhov, V.A.; Nikolaev, G.N. [A.A.Bochvar All-Russia Scientific Research Inst. of Inorganic Materials (VNIINM), Moscow (Russian Federation); Melder, R.R.; Ostrovsky, Z.E.

    1998-01-01

    Beryllium is one of the main candidate materials both for the neutron multiplier in a solid breeding blanket and for the plasma facing components. That is why its behaviour under the typical for fusion reactor loading, in particular, under the neutron irradiation is of a great importance. This paper presents mechanical properties, swelling and microstructure of six beryllium grades (DshG-200, TR-30, TshG-56, TRR, TE-30, TIP-30) fabricated by VNIINM, Russia and also one - (S-65) fabricated by Brush Wellman, USA. The average grain size of the beryllium grades varied from 8 to 25 {mu}m, beryllium oxide content was 0.8-3.2 wt. %, initial tensile strength was 250-680 MPa. All the samples were irradiated in active zone of SM-3 reactor up to the fast neutron fluence (5.5-6.2) {center_dot} 10{sup 21} cm{sup -2} (2.7-3.0 dpa, helium content up to 1150 appm), E > 0.1 MeV at two temperature ranges: T{sub 1} = 130-180degC and T{sub 2} = 650-700degC. After irradiation at 130-180degC no changes in samples dimensions were revealed. After irradiation at 650-700degC swelling of the materials was found to be in the range 0.1-2.1 %. Beryllium grades TR-30 and TRR, having the smallest grain size and highest beryllium oxide content, demonstrated minimal swelling, which was no more than 0.1 % at 650-700degC and fluence 5.5 {center_dot} 10{sup 21} cm{sup -2}. Tensile and compression test results and microstructure parameters measured before and after irradiation are also presented. (author)

  10. Chronic beryllium disease, HLA-DPB1, and the DP peptide binding groove.

    Science.gov (United States)

    Silveira, Lori J; McCanlies, Erin C; Fingerlin, Tasha E; Van Dyke, Michael V; Mroz, Margaret M; Strand, Matthew; Fontenot, Andrew P; Bowerman, Natalie; Dabelea, Dana M; Schuler, Christine R; Weston, Ainsley; Maier, Lisa A

    2012-10-15

    Multiple epidemiologic studies demonstrate associations between chronic beryllium disease (CBD), beryllium sensitization (BeS), and HLA-DPB1 alleles with a glutamic acid residue at position 69 (E69). Results suggest that the less-frequent E69 variants (non-*0201/*0202 alleles) might be associated with greater risk of CBD. In this study, we sought to define specific E69-carrying alleles and their amino acid sequences in the DP peptide binding groove, as well as their relationship to CBD and BeS risk, using the largest case control study to date. We enrolled 502 BeS/CBD subjects and 653 beryllium-exposed controls from three beryllium industries who gave informed consent for participation. Non-Hispanic white cases and controls were frequency-matched by industry. HLA-DPB1 genotypes were determined using sequence-specific primer PCR. The E69 alleles were tested for association with disease individually and grouped by amino acid structure using logistic regression. The results show that CBD cases were more likely than controls to carry a non-*02 E69 allele than an *02 E69, with odds ratios (95% confidence interval) ranging from 3.1 (2.1-4.5) to 3.9 (2.6-5.9) (p < 0.0001). Polymorphic amino acids at positions 84 and 11 were associated with CBD: DD versus GG, 2.8 (1.8-4.6), p < 0.0001; GD versus GG, 2.1 (1.5-2.8), p < 0.0001; LL versus GG, 3.2 (1.8-5.6), p < 0.0001; GL versus GG, 2.8 (2.1-3.8), p < 0.0001. Similar results were found within the BeS group and CBD/BeS combined group. We conclude that the less frequent E69 alleles confer more risk for CBD than does *0201. Recent studies examining how the composition and structure of the binding pockets influence peptide binding in MHC genes, as well of studies showing the topology of the TCR to likely bind DPB1 preferentially, give plausible biological rationale for these findings.

  11. Method for removal of beryllium contamination from an article

    Science.gov (United States)

    Simandl, Ronald F.; Hollenbeck, Scott M.

    2012-12-25

    A method of removal of beryllium contamination from an article is disclosed. The method typically involves dissolving polyisobutylene in a solvent such as hexane to form a tackifier solution, soaking the substrate in the tackifier to produce a preform, and then drying the preform to produce the cleaning medium. The cleaning media are typically used dry, without any liquid cleaning agent to rub the surface of the article and remove the beryllium contamination below a non-detect level. In some embodiments no detectible residue is transferred from the cleaning wipe to the article as a result of the cleaning process.

  12. Relativistic and QED corrections for the beryllium atom.

    Science.gov (United States)

    Pachucki, Krzysztof; Komasa, Jacek

    2004-05-28

    Complete relativistic and quantum electrodynamics corrections of order alpha(2) Ry and alpha(3) Ry are calculated for the ground state of the beryllium atom and its positive ion. A basis set of correlated Gaussian functions is used, with exponents optimized against nonrelativistic binding energies. The results for Bethe logarithms ln(k(0)(Be)=5.750 34(3) and ln(k(0)(Be+)=5.751 67(3) demonstrate the availability of high precision theoretical predictions for energy levels of the beryllium atom and light ions. Our recommended value of the ionization potential 75 192.514(80) cm(-1) agrees with equally accurate available experimental values.

  13. CHAPTER 7. BERYLLIUM ANALYSIS BY NON-PLASMA BASED METHODS

    Energy Technology Data Exchange (ETDEWEB)

    Ekechukwu, A

    2009-04-20

    The most common method of analysis for beryllium is inductively coupled plasma atomic emission spectrometry (ICP-AES). This method, along with inductively coupled plasma mass spectrometry (ICP-MS), is discussed in Chapter 6. However, other methods exist and have been used for different applications. These methods include spectroscopic, chromatographic, colorimetric, and electrochemical. This chapter provides an overview of beryllium analysis methods other than plasma spectrometry (inductively coupled plasma atomic emission spectrometry or mass spectrometry). The basic methods, detection limits and interferences are described. Specific applications from the literature are also presented.

  14. 20 CFR 30.207 - How does a claimant prove a diagnosis of a beryllium disease covered under Part B?

    Science.gov (United States)

    2010-04-01

    ... beryllium disease covered under Part B? 30.207 Section 30.207 Employees' Benefits OFFICE OF WORKERS... Beryllium Illness Under Part B of Eeoicpa § 30.207 How does a claimant prove a diagnosis of a beryllium... employee developed a covered beryllium illness. Proof that the employee developed a covered...

  15. The Convenience of Single Homology Arm Donor DNA and CRISPR/Cas9-Nickase for Targeted Insertion of Long DNA Fragment

    Directory of Open Access Journals (Sweden)

    Mohsen Basiri

    2016-10-01

    Full Text Available Objective: CRISPR/Cas9 technology provides a powerful tool for targeted modification of genomes. In this system, a donor DNA harboring two flanking homology arms is mostly used for targeted insertion of long exogenous DNA. Here, we introduced an alternative design for the donor DNA by incorporation of a single short homology arm into a circular plasmid. Materials and Methods: In this experimental study, single homology arm donor was applied along with a single guide RNA (sgRNA specific to the homology region, and either Cas9 or its mutant nickase variant (Cas9n. Using Pdx1 gene as the target locus the functionality of this system was evaluated in MIN6 cell line and murine embryonic stem cells (ESCs. Results: Both wild type Cas9 and Cas9n could conduct the knock-in process with this system. We successfully applied this strategy with Cas9n for generation of Pdx1GFP knock-in mouse ESC lines. Altogether, our results demonstrated that a combination of a single homology arm donor, a single guide RNA and Cas9n is capable of precisely incorporating DNA fragments of multiple kilo base pairs into the targeted genomic locus. Conclusion: While taking advantage of low off-target mutagenesis of the Cas9n, our new design strategy may facilitate the targeting process. Consequently, this strategy can be applied in knock-in or insertional inactivation studies.

  16. Adaptation prevents the extinction of Chlamydomonas reinhardtii under toxic beryllium

    Directory of Open Access Journals (Sweden)

    Beatriz Baselga-Cervera

    2016-03-01

    Full Text Available The current biodiversity crisis represents a historic challenge for natural communities: the environmental rate of change exceeds the population’s adaptation capability. Integrating both ecological and evolutionary responses is necessary to make reliable predictions regarding the loss of biodiversity. The race against extinction from an eco-evolutionary perspective is gaining importance in ecological risk assessment. Here, we performed a classical study of population dynamics—a fluctuation analysis—and evaluated the results from an adaption perspective. Fluctuation analysis, widely used with microorganisms, is an effective empirical procedure to study adaptation under strong selective pressure because it incorporates the factors that influence demographic, genetic and environmental changes. The adaptation of phytoplankton to beryllium (Be is of interest because human activities are increasing the concentration of Be in freshwater reserves; therefore, predicting the effects of human-induced pollutants is necessary for proper risk assessment. The fluctuation analysis was performed with phytoplankton, specifically, the freshwater microalgae Chlamydomonas reinhardtii, under acute Be exposure. High doses of Be led to massive microalgae death; however, by conducting a fluctuation analysis experiment, we found that C. reinhardtii was able to adapt to 33 mg/l of Be due to pre-existing genetic variability. The rescuing adapting genotype presented a mutation rate of 9.61 × 10−6 and a frequency of 10.42 resistant cells per million wild-type cells. The genetic adaptation pathway that was experimentally obtained agreed with the theoretical models of evolutionary rescue (ER. Furthermore, the rescuing genotype presented phenotypic and physiologic differences from the wild-type genotype, was 25% smaller than the Be-resistant genotype and presented a lower fitness and quantum yield performance. The abrupt distinctions between the wild-type and the Be

  17. Generation of High-Amylose Rice through CRISPR/Cas9-Mediated Targeted Mutagenesis of Starch Branching Enzymes

    Science.gov (United States)

    Sun, Yongwei; Jiao, Guiai; Liu, Zupei; Zhang, Xin; Li, Jingying; Guo, Xiuping; Du, Wenming; Du, Jinlu; Francis, Frédéric; Zhao, Yunde; Xia, Lanqin

    2017-01-01

    Cereals high in amylose content (AC) and resistant starch (RS) offer potential health benefits. Previous studies using chemical mutagenesis or RNA interference have demonstrated that starch branching enzyme (SBE) plays a major role in determining the fine structure and physical properties of starch. However, it remains a challenge to control starch branching in commercial lines. Here, we use CRISPR/Cas9 technology to generate targeted mutagenesis in SBEI and SBEIIb in rice. The frequencies of obtained homozygous or bi-allelic mutant lines with indels in SBEI and SBEIIb in T0 generation were from 26.7 to 40%. Mutations in the homozygous T0 lines stably transmitted to the T1 generation and those in the bi-allelic lines segregated in a Mendelian fashion. Transgene-free plants carrying only the frame-shifted mutagenesis were recovered in T1 generation following segregation. Whereas no obvious differences were observed between the sbeI mutants and wild type, sbeII mutants showed higher proportion of long chains presented in debranched amylopectin, significantly increased AC and RS content to as higher as 25.0 and 9.8%, respectively, and thus altered fine structure and nutritional properties of starch. Taken together, our results demonstrated for the first time the feasibility to create high-amylose rice through CRISPR/Cas9-mediated editing of SBEIIb. PMID:28326091

  18. Beryllium solubility in occupational airborne particles: Sequential extraction procedure and workplace application.

    Science.gov (United States)

    Rousset, Davy; Durand, Thibaut

    2016-01-01

    Modification of an existing sequential extraction procedure for inorganic beryllium species in the particulate matter of emissions and in working areas is described. The speciation protocol was adapted to carry out beryllium extraction in closed-face cassette sampler to take wall deposits into account. This four-step sequential extraction procedure aims to separate beryllium salts, metal, and oxides from airborne particles for individual quantification. Characterization of the beryllium species according to their solubility in air samples may provide information relative to toxicity, which is potentially related to the different beryllium chemical forms. Beryllium salts (BeF(2), BeSO(4)), metallic beryllium (Bemet), and beryllium oxide (BeO) were first individually tested, and then tested in mixtures. Cassettes were spiked with these species and recovery rates were calculated. Quantitative analyses with matched matrix were performed using inductively coupled plasma mass spectrometry (ICP-MS). Method Detection Limits (MDLs) were calculated for the four matrices used in the different extraction steps. In all cases, the MDL was below 4.2 ng/sample. This method is appropriate for assessing occupational exposure to beryllium as the lowest recommended threshold limit values are 0.01 µg.m(-3) in France([) (1) (]) and 0.05 µg.m(-3) in the USA.([ 2 ]) The protocol was then tested on samples from French factories where occupational beryllium exposure was suspected. Beryllium solubility was variable between factories and among the same workplace between different tasks.

  19. Measurement of charged particle production from 450 GeV/c protons on beryllium

    CERN Document Server

    Ambrosini, G; Bernier, K; Biino, C; Bonesini, M; Bonivento, W; Borer, K; Brooijmans, G; Catanesi, M G; Collazuol, G; Daniels, D C; Dittus, F B; Elsener, K; Godley, A; Grant, A; Grégoire, G; Guglielmi, A M; Kabana, S; Kabana, R; Klingenberg, R; Lehmann, G; Lindén, T; Linssen, Lucie; Marchionni, A; Mishra, S R; Moffitt, L; Moser, U; Palladino, Vittorio; Pietropaolo, F; Pretzl, Klaus P; Pullia, Antonio; Radicioni, E; Ragazzi, S; Stachel, J; Sergiampietri, F; Soler, F J P; Stoffel, F; Tabarelli de Fatis, T; Terranova, F; Tovey, Stuart N; Tsesmelis, E; Weber, M

    1999-01-01

    This paper presents the results on charged particle yields and production ratios as measured by the NA56/SPY experiment for 450 GeV/c proton interactions on beryllium targets. The data cover a secondary momentum range from 7 GeV/c to 135 GeV/c and $p_T$ values up to 600~MeV/c. An experimental accuracy on the measured yields in the range from $5 \\%$ to $10 \\%$, depending on the beam momentum, and around $3 \\%$ for the particle production ratios has been achieved. These measurements are relevant for a precise evaluation of fluxes and composition of neutrino beams at accelerators. Results on the target thickness and shape dependence are also reported. Inclusive invariant cross sections in the forward direction have been derived. %An experimental accuracy of about 3\\% has been achieved on the measurements %of the $K/\\pi$ production ratios. These results will greatly reduce %the uncertainty on the estimation of the $\

  20. Cloning,expression and characterization of a single-chain antibody PS-9 targeted to pancreatic cancer

    Institute of Scientific and Technical Information of China (English)

    阎锡蕴; 田波; 李力; 袁玫

    1995-01-01

    Genes encoding single-chain antibodies have been first constructed,which consist of the heavyand light chain variable domains of antibody PS-9 joined together by a flexible peptide linker.The geneswere cloned into coat protein g3p genes of pCANTAB5 phagemids,and expressed as fusion proteins on thephage tips.Immunological assay demonstrated that the engineered antibodies specifically bound to cancer cellsLS-174-T as well as to pure bovine submaxillary gland mucin.Their specificity and affinity appeared the sameas their parent antibodies.Our results supposed that the single-chain antibodies will be a target for thediagnosis and treatment of cancer.

  1. THORIUM-BERYLLIUM ALLOYS AND METHOD OF PRODUCING SAME

    Science.gov (United States)

    Spedding, F.H.; Wilhelm, H.A.; Keller, W.H.

    1959-09-01

    >The preparation is described of thorium-berylium alloys from halides of the metals by stmultaneously reducing thorium fluoride and beryllium fluoride with calcium at approximately 650 deg C and maintaining the temperature until the thorium-beryhltum alloy separates from the slag.

  2. Thermal cycling tests of actively cooled beryllium copper joints

    Energy Technology Data Exchange (ETDEWEB)

    Roedig, M.; Duwe, R.; Linke, J.; Schuster, A.; Wiechers, B. [Forschungszentrum Juelich GmbH (Germany)

    1998-01-01

    Screening tests (steady state heating) and thermal fatigue tests with several kinds of beryllium-copper joints have been performed in an electron beam facility. Joining techniques under investigation were brazing with silver containing and silver-free braze materials, hot isostatic pressing (HIP) and diffusion bonding (hot pressing). Best thermal fatigue performance was found for the brazed samples. (author)

  3. TEM study of impurity segregations in beryllium pebbles

    Science.gov (United States)

    Klimenkov, M.; Chakin, V.; Moeslang, A.; Rolli, R.

    2014-12-01

    Beryllium is planned to be used as a neutron multiplier in the Helium-cooled Pebble Bed European concept of a breeding blanket of demonstration power reactor DEMO. In order to evaluate the irradiation performance, individual pebbles and constrained pebble beds were neutron-irradiated at temperatures typical of fusion blankets. Beryllium pebbles 1 mm in diameter produced by the rotating electrode method were subjected to a TEM study before and after irradiation at High Flux Reactor, Petten, Netherlands at 861 K. The grain size varied in a wide range from sub-micron size up to several tens of micrometers, which indicated formation bimodal grain size distribution. Based on the application of combined electron energy loss spectroscopy and energy dispersive X-ray spectroscopy methods, we suggest that impurity precipitates play an important role in controlling the mechanical properties of beryllium. The impurity elements were present in beryllium at a sub-percent concentration form beryllide particles of a complex (Fe/Al/Mn/Cr)B composition. These particles are often ordered along dislocations lines, forming several micron-long chains. It can be suggested that fracture surfaces often extended along these chains in irradiated material.

  4. TEM study of impurity segregations in beryllium pebbles

    Energy Technology Data Exchange (ETDEWEB)

    Klimenkov, M., E-mail: michael.klimenkov@kit.edu [Institute for Applied Materials – Applied Materials Physics, Karlsruhe Institute of Technology, Hermann-von-Helmholz-Platz 1, 76344 Eggenstein-Leopoldshafen (Germany); Chakin, V.; Moeslang, A. [Institute for Applied Materials – Applied Materials Physics, Karlsruhe Institute of Technology, Hermann-von-Helmholz-Platz 1, 76344 Eggenstein-Leopoldshafen (Germany); Rolli, R. [Institute for Applied Materials – Materials and Biomechanics, Karlsruhe Institute of Technology, Hermann-von-Helmholtz-Platz 1, 76344 Eggenstein-Leopoldshafen (Germany)

    2014-12-15

    Beryllium is planned to be used as a neutron multiplier in the Helium-cooled Pebble Bed European concept of a breeding blanket of demonstration power reactor DEMO. In order to evaluate the irradiation performance, individual pebbles and constrained pebble beds were neutron-irradiated at temperatures typical of fusion blankets. Beryllium pebbles 1 mm in diameter produced by the rotating electrode method were subjected to a TEM study before and after irradiation at High Flux Reactor, Petten, Netherlands at 861 K. The grain size varied in a wide range from sub-micron size up to several tens of micrometers, which indicated formation bimodal grain size distribution. Based on the application of combined electron energy loss spectroscopy and energy dispersive X-ray spectroscopy methods, we suggest that impurity precipitates play an important role in controlling the mechanical properties of beryllium. The impurity elements were present in beryllium at a sub-percent concentration form beryllide particles of a complex (Fe/Al/Mn/Cr)B composition. These particles are often ordered along dislocations lines, forming several micron-long chains. It can be suggested that fracture surfaces often extended along these chains in irradiated material.

  5. Fluorometric determination of beryllium with 2-(o-hydroxylphenyl)benzoxazole

    Energy Technology Data Exchange (ETDEWEB)

    Gladilovich, D.B.; Stolyarov, K.P.

    1985-09-01

    According to the authors, of great interest for the fluorometric determination of small quantities of beryllium is 2-(o-hydroxyphenyl)benzthiazole (HPBT). In this work, 2-(o-hydroxyphenyl)benzoaxzole (HPBO), which is an analog of HPBT and differs from it in that the sulfur atom in the heterocyclic portion of the molecule is replaced by an oxygen atom, is proposed as a reagent for the fluorometric determination of beryllium. The fluorescent reaction of HPBO with beryllium is studied in this paper, in addition to the selection of the optimum conditions for the determination and the development of a procedure for the analysis of complex objects on this basis. The reaction proceeds in aqueous ethanol medium at pH 7.2-7.5. The limit of detection is 0.6 ng/ml. Methods have been developed for the determination of 10/sup -2/% beryllium in alloys based on copper and 10/sup -3/-10/sup -4/% in standard samples of silicate rocks.

  6. Accelerated Homology-Directed Targeted Integration of Transgenes in Chinese Hamster Ovary Cells Via CRISPR/Cas9 and Fluorescent Enrichment

    DEFF Research Database (Denmark)

    Lee, Jae Seong; Grav, Lise Marie; Pedersen, Lasse Ebdrup

    2016-01-01

    Targeted gene integration into site-specific loci can be achieved in Chinese hamster ovary (CHO) cells via CRISPR/Cas9 genome editing technology and the homology-directed repair (HDR) pathway. The low efficiency of HDR often requires antibiotic selection, which limits targeted integration...

  7. Generation of Two Noradrenergic-Specific Dopamine-Beta-Hydroxylase-FLPo Knock-In Mice Using CRISPR/Cas9-Mediated Targeting in Embryonic Stem Cells.

    Directory of Open Access Journals (Sweden)

    Jenny J Sun

    Full Text Available CRISPR/Cas9 mediated DNA double strand cutting is emerging as a powerful approach to increase rates of homologous recombination of large targeting vectors, but the optimization of parameters, equipment and expertise required remain barriers to successful mouse generation by single-step zygote injection. Here, we sought to apply CRISPR/Cas9 methods to traditional embryonic stem (ES cell targeting followed by blastocyst injection to overcome the common issues of difficult vector construction and low targeting efficiency. To facilitate the study of noradrenergic function, which is implicated in myriad behavioral and physiological processes, we generated two different mouse lines that express FLPo recombinase under control of the noradrenergic-specific Dopamine-Beta-Hydroxylase (DBH gene. We found that by co-electroporating a circular vector expressing Cas9 and a locus-specific sgRNA, we could target FLPo to the DBH locus in ES cells with shortened 1 kb homology arms. Two different sites in the DBH gene were targeted; the translational start codon with 6-8% targeting efficiency, and the translational stop codon with 75% targeting efficiency. Using this approach, we established two mouse lines with DBH-specific expression of FLPo in brainstem catecholaminergic populations that are publically available on MMRRC (MMRRC_041575-UCD and MMRRC_041577-UCD. Altogether, this study supports simplified, high-efficiency Cas9/CRISPR-mediated targeting in embryonic stem cells for production of knock-in mouse lines in a wider variety of contexts than zygote injection alone.

  8. Determination of beryllium concentrations in UK ambient air

    Science.gov (United States)

    Goddard, Sharon L.; Brown, Richard J. C.; Ghatora, Baljit K.

    2016-12-01

    Air quality monitoring of ambient air is essential to minimise the exposure of the general population to toxic substances such as heavy metals, and thus the health risks associated with them. In the UK, ambient air is already monitored under the UK Heavy Metals Monitoring Network for a number of heavy metals, including nickel (Ni), arsenic (As), cadmium (Cd) and lead (Pb) to ensure compliance with legislative limits. However, the UK Expert Panel on Air Quality Standards (EPAQS) has highlighted a need to limit concentrations of beryllium (Be) in air, which is not currently monitored, because of its toxicity. The aim of this work was to analyse airborne particulate matter (PM) sampled onto filter papers from the UK Heavy Metals Monitoring Network for quantitative, trace level beryllium determination and compare the results to the guideline concentration specified by EPAQS. Samples were prepared by microwave acid digestion in a matrix of 2% sulphuric acid and 14% nitric acid, verified by the use of Certified Reference Materials (CRMs). The digested samples were then analysed by Inductively Coupled Plasma Mass Spectrometry (ICP-MS). The filters from the UK Heavy Metals Monitoring Network were tested using this procedure and the average beryllium concentration across the network for the duration of the study period was 7.87 pg m-3. The highest site average concentration was 32.0 pg m-3 at Scunthorpe Low Santon, which is significantly lower than levels that are thought to cause harm. However the highest levels were observed at sites monitoring industrial point sources, indicating that beryllium is being used and emitted, albeit at very low levels, from these point sources. Comparison with other metals concentrations and data from the UK National Atmospheric Emissions Inventory suggests that current emissions of beryllium may be significantly overestimated.

  9. Unsuspected exposure to beryllium: potential implications for sarcoidosis diagnoses.

    Science.gov (United States)

    Laczniak, Andrew N; Gross, Nathan A; Fuortes, Laurence J; Field, R William

    2014-07-21

    Exposure to Beryllium (Be) can cause sensitization (BeS) and chronic beryllium disease (CBD) in some individuals.  Even relatively low exposures may be sufficient to generate an asymptomatic, or in some cases a symptomatic, immune response. Since the clinical presentation of CBD is similar to that of sarcoidosis, it is helpful to have information on exposure to beryllium in order to reduce misdiagnosis. The purpose of this pilot study is to explore the occurrence of Be surface deposits at worksites with little or no previous reported use of commercially available Be products.  The workplaces chosen for this study represent a convenience sample of businesses in eastern Iowa. One hundred thirty-six surface dust samples were collected from 27 businesses for analysis of Be. The results were then divided into categories by the amount of detected Be according to U.S. Department of Energy guidelines as described in 10 CFR 850.30 and 10 CFR 850.31. Overall, at least one of the samples at 78% of the work sites tested contained deposited Be above the analytical limit of quantitation (0.035 µg beryllium per sample).  Beryllium was detected in 46% of the samples collected. Twelve percent of the samples exceeded 0.2 µg/100 cm² and 4% of the samples exceeded a Be concentration of 3 µg/100 cm². The findings from this study suggest that there may be a wider range and greater number of work environments that have the potential for Be exposure than has been documented previously.  These findings could have implications for the accurate diagnosis of sarcoidosis.

  10. A new beryllium ion-selective membrane electrode based on dibenzo(perhydrotriazino)aza-14-crown-4 ether.

    Science.gov (United States)

    Gupta, Vinod Kumar; Singh, Ashok Kumar; Mergu, Naveen

    2012-10-24

    Beryllium(II) selective electrodes have been fabricated based on poly(vinyl chloride) (PVC) matrix membranes containing newly synthesized neutral carrier dibenzo(perhydrotriazino)aza-14-crown-4 ethers as ionophore. Best performance was exhibited by the membrane having a composition ionophore (IIa):PVC:sodium tetraphenylborate (NaTPB):tributyl phosphate (TBP) in the ratio (w/w; mg) of 5:30:3:65. This membrane worked well over a wide concentration range 7.6×10(-6) to 1.0×10(-1) M of Be(2+) with a Nernstian slope of 30.7 mV per decade of beryllium activity. The response time of the sensor is 15s and the membrane can be used over a period of 4 months with good reproducibility. The proposed electrode works well in a wide pH range 3.0-9.0. It was successfully applied to the determination of beryllium in a mineral sample.

  11. A novel alternative to environmental monitoring to detect workers at risk for beryllium exposure-related health effects.

    Science.gov (United States)

    Fireman, Elizabeth; Lerman, Yehuda; Stark, Moshe; Pardo, Asher; Schwarz, Yehuda; Van Dyke, Michael V; Elliot, Jill; Barkes, Briana; Newman, Lee; Maier, Lisa

    2014-01-01

    The purpose of this study was to describe a methodology for surveillance and monitoring of beryllium exposure using biological monitoring to complement environmental monitoring. Eighty-three Israeli dental technicians (mean age 41.6 ± 1.36 years) and 80 American nuclear machining workers (54.9 ± 1.21 years) were enrolled. Biological monitoring was carried out by analyzing particle size (laser technique) and shape (image analysis) in 131/163 (80.3%) induced sputum samples (Dipa Analyser, Donner Tech, Or Aquiva, Israel). Environmental monitoring was carried out only in the United States (Sioutas impactor, SKC, Inc., Eighty Four, Pa.). Pulmonary function testing performance and induced sputum retrieval were done by conventional methods. Sixty-three Israeli workers and 37 American workers were followed up for at least 2 years. Biological monitoring by induced sputum indicated that a >92% accumulation of beryllium lymphocyte proliferation test result (OR 3.8, 95% CI 1.2-11.4, p = 0.015) among all participants. Environmental monitoring showed that beryllium particles were machining workers compared to dental technicians. The small fractions positively correlated with induced sputum macrophages (r = 0.21 p = 0.01) and negatively correlated with diffusion lung carbon monoxide single breath (DLCO-SB r = 0.180 p = 0.04) in all subjects. Years of exposure were positively correlated to the number of accumulated particles 2-3 μ in diameter (r = 0.2, p = 0.02) and negatively correlated to forced expiratory volume in one second/forced vital capacity findings (r = -0.18, p = 0.02). DLCO was decreased in both groups after two years of monitoring. Biological monitoring is more informative than environmental monitoring in the surveillance and monitoring of workers in beryllium industries. Induced sputum is a feasible and promising biomonitoring method that should be included in the surveillance of exposed workers.

