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Sample records for actinium 223

  1. Production of high-purity radium-223 from legacy actinium-beryllium neutron sources.

    Soderquist, Chuck Z; McNamara, Bruce K; Fisher, Darrell R

    2012-07-01

    Radium-223 is a short-lived alpha-particle-emitting radionuclide with potential applications in cancer treatment. Research to develop new radiopharmaceuticals employing (223)Ra has been hindered by poor availability due to the small quantities of parent actinium-227 available world-wide. The purpose of this study was to develop innovative and cost-effective methods to obtain high-purity (223)Ra from (227)Ac. We obtained (227)Ac from two surplus actinium-beryllium neutron generators. We retrieved the actinium/beryllium buttons from the sources and dissolved them in a sulfuric-nitric acid solution. A crude actinium solid was recovered from the solution by coprecipitation with thorium fluoride, leaving beryllium in solution. The crude actinium was purified to provide about 40 milligrams of actinium nitrate using anion exchange in methanol-water-nitric acid solution. The purified actinium was then used to generate high-purity (223)Ra. We extracted (223)Ra using anion exchange in a methanol-water-nitric acid solution. After the radium was separated, actinium and thorium were then eluted from the column and dried for interim storage. This single-pass separation produces high purity, carrier-free (223)Ra product, and does not disturb the (227)Ac/(227)Th equilibrium. A high purity, carrier-free (227)Th was also obtained from the actinium using a similar anion exchange in nitric acid. These methods enable efficient production of (223)Ra for research and new alpha-emitter radiopharmaceutical development. PMID:22697483

  2. New method for large scale production of medically applicable Actinium-225 and Radium-223

    Alpha-emitters (211At, 212Bi, 213Bi, 223Ra, 225Ac) are promising for targeted radiotherapy of cancer. Only two alpha decays near a cell membrane result in 50% death of cancer cell and only a single decay inside the cell is required for this. 225Ac may be used either directly or as a mother radionuclide in 213Bi isotope generator. Production of 225Ac is provided by three main suppliers - Institute for Transuranium Elements in Germany, Oak Ridge National Laboratory in USA and Institute of Physics and Power Engineering in Obninsk, Russia. The current worldwide production of 225Ac is approximately 1.7 Ci per year that corresponds to only 100-200 patients that could be treated annually. The common approach for 225Ac production is separation from mother 229Th or irradiation of 226Ra with protons in a cyclotron. Both the methods have some practical limitations to be applied routinely. 225Ac can be also produced by irradiation of natural thorium with medium energy protons . Cumulative cross sections of 225Ac, 227Ac, 227Th, 228Th formations have been obtained recently. Thorium targets (1-9 g) were irradiated by 114-91 MeV proton beam (1-50 μA) at INR linear accelerator. After dissolution in 8 M HNO3 + 0.004 M HF thorium was removed by double LLX by HDEHP in toluene (1:1). Ac and REE were pre-concentrated and separated from Ra and most fission products by DGA-Resin (Triskem). After washing out by 0.01 M HNO3 Ac was separated from REE by TRU Resin (Triskem) in 3 M HNO3 media. About 6 mCi 225Ac were separated in hot cell with chemical yield 85%. The method may be upscaled for production of Ci amounts of the radionuclide. The main impurity is 227Ac (0.1% at the EOB) but it does not hinder 225Ac from being used for medical 225Ac/213Bi generators. (author)

  3. Radium, thorium, and actinium extraction from seawater using an improved manganese-oxide-coated fiber

    Laboratory experiments were conducted to determine the efficiency with which improved manganese-oxide-coated acrylic fibers extract radium, thorium, and actinium from seawater. Tests were made using surface seawater spiked with 227Ac, 227Th and 223Ra. For sample volumes of approximately 30 liters and flow rates up to 0.5 liters per minute, radium and actinium are removed quantitatively. Approximately 80-95% of the thorium is removed under these same conditions. (Auth.)

  4. Separation of Actinium 227 from the uranium minerals

    The purpose of this work was to separate Actinium 227, whose content is 18%, from the mineral carnotite found in Gomez Chihuahua mountain range in Mexico. The mineral before processing is is pre-concentrated and passed, first through anionic exchange resins, later the eluate obtained is passed through cationic resins. The resins were 20-50 MESH QOWEX and 100-200 MESH 50 X 8-20 in some cased 200-400 MESH AG 50W-X8, 1X8 in other cases. The eluates from the ionic exchange were electrodeposited on stainless steel polished disc cathode and platinum electrode as anode; under a current ODF 10mA for 2.5 to 5 hours and of 100mA for .5 of an hour. it was possible to identify the Actinium 227 by means of its descendents, TH-227 and RA-223, through alpha spectroscopy. Due to the radiochemical purity which the electro deposits were obtained the Actinium 227 was low and was not quantitatively determined. A large majority of the members of the natural radioactive series 3 were identified and even alpha energies reported in the literature with very low percentages of non-identified emissions were observed. We conclude that a more precise study is needed concerning ionic exchange and electrodeposit to obtain an Actinium 227 of radiochemical purity. (Author)

  5. A francium-223 reservoir source

    By improving and accelerating a method which had been earlier tried for caesium-rubidium separation on a cellulose column, i.e. elution with 2N HCl-equilibrated phenol, the author succeeded in obtaining consecutive and quasi-selective elutions of francium-223, starting with actinium-227 fixed at the top of a small cellulose column to which ZrO2 had been added. The francium-223, rapidly eluted under pressure, is extracted by water while the phenol is extracted by ether; it can easily be cleared of any residual traces of radioactive contaminants (thallium-207, radium-223, thorium-227) by two consecutive BaSO4 precipitations. The preparation of a Fr223 solution (HCl-H2SO4) requires approximately 20 min; the time noted for Fr223 was closer to 22 than to 21 min. (author)

  6. Extraction of actinium with di-(2-ethylhexyl)phosphoric acid from hydrochloric and nitric acid solutions

    The extraction of actinium with HDEHP from Cl- and NO3- systems has been investigated. It was found that extraction of actinium from HCl solutions is much better than from HNO3 solutions. Stability constants of actinium complexes Ac(X-)+2 with Cl- and NO3- ligands were determined. Our results show that the actinium formed less stable complexes with Cl- than with NO3- ligands. 5 refs., 3 figs., 1 tab. (author)

  7. The sorption of polonium, actinium and protactinium onto geological materials

    This paper describes a combined experimental and modeling program of generic sorption studies to increase confidence in the performance assessment for a potential high-level radioactive waste repository in Japan. The sorption of polonium, actinium and protactinium onto geological materials has been investigated. Sorption of these radioelements onto bentonite, tuff and granodiorite from equilibrated de-ionized water was studied under reducing conditions at room temperature. In addition, the sorption of actinium and protactinium was investigated at 60 C. Thermodynamic chemical modeling was carried out to aid interpretation of the results

  8. Discovery of the actinium, thorium, protactinium, and uranium isotopes

    Fry, C; Thoennessen, M

    2012-01-01

    Currently, 31 actinium, 31 thorium, 28 protactinium, and 23 uranium isotopes have so far been observed; the discovery of these isotopes is discussed. For each isotope a brief summary of the first refereed publication, including the production and identification method, is presented.

  9. Spectroscopic and computational investigation of actinium coordination chemistry.

    Ferrier, Maryline G; Batista, Enrique R; Berg, John M; Birnbaum, Eva R; Cross, Justin N; Engle, Jonathan W; La Pierre, Henry S; Kozimor, Stosh A; Lezama Pacheco, Juan S; Stein, Benjamin W; Stieber, S Chantal E; Wilson, Justin J

    2016-01-01

    Actinium-225 is a promising isotope for targeted-α therapy. Unfortunately, progress in developing chelators for medicinal applications has been hindered by a limited understanding of actinium chemistry. This knowledge gap is primarily associated with handling actinium, as it is highly radioactive and in short supply. Hence, Ac(III) reactivity is often inferred from the lanthanides and minor actinides (that is, Am, Cm), with limited success. Here we overcome these challenges and characterize actinium in HCl solutions using X-ray absorption spectroscopy and molecular dynamics density functional theory. The Ac-Cl and Ac-OH2O distances are measured to be 2.95(3) and 2.59(3) Å, respectively. The X-ray absorption spectroscopy comparisons between Ac(III) and Am(III) in HCl solutions indicate Ac(III) coordinates more inner-sphere Cl(1-) ligands (3.2±1.1) than Am(III) (0.8±0.3). These results imply diverse reactivity for the +3 actinides and highlight the unexpected and unique Ac(III) chemical behaviour. PMID:27531582

  10. Groundwater seepage from the Ranger uranium mine tailings dam: radioisotopes of radium, thorium and actinium. Supervising Scientist report 106

    Monitoring of bores near the Ranger uranium mine tailings dam has revealed deterioration in water quality in several bores since 1983. In a group of bores to the north of the dam, increases have been observed of up to 500 times for sulphate concentrations and of up to 5 times for 226Ra concentrations. Results are presented here of measurements of members of the uranium, thorium and actinium decay series in borewater samples collected between 1985 and 1993. In particular, measurements of all four naturally-occurring radium isotopes have been used in an investigation of the mechanism of radium concentration changes. For the most seepage-affected bores the major findings of the study include: 228Ra/226Ra 223Ra /226Ra and 224Ra/228Ra ratios all increased over the course of the study; barium concentrations show high seasonal variability, being lower in November than May, but strontium concentrations show a steady increase with time. Calculations show that the groundwater is probably saturated with respect to barite but not with respect to celestite or anglesite; sulphide concentrations are low in comparison with sulphate, and are higher in November than in May; and 227Ac concentrations have increased with time, but do not account for the high 223Ra/226Ra ratios. It is concluded on the basis of these observations that increases in Ra isotope concentrations observed in a number of seepage-affected bores arise from increases in salinity leading to desorption of radium from adsorption sites in the vicinity of the bore rather by direct transport of radium from the tailings. Increased salinity is also causing the observed increases in 227Ac and strontium concentrations, while formation of a barite solid phase in the groundwater is causing the removal of some radium from solution. This is the cause of the increasing radium isotope ratios noted above

  11. Production of Actinium-225 via High Energy Proton Induced Spallation of Thorium-232

    Harvey, James T.; Nolen, Jerry; Vandergrift, George; Gomes, Itacil; Kroc, Tom; Horwitz, Phil; McAlister, Dan; Bowers, Del; Sullivan, Vivian; Greene, John

    2011-12-30

    The science of cancer research is currently expanding its use of alpha particle emitting radioisotopes. Coupled with the discovery and proliferation of molecular species that seek out and attach to tumors, new therapy and diagnostics are being developed to enhance the treatment of cancer and other diseases. This latest technology is commonly referred to as Alpha Immunotherapy (AIT). Actinium-225/Bismuth-213 is a parent/daughter alpha-emitting radioisotope pair that is highly sought after because of the potential for treating numerous diseases and its ability to be chemically compatible with many known and widely used carrier molecules (such as monoclonal antibodies and proteins/peptides). Unfortunately, the worldwide supply of actinium-225 is limited to about 1,000mCi annually and most of that is currently spoken for, thus limiting the ability of this radioisotope pair to enter into research and subsequently clinical trials. The route proposed herein utilizes high energy protons to produce actinium-225 via spallation of a thorium-232 target. As part of previous R and D efforts carried out at Argonne National Laboratory recently in support of the proposed US FRIB facility, it was shown that a very effective production mechanism for actinium-225 is spallation of thorium-232 by high energy proton beams. The base-line simulation for the production rate of actinium-225 by this reaction mechanism is 8E12 atoms per second at 200 MeV proton beam energy with 50 g/cm2 thorium target and 100 kW beam power. An irradiation of one actinium-225 half-life (10 days) produces {approx}100 Ci of actinium-225. For a given beam current the reaction cross section increases slightly with energy to about 400 MeV and then decreases slightly for beam energies in the several GeV regime. The object of this effort is to refine the simulations at proton beam energies of 400 MeV and above up to about 8 GeV. Once completed, the simulations will be experimentally verified using 400 MeV and 8 Ge

  12. Production of Actinium-225 via High Energy Proton Induced Spallation of Thorium-232

    The science of cancer research is currently expanding its use of alpha particle emitting radioisotopes. Coupled with the discovery and proliferation of molecular species that seek out and attach to tumors, new therapy and diagnostics are being developed to enhance the treatment of cancer and other diseases. This latest technology is commonly referred to as Alpha Immunotherapy (AIT). Actinium-225/Bismuth-213 is a parent/daughter alpha-emitting radioisotope pair that is highly sought after because of the potential for treating numerous diseases and its ability to be chemically compatible with many known and widely used carrier molecules (such as monoclonal antibodies and proteins/peptides). Unfortunately, the worldwide supply of actinium-225 is limited to about 1,000mCi annually and most of that is currently spoken for, thus limiting the ability of this radioisotope pair to enter into research and subsequently clinical trials. The route proposed herein utilizes high energy protons to produce actinium-225 via spallation of a thorium-232 target. As part of previous R and D efforts carried out at Argonne National Laboratory recently in support of the proposed US FRIB facility, it was shown that a very effective production mechanism for actinium-225 is spallation of thorium-232 by high energy proton beams. The base-line simulation for the production rate of actinium-225 by this reaction mechanism is 8E12 atoms per second at 200 MeV proton beam energy with 50 g/cm2 thorium target and 100 kW beam power. An irradiation of one actinium-225 half-life (10 days) produces ∼100 Ci of actinium-225. For a given beam current the reaction cross section increases slightly with energy to about 400 MeV and then decreases slightly for beam energies in the several GeV regime. The object of this effort is to refine the simulations at proton beam energies of 400 MeV and above up to about 8 GeV. Once completed, the simulations will be experimentally verified using 400 MeV and 8 GeV protons

  13. Neutron-Induced Fission of Actinium-227, Protactinium-231 and Neptunium-237: Mass Distribution

    Results of radiochemical studies on the mass distribution in the neutron-induced fission of actinium-227, protactinium-231 and neptunium-237 have been presented. This work has been carried out as part of a programme to determine the mass distribution in the fission of heavy elements as a function of Z and A. All irradiations have been carried out in the core of the swimming-pool type reactor APSARA with cadmium shielding wherever necessary. Relative yields of several fission product nuclides have been obtained by a method involving a comparison of the fission product activities from the respective targets with those formed from uranium-235 simultaneously irradiated. Thermal-neutron fission yields of uranium-235 have been assumed. These results indicate a predominantly asymmetric mass distribution in all the three cases, and also a distinct though small symmetric peak in the case of actinium-227. (author)

  14. A new method for the determination of low-level actinium-227 in geological samples

    We developed a new method for the determination of 227Ac in geological samples. The method uses extraction chromatographic techniques and alpha-spectrometry and is applicable for a range of natural matrices. Here we report on the procedure and results of the analysis of water (fresh and seawater) and rock samples. Water samples were acidified and rock samples underwent total dissolution via acid leaching. A DGA (N,N,N',N'-tetra-n-octyldiglycolamide) extraction chromatographic column was used for the separation of actinium. The actinium fraction was prepared for alpha spectrometric measurement via cerium fluoride micro-precipitation. Recoveries of actinium in water samples were 80 ± 8 % (number of analyses n = 14) and in rock samples 70 ± 12 % (n = 30). The minimum detectable activities (MDA) were 0.017-0.5 Bq kg-1 for both matrices. Rock sample 227Ac activities ranged from 0.17 to 8.3 Bq kg-1 and water sample activities ranged from below MDA values to 14 Bq kg-1of 227Ac. From the analysis of several standard rock and water samples with the method we found very good agreement between our results and certified values. (author)

  15. Comment: 223 [Taxonomy Icon

    Full Text Available 223.png Shinobu Okamoto (Kazusa DNA Research Institute ) licensed under CC Attribution2.1 Japan シアノバクテリア 電子顕微鏡写真 撮影:岡本忍(かずさDNA研究所) bando 2009/11/05 18:33:52 2010/02/16 10:25:27 ...

  16. 22 CFR 223.11 - Appropriate action.

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Appropriate action. 223.11 Section 223.11...-EMPLOYMENT RESTRICTIONS § 223.11 Appropriate action. The Administrator may take appropriate action in the... action....

  17. Analysis of the gamma spectra of the uranium, actinium, and thorium decay series

    Momeni, M.H.

    1981-09-01

    This report describes the identification of radionuclides in the uranium, actinium, and thorium series by analysis of gamma spectra in the energy range of 40 to 1400 keV. Energies and absolute efficiencies for each gamma line were measured by means of a high-resolution germanium detector and compared with those in the literature. A gamma spectroscopy method, which utilizes an on-line computer for deconvolution of spectra, search and identification of each line, and estimation of activity for each radionuclide, was used to analyze soil and uranium tailings, and ore.

  18. Analysis of the gamma spectra of the uranium, actinium, and thorium decay series

    This report describes the identification of radionuclides in the uranium, actinium, and thorium series by analysis of gamma spectra in the energy range of 40 to 1400 keV. Energies and absolute efficiencies for each gamma line were measured by means of a high-resolution germanium detector and compared with those in the literature. A gamma spectroscopy method, which utilizes an on-line computer for deconvolution of spectra, search and identification of each line, and estimation of activity for each radionuclide, was used to analyze soil and uranium tailings, and ore

  19. 50 CFR 223.203 - Anadromous fish.

    2010-10-01

    ... pursuant to 50 CFR 223.209 and the government-to-government processes therein that implementing and... 50 Wildlife and Fisheries 7 2010-10-01 2010-10-01 false Anadromous fish. 223.203 Section 223.203... Threatened Marine and Anadromous Species § 223.203 Anadromous fish. Available guidance documents cited in...

  20. In-source laser spectroscopy developments at TRILIS—towards spectroscopy on actinium and scandium

    Resonance Ionization Laser Ion Sources (RILIS) have become a versatile tool for production and study of exotic nuclides at Isotope Separator On-Line (ISOL) facilities such as ISAC at TRIUMF. The recent development and addition of a grating tuned spectroscopy laser to the TRIUMF RILIS solid state laser system allows for wide range spectral scans to investigate atomic structures on short lived isotopes, e.g., those from the element actinium, produced in uranium targets at ISAC. In addition, development of new and improved laser ionization schemes for rare isotope production at ISAC is ongoing. Here spectroscopic studies on bound states, Rydberg states and autoionizing (AI) resonances on scandium using the existing off-line capabilities are reported. These results allowed to identify a suitable ionization scheme for scandium via excitation into an autoionizing state at 58,104 cm − 1 which has subsequently been used for ionization of on-line produced exotic scandium isotopes.

  1. 7 CFR 1280.223 - Reports.

    2010-01-01

    ... 7 Agriculture 10 2010-01-01 2010-01-01 false Reports. 1280.223 Section 1280.223 Agriculture... INFORMATION ORDER Lamb Promotion, Research, and Information Order Reports, Books, and Records § 1280.223 Reports. Each first handler required to remit assessments to the Board for live lambs pursuant to §...

  2. 40 CFR 265.223 - Containment system.

    2010-07-01

    ... 40 Protection of Environment 25 2010-07-01 2010-07-01 false Containment system. 265.223 Section 265.223 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES (CONTINUED... FACILITIES Surface Impoundments § 265.223 Containment system. All earthen dikes must have a protective...

  3. 49 CFR 234.223 - Gate arm.

    2010-10-01

    ... 49 Transportation 4 2010-10-01 2010-10-01 false Gate arm. 234.223 Section 234.223 Transportation... Maintenance Standards § 234.223 Gate arm. Each gate arm, when in the downward position, shall extend across... clearly viewed by approaching highway users. Each gate arm shall start its downward motion not less...

  4. 32 CFR 223.5 - Responsibilities.

    2010-07-01

    ... 32 National Defense 2 2010-07-01 2010-07-01 false Responsibilities. 223.5 Section 223.5 National Defense Department of Defense (Continued) OFFICE OF THE SECRETARY OF DEFENSE (CONTINUED) MISCELLANEOUS DEPARTMENT OF DEFENSE UNCLASSIFIED CONTROLLED NUCLEAR INFORMATION (DOD UCNI) § 223.5 Responsibilities....

  5. 36 CFR 223.279 - Personal use.

    2010-07-01

    .... In conjunction with determining sustainable harvest levels under § 223.219, the responsible Forest... 223.279 Parks, Forests, and Public Property FOREST SERVICE, DEPARTMENT OF AGRICULTURE SALE AND DISPOSAL OF NATIONAL FOREST SYSTEM TIMBER Forest Botanical Products § 223.279 Personal use. (a)...

  6. 32 CFR 223.4 - Policy.

    2010-07-01

    ... 32 National Defense 2 2010-07-01 2010-07-01 false Policy. 223.4 Section 223.4 National Defense Department of Defense (Continued) OFFICE OF THE SECRETARY OF DEFENSE (CONTINUED) MISCELLANEOUS DEPARTMENT OF DEFENSE UNCLASSIFIED CONTROLLED NUCLEAR INFORMATION (DOD UCNI) § 223.4 Policy. It is DoD policy: (a)...

  7. 31 CFR 223.5 - Business.

    2010-07-01

    ... 31 Money and Finance: Treasury 2 2010-07-01 2010-07-01 false Business. 223.5 Section 223.5 Money... OF THE TREASURY FINANCIAL MANAGEMENT SERVICE SURETY COMPANIES DOING BUSINESS WITH THE UNITED STATES § 223.5 Business. (a) The company must engage in the business of suretyship whether or not also...

  8. 13 CFR 134.223 - Evidence.

    2010-01-01

    ... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false Evidence. 134.223 Section 134.223... OFFICE OF HEARINGS AND APPEALS Rules of Practice for Most Cases § 134.223 Evidence. (a) Federal Rules of Evidence. Unless contrary to a particular rule in this part, or an order of the Judge, the Federal Rules...

  9. 14 CFR 16.223 - Evidence.