  12. Recognition of H3K9 methylation by GLP is required for efficient establishment of H3K9 methylation, rapid target gene repression, and mouse viability

    Science.gov (United States)

    Liu, Nan; Zhang, Zhuqiang; Jiang, Yonghua; Meng, Lingjun; Xiong, Jun; Zhao, Zuodong; Zhou, Xiaohua; Li, Jia; Li, Hong; Zheng, Yong; Chen, She; Cai, Tao; Gao, Shaorong

    2015-01-01

    GLP and G9a are major H3K9 dimethylases and are essential for mouse early embryonic development. GLP and G9a both harbor ankyrin repeat domains that are capable of binding H3K9 methylation. However, the functional significance of their recognition of H3K9 methylation is unknown. Here, we report that the histone methyltransferase activities of GLP and G9a are stimulated by neighboring nucleosomes that are premethylated at H3K9. These stimulation events function in cis and are dependent on the H3K9 methylation binding activities of ankyrin repeat domains of GLP and G9a. Disruption of the H3K9 methylation-binding activity of GLP in mice causes growth retardation of embryos, ossification defects of calvaria, and postnatal lethality due to starvation of the pups. In mouse embryonic stem cells (ESCs) harboring a mutant GLP that lacks H3K9me1-binding activity, critical pluripotent genes, including Oct4 and Nanog, display inefficient establishment of H3K9me2 and delayed gene silencing during differentiation. Collectively, our study reveals a new activation mechanism for GLP and G9a that plays an important role in ESC differentiation and mouse viability. PMID:25637356

  13. Evaluation of historical beryllium abundance in soils, airborne particulates and facilities at Lawrence Livermore National Laboratory.

    Science.gov (United States)

    Sutton, Mark; Bibby, Richard K; Eppich, Gary R; Lee, Steven; Lindvall, Rachel E; Wilson, Kent; Esser, Bradley K

    2012-10-15

    Beryllium has been historically machined, handled and stored in facilities at Lawrence Livermore National Laboratory (LLNL) since the 1950s. Additionally, outdoor testing of beryllium-containing components has been performed at LLNL's Site 300 facility. Beryllium levels in local soils and atmospheric particulates have been measured over three decades and are comparable to those found elsewhere in the natural environment. While localized areas of beryllium contamination have been identified, laboratory operations do not appear to have increased the concentration of beryllium in local air or water. Variation in airborne beryllium correlates to local weather patterns, PM10 levels, normal sources (such as resuspension of soil and emissions from coal power stations) but not to LLNL activities. Regional and national atmospheric beryllium levels have decreased since the implementation of the EPA's 1990 Clean-Air-Act. Multi-element analysis of local soil and air samples allowed for the determination of comparative ratios for beryllium with over 50 other metals to distinguish between natural beryllium and process-induced contamination. Ten comparative elemental markers (Al, Cs, Eu, Gd, La, Nd, Pr, Sm, Th and Tl) that were selected to ensure background variations in other metals did not collectively interfere with the determination of beryllium sources in work-place samples at LLNL. Multi-element analysis and comparative evaluation are recommended for all workplace and environmental samples suspected of beryllium contamination. The multi-element analyses of soils and surface dusts were helpful in differentiating between beryllium of environmental origin and beryllium from laboratory operations. Some surfaces can act as "sinks" for particulate matter, including carpet, which retains entrained insoluble material even after liquid based cleaning. At LLNL, most facility carpets had beryllium concentrations at or below the upper tolerance limit determined by sampling facilities

  14. Beryllium detection in human lung tissue using electron probe X-ray microanalysis.

    Science.gov (United States)

    Butnor, Kelly J; Sporn, Thomas A; Ingram, Peter; Gunasegaram, Sue; Pinto, John F; Roggli, Victor L

    2003-11-01

    Chronic berylliosis is an uncommon disease that is caused by the inhalation of beryllium particles, dust, or fumes. The distinction between chronic berylliosis and sarcoidosis can be difficult both clinically and histologically, as both entities can have similar presentations and exhibit nonnecrotizing granulomatous inflammation of the lungs. The diagnosis of chronic berylliosis relies on a history of exposure to beryllium, roentgenographic evidence of diffuse nodular disease, and demonstration of beryllium hypersensitivity by ancillary studies, such as lymphocyte proliferation testing. Additional support may be gained by the demonstration of beryllium in lung tissue. Unlike other exogenous particulates, such as asbestos, detection of beryllium in human lung tissue is problematic. The low atomic number of beryllium usually makes it unsuitable for conventional microprobe analysis. We describe a case of chronic berylliosis in which beryllium was detected in lung tissue using atmospheric thin-window energy-dispersive X-ray analysis (ATW EDXA). A woman with a history of occupational exposure to beryllium at a nuclear weapons testing facility presented with progressive cough and dyspnea and a nodular pattern on chest roentgenograph. Open lung biopsy showed nonnecrotizing granulomatous inflammation that was histologically indistinguishable from sarcoidosis. Scanning electron microscopy and ATW EDXA demonstrated particulates containing beryllium within the granulomas. This application of EDXA offers significant advantages over existing methods of beryllium detection in that it is nondestructive, more widely available, and can be performed using routine paraffin sections.

  15. Beryllium alters lipopolysaccharide-mediated intracellular phosphorylation and cytokine release in human peripheral blood mononuclear cells.

    Science.gov (United States)

    Silva, Shannon; Ganguly, Kumkum; Fresquez, Theresa M; Gupta, Goutam; McCleskey, T Mark; Chaudhary, Anu

    2009-12-01

    Beryllium exposure in susceptible individuals leads to the development of chronic beryllium disease, a lung disorder marked by release of inflammatory cytokine and granuloma formation. We have previously reported that beryllium induces an immune response even in blood mononuclear cells from healthy individuals. In this study, we investigate the effects of beryllium on lipopolysaccharide-mediated cytokine release in blood mononuclear and dendritic cells from healthy individuals. We found that in vitro treatment of beryllium sulfate inhibits the secretion of lipopolysaccharide-mediated interleukin 10, while the release of interleukin 1beta is enhanced. In addition, not all lipopolysaccharide-mediated responses are altered, as interleukin 6 release in unaffected upon beryllium treatment. Beryllium sulfate-treated cells show altered phosphotyrosine levels upon lipopolysaccharide stimulation. Significantly, beryllium inhibits the phosphorylation of signal transducer and activator of transducer 3, induced by lipopolysaccharide. Finally, inhibitors of phosphoinositide-3 kinase mimic the effects of beryllium in inhibition of interleukin 10 release, while they have no effect on interleukin 1beta secretion. This study strongly suggests that prior exposures to beryllium could alter host immune responses to bacterial infections in healthy individuals, by altering intracellular signaling.

  16. Interaction Research on the Antiviral Molecule Dufulin Targeting on Southern Rice Black Streaked Dwarf Virus P9-1 Nonstructural Protein

    Directory of Open Access Journals (Sweden)

    Zhenchao Wang

    2015-03-01

    Full Text Available ern rice black streaked dwarf virus (SRBSDV causes severe harm to rice production. Unfortunately, studies on effective antiviral drugs against SRBSDV and interaction mechanism of antiviral molecule targeting on SRBSDV have not been reported. This study found dufulin (DFL, an ideal anti-SRBSDV molecule, and investigated the interactions of DFL targeting on the nonstructural protein P9-1. The biological sequence information and bonding characterization of DFL to four kinds of P9-1 protein were described with fluorescence titration (FT and microscale thermophoresis (MST assays. The sequence analysis indicated that P9-1 had highly-conserved C- and N-terminal amino acid residues and a hypervariable region that differed from 131 aa to 160 aa. Consequently, wild-type (WT-His-P9-1, 23 C-terminal residues truncated (TR-ΔC23-His-P9-1, 6 N-terminal residues truncated (TR-ΔN6-His-P9-1, and Ser138 site-directed (MU-138-His-P9-1 mutant proteins were expressed. The FT and MST assay results indicated that DFL bounded to WT-His-P9-1 with micromole affinity and the 23 C-terminal amino acids were the potential targeting site. This system, which combines a complete sequence analysis, mutant protein expression, and binding action evaluating system, could further advance the understanding of the interaction abilities between antiviral drugs and their targets.

  17. Investigations of the ternary system beryllium-carbon-tungsten and analyses of beryllium on carbon surfaces; Untersuchung des ternaeren Systems Beryllium-Kohlenstoff-Wolfram und Betrachtungen von Beryllium auf Kohlenstoffoberflaechen

    Energy Technology Data Exchange (ETDEWEB)

    Kost, Florian

    2009-05-25

    Beryllium, carbon and tungsten are planned to be used as first wall materials in the future fusion reactor ITER. The aim of this work is a characterization of mixed material formation induced by thermal load. To this end, model systems (layers) were prepared and investigated, which give insight into the basic physical and chemical concepts. Before investigating ternary systems, the first step was to analyze the binary systems Be/C and Be/W (bottom-up approach), where the differences between the substrates PG (pyrolytic graphite) and HOPG (highly oriented pyrolytic graphite) were of special interest. Particularly X-ray photoelectron spectroscopy (XPS), low energy ion scattering (ISS) and Rutherford backscattering spectroscopy (RBS) were used as analysis methods. Beryllium evaporated on carbon shows an island growth mode, whereas a closed layer can be assumed for layer thicknesses above 0.7 nm. Annealing of the Be/C system induces Be{sub 2}C island formation for T{>=}770 K. At high temperatures (T{>=}1170 K), beryllium carbide dissociates, resulting in (metallic) beryllium desorption. For HOPG, carbide formation starts at higher temperatures compared to PG. Activation energies for the diffusion processes were determined by analyzing the decreasing beryllium amount versus annealing time. Surface morphologies were characterized using angle-resolved XPS (ARXPS) and atomic force microscopy (AFM). Experiments were performed to study processes in the Be/W system in the temperature range from 570 to 1270 K. Be{sub 2}W formation starts at 670 K, a complete loss of Be{sub 2}W is observed at 1170 K due to dissociation (and subsequent beryllium desorption). Regarding ternary systems, particularly Be/C/W and C/Be/W were investigated, attaching importance to layer thickness (reservoir) variations. At room temperature, Be{sub 2}C, W{sub 2}C, WC and Be{sub 2}W formation at the respective interfaces was observed. Further Be{sub 2}C is forming with increasing annealing temperatures

  18. 国内外铍及含铍材料的研究进展%Advances in beryllium and beryllium-containing materials

    Institute of Scientific and Technical Information of China (English)

    许德美; 秦高梧; 李峰; 王战宏; 钟景明; 何季麟; 何力军

    2014-01-01

    The research progress of beryllium and beryllium-containing materials was reviewed in the past two decades in the world, and much effort in this work was focused on beryllium metallurgy, beryllium alloys, beryllium oxide, beryllium matrix composites and intermetallics. The advances of beryllium materials in both research and production techniques in China were summarized, especially in technique gap as compared to that in the developed countries. Finally, the new beryllium materials and their key techniques conforming to the requirements of industry were proposed in the next one decade in China.%综述近20年来国外铍及含铍材料的研究进展,主要包括铍的冶金制备、铍合金、铍和氧化铍金属基复合材料、铍金属间化合物等。概括我国在铍材料方面取得的研究与生产技术进展,以及与国外研发水平的差距。并展望未来10年我国铍及含铍材料需要重点发展的新材料以及突破的关键技术。

  19. Rac1/β-Catenin Signalling Pathway Contributes to Trophoblast Cell Invasion by Targeting Snail and MMP9

    Directory of Open Access Journals (Sweden)

    Minghua Fan

    2016-03-01

    Full Text Available Background/Aims: Preeclampsia is an idiopathic and serious complication during gestation in which placental trophoblast cells differentiate into several functional subtypes, including highly invasive extravillous trophoblasts (EVTs. Although the cause and pathogenesis of preeclampsia have remained unclear, numerous studies have suggested that the inadequacy of EVT invasion leads to imperfect uterine spiral artery remodelling, which plays a crucial role in the development of preeclampsia. Rac1, or Ras-related C3 botulinum toxin substrate 1, was found to be a key regulator of the migration, invasion uand apoptosis of various tumour cells. Because EVTs share similar invasive and migratory biological behaviours with malignant cells, this study aimed to determine whether the Rac1 signalling pathway affects trophoblast invasion and is thus involved in the pathogenesis of preeclampsia. Methods: We measured the activity of Rac1 and its downstream targets, β-catenin, Snail and MMP9 in placental tissues from patients experiencing a normal pregnancy and those with preeclampsia. Furthermore, we treated HTR-8/SVneo cells with a shRNA Rac1 vector and the β-catenin inhibitor IWP-2 and explored Rac1 signalling pathway activation as well as the effects of Snail and β-catenin on trophoblast invasion. Results: In placental samples from patients experiencing a normal pregnancy and those with preeclampsia, active Rac1 levels and MMP9 protein and mRNA levels were significantly decreased in term pregnancy samples compared to early pregnancy samples. Lower levels were found in preeclampsia samples than in normal term pregnancy samples, and these levels significantly declined in severe preeclampsia samples compared with mild preeclampsia samples. Further analyses demonstrated that both Rac1 shRNA and the β-catenin inhibitor significantly suppressed MMP9 and Snail activation in trophoblasts, thus impairing trophoblast invasion. Notably, silencing Rac1 down

  20. Modeling the systemic retention of beryllium in rat. Extrapolation to human; Modelizacion de la retencion sistemica del berilio en la rata. Extrapolacion al Hombre

    Energy Technology Data Exchange (ETDEWEB)

    Montero Prieto, M.; Vidania Munoz, R. de

    1994-07-01

    In this work, we analyzed different approaches, assayed in order to numerically describe the systemic behaviour of Beryllium. The experimental results used in this work, were previously obtained by Furchner et al. (1973), using Sprague-Dawley rats, and others animal species. Furchner's work includes the obtained model for whole body retention in rats, but not for each target organ. In this work we present the results obtained by modeling the kinetic behaviour of Beryllium in several target organs. The results of this kind of models were used in order to establish correlations among the estimated kinetic constants. The parameters of the model were extrapolated to humans and, finally, compared with others previously published. (Author) 12 refs.

  1. Beryllium Dust Generation in PISCES-B Due to Plasma-Material Interactions

    Science.gov (United States)

    Doerner, R.; Mays, C.; Hirooka, Y.; Luckhardt, S. C.; Sze, C. F.; Won, J.; Conn, R. W.

    1996-11-01

    The PISCES-B device has started plasma-beryllium experiments in its new location at U.C. San Diego. An improved controlled atmosphere enclosure was constructed to assure safe operation with beryllium materials. In the previous experimental campaign we found that a total of 600 mg of beryllium had been eroded during materials tests. This provided us with a unique opportunity to investigate the lost beryllium. Swipe sampling and vacuum sampling of the PISCES-B vacuum chamber revealed that 3% of the eroded beryllium resided as uniformly distributed loose dust within the vacuum chamber. An additional 33% of the eroded beryllium was coated onto the chamber wall. Filtering through a series of decreasing pore size meshes revealed a uniform distribution of particle sizes in the respirable range (between 10mm - 0.1mm), fewer larger particles (>50mm) were observed. This work is supported by USDOE under grant DE-FG03-95ER-54301.

  2. A joint fracture toughness evaluation of hot-pressed beryllium

    Science.gov (United States)

    Conrad, H.; Sargent, G. A.; Brown, W. F., Jr.

    1977-01-01

    Fracture toughness tests at room temperature were made on three-point bend specimens cut from hot-pressed beryllium obtained from two suppliers. The test specimens had dimensions conforming to ASTM fracture toughness standard E399-72. A total of 42 specimens were machined from each batch of material. Six specimens from each batch were then distributed to seven independent laboratories for testing. The test data from the laboratories were collected and analyzed for differences between the laboratories and the two batches of material. It is concluded that ASTM 399-72 can be used as a valid test procedure for determining the fracture toughness of beryllium, providing that Kf(max) in fatigue cracking could be up to 80 percent of the K(0) value.

  3. Ultrasonic evaluation of beryllium-copper diffusion bonds

    Energy Technology Data Exchange (ETDEWEB)

    Jamieson, E.E.

    2000-06-08

    A study was performed to compare the effectiveness of several advanced ultrasonic techniques when used to determine the strength of diffusion bonded beryllium-copper, which heretofore have each been applied to only a few material systems. The use of integrated backscatter calculations, frequency domain reflection coefficients, and time-of-flight variance was compared in their ability to characterize the bond strength in a series of beryllium-copper diffusion bond samples having a wide variation in bond quality. Correlation of integrated backscatter calculations and time-of-flight variance with bond strength was good. Some correlation of the slope of the frequency based reflection coefficient was shown for medium and high strength bonds, while its Y-intercept showed moderate correlation for all bond strengths.

  4. Beryllium dimer: a bond based on non-dynamical correlation.

    Science.gov (United States)

    El Khatib, Muammar; Bendazzoli, Gian Luigi; Evangelisti, Stefano; Helal, Wissam; Leininger, Thierry; Tenti, Lorenzo; Angeli, Celestino

    2014-08-21

    The bond nature in beryllium dimer has been theoretically investigated using high-level ab initio methods. A series of ANO basis sets of increasing quality, going from sp to spdf ghi contractions, has been employed, combined with HF, CAS-SCF, CISD, and MRCI calculations with several different active spaces. The quality of these calculations has been checked by comparing the results with valence Full-CI calculations, performed with the same basis sets. It is shown that two quasi-degenerated partly occupied orbitals play a crucial role to give a qualitatively correct description of the bond. Their nature is similar to that of the edge orbitals that give rise to the quasi-degenerated singlet-triplet states in longer beryllium chains.

  5. Fabricating thin beryllium windows for X-ray applications

    Science.gov (United States)

    Truhan, John J.; Wagner, Lawrence M.

    1980-10-01

    X-ray windows for diagnostics into vacuum chambers are commonly made of beryllium, which must be as thin as possible to minimize attenuation of the X rays. The windows must be bonded to mounting flanges, and the bond must be leak-tight and able to withstand a pressure differential of one atmosphere. A solid-state bonding process can be used to attach windows of thickness from 0.025 down to 0.015 mm. The process bonds the beryllium window, a silver intermediate layer, and the mounting flange together using compression and heat. The process is not sensitive to the bonding parameters; usual ranges are: pressures of 83-172 MPa, temperatures of 750-950 K, and holding times of 5-60 min. Unsuccessful bonds can often be repaired, or parts can be salvaged for re-use. A variety of window geometries can be accommodated.

  6. VLT beryllium secondary mirror no. 1: performance review

    Science.gov (United States)

    Cayrel, Marc

    1998-08-01

    The four Very Large Telescope secondary mirrors are 1.2-m Beryllium lightweight convex mirrors. REOSC has been selected for the design and manufacturing of the optics and of their supporting system. The first mirror unit has been delivered in September, 1997. Operating from visible to near infrared, the mirror defines the telescope aperture stop and may be chopped during observation. The optical requirements are tight and a high stiffness, low weight and inertia are requested as well. Using beryllium is a technical challenge for such a large optic manufacturing, in particular regarding its stability. The requirements and design are presented, we review the mirror manufacturing steps: blank production, machining, grinding, Nickel plating, polishing, integration and testing. The optical quality control method, a problem for large convex mirrors control, is detailed. The results of acceptance testing of mirror No. 1 are summarized, we present conclusions about the mirror figure stability. The status of the three additional mirrors manufacturing is presented to conclude.

  7. Multiscale modelling of hydrogen behaviour on beryllium (0001 surface

    Directory of Open Access Journals (Sweden)

    Ch. Stihl

    2016-12-01

    Full Text Available Beryllium is proposed to be a neutron multiplier and plasma facing material in future fusion devices. Therefore, it is crucial to acquire an understanding of the microscopic mechanisms of tritium accumulation and release as a result of transmutation processes that Be undergoes under neutron irradiation. A multiscale simulation of ad- and desorption of hydrogen isotopes on the beryllium (0001 surface is developed. It consists of ab initio calculations of certain H adsorption configurations, a suitable cluster expansion approximating the energies of arbitrary configurations, and a kinetic Monte Carlo method for dynamic simulations of adsorption and desorption. The processes implemented in the kinetic Monte Carlo simulation are deduced from further ab initio calculations comprising both, static relaxation as well as molecular dynamics runs. The simulation is used to reproduce experimental data and the results are compared and discussed. Based on the observed results, proposals for a refined model are made.

  8. Beryllium uptake and related biological effects studied in THP-1 differentiated macrophages.

    Science.gov (United States)

    Ding, Jian; Lin, Lin; Hang, Wei; Yan, Xiaomei

    2009-11-01

    Investigation of cellular uptake of metal compounds is important in understanding metal-related toxicity and diseases. Inhalation of beryllium aerosols can cause chronic beryllium disease, a progressive, granulomatous fibrosis of the lung. Studies in laboratory animals and cultured animal cells indicate that alveolar macrophages take up beryllium compounds and participate in a hypersensitivity immune response to a beryllium-containing antigen. In the present work, human monocyte cell line THP-1 was induced with phorbol myristate acetate to differentiate into a macrophage. This cell with characteristics of human alveolar macrophages was employed to study cellular beryllium uptake and related biological effects. Morphological changes, phagocytosis of fluorescent latex beads, and cell surface CD14 expression were used to verify the successful differentiation of THP-1 monocytes into macrophages. An improved mass spectrometry method for quantitative analysis of intracellular beryllium as opposed to the traditional radioisotopic approach was developed using ICP-MS. The influence of the solubility of beryllium compounds, exposure duration, and beryllium concentration on the incorporation of beryllium was studied. Our data indicated that the uptake of particulate BeO was much more significant than that of soluble BeSO(4), suggesting the major cellular uptake pathway is phagocytosis. Nevertheless, subsequent DAPI nuclear staining and PARP cleavage study indicated that beryllium uptake had a negligible effect on the apoptosis of THP-1 macrophages compared to the unstimulated macrophage control. Meanwhile, no substantial variation of tumour necrosis factor-alpha production was observed for THP-1 macrophages upon beryllium exposure. These data imply alveolar macrophages could have some level of tolerance to beryllium and this may explain why most Be-exposed individuals remain healthy throughout life.

  9. Studies on extraction of beryllium from thiocyanate solutions by quaternary ammonium halides.

    Science.gov (United States)

    El-Yamani, I S; El-Messieh, E N

    A 0.4M tricaprylmethylammonium chloride solution in n-hexane was used for the quantitative extraction of beryllium from hydrochloric acid (pH 3) and 5M potassium thiocyanate. Beryllium was stripped from the organic phase with 1M sodium hydroxide, then determined volumetrically with bismuthyl perchlorate and bromocresol green indicator. Beryllium was extracted in presence of a large number of elements which are usually associated with it in beryl and in fission products of nuclear fuel.

  10. Minority Carrier Lifetime in Beryllium-Doped InAs/InAsSb Strained Layer Superlattices

    Science.gov (United States)

    2014-06-03

    SECURITY CLASSIFICATION OF: Minority carrier lifetimes in undoped and Beryllium -doped Type-2 Ga-free, InAs/InAsSb strained layer superlattices (SLS) with...is unlimited. Minority Carrier Lifetime in Beryllium -Doped InAs/InAsSb Strained Layer Superlattices The views, opinions and/or findings contained in...Brook University W-5510 Melville Library West Sayville, NY 11796 -3362 1 ABSTRACT Minority Carrier Lifetime in Beryllium -Doped InAs/InAsSb Strained

  11. Presence of Beryllium (Be) in urban soils: human health risk

    Energy Technology Data Exchange (ETDEWEB)

    Pena, A.; Gonzalez, M. J.; Lobo, M. C.

    2009-07-01

    Berylium (Be) is, together with As, Cd, Hg, Pb and Ti, one of the trace elements more toxic for human being (Vaessen) and Szteke, 2000; Yaman and Avci, 2006), but in spite of the exponential increment of its applications during the last decades, surprisingly there isn't hardly information about its presence and environmental distribution. The aim of this work is to evaluate the presence of Beryllium in urban soils in Alcala de Henares, (Madrid Spain).

  12. Beryllium, Lithium and Oxygen Abundances in F-type Stars

    CERN Document Server

    García-López, R J; Pérez de Taoro, M R; Casares, C; Rasilla, J L; Rebolo, R; Allende-Prieto, C

    1997-01-01

    Beryllium and oxygen abundances have been derived in a sample of F-type field stars for which lithium abundances had been measured previously, with the aim of obtaining observational constraints to discriminate between the different mixing mechanisms proposed. Mixing associated with the transport of angular momentum in the stellar interior and internal gravity waves within the framework of rotating evolutionary models, appear to be promising ways to explain the observations.

  13. Impact of HFIR LEU Conversion on Beryllium Reflector Degradation Factors

    Energy Technology Data Exchange (ETDEWEB)

    Ilas, Dan [ORNL

    2013-10-01

    An assessment of the impact of low enriched uranium (LEU) conversion on the factors that may cause the degradation of the beryllium reflector is performed for the High Flux Isotope Reactor (HFIR). The computational methods, models, and tools, comparisons with previous work, along with the results obtained are documented and discussed in this report. The report documents the results for the gas and neutronic poison production, and the heating in the beryllium reflector for both the highly enriched uranium (HEU) and LEU HFIR configurations, and discusses the impact that the conversion to LEU may have on these quantities. A time-averaging procedure was developed to calculate the isotopic (gas and poisons) production in reflector. The sensitivity of this approach to different approximations is gauged and documented. The results show that the gas is produced in the beryllium reflector at a total rate of 0.304 g/cycle for the HEU configuration; this rate increases by ~12% for the LEU case. The total tritium production rate in reflector is 0.098 g/cycle for the HEU core and approximately 11% higher for the LEU core. A significant increase (up to ~25%) in the neutronic poisons production in the reflector during the operation cycles is observed for the LEU core, compared to the HEU case, for regions close to the core s horizontal midplane. The poisoning level of the reflector may increase by more than two orders of magnitude during long periods of downtime. The heating rate in the reflector is estimated to be approximately 20% lower for the LEU core than for the HEU core. The decrease is due to a significantly lower contribution of the heating produced by the gamma radiation for the LEU core. Both the isotopic (gas and neutronic poisons) production and the heating rates are spatially non-uniform throughout the beryllium reflector volume. The maximum values typically occur in the removable reflector and close to the midplane.

  14. The beryllium quandary: will the lower exposure limits spur new developments in sampling and analysis?

    Energy Technology Data Exchange (ETDEWEB)

    Brisson, Michael

    2013-06-03

    At the time this article was written, new rulemakings were under consideration at OSHA and the U.S. Department of Energy (DOE) that would propose changes to occupational exposure limits for beryllium. Given these developments, it’s a good time to review the tools and methods available to IHs for assessing beryllium air and surface contamination in the workplace—what’s new and different, and what’s tried and true. The article discusses limit values and action levels for beryllium, problematic aspects of beryllium air sampling, sample preparation, sample analysis, and data evaluation.

  15. Vacuum Brazing of Beryllium Copper Components for the National Ignition Facility

    Energy Technology Data Exchange (ETDEWEB)

    Tyhurst, C.C.; Cunningham, M.A.

    2002-06-04

    A process for vacuum brazing beryllium copper anode assemblies was required for the Plasma Electrode Pockels Cell System, or PEPC, a component for the National Ignition Facility (NIF). Initial problems with the joint design and wettability of the beryllium copper drove some minor design changes. Brazing was facilitated by plating the joint surface of the beryllium copper rod with silver 0.0006 inch thick. Individual air sampling during processing and swipe tests of the furnace interior after brazing revealed no traceable levels of beryllium.

  16. Proteomic analysis of beryllium-induced genotoxicity in an Escherichia coli mutant model system.

    Science.gov (United States)

    Taylor-McCabe, Kirsten J; Wang, Zaolin; Sauer, Nancy N; Marrone, Babetta L

    2006-03-01

    Beryllium is the second lightest metal, has a high melting point and high strength-to-weight ratio, and is chemically stable. These unique chemical characteristics make beryllium metal an ideal choice as a component material for a wide variety of applications in aerospace, defense, nuclear weapons, and industry. However, inhalation of beryllium dust or fumes induces significant health effects, including chronic beryllium disease and lung cancer. In this study, the mutagenicity of beryllium sulfate (BeSO(4)) and the comutagenicity of beryllium with a known mutagen 1-methyl-3-nitro-1-nitrosoguanidine (MNNG) were evaluated using a forward mutant detection system developed in Escherichia coli. In this system, BeSO(4) was shown to be weakly mutagenic alone and significantly enhanced the mutagenicity of MNNG up to 3.5-fold over MNNG alone. Based on these results a proteomic study was conducted to identify the proteins regulated by BeSO(4). Using the techniques of 2-DE and oMALDI-TOF MS, we successfully identified 32 proteins being differentially regulated by beryllium and/or MNNG in the E. coli test system. This is the first study to describe the proteins regulated by beryllium in vitro, and the results suggest several potential pathways for the focus of further research into the mechanisms underlying beryllium-induced genotoxicity.

  17. Chest wall shrapnel-induced beryllium-sensitization and associated pulmonary disease.

    Science.gov (United States)

    Fireman, E; Shai, A Bar; Lerman, Y; Topilsky, M; Blanc, P D; Maier, L; Li, L; Chandra, S; Abraham, J M; Fomin, I; Aviram, G; Abraham, J L

    2012-10-01

    Chronic beryllium disease (CBD) is an exposure-related granulomatous disease mimicking sarcoidosis. Beryllium exposure-associated disease occurs mainly via inhalation, but skin may also be a source of sensitization. A 65-year-old male with a history of war-related shrapnel wounds was initially diagnosed with pulmonary sarcoidosis. Twenty years later, the possibility of a metal-related etiology for the lung disease was raised. A beryllium lymphocyte proliferation test, elemental analysis of removed shrapnel, and genetic studies were consistent with a diagnosis of CBD. This case demonstrates that retained beryllium-containing foreign bodies can be linked to a pathophysiologic response in the lung consistent with CBD.

  18. A diethylhydroxylaminate based mixed lithium/beryllium aggregate

    Energy Technology Data Exchange (ETDEWEB)

    Berger, Raphael J.F. [Paris-Lodron Universitaet Salzburg (Austria). Fachbereich fuer Materialwissenschaften und Physik; Jana, Surajit [Asansol Girls College, West-Bengal (India). Dept. of Chemistry; Froehlich, Roland [Muenster Univ. (Germany). Organisch-Chemisches Inst.; Mitzel, Norbert W. [Bielefeld Univ. (Germany). Anorganische Chemie und Strukturchemie

    2015-07-01

    A mixed lithium/beryllium diethylhydroxylaminate compound containing {sup n}butyl beryllium units of total molecular composition {sup n}Be(ONEt{sub 2}){sub 2} [(LiONEt{sub 2}){sup 2} {sup n}BuBeONEt{sub 2}]{sub 2} (1) was isolated from a reaction mixture of {sup n}butyl lithium, N,N-diethylhydroxylamine and BeCl{sub 2} in diethylether/thf. The crystal structure of 1 has been determined by X-ray diffraction. The aggregate is composed of two ladder-type subunits connected in a beryllium-centered distorted tetrahedron of four oxygen atoms. Only the lithium atoms are engaged in coordination with the nitrogen donor atoms. The DFT calculations support the positional occupation determined for Li and Be in the crystal structure. The DFT and the solid-state structure are in excellent agreement, indicating only weak intermolecular interactions in the solid state. Structural details of metal atom coordination are discussed.

  19. Transgenic Clustered Regularly Interspaced Short Palindromic Repeat/Cas9-Mediated Viral Gene Targeting for Antiviral Therapy of Bombyx mori Nucleopolyhedrovirus.

    Science.gov (United States)

    Chen, Shuqing; Hou, Chengxiang; Bi, Honglun; Wang, Yueqiang; Xu, Jun; Li, Muwang; James, Anthony A; Huang, Yongping; Tan, Anjiang

    2017-04-15

    We developed a novel antiviral strategy by combining transposon-based transgenesis and the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated 9 (Cas9) system for the direct cleavage of Bombyx mori nucleopolyhedrovirus (BmNPV) genome DNA to promote virus clearance in silkworms. We demonstrate that transgenic silkworms constitutively expressing Cas9 and guide RNAs targeting the BmNPV immediate early-1 (ie-1) and me53 genes effectively induce target-specific cleavage and subsequent mutagenesis, especially large (∼7-kbp) segment deletions in BmNPV genomes, and thus exhibit robust suppression of BmNPV proliferation. Transgenic animals exhibited higher and inheritable resistance to BmNPV infection than wild-type animals. Our approach will not only contribute to modern sericulture but also shed light on future antiviral therapy.IMPORTANCE Pathogen genome targeting has shown its potential in antiviral research. However, transgenic CRISPR/Cas9 system-mediated viral genome targeting has not been reported as an antiviral strategy in a natural animal host of a virus. Our data provide an effective approach against BmNPV infection in a real-world biological system and demonstrate the potential of transgenic CRISPR/Cas9 systems in antiviral research in other species.

  20. Theoretical research on enhancement of gain for Ni-like Ag 13.9 nm x-ray laser using a new two-layer target

    Institute of Scientific and Technical Information of China (English)

    Zhang Guo-Ping; Zhang Tan-Xin; Zheng Wu-Di; Qiao Xiu-Mei

    2007-01-01

    For experiments such as on Ni-like Ag x-ray laser, driven by 1ω laser, the gain region is only several nrn depth near the target surface, this paper proposes a new two-layer target, in which a thin layer (several nm depth) of silver is plated on the surface of some other materials. Furthermore, the Ni-like Ag 13.9 nm x-ray laser produced by three new kinds of two-layer target with CH, Al and Ge as foundation, was theoretically studied.

  1. A Novel Alternative to Environmental Monitoring to Detect Workers at Risk for Beryllium Exposure-Related Health Effects

    OpenAIRE

    2014-01-01

    The purpose of this study was to describe a methodology for surveillance and monitoring of beryllium exposure using biological monitoring to complement environmental monitoring. Eighty-three Israeli dental technicians (mean age 41.6 ± 1.36 years) and 80 American nuclear machining workers (54.9 ± 1.21 years) were enrolled. Biological monitoring was carried out by analyzing particle size (laser technique) and shape (image analysis) in 131/163 (80.3%) induced sputum samples (Dipa Analyser, Donne...

  2. Beryllium geochemistry constraints on the hydraulic behavior of mud volcanoes: the Trinidad Island case

    Science.gov (United States)

    Castrec-Rouelle, M.; Bourlès, D. L.; Boulègue, J.; Dia, A. N.

    2002-11-01

    To constrain Trinidad mud volcanoes hydraulic behavior, both cosmogenic 10Be ( t1/2=1.5 Myr) and 9Be concentrations have been measured in fluid and associated expelled mud. As previously evidenced [A.N. Dia, M. Castrec, J. Boulègue, P. Comeau, Trinidad Mud Volcanoes: where do the expelled fluids come from? Geochim. Cosmochim. Acta 63 (1999) 1023-1038] from δ 18O values and Cl concentrations, 9Be concentrations in the fluids mostly reflect the mixing of two deep components: REM I and REM II. REM I (δ 18O=10.5‰, Cl≈275 mM and 9Be≈0.05 nM) has characteristics of a continental fluid while REM II (δ 18O=3‰, Cl≈350 mM and 9Be≈1 nM) results from seawater-volcanogenic derived sediment interaction. Although 10Be concentrations in the fluid samples are close to the detection limit, the distribution of both beryllium isotopes between the hydroxylamine leachable and residual phases indicates exchange reaction with fluid younger than 15 Myr. Comparison between the lowest REM I 10Be/ 9Be ratio in fluid recorded by the hydroxylamine leachable phase (TD5 mud sample) and the 10Be/ 9Be ratio representative of meteoric contribution in the recharge area (TD8 fluid sample) yields a circulation rate of REM I fluid in the Trinidad mud volcanoes of several 10 -1 m/yr.

  3. Homeobox A9 directly targeted by miR-196b regulates aggressiveness through nuclear Factor-kappa B activity in non-small cell lung cancer cells.

    Science.gov (United States)

    Yu, Seong-Lan; Lee, Dong Chul; Sohn, Hyun Ahm; Lee, Soo Young; Jeon, Hyo Sung; Lee, Joon H; Park, Chang Gyo; Lee, Hoi Young; Yeom, Young Il; Son, Ji Woong; Yoon, Yoo Sang; Kang, Jaeku

    2016-12-01

    MicroRNAs (miRNAs) are recognized as crucial posttranscriptional regulators of gene expression, and play critical roles as oncogenes or tumor suppressors in various cancers. Here, we show that miR-196b is upregulated in mesenchymal-like-state non-small cell lung cancer (NSCLC) cells and lung cancer tissues. Moreover, miR-196b upregulation stimulates cell invasion and a change in cell morphology to a spindle shape via loss of cell-to-cell contacts. We identified homeobox A9 (HOXA9) as a target gene of miR-196b by using public databases such as TargetScan, miRDB, and microRNA.org. HOXA9 expression is inversely correlated with miR-196b levels in clinical NSCLC samples as compared to that in corresponding control samples, and with the migration and invasion of NSCLC cells. Ectopic expression of HOXA9 resulted in a suppression of miR-196b-induced cell invasion, and HOXA9 reexpression increased E-cadherin expression. Furthermore, HOXA9 potently attenuated the expression of snail family zinc finger 2 (SNAI2/SLUG) and matrix metallopeptidase 9 (MMP9) by controlling the binding of nuclear factor-kappa B to the promoter of SLUG and MMP9 genes, respectively. Therefore, we suggest that HOXA9 plays a central role in controlling the aggressive behavior of lung cancer cells and that miR-196b can serve as a potential target for developing anticancer agents. © 2015 Wiley Periodicals, Inc.

  4. 植物CRISPR/Cas9基因组编辑系统与突变分析%CRISPR/Cas9-based genome editing systems and the analysis of targeted genome mutations in plants

    Institute of Scientific and Technical Information of China (English)

    马兴亮; 刘耀光

    2016-01-01

    Targeted genomic editing technologies use programmable DNA nucleases to cleave genomic target sites, thus inducing targeted mutations in the genomes. The newly prevailed clustered regularly interspaced short palin-dromic repeats/CRISPR-associated protein 9 (CRISPR/Cas9) system that consists of the Cas9 nuclease and single guide RNA (sgRNA) has the advantages of simplicity and high efficiency as compared to other programmable DNA nuclease systems such as zinc finger nucleases (ZFNs) and transcription activator like effector nucleases (TALENs). Currently, a number of cases have been reported on the application of the CRISPR/Cas9 genomic editing technology in plants. In this review, we summarize the strategies for preparing the Cas9 and sgRNA expression constructs, the transformation method for obtaining targeted mutations, the efficiency and features of the resulting mutations and the methods for detecting or genotyping of the mutation sites. We also discuss the existing problems and perspectives of CRISPR/Cas9-based genomic editing in plants.%基因组定点编辑技术通过可编码核酸酶切割基因组特定位点,进而诱导基因组定点突变.CRISPR/Cas9(Clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9)基因组编辑系统由Cas9核酸酶以及sgRNA(Single guide RNA)组成,与其他可编码核酸酶系统如锌指核酸酶(Zinc finger nucleases,ZFNs)和类转录激活因子效应物核酸酶(Transcription activator-like effector nucleases,TALENs)相比具有更简便的操作性和更高的基因组定点编辑效率.目前在植物中已有多例应用CRISPR/Cas9系统进行基因组编辑的报道.本文从Cas9基因与sgRNA表达载体的构建策略,获得基因组定点编辑突变体的转化方法、突变的效率和特征、突变的检测方法等方面进行了总结,最后对植物中利用CRISPR/Cas9系统进行基因组编辑存在的问题以及发展前景进行了讨论.

  5. Beryllium metal I. experimental results on acute oral toxicity, local skin and eye effects, and genotoxicity.

    Science.gov (United States)

    Strupp, Christian

    2011-01-01

    The toxicity of soluble metal compounds is often different from that of the parent metal. Since no reliable data on acute toxicity, local effects, and mutagenicity of beryllium metal have ever been generated, beryllium metal powder was tested according to the respective Organisation for Economical Co-Operation and Development (OECD) guidelines. Acute oral toxicity of beryllium metal was investigated in rats and local effects on skin and eye in rabbits. Skin-sensitizing properties were investigated in guinea pigs (maximization method). Basic knowledge about systemic bioavailability is important for the design of genotoxicity tests on poorly soluble substances. Therefore, it was necessary to experimentally compare the capacities of beryllium chloride and beryllium metal to form ions under simulated human lung conditions. Solubility of beryllium metal in artificial lung fluid was low, while solubility in artificial lysosomal fluid was moderate. Beryllium chloride dissolution kinetics were largely different, and thus, metal extracts were used in the in vitro genotoxicity tests. Genotoxicity was investigated in vitro in a bacterial reverse mutagenicity assay, a mammalian cell gene mutation assay, a mammalian cell chromosome aberration assay, and an unscheduled DNA synthesis (UDS) assay. In addition, cell transformation was tested in a Syrian hamster embryo cell assay, and potential inhibition of DNA repair was tested by modification of the UDS assay. Beryllium metal was found not to be mutagenic or clastogenic based on the experimental in vitro results. Furthermore, treatment with beryllium metal extracts did not induce DNA repair synthesis, indicative of no DNA-damaging potential of beryllium metal. A cell-transforming potential and a tendency to inhibit DNA repair when the cell is severely damaged by an external stimulus were observed. Beryllium metal was also found not to be a skin or eye irritant, not to be a skin sensitizer, and not to have relevant acute oral

  6. Release of beryllium from mineral ores in artificial lung and skin surface fluids.

    Science.gov (United States)

    Duling, Matthew G; Stefaniak, Aleksandr B; Lawrence, Robert B; Chipera, Steve J; Virji, M Abbas

    2012-06-01

    Exposure to some manufactured beryllium compounds via skin contact or inhalation can cause sensitization. A portion of sensitized persons who inhale beryllium may develop chronic beryllium disease (CBD). Little is understood about exposures to naturally occurring beryllium minerals. The purpose of this study was to assess the bioaccessibility of beryllium from bertrandite ore. Dissolution of bertrandite from two mine pits (Monitor and Blue Chalk) was evaluated for both the dermal and inhalation exposure pathways by determining bioaccessibility in artificial sweat (pH 5.3 and pH 6.5), airway lining fluid (SUF, pH 7.3), and alveolar macrophage phagolysosomal fluid (PSF, pH 4.5). Significantly more beryllium was released from Monitor pit ore than Blue Chalk pit ore in artificial sweat buffered to pH 5.3 (0.88 ± 0.01% vs. 0.36 ± 0.00%) and pH 6.5 (0.09 ± 0.00% vs. 0.03 ± 0.01%). Rates of beryllium released from the ores in artificial sweat were faster than previously measured for manufactured forms of beryllium (e.g., beryllium oxide), known to induce sensitization in mice. In SUF, levels of beryllium were below the analytical limit of detection. In PSF, beryllium dissolution was biphasic (initial rapid diffusion followed by latter slower surface reactions). During the latter phase, dissolution half-times were 1,400 to 2,000 days, and rate constants were ~7 × 10(-10) g/(cm(2)·day), indicating that bertrandite is persistent in the lung. These data indicate that it is prudent to control skin and inhalation exposures to bertrandite dusts.

  7. p38 Mitogen-Activated Protein Kinase in beryllium-induced dendritic cell activation.

    Science.gov (United States)

    Li, L; Huang, Z; Gillespie, M; Mroz, P M; Maier, L A

    2014-12-01

    Dendritic cells (DC) play a role in the regulation of immune responses to haptens, which in turn impact DC maturation. Whether beryllium (Be) is able to induce DC maturation and if this occurs via the MAPK pathway is not known. Primary monocyte-derived DCs (moDCs) models were generated from Be non-exposed healthy volunteers as a non-sensitized cell model, while PBMCs from BeS (Be sensitized) and CBD (chronic beryllium disease) were used as disease models. The response of these cells to Be was evaluated. The expression of CD40 was increased significantly (pBeSO₄-stimulation. BeSO₄ induced p38MAPK phosphorylation, while IκB-α was degraded in Be-stimulated moDCs. The p38 MAPK inhibitor SB203580 blocked Be-induced NF-κB activation in moDCs, suggesting that p38MAPK and NF-κB are dependently activated by BeSO₄. Furthermore, in BeS and CBD subjects, SB203580 downregulated Be-stimulated proliferation in a dose-dependent manner, and decreased Be-stimulated TNF-α and IFNγ cytokine production. Taken together, this study suggests that Be-induces non-sensitized Glu69+ DCs maturation, and that p38MAPK signaling is important in the Be-stimulated DCs activation as well as subsequent T cell proliferation and cytokine production in BeS and CBD. In total, the MAPK pathway may serve as a potential therapeutic target for human granulomatous lung diseases.

  8. Raman microscopy investigation of beryllium materials

    Science.gov (United States)

    Pardanaud, C.; Rusu, M. I.; Giacometti, G.; Martin, C.; Addab, Y.; Roubin, P.; Lungu, C. P.; Porosnicu, C.; Jepu, I.; Dinca, P.; Lungu, M.; Pompilian, O. G.; Mateus, R.; Alves, E.; Rubel, M.; contributors, JET

    2016-02-01

    We report for the first time on the ability of Raman microscopy to give information on the structure and composition of Be related samples mimicking plasma facing materials that will be found in ITER. For that purpose, we investigate two types of material. First: Be, W, Be1W9, and Be5W5 deposits containing a few percents of D or N, and second: a Mo mirror exposed to plasma in the main JET chamber (in the framework of the first mirror test in JET with ITER-like wall). We performed atomic quantifications using ion beam analysis for the first samples. We also did atomic force microscopy. We found defect induced Raman bands in Be, Be1W9, and Be5W5 deposits. Molybdenum oxide has been identified showing an enhancement due to a resonance effect in the UV domain.

  9. The dendritic cell subtype-restricted C-type lectin Clec9A is a target for vaccine enhancement

    OpenAIRE

    Caminschi, Irina; Proietto, Anna I.; Ahmet, Fatma; Kitsoulis, Susie; Shin Teh, Joo; Lo, Jennifer C. Y.; Rizzitelli, Alexandra; Wu, Li; Vremec, David; van Dommelen, Serani L.H.; Campbell, Ian K.; Maraskovsky, Eugene; Braley, Hal; Davey, Gayle M.; Mottram, Patricia

    2008-01-01

    A novel dendritic cell (DC)–restricted molecule, Clec9A, was identified by gene expression profiling of mouse DC subtypes. Based on sequence similarity, a human ortholog was identified. Clec9A encodes a type II membrane protein with a single extracellular C-type lectin domain. Both the mouse Clec9A and human CLEC9A were cloned and expressed, and monoclonal antibodies (mAbs) against each were generated. Surface staining revealed that Clec9A was selective for mouse DCs and was restricted to the...

  10. mCAL: A New Approach for Versatile Multiplex Action of Cas9 Using One sgRNA and Loci Flanked by a Programmed Target Sequence.

    Science.gov (United States)

    Finnigan, Gregory C; Thorner, Jeremy

    2016-07-07

    Genome editing exploiting CRISPR/Cas9 has been adopted widely in academia and in the biotechnology industry to manipulate DNA sequences in diverse organisms. Molecular engineering of Cas9 itself and its guide RNA, and the strategies for using them, have increased efficiency, optimized specificity, reduced inappropriate off-target effects, and introduced modifications for performing other functions (transcriptional regulation, high-resolution imaging, protein recruitment, and high-throughput screening). Moreover, Cas9 has the ability to multiplex, i.e., to act at different genomic targets within the same nucleus. Currently, however, introducing concurrent changes at multiple loci involves: (i) identification of appropriate genomic sites, especially the availability of suitable PAM sequences; (ii) the design, construction, and expression of multiple sgRNA directed against those sites; (iii) potential difficulties in altering essential genes; and (iv) lingering concerns about "off-target" effects. We have devised a new approach that circumvents these drawbacks, as we demonstrate here using the yeast Saccharomyces cerevisiae First, any gene(s) of interest are flanked upstream and downstream with a single unique target sequence that does not normally exist in the genome. Thereafter, expression of one sgRNA and cotransformation with appropriate PCR fragments permits concomitant Cas9-mediated alteration of multiple genes (both essential and nonessential). The system we developed also allows for maintenance of the integrated, inducible Cas9-expression cassette or its simultaneous scarless excision. Our scheme-dubbed mCAL for " M: ultiplexing of C: as9 at A: rtificial L: oci"-can be applied to any organism in which the CRISPR/Cas9 methodology is currently being utilized. In principle, it can be applied to install synthetic sequences into the genome, to generate genomic libraries, and to program strains or cell lines so that they can be conveniently (and repeatedly

  11. Quasi-elastic scattering of a secondary sup 6 He beam on a sup 9 Be target at 25 MeV/nucleon

    CERN Document Server

    Chen Tao; Li Zhi Huan; Jiang Dong Xing; Hua Hui; Li Xiang Qing; Wang Quan Jin; Ge Yuch Eng; Pang Dan Yang; Di Zhenyu; Jin Ge; Xiao Guo Qing; Guo Zhong Yan; Xiao Zhi Gang; Wang Hong Wei; Zhang Bao Guo; Wu He Yu; Li Jia Xing; Sun Zhi Yu; Zhan Wen Long

    2002-01-01

    The quasi-elastic scattering of a secondary sup 6 He beam (25 MeV/n) on a sup 9 Be target has been measured for the first time with the application of a sophisticated tracking detector system. The angular distribution is reported. A phenomenological optical potential is obtained by fitting the experimental data, which encourages more accurate experimental measurements

  12. Quasi-elastic Scattering of a Secondary 6He Beam on a 9Be Target at 25MeV/Nucleon

    Institute of Scientific and Technical Information of China (English)

    陈陶; 叶沿林; 李智焕; 江栋兴; 华辉; 李湘庆; 王全进; 葛榆成; 庞丹阳; 狄振宇; 靳根明; 肖国青; 郭忠言; 肖志刚; 王宏伟; 张保国; 吴和宇; 李家兴; 孙志宇; 詹文龙

    2002-01-01

    The quasi-elastic scattering of a secondary 6He beam (25 MeV/n) on a 9Be target has been measured for the firsttime with the application of a sophisticated tracking detector system. The angular distribution is reported. Aphenomenological optical potential is obtained by fitting the experimental data, which encourages more accurateexperimental measurements.

  13. 通过CRISPR/Cas 9技术打靶兔Myostatin基因%Targeting Rabbit Myostatin Gene through CRISPR/Cas 9 Technology

    Institute of Scientific and Technical Information of China (English)

    柳婧; 潘求真; 赵文博; 王静宜; 宗严; 连正兴

    2015-01-01

    细菌和古生菌利用自身的获得性免疫系统(CRISPR)抵御外来侵略,使外源DNA降解.为了基因突变兔子成纤维细胞的Myostatin基因,研究构建了CRISPR和gRNA质粒,当Cas9与gRNA摩尔数之比分别为1:2、1:1时进行转染到兔子成纤维细胞中,结果显示有打靶效率差异,经过鉴定均有碱基突变.结果表明:利用(CRISPR/Cas9)系统可成功突变目的基因.

  14. 20 CFR 30.615 - What type of tort suits filed against beryllium vendors or atomic weapons employers may...

    Science.gov (United States)

    2010-04-01

    ... beryllium vendors or atomic weapons employers may disqualify certain claimants from receiving benefits under... Special Provisions Effect of Tort Suits Against Beryllium Vendors and Atomic Weapons Employers § 30.615 What type of tort suits filed against beryllium vendors or atomic weapons employers may...

  15. 20 CFR 30.507 - What compensation will be provided to covered Part B employees who only establish beryllium...

    Science.gov (United States)

    2010-04-01

    ... Part B employees who only establish beryllium sensitivity under Part B of EEOICPA? 30.507 Section 30... Part B employees who only establish beryllium sensitivity under Part B of EEOICPA? The establishment of beryllium sensitivity does not entitle a covered Part B employee, or the eligible surviving beneficiary...

  16. 20 CFR 30.205 - What are the criteria for eligibility for benefits relating to beryllium illnesses covered under...

    Science.gov (United States)

    2010-04-01

    ... benefits relating to beryllium illnesses covered under Part B of EEOICPA? 30.205 Section 30.205 Employees... Relating to Covered Beryllium Illness Under Part B of Eeoicpa § 30.205 What are the criteria for eligibility for benefits relating to beryllium illnesses covered under Part B of EEOICPA? To...

  17. DETERMINING BERYLLIUM IN DRINKING WATER BY GRAPHITE FURNACE ATOMIC ABSORPTION SPECTROSCOPY

    Science.gov (United States)

    A direct graphite furnace atomic absorption spectroscopy method for the analysis of beryllium in drinking water has been derived from a method for determining beryllium in urine. Ammonium phosphomolybdate and ascorbic acid were employed as matrix modifiers. The matrix modifiers s...

  18. The development and advantages of beryllium capsules for the National Ignition Facility

    Energy Technology Data Exchange (ETDEWEB)

    Wilson, D.C.; Bradley, P.A.; Hoffman, N.M. [Los Alamos National Lab., NM (United States)] [and others

    1998-02-01

    Capsules with beryllium ablators have long been considered as alternatives to plastic for the National Ignition Facility laser ; now the superior performance of beryllium is becoming well substantiated. Beryllium capsules have the advantages of relative insensitivity to instability growth, low opacity, high tensile strength, and high thermal conductivity. 3-D calculation with the HYDRA code NTIS Document No. DE-96004569 (M. M. Marinak et.al. in UCRL-LR-105821-95-3) confirm 2-D LASNEX U. B. Zimmerman and W. L. Kruer, Comments Plasmas Phys. Controlled Thermonucl. Fusion, 2, 51(2975) results that particular beryllium capsule designs are several times less sensitive than the CH point design to instability growth from DT ice roughness. These capsule designs contain more ablator mass and leave some beryllium unablated at ignition. By adjusting the level of copper dopant, the unablated mass can increase or decrease, with a corresponding decrease or increase in sensitivity to perturbations. A plastic capsule with the same ablator mass as the beryllium and leaving the same unablated mass also shows this reduced perturbation sensitivity. Beryllium`s low opacity permits the creation of 250 eV capsule designs. Its high tensile strength allows it to contain DT fuel at room temperature. Its high thermal conductivity simplifies cryogenic fielding.