    2010-01-01

    ... party other than the agency except as provided in Department of Transportation regulations at 49 CFR... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Evidence. 16.223 Section 16.223 Aeronautics... PRACTICE FOR FEDERALLY-ASSISTED AIRPORT ENFORCEMENT PROCEEDINGS Hearings § 16.223 Evidence. (a) General....

  10. 36 CFR 223.227 - Sale advertisement.

    2010-07-01

    ... 36 Parks, Forests, and Public Property 2 2010-07-01 2010-07-01 false Sale advertisement. 223.227 Section 223.227 Parks, Forests, and Public Property FOREST SERVICE, DEPARTMENT OF AGRICULTURE SALE AND DISPOSAL OF NATIONAL FOREST SYSTEM TIMBER Special Forest Products Advertisement and Bids § 223.227 Sale advertisement. (a) The Forest Service...

  11. Developments towards in-gas-jet laser spectroscopy studies of actinium isotopes at LISOL

    Raeder, S.; Bastin, B.; Block, M.; Creemers, P.; Delahaye, P.; Ferrer, R.; Fléchard, X.; Franchoo, S.; Ghys, L.; Gaffney, L. P.; Granados, C.; Heinke, R.; Hijazi, L.; Huyse, M.; Kron, T.; Kudryavtsev, Yu.; Laatiaoui, M.; Lecesne, N.; Luton, F.; Moore, I. D.; Martinez, Y.; Mogilevskiy, E.; Naubereit, P.; Piot, J.; Rothe, S.; Savajols, H.; Sels, S.; Sonnenschein, V.; Traykov, E.; Van Beveren, C.; Van den Bergh, P.; Van Duppen, P.; Wendt, K.; Zadvornaya, A.

    2016-06-01

    To study exotic nuclides at the borders of stability with laser ionization and spectroscopy techniques, highest efficiencies in combination with a high spectral resolution are required. These usually opposing requirements are reconciled by applying the in-gas-laser ionization and spectroscopy (IGLIS) technique in the supersonic gas jet produced by a de Laval nozzle installed at the exit of the stopping gas cell. Carrying out laser ionization in the low-temperature and low density supersonic gas jet eliminates pressure broadening, which will significantly improve the spectral resolution. This article presents the required modifications at the Leuven Isotope Separator On-Line (LISOL) facility that are needed for the first on-line studies of in-gas-jet laser spectroscopy. Different geometries for the gas outlet and extraction ion guides have been tested for their performance regarding the acceptance of laser ionized species as well as for their differential pumping capacities. The specifications and performance of the temporarily installed high repetition rate laser system, including a narrow bandwidth injection-locked Ti:sapphire laser, are discussed and first preliminary results on neutron-deficient actinium isotopes are presented indicating the high capability of this novel technique.

  12. Level Scheme of 223Fr

    A study has been made of the decay of 227 Ac at levels of 223Fr, means of alpha Spectrometers of Si barrier detector and gamma Spectrometers of Ge(Li). The rotational bands 1/2-(541 ↓ ] , 1/2-(530 ↑ ) and 3/2-(532 ↓ ) have been identified, as well as two octupolar bands associated with the fundamental one. The results obtained indicate that the unified model is applicable in this intermediate zone of the nuclide chart. (Author) 150 refs

  13. 27 CFR 46.223 - Tax credit.

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 2 2010-04-01 2010-04-01 false Tax credit. 46.223 Section 46.223 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF... PAPERS AND TUBES Floor Stocks Tax on Certain Tobacco Products, Cigarette Papers, and Cigarette Tubes...

  14. 31 CFR 223.20 - Final decisions.

    2010-07-01

    ... 31 Money and Finance: Treasury 2 2010-07-01 2010-07-01 false Final decisions. 223.20 Section 223.20 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) FISCAL SERVICE, DEPARTMENT OF THE TREASURY FINANCIAL MANAGEMENT SERVICE SURETY COMPANIES DOING BUSINESS WITH THE...

  15. 31 CFR 223.21 - Reinstatement.

    2010-07-01

    ... 31 Money and Finance: Treasury 2 2010-07-01 2010-07-01 false Reinstatement. 223.21 Section 223.21 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) FISCAL SERVICE, DEPARTMENT OF THE TREASURY FINANCIAL MANAGEMENT SERVICE SURETY COMPANIES DOING BUSINESS WITH THE...

  16. 31 CFR 223.17 - Revocation.

    2010-07-01

    ... 31 Money and Finance: Treasury 2 2010-07-01 2010-07-01 false Revocation. 223.17 Section 223.17 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) FISCAL SERVICE, DEPARTMENT OF THE TREASURY FINANCIAL MANAGEMENT SERVICE SURETY COMPANIES DOING BUSINESS WITH THE...

  17. 31 CFR 223.4 - Deposits.

    2010-07-01

    ... 31 Money and Finance: Treasury 2 2010-07-01 2010-07-01 false Deposits. 223.4 Section 223.4 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) FISCAL SERVICE, DEPARTMENT OF THE TREASURY FINANCIAL MANAGEMENT SERVICE SURETY COMPANIES DOING BUSINESS WITH THE UNITED...

  18. 36 CFR 2.23 - Recreation fees.

    2010-07-01

    ... 36 Parks, Forests, and Public Property 1 2010-07-01 2010-07-01 false Recreation fees. 2.23 Section... PROTECTION, PUBLIC USE AND RECREATION § 2.23 Recreation fees. (a) Recreation fees shall be established as... sites, facilities, equipment or services, or participating in group activities, recreation events,...

  19. 18 CFR 3b.223 - Fees.

    2010-04-01

    ... 18 Conservation of Power and Water Resources 1 2010-04-01 2010-04-01 false Fees. 3b.223 Section 3b... INFORMATION Rules for Disclosure of Records § 3b.223 Fees. (a) Fees will be charged for the direct cost of... the records. Any person may obtain a copy of the Commission's schedule of fees by telephone, by...

  20. 36 CFR 223.63 - Advertised rates.

    2010-07-01

    ... 36 Parks, Forests, and Public Property 2 2010-07-01 2010-07-01 false Advertised rates. 223.63... DISPOSAL OF NATIONAL FOREST SYSTEM TIMBER Timber Sale Contracts Appraisal and Pricing § 223.63 Advertised rates. Timber shall be advertised for sale at its appraised value. The road construction cost used...

  1. 36 CFR 223.35 - Performance bond.

    2010-07-01

    ... 36 Parks, Forests, and Public Property 2 2010-07-01 2010-07-01 false Performance bond. 223.35 Section 223.35 Parks, Forests, and Public Property FOREST SERVICE, DEPARTMENT OF AGRICULTURE SALE AND... Performance bond. Timber sale contracts may require the purchaser to furnish a performance bond...

  2. 31 CFR 223.8 - Financial reports.

    2010-07-01

    ... 31 Money and Finance: Treasury 2 2010-07-01 2010-07-01 false Financial reports. 223.8 Section 223.8 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) FISCAL SERVICE, DEPARTMENT OF THE TREASURY FINANCIAL MANAGEMENT SERVICE SURETY COMPANIES DOING BUSINESS WITH THE...

  3. 7 CFR 1220.223 - Assessments.

    2010-01-01

    ... CONSUMER INFORMATION Soybean Promotion and Research Order Expenses and Assessments § 1220.223 Assessments... the first purchaser must establish to the satisfaction of the Board that the producer has...

  4. Dosimetry of radium-223 and progeny

    Fisher, D.R. [Pacific Northwest National Lab., Richland, WA (United States); Sgouros, G. [Memorial Sloan-Kettering Cancer Center, New York, NY (United States)

    1999-01-01

    Radium-223 is a short-lived (11.4 d) alpha emitter with potential applications in radioimmunotherapy of cancer. Radium-223 can be complexed and linked to protein delivery molecules for specific tumor-cell targeting. It decays through a cascade of short-lived alpha- and beta-emitting daughters with emission of about 28 MeV of energy through complete decay. The first three alpha particles are essentially instantaneous. Photons associated with Ra-223 and progeny provide the means for tumor and normal-organ imaging and dosimetry. Two beta particles provide additional therapeutic value. Radium-223 may be produced economically and in sufficient amounts for widescale application. Many aspects of the chemistry of carrier-free isotope preparation, complexation, and linkage to the antibody have been developed and are being tested. The radiation dosimetry of a Ra-223-labeled antibody shows favorable tumor to normal tissue dose ratios for therapy. The 11.4-d half-life of Ra-223 allows sufficient time for immunoconjugate preparation, administration, and tumor localization by carrier antibodies before significant radiological decay takes place. If 0.01 percent of a 37 MBq (1 mCi) injection deposits in a one gram tumor mass, and if the activity is retained with a typical effective half-time (75 h), the absorbed dose will be 163 mGy MBq{sup {minus}1} (600 rad mCi{sup {minus}1}) administered. 49 refs., 5 figs., 2 tabs.

  5. Recrystallization of 223Ra with barium sulfate

    In this work, the kinetics of barium sulfate recrystallization has been studied in acidic 0.01 mol dm-3 sodium sulfate solution using 223Ra and 133Ba tracers at very low total radium concentration, i.e. less than 10-13 mol dm-3. It was found that the system follows the homogeneous recrystallization model and that recrystallization rates, inferred by the decrease of 223Ra and 133Ba in the aqueous solution, are fast. Therefore, even at very low concentrations, below the solubility limit, radium will be retained by barium sulfate-a mineral present in the deep underground repository. (author)

  6. 36 CFR 223.88 - Bidding methods.

    2010-07-01

    ... 36 Parks, Forests, and Public Property 2 2010-07-01 2010-07-01 false Bidding methods. 223.88... methods. (a) Competitive sales of National Forest timber shall be offered through either sealed or oral auction bidding. The method chosen for each sale will: (1) Insure open and fair competition, (2)...

  7. 36 CFR 223.231 - Bidding methods.

    2010-07-01

    ... 36 Parks, Forests, and Public Property 2 2010-07-01 2010-07-01 false Bidding methods. 223.231... methods. The Contracting Officer or designated forest officer shall offer advertised sales of special forest products through sealed bid or sealed bid followed by oral auction. The method selected shall:...

  8. 31 CFR 223.7 - Investment of capital and assets.

    2010-07-01

    ... 31 Money and Finance: Treasury 2 2010-07-01 2010-07-01 false Investment of capital and assets. 223.7 Section 223.7 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued... WITH THE UNITED STATES § 223.7 Investment of capital and assets. The cash capital and other funds...

  9. 31 CFR 223.2 - Application for certificate of authority.

    2010-07-01

    ... 31 Money and Finance: Treasury 2 2010-07-01 2010-07-01 false Application for certificate of authority. 223.2 Section 223.2 Money and Finance: Treasury Regulations Relating to Money and Finance... BUSINESS WITH THE UNITED STATES § 223.2 Application for certificate of authority. Every company wishing...

  10. 31 CFR 223.9 - Valuation of assets and liabilities.

    2010-07-01

    ... 31 Money and Finance: Treasury 2 2010-07-01 2010-07-01 false Valuation of assets and liabilities. 223.9 Section 223.9 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued... WITH THE UNITED STATES § 223.9 Valuation of assets and liabilities. In determining the...

  11. 17 CFR 256.223 - Advances from associate companies.

    2010-04-01

    ... companies. 256.223 Section 256.223 Commodity and Securities Exchanges SECURITIES AND EXCHANGE COMMISSION (CONTINUED) UNIFORM SYSTEM OF ACCOUNTS FOR MUTUAL SERVICE COMPANIES AND SUBSIDIARY SERVICE COMPANIES, PUBLIC UTILITY HOLDING COMPANY ACT OF 1935 6. Long-Term Debt § 256.223 Advances from associate companies....

  12. 31 CFR 223.6 - Requirements applicable to surety companies.

    2010-07-01

    ... companies. 223.6 Section 223.6 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) FISCAL SERVICE, DEPARTMENT OF THE TREASURY FINANCIAL MANAGEMENT SERVICE SURETY COMPANIES DOING BUSINESS WITH THE UNITED STATES § 223.6 Requirements applicable to surety companies. Every company now...

  13. 48 CFR 223.570 - Drug-free work force.

    2010-10-01

    ... 48 Federal Acquisition Regulations System 3 2010-10-01 2010-10-01 false Drug-free work force. 223.570 Section 223.570 Federal Acquisition Regulations System DEFENSE ACQUISITION REGULATIONS SYSTEM... TECHNOLOGIES, OCCUPATIONAL SAFETY, AND DRUG-FREE WORKPLACE Drug-Free Workplace 223.570 Drug-free work force....

  14. 14 CFR 223.3 - Mandatory free transportation.

    2010-01-01

    ... 14 Aeronautics and Space 4 2010-01-01 2010-01-01 false Mandatory free transportation. 223.3 Section 223.3 Aeronautics and Space OFFICE OF THE SECRETARY, DEPARTMENT OF TRANSPORTATION (AVIATION PROCEEDINGS) ECONOMIC REGULATIONS FREE AND REDUCED-RATE TRANSPORTATION General Provisions § 223.3...

  15. 50 CFR 223.202 - Steller sea lion.

    2010-10-01

    ... 50 Wildlife and Fisheries 7 2010-10-01 2010-10-01 false Steller sea lion. 223.202 Section 223.202... Threatened Marine and Anadromous Species § 223.202 Steller sea lion. (a) General prohibitions. The... the eastern population of Steller sea lions: (1) No discharge of firearms. Except as provided...

  16. 36 CFR 223.164 - Penalty for falsification.

    2010-07-01

    .... 223.164 Section 223.164 Parks, Forests, and Public Property FOREST SERVICE, DEPARTMENT OF AGRICULTURE SALE AND DISPOSAL OF NATIONAL FOREST SYSTEM TIMBER Timber Export and Substitution Restrictions § 223.164 Penalty for falsification. For false certification of documents relating to export or...

  17. 31 CFR 223.10 - Limitation of risk.

    2010-07-01

    ... SERVICE, DEPARTMENT OF THE TREASURY FINANCIAL MANAGEMENT SERVICE SURETY COMPANIES DOING BUSINESS WITH THE UNITED STATES § 223.10 Limitation of risk. Except as provided in § 223.11, no company holding a... 31 Money and Finance: Treasury 2 2010-07-01 2010-07-01 false Limitation of risk. 223.10...

  18. 50 CFR 223.201 - Guadalupe fur seal.

    2010-10-01

    ... 50 Wildlife and Fisheries 7 2010-10-01 2010-10-01 false Guadalupe fur seal. 223.201 Section 223... Applicable to Threatened Marine and Anadromous Species § 223.201 Guadalupe fur seal. (a) Prohibitions. The... seal except as provided in paragraph (b) of this section. (b) Exceptions. (1) The...

  19. 36 CFR 223.228 - Contents of advertisement.

    2010-07-01

    ... 36 Parks, Forests, and Public Property 2 2010-07-01 2010-07-01 false Contents of advertisement. 223.228 Section 223.228 Parks, Forests, and Public Property FOREST SERVICE, DEPARTMENT OF AGRICULTURE SALE AND DISPOSAL OF NATIONAL FOREST SYSTEM TIMBER Special Forest Products Advertisement and Bids § 223.228 Contents of advertisement. The...

  20. 36 CFR 223.82 - Contents of advertisement.

    2010-07-01

    ... 36 Parks, Forests, and Public Property 2 2010-07-01 2010-07-01 false Contents of advertisement. 223.82 Section 223.82 Parks, Forests, and Public Property FOREST SERVICE, DEPARTMENT OF AGRICULTURE SALE AND DISPOSAL OF NATIONAL FOREST SYSTEM TIMBER Timber Sale Contracts Advertisement and Bids § 223.82 Contents of advertisement. (a) A timber...

  1. 36 CFR 223.80 - When advertisement is required.

    2010-07-01

    ... 36 Parks, Forests, and Public Property 2 2010-07-01 2010-07-01 false When advertisement is required. 223.80 Section 223.80 Parks, Forests, and Public Property FOREST SERVICE, DEPARTMENT OF AGRICULTURE SALE AND DISPOSAL OF NATIONAL FOREST SYSTEM TIMBER Timber Sale Contracts Advertisement and Bids § 223.80 When advertisement is required. Except...

  2. 24 CFR 248.223 - Alternative State strategy.

    2010-04-01

    ... 24 Housing and Urban Development 2 2010-04-01 2010-04-01 false Alternative State strategy. 248.223... Preservation Act of 1987 § 248.223 Alternative State strategy. (a) The Commissioner may approve a State strategy providing for State approval of plans of action that involve termination of low...

  3. 49 CFR 223.15 - Requirements for existing passenger cars.

    2010-10-01

    ... 49 Transportation 4 2010-10-01 2010-10-01 false Requirements for existing passenger cars. 223.15... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION SAFETY GLAZING STANDARDS-LOCOMOTIVES, PASSENGER CARS AND CABOOSES Specific Requirements § 223.15 Requirements for existing passenger cars. (a) Passenger cars built...

  4. 14 CFR 21.223 - Class II provisional airworthiness certificates.

    2010-01-01

    ... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Class II provisional airworthiness certificates. 21.223 Section 21.223 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF... the aircraft has been issued to the manufacturer. (c) The applicant must submit a statement by...

  5. 46 CFR 108.223 - Guards on exposed equipment.

    2010-10-01

    ... 46 Shipping 4 2010-10-01 2010-10-01 false Guards on exposed equipment. 108.223 Section 108.223 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) A-MOBILE OFFSHORE DRILLING UNITS DESIGN... contact by personnel. Helicopter Facilities...

  6. 31 CFR 223.3 - Issuance of certificates of authority.

    2010-07-01

    ... 31 Money and Finance: Treasury 2 2010-07-01 2010-07-01 false Issuance of certificates of authority. 223.3 Section 223.3 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued... United States or of any State, or it is limited by its articles of incorporation or corporate charter...

  7. 31 CFR 223.1 - Certificate of authority.

    2010-07-01

    ... 31 Money and Finance: Treasury 2 2010-07-01 2010-07-01 false Certificate of authority. 223.1 Section 223.1 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) FISCAL SERVICE, DEPARTMENT OF THE TREASURY FINANCIAL MANAGEMENT SERVICE SURETY COMPANIES DOING BUSINESS WITH...

  8. 31 CFR 223.12 - Recognition as reinsurer.

    2010-07-01

    ... 31 Money and Finance: Treasury 2 2010-07-01 2010-07-01 false Recognition as reinsurer. 223.12 Section 223.12 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) FISCAL SERVICE, DEPARTMENT OF THE TREASURY FINANCIAL MANAGEMENT SERVICE SURETY COMPANIES DOING BUSINESS WITH...

  9. Dicty_cDB: SLI223 [Dicty_cDB

    Full Text Available SL (Link to library) SLI223 (Link to dictyBase) - - - Contig-U15456-1 SLI223Z (Link to Original ... 85_1( EF193385 |pid:none) Musca domestica aspartic proteinas ... 47 4e-09 EF070454_1( EF070454 |pid:none) Macone ...

  10. Dicty_cDB: CHB223 [Dicty_cDB

    Full Text Available CH (Link to library) CHB223 (Link to dictyBase) - - - Contig-U16243-1 CHB223P (Link to Original ... o... 657 0.0 X75329_1( X75329 |pid:none) M.indica (Manila ) THMF5 mRNA for 3-ket... 370 e-101 AF062589_2( AF0 ...

  11. 36 CFR 223.89 - Relation to other bidders.

    2010-07-01

    ... 36 Parks, Forests, and Public Property 2 2010-07-01 2010-07-01 false Relation to other bidders. 223.89 Section 223.89 Parks, Forests, and Public Property FOREST SERVICE, DEPARTMENT OF AGRICULTURE....89 Relation to other bidders. Any bidder or applicant for a sale may be required to furnish...

  12. Complete Genome Sequence of Biocontrol Strain Pseudomonas fluorescens LBUM 223

    Roquigny, Roxane; Arseneault, Tanya; Gadkar, Vijay J.; Novinscak, Amy; Joly, David L.; Filion, Martin

    2015-01-01

    Pseudomonas fluorescens LBUM 223 is a plant growth-promoting rhizobacterium (PGPR) with biocontrol activity against various plant pathogens. It produces the antimicrobial metabolite phenazine-1-carboxylic acid, which is involved in the biocontrol of Streptomyces scabies, the causal agent of common scab of potato. Here, we report the complete genome sequence of P. fluorescens LBUM 223.

  13. 36 CFR 223.137 - Causes for debarment.

    2010-07-01

    ... 36 Parks, Forests, and Public Property 2 2010-07-01 2010-07-01 false Causes for debarment. 223.137... DISPOSAL OF NATIONAL FOREST SYSTEM TIMBER Suspension and Debarment of Timber Purchasers § 223.137 Causes for debarment. The debarring official may debar a purchaser for any of the following causes:...

  14. 48 CFR 1852.223-70 - Safety and health.

    2010-10-01

    ... 48 Federal Acquisition Regulations System 6 2010-10-01 2010-10-01 true Safety and health. 1852.223... 1852.223-70 Safety and health. As prescribed in 1823.7004(c), insert the following clause: Safety and Health (APR 2002) (a) Safety is the freedom from those conditions that can cause death,...

  15. Dicty_cDB: CHM223 [Dicty_cDB

    Full Text Available CH (Link to library) CHM223 (Link to dictyBase) - - - Contig-U10738-1 | Contig-U12609-1 CHM223P ... significant alignments: (bits) Value N BU803755 | polymer ase (RNA) II (DNA directed) polypeptide B (140kD) [ ... 5 |AY485615.1 Candida tropicalis DNA-dependent RNA polymer ase II second largest subunit gene, partial cds. 80 ...

  16. Level Scheme of {sup 223}Fr; Estudio del esquema de niveles del {sup 223}Fr

    Gaeta, R.; Gonzalez, L.; Roldan, C.