  19. Discovery of a biomarker and lead small molecules to target r(GGGGCC)-associated defects in c9FTD/ALS.

    Science.gov (United States)

    Su, Zhaoming; Zhang, Yongjie; Gendron, Tania F; Bauer, Peter O; Chew, Jeannie; Yang, Wang-Yong; Fostvedt, Erik; Jansen-West, Karen; Belzil, Veronique V; Desaro, Pamela; Johnston, Amelia; Overstreet, Karen; Oh, Seok-Yoon; Todd, Peter K; Berry, James D; Cudkowicz, Merit E; Boeve, Bradley F; Dickson, Dennis; Floeter, Mary Kay; Traynor, Bryan J; Morelli, Claudia; Ratti, Antonia; Silani, Vincenzo; Rademakers, Rosa; Brown, Robert H; Rothstein, Jeffrey D; Boylan, Kevin B; Petrucelli, Leonard; Disney, Matthew D

    2014-09-03

    A repeat expansion in C9ORF72 causes frontotemporal dementia and amyotrophic lateral sclerosis (c9FTD/ALS). RNA of the expanded repeat (r(GGGGCC)exp) forms nuclear foci or undergoes repeat-associated non-ATG (RAN) translation, producing "c9RAN proteins." Since neutralizing r(GGGGCC)exp could inhibit these potentially toxic events, we sought to identify small-molecule binders of r(GGGGCC)exp. Chemical and enzymatic probing of r(GGGGCC)8 indicate that it adopts a hairpin structure in equilibrium with a quadruplex structure. Using this model, bioactive small molecules targeting r(GGGGCC)exp were designed and found to significantly inhibit RAN translation and foci formation in cultured cells expressing r(GGGGCC)66 and neurons transdifferentiated from fibroblasts of repeat expansion carriers. Finally, we show that poly(GP) c9RAN proteins are specifically detected in c9ALS patient cerebrospinal fluid. Our findings highlight r(GGGGCC)exp-binding small molecules as a possible c9FTD/ALS therapeutic and suggest that c9RAN proteins could potentially serve as a pharmacodynamic biomarker to assess efficacy of therapies that target r(GGGGCC)exp.

  20. CRISPR/Cas9的应用及脱靶效应研究进展%Progress of application and off-target effects of CRISPR/Cas9

    Institute of Scientific and Technical Information of China (English)

    郑武; 谷峰

    2015-01-01

    The clustered regulatory interspaced short palindromic repeat/Cas9 (CRISPR/Cas9) system mediates genome editing and is revolutionizing genetic researches. Scientists are able to manipulate the gene of interest from any organism with CRISPR/Cas9. Compared with zinc finger nucleases (ZFNs) and transcription activator-like ef-fector nucleases (TALENs) technologies, the CRISPR/Cas9 technology provides an easy and efficient approach to manipulate the genome. In this system, sgRNA (Single guide RNA), a short RNA matching the targeted DNA frag-ment, guides the CRISPR/Cas9 to interrogate the genome. Because sgRNA can tolerate certain mismatches to the DNA targets and thereby promote undesired off-target mutagenesis, the key limit of this technology is off-target ef-fects. To eliminate the off-target effects, different strategies have been adopted. In this review, we summarize the application of CRISPR/Cas9 and different strategies for addressing off-target effects.%CRISPR/Cas9基因编辑技术在生命科学领域掀起了一场全新的技术革命,该技术可以对基因组特定位点进行靶向编辑,包括缺失、插入、修复等。CRISPR/Cas9比锌指核酸酶(ZFNs)和转录激活因子样效应物核酸酶(TALENs)技术更易于操作,而且更高效。CRISPR/Cas9系统中的向导RNA(Single guide RNA, sgRNA)是一段与目标DNA片段匹配的RNA序列,指导Cas9蛋白对基因组进行识别。研究发现,设计的sgRNA会与非靶点DNA 序列错配,引入非预期的基因突变,即脱靶效应(Off-target effects)。脱靶效应严重制约了 CRISPR/Cas9基因编辑技术的广泛应用。为了避免脱靶效应,研究者对影响脱靶效应的因素进行了系统研究并提出了许多降低脱靶效应的方法。文章总结了 CRISPR/Cas9系统的应用及脱靶效应研究进展,以期为相关领域的工作提供参考。

  1. Rotenone affects p53 transcriptional activity and apoptosis via targeting SIRT1 and H3K9 acetylation in SH-SY5Y cells.

    Science.gov (United States)

    Feng, Ya; Liu, Te; Dong, Su-Yan; Guo, Yan-Jie; Jankovic, Joseph; Xu, Huaxi; Wu, Yun-Cheng

    2015-08-01

    The protein deacetylase SIRT1 has been recognized to exert its protective effect by directly deacetylasing histone and many other transcriptional factors including p53. However, the effect of SIRT1 on p53 expression at the transcriptional level still remains to be elucidated. In this study, we found that rotenone treatment decreased cell viability, induced apoptosis, reduced SIRT1 level, and promoted p53 expression. Pre-treatment with resveratrol, a SIRT1 activator, could attenuate rotenone-induced cell injury and p53 expression, whereas down-regulation of SIRT1 directly increased p53 expression. Moreover, chromatin immunoprecipitation experiments showed that SIRT1 bound to H3K9 within the p53 promoter region, and this binding resulted in decreased H3K9 acetylation and increased H3K9 tri-methylation, thereby inhibiting p53 gene transcription. In conclusion, our data indicate that rotenone promotes p53 transcription and apoptosis through targeting SIRT1 and H3K9. This leads to nigrostriatal degeneration, the main pathogenic mechanism of motor features of Parkinson's disease. SIRT1, a deacetylase enzyme, has neuroprotective effects for Parkinson's disease via targeting various factors. Resveratrol activated SIRT1 can target H3K9 and regulate p53 gene expression at the transcriptional level, thus inhibiting p53 transcription to enhance neuroprotection, alleviating rotenone induced dopaminergic neurodegeneration. We think these findings should provide a new strategy for the treatment of Parkinson's disease.

  2. Three-coordinate beryllium β-diketiminates: synthesis and reduction chemistry.

    Science.gov (United States)

    Arrowsmith, Merle; Hill, Michael S; Kociok-Köhn, Gabriele; MacDougall, Dugald J; Mahon, Mary F; Mallov, Ian

    2012-12-17

    A series of mononuclear, heteroleptic beryllium complexes supported by the monoanionic β-diketiminate ligand [HC{CMeNDipp}(2)](-) (L; Dipp = 2,6-diisopropylphenyl) have been synthesized. Halide complexes of the form [LBeX] (X = Cl, I) and a bis(trimethylsilyl)amide complex were produced via salt metathesis routes. Alkylberyllium β-diketiminate complexes of the form [LBeR] (R = Me, (n)Bu) were obtained by salt metathesis from the chloride precursor [LBeCl]. Controlled hydrolysis of [LBeMe] afforded an air-stable, monomeric β-diketiminatoberyllium hydroxide complex. [LBeMe] also underwent facile protonolysis with alcohols to form the corresponding β-diketiminatoberyllium alkoxides [LBeOR] (R = Me, (t)Bu, Ph). High temperatures and prolonged reaction times were required for protonolysis of [LBeMe] with primary amines to yield the β-diketiminatoberyllium amide complexes [LBeNHR] (R = (n)Bu, CH(2)Ph, Ph). No reactions were observed between [LBeMe] and silanes, terminal acetylenes, or secondary amines. All compounds were characterized by (1)H, (13)C, and (9)Be NMR spectroscopy and, in most cases, by X-ray crystallography. Reduction of the beryllium chloride complex with potassium metal resulted in apparent hydrogen-atom transfer between two β-diketiminate backbones, yielding two dimeric, potassium chloride bridged diamidoberyllium species. X-ray analysis of a cocrystallized mixture of the 18-crown-6 adducts of these species allowed unambiguous identification of the two reduced diketiminate ligands, one of which had been deprotonated at a backbone methyl substituent and the other reduced by hydride addition to the β-imine position. It is proposed that this process occurs by the formation of an unobserved radical anion species and intermolecular hydrogen-atom transfer by a radical-based hydrogen abstraction mechanism.

  3. Simultaneous determination of aluminium and beryllium by first-derivative synchronous solid-phase spectrofluorimetry.

    Science.gov (United States)

    Capitán, F; Manzano, E; Navalón, A; Luis Vilchez, J; Capitán-Vallvey, L F

    1992-01-01

    A method for the simultaneous determination of aluminium and beryllium in mixtures by first-deravative synchronous solid-phase spectrofluorimetry has been developed. Aluminium and beryllium reacted with morin to give fluorescent complexes, which were fixed on a dextran-type resin. The fluoresnce of the resin, packed in a 1-mm silica cell, was measured directly with a solid-surface attachment. The constant wavelength difference chosen to optimize the determination was Deltalambda = lambda(em) = 75 nm. Aluminium was measured at lambda(em)lambda = 445/520 nm and beryllium at lambda(em)lambda(em) = 430/505 nm. The range of application is between 0.5 and 5.0 ng/ml for both aluminium and beryllium. The accuracy and precision of the method are reported. The method has been successfully applied to the determination of aluminium and beryllium in synthetic mixtures and natural waters.

  4. Beryllium, an adjuvant that promotes gamma interferon production.

    Science.gov (United States)

    Lee, J Y; Atochina, O; King, B; Taylor, L; Elloso, M; Scott, P; Rossman, M D

    2000-07-01

    Beryllium is associated with a human pulmonary granulomatosis characterized by an accumulation of CD4(+) T cells in the lungs and a heightened specific lymphocyte proliferative response to beryllium (Be) with gamma interferon (IFN-gamma) release (i.e., a T helper 1 [Th1] response). While an animal model of Be sensitization is not currently available, Be has exhibited adjuvant effects in animals. The effects of Be on BALB/c mice immunized with soluble leishmanial antigens (SLA) were investigated to determine if Be had adjuvant activity for IFN-gamma production, an indicator of the Th1 response. In this strain of Leishmania-susceptible BALB/c mice, a Th2 response is normally observed after in vivo SLA sensitization and in vitro restimulation with SLA. If interleukin-12 (IL-12) is given during in vivo sensitization with SLA, markedly increased IFN-gamma production and decreased IL-4 production are detected. We show here that when beryllium sulfate (BeSO(4)) was added during in vivo sensitization of BALB/c mice with SLA and IL-12, significantly increased IFN-gamma production and decreased IL-4 production from lymph node and spleen cells were detected upon in vitro SLA restimulation. No specific responses were observed to Be alone. Lymph node and spleen cells from all mice proliferated strongly and comparably upon in vitro restimulation with SLA and with SLA plus Be; no differences were noted among groups of mice that received different immunization regimens. In vivo, when Be was added to SLA and IL-12 for sensitization of BALB/c mice, more effective control of Leishmania infection was achieved. This finding has implications for understanding not only the development of granulomatous reactions but also the potential for developing Be as a vaccine adjuvant.

  5. Beryllium-stimulated apoptosis in macrophage cell lines.

    Science.gov (United States)

    Sawyer, R T; Fadok, V A; Kittle, L A; Maier, L A; Newman, L S

    2000-08-21

    In vitro stimulation of bronchoalveolar lavage cells from patients with chronic beryllium disease (CBD) induces the production of TNF-alpha. We tested the hypothesis that beryllium (Be)-stimulated TNF-alpha might induce apoptosis in mouse and human macrophage cell lines. These cell lines were selected because they produce a range of Be-stimulated TNF-alpha. The mouse macrophage cell line H36.12j produces high levels of Be-stimulated TNF-alpha. The mouse macrophage cell line P388D.1 produces low, constitutive, levels of TNF-alpha and does not up-regulate Be-stimulated TNF-alpha production. The DEOHS-1 human CBD macrophage cell line does not produce constitutive or Be-stimulated TNF-alpha. Apoptosis was determined by microscopic observation of propidium iodide stained fragmented nuclei in unstimulated and BeSO(4)-stimulated macrophage cell lines. BeSO(4) induced apoptosis in all macrophage cell lines tested. Beryllium-stimulated apoptosis was dose-responsive and maximal after 24 h of exposure to 100 microM BeSO(4). In contrast, unstimulated and Al(2)(SO(4))(3)-stimulated macrophage cell lines did not undergo apoptosis. The general caspase inhibitor BD-fmk inhibited Be-stimulated macrophage cell line apoptosis at concentrations above 50 microM. Our data show that Be-stimulated macrophage cell line apoptosis was caspase-dependent and not solely dependent on Be-stimulated TNF-alpha levels. We speculate that the release of Be-antigen from apoptotic macrophages may serve to re-introduce Be material back into the lung microenvironment, make it available for uptake by new macrophages, and thereby amplify Be-stimulated cytokine production, promoting ongoing inflammation and granuloma maintenance in CBD.

  6. Model study in chemisorption: atomic hydrogen on beryllium clusters

    Energy Technology Data Exchange (ETDEWEB)

    Bauschlicher, C.W. Jr.

    1976-08-01

    The interaction between atomic hydrogen and the (0001) surface of Be metal has been studied by ab initio electronic structure theory. Self-consistent-field (SCF) calculations have been performed using minimum, optimized minimum, double zeta and mixed basis sets for clusters as large as 22 Be atoms. The binding energy and equilibrium geometry (the distance to the surface) were determined for 4 sites. Both spatially restricted (the wavefunction was constrained to transform as one of the irreducible representations of the molecular point group) and unrestricted SCF calculations were performed. Using only the optimized minimum basis set, clusters containing as many as 22 beryllium atoms have been investigated. From a variety of considerations, this cluster is seen to be nearly converged within the model used, providing the most reliable results for chemisorption. The site dependence of the frequency is shown to be a geometrical effect depending on the number and angle of the bonds. The diffusion of atomic hydrogen through a perfect beryllium crystal is predicted to be energetically unfavorable. The cohesive energy, the ionization energy and the singlet-triplet separation were computed for the clusters without hydrogen. These quantities can be seen as a measure of the total amount of edge effects. The chemisorptive properties are not related to the total amount of edge effects, but rather the edge effects felt by the adsorbate bonding berylliums. This lack of correlation with the total edge effects illustrates the local nature of the bonding, further strengthening the cluster model for chemisorption. A detailed discussion of the bonding and electronic structure is included. The remaining edge effects for the Be/sub 22/ cluster are discussed.

  7. Microstructure and mechanical properties of neutron irradiated beryllium

    Energy Technology Data Exchange (ETDEWEB)

    Ishitsuka, E.; Kawamura, H. [Japan Atomic Energy Research Inst., Oarai, Ibaraki (Japan). Oarai Research Establishment; Terai, T.; Tanaka, S.

    1998-01-01

    Microstructure and mechanical properties of the neutron irradiated beryllium with total fast neutron fluences of 1.3 - 4.3 x 10{sup 21} n/cm{sup 2} (E>1 MeV) at 327 - 616degC were studied. Swelling increased by high irradiation temperature, high fluence, and by the small grain size and high impurity. Obvious decreasing of the fracture stress was observed in the bending test and in small grain specimens which had many helium bubbles on the grain boundary. Decreasing of the fracture stress for small grain specimens was presumably caused by crack propagation on the grain boundaries which weekend by helium bubbles. (author)

  8. Use of notched beams to establish fracture criteria for beryllium

    Energy Technology Data Exchange (ETDEWEB)

    Mayville, R.A.

    1980-01-04

    The fracture of an improved form of pure beryllium was studied under triaxial tensile stresses. This state of stress was produced by testing notched beams, which were thick enough to be in a state of plane strain at the center. A plane strain, elastic-incremental plasticity finite element program was then used to determine the stress and strain distributions at fracture. A four-point bend fixture was used to load the specimens. It was carefully designed and manufactured to eliminate virtually all of the shear stresses at the reduced section of the notched beams. The unixial properties were obtained.

  9. Atomic, Crystal, Elastic, Thermal, Nuclear, and Other Properties of Beryllium

    Energy Technology Data Exchange (ETDEWEB)

    Goldberg, A

    2006-02-01

    This report is part of a series of documents that provide a background to those involved in the construction of beryllium components and their applications. This report is divided into five sub-sections: Atomic/Crystal Structure, Elastic Properties, Thermal Properties, Nuclear Properties, and Miscellaneous Properties. In searching through different sources for the various properties to be included in this report, inconsistencies were at times observed between these sources. In such cases, the values reported by the Handbook of Chemistry and Physics was usually used. In equations, except where indicated otherwise, temperature (T) is in degrees Kelvin.

  10. Inorganic arrangement crystal beryllium, lithium, selenium and silicon

    CERN Document Server

    Gobato, Ricardo; Fedrigo, Desire Francine Gobato

    2015-01-01

    The use of inorganic crystals technology has been widely date. Since quartz crystals for watches in the nineteenth century, and common way radio in the early twentieth century, to computer chips with new semiconductor materials. Chemical elements such as beryllium, lithium, selenium and silicon, are widely used in technology. The development of new crystals arising from that arrangement can bring technological advances in several areas of knowledge. The likely difficulty of finding such crystals in nature or synthesized, suggest an advanced study of the subject. A study using computer programs with ab initio method was applied. As a result of the likely molecular structure of the arrangement of a crystal was obtained.

  11. Tritium analyses of COBRA-1A2 beryllium pebbles

    Energy Technology Data Exchange (ETDEWEB)

    Baldwin, D.L. [Pacific Northwest National Lab., Richland, WA (United States)

    1998-03-01

    Selected tritium measurements have been completed for the COBRA-1A2 experiment C03 and D03 beryllium pebbles. The completed results, shown in Tables 1, 2, and 3, include the tritium assay results for the 1-mm and 3-mm C03 pebbles, and the 1-mm D03 pebbles, stepped anneal test results for both types of 1-mm pebbles, and the residual analyses for the stepped-anneal specimens. All results have been reported with date-of-count and are not corrected for decay. Stepped-anneal tritium release response is provided in addenda.

  12. Cryogenic optical tests of a lightweight HIP beryllium mirror

    Science.gov (United States)

    Melugin, Ramsey K.; Miller, Jacob H.; Young, J. A.; Howard, Steven D.; Pryor, G. Mark

    Five interferometric tests were conducted at cryogenic temperatures on a lightweight, 50 cm diameter, hot isostatic pressed (HIP) beryllium mirror in the Ames Research Center (ARC) Cryogenic Optics Test Facility. The purpose of the tests was to determine the stability of the mirror's figure when cooled to cryogenic temperatures. Test temperatures ranged from room ambient to 8 K. One cycle to 8 K and five cycles to 80 K were performed. Optical and thermal test methods are described. Data is presented to show the amount of cryogenic distortion and hysteresis present in the mirror when measured with an earlier, Shack interferometer, and with a newly-acquired, phase-measuring interferometer.

  13. 曝气生物滤池处理高氨氮含铍废水研究%Treatment of Beryllium Containing Wastewater with High Ammonia Concentration by Biological Aerated Filters

    Institute of Scientific and Technical Information of China (English)

    孙芳; 孙卫玲

    2012-01-01

    含铍废水具有较高的毒性,目前关于其处理方法的研究较少.文章针对铍冶炼废水中铍超标以及高氨氮浓度的问题,选取接种有微生物的曝气生物滤池(BAF)工艺同时去除氨氮和铍,并分析其去除铍的机理.反应器系统的长期运行结果表明,BAF对高氨氮含铍废水具有较好的处理效果.在进水氨氮浓度200 mg/L,铍浓度50~100μg/L,停留时间24h条件下,处理出水氨氮浓度稳定在1.8~10.0 mg/L,铍浓度小于5μg/L.BAF主要通过系统中的微生物去除铍,载体对铍的吸附量较小,用Langmuir模型对吸附数据进行拟合,得到微生物对铍的吸附容量为684.9 μg/g.形态提取实验表明,被微生物去除的铍主要以有机结合态存在,且微生物细胞表面对铍的吸附量有限,大量的铍富集于微生物细胞内,为此,BAF对铍有长期稳定的处理效果.%Beryllium-containing waste water is of high toxicity, but there are limited researches concerning its treatment. Beryllium smelting wastewater contains high concentrations of beryllium and ammonia. Biological aerated filters (BAF), which was inoculated with microorganisms, was used to treat beryllium smelting wastewater, and the mechanisms involved were investigated. Results show that BAF could remove beryllium and ammonia simultaneously. When influent concentrations of ammonia nitrogen and beryllium were 200 mg/L and 50-100 μg/L respectively, HRT was 24 h, the concentration ammonia was in the range of 1.8~10.0 mg/L, and beryllium concentration was less than 5 μg/L in the effluent. The removal of beryllium was mainly attributed to the microorganisms in BAF, and the maximum uptake of beryllium by microorganisms calculated by Langmuir equation was 684.9 μg/g. The beryllium removed by BAF was mainly combined to organic fraction. Moreover, large amount of beryllium accumulated inside the cell with limited biosorption by the external surface of microorganisms. Therefore, high removal

  14. Accelerating Genome Editing in CHO Cells Using CRISPR Cas9 and CRISPy, a Web-Based Target Finding Tool

    DEFF Research Database (Denmark)

    Ronda, Carlotta; Pedersen, Lasse Ebdrup; Hansen, Henning Gram

    2014-01-01

    by applying lectin selection. All eight sgRNAs examined in this study resulted in relatively high indel frequencies, demonstrating that the Cas9 system is a robust and efficient genomeediting methodology in CHO cells. Deep sequencing revealed that 85% of the indels created by Cas9 resulted in frameshift...

  15. Physicochemical characteristics of aerosol particles generated during the milling of beryllium silicate ores: implications for risk assessment.

    Science.gov (United States)

    Stefaniak, Aleksandr B; Chipera, Steve J; Day, Gregory A; Sabey, Phil; Dickerson, Robert M; Sbarra, Deborah C; Duling, Mathew G; Lawrence, Robert B; Stanton, Marcia L; Scripsick, Ronald C

    2008-01-01

    Inhalation of beryllium dusts generated during milling of ores and cutting of beryl-containing gemstones is associated with development of beryllium sensitization and low prevalence of chronic beryllium disease (CBD). Inhalation of beryllium aerosols generated during primary beryllium production and machining of the metal, alloys, and ceramics are associated with sensitization and high rates of CBD, despite similar airborne beryllium mass concentrations among these industries. Understanding the physicochemical properties of exposure aerosols may help to understand the differential immunopathologic mechanisms of sensitization and CBD and lead to more biologically relevant exposure standards. Properties of aerosols generated during the industrial milling of bertrandite and beryl ores were evaluated. Airborne beryllium mass concentrations among work areas ranged from 0.001 microg/m(3) (beryl ore grinding) to 2.1 microg/m(3) (beryl ore crushing). Respirable mass fractions of airborne beryllium-containing particles were 80% in high-energy input areas (beryl melting, beryl grinding). Particle specific surface area decreased with processing from feedstock ores to drumming final product beryllium hydroxide. Among work areas, beryllium was identified in three crystalline forms: beryl, poorly crystalline beryllium oxide, and beryllium hydroxide. In comparison to aerosols generated by high-CBD risk primary production processes, aerosol particles encountered during milling had similar mass concentrations, generally lower number concentrations and surface area, and contained no identifiable highly crystalline beryllium oxide. One possible explanation for the apparent low prevalence of CBD among workers exposed to beryllium mineral dusts may be that characteristics of the exposure material do not contribute to the development of lung burdens sufficient for progression from sensitization to CBD. In comparison to high-CBD risk exposures where the chemical nature of aerosol

  16. Inhibition of hepatitis B virus by the CRISPR/Cas9 system via targeting the conserved regions of the viral genome.

    Science.gov (United States)

    Liu, Xing; Hao, Ruidong; Chen, Shuliang; Guo, Deyin; Chen, Yu

    2015-08-01

    Hepatitis B virus (HBV) remains a global health threat as chronic HBV infection may lead to liver cirrhosis or cancer. Current antiviral therapies with nucleoside analogues can inhibit the replication of HBV, but do not disrupt the already existing HBV covalently closed circular DNA. The newly developed CRISPR (clustered regularly interspaced short palindromic repeats)/Cas9 (CRISPR-associated 9) system is a powerful tool to target cellular genome DNA for gene editing. In order to investigate the possibility of using the CRISPR/Cas9 system to disrupt the HBV DNA templates, we designed eight guide RNAs (gRNAs) that targeted the conserved regions of different HBV genotypes, which could significantly inhibit HBV replication both in vitro and in vivo. Moreover, the HBV-specific gRNA/Cas9 system could inhibit the replication of HBV of different genotypes in cells, and the viral DNA was significantly reduced by a single gRNA/Cas9 system and cleared by a combination of different gRNA/Cas9 systems.

  17. Random Splicing of Several Exons Caused by a Single Base Change in the Target Exon of CRISPR/Cas9 Mediated Gene Knockout

    Directory of Open Access Journals (Sweden)

    Marcel Kapahnke

    2016-12-01

    Full Text Available The clustered regularly interspaced short palindromic repeats (CRISPR-associated sequence 9 (CRISPR/Cas9 system is widely used for genome editing purposes as it facilitates an efficient knockout of a specific gene in, e.g. cultured cells. Targeted double-strand breaks are introduced to the target sequence of the guide RNAs, which activates the cellular DNA repair mechanism for non-homologous-end-joining, resulting in unprecise repair and introduction of small deletions or insertions. Due to this, sequence alterations in the coding region of the target gene frequently cause frame-shift mutations, facilitating degradation of the mRNA. We here show that such CRISPR/Cas9-mediated alterations in the target exon may also result in altered splicing of the respective pre-mRNA, most likely due to mutations of splice-regulatory sequences. Using the human FLOT-1 gene as an example, we demonstrate that such altered splicing products also give rise to aberrant protein products. These may potentially function as dominant-negative proteins and thus interfere with the interpretation of the data generated with these cell lines. Since most researchers only control the consequences of CRISPR knockout at genomic and protein level, our data should encourage to also check the alterations at the mRNA level.

  18. mCAL: A New Approach for Versatile Multiplex Action of Cas9 Using One sgRNA and Loci Flanked by a Programmed Target Sequence

    Directory of Open Access Journals (Sweden)

    Gregory C. Finnigan

    2016-07-01

    Full Text Available Genome editing exploiting CRISPR/Cas9 has been adopted widely in academia and in the biotechnology industry to manipulate DNA sequences in diverse organisms. Molecular engineering of Cas9 itself and its guide RNA, and the strategies for using them, have increased efficiency, optimized specificity, reduced inappropriate off-target effects, and introduced modifications for performing other functions (transcriptional regulation, high-resolution imaging, protein recruitment, and high-throughput screening. Moreover, Cas9 has the ability to multiplex, i.e., to act at different genomic targets within the same nucleus. Currently, however, introducing concurrent changes at multiple loci involves: (i identification of appropriate genomic sites, especially the availability of suitable PAM sequences; (ii the design, construction, and expression of multiple sgRNA directed against those sites; (iii potential difficulties in altering essential genes; and (iv lingering concerns about “off-target” effects. We have devised a new approach that circumvents these drawbacks, as we demonstrate here using the yeast Saccharomyces cerevisiae. First, any gene(s of interest are flanked upstream and downstream with a single unique target sequence that does not normally exist in the genome. Thereafter, expression of one sgRNA and cotransformation with appropriate PCR fragments permits concomitant Cas9-mediated alteration of multiple genes (both essential and nonessential. The system we developed also allows for maintenance of the integrated, inducible Cas9-expression cassette or its simultaneous scarless excision. Our scheme—dubbed mCAL for “Multiplexing of Cas9 at Artificial Loci”—can be applied to any organism in which the CRISPR/Cas9 methodology is currently being utilized. In principle, it can be applied to install synthetic sequences into the genome, to generate genomic libraries, and to program strains or cell lines so that they can be conveniently (and

  19. 高氟铍矿石熔炼过程中脱氟研究%Study on Defluorination of High Fluorine Bearing Beryllium Ore in Smelting Process

    Institute of Scientific and Technical Information of China (English)

    雷湘

    2013-01-01

    高氟铍矿石在熔炼过程中配入氢氧化铝来脱除其中的氟.结果表明,在配入5%Na2CO3、9.3%Al(OH)3、1400~1500℃熔炼20 min的情况下,BeO回收率达到96%以上,脱氟效果良好(铍玻璃F/BeO能控制在15%以内).为高氟铍矿石的工业应用探索出新的冶炼途径.%Defluorination with addition of aluminum hydroxide in smelting process of high fluorine bearing beryllium ore was investigated. The results show that BeO recovery is above 96% under the conditions including dosage of Na2CO3 of 5%, dosage of A1(OH)3 of 9.3%, smelting temperature of 1 400~1 500℃, and time of 20 min. Defluorination effect is fine in that the ratio of F/BeO of beryllium glass could be controlled below 15%. This new smelting process facilitates the industrial application of high fluorine bearing beryllium ore.

  20. Determination of picomolar beryllium levels in seawater with inductively coupled plasma mass spectrometry following silica-gel preconcentration

    Energy Technology Data Exchange (ETDEWEB)

    Tazoe, Hirofumi, E-mail: tazoe@cc.hirosaki-u.ac.jp [Department of Radiation Chemistry, Institute of Radiation Emergency Mediation, Hirosaki University, 66-1 Hon-cho, Hirosaki, Aomori 036-8564 (Japan); College of Humanities and Sciences, Nihon University, 3-25-40, Sakurajosui, Setagaya-ku, Tokyo 156-8550 (Japan); Yamagata, Takeyasu [College of Humanities and Sciences, Nihon University, 3-25-40, Sakurajosui, Setagaya-ku, Tokyo 156-8550 (Japan); Obata, Hajime [Atmosphere and Ocean Research Institute, The Tokyo University, 5-1-5 Kashiwanoha, Kashiwa-shi, Chiba 277-8564 (Japan); Nagai, Hisao [College of Humanities and Sciences, Nihon University, 3-25-40, Sakurajosui, Setagaya-ku, Tokyo 156-8550 (Japan)

    2014-12-10

    Highlights: • We developesd the simplest and robust SPE method for ultra low picomolar level beryllium in seawater. • Just silica gel column can quantitatively adsorb beryllium in neutral pH condition containing natural seawater. • EDTA solution can eliminate seawater matrixes retaining Be in the column, which optimize to ICP-MS detemination. • Accurate and precise Be data have been obtained for natural seawater from North Pacific Ocean. - Abstract: A robust and rapid method for the determination of natural levels of beryllium (Be) in seawater was developed to facilitate mapping Be concentrations in the ocean. A solid-phase extraction method using a silica gel column was applied for preconcentration and purification of Be in seawater prior to determination of Be concentrations with inductively coupled plasma mass spectrometry (ICP-MS). Be was quantitatively adsorbed onto silica gel from solutions with pH values ranging from 6.3 to 9, including natural seawater. The chelating agent ethylenediamine tetraacetic acid was used to remove other ions in the seawater matrix (Na, Mg, and Ca) that interfere with the ICP-MS analysis. The reproducibility of the method was 3% based on triplicate analyses of natural seawater samples, and the detection limit was 0.4 pmol kg{sup −1} for 250 mL of seawater, which is sufficient for the analysis of seawater in the open ocean. The method was then used to determine the vertical profile of Be in the eastern North Pacific Ocean, which was found to be a recycled-type profile in which the Be concentration increased with depth from the surface (7.2 pmol kg{sup −1} at <200 m) to deep water (29.2 pmol kg{sup −1} from 3500 m to the bottom)

  1. miR-132 Regulates Dendritic Spine Structure by Direct Targeting of Matrix Metalloproteinase 9 mRNA.

    Science.gov (United States)

    Jasińska, Magdalena; Miłek, Jacek; Cymerman, Iwona A; Łęski, Szymon; Kaczmarek, Leszek; Dziembowska, Magdalena

    2016-09-01

    Mir-132 is a neuronal activity-regulated microRNA that controls the morphology of dendritic spines and neuronal transmission. Similar activities have recently been attributed to matrix metalloproteinase-9 (MMP-9), an extrasynaptic protease. In the present study, we provide evidence that miR-132 directly regulates MMP-9 mRNA in neurons to modulate synaptic plasticity. With the use of luciferase reporter system, we show that miR-132 binds to the 3'UTR of MMP-9 mRNA to regulate its expression in neurons. The overexpression of miR-132 in neurons reduces the level of endogenous MMP-9 protein secretion. In synaptoneurosomes, metabotropic glutamate receptor (mGluR)-induced signaling stimulates the dissociation of miR-132 from polyribosomal fractions and shifts it towards the messenger ribonucleoprotein (mRNP)-containing fraction. Furthermore, we demonstrate that the overexpression of miR-132 in the cultured hippocampal neurons from Fmr1 KO mice that have increased synaptic MMP-9 level provokes enlargement of the dendritic spine heads, a process previously implicated in enhanced synaptic plasticity. We propose that activity-dependent miR-132 regulates structural plasticity of dendritic spines through matrix metalloproteinase 9.

  2. SOURCE AND PATHWAY DETERMINATION FOR BERYLLIUM FOUND IN BECHTEL NEVADA NORTH LAS VEGAS FACILITIES

    Energy Technology Data Exchange (ETDEWEB)

    BECHTEL NEVADA

    2004-07-01

    In response to the report ''Investigation of Beryllium Exposure Cases Discovered at the North Las Vegas Facility of the National Nuclear Security Administration'', published by the U.S. Department of Energy (DOE), National Nuclear Security Administration (NNSA) in August 2003, Bechtel Nevada (BN) President and General Manager Dr. F. A. Tarantino appointed the Beryllium Investigation & Assessment Team (BIAT) to identify both the source and pathway for the beryllium found in the North Las Vegas (NLV) B-Complex. From September 8 to December 18, 2003, the BIAT investigated the pathway for beryllium and determined that a number of locations existed at the Nevada Test Site (NTS) which could have contained sufficient quantities of beryllium to result in contamination if transported. Operations performed in the B-1 Building as a result of characterization activities at the Engine Maintenance, Assembly, and Disassembly (EMAD); Reactor Maintenance, Assembly, and Disassembly (RMAD); Test Cells A and C; and the Central Support Facility in Area 25 had the greatest opportunity for transport of beryllium. Investigative monitoring and sampling was performed at these sites with subsequent transport of sample materials, equipment, and personnel from the NTS to the B-1 Building. The timeline established by the BIAT for potential transport of the beryllium contamination into the B-1 Building was from September 1997 through November 2002. Based on results of recently completed swipe sampling, no evidence of transport of beryllium from test areas has been confirmed. Results less than the DOE beryllium action level of 0.2 ???g/100 cm2 were noted for work support facilities located in Area 25. All of the identified sites in Area 25 worked within the B-1 tenant's residency timeline have been remediated. Legacy contaminants have either been disposed of or capped with clean borrow material. As such, no current opportunity exists for release or spread of beryllium

  3. The mechanism for production of beryllium fluoride from the product of ammonium fluoride processing of beryllium- containing raw material

    Science.gov (United States)

    Kraydenko, R. I.; Dyachenko, A. N.; Malyutin, L. N.; Petlin, I. V.

    2016-06-01

    The technique of fluorite-phenacite-bertrandite ores from Russian Ermakovskoe deposit processing by ammonium bifluoride is described. To determine the temperature mode and the thermal dissociation mechanism of ammonium tetrafluoroberyllate (the product of ammonium-fluoride leaching of the ore) the TG/DTA have been carried out. By IR spectroscopy and XRD the semi-products of ammonium tetrafluoroberyllate thermal dissociation have been identified. The hygroscopic low-temperature beryllium fluoride forms higher than 380°C. The less hydroscopic form of BeF2 have been produced at 600°C.

  4. A comparison of Agrobacterium-mediated transformation and protoplast-mediated transformation with CRISPR-Cas9 and bipartite gene targeting substrates, as effective gene targeting tools for Aspergillus carbonarius.

    Science.gov (United States)

    Weyda, István; Yang, Lei; Vang, Jesper; Ahring, Birgitte K; Lübeck, Mette; Lübeck, Peter S

    2017-04-01

    In recent years, versatile genetic tools have been developed and applied to a number of filamentous fungi of industrial importance. However, the existing techniques have limitations when it comes to achieve the desired genetic modifications, especially for efficient gene targeting. In this study, we used Aspergillus carbonarius as a host strain due to its potential as a cell factory, and compared three gene targeting techniques by disrupting the ayg1 gene involved in the biosynthesis of conidial pigment in A. carbonarius. The absence of the ayg1 gene leads to phenotypic change in conidia color, which facilitated the analysis on the gene targeting frequency. The examined transformation techniques included Agrobacterium-mediated transformation (AMT) and protoplast-mediated transformation (PMT). Furthermore, the PMT for the disruption of the ayg1 gene was carried out with bipartite gene targeting fragments and the recently adapted CRISPR-Cas9 system. All three techniques were successful in generating Δayg1 mutants, but showed different efficiencies. The most efficient method for gene targeting was AMT, but further it was shown to be dependent on the choice of Agrobacterium strain. However, there are different advantages and disadvantages of all three gene targeting methods which are discussed, in order to facilitate future approaches for fungal strain improvements.

  5. Molecular Targets of Chromatin Repressive Mark H3K9me3 in Primate Progenitor Cells within Adult Neurogenic Niches

    Directory of Open Access Journals (Sweden)

    Michael R Foret

    2014-07-01

    Full Text Available Histone 3 Lysine 9 (H3K9 methylation is known to be associated with pericentric heterochromatin and important in genomic stability. In this study, we show that trimethylation at H3K9 (H3K9me3 is enriched in an adult neural stem cell niche- the subventricular zone (SVZ on the walls of the lateral ventricle in both rodent and non-human primate baboon brain. Previous studies have shown that there is significant correlation between baboon and human regarding genomic similarity and brain structure, suggesting that findings in baboon are relevant to human. To understand the function of H3K9me3 in this adult neurogenic niche, we performed genome-wide analyses using ChIP-Seq (chromatin immunoprecipitation and deep-sequencing and RNA-Seq for in vivo SVZ cells purified from baboon brain. Through integrated analyses of ChIP-Seq and RNA-Seq, we found that H3K9me3-enriched genes associated with cellular maintenance, post-transcriptional and translational modifications, signaling pathways, and DNA replication are expressed, while genes involved in axon/neuron, hepatic stellate cell, or immune-response activation are not expressed. As neurogenesis progresses in the adult SVZ, cell fate restriction is essential to direct proper lineage commitment. Our findings highlight that H3K9me3 repression in undifferentiated SVZ cells is engaged in the maintenance of cell type integrity, implicating a role for H3K9me3 as an epigenetic mechanism to control cell fate transition within this adult germinal niche.

  6. microRNA-9 targets the long non-coding RNA MALAT1 for degradation in the nucleus

    DEFF Research Database (Denmark)

    Leucci, Eleonora; Patella, Francesca; Waage, Johannes;

    2013-01-01

    microRNAs regulate the expression of over 60% of protein coding genes by targeting their mRNAs to AGO2-containing complexes in the cytoplasm and promoting their translational inhibition and/or degradation. There is little evidence so far for microRNA-mediated regulation of other classes of non...

  7. Influence of neutron irradiation on the tritium retention in beryllium

    Energy Technology Data Exchange (ETDEWEB)

    Rolli, R.; Ruebel, S.; Werle, H. [Forschungszentrum Karlsruhe, Inst. fuer Neutronenphysik und Reaktortechnik, Karlsruhe (Germany); Wu, C.H.

    1998-01-01

    Carbon-based materials and beryllium are the candidates for protective layers on the components of fusion reactors facing plasma. In contact with D-T plasma, these materials absorb tritium, and it is anticipated that tritium retention increases with the neutron damage due to neutron-induced traps. Because of the poor data base for beryllium, the work was concentrated on it. Tritium was loaded into the samples from stagnant T{sub 2}/H{sub 2} atmosphere, and afterwards, the quantity of the loaded tritium was determined by purged thermal annealing. The specification of the samples is shown. The samples were analyzed by SEM before and after irradiation. The loading and the annealing equipments are contained in two different glove boxes with N{sub 2} inert atmosphere. The methods of loading and annealing are explained. The separation of neutron-produced and loaded tritium and the determination of loaded tritium in irradiated samples are reported. Also the determination of loaded tritium in unirradiated samples is reported. It is evident that irradiated samples contained much more loaded tritium than unirradiated samples. The main results of this investigation are summarized in the table. (K.I.)

  8. Review and interpretation of recent cosmic ray beryllium isotope measurements

    Energy Technology Data Exchange (ETDEWEB)

    Buffington, A.

    1978-04-26

    Be/sup 10/ has long been of interest for cosmic ray propagation, because its radioactive decay half-life is well matched to the expected cosmic ray age. Recent beryllium isotope measurements from satellites and balloons have covered an energy range from about 30 to 300 MeV/nucleon/sup 1-3/. At the lowest energies, most of the Be/sup 10/ is absent, indicating a cosmic ray lifetime of order 2 x 10/sup 7/ years and the rather low average density of 0.2 atoms/cc traversed by the cosmic rays. At higher energies, a greater proportion of Be/sup 10/ is observed, indicating a somewhat shorter lifetime. These experiments will be reviewed and then compared with a new experiment covering from 100 to 1000 Mev/nucleon/sup 4/. Although improved experiments will be necessary to realize the full potential of cosmic ray beryllium isotope measurements, these first results are already disclosing interesting and unexpected facts about cosmic ray acceleration and propagation.

  9. Microstructural Characterization of Beryllium Treated Al-Si Alloys

    Directory of Open Access Journals (Sweden)

    M. F. Ibrahim

    2015-01-01

    Full Text Available The present study was carried out on B356 and B357 alloys using the thermal analysis technique. Metallographic samples prepared from these castings were examined using optical microscopy and FESEM. Results revealed that beryllium causes partial modification of the eutectic Si, similar to that reported for magnesium additions. Addition of 0.8 wt.% Mg reduces the eutectic temperature by ~10°C. During solidification of alloys containing high levels of Fe and Mg, but no Sr, formation of a Be-Fe phase was detected at 611°C, close to that of α-Al. The Be-Fe phase precipitates in script-like form at or close to the β-Al5SiFe platelets. A new reaction, composed of fine particles of Si and π-Fe phase, was observed to occur near the end of solidification in high Mg-, high Fe-, and Be-containing alloys. The amount of this reaction decreased with the addition of Sr. Occasionally, Be-containing phase particles were observed as part of the reaction. Addition of Be has a noticeable effect on decreasing the β-Al5FeSi platelet length; this effect may be enhanced by addition of Sr. Beryllium addition also results in precipitation of the β-Al5FeSi phase in nodular form, which lowers its harmful effects on the alloy mechanical properties.

  10. Remarkable Hydrogen Storage on Beryllium Oxide Clusters: First Principles Calculations

    CERN Document Server

    Shinde, Ravindra

    2016-01-01

    Since the current transportation sector is the largest consumer of oil, and subsequently responsible for major air pollutants, it is inevitable to use alternative renewable sources of energies for vehicular applications. The hydrogen energy seems to be a promising candidate. To explore the possibility of achieving a solid-state high-capacity storage of hydrogen for onboard applications, we have performed first principles density functional theoretical calculations of hydrogen storage properties of beryllium oxide clusters (BeO)$_{n}$ (n=2 -- 8). We observed that polar BeO bond is responsible for H$_{2}$ adsorption. The problem of cohesion of beryllium atoms does not arise, as they are an integral part of BeO clusters. The (BeO)$_{n}$ (n=2 -- 8) adsorbs 8--12 H$_{2}$ molecules with an adsorption energy in the desirable range of reversible hydrogen storage. The gravimetric density of H$_{2}$ adsorbed on BeO clusters meets the ultimate 7.5 wt% limit, recommended for onboard practical applications. In conclusion,...

  11. Neutron field produced by 25 MeV deuteron on thick beryllium for radiobiological study; energy spectrum.

    Science.gov (United States)

    Takada, Masashi; Mihara, Erika; Sasaki, Michiya; Nakamura, Takashi; Honma, Toshihiko; Kono, Koji; Fujitaka, Kazunobu

    2004-01-01

    Biological data is necessary for estimation of protection from neutrons, but there is a lack of data on biological effects of neutrons for radiation protection. Radiological study on fast neutrons has been done at the National Institute of Radiological Sciences. An intense neutron source has been produced by 25 MeV deuterons on a thick beryllium target. The neutron energy spectrum, which is essential for neutron energy deposition calculation, was measured from thermal to maximum energy range by using an organic liquid scintillator and multi-sphere moderated 3He proportional counters. The spectrum of the gamma rays accompanying the neutron beam was measured simultaneously with the neutron spectrum using the organic liquid scintillator. The transmission by the shield of the spurious neutrons originating from the target was measured to be less than 1% by using the organic liquid scintillator placed behind the collimator. The measured neutron energy spectrum is useful in dose calculations for radiobiology studies.

  12. The Caenorhabditis elegans pumilio homolog, puf-9, is required for the 3'UTR-mediated repression of the let-7 microRNA target gene, hbl-1.

    Science.gov (United States)

    Nolde, Mona J; Saka, Nazli; Reinert, Kristy L; Slack, Frank J

    2007-05-15

    The Puf family of RNA-binding proteins directs cell fates by regulating gene expression at the level of translation and RNA stability. Here, we report that the Caenorhabditis elegans pumilio homolog, puf-9, controls the differentiation of epidermal stem cells at the larval-to-adult transition. Genetic analysis reveals that loss-of-function mutations in puf-9 enhance the lethality and heterochronic phenotypes caused by mutations in the let-7 microRNA (miRNA), while suppressing the heterochronic phenotypes of lin-41, a let-7 target and homolog of Drosophila Brat. puf-9 interacts with another known temporal regulator hbl-1, the Caenorhabditis elegans ortholog of hunchback. We present evidence demonstrating that puf-9 is required for the 3'UTR-mediated regulation of hbl-1, in both the hypodermis and the ventral nerve cord. Finally, we show that this regulation is dependent on a region of the hbl-1 3'UTR that contains putative Puf family binding sites as well as binding sites for the let-7 miRNA family, suggesting that puf-9 and let-7 may mediate hypodermal seam cell differentiation by regulating common targets.

  13. METACASPASE9 modulates autophagy to confine cell death to the target cells during Arabidopsis vascular xylem differentiation

    Directory of Open Access Journals (Sweden)

    Sacha Escamez

    2016-02-01

    Full Text Available We uncovered that the level of autophagy in plant cells undergoing programmed cell death determines the fate of the surrounding cells. Our approach consisted of using Arabidopsis thaliana cell cultures capable of differentiating into two different cell types: vascular tracheary elements (TEs that undergo programmed cell death (PCD and protoplast autolysis, and parenchymatic non-TEs that remain alive. The TE cell type displayed higher levels of autophagy when expression of the TE-specific METACASPASE9 (MC9 was reduced using RNAi (MC9-RNAi. Misregulation of autophagy in the MC9-RNAi TEs coincided with ectopic death of the non-TEs, implying the existence of an autophagy-dependent intercellular signalling from within the TEs towards the non-TEs. Viability of the non-TEs was restored when AUTOPHAGY2 (ATG2 was downregulated specifically in MC9-RNAi TEs, demonstrating the importance of autophagy in the spatial confinement of cell death. Our results suggest that other eukaryotic cells undergoing PCD might also need to tightly regulate their level of autophagy to avoid detrimental consequences for the surrounding cells.

  14. Adenylyl cyclase-associated protein-1/CAP1 as a biological target substrate of gelatinase B/MMP-9.

    Science.gov (United States)

    Cauwe, Bénédicte; Martens, Erik; Van den Steen, Philippe E; Proost, Paul; Van Aelst, Ilse; Blockmans, Daniel; Opdenakker, Ghislain

    2008-09-10

    Matrix metalloproteinases (MMPs) are classically associated with the turnover of secreted structural and functional proteins. Although MMPs have been shown to process also a kaleidoscope of membrane-associated substrates, little is known about the processing of intracellular proteins by MMPs. Physiological and pathological cell apoptosis, necrosis and tumor lysis by chemotherapy, radiotherapy or immunological cytotoxicity, are examples of conditions in which an overload of intracellular proteins becomes accessible to the action of MMPs. We used a model system of dying human myelomonocytic cells to study the processing of intracellular protein substrates by gelatinase B/MMP-9 in vitro. Adenylyl cyclase-associated protein-1 or CAP1 was identified as a novel and most efficient substrate of gelatinase B/MMP-9. The presence of CAP1 in the extracellular milieu in vivo was documented by analysis of urine of patients with systemic autoimmune diseases. Whereas no active MMP-9 could be detected in urines of healthy controls, all urine samples of patients with clinical parameters of renal failure contained activated MMP-9 and/or MMP-2. In addition, in some of these patients indications of CAP1 cleavage are observed, implying CAP1 degradation in vivo. The high turnover rate of CAP1 by MMP-9, comparable to that of gelatin as the natural extracellular substrate of this enzyme, may be critical to prevent pathological conditions associated with considerable cytolysis.

  15. New and Emerging Technologies for Real-Time Air and Surface Beryllium Monitoring

    Energy Technology Data Exchange (ETDEWEB)

    Phifer, B.E. Jr.; Churnetski, E.L.; Cooke, L.E.; Reed, J.J.; Howell, M.L.; Smith, V.D.

    2001-09-01

    In this study, five emerging technologies were identified for real-time monitoring of airborne beryllium: Microwave-Induced Plasma Spectroscopy (MIPS), Aerosol Beam-Focused Laser-Induced Plasma Spectroscopy (ABFLIPS), Laser-Induced Breakdown Spectroscopy (LIBS), Surfaced-Enhanced Raman Scattering (SERS) Spectroscopy, and Micro-Calorimetric Spectroscopy (CalSpec). Desired features of real-time air beryllium monitoring instrumentation were developed from the Y-12 CBDPP. These features were used as guidelines for the identification of potential technologies as well as their unique demonstrated capability to provide real-time monitoring of similar materials. However, best available technologies were considered, regardless of their ability to comply with the desired features. None of the five technologies have the capability to measure the particle size of airborne beryllium. Although reducing the total concentration of airborne beryllium is important, current literature suggests that reducing or eliminating the concentration of respirable beryllium is critical for worker health protection. Eight emerging technologies were identified for surface monitoring of beryllium. CalSpec, MIPS, SERS, LIBS, Laser Ablation, Absorptive Stripping Voltametry (ASV), Modified Inductively Coupled Plasma (ICP) Spectroscopy, and Gamma BeAST. Desired features of real-time surface beryllium monitoring were developed from the Y-12 CBDPP. These features were used as guidelines for the identification of potential technologies. However, the best available technologies were considered regardless of their ability to comply with the desired features.

  16. Use of 41Ar production to measure ablator areal density in NIF beryllium implosions

    Science.gov (United States)

    Wilson, D. C.; Cassata, W. B.; Sepke, S. M.; Velsko, C. A.; Huang, H.; Yeamans, C. B.; Kline, J. L.; Yi, A.; Simakov, A. N.; Haan, S. W.; Batha, S. H.; Dewald, E. L.; Rygg, J. R.; Tommasini, R.; Xu, H.; Kong, C.; Bae, J.; Rice, N.

    2017-02-01

    For the first time, 41Ar produced by the (n,ϒ) reaction from 40Ar in the beryllium shell of a DT filled Inertial Confinement Fusion capsule has been measured. Ar is co-deposited with beryllium in the sputter deposition of the capsule shell. Combined with a measurement of the neutron yield, the radioactive 41Ar then quantifies the areal density of beryllium during the DT neutron production. The measured 1.15 ± 0.17 × 10+8 atoms of 41Ar are 2.5 times that from the best post-shot calculation, suggesting that the Ar and Be areal densities are correspondingly higher than those calculated. Possible explanations are that (1) the beryllium shell is compressed more than calculated, (2) beryllium has mixed into the cold DT ice, or more likely (3) less beryllium is ablated than calculated. Since only one DT filled beryllium capsule has been fielded at NIF, these results can be confirmed and expanded in the future.

  17. Design and modeling of ignition targets for the National Ignition Facility

    Energy Technology Data Exchange (ETDEWEB)

    Haan, S.W.; Pollaine, S.M.; Lindl, J.D.; Suter, L.J.; Berger, R.L.; Powers, L.V.; Alley, W.E.; Amendt, P.A.; Futterman, J.A.; Levedahl, W.K.; Rosen, M.D.; Rowley, D.P.; Sacks, R.A.; Shestakov, A.I.; Strobel, G.L.; Tabak, M.; Weber, S.V.; Zimmerman, G.B. [Lawrence Livermore National Laboratory, Livermore, California 94550 (United States); Krauser, W.J.; Wilson, D.C.; Coggeshall, S.V.; Harris, D.B.; Hoffman, N.M.; Wilde, B.H. [Los Alamos National Laboratory, Los Alamos, New Mexico 87545 (United States)

    1995-06-01

    Several targets are described that in simulations give yields of 1--30 MJ when indirectly driven by 0.9--2 MJ of 0.35 {mu}m laser light. The article describes the targets, the modeling that was used to design them, and the modeling done to set specifications for the laser system in the proposed National Ignition Facility. Capsules with beryllium or polystyrene ablators are enclosed in gold hohlraums. All the designs utilize a cryogenic fuel layer; it is very difficult to achieve ignition at this scale with a noncryogenic capsule. It is necessary to use multiple bands of illumination in the hohlraum to achieve sufficiently uniform x-ray irradiation, and to use a low-{ital Z} gas fill in the hohlraum to reduce filling of the hohlraum with gold plasma. Critical issues are hohlraum design and optimization, Rayleigh--Taylor instability modeling, and laser--plasma interactions.

  18. A homozygous Keap1-knockout human embryonic stem cell line generated using CRISPR/Cas9 mediates gene targeting

    Directory of Open Access Journals (Sweden)

    So-Jung Kim

    2017-03-01

    Full Text Available Kelch-like ECH-associated protein 1 (keap1 is a cysteine-rich protein that interacts with transcription factor Nrf2 in a redox-sensitive manner, leading to the degradation of Nrf2 (Kim et al., 2014a. Disruption of Keap1 results in the induction of Nrf2-related signaling pathways involving the expression of a set of anti-oxidant and anti-inflammatory genes. We generated biallelic mutants of the Keap1 gene using a CRISPR-Cas9 genome editing method in the H9 human embryonic stem cell (hESC. The Keap1 homozygous-knockout H9 cell line retained normal morphology, gene expression, and in vivo differentiation potential.

  19. Controlled delivery of β-globin-targeting TALENs and CRISPR/Cas9 into mammalian cells for genome editing using microinjection.

    Science.gov (United States)

    Cottle, Renee N; Lee, Ciaran M; Archer, David; Bao, Gang

    2015-11-12

    Tal-effector nucleases (TALEN) and clustered regularly interspaced short palindromic repeats (CRISPR) with CRISPR-associated (Cas) proteins are genome editing tools with unprecedented potential. However, the ability to deliver optimal amounts of these nucleases into mammalian cells with minimal toxicity poses a major challenge. Common delivery approaches are transfection- and viral-based methods; each associated with significant drawbacks. An alternative method for directly delivering genome-editing reagents into single living cells with high efficiency and controlled volume is microinjection. Here, we characterize a glass microcapillary-based injection system and demonstrate controlled co-injection of TALENs or CRISPR/Cas9 together with donor template into single K562 cells for targeting the human β-globin gene. We quantified nuclease induced insertions and deletions (indels) and found that, with β-globin-targeting TALENs, similar levels of on- and off-target activity in cells could be achieved by microinjection compared with nucleofection. Furthermore, we observed 11% and 2% homology directed repair in single K562 cells co-injected with a donor template along with CRISPR/Cas9 and TALENs respectively. These results demonstrate that a high level of targeted gene modification can be achieved in human cells using glass-needle microinjection of genome editing reagents.

  20. Considerations for the development of health-based surface dust cleanup criteria for beryllium.

    Science.gov (United States)

    Shay, Erin; De Gandiaga, Elise; Madl, Amy K

    2013-03-01

    The exposure-response patterns with beryllium sensitization (BeS), chronic beryllium disease (CBD) and lung cancer are influenced by a number of biological and physicochemical factors. Recent studies have suggested dermal exposure as a pathway for BeS. In light of the current non-health-based DOE Beryllium Rule surface criteria, the feasibility of deriving a human health-based surface dust cleanup criteria (SDCC) for beryllium was assessed based on toxicology and health risk factors via all potential routes of exposure. Beryllium-specific and general exposure factors were evaluated, including (1) beryllium physicochemical characteristics, bioavailability and influence on disease prevalence, and (2) chemical dissipation, resuspension and transfer. SDCC for non-cancer (SDCC) and cancer (SDCC) endpoints were derived from a combination of modern methods applied for occupational, residential and building reentry surface dust criteria. The most conservative SDCC estimates were derived for dermal exposure (5-379 μg/100 cm for 0.1-1% damaged skin and 17-3337 μg/100 cm for intact skin), whereas the SDCC for inhalation exposure ranged from 51 to 485 μg/100 cm. Considering this analysis, the lowest DOE surface criterion of 0.2 μg/100 cm is conservative for minimizing exposure and potential risks associated with beryllium-contaminated surfaces released for non-beryllium industrial or public sector use. Although methodological challenges exist with sampling and analysis procedures, data variability and interpretation of surface dust information in relation to anthropogenic and natural background concentrations, this evaluation should provide useful guidance with regard to cleanup of manufacturing equipment or remediation of property for transfer to the general public or non-beryllium industrial facilities.