    1972-07-01

    A study has been made of the decay of {sup 227}Ac at levels of {sub 223}Fr, means of alpha Spectrometers of Si barrier detector and gamma Spectrometers of Ge(Li). The rotational bands 1/2-(541 {down_arrow}), 1/2-(530 {up_arrow}) and 3/2-(532 {down_arrow}) have been identified, as well as two octupolar bands associated with the fundamental one. The results obtained indicate that the unified model is applicable in this intermediate zone of the nuclide chart. (Author) 150 refs.

  17. Direct measurement of the half-life of 223Ra

    Radioactive decay half-life measurements of 223Ra, a member of the 235U naturally occurring radioactive decay series, have been performed of a radiochemically pure solution with an ionisation chamber. The radioactive decay of 223Ra was followed for 50 days, approximately 4.4 half-lives. The deduced half-life of 223Ra was found to be 11.4358 (28) days, supporting the other published direct measurements. A detailed uncertainty budget is presented. A new evaluation of the published half-life values was performed, indicating significant variation across the existing published values, suggesting that further measurements of the half-life of 223Ra are required. A new evaluated half-life has been calculated using a power moderated weighted mean of selected experimental values, with a new value of the recommended half-life for 223Ra of 11.4354 (17) days. - Highlights: • Direct measurement of the 223Ra half-life using an ionisation chamber. • New measured half-life of 11.4358 (28) days. • Result consistent with the most precise published value

  18. New 223-nm excimer laser surgical system for photorefractive keratectomy

    Bagaev, Sergei N.; Razhev, Alexander M.; Zhupikov, Andrey A.

    1999-02-01

    The using of KrCl (223 nm) excimer laser in ophthalmic devices for Photorefractive Keratectomy (PRK) and phototherapeutic Keratectomy (PTK) is offered. The structure and functions of a new surgical UV ophthalmic laser systems Medilex using ArF (193 nm) or KrCl (223 nm) excimer laser for corneal surgery are presented. The systems Medilex with the new optical delivery system is used for photoablative reprofiling of the cornea to correct refraction errors (myopia, hyperopia and astigmatism) and to treat a corneal pathologies. The use of the 223 nanometer laser is proposed to have advantages over the 193 nanometer laser. The results of application of the ophthalmic excimer laser systems Medilex for treatment of myopia are presented.

  19. 76 FR 72996 - Eleventh Meeting: RTCA Special Committee 223 Airport Surface Wireless Communications

    2011-11-28

    ... Federal Aviation Administration Eleventh Meeting: RTCA Special Committee 223 Airport Surface Wireless...: Notice of RTCA Special Committee 223 Airport Surface Wireless Communications Eleventh Meeting. SUMMARY..., Airport Surface Wireless Communications Eleventh Meeting DATES: The meeting will be held December...

  20. THE METABOLSIM AND TOXICITY OF RADIUM-223 IN RATS

    Durbin, Patricia; Durbin, Patricia W.; Asling, C. Willet.; Jeung, Nylan; Williams, Marilyn H.; Post, James.; Johnston, Muriel E.; Hamilton, Joseph G.

    1958-02-21

    This report covers studies of the excretion and retention of 'tracer' and toxic doses of the 11.2-day Ra{sup 223} isotope, its acute toxicity (organ weight changes, gross and microscopic pathology, and Fe{sup 59} utilization by the bone marrow), and long-term histopathological changes and alterations in the hemogram.

  1. 36 CFR 223.229 - Contents of prospectus.

    2010-07-01

    ... AND DISPOSAL OF NATIONAL FOREST SYSTEM TIMBER Special Forest Products Advertisement and Bids § 223.229...: (a) The minimum acceptable value or unit price for a product and the amount or rate of any deposits required in addition to the unit price of a product; (b) The amount of the bid guarantee that...

  2. 36 CFR 223.85 - Noncompetitive sale of timber.

    2010-07-01

    ... SALE AND DISPOSAL OF NATIONAL FOREST SYSTEM TIMBER Timber Sale Contracts Advertisement and Bids § 223... further advertisement, at not less than appraised value, any timber previously advertised for competitive... of competitive interest in the product. (b) Extraordinary conditions, as provided for in 16...

  3. 36 CFR 223.185 - Scope and applicability.

    2010-07-01

    ....185 Section 223.185 Parks, Forests, and Public Property FOREST SERVICE, DEPARTMENT OF AGRICULTURE SALE AND DISPOSAL OF NATIONAL FOREST SYSTEM TIMBER The Forest Resources Conservation and Shortage Relief... Forest Resources Conservation and Shortage Relief Act of 1990 (16 U.S.C. 620, et seq.) that...

  4. 31 CFR 223.16 - List of certificate holding companies.

    2010-07-01

    ... 31 Money and Finance: Treasury 2 2010-07-01 2010-07-01 false List of certificate holding companies...) FISCAL SERVICE, DEPARTMENT OF THE TREASURY FINANCIAL MANAGEMENT SERVICE SURETY COMPANIES DOING BUSINESS WITH THE UNITED STATES § 223.16 List of certificate holding companies. A list of qualified companies...

  5. 36 CFR 223.62 - Timber purchaser road construction credit.

    2010-07-01

    ... § 223.62 Timber purchaser road construction credit. Appraisal may also establish stumpage value as if... timber is appraised and sold on such basis, purchaser credit for road construction, not to exceed the... deposits for slash disposal and road maintenance. As used in this section estimated construction...

  6. 40 CFR 98.223 - Calculating GHG emissions.

    2010-07-01

    ... (CONTINUED) MANDATORY GREENHOUSE GAS REPORTING Nitric Acid Production § 98.223 Calculating GHG emissions. (a... nitric acid train “t” (fraction of annual production that abatement technology is operating). Pa t = Total annual nitric acid production from nitric acid train “t” (ton acid produced, 100 percent...

  7. 31 CFR 223.11 - Limitation of risk: Protective methods.

    2010-07-01

    ... 31 Money and Finance: Treasury 2 2010-07-01 2010-07-01 false Limitation of risk: Protective... BUSINESS WITH THE UNITED STATES § 223.11 Limitation of risk: Protective methods. The limitation of risk... underwriting limitations. Each company shall limit its liability upon the face of the bond or policy, to...

  8. Radium-223 in metastatic castration resistant prostate cancer

    Winston Vuong; Oliver Sartor; Sumanta K Pal

    2014-01-01

    In 2004, docetaxel was approved for the treatment of metastatic castration-resistant prostate cancer (mCRPC). For the next several years, there was a lull in drug approvals. However, from 2010 onwards, 5 additional therapies have been approved on the basis of showing a survival beneift in phase III studies. These agents include sipuleucel-T, cabazitaxel, abiraterone, enzalutamide and (most recently) radium-223. Amongst radiopharmaceuticals currently used for advanced prostate cancer (e.g. samarium-153 and strontium-89), radium-223 possesses several unique properties. As an alpha-emitting compound, the agent produces a high-energy output over a short range, facilitating selective destruction of tissue within the bone in the region of osteoblastic lesions while sparing surrounding normal tissue. The current review will outline biological rationale for radium-223 and also provide an overview of preclinical and clinical development of the agent. Rational sequencing of radium-223 and combinations, in the increasingly complex landscape of mCRPC will be discussed, along with factors inlfuencing clinical implementation.

  9. Dicty_cDB: SHJ223 [Dicty_cDB

    Full Text Available SH (Link to library) SHJ223 (Link to dictyBase) - - - Contig-U16405-1 - (Link to Original site) ... ikyc*glyi*cfgfsilsksiqfei* *ktkniw*ryshywlifkiiwws*fpy *fh*ck*tfcc*r*fl*sif*l**yycnistri rki*vvl**nwg*scti ...

  10. 31 CFR 223.14 - Schedules of single risks.

    2010-07-01

    ... SERVICE, DEPARTMENT OF THE TREASURY FINANCIAL MANAGEMENT SERVICE SURETY COMPANIES DOING BUSINESS WITH THE UNITED STATES § 223.14 Schedules of single risks. During the months of January, April, July, and October... 31 Money and Finance: Treasury 2 2010-07-01 2010-07-01 false Schedules of single risks....

  11. 14 CFR 125.223 - Airborne weather radar equipment requirements.

    2010-01-01

    ... 14 Aeronautics and Space 3 2010-01-01 2010-01-01 false Airborne weather radar equipment... Equipment Requirements § 125.223 Airborne weather radar equipment requirements. (a) No person may operate an airplane governed by this part in passenger-carrying operations unless approved airborne weather...

  12. 36 CFR 223.142 - Causes for suspension.

    2010-07-01

    ... 36 Parks, Forests, and Public Property 2 2010-07-01 2010-07-01 false Causes for suspension. 223... Causes for suspension. (a) The suspending official may suspend a purchaser suspected, upon adequate... responsibility of a purchase of Government timber. (2) Indictment for any of the causes listed in paragraph...

  13. 48 CFR 52.223-6 - Drug-Free Workplace.

    2010-10-01

    ... further defined in regulation at 21 CFR 1308.11-1308.15. Conviction means a finding of guilt (including a... 48 Federal Acquisition Regulations System 2 2010-10-01 2010-10-01 false Drug-Free Workplace. 52....223-6 Drug-Free Workplace. As prescribed in 23.505, insert the following clause: Drug-Free...

  14. 31 CFR 223.22 - Fees for services of the Treasury Department.

    2010-07-01

    ... 31 Money and Finance: Treasury 2 2010-07-01 2010-07-01 false Fees for services of the Treasury Department. 223.22 Section 223.22 Money and Finance: Treasury Regulations Relating to Money and Finance... BUSINESS WITH THE UNITED STATES § 223.22 Fees for services of the Treasury Department. (a) Fees shall...

  15. 12 CFR 303.223 - Applicant's right to hearing following denial.

    2010-01-01

    ... Criminal Offenses) § 303.223 Applicant's right to hearing following denial. An applicant may request a... 12 Banks and Banking 4 2010-01-01 2010-01-01 false Applicant's right to hearing following denial. 303.223 Section 303.223 Banks and Banking FEDERAL DEPOSIT INSURANCE CORPORATION PROCEDURE AND RULES...

  16. 36 CFR 223.281 - Monitoring and revising sustainable harvest levels.

    2010-07-01

    ... sustainable harvest levels. 223.281 Section 223.281 Parks, Forests, and Public Property FOREST SERVICE....281 Monitoring and revising sustainable harvest levels. The Forest Service shall monitor and revise sustainable harvest levels for forest botanical products in accordance with § 223.219 of subpart G....

  17. 18 CFR 2.23 - Use of reserved authority in hydropower licenses to ameliorate cumulative impacts.

    2010-04-01

    ... authority in hydropower licenses to ameliorate cumulative impacts. 2.23 Section 2.23 Conservation of Power... § 2.23 Use of reserved authority in hydropower licenses to ameliorate cumulative impacts. The... opportunity for hearing by the licensee and all interested parties. Hydropower licenses also contain...

  18. 36 CFR 223.38 - Standards for road design and construction.

    2010-07-01

    ... Provisions § 223.38 Standards for road design and construction. Road construction authorized under timber... 36 Parks, Forests, and Public Property 2 2010-07-01 2010-07-01 false Standards for road design and construction. 223.38 Section 223.38 Parks, Forests, and Public Property FOREST SERVICE, DEPARTMENT...

  19. 36 CFR 223.84 - Small business bid form provisions on sales with specified road construction.

    2010-07-01

    ... provisions on sales with specified road construction. 223.84 Section 223.84 Parks, Forests, and Public... specified road construction. For each sale described in § 223.82(b), the bid form must include provision for a small business concern: (a) To elect road construction by the Forest Service and where...

  20. 36 CFR 223.41 - Payment when purchaser elects government road construction.

    2010-07-01

    ... government road construction. 223.41 Section 223.41 Parks, Forests, and Public Property FOREST SERVICE... Conditions and Provisions § 223.41 Payment when purchaser elects government road construction. Each contract... or more shall include a provision to ensure that if the purchaser elects government road...

  1. 36 CFR 223.47 - Date of completion of permanent road construction.

    2010-07-01

    ... permanent road construction. 223.47 Section 223.47 Parks, Forests, and Public Property FOREST SERVICE... Conditions and Provisions § 223.47 Date of completion of permanent road construction. (a) The date of completion of permanent road construction obligations as set forth in the Notice of Sale shall...

  2. 14 CFR 223.21 - Free and reduced-rate transportation authorized by statute or regulation.

    2010-01-01

    ... authorized by statute or regulation. 223.21 Section 223.21 Aeronautics and Space OFFICE OF THE SECRETARY, DEPARTMENT OF TRANSPORTATION (AVIATION PROCEEDINGS) ECONOMIC REGULATIONS FREE AND REDUCED-RATE TRANSPORTATION International Travel § 223.21 Free and reduced-rate transportation authorized by statute or regulation. (a)...

  3. 36 CFR 223.232 - Disclosure of relation to other bidders.

    2010-07-01

    ... 36 Parks, Forests, and Public Property 2 2010-07-01 2010-07-01 false Disclosure of relation to other bidders. 223.232 Section 223.232 Parks, Forests, and Public Property FOREST SERVICE, DEPARTMENT OF... § 223.232 Disclosure of relation to other bidders. The Forest Service may require any prospective...

  4. 36 CFR 223.12 - Permission to cut, damage, or destroy trees without advertisement.

    2010-07-01

    ... 36 Parks, Forests, and Public Property 2 2010-07-01 2010-07-01 false Permission to cut, damage, or destroy trees without advertisement. 223.12 Section 223.12 Parks, Forests, and Public Property FOREST SERVICE, DEPARTMENT OF AGRICULTURE SALE AND DISPOSAL OF NATIONAL FOREST SYSTEM TIMBER General Provisions § 223.12 Permission to cut, damage,...

  5. Radiation exposure of relatives of patients treated with Ra-223 dichloride; Strahlenexposition von Angehoerigen bei Therapie mit Ra-223-Dichlorid

    Wanke, C.; Szermerski, B.; Solle, A.; Geworski, L. [Medizinische Hochschule Hannover (Germany). Stabsstelle Strahlenschutz und Abt. Medizinische Physik; Pinkert, J. [Bayer Vital GmbH, Leverkusen (Germany); Kranert, W.T. [Frankfurt Univ. (Germany). Klinik fuer Nuklearmedizin; Andreeff, M. [Universitaetsklinikum ' ' Carl Gustav Carus' ' TU Dresden (Germany). Klinik fuer Nuklearmedizin

    2015-07-01

    Since November 2013, a radiopharmaceutical containing Ra-223 dichloride as active substance is approved in the European Union for patients with castration resistant prostate cancer with symptomatic bone metastases and no known visceral metastases. Ra-223 (T{sub 1/2} = 11.43 d) decays via a chain of 4 alpha and 2 beta decays. This therapy is presently the only application of an alpha emitter in clinical routine therapy. To show that the exposure of relatives and caregivers of patients treated with Ra-223 dichloride in an outpatient setting does not exceed a value of 1 mSv, the multicenter study ''RAPSODY'' was conducted. As Ra-223 and most of its progeny emit alpha particles, the internal exposure had to be evaluated in particular. Within this study, measurements of the radiation emitted from the patient were performed using standard dose-rate meters. Wipe-tests were taken in the patients' homes to identify significant contaminations and evaluated by liquid scintillation counting. Samples of saliva and sweat were taken and measured using gamma spectrometry. Ra-223 disintegrates to the noble gas Rn-219 and was measured in the exhaled breath from the patients using conventional Radon Monitors. Furthermore, a computational fluid dynamics simulation (CFD) was performed to assess the radioactivity in the air, which could be inhaled by persons close to the patient. Conclusions: The potential exposure of relatives and caregivers by external irradiation and incorporation of radioactivity exhaled or excreted by the patient with saliva or sweat is well below 1 mSv. No objections are seen regarding outpatient treatment. This paper summarizes contents of a poster presented at the Annual Meeting of the Society of Nuclear Medicine and Molecular Imaging.

  6. Radium-223 dichloride in clinical practice: a review.

    Florimonte, Luigia; Dellavedova, Luca; Maffioli, Lorenzo Stefano

    2016-09-01

    The onset of skeletal metastases is typical of advanced-stage prostate cancer and requires a multidisciplinary approach to alleviate bone pain and try to delay disease progression. The current therapeutic armamentarium includes conventional analgesics, chemotherapeutic agents, immunotherapy, androgen-deprivation therapy, osteoclast inhibitors (bisphosphonates, denosumab), surgical interventions, external-beam radiotherapy and radionuclide metabolic therapy. Many studies in recent decades have demonstrated the efficacy of various radiopharmaceuticals, including strontium-89 and samarium-153, for palliation of pain from diffuse skeletal metastases, but no significant benefit in terms of disease progression and overall survival has been shown. The therapeutic landscape of metastatic skeletal cancer significantly changed after the introduction of radium-223, the first bone-homing radiopharmaceutical with disease-modifying properties. In this paper we extensively review the literature on the use of radium-223 dichloride in metastatic castration-resistant prostate cancer. PMID:27121689

  7. Determination of Ra-223 in human excretion samples by means of α-spectrometry; Bestimmung von {sup 223}Ra in Ausscheidungsproben mittels α-Spektrometrie

    Zoriy, M.V.; Froning, M.; Hill, P. [Forschungszentrum Juelich GmbH (Germany). Geschaeftsbereich Strahlenschutz und Sicherheit

    2015-07-01

    To ensure the safety of occupationally exposed person for possible incorporation of {sup 223}Ra during the handling with Alpharadin / Xofigo {sup registered}, the determination of {sup 223}Ra activity in its excretion sample (e.g, in a stool sample) might be of great importance. To assess the {sup 223}Ra activity in human faeces samples a new analytical method was developed in our laboratory. The determination is performed by means of grid-ionization a-spectrometry. After a relatively simple sample preparation procedure (usually within max. 6 hours) and the addition of an internal standard, a direct determination of {sup 223}Ra with the grid ionization chamber (GIK) is possible. The method was optimized and successfully tested. The procedure-related LOD for {sup 223}Ra in a 24-hour faeces sample was 0.1 Bq/Probe.

  8. 223Ra for endoradiotherapeutic applications prepared from an immobilized 227Ac/227Th source

    A method is described for the production of 223Ra (t1/2 = 11.4 d) in a quality useful for endoradiotherapeutic applications. The method is based on a long term operating generator with a source of 227Ac (t1/2 = 21.7 years), from which 223Ra is eluted. The 227Ac was isolated from a 231Pa source using the f-element selective extraction chromatographic material TRU-resin. The purified 227Ac/227Th source was subsequently applied to another extraction chromatographic resin, containing the extractant P,P'-di(2-ethylhexyl)methanediphosphonic acid on silica (Dipex-2) and used as a generator for 223Ra. From the generator column, the yield of 223Ra was about 60 kBq per 100 kBq of 227Ac with a highly effective separation of 223Ra from the precursors. In production runs, the activity of 227Ac was found to be 6 x 10-6 relative to the eluted activity of 223Ra. By using a second column of Dipex-2 for additional purification, the activity of Ac was reduced to below 7 x 10-8 relative to 223Ra with nearly quantitative recovery of 223Ra. The described procedure resulted in a high purity 223Ra preparation, potentially useful in, e.g., targeted radiotherapy of tumors. (orig.)

  9. Therapy palliative with 223Ra without special radiation protection measures?

    For nearly 2 years now as a therapy of the castration resistant prostata carcinoma a nuclide therapy with 223Ra-Dichloride (trade-mark Xofigo) is applied. Xofigo is applied by a medical specialist for nuclear medicine altogether 6 times in a monthly distance. The activity used in each case is according to the body weight (50 kBq/kg BW). This therapy is licensed by the supervisory authorities of the German federal countries as an ambulant therapy. Special radiation protection measures are only required when exceeding a given number of 17 patients per year as incorparation measurements.

  10. 75 FR 30899 - Fourth Meeting: RTCA Special Committee 223: Airport Surface Wireless Communications

    2010-06-02

    ... Federal Aviation Administration Fourth Meeting: RTCA Special Committee 223: Airport Surface Wireless...: Airport Surface Wireless Communications meeting. SUMMARY: The FAA is issuing this notice to advise the public of a meeting of RTCA Special Committee 223: Airport Surface Wireless Communications. DATES:...

  11. 78 FR 13395 - Meeting: RTCA Special Committee 223, Airport Surface Wireless Communications

    2013-02-27

    ... Federal Aviation Administration Meeting: RTCA Special Committee 223, Airport Surface Wireless...: Meeting Notice of RTCA Special Committee 223, Airport Surface Wireless Communications SUMMARY: The FAA is... Wireless Communications. DATES: The meeting will be held March 19-21, 2013, from 9:00 a.m.--5:00 p.m....

  12. 76 FR 6179 - Eighth Meeting: RTCA Special Committee 223: Airport Surface Wireless Communications

    2011-02-03

    ... Federal Aviation Administration Eighth Meeting: RTCA Special Committee 223: Airport Surface Wireless... of RTCA Special Committee 223: Airport Surface Wireless Communications meeting. SUMMARY: The FAA is... Wireless Communications. DATES: The meeting will be held February 22-23, 2011 from 9 a.m. to 5...

  13. 75 FR 14483 - Third Meeting: RTCA Special Committee 223: Airport Surface Wireless Communications

    2010-03-25

    ... Federal Aviation Administration Third Meeting: RTCA Special Committee 223: Airport Surface Wireless...: Airport Surface Wireless Communications meeting. SUMMARY: The FAA is issuing this notice to advise the public of a meeting of RTCA Special Committee 223: Airport Surface Wireless Communications. DATES:...

  14. 75 FR 66423 - Seventh Meeting: RTCA Special Committee 223: Airport Surface Wireless Communications

    2010-10-28

    ... Federal Aviation Administration Seventh Meeting: RTCA Special Committee 223: Airport Surface Wireless... of RTCA Special Committee 223: Airport Surface Wireless Communications meeting. SUMMARY: The FAA is... Wireless Communications. DATES: The meeting will be held November 16-17, 2010 from 9 a.m.-5 p.m....

  15. 77 FR 55894 - Thirteenth Meeting: RTCA Special Committee 223, Airport Surface Wireless Communications

    2012-09-11

    ... Federal Aviation Administration Thirteenth Meeting: RTCA Special Committee 223, Airport Surface Wireless...: Meeting Notice of RTCA Special Committee 223, Airport Surface Wireless Communications. SUMMARY: The FAA is..., Airport Surface Wireless Communications. DATES: The meeting will be held October 2-3, 2012, from 9...

  16. 78 FR 33145 - Meeting: RTCA Special Committee 223, Airport Surface Wireless Communications

    2013-06-03

    ... Federal Aviation Administration Meeting: RTCA Special Committee 223, Airport Surface Wireless...: Meeting Notice of RTCA Special Committee 223, Airport Surface Wireless Communications. SUMMARY: The FAA is... Wireless Communications. DATES: The meeting will be held June 26-28, 2013, from 9:00 a.m.-5:00 p.m....

  17. 75 FR 54421 - Sixth Meeting: RTCA Special Committee 223: Airport Surface Wireless Communications

    2010-09-07

    ... Federal Aviation Administration Sixth Meeting: RTCA Special Committee 223: Airport Surface Wireless... of RTCA Special Committee 223: Airport Surface Wireless Communications meeting. SUMMARY: The FAA is... Wireless Communications. DATES: The meeting will be held September 28-30, 2010 from 0900 a.m.- 1600...

  18. 77 FR 71028 - Twelfth Meeting: RTCA Special Committee 223, Airport Surface Wireless Communications

    2012-11-28

    ... Federal Aviation Administration Twelfth Meeting: RTCA Special Committee 223, Airport Surface Wireless...: Meeting Notice of RTCA Special Committee 223, Airport Surface Wireless Communications. SUMMARY: The FAA is... Wireless Communications. DATES: The meeting will be held December 4-6, 2012, from 9:00 a.m.-5:00...

  19. 75 FR 44306 - Fifth Meeting: RTCA Special Committee 223: Airport Surface Wireless Communications

    2010-07-28

    ... Federal Aviation Administration Fifth Meeting: RTCA Special Committee 223: Airport Surface Wireless... of RTCA Special Committee 223: Airport Surface Wireless Communications meeting. SUMMARY: The FAA is... Wireless Communications. DATES: The meeting will be held August 17-18, 2010 from 9 a.m.-5 p.m....

  20. 14 CFR 120.223 - Alcohol misuse information, training, and substance abuse professionals.

    2010-01-01

    ... personal life; signs and symptoms of an alcohol problem; available methods of evaluating and resolving... 14 Aeronautics and Space 3 2010-01-01 2010-01-01 false Alcohol misuse information, training, and substance abuse professionals. 120.223 Section 120.223 Aeronautics and Space FEDERAL AVIATION...

  1. 48 CFR 952.223 - Clauses related to environment, energy and water efficiency, renewable energy technologies...

    2010-10-01

    ... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Clauses related to environment, energy and water efficiency, renewable energy technologies, occupational safety, and drug-free workplace. 952.223 Section 952.223 Federal Acquisition Regulations System DEPARTMENT OF ENERGY CLAUSES AND FORMS SOLICITATION PROVISIONS AND...

  2. 36 CFR 223.280 - Waiver of fees and/or fair market value.

    2010-07-01

    ... 36 Parks, Forests, and Public Property 2 2010-07-01 2010-07-01 false Waiver of fees and/or fair market value. 223.280 Section 223.280 Parks, Forests, and Public Property FOREST SERVICE, DEPARTMENT OF... fees and/or fair market value. The Forest Service waives the collection of fees otherwise...

  3. Radium-223 treatment of bone metastases from castration-resistant prostate cancer

    Mortensen, Jann; Højgaard, Liselotte

    2014-01-01

    The alpha emitter Radium-223 ((22)3Ra-Cl2) is a bone-seeking radionuclide studied as a new treatment for patients with bone metastases from hormone refractory prostate cancer. More than 1,000 patients have been included in clinical phase I-III tests showing significant reduction in alkaline...

  4. 40 CFR 86.223-94 - Oxides of nitrogen analyzer calibration.

    2010-07-01

    ... 40 Protection of Environment 18 2010-07-01 2010-07-01 false Oxides of nitrogen analyzer calibration. 86.223-94 Section 86.223-94 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED... nitrogen analyzer calibration. The provisions of § 86.123-78 apply to this subpart if NOX measurements...

  5. MiR-223 suppresses cell proliferation by targeting IGF-1R.

    Cheng You Jia

    Full Text Available To study the roles of microRNA-223 (miR-223 in regulation of cell growth, we established a miR-223 over-expression model in HeLa cells infected with miR-223 by Lentivirus pLL3.7 system. We observed in this model that miR-223 significantly suppressed the proliferation, growth rate, colony formation of HeLa cells in vitro, and in vivo tumorigenicity or tumor formation in nude mice. To investigate the mechanisms involved, we scanned and examined the potential and putative target molecules of miR-223 by informatics, quantitative PCR and Western blot, and found that insulin-like growth factor-1 receptor (IGF-1R was the functional target of miR-223 inhibition of cell proliferation. Targeting IGF-1R by miR-223 was not only seen in HeLa cells, but also in leukemia and hepatoma cells. The downstream pathway, Akt/mTOR/p70S6K, to which the signal was mediated by IGF-1R, was inhibited as well. The relative luciferase activity of the reporter containing wild-type 3'UTR(3'untranslated region of IGF-1R was significantly suppressed, but the mutant not. Silence of IGF-1R expression by vector-based short hairpin RNA resulted in the similar inhibition with miR-223. Contrarily, rescued IGF-1R expression in the cells that over-expressed miR-223, reversed the inhibition caused by miR-223 via introducing IGF-1R cDNA that didn't contain the 3'UTR. Meanwhile, we also noted that miR-223 targeted Rasa1, but the downstream molecules mediated by Rasa1 was neither targeted nor regulated. Therefore we believed that IGF-1R was the functional target for miR-223 suppression of cell proliferation and its downstream PI3K/Akt/mTOR/p70S6K pathway suppressed by miR-223 was by targeting IGF-1R.

  6. Determination of Ra-223 in human excretion samples by means of α-spectrometry

    To ensure the safety of occupationally exposed person for possible incorporation of 223Ra during the handling with Alpharadin / Xofigo registered, the determination of 223Ra activity in its excretion sample (e.g, in a stool sample) might be of great importance. To assess the 223Ra activity in human faeces samples a new analytical method was developed in our laboratory. The determination is performed by means of grid-ionization a-spectrometry. After a relatively simple sample preparation procedure (usually within max. 6 hours) and the addition of an internal standard, a direct determination of 223Ra with the grid ionization chamber (GIK) is possible. The method was optimized and successfully tested. The procedure-related LOD for 223Ra in a 24-hour faeces sample was 0.1 Bq/Probe.

  7. 48 CFR 952.223-71 - Integration of environment, safety, and health into work planning and execution.

    2010-10-01

    ... Provisions and Clauses 952.223-71 Integration of environment, safety, and health into work planning and... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Integration of environment, safety, and health into work planning and execution. 952.223-71 Section 952.223-71 Federal...

  8. Daily temperature and precipitation data for 223 USSR Stations

    Razuvaev, V.N.; Apasova, E.G.; Martuganov, R.A. [Research Institute of Hydrometeorological Information, Obninsk (Russian Federation); Vose, R.S. [Univ. of Tennessee, Knoxville, TN (United States); Steurer, P.M. [National Climatic Data Center, Asheville, NC (United States)

    1993-11-01

    On- May 23, 1972, the United States and the USSR established a bilateral initiative known as the Agreement on Protection of the Environment. Given recent interest in possible greenhouse gas-induced climate change, Working Group VIII (Influence of Environmental Changes on Climate) has become particularly useful to the scientific communities of both nations. Among its many achievements, Working Group VIII has been instrumental in the exchange of climatological information between the principal climate data centers of each country [i.e., the National Climatic Data Center (NCDC) in Asheville, North Carolina, and the Research Institute of Hydrometeorological Information in Obninsk, Russia]. Considering the relative lack of climate records previously available for the USSR, data obtained via this bilateral exchange are particularly valuable to researchers outside the former Soviet Union. To expedite the dissemination of these data, NOAA`s Climate and Global Change Program funded the Carbon Dioxide Information Analysis Center (CDIAC) and NCDC to distribute one of the more useful archives acquired through this exchange: a 223-station daily data set covering the period 1881-1989. This data set contains: (1) daily mean, minimum, and maximum temperature data; (2) daily precipitation data; (3) station inventory information (WMO No., name, coordinates, and elevation); (4) station history information (station relocation and rain gauge replacement dates); and (5) quality assurance information (i.e., flag codes that were assigned as a result of various data checks). The data set is available, free of charge, as a Numeric Data Package (NDP) from CDIAC. The NDP consists of 18 data files and a printed document which describes both the data files and the 223-station network in detail.

  9. Radium-223 behandling af knoglemetastaser ved kastrationsrefraktær prostatacancer

    Mortensen, Jann; Højgaard, Liselotte

    2014-01-01

    The alpha emitter Radium-223 ((22)3Ra-Cl2) is a bone-seeking radionuclide studied as a new treatment for patients with bone metastases from hormone refractory prostate cancer. More than 1,000 patients have been included in clinical phase I-III tests showing significant reduction in alkaline...... phosphatase- and PSA level and prolonged survival. Adverse events are usually mild to moderate and comprise gastrointestinal and myelotoxic symp-toms. Intravenously administered (22)3Ra-Cl2 (half-life 11.4 days) will likely be given every four weeks for six treatments to out-patients....

  10. First In Vivo Evaluation of Liposome-encapsulated 223Ra as a Potential Alpha-particle-emitting Cancer Therapeutic Agent

    Jonasdottir, Thora J.; Fisher, Darrell R.; Borrebaek, Jorgen; Bruland, Oyvind S.; Larsen, Roy H.

    2006-09-13

    Liposomes carrying chemotherapeutics have had some success in cancer treatment and may be suitable carriers for therapeutic radionuclides. This study was designed to evaluate the biodistribution of and to estimate the radiation doses from the alpha emitter 223Ra loaded into pegylated liposomes in selected tissues. 223Ra was encapsulated in pegylated liposomal doxorubicin by ionophore-mediated loading. The biodistribution of liposomal 223Ra was compared to free cationic 223Ra in Balb/C mice. We showed that liposomal 223 Ra circulated in the blood with an initial half-time in excess of 24 hours, which agreed well with that reported for liposomal doxorubicin in rodents, while the blood half-time of cationic 223Ra was considerably less than one hour. When liposomal 223 Ra was catabolized, the released 223Ra was either excreted or taken up in the skeleton. This skeletal uptake increased up to 14 days after treatment, but did not reach the level seen with free 223Ra. Pre-treatment with non-radioactive liposomal doxorubicin 4 days in advance lessened the liver uptake of liposomal 223 Ra. Dose estimates showed that the spleen, followed by bone surfaces, received the highest absorbed doses. Liposomal 223 Ra was relatively stable in vivo and may have potential for radionuclide therapy and combination therapy with chemotherapeutic agents.

  11. Dosing, administration, and safety of radium-223: How I do it.

    Dan, Tu D; Doyle, Laura; Raval, Amar J; Pridjian, Andrew; Gomella, Leonard G; Den, Robert B

    2016-06-01

    Radium-223 dichloride is a first-in-class bone-directed radiopharmaceutical that has been shown to prolong survival in men with metastatic castrate resistant prostate cancer (mCRPC). Unlike other radiopharmaceuticals, radium-223 uniquely uses alpha-emission to deliver high intensity, short range cytoxic treatments resulting in minimal myelosuppression. Following the results of the ALSYMPCA trial, radium-223 (Xofigo) was FDA approved in the United States in May 2013 and approved by Health Canada in December 2013 for the treatment of mCRPC with symptomatic bone metastases and no visceral disease. This 'How I do it' article describes the background of radium 223 as well as the methods and techniques that our institution uses for safe and effective administration and notes the subtle differences when administering the drug in Canada. PMID:27347625

  12. The Q223R polymorphism in LEPR is associated with obesity in Pacific Islanders.

    Furusawa, Takuro; Naka, Izumi; Yamauchi, Taro; Natsuhara, Kazumi; Kimura, Ryosuke; Nakazawa, Minato; Ishida, Takafumi; Inaoka, Tsukasa; Matsumura, Yasuhiro; Ataka, Yuji; Nishida, Nao; Tsuchiya, Naoyuki; Ohtsuka, Ryutaro; Ohashi, Jun

    2010-03-01

    Various Pacific Island populations have experienced a marked increase in the prevalence of obesity in past decades. This study examined the association of a promoter polymorphism of the leptin gene (LEP), G-2548A (rs7799039), and two non-synonymous single nucleotide polymorphisms of the leptin receptor gene (LEPR), K109R (rs1137100) and Q223R (rs1137101), with body weight, body mass index (BMI) and obesity (BMI > or = 30) in Pacific Islanders. A total of 745 Austronesian (AN)-speaking participants were analyzed after adjusting for age, gender, and population differences. The results revealed that carriers of the 223Q alleles of LEPR had significantly higher body weight (P = 0.0009) and BMI (P = 0.0022) than non-carriers (i.e., 223R homozygotes); furthermore, the 223Q carriers also had a signiWcantly higher risk of obesity in comparison to non-carriers (P = 0.0222). The other two polymorphisms, G-2548A and K109R, were associated with neither body weight, BMI, nor obesity. The 223Q allele was widely found among the AN-speaking study subjects, thus suggesting that the LEPR Q223R polymorphism is one of the factors contributing to the high prevalence of obesity in the Pacific Island populations. PMID:20183928

  13. 2-(2,3-Dihydro-1H-indol-3-yl)ethanol

    Frydenvang, Karla Andrea; Sommer, Michael Bech; Heckmann, Dieter;

    2004-01-01

    The first direct resolution of racemic 2-(2,3-dihydro-lH-indol-3-yl)ethanol-prepared by catalytic hydrogenation of 2-(lH-indol-3-yl)ethanol-has been accomplished by chiral simulated moving bed (SMB) chromatography. The single enantiomers were isolated as their dihydrogen phosphate salts. Single......-crystal X-ray analyses were successful, revealing that the (+)-enantiomer of 2-(2,3-dihydro-lH-indol-3-yl)ethanol has the (S) configuration. Chirality 16:126-130, 2004....

  14. 30 CFR 285.223 - What does MMS do if there is a tie for the highest bid?

    2010-07-01

    ... 30 Mineral Resources 2 2010-07-01 2010-07-01 false What does MMS do if there is a tie for the highest bid? 285.223 Section 285.223 Mineral Resources MINERALS MANAGEMENT SERVICE, DEPARTMENT OF THE... is a tie for the highest bid? (a) Unless otherwise specified in the Final Sale Notice, except in...

  15. 5 CFR 531.223 - Rates of basic pay that may not be used as the highest previous rate.

    2010-01-01

    .... 7701(b)(2)(A); (g) A special rate established under 5 U.S.C. 5305 and 5 CFR part 530, subpart C, or 38... rate otherwise contrary to applicable law or regulation; (i) A rate received as a member of the... as the highest previous rate. 531.223 Section 531.223 Administrative Personnel OFFICE OF...

  16. 12 CFR 223.52 - What transactions with affiliates or others must comply with section 23B's market terms requirement?

    2010-01-01

    ... must comply with section 23B's market terms requirement? 223.52 Section 223.52 Banks and Banking... transactions with affiliates or others must comply with section 23B's market terms requirement? (a) The market..., including an asset subject to an agreement to repurchase; (3) The payment of money or the furnishing of...

  17. 77 FR 52696 - Federal Acquisition Regulation; Information Collection; Drug-Free Workplace (FAR 52.223-6)

    2012-08-30

    ... clause 52.223-6, Drug-Free Workplace, requires (1) Contractor employees to notify their employer of any... Regulation; Information Collection; Drug-Free Workplace (FAR 52.223-6) AGENCY: Department of Defense (DOD... approved information collection requirement concerning drug- free workplace. Public comments...

  18. 78 FR 5445 - Federal Acquisition Regulation; Submission for OMB Review; Drug-Free Workplace (FAR 52.223-6)

    2013-01-25

    ... FAR clause 52.223-6, Drug-Free Workplace, requires (1) contractor employees to notify their employer... Regulation; Submission for OMB Review; Drug- Free Workplace (FAR 52.223-6) AGENCY: Department of Defense (DOD... approved information collection requirement concerning drug- free workplace. A notice was published in...

  19. Determination of photon emission probabilities for the main gamma-rays of 223Ra in equilibrium with its progeny

    The currently published 223Ra gamma-ray emission probabilities display a wide variation in the values depending on the source of the data. The National Institute of Standards and Technology performed activity measurements on a 223Ra solution that was used to prepare several sources that were used to determine the photon emission probabilities for the main gamma-rays of 223Ra in equilibrium with its progeny. Several high purity germanium (HPGe) detectors were used to perform the gamma-ray spectrometry measurements. - Highlights: • Measurements of photon emission probabilities of 223Ra in equilibrium with its progeny. • Use of high purity germanium detectors for gamma-ray spectrometry measurements. • Use of the primary activity determination of 223Ra sources

  20. MicroRNA223 promotes pathogenic T-cell development and autoimmune inflammation in central nervous system in mice.

    Satoorian, Tiffany; Li, Bo; Tang, Xiaolei; Xiao, Jidong; Xing, Weirong; Shi, Weixing; Lau, Kin-Hing William; Baylink, David J; Qin, Xuezhong

    2016-08-01

    Multiple sclerosis (MS) is an incurable central nervous system autoimmune disease. Understanding MS pathogenesis is essential for the development of new MS therapies. In the present study, we identified a novel microRNA (miR) that regulates experimental autoimmune encephalomyelitis (EAE), an animal model of MS. Expression of miR223 was up-regulated specifically in spinal cords and lymphoid organs but not in other examined tissues. A global miR223 knockout (miR223(-/-) ) in mice led to a significant delay in EAE onset, reduction in spinal cord lesion, and lessening of neurological symptoms. These protective effects could be reproduced in bone marrow chimeras reconstituted with miR223(-/-) haematopoietic stem cells. We also found that miR223 deficiency reduced T helper type 1 (Th1) and Th17 infiltration into spinal cords. To address underlying mechanisms, we investigated the role of miR223 in regulating the function, development and interaction of the major immune cells. Expression of the genes associated with dendritic cell (DC) activation (CD86 and MHC II) and Th1 and Th17 differentiation [interleukin-12 (IL-12) and IL-23, respectively] was significantly decreased in the spleens of miR223(-/-) mice bearing EAE. The miR223(-/-) DCs expressed significantly lower levels of basal and lipopolysaccharide-induced IL-12 and IL-23 compared with the wild-type DCs. These data are consistent with the observed lower efficiency of miR223(-/-) DCs to support Th1 and Th17 differentiation from naive T cells over-expressing an EAE antigen-specific T-cell receptor. Our data suggest that miR223 promotes EAE, probably through enhancing DC activation and subsequently the differentiation of naive T cells toward Th1 and Th17 effector cells. PMID:27083389

  1. X-ray crystal structure of divalent metal-activated ß-xyloisdase, RS223BX

    We report the first X-ray structure of a glycoside hydrolase family 43 ß-xylosidase, RS223BX, which is strongly activated by the addition of divalent metal cations. The 2.69 Å structure reveals that the Ca2+ cation is located at the back of the active site pocket. The Ca2+ coordinates to H274 to sta...

  2. 48 CFR 52.223-12 - Refrigeration Equipment and Air Conditioners.

    2010-10-01

    ... 48 Federal Acquisition Regulations System 2 2010-10-01 2010-10-01 false Refrigeration Equipment... Provisions and Clauses 52.223-12 Refrigeration Equipment and Air Conditioners. As prescribed in 23.804(b), insert the following clause: Refrigeration Equipment and Air Conditioners (MAY 1995) The Contractor...

  3. 48 CFR 52.223-18 - Contractor Policy to Ban Text Messaging While Driving.

    2010-10-01

    ... 48 Federal Acquisition Regulations System 2 2010-10-01 2010-10-01 false Contractor Policy to Ban... Text of Provisions and Clauses 52.223-18 Contractor Policy to Ban Text Messaging While Driving. As prescribed in 23.1105, insert the following clause: CONTRACTOR POLICY TO BAN TEXT MESSAGING WHILE...

  4. Yeast Interacting Proteins Database: YBR223C, YDR510W [Yeast Interacting Proteins Database

    Full Text Available YBR223C TDP1 Tyrosyl-DNA Phosphodiesterase I, hydrolyzes 3' and 5'-phosphotyrosyl bonds, involve ... iated proteolysis, DNA replication and septin ring dynamics ; phosphorylated at Ser2 Rows with this prey as pre ... iated proteolysis, DNA replication and septin ring dynamics ; phosphorylated at Ser2 Rows with this prey as pre ...

  5. 12 CFR 223.21 - What valuation and timing principles apply to credit transactions?

    2010-01-01

    ... 12 Banks and Banking 3 2010-01-01 2010-01-01 false What valuation and timing principles apply to...) Valuation and Timing Principles Under Section 23A § 223.21 What valuation and timing principles apply to credit transactions? (a) Valuation—(1) Initial valuation. Except as provided in paragraph (a)(2) or...

  6. 12 CFR 223.22 - What valuation and timing principles apply to asset purchases?

    2010-01-01

    ... 12 Banks and Banking 3 2010-01-01 2010-01-01 false What valuation and timing principles apply to...) Valuation and Timing Principles Under Section 23A § 223.22 What valuation and timing principles apply to asset purchases? (a) Valuation—(1) In general. Except as provided in paragraph (a)(2) of this section,...