  1. MicroRNA-125b suppresses the epithelial-mesenchymal transition and cell invasion by targeting ITGA9 in melanoma.

    Science.gov (United States)

    Zhang, Jie; Na, Sijia; Liu, Caiyue; Pan, Shuting; Cai, Junying; Qiu, Jiaxuan

    2016-05-01

    Increasing evidence has shown that aberrant miRNAs contribute to the development and progression of human melanoma. Previous studies have shown that miR-125b functions as a suppressor in malignant melanoma. However, the molecular function and mechanism by which miR-125b influences melanoma growth and invasion are still unclear. In this study, we aimed to investigate the role of miR-125b in melanoma progression and metastasis. We found that miR-125b expression is significantly downregulated in primary melanoma, and an even greater downregulation was observed in metastatic invasion. Restored expression of miR-125b in melanoma suppressed cell proliferation and invasion both in vitro and in vivo. Furthermore, our findings demonstrate that upregulating miR-125b significantly inhibits malignant phenotypes by repressing the expression of integrin alpha9 (ITGA9). Finally, our data reveal that upregulated expression of ITGA9 in melanoma tissues is inversely associated with miR-125b levels. Together, our results demonstrate that upregulation of ITGA9 in response to the decrease in miR-125b in metastatic melanoma is responsible for melanoma tumor cell migration and invasion.

  2. Targeting malignant B cells as antigen-presenting cells: TLR-9 agonist induces systemic regression of lymphoma.

    Science.gov (United States)

    Klein-González, Nela; Holtick, Udo; Fairfax, Kirsten; Weihrauch, Martin R; von Bergwelt-Baildon, Michael S

    2011-03-01

    Evaluation of: Brody JD, Ai WZ, Czerwinski DK et al. In situ vaccination with a TLR9 agonist induces systemic lymphoma regression: a Phase I/II study. J. Clin. Oncol. 28(28), 4324-4332 (2010). Despite high response rates of the follicular B-cell lymphoma to monoclonal antibodies, the clinical course of lymphoma is still characterized by a continuous pattern of relapse. Brody and colleagues treated 15 patients with relapsed, low-grade lymphoma using low-dose radiotherapy applied to one of the tumor sites with combined injection of a TLR-9 agonist at the same site. This strategy induced specific immunity and tumor regression in several patients with an objective response rate of 27%. The results indicate an involvement of the tumor TLR-9-expressing B cells acting as antigen-presenting cells. TLR-9 in situ vaccination combined with local radiotherapy clearly warrants further in-depth analysis and investigation in a Phase III randomized trial, and may provide a new opportunity for the treatment of B-cell malignancies.

  3. Conditions for preparation of ultrapure beryllium by electrolytic refining in molten alkali-metal chlorides

    Energy Technology Data Exchange (ETDEWEB)

    Wohlfarth, Hagen

    1982-02-01

    Electrolytic refining is regarded as the most suitable process for the production of beryllium with impurity contents below 1 at.-ppM. Several parameters are important for electrolytic refining of beryllium in a BeCl/sub 2/-containing LiCl-KCl melt: current density, BeCl/sub 2/ content, electrolyte temperature, composition of the unpurified beryllium and impurity-ion concentrations in the melt, as well as apparatus characteristics such as rotation speed of the cathode and condition of the crucible material. These factors were studied and optimized such that extensive removal of the maximum number of accompanying and alloying elements was achieved.

  4. The structure and the Raman vibrational spectrum of the beryllium aquacation.

    Science.gov (United States)

    Rozmanov, Dmitry A; Sizova, Olga V; Skripkin, Mikhail Yu; Burkov, Kim A

    2005-11-01

    The experimental Raman vibrational spectrum of the 5.94 m water solution of the beryllium(II) chloride has been acquired. Theoretical frequencies, infrared and Raman intensities of the vibrational spectrum of the beryllium cation tetrahydrate have been calculated by means of quantum chemical approach. The peaks of the experimental spectrum have been assigned on the basis of the results of the quantum-chemical calculations. It has been shown that the hydrating surrounding of the aquacation increases effectively the frequency of the beryllium-oxygen stretching vibration by 16% in comparison with the free complex.

  5. Reprogrammed CRISPR-Cas9 targeting the conserved regions of HPV6/11 E7 genes inhibits proliferation and induces apoptosis in E7-transformed keratinocytes

    Directory of Open Access Journals (Sweden)

    Yu-Chen Liu

    2016-01-01

    Full Text Available The persistence infection of low-risk type (type 6 or type 11 of human papillomavirus (HPV is the main cause of genital warts. Given the high rate of recurrence after treatment, the use of a new molecular agent is certain to be of value. The aim of this study was to achieve targeted inactivation of viral E 7 gene in keratinocytes using the reprogrammed clustered regularly interspaced short palindromic repeats (CRISPR/CRISPR-associated (Cas 9 system. To accomplish this, a universal CRISPR-Cas9 system for targeting both HPV6/11 E 7 genes was constructed by using a dual guide RNA vector. After transfection of the vector into E 7-transfromed keratinocytes, the expression level of E 7 protein was measured using western-blot analysis and the sequence of the E 7 gene was determined using Sanger sequencing. Cell proliferation was analyzed by CCK-8 assay, and cell apoptosis was evaluated by Hoechst 33258 staining, flow cytometry analysis and ELISA assay. The results indicated that both HPV6/11 E 7 genes can be inactivated by the single CRISPR-Cas9 system. Furthermore, silencing of E 7 led to inhibition of cell proliferation and induction of apoptosis in E 7-transfromed keratinocytes but not in normal keratinocytes. Our data suggested that the reprogrammed CRISPR-Cas9 system has the potential for the development of an adjuvant therapy for genital warts.

  6. CRISPR/Cas9 DNA cleavage at SNP-derived PAM enables both in vitro and in vivo KRT12 mutation-specific targeting.

    Science.gov (United States)

    Courtney, D G; Moore, J E; Atkinson, S D; Maurizi, E; Allen, E H A; Pedrioli, D M L; McLean, W H I; Nesbit, M A; Moore, C B T

    2016-01-01

    CRISPR/Cas9-based therapeutics hold the possibility for permanent treatment of genetic disease. The potency and specificity of this system has been used to target dominantly inherited conditions caused by heterozygous missense mutations through inclusion of the mutated base in the short-guide RNA (sgRNA) sequence. This research evaluates a novel approach for targeting heterozygous single-nucleotide polymorphisms (SNPs) using CRISPR/Cas9. We determined that a mutation within KRT12, which causes Meesmann's epithelial corneal dystrophy (MECD), leads to the occurrence of a novel protospacer adjacent motif (PAM). We designed an sgRNA complementary to the sequence adjacent to this SNP-derived PAM and evaluated its potency and allele specificity both in vitro and in vivo. This sgRNA was found to be highly effective at reducing the expression of mutant KRT12 mRNA and protein in vitro. To assess its activity in vivo we injected a combined Cas9/sgRNA expression construct into the corneal stroma of a humanized MECD mouse model. Sequence analysis of corneal genomic DNA revealed non-homologous end-joining repair resulting in frame-shifting deletions within the mutant KRT12 allele. This study is the first to demonstrate in vivo gene editing of a heterozygous disease-causing SNP that results in a novel PAM, further highlighting the potential for CRISPR/Cas9-based therapeutics.

  7. Reprogrammed CRISPR-Cas9 targeting the conserved regions of HPV6/11 E7 genes inhibits proliferation and induces apoptosis in E7-transformed keratinocytes.

    Science.gov (United States)

    Liu, Yu-Chen; Cai, Zhi-Ming; Zhang, Xue-Jun

    2016-01-01

    The persistence infection of low-risk type (type 6 or type 11) of human papillomavirus (HPV) is the main cause of genital warts. Given the high rate of recurrence after treatment, the use of a new molecular agent is certain to be of value. The aim of this study was to achieve targeted inactivation of viral E 7 gene in keratinocytes using the reprogrammed clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated (Cas) 9 system. To accomplish this, a universal CRISPR-Cas9 system for targeting both HPV6/11 E 7 genes was constructed by using a dual guide RNA vector. After transfection of the vector into E 7-transformed keratinocytes, the expression level of E 7 protein was measured using western-blot analysis and the sequence of the E 7 gene was determined using Sanger sequencing. Cell proliferation was analyzed by CCK-8 assay, and cell apoptosis was evaluated by Hoechst 33258 staining, flow cytometry analysis and ELISA assay. The results indicated that both HPV6/11 E 7 genes can be inactivated by the single CRISPR-Cas9 system. Furthermore, silencing of E 7 led to inhibition of cell proliferation and induction of apoptosis in E 7-transformed keratinocytes but not in normal keratinocytes. Our data suggested that the reprogrammed CRISPR-Cas9 system has the potential for the development of an adjuvant therapy for genital warts.

  8. Atmospheric deposition of beryllium in Central Europe: comparison of soluble and insoluble fractions in rime and snow across a pollution gradient.

    Science.gov (United States)

    Bohdalkova, Leona; Novak, Martin; Voldrichova, Petra; Prechova, Eva; Veselovsky, Frantisek; Erbanova, Lucie; Krachler, Michael; Komarek, Arnost; Mikova, Jitka

    2012-11-15

    Little is known about atmospheric input of beryllium (Be) into ecosystems, despite its highly toxic behavior. For three consecutive winters (2009-2011), we measured Be concentrations in horizontal deposition (rime) and vertical deposition (snow) at 10 remote mountain-top locations in the Czech Republic, Central Europe. Beryllium was determined both in filtered waters, and in HF digests of insoluble particles. Across the sites, soluble Be concentrations in rime were 7 times higher, compared to snow (6.1 vs. 0.9ng·L(-1)). Rime scavenged the pollution-rich lower segments of clouds. The lowest Be concentrations were detected in the soluble fraction of snow. Across the sites, 34% of total Be deposition occurred in the form of soluble (bioavailable) Be, the rest were insoluble particles. Beryllium fluxes decreased in the order: vertical dry deposition insoluble>vertical dry deposition soluble>horizontal deposition soluble>vertical wet deposition insoluble>vertical wet deposition soluble>horizontal deposition insoluble. The average contributions of these Be forms to total deposition were 56, 21, 8, 7, 5 and 3%, respectively. Sites in the northeast were more Be-polluted than the rest of the country with sources of pollution in industrial Silesia.

  9. Photoluminescence enhancement from GaN by beryllium doping

    Science.gov (United States)

    García-Gutiérrez, R.; Ramos-Carrazco, A.; Berman-Mendoza, D.; Hirata, G. A.; Contreras, O. E.; Barboza-Flores, M.

    2016-10-01

    High quality Be-doped (Be = 0.19 at.%) GaN powder has been grown by reacting high purity Ga diluted alloys (Be-Ga) with ultra high purity ammonia in a horizontal quartz tube reactor at 1200 °C. An initial low-temperature treatment to dissolve ammonia into the Ga melt produced GaN powders with 100% reaction efficiency. Doping was achieved by dissolving beryllium into the gallium metal. The powders synthesized by this method regularly consist of two particle size distributions: large hollow columns with lengths between 5 and 10 μm and small platelets in a range of diameters among 1 and 3 μm. The GaN:Be powders present a high quality polycrystalline profile with preferential growth on the [10 1 bar 1] plane, observed by means of X-ray diffraction. The three characteristics growth planes of the GaN crystalline phase were found by using high resolution TEM microscopy. The optical enhancing of the emission in the GaN powder is attributed to defects created with the beryllium doping. The room temperature photoluminescence emission spectra of GaN:Be powders, revealed the presence of beryllium on a shoulder peak at 3.39 eV and an unusual Y6 emission at 3.32eV related to surface donor-acceptor pairs. Also, a donor-acceptor-pair transition at 3.17 eV and a phonon replica transition at 3.1 eV were observed at low temperature (10 K). The well-known yellow luminescence band coming from defects was observed in both spectra at room and low temperature. Cathodoluminescence emission from GaN:Be powders presents two main peaks associated with an ultraviolet band emission and the yellow emission known from defects. To study the trapping levels related with the defects formed in the GaN:Be, thermoluminescence glow curves were obtained using UV and β radiation in the range of 50 and 150 °C.

  10. Studies on the genotoxic effect of beryllium chloride and the possible protective role of selenium/vitamins A, C and E.

    Science.gov (United States)

    Fahmy, Maha A; Hassan, Nagwa H A; Farghaly, Ayman A; Hassan, Entesar E S

    2008-04-30

    The genotoxic potential of beryllium chloride (BeCl2) was evaluated in vivo in mice using different endpoints. Chromosomal aberrations in bone marrow cells and in spermatocytes as well as sperm abnormalities were determined in the tested mice. The protective role of an orally administered drug consisting of selenium and vitamins A, C and E (selenium-ACE) was also studied. For analysis of chromosomal aberrations, both single and repeated oral treatments for a period of 3 weeks were performed. The doses used were 93.75, 187.50, 375, and 750 mg BeCl2/kg bw, which corresponds to 1/16, 1/8, 1/4, and 1/2 of the experimental LD50. BeCl2 induced a statistically significant increase in the percentage of chromosomal aberrations in both somatic and germ cells, with a dose- and time-response. The percentage of induced chromosomal aberrations was significantly reduced in all BeCl2-treated groups after oral administration of selenium-ACE. Beryllium chloride also induced a significant increase in the percentage of abnormal sperm. This percentage reached values of 9.62 +/- 0.32 and 5.56 +/- 0.31 in mice treated with the highest test dose of BeCl2 and with BeCl2+selenium-ACE, respectively, compared with 1.96 +/- 0.14 for the control. In conclusion, the results demonstrate the genotoxic effect of beryllium chloride and confirm the protective role of selenium-ACE against the genotoxicity of beryllium chloride.

  11. Gain of Toxicity from ALS/FTD-Linked Repeat Expansions in C9ORF72 Is Alleviated by Antisense Oligonucleotides Targeting GGGGCC-Containing RNAs.

    Science.gov (United States)

    Jiang, Jie; Zhu, Qiang; Gendron, Tania F; Saberi, Shahram; McAlonis-Downes, Melissa; Seelman, Amanda; Stauffer, Jennifer E; Jafar-Nejad, Paymaan; Drenner, Kevin; Schulte, Derek; Chun, Seung; Sun, Shuying; Ling, Shuo-Chien; Myers, Brian; Engelhardt, Jeffery; Katz, Melanie; Baughn, Michael; Platoshyn, Oleksandr; Marsala, Martin; Watt, Andy; Heyser, Charles J; Ard, M Colin; De Muynck, Louis; Daughrity, Lillian M; Swing, Deborah A; Tessarollo, Lino; Jung, Chris J; Delpoux, Arnaud; Utzschneider, Daniel T; Hedrick, Stephen M; de Jong, Pieter J; Edbauer, Dieter; Van Damme, Philip; Petrucelli, Leonard; Shaw, Christopher E; Bennett, C Frank; Da Cruz, Sandrine; Ravits, John; Rigo, Frank; Cleveland, Don W; Lagier-Tourenne, Clotilde

    2016-05-04

    Hexanucleotide expansions in C9ORF72 are the most frequent genetic cause of amyotrophic lateral sclerosis and frontotemporal dementia. Disease mechanisms were evaluated in mice expressing C9ORF72 RNAs with up to 450 GGGGCC repeats or with one or both C9orf72 alleles inactivated. Chronic 50% reduction of C9ORF72 did not provoke disease, while its absence produced splenomegaly, enlarged lymph nodes, and mild social interaction deficits, but not motor dysfunction. Hexanucleotide expansions caused age-, repeat-length-, and expression-level-dependent accumulation of RNA foci and dipeptide-repeat proteins synthesized by AUG-independent translation, accompanied by loss of hippocampal neurons, increased anxiety, and impaired cognitive function. Single-dose injection of antisense oligonucleotides (ASOs) that target repeat-containing RNAs but preserve levels of mRNAs encoding C9ORF72 produced sustained reductions in RNA foci and dipeptide-repeat proteins, and ameliorated behavioral deficits. These efforts identify gain of toxicity as a central disease mechanism caused by repeat-expanded C9ORF72 and establish the feasibility of ASO-mediated therapy.

  12. The tumor targeted superantigen ABR-217620 selectively engages TRBV7-9 and exploits TCR-pMHC affinity mimicry in mediating T cell cytotoxicity.

    Directory of Open Access Journals (Sweden)

    Gunnar Hedlund

    Full Text Available The T lymphocytes are the most important effector cells in immunotherapy of cancer. The conceptual objective for developing the tumor targeted superantigen (TTS ABR-217620 (naptumomab estafenatox, 5T4Fab-SEA/E-120, now in phase 3 studies for advanced renal cell cancer, was to selectively coat tumor cells with cytotoxic T lymphocytes (CTL target structures functionally similar to natural CTL pMHC target molecules. Here we present data showing that the molecular basis for the anti-tumor activity by ABR-217620 resides in the distinct interaction between the T cell receptor β variable (TRBV 7-9 and the engineered superantigen (Sag SEA/E-120 in the fusion protein bound to the 5T4 antigen on tumor cells. Multimeric but not monomeric ABR-217620 selectively stains TRBV7-9 expressing T lymphocytes from human peripheral blood similar to antigen specific staining of T cells with pMHC tetramers. SEA/E-120 selectively activates TRBV7-9 expressing T lymphocytes resulting in expansion of the subset. ABR-217620 selectively triggers TRBV7-9 expressing cytotoxic T lymphocytes to kill 5T4 positive tumor cells. Furthermore, ABR-217620 activates TRBV7-9 expressing T cell line cells in the presence of cell- and bead-bound 5T4 tumor antigen. Surface plasmon resonance analysis revealed that ABR-217620 binds to 5T4 with high affinity, to TRBV7-9 with low affinity and to MHC class II with very low affinity. The T lymphocyte engagement by ABR-217620 is constituted by displaying high affinity binding to the tumor cells (KD approximately 1 nM and with the mimicry of natural productive immune TCR-pMHC contact using affinities of around 1 µM. This difference in kinetics between the two components of the ABR-217620 fusion protein will bias the binding towards the 5T4 target antigen, efficiently activating T-cells via SEA/E-120 only when presented by the tumor cells.

  13. Targeted mutagenesis in Atlantic salmon (Salmo salar L. using the CRISPR/Cas9 system induces complete knockout individuals in the F0 generation.

    Directory of Open Access Journals (Sweden)

    Rolf B Edvardsen

    Full Text Available Understanding the biological function behind key proteins is of great concern in Atlantic salmon, both due to a high commercial importance and an interesting life history. Until recently, functional studies in salmonids appeared to be difficult. However, the recent discovery of targeted mutagenesis using the CRISPR/Cas9 (clustered regularly interspaced palindromic repeats/CRISPR-associated system enables performing functional studies in Atlantic salmon to a great extent. We used the CRISPR/Cas9 system to target two genes involved in pigmentation, tyrosinase (tyr and solute carrier family 45, member 2 (slc45a2. Embryos were assayed for mutation rates at the 17 somite stage, where 40 and 22% of all injected embryos showed a high degree of mutation induction for slc45a2 and tyr, respectively. At hatching this mutation frequency was also visible for both targeted genes, displaying a graded phenotype ranging from complete lack of pigmentation to partial loss and normal pigmentation. CRISPRslc45a2/Cas9 injected embryos showing a complete lack of pigmentation or just a few spots of pigments also lacked wild type sequences when assaying more than 80 (slc45a2 sequence clones from whole embryos. This indicates that CRISPR/Cas9 can induce double-allelic knockout in the F0 generation. However, types and frequency of indels might affect the phenotype. Therefore, the variation of indels was assayed in the graded pigmentation phenotypes produced by CRISPR/Cas9-slc45a2. The results show a tendency for fewer types of indels formed in juveniles completely lacking pigmentation compared to juveniles displaying partial pigmentation. Another interesting observation was a high degree of the same indel type in different juveniles. This study shows for the first time successful use of the CRISPR/Cas9 technology in a marine cold water species. Targeted double-allelic mutations were obtained and, though the level of mosaicism has to be considered, we demonstrate that F0

  14. Targeted mutagenesis in Atlantic salmon (Salmo salar L.) using the CRISPR/Cas9 system induces complete knockout individuals in the F0 generation.

    Science.gov (United States)

    Edvardsen, Rolf B; Leininger, Sven; Kleppe, Lene; Skaftnesmo, Kai Ove; Wargelius, Anna

    2014-01-01

    Understanding the biological function behind key proteins is of great concern in Atlantic salmon, both due to a high commercial importance and an interesting life history. Until recently, functional studies in salmonids appeared to be difficult. However, the recent discovery of targeted mutagenesis using the CRISPR/Cas9 (clustered regularly interspaced palindromic repeats/CRISPR-associated) system enables performing functional studies in Atlantic salmon to a great extent. We used the CRISPR/Cas9 system to target two genes involved in pigmentation, tyrosinase (tyr) and solute carrier family 45, member 2 (slc45a2). Embryos were assayed for mutation rates at the 17 somite stage, where 40 and 22% of all injected embryos showed a high degree of mutation induction for slc45a2 and tyr, respectively. At hatching this mutation frequency was also visible for both targeted genes, displaying a graded phenotype ranging from complete lack of pigmentation to partial loss and normal pigmentation. CRISPRslc45a2/Cas9 injected embryos showing a complete lack of pigmentation or just a few spots of pigments also lacked wild type sequences when assaying more than 80 (slc45a2) sequence clones from whole embryos. This indicates that CRISPR/Cas9 can induce double-allelic knockout in the F0 generation. However, types and frequency of indels might affect the phenotype. Therefore, the variation of indels was assayed in the graded pigmentation phenotypes produced by CRISPR/Cas9-slc45a2. The results show a tendency for fewer types of indels formed in juveniles completely lacking pigmentation compared to juveniles displaying partial pigmentation. Another interesting observation was a high degree of the same indel type in different juveniles. This study shows for the first time successful use of the CRISPR/Cas9 technology in a marine cold water species. Targeted double-allelic mutations were obtained and, though the level of mosaicism has to be considered, we demonstrate that F0 fish can be used

  15. Porcine bocavirus NP1 negatively regulates interferon signaling pathway by targeting the DNA-binding domain of IRF9

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Ruoxi [State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070 (China); The Cooperative Innovation Center for Sustainable Pig Production, Wuhan 430070 (China); Fang, Liurong, E-mail: fanglr@mail.hzau.edu.cn [State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070 (China); The Cooperative Innovation Center for Sustainable Pig Production, Wuhan 430070 (China); Wang, Dang; Cai, Kaimei; Zhang, Huan [State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070 (China); The Cooperative Innovation Center for Sustainable Pig Production, Wuhan 430070 (China); Xie, Lilan; Li, Yi [College of Life Science and Technology, Wuhan Institute of Bioengineering, Wuhan 430415 (China); Chen, Huanchun; Xiao, Shaobo [State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070 (China); The Cooperative Innovation Center for Sustainable Pig Production, Wuhan 430070 (China)

    2015-11-15

    To subvert host antiviral immune responses, many viruses have evolved countermeasures to inhibit IFN signaling pathway. Porcine bocavirus (PBoV), a newly identified porcine parvovirus, has received attention because it shows clinically high co-infection prevalence with other pathogens in post-weaning multisystemic wasting syndrome (PWMS) and diarrheic piglets. In this study, we screened the structural and non-structural proteins encoded by PBoV and found that the non-structural protein NP1 significantly suppressed IFN-stimulated response element (ISRE) activity and subsequent IFN-stimulated gene (ISG) expression. However, NP1 affected neither the activation and translocation of STAT1/STAT2, nor the formation of the heterotrimeric transcription factor complex ISGF3 (STAT1/STAT2/IRF9). Detailed analysis demonstrated that PBoV NP1 blocked the ISGF3 DNA-binding activity by combining with the DNA-binding domain (DBD) of IRF9. In summary, these results indicate that PBoV NP1 interferes with type I IFN signaling pathway by blocking DNA binding of ISGF3 to attenuate innate immune responses. - Highlights: • Porcine bocavirus (PBoV) NP1 interferes with the IFN α/β signaling pathway. • PBoV NP1 does not prevent STAT1/STAT2 phosphorylation and nuclear translocation. • PBoV NP1 inhibits the DNA-binding activity of ISGF3. • PBoV NP1 interacts with the DNA-binding domain of IRF9.

  16. Beryllium Separation from Beryllium Containing Solution with Solvent Extraction Method%溶剂萃取法从含铍溶液中分离铍

    Institute of Scientific and Technical Information of China (English)

    刘珍珍; 刘勇; 刘牡丹

    2012-01-01

    Beryllium was extracted from the sulphuric acid leaching solution of complex low grade beryllium ore with solvent extraction process. The effecting factors on beryllium single stage extraction rate were researched. The results show that the optimal conditions were pH in aqueous phase of 2?. 5, concentration of beryllium in leaching solution of 1. 5~2. 5 g/L, volume fraction of P204 of 30%, extraction time of 20 min, and W/O=l. In this conditions, more than 98. 50% beryllium is separated by four stage countercur-rent extraction.%采用溶剂萃取法从某复杂低品位铍矿的硫酸浸出液中进行铍的分离,研究了不同因素对铍的单级萃取效果的影响.结果表明,最佳条件为:水相pH=2~2.5、浸出液初始铍浓度1.5~2.5 g/L、P204体积分数30%、萃取时间20 min、相比为1.在此条件下四级逆流萃取后铍萃取率可达到98.50%.

  17. Modes of Occurrence and Geological Origin of Beryllium in Coals from the Pu'an Coalfield, Guizhou, Southwest China

    Institute of Scientific and Technical Information of China (English)

    YANG Jianye

    2007-01-01

    The concentration, modes of occurrence and geological origin of beryllium in five workable coal beds from the Pu'an Coalfield of Guizbou were studied using the inductively coupled-plasma mass spectrometry (ICP-MS), floating and sinking experiments (FSE) and sequential chemical extraction procedures (SCEP). The results show that the average concentration of beryllium in coals from the Pu'an Coalfield is 1.54 μg/g, much lower than that in most Chinese and worldwide coals.Beryllium in the Pu'an coals was not significantly enriched. However, it should be noted that the No. 8 coal bed from the study area has a high concentration of beryllium, 6.89 μg/g, three times higher than the background value of beryllium in coal. Beryllium in coal mainly occurs as organic association and has predominantly originated from coal-forming plants when its concentration is relatively low. The concentration of beryllium occurring as organic association is close to that distributed in inorganic matter when beryllium concentration of coal is similar to its background value, and in addition to coal-forming plants, beryllium is mainly derived from detrital materials of terrigenous origin. When beryllium is anomalously enriched in coal, it mainly occurs as organic association and is derived from volcanic tonsteins leached for a long geological time and then adsorbed by organic matter in peat mire.

  18. Optical properties and structure of beryllium lead silicate glasses

    Energy Technology Data Exchange (ETDEWEB)

    Zhidkov, I. S., E-mail: i.s.zhidkov@urfu.ru [Ural Federal University, Mira Str. 19, Yekaterinburg, 620002, Russia and Institute of Metal Physics, Russian Academy of Sciences-Ural Division, S. Kovalevskoi Str. 18, 620990 Yekaterinburg (Russian Federation); Zatsepin, A. F.; Cholakh, S. O.; Kuznetsova, Yu. A. [Ural Federal University, Mira Str. 19, Yekaterinburg, 620002 (Russian Federation)

    2014-10-21

    Luminescence and optical properties and structural features of (BeO){sub x}(PbO⋅SiO{sub 2}){sub 1−x} glasses (x = 0 ÷ 0.3) are investigated by means of optical absorption and photoluminescence spectroscopy and X-ray diffraction. The regularities of the formation of the optical absorption edge and static disorder are studied. It is shown that the optical absorption and luminescence are determined by transitions between localized states of lead ions. The impact of beryllium oxide on optical and luminescence properties and electronic structure of bands tails is discussed. The presence of two different concentration ranges with various short-range order structure and band tails nature has been established.