  7. 48 CFR 952.223-72 - Radiation protection and nuclear criticality.

    2010-10-01

    ... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Radiation protection and....223-72 Radiation protection and nuclear criticality. As prescribed in 923.7003 the clause set forth... (including agreements with states under section 274 of the Atomic Energy Act): Radiation Protection...

  8. Fine structures in 14C emission of 223Ra and 224Ra

    The measurement of the energy spectrum of 14C nuclei emitted in the spontaneous radioactivity from 223Ra and 224Ra has been carried out, using thin and intense sources (480 MBq for 223Ra and 3550 MBq for 224Ra). The sources were obtained by implanting mass-separated beams from ISOLDE (CERN) into Al and vitreous C catchers. The measurement was performed with the supraconducting solenoidal spectrometer SOLENO installed at Orsay. The discovery, of a fine structure in the energy spectrum of 14C emission from 223Ra, which is analogous to the one known for α emission, is confirmed. Only 13% of the branching ratio in 14C decay leads to the ground state of the residual nucleus, while 8l% to the first excited state. For 14C emission of 224Ra, a lower limit of 2 for the hindrance factor has been measured for the transition to the first excited state in the residual nucleus. Also, a precise identification in Z with a E·ΔE telescope has been performed for the radiation from the 223Ra source. (author) 22 refs., 11 figs., 1 tab

  9. Fine structure in 14C emission from 223Ra and 224Ra

    The measurement of the energy spectrum of 14C nuclei emitted in the spontaneous radioactivity of 223Ra and 224Ra has been carried out, using thin and intense sources (480 MBq for 223Ra and 3550 MBq for 224Ra). The sources were obtained by implanting mass-separated beams into Al and vitreous C catchers. The measurement was performed with a superconducting solenoidal spectrometer. Our discovery, previously reported, of fine structure in the energy spectrum of 14C emission from 223Ra, which is analogous to the one known for α emission, is confirmed. Only 13% of the branching ratio in 14C decay leads to the ground state of the residual nucleus, while 81% to the first excited state. For 14C emission from 224Ra, a lower limit of 2 for the hindrance factor has been measured for the transition to the first excited state in the residual nucleus. Also, a precise identification in Z with an ExΔE telescope has been performed for the radiation from the 223Ra source. Our measurements of fine structure in 14C emissions open this field to nuclear structure studies

  10. A single VLSI chip for computing syndromes in the (225, 223) Reed-Solomon decoder

    Hsu, I. S.; Truong, T. K.; Shao, H. M.; Deutsch, L. J.

    1986-11-01

    A description of a single VLSI chip for computing syndromes in the (255, 223) Reed-Solomon decoder is presented. The architecture that leads to this single VLSI chip design makes use of the dual basis multiplication algorithm. The same architecture can be applied to design VLSI chips to compute various kinds of number theoretic transforms.

  11. INFLUENCE OF SODIUM METABISULPHITE (E 223) ON MITOTIC DIVISION IN CALENDULA OFFICINALIS L.s

    Romeo-Cristian Marc; Gabriela Capraru

    2008-01-01

    This paper presents the cytogenetic effects induced by sodium metabisulphite (E 223) (a food additive used as preservative) in meristematic cells of Calendula officinalis L. root tips. The treatment has determined the lessening of the mitotic index (comparative with the control variant), until mitotic division total inhibition, as well as a growth frequency of division aberration in anaphase and telophase.

  12. 12 CFR 223.54 - What advertisements and statements are prohibited by section 23B?

    2010-01-01

    ... 12 Banks and Banking 3 2010-01-01 2010-01-01 false What advertisements and statements are... (REGULATION W) General Provisions of Section 23B § 223.54 What advertisements and statements are prohibited by section 23B? (a) In general. A member bank and its affiliates may not publish any advertisement or...

  13. 48 CFR 3052.223-90 - Accident and fire reporting (USCG).

    2010-10-01

    ... PROVISIONS AND CONTRACT CLAUSES Text of Provisions and Clauses 3052.223-90 Accident and fire reporting (USCG). As prescribed in USCG guidance at (HSAR) 48 CFR 3023.9000(a), insert the following clause: Accident... 48 Federal Acquisition Regulations System 7 2010-10-01 2010-10-01 false Accident and...

  14. Treatment of Metastatic Bone Disease and the Emerging Role of Radium-223.

    Coleman, Robert

    2016-03-01

    Bone metastases are common in advanced malignancy and, despite the developments in both anticancer and bone-targeted therapies in recent years, new therapeutic strategies are still needed. Traditionally, radioisotopes have been rarely used in part owing to concerns about bone marrow toxicity that limits retreatment and may prevent safe administration of subsequent chemotherapy. Radium-223 dichloride (Ra-223) is a calcium mimetic that binds preferentially to newly formed bone in areas of bone metastases, is the first alpha-emitting radionuclide to be developed for clinical use, and is approved for treatment of castration-resistant prostate cancer and symptomatic bone metastases. In this setting, it improves overall survival and delays symptomatic skeletal complications. The high linear energy transfer of the emitted alpha particles causes predominantly nonrepairable double-stranded deoxyribonucleic acid breaks in tumor cells, and the large size of the alpha particle, compared with other forms of radiation, results in a short path length and highly localized tissue destruction. As a result, Ra-223 has a highly favorable safety profile with a low level of myelosuppression. The role of Ra-223 in malignancy is discussed and the prospects for future development outlined. PMID:26897713

  15. 39 CFR 223.2 - Channels of communication, headquarters with area offices.

    2010-07-01

    ... 39 Postal Service 1 2010-07-01 2010-07-01 false Channels of communication, headquarters with area... RELATIONSHIPS AND COMMUNICATION CHANNELS § 223.2 Channels of communication, headquarters with area offices. (a) General. Headquarters organizational units formulate the directives to provide guidance to area...

  16. 36 CFR 223.193 - Procedures for reporting acquisition and disposition of unprocessed Federal timber.

    2010-07-01

    ... Regulations at 13 CFR part 121; and (ix) A certificate stating that the certifier has read and understands the... Property FOREST SERVICE, DEPARTMENT OF AGRICULTURE SALE AND DISPOSAL OF NATIONAL FOREST SYSTEM TIMBER The Forest Resources Conservation and Shortage Relief Act of 1990 Program § 223.193 Procedures for...

  17. Dosimetry of 223Ra-chloride: dose to normal organs and tissues

    223Ra-Chloride (also called Alpharadin registered) targets bone metastases with short range alpha particles. In recent years several clinical trials have been carried out showing, in particular, the safety and efficacy of palliation of painful bone metastases in patients with castration-resistant prostate cancer using 223Ra-chloride. The purpose of this work was to provide a comprehensive dosimetric calculation of organ doses after intravenous administration of 223Ra-chloride according to the present International Commission on Radiological Protection (ICRP) model for radium. Absorbed doses were calculated for 25 organs or tissues. Bone endosteum and red bone marrow show the highest dose coefficients followed by liver, colon and intestines. After a treatment schedule of six intravenous injections with 0.05 MBq/kg of 223Ra-chloride each, corresponding to 21 MBq for a 70 kg patient, the absorbed alpha dose to the bone endosteal cells is about 16 Gy and the corresponding absorbed dose to the red bone marrow is approximately 1.5 Gy. The comprehensive list of dose coefficients presented in this work will assist in comparing and evaluating organ doses from various therapy modalities used in nuclear medicine and will provide a base for further development of patient-specific dosimetry. (orig.)

  18. 12 CFR 223.33 - What rules apply to derivative transactions?

    2010-01-01

    ... Requirements Under Section 23A § 223.33 What rules apply to derivative transactions? (a) Market terms requirement. Derivative transactions between a member bank and its affiliates (other than depository... 12 Banks and Banking 3 2010-01-01 2010-01-01 false What rules apply to derivative...

  19. 27 CFR 25.223 - Destruction of beer off brewery premises.

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Destruction of beer off... TRADE BUREAU, DEPARTMENT OF THE TREASURY LIQUORS BEER Voluntary Destruction § 25.223 Destruction of beer off brewery premises. (a) Destruction without supervision. A brewer may destroy beer...

  20. 48 CFR 52.223-15 - Energy Efficiency in Energy-Consuming Products.

    2010-10-01

    ... 48 Federal Acquisition Regulations System 2 2010-10-01 2010-10-01 false Energy Efficiency in... Provisions and Clauses 52.223-15 Energy Efficiency in Energy-Consuming Products. As prescribed in 23.206, insert the following clause: Energy Efficiency in Energy-Consuming Products (DEC 2007) (a) Definition....

  1. 42 CFR 435.223 - Individuals who would be eligible for AFDC if coverage under the State's AFDC plan were as broad...

    2010-10-01

    ... 42 Public Health 4 2010-10-01 2010-10-01 false Individuals who would be eligible for AFDC if coverage under the State's AFDC plan were as broad as allowed under title IV-A. 435.223 Section 435.223... and Children § 435.223 Individuals who would be eligible for AFDC if coverage under the State's...

  2. Radiation exposure of relatives of patients treated with Ra-223 dichloride

    Since November 2013, a radiopharmaceutical containing Ra-223 dichloride as active substance is approved in the European Union for patients with castration resistant prostate cancer with symptomatic bone metastases and no known visceral metastases. Ra-223 (T1/2 = 11.43 d) decays via a chain of 4 alpha and 2 beta decays. This therapy is presently the only application of an alpha emitter in clinical routine therapy. To show that the exposure of relatives and caregivers of patients treated with Ra-223 dichloride in an outpatient setting does not exceed a value of 1 mSv, the multicenter study ''RAPSODY'' was conducted. As Ra-223 and most of its progeny emit alpha particles, the internal exposure had to be evaluated in particular. Within this study, measurements of the radiation emitted from the patient were performed using standard dose-rate meters. Wipe-tests were taken in the patients' homes to identify significant contaminations and evaluated by liquid scintillation counting. Samples of saliva and sweat were taken and measured using gamma spectrometry. Ra-223 disintegrates to the noble gas Rn-219 and was measured in the exhaled breath from the patients using conventional Radon Monitors. Furthermore, a computational fluid dynamics simulation (CFD) was performed to assess the radioactivity in the air, which could be inhaled by persons close to the patient. Conclusions: The potential exposure of relatives and caregivers by external irradiation and incorporation of radioactivity exhaled or excreted by the patient with saliva or sweat is well below 1 mSv. No objections are seen regarding outpatient treatment. This paper summarizes contents of a poster presented at the Annual Meeting of the Society of Nuclear Medicine and Molecular Imaging.

  3. MicroRNA-223 Regulates the Differentiation and Function of Intestinal Dendritic Cells and Macrophages by Targeting C/EBPβ

    Haibo Zhou

    2015-11-01

    Full Text Available Dendritic cells (DCs and macrophages play important roles in maintaining intestinal homeostasis. However, the molecular mechanisms that regulate the differentiation and responses of intestinal DCs and macrophages remain poorly understood. Here, we have identified microRNA miR-223 as a key molecule for regulating these processes. Deficiency of miR-223 led to a significantly decreased number of intestinal CX3CR1hi macrophages at steady state. Both intestinal CX3CR1hi macrophages and CD103+ conventional DCs (cDCs in miR-223-deficient mice exhibited a strong pro-inflammatory phenotype. Moreover, miR-223-deficient monocytes gave rise to more monocyte-derived DCs (moDCs and produced more pro-inflammatory cytokines upon stimulation. Using a mouse model of colitis, we demonstrated that the miR-223 deficiency resulted in more severe colitis. Target gene analysis further identified that the effects of miR-223 on DCs and macrophages were mediated by directly targeting C/EBPβ. Taken together, our study identifies a role for miR-223 as a critical regulator of intestinal homeostasis.

  4. Estimation of dose rate of a package ({sup 223+}Ra) and evaluation of transport index; Dosisleistungsabschaetzung bei einem Versandstueck ({sup 223+}Ra) und Ermittlung der Transportkennzahl nach ADR

    Bittner, Michael [TUEV SUED Industrie Services GmbH, Region Nordost, Leipzig (Germany). Anlagensicherheit/Strahlenschutz; Richter, Jens [TUEV SUED Industrie Services GmbH, Region Nordost, Dresden (Germany). Anlagensicherheit/Strahlenschutz

    2016-08-01

    The transport index of a package is to be determined according to provisions of the ADR. It is directly related to the maximum radiation level in mSv/h at a distance of 1 m from the external surface of the package or pallet. To evaluate the existing distribution of the dose equivalent outside the package or pallet calculations of photon dose rates are required. For Monte-Carlo simulations with MCNP5 a three-dimensional model of a package containing Xofigo trademark was created, which contains all relevant sources from {sup 223}Ra and its decay chain.

  5. Therapy palliative with {sup 2}23Ra without special radiation protection measures?; Palliative Therapie mit {sup 223}Ra ohne besondere Strahlenschutzmassnahmen?

    Just, Guenther [Forschungsbuero Radonbalneologie (FRB), Grosspoesna (Germany); Petzold, Juergen

    2015-07-01

    For nearly 2 years now as a therapy of the castration resistant prostata carcinoma a nuclide therapy with {sup 223}Ra-Dichloride (trade-mark Xofigo) is applied. Xofigo is applied by a medical specialist for nuclear medicine altogether 6 times in a monthly distance. The activity used in each case is according to the body weight (50 kBq/kg BW). This therapy is licensed by the supervisory authorities of the German federal countries as an ambulant therapy. Special radiation protection measures are only required when exceeding a given number of 17 patients per year as incorparation measurements.

  6. Factors affecting {sup 223}Ra therapy: clinical experience after 532 cycles from a single institution

    Etchebehere, Elba C. [The University of Texas MD Anderson Cancer Center, Department of Nuclear Medicine, Houston, TX (United States); Campinas State University (Unicamp), Department of Nuclear Medicine, Campinas (Brazil); Milton, Denai R. [The University of Texas MD Anderson Cancer Center, Department of Biostatistics, Houston, TX (United States); Araujo, John C. [The University of Texas MD Anderson Cancer Center, Department of Genitourinary Medical Oncology, Houston, TX (United States); Swanston, Nancy M.; Macapinlac, Homer A.; Rohren, Eric M. [The University of Texas MD Anderson Cancer Center, Department of Nuclear Medicine, Houston, TX (United States)

    2016-01-15

    The aim of this study was to identify baseline features that predict outcome in {sup 223}Ra therapy. We retrospectively reviewed 110 patients with metastatic castration-resistant prostate cancer treated with {sup 223}Ra. End points were overall survival (OS), progression-free survival (PFS), bone event-free survival (BeFS), and bone marrow failure (BMF). The following parameters were evaluated prior to the first {sup 223}Ra cycle: serum levels of hemoglobin (Hb), prostate-specific antigen (PSA), alkaline phosphatase (ALP), Eastern Cooperative Oncology Group (ECOG) status, pain score, use of chemotherapy, and external beam radiation therapy (EBRT). During/after {sup 223}Ra we evaluated: the total number of radium cycles (Ra{sub Tot}), the PSA doubling time (PSA{sub DT}), and the use of chemotherapy, EBRT, abiraterone, and enzalutamide. A significant reduction of ALP (p < 0.001) and pain score (p = 0.041) occurred throughout the {sup 223} Ra cycles. The risk of progression was associated with declining ECOG status [hazard ratio (HR) = 3.79; p < 0.001] and decrease in PSA{sub DT} (HR = 8.22; p < 0.001). Ra{sub Tot}, ALP, initial ECOG status, initial pain score, and use of abiraterone were associated with OS (p ≤ 0.008), PFS (p ≤ 0.003), and BeFS (p ≤ 0.020). Ra{sub Tot}, ALP, initial ECOG status, and initial pain score were significantly associated with BMF (p ≤ 0.001) as well as Hb (p < 0.001) and EBRT (p = 0.009). On multivariable analysis, only Ra{sub Tot} and abiraterone remained significantly associated with OS (p < 0.001; p = 0.033, respectively), PFS (p < 0.001; p = 0.041, respectively), and BeFS (p < 0.001; p = 0.019, respectively). Additionally, Ra{sub Tot} (p = 0.027) and EBRT (p = 0.013) remained significantly associated with BMF. Concomitant use of abiraterone and {sup 223}Ra seems to have a beneficial effect, while the EBRT may increase the risk of BMF. (orig.)

  7. Factors affecting 223Ra therapy: clinical experience after 532 cycles from a single institution

    The aim of this study was to identify baseline features that predict outcome in 223Ra therapy. We retrospectively reviewed 110 patients with metastatic castration-resistant prostate cancer treated with 223Ra. End points were overall survival (OS), progression-free survival (PFS), bone event-free survival (BeFS), and bone marrow failure (BMF). The following parameters were evaluated prior to the first 223Ra cycle: serum levels of hemoglobin (Hb), prostate-specific antigen (PSA), alkaline phosphatase (ALP), Eastern Cooperative Oncology Group (ECOG) status, pain score, use of chemotherapy, and external beam radiation therapy (EBRT). During/after 223Ra we evaluated: the total number of radium cycles (RaTot), the PSA doubling time (PSADT), and the use of chemotherapy, EBRT, abiraterone, and enzalutamide. A significant reduction of ALP (p < 0.001) and pain score (p = 0.041) occurred throughout the 223 Ra cycles. The risk of progression was associated with declining ECOG status [hazard ratio (HR) = 3.79; p < 0.001] and decrease in PSADT (HR = 8.22; p < 0.001). RaTot, ALP, initial ECOG status, initial pain score, and use of abiraterone were associated with OS (p ≤ 0.008), PFS (p ≤ 0.003), and BeFS (p ≤ 0.020). RaTot, ALP, initial ECOG status, and initial pain score were significantly associated with BMF (p ≤ 0.001) as well as Hb (p < 0.001) and EBRT (p = 0.009). On multivariable analysis, only RaTot and abiraterone remained significantly associated with OS (p < 0.001; p = 0.033, respectively), PFS (p < 0.001; p = 0.041, respectively), and BeFS (p < 0.001; p = 0.019, respectively). Additionally, RaTot (p = 0.027) and EBRT (p = 0.013) remained significantly associated with BMF. Concomitant use of abiraterone and 223Ra seems to have a beneficial effect, while the EBRT may increase the risk of BMF. (orig.)

  8. Precise Study of Fine Structure in $^{14}$C Emission from $^{223}$Ra

    2002-01-01

    We request 10 shifts in two sessions of beam time at ISOLDE for the production of a $^{223}$Ra source. This source will be used with the superconducting spectrometer SOLENO at Orsay for a precise measurement (good statistics and energy resolution) of the fine stucture in the energy spectrum of $^{14}$C nuclei emitted by $^{223}$Ra, discovered at Orsay in July 1989. The measurement will be devoted to carry out the hindrance factors of the transitions to 15$\\!^-\\!$/2$\\,$ (1.423 MeV) and 5$\\!^+\\!$/2$\\,$ (1.567 MeV) excited states of $^{209}$Pb, which present a particular interest for obtaining spectroscopic information and testing nuclear models.

  9. Kinetics of leptin binding to the Q223R leptin receptor.

    Hans Verkerke

    Full Text Available Studies in human populations and mouse models of disease have linked the common leptin receptor Q223R mutation to obesity, multiple forms of cancer, adverse drug reactions, and susceptibility to enteric and respiratory infections. Contradictory results cast doubt on the phenotypic consequences of this variant. We set out to determine whether the Q223R substitution affects leptin binding kinetics using surface plasmon resonance (SPR, a technique that allows sensitive real-time monitoring of protein-protein interactions. We measured the binding and dissociation rate constants for leptin to the extracellular domain of WT and Q223R murine leptin receptors expressed as Fc-fusion proteins and found that the mutant receptor does not significantly differ in kinetics of leptin binding from the WT leptin receptor. (WT: ka 1.76×106±0.193×106 M-1 s-1, kd 1.21×10-4±0.707×10-4 s-1, KD 6.47×10-11±3.30×10-11 M; Q223R: ka 1.75×106±0.0245×106 M-1 s-1, kd 1.47×10-4±0.0505×10-4 s-1, KD 8.43×10-11±0.407×10-11 M. Our results support earlier findings that differences in affinity and kinetics of leptin binding are unlikely to explain mechanistically the phenotypes that have been linked to this common genetic variant. Future studies will seek to elucidate the mechanism by which this mutation influences susceptibility to metabolic, infectious, and malignant pathologies.

  10. XTE J1752-223: Optical spectroscopy and infrared counterpart detection

    Torres, M. A. P.; Steeghs, D.; Jonker, P. G.; Thompson, I.; Soderberg, A. M.

    2009-10-01

    Prompted by the discovery of its bright optical counterpart and the announcement of increased X-ray activity (ATels #2258, #2259, #2261, #2265, #2263), we have acquired additional observations of XTE J1752-223 at optical and near-infrared wavelengths. OPTICAL SPECTROSCOPY: An optical spectrum covering 3330-9165 Angstrom was obtained with the MIKE echelle spectrograph on the Magellan Clay telescope starting on 2009 Oct 26 UT 23:52.

  11. Swift observations of black hole candidate XTE J1752-223 during outburst

    Curran, P. A.; Casella, P.; Maccarone, T.J.; Evans, P. A.; Landsman, W.; Krimm, H. A.; Brocksopp, C.; Still, M.

    2011-01-01

    Here we summarise the Swift broadband observations of the recently discovered X-ray transient and black hole candidate, XTE J1752-223,obtained over the period of outburst from October 2009 to June 2010. We offer a phenomenological treatment of the spectra as an indication of the canonical spectral state of the source during different periods of the outburst. We find that the high energy hardness-intensity diagrams over two separate bands follows the canonical behavior, confirming the spectral...