  19. Optical properties and structure of beryllium lead silicate glasses

    Science.gov (United States)

    Zhidkov, I. S.; Zatsepin, A. F.; Cholakh, S. O.; Kuznetsova, Yu. A.

    2014-10-01

    Luminescence and optical properties and structural features of (BeO)x(PbOṡSiO2)1-x glasses (x = 0 ÷ 0.3) are investigated by means of optical absorption and photoluminescence spectroscopy and X-ray diffraction. The regularities of the formation of the optical absorption edge and static disorder are studied. It is shown that the optical absorption and luminescence are determined by transitions between localized states of lead ions. The impact of beryllium oxide on optical and luminescence properties and electronic structure of bands tails is discussed. The presence of two different concentration ranges with various short-range order structure and band tails nature has been established.

  20. Near real-time fluorescence detection of beryllium

    Energy Technology Data Exchange (ETDEWEB)

    McCleskey, T. M. (Thomas Mark); Ehler, D. S. (Deborah S.); Minogue, E. M. (Edel Mary); Collis, G. E. (Gavin E.); Keizer, T. S. (Timothy S.); Burrell, A. K. (Anthony K.); Sauer, N. N. (Nancy N.); John, K. D. (Kevin D.)

    2004-01-01

    We report on a fluorescent test for beryllium designed for analyzing swipes. The detection is rapid, quantitative and deployable in the field with $5,000 portable fluorimeter. Swipes are placed in a vial and a dilution solution is added. The vials are then rotated for 30 minutes and then syringe filtered. An aliquot of 100 pL is added to a detector solution and fluorescence measured with a portable ocean optics unit. We can readily detect down to 0.02 {micro}g on a filter paper. Interference studies have been carried out with various metals including Al, Fe, Pb, U, Ca, W, Ni, Co and Cu. The technique has proven to be successful under various conditions including a variety of surfaces both in the lab and in field. It is a user-friendly, cost effective method.

  1. Tensile and fracture toughness test results of neutron irradiated beryllium

    Energy Technology Data Exchange (ETDEWEB)

    Chaouadi, R.; Moons, F.; Puzzolante, J.L. [Centre d`Etude de l`Energie Nucleaire, Mol (Belgium)

    1998-01-01

    Tensile and fracture toughness test results of four Beryllium grades are reported here. The flow and fracture properties are investigated by using small size tensile and round compact tension specimens. Irradiation was performed at the BR2 material testing reactor which allows various temperature and irradiation conditions. The fast neutron fluence (>1 MeV) ranges between 0.65 and 2.45 10{sup 21} n/cm{sup 2}. In the meantime, un-irradiated specimens were aged at the irradiation temperatures to separate if any the effect of temperature from irradiation damage. Test results are analyzed and discussed, in particular in terms of the effects of material grade, test temperature, thermal ageing and neutron irradiation. (author)

  2. Specification for nuclear-grade beryllium oxide powder

    CERN Document Server

    American Society for Testing and Materials. Philadelphia

    2008-01-01

    1.1 This specification defines the physical and chemical requirements of nuclear-grade beryllium oxide (BeO) powder to be used in fabricating nuclear components. 1.2 This specification does not include requirements for health and safety. , , It recognizes the material as a Class B poison and suggests that producers and users become thoroughly familiar with and comply to applicable federal, state, and local regulations and handling guidelines. 1.3 Special tests and procedures are given in Annex A1 and Annex A2. 1.4 The values stated in SI units are to be regarded as standard. No other units of measurement are included in this standard.

  3. Notched strength of beryllium powder and ingot sheets.

    Science.gov (United States)

    Moss, R. G.

    1972-01-01

    The effects of notches in thin beryllium sheets were studied as functions of material variables and notch severity. Double edge notched samples having stress concentration factors of 1.0 to 15.4 were prepared by milling to size, etching, and electrical discharge machining the notches. Strength was not reduced greatly by sharp notches, and duller notches were more deleterious than sharp notches. The trend was for reduced strength for dull notches, increased strength for sharper notches, and reduced strength for very sharp notches. Differences in material purity or source of the sheet had little affect on notch sensitivity. The most important factors appear to be oxide content and directionality of the sheet microstructure; high oxide content and highly directional microstructure tend to give more notch sensitivity than low oxide content, and more bidirectional microstructure. Postulated causes of the change in notched/unnotched strength are given.

  4. Electromagnetic properties of the Beryllium-11 nucleus in Halo EFT

    Directory of Open Access Journals (Sweden)

    Hammer H.-W.

    2010-04-01

    Full Text Available We compute electromagnetic properties of the Beryllium-11 nucleus using an effective field theory that exploits the separation of scales in this halo system. We fix the parameters of the EFT from measured data on levels and scattering lengths in the 10Be plus neutron system. We then obtain predictions for the B(E1 strength of the 1/2+ to 1/2− transition in the 11Be nucleus. We also compute the charge radius of the ground state of 11Be. Agreement with experiment within the expected accuracy of a leading-order computation in this EFT is obtained. We also indicate how higher-order corrections that affect both s-wave and p-wave 10 Be-neutron interactions will affect our results.

  5. Damage production in atomic displacement cascades in beryllium

    Directory of Open Access Journals (Sweden)

    V.A. Borodin

    2016-12-01

    Full Text Available The paper presents the results of a molecular dynamics simulation of cascade damage production in beryllium caused by self-ion recoils in the energy range of 0.5–3keV. It is demonstrated that point defects are produced in Be preferentially in well-separated subcascades generated by secondary and higher order recoils. A linear dependence of the point defect number on the primary recoil energy is obtained with the slope that corresponds to formal atom displacement energy of ∼21eV. Most of the damage is created as single defects and the relatively high part of created point defects (∼50% survives the correlated recombination following the ballistic cascade stage and becomes freely-migrating.

  6. A new module in neural differentiation control: two microRNAs upregulated by retinoic acid, miR-9 and -103, target the differentiation inhibitor ID2.

    Directory of Open Access Journals (Sweden)

    Daniela Annibali

    Full Text Available The transcription factor ID2 is an important repressor of neural differentiation strongly implicated in nervous system cancers. MicroRNAs (miRNAs are increasingly involved in differentiation control and cancer development. Here we show that two miRNAs upregulated on differentiation of neuroblastoma cells--miR-9 and miR-103--restrain ID2 expression by directly targeting the coding sequence and 3' untranslated region of the ID2 encoding messenger RNA, respectively. Notably, the two miRNAs show an inverse correlation with ID2 during neuroblastoma cell differentiation induced by retinoic acid. Overexpression of miR-9 and miR-103 in neuroblastoma cells reduces proliferation and promotes differentiation, as it was shown to occur upon ID2 inhibition. Conversely, an ID2 mutant that cannot be targeted by either miRNA prevents retinoic acid-induced differentiation more efficient than wild-type ID2. These findings reveal a new regulatory module involving two microRNAs upregulated during neural differentiation that directly target expression of the key differentiation inhibitor ID2, suggesting that its alteration may be involved in neural cancer development.

  7. Cost effective aluminum beryllium mirrors for critical optics applications

    Science.gov (United States)

    Say, Carissa; Duich, Jack; Huskamp, Chris; White, Ray

    2013-09-01

    The unique performance of aluminum-beryllium frequently makes it an ideal material for manufacturing precision optical-grade metal mirrors. Traditional methods of manufacture utilize hot-pressed powder block in billet form which is subsequently machined to final dimensions. Complex component geometries such as lightweighted, non-plano mirrors require extensive tool path programming, fixturing, and CNC machining time and result in a high buy-to-fly ratio (the ratio of the mass of raw material purchased to the mass of the finished part). This increases the cost of the mirror structure as a significant percentage of the procurement cost is consumed in the form of machining, tooling, and scrap material that do not add value to the final part. Inrad Optics, Inc. and IBC Advanced Alloys Corp. undertook a joint study to evaluate the suitability of investment-cast Beralcast® 191 and 363 aluminum-beryllium as a precision mirror substrate material. Net shape investment castings of the desired geometry minimizes machining to just cleanup stock, thereby reducing the recurring procurement cost while still maintaining performance. The thermal stability of two mirrors, (one each of Beralcast® 191 and Beralcast® 363), was characterized from -40°F to +150°F. A representative pocketed mirror was developed, including the creation of a relevant geometry and production of a cast component to validate the approach. Information from the demonstration unit was used as a basis for a comparative cost study of the representative mirror produced in Beralcast® and one machined from a billet of AlBeMet® 162 (AlBeMet® is a registered trademark of Materion Corporation). The technical and financial results of these studies will be discussed in detail.

  8. Solvent extraction of beryllium from malonate solutions with liquid anion exchangers

    Energy Technology Data Exchange (ETDEWEB)

    Rao, R.R.; Khopkar, S.M.

    1983-12-01

    Beryllium was quantitatively extracted at pH 5.5-7.0 in microgram amounts with 0.06 M Aliquat 336S in xylene from 5 x 10/sup -3/ M malonic acid solution, stripped with 0.5 M hydrochloric acid, and determined spectrophotometrically at 523 nm as its complex with thorin. Those metals which could not form anionic complexes with malonic acid and were not extracted with beryllium at pH 6.5 were separated from it. Metals forming weak malonato complexes were scrubbed from the organic phase with water. The elements like bismuth, antimony, iron, uranium, gallium, and vanadium which form strong malonato complexes were separated by selective stripping with hydrochloric, sulfuric, or nitric acid. The method was extended for the analysis of beryllium in beryl and beryllium alloys. 1 figure, 6 tables.

  9. REMOVAL OF BERYLLIUM FROM DRINKING WATER BY CHEMICAL COAGULATION AND LIME SOFTENING

    Science.gov (United States)

    The effectiveness of conventional drinking water treatment and lime softening was evaluated for beryllium removal from two drinking water sources. ar test studies were conducted to determine how common coagulants (aluminum sulfate and ferric chloride and lime softening performed ...

  10. The impact of particle size selective sampling methods on occupational assessment of airborne beryllium particulates.

    Science.gov (United States)

    Sleeth, Darrah K

    2013-05-01

    In 2010, the American Conference of Governmental Industrial Hygienists (ACGIH) formally changed its Threshold Limit Value (TLV) for beryllium from a 'total' particulate sample to an inhalable particulate sample. This change may have important implications for workplace air sampling of beryllium. A history of particle size-selective sampling methods, with a special focus on beryllium, will be provided. The current state of the science on inhalable sampling will also be presented, including a look to the future at what new methods or technology may be on the horizon. This includes new sampling criteria focused on particle deposition in the lung, proposed changes to the existing inhalable convention, as well as how the issues facing beryllium sampling may help drive other changes in sampling technology.

  11. IRIS Toxicological Review of Beryllium and Compounds (2008 External Review Draft)

    Science.gov (United States)

    EPA is conducting a peer review and public comment of the scientific basis supporting the human health hazard and dose-response assessment of Beryllium that when finalized will appear on the Integrated Risk Information System (IRIS) database.

  12. Porcine bocavirus NP1 negatively regulates interferon signaling pathway by targeting the DNA-binding domain of IRF9.

    Science.gov (United States)

    Zhang, Ruoxi; Fang, Liurong; Wang, Dang; Cai, Kaimei; Zhang, Huan; Xie, Lilan; Li, Yi; Chen, Huanchun; Xiao, Shaobo

    2015-11-01

    To subvert host antiviral immune responses, many viruses have evolved countermeasures to inhibit IFN signaling pathway. Porcine bocavirus (PBoV), a newly identified porcine parvovirus, has received attention because it shows clinically high co-infection prevalence with other pathogens in post-weaning multisystemic wasting syndrome (PWMS) and diarrheic piglets. In this study, we screened the structural and non-structural proteins encoded by PBoV and found that the non-structural protein NP1 significantly suppressed IFN-stimulated response element (ISRE) activity and subsequent IFN-stimulated gene (ISG) expression. However, NP1 affected neither the activation and translocation of STAT1/STAT2, nor the formation of the heterotrimeric transcription factor complex ISGF3 (STAT1/STAT2/IRF9). Detailed analysis demonstrated that PBoV NP1 blocked the ISGF3 DNA-binding activity by combining with the DNA-binding domain (DBD) of IRF9. In summary, these results indicate that PBoV NP1 interferes with type I IFN signaling pathway by blocking DNA binding of ISGF3 to attenuate innate immune responses.

  13. In Vivo Silencing of A20 via TLR9-Mediated Targeted SiRNA Delivery Potentiates Antitumor Immune Response.

    Directory of Open Access Journals (Sweden)

    Floriane C M Braun

    Full Text Available A20 is an ubiquitin-editing enzyme that ensures the transient nature of inflammatory signaling pathways induced by cytokines like TNF-α and IL-1 or pathogens via Toll-like receptor (TLR pathways. It has been identified as a negative regulator of dendritic cell (DC maturation and attenuator of their immunostimulatory properties. Ex vivo A20-depleted dendritic cells showed enhanced expression of pro-inflammatory cytokines and costimulatory molecules, which resulted in hyperactivation of tumor-infiltrating T lymphocytes and inhibition of regulatory T cells. In the present study, we demonstrate that a synthetic molecule consisting of a CpG oligonucleotide TLR9 agonist linked to A20-specific siRNAs silences its expression in TLR9+ mouse dendritic cells in vitro and in vivo. In the B16 mouse melanoma tumor model, silencing of A20 enhances the CpG-triggered induction of NFκB activity followed by elevated expression of IL-6, TNF-α and IL-12. This leads to potentiated antitumor immune responses manifested by increased numbers of tumor-specific cytotoxic T cells, high levels of tumor cell apoptosis and delayed tumor growth. Our findings confirm the central role of A20 in controlling the immunostimulatory potency of DCs and provide a strategy for simultaneous A20 silencing and TLR activation in vivo.

  14. RNA interference targeting CD147 inhibits the invasion of human cervical squamous carcinoma cells by downregulating MMP-9.

    Science.gov (United States)

    Fan, Xiaobin; Wu, Weiguang; Shi, Haixia; Han, Jianqiu

    2013-07-01

    Cervical squamous carcinoma is a highly invasive tumour that has a great capacity to metastasise. Extracellular matrix metalloproteinase inducer (EMMPRIN or CD147), a member of the immunoglobulin superfamily, is a widely distributed cell surface glycoprotein. It is highly expressed on malignant tumour cell surfaces, including human cervical squamous carcinoma. It also plays a critical role in the invasive and metastatic activity of malignant cells by stimulating the expression of matrix metalloproteinases (MMPs). The anti-invasive effect of small interfering RNA (siRNA) against CD147 on human cervical squamous carcinoma cells and its possible pathways has been investigated. The downregulation of CD147 by transfection with siRNA resulted in MMP-9 expression and decreased activity in the cervical squamous carcinoma cell line SiHa. In vitro analysis showed that the invasive capacity of SiHa cells decreased. Thus CD147 inhibition and subsequent MMP-9 deletion may have anti-tumour effects by inhibiting the invasiveness of human cervical squamous carcinoma cells.

  15. MicroRNA miR-24 enhances tumor invasion and metastasis by targeting PTPN9 and PTPRF to promote EGF signaling.

    Science.gov (United States)

    Du, William W; Fang, Ling; Li, Minhui; Yang, Xiangling; Liang, Yaoyun; Peng, Chun; Qian, Wei; O'Malley, Yunxia Q; Askeland, Ryan W; Sugg, Sonia L; Qian, Jun; Lin, Jiang; Jiang, Zide; Yee, Albert J; Sefton, Michael; Deng, Zhaoqun; Shan, Sze Wan; Wang, Chia-Hui; Yang, Burton B

    2013-03-15

    MicroRNAs are known to play regulatory roles in gene expression associated with cancer development. We analyzed levels of the microRNA miR-24 in patients with breast carcinoma and found that miR-24 was higher in breast carcinoma samples than in benign breast tissues. We generated constructs expressing miR-24 and studied its functions using both in vitro and in vivo techniques. We found that the ectopic expression of miR-24 promoted breast cancer cell invasion and migration. In vivo experiments in mice indicated that the expression of miR-24 enhanced tumor growth, invasion into local tissues, metastasis to lung tissues and decreased overall mouse survival. In the miR-24-expressing cells and tumors, EGFR was highly phosphorylated, whereas expression of the phosphatases tyrosine-protein phosphatase non-receptor type 9 (PTPN9) and receptor-type tyrosine-protein phosphatase F (PTPRF) were repressed. We confirmed that miR-24 could directly target both PTPN9 and PTPRF. Consistent with this, we found that the levels of phosphorylated epidermal growth factor receptor (pEGFR) were higher whereas the levels of PTPN9 and PTPRF were lower in the patients with metastatic breast carcinoma. Ectopic expression of PTPN9 and PTPRF decreased pEGFR levels, cell invasion, migration and tumor metastasis. Furthermore, we found that MMP2, MMP11, pErk, and ADAM15 were upregulated, whereas TIMP2 was downregulated; all of which supported the roles of miR-24 in tumor invasion and metastasis. Our results suggest that miR-24 plays a key role in breast cancer invasion and metastasis. miR-24 could potentially be a target for cancer intervention.

  16. Epitaxial Zn{sub 0.9}Mn{sub 0.1}O thin films ablated from targets synthesized by wet chemistry method

    Energy Technology Data Exchange (ETDEWEB)

    Mera, J. [Centro de Investigaciones en Materiales, Facultad de Ingenieria, Universidad de Narino, Ciudad Universitaria Torobajo, Pasto (Colombia); Doria, J. [Laboratorio de Materiales Ceramicos y Vitreos, Departamento de Fisica, Universidad Nacional de Colombia, Sede Medellin, A.A. 568, Medellin (Colombia); Cordoba, C.; Paredes, O. [Centro de Investigaciones en Materiales, Facultad de Ingenieria, Universidad de Narino, Ciudad Universitaria Torobajo, Pasto (Colombia); Gomez, A. [Laboratorio de caracterizacion de materiales, Universidad Nacional de Colombia, Sede Medellin, A.A. 568, Medellin (Colombia); Paucar, C. [Laboratorio de Materiales Ceramicos y Vitreos, Departamento de Fisica, Universidad Nacional de Colombia, Sede Medellin, A.A. 568, Medellin (Colombia); Fuchs, D. [Karlsruhe Institute of Technology, Institut fuer Festkoerperphysik, Postfach 3640, Karlsruhe (Germany); Moran, O., E-mail: omoranc@unal.edu.c [Laboratorio de Materiales Ceramicos y Vitreos, Departamento de Fisica, Universidad Nacional de Colombia, Sede Medellin, A.A. 568, Medellin (Colombia)

    2010-08-15

    Zn{sub 0.9}Mn{sub 0.1}O thin films were prepared by pulsed laser deposition (PLD) on c-Al{sub 2}O{sub 3}(0 0 0 1) substrates. The polymeric precursor method was used to synthesize the powders from which the ablation targets were fabricated. Zn{sub 0.9}Mn{sub 0.1}O films ablated from these targets showed excellent epitaxial growth with a full-width at half-maximum (FWHM) {approx}0.07{sup o}. Probably, the purity offered by the soft chemistry methods to prepare ceramic-type polycrystalline compounds with nanometric particle size plays an important role in achieving high-quality films of novel oxides as Mn-doped ZnO. Interestingly, the Zn{sub 0.9}Mn{sub 0.1}O films displayed well-defined magnetic hysteresis loops both at room temperature and 5 K, which points out to the presence of ferromagnetic order in the films. Nevertheless, the mechanism leading to room temperature ferromagnetism in the Mn-doped ZnO is not fully established. Probably, unpaired electron spins responsible for ferromagnetism in the films have their origin in the oxygen vacancies, especially on the surfaces of the oxide nanoparticles. The oxygen deficiency would result from thin film growth conditions as the studied samples were grown in low-pressure oxygen atmosphere (1x10{sup -4} mbar).

  17. In vivo targeting of ADAM9 gene expression using lentivirus-delivered shRNA suppresses prostate cancer growth by regulating REG4 dependent cell cycle progression.

    Directory of Open Access Journals (Sweden)

    Che-Ming Liu

    Full Text Available Cancer cells respond to stress by activating a variety of survival signaling pathways. A disintegrin and metalloproteinase (ADAM 9 is upregulated during cancer progression and hormone therapy, functioning in part through an increase in reactive oxygen species. Here, we present in vitro and in vivo evidence that therapeutic targeting of ADAM9 gene expression by lentivirus-delivered small hairpin RNA (shRNA significantly inhibited proliferation of human prostate cancer cell lines and blocked tumor growth in a murine model of prostate cancer bone metastasis. Cell cycle studies confirmed an increase in the G1-phase and decrease in the S-phase population of cancer cells under starvation stress conditions, which correlated with elevated intracellular superoxide levels. Microarray data showed significantly decreased levels of regenerating islet-derived family member 4 (REG4 expression in prostate cancer cells with knockdown of ADAM9 gene expression. This REG4 downregulation also resulted in induction of expression of p21(Cip1/WAF1, which negatively regulates cyclin D1 and blocks the G1/S transition. Our data reveal a novel molecular mechanism of ADAM9 in the regulation of prostate cancer cell proliferation, and suggests a combined modality of ADAM9 shRNA gene therapy and cytotoxic agents for hormone refractory and bone metastatic prostate cancer.

  18. Targeted genetic dependency screen facilitates identification of actionable mutations in FGFR4, MAP3K9, and PAK5 in lung cancer.

    Science.gov (United States)

    Fawdar, Shameem; Trotter, Eleanor W; Li, Yaoyong; Stephenson, Natalie L; Hanke, Franziska; Marusiak, Anna A; Edwards, Zoe C; Ientile, Sara; Waszkowycz, Bohdan; Miller, Crispin J; Brognard, John

    2013-07-23

    Approximately 70% of patients with non-small-cell lung cancer present with late-stage disease and have limited treatment options, so there is a pressing need to develop efficacious targeted therapies for these patients. This remains a major challenge as the underlying genetic causes of ~50% of non-small-cell lung cancers remain unknown. Here we demonstrate that a targeted genetic dependency screen is an efficient approach to identify somatic cancer alterations that are functionally important. By using this approach, we have identified three kinases with gain-of-function mutations in lung cancer, namely FGFR4, MAP3K9, and PAK5. Mutations in these kinases are activating toward the ERK pathway, and targeted depletion of the mutated kinases inhibits proliferation, suppresses constitutive activation of downstream signaling pathways, and results in specific killing of the lung cancer cells. Genomic profiling of patients with lung cancer is ushering in an era of personalized medicine; however, lack of actionable mutations presents a significant hurdle. Our study indicates that targeted genetic dependency screens will be an effective strategy to elucidate somatic variants that are essential for lung cancer cell viability.

  19. Impact of beryllium reflector ageing on Safari–1 reactor core parameters / L.E. Moloko

    OpenAIRE

    Moloko, Lesego Ernest

    2011-01-01

    The build–up of 6Li and 3He, that is, the strong thermal neutron absorbers or the so called "neutron poisons", in the beryllium reflector changes the physical characteristics of the reactor, such as reactivity, neutron spectra, neutron flux level, power distribution, etc.; furthermore,gaseous isotopes such as 3H and 4He induce swelling and embrittlement of the reflector. The SAFARI–1 research reactor, operated by Necsa at Pelindaba in South Africa, uses a beryllium reflector on...

  20. Calculated power distribution of a thermionic, beryllium oxide reflected, fast-spectrum reactor

    Science.gov (United States)

    Mayo, W.; Lantz, E.

    1973-01-01

    A procedure is developed and used to calculate the detailed power distribution in the fuel elements next to a beryllium oxide reflector of a fast-spectrum, thermionic reactor. The results of the calculations show that, although the average power density in these outer fuel elements is not far from the core average, the power density at the very edge of the fuel closest to the beryllium oxide is about 1.8 times the core avearge.

  1. Characterization of phagolysosomal simulant fluid for study of beryllium aerosol particle dissolution.

    Science.gov (United States)

    Stefaniak, A B; Guilmette, R A; Day, G A; Hoover, M D; Breysse, P N; Scripsick, R C

    2005-02-01

    A simulant of phagolysosomal fluid is needed for beryllium particle dissolution research because intraphagolysosomal dissolution is believed to be a necessary step in the cellular immune response associated with development of chronic beryllium disease. Thus, we refined and characterized a potassium hydrogen phthalate (KHP) buffered solution with pH 4.55, termed phagolysosomal simulant fluid (PSF), for use in a static dissolution technique. To characterize the simulant, beryllium dissolution in PSF was compared to dissolution in the J774A.1 murine cell line. The effects of ionic composition, buffer strength, and the presence of the antifungal agent alkylbenzyldimethylammonium chloride (ABDC) on beryllium dissolution in PSF were evaluated. Beryllium dissolution in PSF was not different from dissolution in the J774A.1 murine cell line (p = 0.78) or from dissolution in another simulant having the same pH but different ionic composition (p = 0.73). A buffer concentration of 0.01-M KHP did not appear adequate to maintain pH under all conditions. There was no difference between dissolution in PSF with 0.01-M KHP and 0.02-M KHP (p = 0.12). At 0.04-M KHP, beryllium dissolution was increased relative to 0.02-M KHP (p = 0.02). Use of a 0.02-M KHP buffer concentration in the standard formulation for PSF provided stability in pH without alteration of the dissolution rate. The presence of ABDC did not influence beryllium dissolution in PSF (p = 0.35). PSF appears to be a useful and appropriate model of in vitro beryllium dissolution when using a static dissolution technique. In addition, the critical approach used to evaluate and adjust the composition of PSF may serve as a framework for characterizing PSF to study dissolution of other metal and oxide particles.

  2. Suivi médical de salariés exposés au beryllium

    OpenAIRE

    2009-01-01

    International audience; Purpose of the study: determination of a systematised procedure for medical follow-up of beryllium-exposed workers. Method: a medical follow-up of workers from a factory machining beryllium (Be) either plain or as an alloy started in 2001. Be Lymphocyte Proliferation Tests (LPT) were performed for screening Be sensitisation and were calculated again according to 1142-2001 speciation of the American Department Of Energy. A working group included occupational physicians,...

  3. Value of the radiolabelled GLP-1 receptor antagonist exendin(9-39) for targeting of GLP-1 receptor-expressing pancreatic tissues in mice and humans

    Energy Technology Data Exchange (ETDEWEB)

    Waser, Beatrice; Reubi, Jean Claude [University of Berne, Division of Cell Biology and Experimental Cancer Research, Institute of Pathology, P.O. Box 62, Bern (Switzerland)

    2011-06-15

    Radiolabelled glucagon-like peptide 1 (GLP-1) receptor agonists have recently been shown to successfully image benign insulinomas in patients. Moreover, it was recently reported that antagonist tracers were superior to agonist tracers for somatostatin and gastrin-releasing peptide receptor targeting of tumours. The present preclinical study determines therefore the value of an established GLP-1 receptor antagonist for the in vitro visualization of GLP-1 receptor-expressing tissues in mice and humans. Receptor autoradiography studies with {sup 125}I-GLP-1(7-36)amide agonist or {sup 125}I-Bolton-Hunter-exendin(9-39) antagonist radioligands were performed in mice pancreas and insulinomas as well as in human insulinomas; competition experiments were performed in the presence of increasing concentration of GLP-1(7-36)amide or exendin(9-39). The antagonist {sup 125}I-Bolton-Hunter-exendin(9-39) labels mouse pancreatic {beta}-cells and mouse insulinomas, but it does not label human pancreatic {beta}-cells and insulinomas. High affinity displacement (IC{sub 50} approximately 2 nM) is observed in mouse {beta}-cells and insulinomas with either the exendin(9-39) antagonist or GLP-1(7-36)amide agonist. For comparison, the agonist {sup 125}I-GLP-1(7-36)amide intensively labels mouse pancreatic {beta}-cells, mouse insulinoma and human insulinomas; high affinity displacement is observed for the GLP-1(7-36)amide in all tissues; however, a 5 and 20 times lower affinity is found for exendin(9-39) in the mouse and human tissues, respectively. This study reports a species-dependent behaviour of the GLP-1 receptor antagonist exendin(9-39) that can optimally target GLP-1 receptors in mice but not in human tissue. Due to its overly low binding affinity, this antagonist is an inadequate targeting agent for human GLP-1 receptor-expressing tissues, as opposed to the GLP-1 receptor agonist, GLP-1(7-36)amide. (orig.)