  12. Potential role of miR-9 and miR-223 in recurrent ovarian cancer

    McGuinness Eamonn

    2008-04-01

    Full Text Available Abstract Background MicroRNAs (miRNAs are small, noncoding RNAs that negatively regulate gene expression by binding to target mRNAs. miRNAs have not been comprehensively studied in recurrent ovarian cancer, yet an incurable disease. Results Using real-time RT-PCR, we obtained distinct miRNA expression profiles between primary and recurrent serous papillary ovarian adenocarcinomas (n = 6 in a subset of samples previously used in a transcriptome approach. Expression levels of top dysregulated miRNA genes, miR-223 and miR-9, were examined using TaqMan PCR in independent cohorts of fresh frozen (n = 18 and FFPE serous ovarian tumours (n = 22. Concordance was observed on TaqMan analysis for miR-223 and miR-9 between the training cohort and the independent test cohorts. Target prediction analysis for the above miRNA "recurrent metastatic signature" identified genes previously validated in our transcriptome study. Common biological pathways well characterised in ovarian cancer were shared by miR-9 and miR-223 lists of predicted target genes. We provide strong evidence that miR-9 acts as a putative tumour suppressor gene in recurrent ovarian cancer. Components of the miRNA processing machinery, such as Dicer and Drosha are not responsible for miRNA deregulation in recurrent ovarian cancer, as deluded by TaqMan and immunohistochemistry. Conclusion We propose a miRNA model for the molecular pathogenesis of recurrent ovarian cancer. Some of the differentially deregulated miRNAs identified correlate with our previous transcriptome findings. Based on integrated transcriptome and miRNA analysis, miR-9 and miR-223 can be of potential importance as biomarkers in recurrent ovarian cancer.

  13. Kepler-223: A Resonant Chain of Four Transiting, Sub-Neptune Planets

    Mills, Sean; Fabrycky, Daniel C.; Migaszewski, Cezary; Ford, Eric B.; Petigura, Erik; Isaacson, Howard T.

    2016-05-01

    Surveys have revealed an abundance of multi-planet systems containing super-Earths and Neptunes in few-day to few-month orbits. Orbital periods of pairs of planets in the same system occasionally lie near, but generally not exactly on, ratios of small integers (resonances), allowing for the detection of the planets perturbing each other. There is debate whether in situ assembly or significant inward migration is the dominant mechanism of their formation. Simulations suggest migration creates tightly-packed, resonant systems, often in chains of resonance. Of the hundreds of multi-planet systems of sub-Neptunes, there is weak statistical enhancement near resonances, but no individual system has been identified that requires migration. Here we describe dynamical modeling of the system Kepler-223, which has a series of resonances among its four planets. We observe transit timing variations (TTVs), model them as resonant angle librations, and compute long-term stability, combining these analyses to constrain dynamical parameters and planetary masses. The detailed architecture of Kepler-223 is too finely tuned for formation by scattering, whereas numerical simulations demonstrate its properties are natural outcomes of the migration hypothesis. Similar systems could be destabilized by many mechanisms contributing to the observed period distribution. Planetesimal interactions in particular are thought to be responsible for establishing thecurrent orbits of the four giant planets in our own Solar System by disrupting a theoretical initial resonant chain like that actually observed in Kepler-223.

  14. MicroRNA-223 and miR-143 are important systemic biomarkers for disease activity in psoriasis

    Løvendorf, Marianne B; Zibert, John R; Gyldenløve, Mette; Røpke, Mads A; Skov, Lone

    2014-01-01

    including miR-223 and miR-143 which were found to be significantly upregulated in the PBMCs from patients with psoriasis compared with healthy controls (FCH=1.63, P<0.01; FCH=2.18, P<0.01, respectively). In addition, miR-223 and miR-143 significantly correlated with the PASIscore (r=0.46, P<0.05; r=0.55, P......<0.02, respectively). Receiver-operating characteristic analysis (ROC) showed that miR-223 and -143 have the potential to distinguish between psoriasis and healthy controls (miR-223: area under the curve (AUC)=0.80, miR-143: AUC=0.75). Interestingly, after 3-5 weeks of treatment with methotrexate...... following a significant decrease in psoriasis severity, miR-223 and miR-143 were significantly downregulated in the PBMCs from patients with psoriasis. CONCLUSION: We suggest that changes in the miR-223 and miR-143 expressions in PBMCs from patients with psoriasis may serve as novel biomarkers for disease...

  15. MicroRNA-223 Attenuates Hypoxia-induced Vascular Remodeling by Targeting RhoB/MLC2 in Pulmonary Arterial Smooth Muscle Cells

    Zeng, Yan; Zhang, Xiaoying; Kang, Kang; Chen, Jidong; Wu, Zhiqin; Huang, Jinyong; Lu, Wenju; Chen, Yuqin; Zhang, Jie; Wang, Zhiwei; Zhai, Yujia; Qu, Junle; Ramchandran, Ramaswamy; Raj, J. Usha; Wang, Jian; Gou, Deming

    2016-01-01

    There is growing evidence that microRNAs are implicated in pulmonary arterial hypertension (PAH), but underlying mechanisms remain elusive. Here, we identified that miR-223 was significantly downregulated in chronically hypoxic mouse and rat lungs, as well as in pulmonary artery and pulmonary artery smooth muscle cells (PASMC) exposed to hypoxia. Knockdown of miR-223 increased PASMC proliferation. In contrast, miR-223 overexpression abrogated cell proliferation, migration and stress fiber formation. Administering miR-223 agomir in vivo antagonized hypoxia-induced increase in pulmonary artery pressure and distal arteriole muscularization. RhoB, which was increased by hypoxia, was identified as one of the targets of miR-223. Overexpressed miR-223 suppressed RhoB and inhibited the consequent phosphorylation of myosin phosphatase target subunit (MYPT1) and the expression of myosin light chain of myosin II (MLC2), which was identified as another target of miR-223. Furthermore, serum miR-223 levels were decreased in female patients with PAH associated with congenital heart disease. Our study provides the first evidence that miR-223 can regulate PASMC proliferation, migration, and actomyosin reorganization through its novel targets, RhoB and MLC2, resulting in vascular remodeling and the development of PAH. It also highlights miR-223 as a potential circulating biomarker and a small molecule drug for diagnosis and treatment of PAH. PMID:27121304

  16. MicroRNA-223 Induced Repolarization of Peritoneal Macrophages Using CD44 Targeting Hyaluronic Acid Nanoparticles for Anti-Inflammatory Effects

    Tran, Thanh-Huyen; Krishnan, Swathi; Amiji, Mansoor M.

    2016-01-01

    The aim of this study was to evaluate macrophages repolarization from pro-inflammatory M1 to anti-inflammatory M2 phenotype upon transfection with microRNA-223 (miR-223) duplexes and miR-223 expressing plasmid DNA encapsulated in CD44-targeting hyaluronic acid-poly(ethyleneimine) (HA-PEI) nanoparticles (NPs). The HA-PEI/miR-223 NPs with spherical shape and an average diameter of 200 nm were efficiently internalized by J774A.1 alveolar and primary peritoneal macrophages and non-cytotoxic at HA-PEI concentration less than 200 μg/mL. Transfection of HA-PEI/miR-223 NPs in J774A.1 macrophages showed significantly higher miR-223 expression than that with HA-PEI/plasmid DNA expressing miR-223 (pDNA-miR-223). HA-PEI/miR-223 NPs mediated transfection increased miR-223 expression to 90 fold in primary peritoneal macrophages compared to untreated cells. The overexpression of miR-223 in both J774A.1 and peritoneal macrophages induced a phenotypic change from M1 to M2 state as indicated by a decrease in iNOS-2 (M1 marker) and an increase in Arg-1 (M2 marker) levels compared to those in lipopolysaccharide (LPS) and interferon-gamma (IFN-γ)-stimulated macrophages (M1). The change in macrophage phenotype by HA-PEI/miR-223 NPs could suppress the inflammation in peritoneal macrophages induced by LPS as evidenced by a significant decrease in pro-inflammatory cytokine levels TNF-α, IL-1β and IL-6, compared to LPS-stimulated peritoneal macrophages without treatment. The results demonstrated that miR-223-encapsulated HA-PEI NPs modulated macrophage polarity toward an anti-inflammatory M2 phenotype, which has potential for the treatment of inflammatory diseases. PMID:27148749

  17. Dosimetry of bone metastases in targeted radionuclide therapy with alpha-emitting 223Ra-dichloride

    Ra-dichloride is an alpha-emitting radiopharmaceutical used in the treatment of bone metastases from castration-resistant prostate cancer. Image-based dosimetric studies remain challenging because the emitted photons are few. The aim of this study was to implement a methodology for in-vivo quantitative planar imaging, and to assess the absorbed dose to lesions using the MIRD approach. The study included nine Caucasian patients with 24 lesions (6 humeral head lesions, 4 iliac wing lesions, 2 scapular lesions, 5 trochanter lesions, 3 vertebral lesions, 3 glenoid lesions, 1 coxofemoral lesion). The treatment consisted of six injections (one every 4 weeks) of 50 kBq per kg body weight. Gamma-camera calibrations for 223Ra included measurements of sensitivity and transmission curves. Patients were statically imaged for 30 min, using an MEGP collimator, double-peak acquisition, and filtering to improve the image quality. Lesions were delineated on 99mTc-MDP whole-body images, and the ROIs superimposed on the 223Ra images after image coregistration. The activity was quantified with background, attenuation, and scatter correction. Absorbed doses were assessed deriving the S values from the S factors for soft-tissue spheres of OLINDA/EXM, evaluating the lesion volumes by delineation on the CT images. In 12 lesions with a wash-in phase the biokinetics were assumed to be biexponential, and to be monoexponential in the remainder. The optimal timing for serial acquisitions was between 1 and 5 h, between 18 and 24 h, between 48 and 60 h, and between 7 and 15 days. The error in cumulated activity neglecting the wash-in phase was between 2 % and 12 %. The mean effective half-life (T1/2eff) of 223Ra was 8.2 days (range 5.5-11.4 days). The absorbed dose (D) after the first injection was 0.7 Gy (range 0.2-1.9 Gy). Considering the relative biological effectiveness (RBE) of alpha particles (RBE = 5), DRBE = 899 mGy/MBq (range 340-2,450 mGy/MBq). The percent uptake of 99mTc and 223Ra

  18. Effects of miR-223 on expression of IL-1β and IL-6 in human gingival fibroblasts.

    Matsui, Sari; Ogata, Yorimasa

    2016-01-01

    MicroRNAs (miRNAs) are small non-coding RNAs that regulate post-transcriptional expression by translational inhibition or mRNA degradation. miRNAs bind to target mRNAs through partial complementarity, and can regulate many genes. In the present study, we investigated the effects of miR-223 on the expression of inflammatory cytokines in human gingival fibroblasts (HGF). To determine the effects of miR-223 on the expressions of interleukin-1β (IL-1β) and IL-6, HGF were stimulated by IL-1β (1 ng/mL) or tumor necrosis factor-α (TNF-α; 10 ng/mL) and transfected with a miR-223 expression plasmid. Levels of mRNA for IL-1β, IL-6, inhibitor of kappa-B kinase α (IKKα) and mitogen-activated protein kinase phosphatase-5 (MKP-5) were measured by real-time PCR, and levels IL-1β, IL-6 and IKKα protein were determined by enzyme-linked immunosorbent assay and Western blotting. Expression of IL-1β and IL-6 mRNAs was induced by IL-1β and TNF-α and further increased by miR-223 overexpression. IL-1β and TNF-α induced the expression of IL-1β and IL-6 mRNAs, and this was reduced by miR-223 inhibitor. Overexpression of miR-223 decreased the levels of IKKα protein and MKP-5 mRNA in HGF. These findings indicate that miR-223 might control the inflammatory response via IKKα and MKP-5 in periodontal tissue. (J Oral Sci 58, 101-108, 2016). PMID:27021546

  19. MicroRNA-223 Enhances Radiation Sensitivity of U87MG Cells In Vitro and In Vivo by Targeting Ataxia Telangiectasia Mutated

    Liang, Liping; Zhu, Ji [Departments of Radiation Oncology, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai (China); Zaorsky, Nicholas G. [Department of Radiation Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania (United States); Deng, Yun [Departments of Radiation Oncology, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai (China); Wu, Xingzhong [Department of Biochemistry and Molecular Biology, Shanghai Medical College, Fudan University, Shanghai (China); Liu, Yong [Departments of Radiation Oncology, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai (China); Liu, Fangqi; Cai, Guoxiang; Gu, Weilie [Department of Colorectal Cancer, Fudan University, Shanghai Cancer Center, Shanghai (China); Shen, Lijun [Departments of Radiation Oncology, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai (China); Zhang, Zhen, E-mail: zhenzhang6@hotmail.com [Departments of Radiation Oncology, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai (China)

    2014-03-15

    Purpose: Ataxia telangiectasia mutated (ATM) protein is important in the DNA damage response because it repairs radiation-induced damage in cancers. We examined the effect of microRNA-223 (miR-223), a regulator of ATM expression, on radiation sensitivity of cancer cells. Methods and Materials: Human embryonic kidney 293 T (293T) cells were infected with pLL3.7-miR-223 plasmid to generate the pLL3.7-miR-223 and -empty virus (EV) lentivirus (miR-223 and EV). A dual luciferase assay in which the reporter contained wild-type 3′ untranslated region (UTR) of ATM was performed. U87MG cells were infected with miR-223 or EV to establish the overexpressed stable cell lines (U87-223 or U87-EV, respectively). Cells were irradiated in vitro, and dose enhancement ratios at 2 Gy (DER{sub 2}) were calculated. Hind legs of BALB/c athymic mice were injected with U87-223 or U87-EV cells; after 2 weeks, half of the tumors were irradiated. Tumor volumes were tracked for a total of 5 weeks. Results: The dual luciferase reporter assay showed a significant reduction in luciferase activity of 293T cells cotransfected with miR-223 and the ATM 3′UTR compared to that in EV control. Overexpression of miR-223 in U87MG cells showed that ATM expression was significantly downregulated in the U87-223 cells compared to that in U87-EV (ATM/β-actin mRNA 1.0 vs 1.5, P<.05). U87-223 cells were hypersensitive to radiation compared to U87-EV cells in vitro (DER{sub 2} = 1.32, P<.01). Mice injected with miR-223-expressing tumors had almost the same tumors after 3 weeks (1.5 cm{sup 3} vs 1.7 cm{sup 3}). However, irradiation significantly decreased tumor size in miR-223-expressing tumors compared to those in controls (0.033 cm{sup 3} vs 0.829 cm{sup 3}). Conclusions: miR-223 overexpression downregulates ATM expression and sensitizes U87 cells to radiation in vitro and in vivo. MicroRNA-223 may be a novel cancer-targeting therapy, although its cancer- and patient-specific roles are

  20. MicroRNA-223 Enhances Radiation Sensitivity of U87MG Cells In Vitro and In Vivo by Targeting Ataxia Telangiectasia Mutated

    Purpose: Ataxia telangiectasia mutated (ATM) protein is important in the DNA damage response because it repairs radiation-induced damage in cancers. We examined the effect of microRNA-223 (miR-223), a regulator of ATM expression, on radiation sensitivity of cancer cells. Methods and Materials: Human embryonic kidney 293 T (293T) cells were infected with pLL3.7-miR-223 plasmid to generate the pLL3.7-miR-223 and -empty virus (EV) lentivirus (miR-223 and EV). A dual luciferase assay in which the reporter contained wild-type 3′ untranslated region (UTR) of ATM was performed. U87MG cells were infected with miR-223 or EV to establish the overexpressed stable cell lines (U87-223 or U87-EV, respectively). Cells were irradiated in vitro, and dose enhancement ratios at 2 Gy (DER2) were calculated. Hind legs of BALB/c athymic mice were injected with U87-223 or U87-EV cells; after 2 weeks, half of the tumors were irradiated. Tumor volumes were tracked for a total of 5 weeks. Results: The dual luciferase reporter assay showed a significant reduction in luciferase activity of 293T cells cotransfected with miR-223 and the ATM 3′UTR compared to that in EV control. Overexpression of miR-223 in U87MG cells showed that ATM expression was significantly downregulated in the U87-223 cells compared to that in U87-EV (ATM/β-actin mRNA 1.0 vs 1.5, P<.05). U87-223 cells were hypersensitive to radiation compared to U87-EV cells in vitro (DER2 = 1.32, P<.01). Mice injected with miR-223-expressing tumors had almost the same tumors after 3 weeks (1.5 cm3 vs 1.7 cm3). However, irradiation significantly decreased tumor size in miR-223-expressing tumors compared to those in controls (0.033 cm3 vs 0.829 cm3). Conclusions: miR-223 overexpression downregulates ATM expression and sensitizes U87 cells to radiation in vitro and in vivo. MicroRNA-223 may be a novel cancer-targeting therapy, although its cancer- and patient-specific roles are currently undefined

  1. Superconductivity in 2-2-3 system Y2Ba2Cu2O(8+delta)

    Joshi, H. H.; Baldha, G. J.; Jotania, R. B.; Joshi, S. M.; Mohan, H.; Pandya, P. B.; Pandya, H. N.; Kulkarni, R. G.

    1991-01-01

    Researchers synthesized a new high T(sub c) 2-2-3 superconductor Y2Ba2Cu3O(8+delta) by a special preparation technique and characterized it by ac-susceptibility measurements. Diamagnetism and Meissner effect sets in at low fields and superconducting transition onsets at 90 K. The systematic investigation of the real and imaginary components of ac-susceptibility as a function of temperature and applied ac magnetic field reveals that the magnetic behavior is that of a granular type superconductor.

  2. A software simulation study of a (255,223) Reed-Solomon encoder-decoder

    Pollara, F.

    1985-04-01

    A set of software programs which simulates a (255,223) Reed-Solomon encoder/decoder pair is described. The transform decoder algorithm uses a modified Euclid algorithm, and closely follows the pipeline architecture proposed for the hardware decoder. Uncorrectable error patterns are detected by a simple test, and the inverse transform is computed by a finite field FFT. Numerical examples of the decoder operation are given for some test codewords, with and without errors. The use of the software package is briefly described.

  3. Cutting Edge: MicroRNA-223 Regulates Myeloid Dendritic Cell-Driven Th17 Responses in Experimental Autoimmune Encephalomyelitis.

    Ifergan, Igal; Chen, Siqi; Zhang, Bin; Miller, Stephen D

    2016-02-15

    Myeloid cells play a crucial role in the induction and sustained inflammation in neuroinflammatory disorders, such as multiple sclerosis. miR-223, a myeloid cell-specific microRNA, is one of the most upregulated microRNAs in multiple sclerosis patients. We demonstrate that miR-223-knockout mice display significantly reduced active and adoptive-transfer experimental autoimmune encephalomyelitis that is characterized by reduced numbers of myeloid dendritic cells (mDCs) and Th17 cells in the CNS. Knockout mDCs have increased PD-L1 and decreased IL-1β, IL-6, and IL-23 expression, as well as a reduced capacity to drive Th17, but not Th1, cell differentiation. Thus, miR-223 controls mDC-induced activation of pathologic Th17 responses during autoimmune inflammation. PMID:26783338

  4. STRUCTURAL CONSEQUENCES OF THE POLYMORPHISM Q223R IN THE HUMAN LEPTIN RECEPTOR: A MOLECULAR DYNAMICS STUDY

    Jonathan P. Carrillo-Vázquez

    2013-01-01

    Full Text Available Leptin Receptor (LEPR is a component of a signaling pathway related to appetite and energy expenditure. Single Nucleotide Polymorphisms (SNP of Leptin receptor gene (lepr have been proposed as possible modulator of adipose tissue and body weight. The main phenomenological consequence reported of these SNPs is the modulation of the LEP-LEPR interaction promoting the weight gain. Particularly, Q223R polymorphism has been associated with human obesity in some populations. In this work, we analyze the structural effects of Q223R substitution in a model of the extracellular region of LEPR comparing the stability between LEPR-Q and its Q223R variant (rs1137101 by Molecular Dynamics (MD simulations. These results showed different behavior between both molecules after one nanosecond (ns of simulation and significant differences in the secondary structure content were evidenced.

  5. The design plan of a VLSI single chip (255, 223) Reed-Solomon decoder

    Hsu, I. S.; Shao, H. M.; Deutsch, L. J.

    1987-11-01

    The very large-scale integration (VLSI) architecture of a single chip (255, 223) Reed-Solomon decoder for decoding both errors and erasures is described. A decoding failure detection capability is also included in this system so that the decoder will recognize a failure to decode instead of introducing additional errors. This could happen whenever the received word contains too many errors and erasures for the code to correct. The number of transistors needed to implement this decoder is estimated at about 75,000 if the delay for received message is not included. This is in contrast to the older transform decoding algorithm which needs about 100,000 transistors. However, the transform decoder is simpler in architecture than the time decoder. It is therefore possible to implement a single chip (255, 223) Reed-Solomon decoder with today's VLSI technology. An implementation strategy for the decoder system is presented. This represents the first step in a plan to take advantage of advanced coding techniques to realize a 2.0 dB coding gain for future space missions.

  6. Stochastic simulation of radium-223 dichloride therapy at the sub-cellular level.

    Gholami, Y; Zhu, X; Fulton, R; Meikle, S; El-Fakhri, G; Kuncic, Z

    2015-08-01

    Radium-223 dichloride ((223)Ra) is an alpha particle emitter and a natural bone-seeking radionuclide that is currently used for treating osteoblastic bone metastases associated with prostate cancer. The stochastic nature of alpha emission, hits and energy deposition poses some challenges for estimating radiation damage. In this paper we investigate the distribution of hits to cells by multiple alpha particles corresponding to a typical clinically delivered dose using a Monte Carlo model to simulate the stochastic effects. The number of hits and dose deposition were recorded in the cytoplasm and nucleus of each cell. Alpha particle tracks were also visualized. We found that the stochastic variation in dose deposited in cell nuclei ([Formula: see text]40%) can be attributed in part to the variation in LET with pathlength. We also found that [Formula: see text]18% of cell nuclei receive less than one sigma below the average dose per cell ([Formula: see text]15.4 Gy). One possible implication of this is that the efficacy of cell kill in alpha particle therapy need not rely solely on ionization clustering on DNA but possibly also on indirect DNA damage through the production of free radicals and ensuing intracellular signaling. PMID:26216391

  7. Phosphazene like film formation on InP in liquid ammonia (223 K)

    An anodic photo-galvanostatic treatment at low current density (1 μA·cm−2) is carried out on n-InP semiconductor in liquid ammonia (223 K). The gradual chemical evolution of the surface is studied as a function of the anodic charge. Proof and reproducibility of the chemical transformation of the surface are clearly evidenced by X-ray photoelectron spectroscopy (XPS) analyses. Like by cyclic voltammetry, the perfect coverage of the InP surface by a thin phosphazene like film is also revealed by XPS data. However, a low anodic charge (≈ 0.5 mC·cm−2) is required by photo-galvanostatic treatment while a higher anodic charge (≈ 7 mC·cm−2) is involved by cyclic voltammetry. The excess of charge could be related to ammonia oxidation during the formation of the passivating film. This result proves the electrochemical oxidation of the solvent as a determinant step of the mechanism film formation. - Highlights: ► Cyclic voltammetry and galvanostatic modes on n-InP in liquid ammonia (223 K). ► A thin film growth is reached by photo-anodic polarization. ► The same phosphazene like film is evidenced by X-ray photoelectron spectroscopy. ► An excess of charge is observed by cyclic voltammetry. ► An electrochemical oxidation step of the solvent is assumed

  8. Integral Field Spectroscopy Of The Brightest Knots Of Hh 223 In L723

    López, R; Estalella, R; Riera, A; Carrasco-González, C; Gómez, G

    2012-01-01

    HH 223 is the optical counterpart of a larger scale H2 outflow, driven by the protostellar source VLA 2A, in L723. Its poorly collimated and rather chaotic morphology suggested the Integral Field Spectroscopy (IFS) as an appropriate option to map the emission for deriving the physical conditions and the kinematics. Here we present new results based on the IFS observations made with the INTEGRAL system at the WHT. The brightest knots of HH 223 (\\sim16 arcsec, 0.02 pc at a distance of 300 pc) were mapped with a single pointing in the spectral range 6200-7700 A. We obtained the emission-line intensity maps for Halpha, [NII] 6584 A and [SII] 6716, 6731 A, and explored the distribution of the excitation and electron density from [NII]/Halpha, [SII]/Halpha, and [SII] 6716/6731 line-ratio maps. Maps of the radial velocity field were obtained. We analysed the 3D-kinematics by combining the knot radial velocities, derived from IFS data, with the knot proper motions derived from multi-epoch, narrow-band images. The int...

  9. Precise measurements of the absolute γ-ray emission probabilities of 223Ra and decay progeny in equilibrium

    Precise measurements of the absolute γ-ray emission probabilities have been made of radiochemically pure solutions of 223Ra in equilibrium with its decay progeny, which had been previously standardised by 4π(liquid scintillation)-γ digital coincidence counting techniques. Two high-purity germanium γ-ray spectrometers were used which had been accurately calibrated using a suite of primary and secondary radioactive standards. Comparison of the activity concentration determined by the primary technique against γ-ray spectrometry measurements using the nuclear data evaluations of the Decay Data Evaluation Project exhibited a range of ~18% in the most intense γ-ray emissions (>1% probability) of the 223Ra decay series. Absolute γ-ray emission probabilities and standard uncertainties have been determined for the decay of 223Ra, 219Rn, 215Po, 211Pb, 211Bi and 207Tl in equilibrium. The standard uncertainties of the measured γ-ray emission probabilities quoted in this work show a significant improvement over previously reported γ-ray emission probabilities. Correlation coefficients for pairs of the measured γ-ray emission probabilities from the decays of the radionuclides 223Ra, 219Rn and 211Pb have been determined and are presented. The α-transition probabilities of the 223Ra have been deduced from P(γ+ce) balance using the γ-ray emission probabilities determined in this work with some agreement observed with the published experimental values of the α-emission probabilities. - Highlights: • Discrepancies found within currently published γ-ray emission probabilities. • Absolute γ-ray emission probabilities of decay series in equilibrium determined. • Significant improvement in precision of measured values. • Closer agreement between deduced and experimental α transition probabilities. • Correlation coefficients presented for γ-emissions of 223Ra, 219Rn and 211Pb

  10. Radium-223 chloride: a potential new treatment for castration-resistant prostate cancer patients with metastatic bone disease

    Radium-223 chloride (223Ra; Alpharadin) is an alpha-emitting radioisotope that targets areas of osteoblastic metastasis and is excreted by the small intestine. When compared with beta-emitters (eg, strontium-89, samarium-153), 223Ra delivers a high quantity of energy per track length with short tissue penetration. This review describes the mechanism, radiobiology, and preclinical development of 223Ra and discusses the clinical data currently available regarding its safety and efficacy profile. Data from clinical trials including abstracts were collected and reviewed using the PubMed Database, as well as the American Society of Clinical Oncology abstract database. Current bone-targeted therapies fall into two main categories: antiresorptive agents (eg, zoledronic acid, denosumab), which have been shown to delay skeletal-related events, and radiopharmaceuticals (eg, samarium-153), which may have a role in pain palliation. Historically, neither antiresorptive agents nor radiopharmaceuticals have shown definitive evidence of improved overall survival or other antitumor effects in metastatic castrate-resistant prostate cancer (mCRPC). Radiopharmaceuticals are limited by myelosuppresion, thrombocytopenia, and renal excretion. In a recently reported randomized Phase III trial in men with symptomatic bone-metastatic CRPC who had received or were ineligible for docetaxel chemotherapy, 223Ra treatment resulted in improved overall survival and delayed skeletal-related events. Toxicity consisted of minor gastrointestinal side effects and mild neutropenia and thrombocytopenia that were rarely severe. Pending regulatory approval, 223Ra may represent a unique and distinct option for an important subgroup of patients with mCRPC; future trials should address its use in combination or in sequence with existing and novel agents

  11. Preparation and Photo-thermal Isomerization of Azo [2.2.1]-and Azo[2.2.3]metacyclophane Tweezers

    Sawada, Tsuyoshi; Thiemann, Thies; Mataka, Shuntaro

    1999-01-01

    Azo[2.2.1]metacyclophane (MCP) tweezer 11 and azo[2.2.3]MCP tweezer 12 were prepared from [2.2.1]MCP 1a and [2.2.3]MCP 8, respectively, by ipso-nitration followed by reductive coupling using LiAlH_4. The photochemical and thermal isomerization of azo[2.2.n]MCP tweezers were studied by UV spectroscopy. The activation parameter (E_a) of the thermal cis-trans isomerization of 11 and 12 was determined as 81.7 kJmol^ and 90.9 kJmol^, respectively.

  12. Determination of 226Ra, 224Ra, 223Ra and 228Ra in mineral water samples of the Slovak Republic

    The Slovak Republic is very rich in mineral water sources. In recent years, it has been discovered that a number of mineral waters in the Slovak Republic contain high levels of 226Ra and 228Ra. Moreover, there is a lack of information on 224Ra and 223Ra concentrations in mineral waters as well. The currently approved techniques for alpha emitting radium isotopes are based on radon emanation methods. Due to the long ingrowth periods required by these techniques, any 224Ra and 223Ra in the sample decay away and go undetected. For this reason, we have used an alpha spectrometric method for the simultaneous determination of 226Ra, 223Ra and 224Ra. Radium was concentrated by a lead sulphate co-precipitation. The precipitate was dissolved in EDTA and the radium isotopes were separated from possible interfering radionuclides using barium sulphate micro precipitation. The radium-barium precipitate was filtered and counted by alpha spectrometry. 133Ba was used to quantify the yield by gamma spectrometry. In our laboratory, gamma spectrometry was also used for the determination of 228Ra in mineral water samples. Radium was concentrated by a lead-barium sulphate co-precipitation. 133Ba was used to quantify the yield, found to be 97 % on the average, by gamma spectrometry. Furthermore, the committed effective doses for 226Ra, 224Ra, 223Ra, 228Ra intake via ingestion of mineral waters for the members of public were calculated. (author)

  13. A 380-kb Duplication in 7p22.3 Encompassing the LFNG Gene in a Boy with Asperger Syndrome

    Vulto-van Silfhout, A.T.; Brouwer, A.F. de; Leeuw, N. de; Obihara, C.C.; Brunner, H.G.; Vries, B.B. de

    2012-01-01

    De novo genomic aberrations are considered an important cause of autism spectrum disorders. We describe a de novo 380-kb gain in band p22.3 of chromosome 7 in a patient with Asperger syndrome. This duplicated region contains 9 genes including the LNFG gene that is an important regulator of NOTCH sig

  14. 12 CFR 223.24 - What valuation principles apply to extensions of credit secured by affiliate securities?

    2010-01-01

    ... 12 Banks and Banking 3 2010-01-01 2010-01-01 false What valuation principles apply to extensions... THEIR AFFILIATES (REGULATION W) Valuation and Timing Principles Under Section 23A § 223.24 What valuation principles apply to extensions of credit secured by affiliate securities? (a) Valuation...

  15. Leptin receptor polymorphism Gln223Arg (rs1137101) in oral squamous cell carcinoma and potentially malignant oral lesions.

    Domingos, Patrícia Luciana Batista; Farias, Lucyana Conceição; Pereira, Camila Santos; das Graças Pena, Geórgia; Reis, Tatiana Carvalho; Silva, Rosângela Ramos Veloso; Fraga, Carlos Alberto de Carvalho; de Souza, Marcela Gonçalves; Soares, Mariana Batista; Jones, Kimberly Marie; Menezes, Elytania Veiga; Nobre, Sérgio Avelino Mota; Rodrigues Neto, João Felício; de Paula, Alfredo Maurício Batista; Velásquez-Meléndez, Jorge Gustavo; Sena Guimarães, André Luiz

    2014-01-01

    The purpose of this study was to assess the LEPR gene Gln223Arg polymorphism (rs1137101) in oral squamous cell carcinoma (OSCC) and in potentially malignant oral lesions (PMOL) in comparison to normal oral mucosa in a Brazilian population. Smokers (n = 89) were selected from a representative sample of 471 individuals from the general population of Montes Claros, Brazil. Participants were age and gender matched to patients with OSCC (n = 25) and oral epithelial dysplasia (n = 25). We investigated the LEPR Gln223Arg polymorphism (A>G; rs1137101) in these groups. Genotype variants were assessed by RFLP-PCR, using MspI (HPAII) restriction endonuclease. The institutional review board of the Universidade Estadual de Montes Claros approved the study (process number 2667/2011). Written informed consent for this study was obtained from all participants. The GG genotype (Arg223Arg) appears to be the more relevant polymorphic variant in OSCC. It occurred, approximately, twice as frequently in OSCC patients than in the general population. In contrast, the A allele in its homozygosis form (Gln223Gln) is significantly associated with the development of PMOL; 80% of the samples from the PMOL group exhibit AA genotype. Our findings suggest new insights regarding LEPR gene variations in the development of OSCC and PMOL. PMID:26034683

  16. IMAGING OF THE CCS 22.3 GHz EMISSION IN THE TAURUS MOLECULAR CLOUD COMPLEX

    Thioxoethenylidene (CCS) is an abundant interstellar molecule and a good tracer of high density and evolutionary stage of dense molecular clouds. It is also a suitable candidate for Zeeman splitting observations for its high splitting factor and narrow thermal line widths. We report here Expanded Very Large Array 22.3 GHz observations of three dense molecular cores TMC-1, TMC-1C, and L1521B in the Taurus molecular cloud complex to image the CCS 21-10 transition. For all three sources, the clumpy CCS emission is most likely tracing the starless cores. However, these compact structures account for only ∼1%-13% of the integrated emission detected in single-dish observations, indicating the presence of significant large-scale diffuse emission in favorable conditions for producing CCS.

  17. A transcription map of the 6p22.3 reading disability locus identifying candidate genes

    Gruen Jeffrey R

    2003-06-01

    Full Text Available Abstract Background Reading disability (RD is a common syndrome with a large genetic component. Chromosome 6 has been identified in several linkage studies as playing a significant role. A more recent study identified a peak of transmission disequilibrium to marker JA04 (G72384 on chromosome 6p22.3, suggesting that a gene is located near this marker. Results In silico cloning was used to identify possible candidate genes located near the JA04 marker. The 2 million base pairs of sequence surrounding JA04 was downloaded and searched against the dbEST database to identify ESTs. In total, 623 ESTs from 80 different tissues were identified and assembled into 153 putative coding regions from 19 genes and 2 pseudogenes encoded near JA04. The identified genes were tested for their tissue specific expression by RT-PCR. Conclusions In total, five possible candidate genes for RD and other diseases mapping to this region were identified.

  18. Crystal Structure of D-Valine at the Temperature of 293, 270, 223 and 173K

    WANG Wen-Qing; GONG Yan; WANG Zhe-Ming; YAN Chun-Hua

    2003-01-01

    The crystal structure of D-valine has been determined by Mo-Kα (λ = 0.71073 A) X-ray diffraction method for the first time. It crystallizes in monoclinic, space group P21 (Z = 4) with a = 9.6728(5), b = 5.2722(3), c = 12.0425(8) A, β = 90.750(2)° at 293 K. The asymmetric unit contains two crystallographically independent molecules — A (trans form) and B (gauche I form). They are rotational isomers with two kinds of conformations about the Cα -Cβ bond. The results of measurements of crystal structure at 293, 270, 223 and 173 K show a little change in bond lengths and geometries as a function of temperature. No evidence was obtained for the existence of configuration transformation from D- to L-valine.

  19. Integral field spectroscopy of the brightest knots of HH 223 in L723

    López, R.; García-Lorenzo, B.; Estalella, R.; Riera, A.; Carrasco-González, C.; Gómez, G.

    2012-08-01

    HH 223 is the optical counterpart of a larger scale H2 outflow, driven by the protostellar source VLA 2A, in L723. Its poorly collimated and rather chaotic morphology suggested Integral Field Spectroscopy (IFS) as an appropriate option to map the emission in order to derive the physical conditions and kinematics. Here we present new results based on IFS observations made with the INTEGRAL system at the William Herschel Telescope. The brightest knots of HH 223 (˜16 arcsec, ≃0.02 pc at a distance of 300 pc) were mapped with a single pointing in the spectral range 6200-7700 Å. We obtained emission-line intensity maps for Hα, [N II] 6584 Å and [S II] 6716, 6731 Å and explored the distribution of the excitation and electron density from [N II]/Hα, [S II]/Hα and [S II] 6716/6731 line-ratio maps. Maps of the radial velocity field were obtained. We analysed the three-dimensional kinematics by combining the knot radial velocities derived from IFS data with the knot proper motions derived from multi-epoch narrow-band images. The intensity maps built from IFS data reproduced the morphology found in the narrow-band images well. We checked the results obtained from previous long-slit observations with those derived from IFS spectra extracted with a similar spatial sampling. At the positions intersected by the slit, the physical conditions and kinematics derived from IFS are compatible with those derived from long-slit data. In contrast, significant discrepancies were found when the results from long-slit data were compared with the ones derived from IFS spectra extracted at positions shifted a few arcsec from those intersected by the slit. This clearly revealed IFS observations as the best choice to obtain a reliable picture of the HH emission properties.

  20. A Turner syndrome neurocognitive phenotype maps to Xp22.3

    Elder Frederick F

    2007-05-01

    Full Text Available Abstract Background Turner syndrome (TS is associated with a neurocognitive phenotype that includes selective nonverbal deficits, e.g., impaired visual-spatial abilities. We previously reported evidence that this phenotype results from haploinsufficiency of one or more genes on distal Xp. This inference was based on genotype/phenotype comparisons of individual girls and women with partial Xp deletions, with the neurocognitive phenotype considered a dichotomous trait. We sought to confirm our findings in a large cohort (n = 47 of adult women with partial deletions of Xp or Xq, enriched for subjects with distal Xp deletions. Methods Subjects were recruited from North American genetics and endocrinology clinics. Phenotype assessment included measures of stature, ovarian function, and detailed neurocognitive testing. The neurocognitive phenotype was measured as a quantitative trait, the Turner Syndrome Cognitive Summary (TSCS score, derived from discriminant function analysis. Genetic analysis included karyotyping, X inactivation studies, fluorescent in situ hybridization, microsatellite marker genotyping, and array comparative genomic hybridization. Results We report statistical evidence that deletion of Xp22.3, an interval containing 31 annotated genes, is sufficient to cause the neurocognitive phenotype described by the TSCS score. Two other cardinal TS features, ovarian failure and short stature, as well as X chromosome inactivation pattern and subject's age, were unrelated to the TSCS score. Conclusion Detailed mapping suggests that haploinsufficiency of one or more genes in Xp22.3, the distal 8.3 megabases (Mb of the X chromosome, is responsible for a TS neurocognitive phenotype. This interval includes the 2.6 Mb Xp-Yp pseudoautosomal region (PAR1. Haploinsufficiency of the short stature gene SHOX in PAR1 probably does not cause this TS neurocognitive phenotype. Two genes proximal to PAR1 within the 8.3 Mb critical region, STS and NLGN4X, are

  1. A bone marrow toxicity model for 223Ra alpha-emitter radiopharmaceutical therapy

    Hobbs, Robert F.; Song, Hong; Watchman, Christopher J.; Bolch, Wesley E.; Aksnes, Anne-Kirsti; Ramdahl, Thomas; Flux, Glenn D.; Sgouros, George

    2012-05-01

    Ra-223, an α-particle emitting bone-seeking radionuclide, has recently been used in clinical trials for osseous metastases of prostate cancer. We investigated the relationship between absorbed fraction-based red marrow dosimetry and cell level-dosimetry using a model that accounts for the expected localization of this agent relative to marrow cavity architecture. We show that cell level-based dosimetry is essential to understanding potential marrow toxicity. The GEANT4 software package was used to create simple spheres representing marrow cavities. Ra-223 was positioned on the trabecular bone surface or in the endosteal layer and simulated for decay, along with the descendants. The interior of the sphere was divided into cell-size voxels and the energy was collected in each voxel and interpreted as dose cell histograms. The average absorbed dose values and absorbed fractions were also calculated in order to compare those results with previously published values. The absorbed dose was predominantly deposited near the trabecular surface. The dose cell histogram results were used to plot the percentage of cells that received a potentially toxic absorbed dose (2 or 4 Gy) as a function of the average absorbed dose over the marrow cavity. The results show (1) a heterogeneous distribution of cellular absorbed dose, strongly dependent on the position of the cell within the marrow cavity; and (2) that increasing the average marrow cavity absorbed dose, or equivalently, increasing the administered activity resulted in only a small increase in potential marrow toxicity (i.e. the number of cells receiving more than 4 or 2 Gy), for a range of average marrow cavity absorbed doses from 1 to 20 Gy. The results from the trabecular model differ markedly from a standard absorbed fraction method while presenting comparable average dose values. These suggest that increasing the amount of radioactivity may not substantially increase the risk of toxicity, a result unavailable to the

  2. miR-223 enhances the sensitivity of non-small cell lung cancer cells to erlotinib by targeting the insulin-like growth factor-1 receptor.