  4. Hybrid Orbital and Numerical Grid Representationfor Electronic Continuum Processes: Double Photoionization of Atomic Beryllium

    Energy Technology Data Exchange (ETDEWEB)

    Yip, Frank L; McCurdy, C. William; Rescigno, Thomas N

    2010-04-19

    A general approach for ab initio calculations of electronic continuum processes is described in which the many-electron wave function is expanded using a combination of orbitals at short range and the finite-element discrete variable representation(FEM-DVR) at larger distances. The orbital portion of the basis allows the efficient construction of many-electron configurations in which some of the electrons are bound, but because the orbitals are constructed from an underlying FEM-DVR grid, the calculation of two-electron integrals retains the efficiency of the primitive FEM-DVR approach. As an example, double photoionization of beryllium is treated in a calculation in which the 1s{sup 2} core is frozen. This approach extends the use of exterior complex scaling (ECS) successfully applied to helium and H{sub 2} to calculations with two active electrons on more complicated targets. Integrated, energy-differential and triply-differential cross sections are exhibited, and the results agree well with other theoretical investigations.

  5. Erosion behaviour of ultrathin carbon layers and hydrogen retention in beryllium; Untersuchungen zur Erosion ultraduenner Kohlenstoffschichten und Wasserstoffrueckhaltung in Beryllium

    Energy Technology Data Exchange (ETDEWEB)

    Reinelt, Matthias

    2008-04-16

    Plasma-wall-interaction plays an important role on the way to technical feasibility of thermonuclear fusion. In this context, the erosion behavior of few nanometer thin amorphous carbon layers on different metallic substrates by energetic deuterium and helium ions is investigated. Several aspects of the interaction are distinguishable by XPS. Ion induced carbide formation is governed by kinematic intermixing of carbon and metal substrate. Several methods of quantification of XPS measurements are developed and discussed. Comparison of results from these methods with NRA measurements show that surface roughness and implantation of particles into the carbon layer and intermixing zone influence the XPS measurements, which are sensitive to parameters such as material density. The retention of 1 keV deuterium ions implanted into single crystalline and cleaned beryllium at room temperature is investigated by temperature programmed desorption (TPD). The residual BeO coverage was 0.2 ML. The retention is 78% at low fluences and saturates above a bombardment with a fluence of 2.10{sup 17} cm{sup -2}. The retained maximum areal density is 2.10{sup 17} cm{sup -2}. Above 900 K, no deuterium is retained in the sample. An onset of self diffusion is observed at this temperature and metallic beryllium from the bulk segregates though thin BeO layers on the surface. From deuterium desorption traces, retention mechanisms are obtained. The measured TPDspectra are modeled by TMAP7 and rate equations to obtain activation energies for the release processes. From these, binding energies for the system Be-D are derived. Up to a implantation fluence of 1.10{sup 17} cm{sup -2}, deuterium is trapped in ion induced defects in the beryllium lattice with binding energies of 1.69 eV and 1.86 eV and release temperatures of 770 K and 840 K, respectively. The occupation of these states shows a different isotope behavior for {sup 1}H and {sup 2}H. The states are filled by diffusion of deuterium at the

  6. Characterization of beryllium deformation using in-situ x-ray diffraction

    Energy Technology Data Exchange (ETDEWEB)

    Magnuson, Eric Alan [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Brown, Donald William [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Clausen, Bjorn [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Sisneros, Thomas A. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Park, Jun-Sang [Argonne National Lab. (ANL), Argonne, IL (United States)

    2015-08-24

    Beryllium’s unique mechanical properties are extremely important in a number of high performance applications. Consequently, accurate models for the mechanical behavior of beryllium are required. However, current models are not sufficiently microstructure aware to accurately predict the performance of beryllium under a range of processing and loading conditions. Previous experiments conducted using the SMARTS and HIPPO instruments at the Lujan Center(LANL), have studied the relationship between strain rate and texture development, but due to the limitations of neutron diffraction studies, it was not possible to measure the response of the material in real-time. In-situ diffraction experiments conducted at the Advanced Photon Source have allowed the real time measurement of the mechanical response of compressed beryllium. Samples of pre-strained beryllium were reloaded orthogonal to their original load path to show the reorientation of already twinned grains. Additionally, the in-situ experiments allowed the real time tracking of twin evolution in beryllium strained at high rates. The data gathered during these experiments will be used in the development and validation of a new, microstructure aware model of the constitutive behavior of beryllium.

  7. Extraction and optical fluorescence method for the measurement of trace beryllium in soils.

    Science.gov (United States)

    Agrawal, Anoop; Cronin, John P; Agrawal, Akshay; Tonazzi, Juan C L; Adams, Lori; Ashley, Kevin; Brisson, Michael J; Duran, Brandy; Whitney, Gary; Burrell, Anthony K; McCleskey, T Mark; Robbins, James; White, Kenneth T

    2008-03-15

    Beryllium metal and beryllium oxide are important industrial materials used in a variety of applications in the electronics, nuclear energy, and aerospace industries. These materials are highly toxic, they must be disposed of with care, and exposed workers need to be protected. Recently, a new analytical method was developed that uses dilute ammonium bifluoride for extraction of beryllium and a high quantum yield optical fluorescence reagent to determine trace amounts of beryllium in airborne and surface samples. The sample preparation and analysis procedure was published by both ASTM International and the National Institute for Occupational Safety and Health (NIOSH). The main advantages of this method are its sensitivity, simplicity, use of lower toxicity materials, and low capital costs. Use of the technique for analyzing soils has been initiated to help meet a need at several of the U.S. Department of Energy legacy sites. So far this work has mainly concentrated on developing a dissolution protocol for effectively extracting beryllium from a variety of soils and sediments so that these can be analyzed by optical fluorescence. Certified reference materials (CRM) of crushed rock and soils were analyzed for beryllium content using fluorescence, and results agree quantitatively with reference values.

  8. The Status of Beryllium Research for Fusion in the United States

    Energy Technology Data Exchange (ETDEWEB)

    Glen R. Longhurst

    2003-12-01

    Use of beryllium in fusion reactors has been considered for neutron multiplication in breeding blankets and as an oxygen getter for plasma-facing surfaces. Previous beryllium research for fusion in the United States included issues of interest to fission (swelling and changes in mechanical and thermal properties) as well as interactions with plasmas and hydrogen isotopes and methods of fabrication. When the United States formally withdrew its participation in the International Thermonuclear Experimental Reactor (ITER) program, much of this effort was terminated. The focus in the U.S. has been mainly on toxic effects of beryllium and on industrial hygiene and health-related issues. Work continued at the INEEL and elsewhere on beryllium-containing molten salts. This activity is part of the JUPITER II Agreement. Plasma spray of ITER first wall samples at Los Alamos National Laboratory has been performed under the European Fusion Development Agreement. Effects of irradiation on beryllium structure are being studied at Oak Ridge National Laboratory. Numerical and phenomenological models are being developed and applied to better understand important processes and to assist with design. Presently, studies are underway at the University of California Los Angeles to investigate thermo-mechanical characteristics of beryllium pebble beds, similar to research being carried out at Forschungszentrum Karlsruhe and elsewhere. Additional work, not funded by the fusion program, has dealt with issues of disposal, and recycling.

  9. Sensitive detection of beryllium using a fiber optic liquid waveguide cell.

    Science.gov (United States)

    Deng, Gang; Wei, Lily; Collins, Greg E

    2003-05-28

    The metallochromic chelating agent, Chromazurol S, has been utilized in conjunction with a fiber optic liquid waveguide capillary cell to enable the sensitive detection of beryllium in solution (30 ng l(-1) detection limit) and following extraction from a contaminated plexiglas surface (0.5 ng cm(-2) detection limit). The addition of a cationic surfactant, cetylpyridinium chloride, to Chromazurol S at pH 10 in Tris-HCl buffer results in the formation of two bathochromic peaks in the visible spectrum following metal chelation by beryllium. The first absorbance band, at 515 nm, is intermediate in nature, permitting maximal sensitivity for low beryllium concentrations, but diminishing in intensity at concentrations above 100 mug l(-1). The second absorbance band, centered at 610 nm, dominates for beryllium concentrations of 100 mug l(-1) and above. Experimental conditions including pH, buffer type, additive surfactants, masking agents, and dye concentration were investigated in order to optimize detection sensitivity and selectivity. A fiber optic spectrometer is used with both a liquid waveguide capillary cell and 1 cm cuvette cell, to give a sensitive and broad dynamic range for beryllium detection that capitalizes on both beryllium metal chelate absorbance bands formed under these conditions.

  10. Src is a novel potential off-target of RXR agonists, 9-cis-UAB30 and Targretin, in human breast cancer cells.

    Science.gov (United States)

    Kim, Mi-Sung; Lim, Do Young; Kim, Jong-Eun; Chen, Hanyong; Lubet, Ronald A; Dong, Zigang; Bode, Ann M

    2015-12-01

    9-cis-UAB30 (UAB30) and Targretin are well-known retinoid X receptor (RXR) agonists. They were highly effective in decreasing the incidence of methylnitrosourea (MNU)-induced mammary cancers. However, whether the anti-mammary cancer effects of UAB30 or Targretin originate from the activation of RXR is unclear. In the present study, we hypothesized that UAB30 and Targretin not only affect RXR, but likely influence one or more off-target proteins. Virtual screening results suggest that Src is a potential target for UAB30 and Targretin that regulates extracellular matrix (ECM) molecules and cell motility and invasiveness. In vitro kinase assay data revealed that UAB30 or Targretin interacted with Src and attenuated its kinase activity. We found that UAB30 or Targretin substantially inhibited invasiveness and migration of MCF-7 and SK-BR-3 human breast cancer cells. We examined the effects of UAB30 and Targretin on the expression of matrix metalloproteinases (MMP)-9, which are known to play an essential role in tumor invasion. We show that activity and expression of MMP-9 were decreased by UAB30 or Targretin. Western blot data showed that UAB30 or Targretin decreased AKT and its substrate molecule p70(s6k), which are downstream of Src in MCF-7 and SK-BR-3 cells. Moreover, knocking down the expression of Src effectively reduced the sensitivity of SK-BR-3 cells to the inhibitory effects of UAB30 and Targretin on invasiveness. Taken together, our results demonstrate that UAB30 and Targretin each inhibit invasion and migration by targeting Src in human breast cancer cells.

  11. Insertional Mutagenesis by CRISPR/Cas9 Ribonucleoprotein Gene Editing in Cells Targeted for Point Mutation Repair Directed by Short Single-Stranded DNA Oligonucleotides.

    Science.gov (United States)

    Rivera-Torres, Natalia; Banas, Kelly; Bialk, Pawel; Bloh, Kevin M; Kmiec, Eric B

    2017-01-01

    CRISPR/Cas9 and single-stranded DNA oligonucleotides (ssODNs) have been used to direct the repair of a single base mutation in human genes. Here, we examine a method designed to increase the precision of RNA guided genome editing in human cells by utilizing a CRISPR/Cas9 ribonucleoprotein (RNP) complex to initiate DNA cleavage. The RNP is assembled in vitro and induces a double stranded break at a specific site surrounding the mutant base designated for correction by the ssODN. We use an integrated mutant eGFP gene, bearing a single base change rendering the expressed protein nonfunctional, as a single copy target in HCT 116 cells. We observe significant gene correction activity of the mutant base, promoted by the RNP and single-stranded DNA oligonucleotide with validation through genotypic and phenotypic readout. We demonstrate that all individual components must be present to obtain successful gene editing. Importantly, we examine the genotype of individually sorted corrected and uncorrected clonally expanded cell populations for the mutagenic footprint left by the action of these gene editing tools. While the DNA sequence of the corrected population is exact with no adjacent sequence modification, the uncorrected population exhibits heterogeneous mutagenicity with a wide variety of deletions and insertions surrounding the target site. We designate this type of DNA aberration as on-site mutagenicity. Analyses of two clonal populations bearing specific DNA insertions surrounding the target site, indicate that point mutation repair has occurred at the level of the gene. The phenotype, however, is not rescued because a section of the single-stranded oligonucleotide has been inserted altering the reading frame and generating truncated proteins. These data illustrate the importance of analysing mutagenicity in uncorrected cells. Our results also form the basis of a simple model for point mutation repair directed by a short single-stranded DNA oligonucleotides and

  12. Insertional Mutagenesis by CRISPR/Cas9 Ribonucleoprotein Gene Editing in Cells Targeted for Point Mutation Repair Directed by Short Single-Stranded DNA Oligonucleotides

    Science.gov (United States)

    Rivera-Torres, Natalia; Bialk, Pawel; Bloh, Kevin M.; Kmiec, Eric B.

    2017-01-01

    CRISPR/Cas9 and single-stranded DNA oligonucleotides (ssODNs) have been used to direct the repair of a single base mutation in human genes. Here, we examine a method designed to increase the precision of RNA guided genome editing in human cells by utilizing a CRISPR/Cas9 ribonucleoprotein (RNP) complex to initiate DNA cleavage. The RNP is assembled in vitro and induces a double stranded break at a specific site surrounding the mutant base designated for correction by the ssODN. We use an integrated mutant eGFP gene, bearing a single base change rendering the expressed protein nonfunctional, as a single copy target in HCT 116 cells. We observe significant gene correction activity of the mutant base, promoted by the RNP and single-stranded DNA oligonucleotide with validation through genotypic and phenotypic readout. We demonstrate that all individual components must be present to obtain successful gene editing. Importantly, we examine the genotype of individually sorted corrected and uncorrected clonally expanded cell populations for the mutagenic footprint left by the action of these gene editing tools. While the DNA sequence of the corrected population is exact with no adjacent sequence modification, the uncorrected population exhibits heterogeneous mutagenicity with a wide variety of deletions and insertions surrounding the target site. We designate this type of DNA aberration as on-site mutagenicity. Analyses of two clonal populations bearing specific DNA insertions surrounding the target site, indicate that point mutation repair has occurred at the level of the gene. The phenotype, however, is not rescued because a section of the single-stranded oligonucleotide has been inserted altering the reading frame and generating truncated proteins. These data illustrate the importance of analysing mutagenicity in uncorrected cells. Our results also form the basis of a simple model for point mutation repair directed by a short single-stranded DNA oligonucleotides and

  13. Enhanced Rice Blast Resistance by CRISPR/Cas9-Targeted Mutagenesis of the ERF Transcription Factor Gene OsERF922.

    Directory of Open Access Journals (Sweden)

    Fujun Wang

    Full Text Available Rice blast is one of the most destructive diseases affecting rice worldwide. The adoption of host resistance has proven to be the most economical and effective approach to control rice blast. In recent years, sequence-specific nucleases (SSNs have been demonstrated to be powerful tools for the improvement of crops via gene-specific genome editing, and CRISPR/Cas9 is thought to be the most effective SSN. Here, we report the improvement of rice blast resistance by engineering a CRISPR/Cas9 SSN (C-ERF922 targeting the OsERF922 gene in rice. Twenty-one C-ERF922-induced mutant plants (42.0% were identified from 50 T0 transgenic plants. Sanger sequencing revealed that these plants harbored various insertion or deletion (InDel mutations at the target site. We showed that all of the C-ERF922-induced allele mutations were transmitted to subsequent generations. Mutant plants harboring the desired gene modification but not containing the transferred DNA were obtained by segregation in the T1 and T2 generations. Six T2 homozygous mutant lines were further examined for a blast resistance phenotype and agronomic traits, such as plant height, flag leaf length and width, number of productive panicles, panicle length, number of grains per panicle, seed setting percentage and thousand seed weight. The results revealed that the number of blast lesions formed following pathogen infection was significantly decreased in all 6 mutant lines compared with wild-type plants at both the seedling and tillering stages. Furthermore, there were no significant differences between any of the 6 T2 mutant lines and the wild-type plants with regard to the agronomic traits tested. We also simultaneously targeted multiple sites within OsERF922 by using Cas9/Multi-target-sgRNAs (C-ERF922S1S2 and C-ERF922S1S2S3 to obtain plants harboring mutations at two or three sites. Our results indicate that gene modification via CRISPR/Cas9 is a useful approach for enhancing blast resistance in

  14. The target silicon detector for the FOCUS spectrometer

    Energy Technology Data Exchange (ETDEWEB)

    Link, J.M.; Reyes, M.; Yager, P.M.; Anjos, J.C.; Bediaga, I.; Goebel, C.; Magnin, J.; Massafferri, A.; Miranda, J.M. de; Pepe, I.M.; Reis, A.C. dos; Carrillo, S.; Casimiro, E.; Cuautle, E.; Sanchez-Hernandez, A.; Uribe, C.; Vazquez, F.; Agostino, L.; Cinquini, L.; Cumalat, J.P.; O' Reilly, B.; Ramirez, J.E.; Segoni, I.; Butler, J.N.; Cheung, H.W.K.; Chiodini, G.; Gaines, I.; Garbincius, P.H.; Garren, L.A.; Gottschalk, E.; Kasper, P.H.; Kreymer, A.E.; Kutschke, R.; Benussi, L.; Bianco, S.; Fabbri, F.L.; Zallo, A.; Cawlfield, C.; Kim, D.Y.; Rahimi, A.; Wiss, J.; Gardner, R.; Kryemadhi, A.; Chung, Y.S.; Kang, J.S.; Ko, B.R.; Kwak, J.W.; Lee, K.B.; Cho, K.; Park, H.; Alimonti, G.; Barberis, S.; Boschini, M.; D' Angelo, P.; DiCorato, M.; Dini, P.; Edera, L.; Erba, S.; Giammarchi, M.; Inzani, P.; Leveraro, F.; Malvezzi, S.; Menasce, D.; Mezzadri, M.; Milazzo, L.; Moroni, L.; Pedrini, D.; Pontoglio, C.; Prelz, F.; Rovere, M.; Sala, S.; Davenport III, T.F.; Arena, V.; Boca, G.; Bonomi, G.; Gianini, G.; Liguori, G.; Merlo, M.M.; Pantea, D.; Ratti, S.P.; Riccardi, C.; Vitulo, P.; Hernandez, H.; Lopez, A.M.; Mendez, H.; Mendez, L.; Montiel, E.; Olaya, D.; Paris, A.; Quinones, J.; Rivera, C.; Xiong, W.; Zhang, Y.; Purohit, M.; Copty, N.; Wilson, J.R.; Handler, T.; Mitchell, R.; Engh, D.; Helms, R.W.; Hosack, M.; Johns, W.E. E-mail: will.johns@vanderbilt.edu; Nehring, M.; Sheldon, P.D.; Stenson, K.; Webster, M.; Sheaff, M

    2004-01-11

    We describe a silicon microstrip detector interleaved with segments of a beryllium oxide target which was used in the FOCUS photoproduction experiment at Fermilab. The detector was designed to improve the vertex resolution and to enhance the reconstruction efficiency of short-lived charm particles.

  15. Targeted genome editing in the rare actinomycete Actinoplanes sp. SE50/110 by using the CRISPR/Cas9 System.

    Science.gov (United States)

    Wolf, Timo; Gren, Tetiana; Thieme, Eric; Wibberg, Daniel; Zemke, Till; Pühler, Alfred; Kalinowski, Jörn

    2016-08-10

    The application of genome editing technologies, like CRISPR/Cas9 for industrially relevant microorganisms, is becoming increasingly important. Compared to other methods of genetic engineering the decisive factor is that CRISPR/Cas9 is relatively easy to apply and thus time and effort can be significantly reduced in organisms, which are otherwise genetically difficult to access. Because of its many advantages and opportunities, we adopted the CRISPR/Cas9 technology for Actinoplanes sp. SE50/110, the producer of the diabetes type II drug acarbose. The functionality of genome editing was successfully shown by the scarless and antibiotic marker-free deletion of the gene encoding the tyrosinase MelC, which catalyzes the formation of the dark pigment eumelanin in the wild type strain. The generated ΔmelC2 mutant of Actinoplanes sp. SE50/110 no longer produces this pigment and therefore the supernatant does not darken. Furthermore, it was shown that the plasmid containing the gene for the Cas9 protein was removed by increasing the temperature due to its temperature-sensitive replication. The precision of the intended mutation was proven and possible off-target effects caused by the genome editing system were ruled out by genome sequencing of several mutants.

  16. BD +44 493: A Ninth Magnitude Messenger from the Early Universe; Carbon Enhanced and Beryllium Poor

    CERN Document Server

    Ito, Hiroko; Honda, Satoshi; Beers, Timothy C

    2009-01-01

    We present a 1D LTE chemical abundance analysis of the very bright (V=9.1) Carbon-Enhanced Metal-Poor (CEMP) star BD +44 493, based on high-resolution, high signal-to-noise spectra obtained with Subaru/HDS. The star is shown to be a subgiant with an extremely low iron abundance ([Fe/H]=-3.7), while it is rich in C ([C/Fe]=+1.3) and O ([O/Fe]=+1.6). Although astronomers have been searching for extremely metal-poor stars for decades, this is the first star found with [Fe/H]<-3.5 and an apparent magnitude V<12. Based on its low abundances of neutron-capture elements (e.g., [Ba/Fe]=-0.59), BD +44 493 is classified as a "CEMP-no" star. Its abundance pattern implies that a first-generation faint supernova is the most likely origin of its carbon excess, while scenarios related to mass loss from rapidly-rotating massive stars or mass transfer from an AGB companion star are not favored. From a high-quality spectrum in the near-UV region, we set an very low upper limit on this star's beryllium abundance (A(Be)=lo...

  17. Adsorption of beryllium atoms and clusters both on graphene and in a bilayer of graphite investigated by DFT.

    Science.gov (United States)

    Ferro, Yves; Fernandez, Nicolas; Allouche, Alain; Linsmeier, Christian

    2013-01-09

    We herein investigate the interaction of beryllium with a graphene sheet and in a bilayer of graphite by means of periodic DFT calculations. In all cases, we find the beryllium atoms to be more weakly bonded on graphene than in the bilayer. Be(2) forms both magnetic and non-magnetic structures on graphene depending on the geometrical configuration of adsorption. We find that the stability of the Be/bilayer system increases with the size of the beryllium clusters inserted into the bilayer of graphite. We also find a charge transfer from beryllium to the graphite layers. All these results are analysed in terms of electronic structure.

  18. Targeted delivery of self-complementary adeno-associated virus serotype 9 to the brain, using magnetic resonance imaging-guided focused ultrasound.

    Science.gov (United States)

    Thévenot, Emmanuel; Jordão, Jessica F; O'Reilly, Meaghan A; Markham, Kelly; Weng, Ying-Qi; Foust, Kevin D; Kaspar, Brian K; Hynynen, Kullervo; Aubert, Isabelle

    2012-11-01

    Noninvasive drug delivery to the brain remains a major challenge for the treatment of neurological disorders. Transcranial focused ultrasound combined with lipid-coated gas microspheres injected into the bloodstream has been shown to increase the permeability of the blood-brain barrier locally and transiently. Coupled with magnetic resonance imaging, ultrasound can be guided to allow therapeutics administered in the blood to reach brain regions of interest. Using this approach, we perform gene transfer from the blood to specific regions of the mouse brain. Focused ultrasound was targeted to the right hemisphere, at multiple foci, or restricted to one focal point of the hippocampus or the striatum. Doses from 5 × 10(8) to 1.25 × 10(10) vector genomes per gram (VG/g) of self-complementary adeno-associated virus serotype 9 carrying the green fluorescent protein were injected into the tail vein. A dose of 2.5 × 10(9) VG/g was optimal to express the transgene, 12 days later, in neurons, astrocytes, and oligodendrocytes in brain regions targeted with ultrasound, while minimizing the infection of peripheral organs. In the hippocampus and striatum, predominantly neurons and astrocytes were infected, respectively. Transcranial focused ultrasound applications could fulfill a long-term goal of gene therapy: delivering vectors to diseased brain areas directly from the circulation, in a noninvasive manner.

  19. Highly efficient CRISPR/Cas9-mediated targeted mutagenesis of multiple genes in Populus%应用CRISPR/Cas9技术在杨树中高效敲除多个靶基因

    Institute of Scientific and Technical Information of China (English)

    刘婷婷; 范迪; 冉玲玉; 姜渊忠; 刘瑞; 罗克明

    2015-01-01

    The typeⅡCRISPR/Cas9 system (Clustered regularly interspaced short palindromic repeats/CRISPR-associated 9) has been widely used in bacteria, yeast, animals and plants as a targeted genome editing tech-nique. In previous work, we have successfully knocked out the endogenous phytoene dehydrogenase (PDS) gene in Populus tomentosa Carr. using this system. To study the effect of target design on the efficiency of CRISPR/Cas9-mediated gene knockout in Populus, we analyzed the efficiency of mutagenesis using different sin-gle-guide RNA (sgRNA) that target PDS DNA sequence. We found that mismatches between the sgRNA and the tar-get DNA resulted in decreased efficiency of mutagenesis and even failed mutagenesis. Moreover, complementari-ty between the 3′ end nucleotide of sgRNA and target DNA is especially crucial for efficient mutagenesis. Further sequencing analysis showed that two PDS homologs in Populus, PtPDS1 and PtPDS2, could be knocked out simul-taneously using this system with 86.4% and 50% efficiency, respectively. These results indicated the possibility of introducing mutations in two or more endogenous genes efficiently and obtaining multi-mutant strains of Populus using this system. We have indeed generated several knockout mutants of transcription factors and structural genes in Populus, which establishes a foundation for future studies of gene function and genetic improvement of Populus.%CRISPR/Cas9系统是一种广泛应用于细菌、酵母、动物和植物中的基因组定点编辑技术。本课题组在前期工作中利用该系统在毛白杨(Populus tomentosa Carr.)中率先实现了对内源基因—八氢番茄红素脱氢酶(Phytoene dehydrogenase, PDS)基因的定点敲除。为研究靶点的设计和选择对该系统介导的杨树内源基因敲除效率的影响,本文分析了不同单向导RNA(Single-guide RNA, sgRNA)结合毛白杨PDS(PtPDS)靶基因DNA序列后对突变效率的影响。结果发现 sgRNA 与靶基因间的碱

  20. CRISPR/Cas9系统中sgRNA设计与脱靶效应评估%sgRNA design for the CRISPR/Cas9 system and evaluation of its off-target effects

    Institute of Scientific and Technical Information of China (English)

    谢胜松; 张懿; 张利生; 李广磊; 赵长志; 倪攀; 赵书红

    2015-01-01

    基于 CRISPR/Cas9系统介导的第三代基因组编辑技术,已成功应用于动物、植物和微生物等诸多物种的基因组改造。如何提高 CRISPR/Cas9技术的基因组编辑效率和最大限度降低脱靶风险一直是本领域的研究热点,而使用高效且特异的sgRNA(Small guide RNA)是基因组改造成功的关键性因素之一。目前,已有多款针对 CRISPR/Cas9技术的 sgRNA 设计和/或脱靶效应评估软件,但不同的软件各有优缺点。本文重点对16款sgRNA 设计和脱靶效应评估在线和单机版软件的特点进行了阐述,通过制定38项评估指标对不同软件进行了比较分析,最后对11种用于检测基因组编辑效率和脱靶的实验方法,以及如何筛选高效且特异的sgRNA进行了归纳总结。%The third generation of CRISPR/Cas9-mediated genome editing technology has been successfully ap-plied to genome modification of various species including animals, plants and microorganisms. How to improve the efficiency of CRISPR/Cas9 genome editing and reduce its off-target effects has been extensively explored in this field. Using sgRNA (Small guide RNA) with high efficiency and specificity is one of the critical factors for successful ge-nome editing. Several software have been developed for sgRNA design and/or off-target evaluation, which have ad-vantages and disadvantages respectively. In this review, we summarize characters of 16 kinds online and standalone software for sgRNA design and/or off-target evaluation and conduct a comparative analysis of these different kinds of software through developing 38 evaluation indexes. We also summarize 11 experimental approaches for testing ge-nome editing efficiency and off-target effects as well as how to screen highly efficient and specific sgRNA.