    Zhao, Feng-Yi; Han, Jing; Chen, Xie-Wan; Wang, Jiang; Wang, Xu-Dong; Sun, Jian-Guo; Chen, Zheng-Tang

    2016-07-01

    Lung cancer is the leading cause of cancer-related fatalities worldwide, and non-small cell lung cancer (NSCLC) is the main pathological type. MicroRNAs (miRNAs or miRs) are a class of small non-coding RNAs, which are involved in tumor initiation and progression. miR‑223 is a tumor suppressor miRNA that has been reported in various types of cancer, including lung cancer. In the present study, to characterize the biological behavior of miR‑223 in NSCLC, we established an miR‑223 overexpression model in erlotinib-resistant PC‑9 (PC‑9/ER) cells by infection with lentivirus to induce the overexpression of miR‑223. As a result, miR‑223 enhanced the sensitivity of the PC‑9/ER cells to erlotinib by inducing apoptosis in vitro. Additionally, in vivo experiments were performed using nude mice which were injected with the cancer cells [either the PC‑9 (not resistant), PC‑9/ER, or the PC‑9/ER cells infected with miR‑223)]. We found that the tumor volumes were reduced in the rats injected with the cells infected with miR‑223. To further explore the underlying mechanisms, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot analysis were used to identify the target molecules of miR‑223. miR‑223 was demonstrated to act as a local regulator of insulin-like growth factor-1 receptor (IGF-1R) in the acquired resistance to tyrosine kinase inhibitors (TKIs). Notably, the οverexpression of IGF-1R in NSCLC was downregulated by miR‑223, and the activation of Akt/S6, the downstream pathway, was also inhibited. The inhibition of IGF-1R by miR‑223 was attenuated by exogenous IGF-1 expression. Therefore, miR‑223 may regulate the acquired resistance of PC‑9/ER cells to erlotinib by targeting the IGF-1R/Akt/S6 signaling pathway. The overexpression of miR‑223 may partially reverse the acquired resistance to epidermal growth factor receptor-TKIs, thus, providing a potential therapeutic strategy for TKI

  3. Leptin receptor Gln223Arg polymorphism and breast cancer risk in Nigerian women: A case control study

    Leptin, a 16 kDa polypeptide hormone, implicated in various physiological processes, exerts its action through the leptin receptor, a member of the class I cytokine receptor family. Both leptin and leptin receptor have recently been implicated in processes leading to breast cancer initiation and progression in animal models and humans. An A to G transition mutation in codon 223 in exon 6 of the leptin receptor gene, resulting in glutamine to arginine substitution (Gln223Arg), lies within the first of two putative leptin-binding regions and may be associated with impaired signaling capacity of the leptin receptor. This study was designed to assess the role of this polymorphism in breast cancer susceptibility in Nigerian women. We utilized a polymerase chain reaction (PCR)-based restriction fragment length polymorphism (RFLP) assay to evaluate the association between the Gln223Arg polymorphism of the leptin receptor gene and breast risk in Nigeria in a case control study involving 209 women with breast cancer and 209 controls without the disease. Study participants were recruited from surgical outpatient clinics and surgical wards of four University Teaching Hospitals located in Midwestern and southeastern Nigeria between September 2002 and April 2004. Premenopausal women carrying at least one LEPR 223Arg allele were at a modestly increased risk of breast cancer after adjusting for confounders (OR = 1.8, 95% confidence interval [CI] 1.0–3.2, p = 0.07). There was no association with postmenopausal breast cancer risk (OR = 0.9, 95% CI 0.4–1.8, p = 0.68). Our results suggest that the LEPR Gln223Arg polymorphism in the extracellular domain of the LEPR receptor gene is associated with a modestly increased risk of premenopausal breast cancer in Nigerian women

  4. Oxidized Low-density Lipoprotein (ox-LDL) Cholesterol Induces the Expression of miRNA-223 and L-type Calcium Channel Protein in Atrial Fibrillation

    He, Fengping; Xu, Xin; Yuan, Shuguo; Tan, Liangqiu; Gao, Lingjun; Ma, Shaochun; Zhang, Shebin; Ma, Zhanzhong; Jiang, Wei; Liu, Fenglian; Chen, Baofeng; Zhang, Beibei; Pang, Jungang; Huang, Xiuyan; Weng, Jiaqiang

    2016-08-01

    Atrial fibrillation (AF) is the most common sustained arrhythmia causing high morbidity and mortality. While changing of the cellular calcium homeostasis plays a critical role in AF, the L-type calcium channel α1c protein has suggested as an important regulator of reentrant spiral dynamics and is a major component of AF-related electrical remodeling. Our computational modeling predicted that miRNA-223 may regulate the CACNA1C gene which encodes the cardiac L-type calcium channel α1c subunit. We found that oxidized low-density lipoprotein (ox-LDL) cholesterol significantly up-regulates both the expression of miRNA-223 and L-type calcium channel protein. In contrast, knockdown of miRNA-223 reduced L-type calcium channel protein expression, while genetic knockdown of endogenous miRNA-223 dampened AF vulnerability. Transfection of miRNA-223 by adenovirus-mediated expression enhanced L-type calcium currents and promoted AF in mice while co-injection of a CACNA1C-specific miR-mimic counteracted the effect. Taken together, ox-LDL, as a known factor in AF-associated remodeling, positively regulates miRNA-223 transcription and L-type calcium channel protein expression. Our results implicate a new molecular mechanism for AF in which miRNA-223 can be used as an biomarker of AF rheumatic heart disease.

  5. Oxidized Low-density Lipoprotein (ox-LDL) Cholesterol Induces the Expression of miRNA-223 and L-type Calcium Channel Protein in Atrial Fibrillation.

    He, Fengping; Xu, Xin; Yuan, Shuguo; Tan, Liangqiu; Gao, Lingjun; Ma, Shaochun; Zhang, Shebin; Ma, Zhanzhong; Jiang, Wei; Liu, Fenglian; Chen, Baofeng; Zhang, Beibei; Pang, Jungang; Huang, Xiuyan; Weng, Jiaqiang

    2016-01-01

    Atrial fibrillation (AF) is the most common sustained arrhythmia causing high morbidity and mortality. While changing of the cellular calcium homeostasis plays a critical role in AF, the L-type calcium channel α1c protein has suggested as an important regulator of reentrant spiral dynamics and is a major component of AF-related electrical remodeling. Our computational modeling predicted that miRNA-223 may regulate the CACNA1C gene which encodes the cardiac L-type calcium channel α1c subunit. We found that oxidized low-density lipoprotein (ox-LDL) cholesterol significantly up-regulates both the expression of miRNA-223 and L-type calcium channel protein. In contrast, knockdown of miRNA-223 reduced L-type calcium channel protein expression, while genetic knockdown of endogenous miRNA-223 dampened AF vulnerability. Transfection of miRNA-223 by adenovirus-mediated expression enhanced L-type calcium currents and promoted AF in mice while co-injection of a CACNA1C-specific miR-mimic counteracted the effect. Taken together, ox-LDL, as a known factor in AF-associated remodeling, positively regulates miRNA-223 transcription and L-type calcium channel protein expression. Our results implicate a new molecular mechanism for AF in which miRNA-223 can be used as an biomarker of AF rheumatic heart disease. PMID:27488468

  6. H1N1 2009 pandemic influenza virus: resistance of the I223R neuraminidase mutant explained by kinetic and structural analysis.

    Erhard van der Vries

    2012-09-01

    Full Text Available Two classes of antiviral drugs, neuraminidase inhibitors and adamantanes, are approved for prophylaxis and therapy against influenza virus infections. A major concern is that antiviral resistant viruses emerge and spread in the human population. The 2009 pandemic H1N1 virus is already resistant to adamantanes. Recently, a novel neuraminidase inhibitor resistance mutation I223R was identified in the neuraminidase of this subtype. To understand the resistance mechanism of this mutation, the enzymatic properties of the I223R mutant, together with the most frequently observed resistance mutation, H275Y, and the double mutant I223R/H275Y were compared. Relative to wild type, K(M values for MUNANA increased only 2-fold for the single I223R mutant and up to 8-fold for the double mutant. Oseltamivir inhibition constants (K(I increased 48-fold in the single I223R mutant and 7500-fold in the double mutant. In both cases the change was largely accounted for by an increased dissociation rate constant for oseltamivir, but the inhibition constants for zanamivir were less increased. We have used X-ray crystallography to better understand the effect of mutation I223R on drug binding. We find that there is shrinkage of a hydrophobic pocket in the active site as a result of the I223R change. Furthermore, R223 interacts with S247 which changes the rotamer it adopts and, consequently, binding of the pentoxyl substituent of oseltamivir is not as favorable as in the wild type. However, the polar glycerol substituent present in zanamivir, which mimics the natural substrate, is accommodated in the I223R mutant structure in a similar way to wild type, thus explaining the kinetic data. Our structural data also show that, in contrast to a recently reported structure, the active site of 2009 pandemic neuraminidase can adopt an open conformation.

  7. Notch-regulated miR-223 targets the aryl hydrocarbon receptor pathway and increases cytokine production in macrophages from rheumatoid arthritis patients

    Ogando, Jesús; Tardáguila, Manuel; Díaz-Alderete, Andrea; Usategui, Alicia; Miranda-Ramos, Vanessa; Martínez-Herrera, Dannys Jorge; de la Fuente, Lorena; García-León, María J.; Moreno, María C.; Escudero, Sara; Cañete, Juan D.; Toribio, María L.; Cases, Ildefonso; Pascual-Montano, Alberto; Pablos, José Luis; Mañes, Santos

    2016-01-01

    Evidence links aryl hydrocarbon receptor (AHR) activation to rheumatoid arthritis (RA) pathogenesis, although results are inconsistent. AHR agonists inhibit pro-inflammatory cytokine expression in macrophages, pivotal cells in RA aetiopathogenesis, which hints at specific circuits that regulate the AHR pathway in RA macrophages. We compared microRNA (miR) expression in CD14+ cells from patients with active RA or with osteoarthritis (OA). Seven miR were downregulated and one (miR-223) upregulated in RA compared to OA cells. miR-223 upregulation correlated with reduced Notch3 and Notch effector expression in RA patients. Overexpression of the Notch-induced repressor HEY-1 and co-culture of healthy donor monocytes with Notch ligand-expressing cells showed direct Notch-mediated downregulation of miR-223. Bioinformatics predicted the AHR regulator ARNT (AHR nuclear translocator) as a miR-223 target. Pre-miR-223 overexpression silenced ARNT 3’UTR-driven reporter expression, reduced ARNT (but not AHR) protein levels and prevented AHR/ARNT-mediated inhibition of pro-inflammatory cytokine expression. miR-223 counteracted AHR/ARNT-induced Notch3 upregulation in monocytes. Levels of ARNT and of CYP1B1, an AHR/ARNT signalling effector, were reduced in RA compared to OA synovial tissue, which correlated with miR-223 levels. Our results associate Notch signalling to miR-223 downregulation in RA macrophages, and identify miR-223 as a negative regulator of the AHR/ARNT pathway through ARNT targeting. PMID:26838552

  8. Isolation of generator-produced 223Ra in 0.9-% NaCl solutions containing EDTA for direct radiotherapeutic studies

    A novel approach to the preparation of the α-emitting radionuclide 223Ra was proposed to be applied for direct treatment of bone metastases and targeted alpha-radioimmunotherapy. The tandem generator system based on ion exchange columns was developed for isolation of 223Ra in the form of 223Ra-EDTA complexes in 0.9 % NaCl solutions at pH = 7.4-8.0. Advantages of the method for routine laboratory work and clinical implementations are discussed. (author)

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

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

    2013-01-01

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

  10. Dosimetric study of radium-223 chloride and 153Sm-EDTMP for treatment of bone metastases using MCNPX code and available experimental data

    Radium-223 chloride is an alpha emitter radiopharmaceutical which recently has been used for treatment of bone metastases. Absorbed and equivalent doses of 223RaCl2 were studied using MCNPX Monte Carlo code in a phantom consisted of bone marrow, bone and soft tissue. 153Sm-EDTMP as a beta emitter was also simulated for comparison with 223RaCl2. Results show that by injection of 100 µCi 223RaCl2 against 70 mCi 153Sm-EDTMP to a 70 kg adult man, equivalent dose of metastatic bone can be increased about six times without significant increase in delivered dose to healthy tissues. These results demonstrated acceptable agreement with experimental data. (author)

  11. STRUCTURAL CONSEQUENCES OF THE POLYMORPHISM Q223R IN THE HUMAN LEPTIN RECEPTOR: A MOLECULAR DYNAMICS STUDY

    Jonathan P. Carrillo-Vázquez; Brenda Chimal-Vega; Beatriz Zamora-López; Marchat, Laurence A.; Claudia G. Benítez-Cardoza; César A.S. Reyes-López; Absalom Zamorano-Carrillo

    2013-01-01

    Leptin Receptor (LEPR) is a component of a signaling pathway related to appetite and energy expenditure. Single Nucleotide Polymorphisms (SNP) of Leptin receptor gene (lepr) have been proposed as possible modulator of adipose tissue and body weight. The main phenomenological consequence reported of these SNPs is the modulation of the LEP-LEPR interaction promoting the weight gain. Particularly, Q223R polymorphism has been associated with human obesity in some populations. In this work, we ana...

  12. Multidrug resistant 2009 A/H1N1 influenza clinical isolate with a neuraminidase I223R mutation retains its virulence and transmissibility in ferrets.

    Erhard van der Vries

    2011-09-01

    Full Text Available Only two classes of antiviral drugs, neuraminidase inhibitors and adamantanes, are approved for prophylaxis and therapy against influenza virus infections. A major concern is that influenza virus becomes resistant to these antiviral drugs and spreads in the human population. The 2009 pandemic A/H1N1 influenza virus is naturally resistant to adamantanes. Recently a novel neuraminidase I223R mutation was identified in an A/H1N1 virus showing cross-resistance to the neuraminidase inhibitors oseltamivir, zanamivir and peramivir. However, the ability of this virus to cause disease and spread in the human population is unknown. Therefore, this clinical isolate (NL/2631-R223 was compared with a well-characterized reference virus (NL/602. In vitro experiments showed that NL/2631-I223R replicated as well as NL/602 in MDCK cells. In a ferret pathogenesis model, body weight loss was similar in animals inoculated with NL/2631-R223 or NL/602. In addition, pulmonary lesions were similar at day 4 post inoculation. However, at day 7 post inoculation, NL/2631-R223 caused milder pulmonary lesions and degree of alveolitis than NL/602. This indicated that the mutant virus was less pathogenic. Both NL/2631-R223 and a recombinant virus with a single I223R change (recNL/602-I223R, transmitted among ferrets by aerosols, despite observed attenuation of recNL/602-I223R in vitro. In conclusion, the I223R mutated virus isolate has comparable replicative ability and transmissibility, but lower pathogenicity than the reference virus based on these in vivo studies. This implies that the 2009 pandemic influenza A/H1N1 virus subtype with an isoleucine to arginine change at position 223 in the neuraminidase has the potential to spread in the human population. It is important to be vigilant for this mutation in influenza surveillance and to continue efforts to increase the arsenal of antiviral drugs to combat influenza.

  13. Radiation dosimetry in digital breast tomosynthesis: Report of AAPM Tomosynthesis Subcommittee Task Group 223

    Sechopoulos, Ioannis, E-mail: isechop@emory.edu [Departments of Radiology and Imaging Sciences, Hematology and Medical Oncology and Winship Cancer Institute, Emory University, 1701 Uppergate Drive Northeast, Suite 5018, Atlanta, Georgia 30322 (United States); Sabol, John M. [GE Healthcare, Global Diagnostic X-Ray, Mailstop W-701, 3000 North Grandview Boulevard, Waukesha, Wisconsin 53188 (United States); Berglund, Johan [Research and Development, Philips Women' s Healthcare, Solna (Sweden); Bolch, Wesley E. [J. Crayton Pruitt Family Department of Biomedical Engineering, University of Florida, Gainesville, Florida 32611 (United States); Brateman, Libby [University of Florida, Gainesville, Florida 32611 (United States); Christodoulou, Emmanuel; Goodsitt, Mitchell [Department of Radiology, University of Michigan, 1500 East Medical Center Drive, Ann Arbor, Michigan 48109 (United States); Flynn, Michael [Department of Radiology, Henry Ford Health System, Radiology Research 2F, 1 Ford Place, Detroit, Michigan 48202 (United States); Geiser, William [Department of Imaging Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030-4009 (United States); Kyle Jones, A. [Department of Imaging Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030 (United States); Lo, Joseph Y.; Paul Segars, W. [Department of Radiology, Medical Physics Graduate Program, and Department of Biomedical Engineering, Carl E. Ravin Advanced Imaging Laboratories, Duke University, Durham, North Carolina 27705 (United States); Maidment, Andrew D. A. [Department of Radiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania 19104-4206 (United States); Nishino, Kazuyoshi [R and D X-ray Products Group, Shimadzu Corporation, Tokyo (Japan); Nosratieh, Anita [Biomedical Engineering Graduate Group, Department of Radiology, University of California, Davis, California 95817 (United States); and others

    2014-09-15

    The radiation dose involved in any medical imaging modality that uses ionizing radiation needs to be well understood by the medical physics and clinical community. This is especially true of screening modalities. Digital breast tomosynthesis (DBT) has recently been introduced into the clinic and is being used for screening for breast cancer in the general population. Therefore, it is important that the medical physics community have the required information to be able to understand, estimate, and communicate the radiation dose levels involved in breast tomosynthesis imaging. For this purpose, the American Association of Physicists in Medicine Task Group 223 on Dosimetry in Tomosynthesis Imaging has prepared this report that discusses dosimetry in breast imaging in general, and describes a methodology and provides the data necessary to estimate mean breast glandular dose from a tomosynthesis acquisition. In an effort to maximize familiarity with the procedures and data provided in this Report, the methodology to perform the dose estimation in DBT is based as much as possible on that used in mammography dose estimation.

  14. Studying Gender in Conference Talks -- data from the 223rd meeting of the American Astronomical Society

    Davenport, James R A; Grand, Erin; Hagen, Alex; Poppenhaeger, Katja; Watkins, Laura L

    2014-01-01

    We present a study on the gender balance, in speakers and attendees, at the recent major astronomical conference, the American Astronomical Society meeting 223, in Washington, DC. We conducted an informal survey, yielding over 300 responses by volunteers at the meeting. Each response included gender data about a single talk given at the meeting, recording the gender of the speaker and all question-askers. In total, 225 individual AAS talks were sampled. We analyze basic statistical properties of this sample. We find that the gender ratio of the speakers closely matched the gender ratio of the conference attendees. The audience asked an average of 2.8 questions per talk. Talks given by women had a slightly higher number of questions asked (3.2$\\pm$0.2) than talks given by men (2.6$\\pm$0.1). The most significant result from this study is that while the gender ratio of speakers very closely mirrors that of conference attendees, women are under-represented in the question-asker category. We interpret this to be a...

  15. Six- and three-hourly meteorological observations from 223 USSR stations

    Razuvaev, V.N.; Apasova, E.B.; Martuganov, R.A. [All-Russian Research Inst. of Hydrometeorologicl Information, Obninsk (Russia). World Data Centre; Kaiser, D.P. [Oak Ridge National Lab., TN (United States)

    1995-04-01

    This document describes a database containing 6- and 3-hourly meteorological observations from a 223-station network of the former Soviet Union. These data have been made available through cooperation between the two principal climate data centers of the United States and Russia: the National Climatic Data Center (NCDC), in Asheville, North Carolina, and the All-Russian Research Institute of Hydrometeorological Information -- World Data Centre (RIHMI-WDC) in Obninsk. Station records consist of 6- and 3-hourly observations of some 24 meteorological variables including temperature, weather type, precipitation amount, cloud amount and type, sea level pressure, relative humidity, and wind direction and speed. The 6-hourly observations extend from 1936 to 1965; the 3-hourly observations extend from 1966 through the mid-1980s (1983, 1984, 1985, or 1986; depending on the station). These data have undergone extensive quality assurance checks by RIHMI-WDC, NCDC, and the Carbon Dioxide Information Analysis Center (CDIAC). The database represents a wealth of meteorological information for a large and climatologically important portion of the earth`s land area, and should prove extremely useful for a wide variety of regional climate change studies. These data are available free of charge as a numeric data package (NDP) from CDIAC. The NDP consists of this document and 40 data files that are available via the Internet or on 8mm tape. The total size of the database is {approximately}2.6 gigabytes.

  16. Notch and NF-kB signaling pathways regulate miR-223/FBXW7 axis in T-cell acute lymphoblastic leukemia.

    Kumar, V; Palermo, R; Talora, C; Campese, A F; Checquolo, S; Bellavia, D; Tottone, L; Testa, G; Miele, E; Indraccolo, S; Amadori, A; Ferretti, E; Gulino, A; Vacca, A; Screpanti, I

    2014-12-01

    Notch signaling deregulation is linked to the onset of several tumors including T-cell acute lymphoblastic leukemia (T-ALL). Deregulated microRNA (miRNA) expression is also associated with several cancers, including leukemias. However, the transcriptional regulators of miRNAs, as well as the relationships between Notch signaling and miRNA deregulation, are poorly understood. To identify miRNAs regulated by Notch pathway, we performed microarray-based miRNA profiling of several Notch-expressing T-ALL models. Among seven miRNAs, consistently regulated by overexpressing or silencing Notch3, we focused our attention on miR-223, whose putative promoter analysis revealed a conserved RBPjk binding site, which was nested to an NF-kB consensus. Luciferase and chromatin immunoprecipitation assays on the promoter region of miR-223 show that both Notch and NF-kB are novel coregulatory signals of miR-223 expression, being able to activate cooperatively the transcriptional activity of miR-223 promoter. Notably, the Notch-mediated activation of miR-223 represses the tumor suppressor FBXW7 in T-ALL cell lines. Moreover, we observed the inverse correlation of miR-223 and FBXW7 expression in a panel of T-ALL patient-derived xenografts. Finally, we show that miR-223 inhibition prevents T-ALL resistance to γ-secretase inhibitor (GSI) treatment, suggesting that miR-223 could be involved in GSI sensitivity and its inhibition may be exploited in target therapy protocols. PMID:24727676

  17. Analysis of Gln223Agr Polymorphism of Leptin Receptor Gene in Type II Diabetic Mellitus Subjects among Malaysians

    Chong Pei Pei

    2013-09-01

    Full Text Available Leptin is known as the adipose peptide hormone. It plays an important role in the regulation of body fat and inhibits food intake by its action. Moreover, it is believed that leptin level deductions might be the cause of obesity and may play an important role in the development of Type 2 Diabetes Mellitus (T2DM, as well as in cardiovascular diseases (CVD. The Leptin Receptor (LEPR gene and its polymorphisms have not been extensively studied in relation to the T2DM and its complications in various populations. In this study, we have determined the association of Gln223Agr loci of LEPR gene in three ethnic groups of Malaysia, namely: Malays, Chinese and Indians. A total of 284 T2DM subjects and 281 healthy individuals were recruited based on International Diabetes Federation (IDF criteria. Genomic DNA was extracted from the buccal specimens of the subjects. The commercial polymerase chain reaction (PCR method was carried out by proper restriction enzyme MSP I to both amplify and digest the Gln223Agr polymorphism. The p-value among the three studied races was 0.057, 0.011 and 0.095, respectively. The values such as age, WHR, FPG, HbA1C, LDL, HDL, Chol and Family History were significantly different among the subjects with Gln223Agr polymorphism of LEPR (p < 0.05.

  18. Biocontrol of Potato Common Scab is Associated with High Pseudomonas fluorescens LBUM223 Populations and Phenazine-1-Carboxylic Acid Biosynthetic Transcript Accumulation in the Potato Geocaulosphere.

    Arseneault, Tanya; Goyer, Claudia; Filion, Martin

    2016-09-01

    Pseudomonads are often used as biocontrol agents because they display a broad range of mechanisms to control diseases. Common scab of potato, caused by Streptomyces scabies, was previously reported to be controlled by Pseudomonas fluorescens LBUM223 through phenazine-1-carboxylic acid (PCA) production. In this study, we aimed at characterizing the population dynamics of LBUM223 and the expression of phzC, a key gene involved in the biosynthesis of PCA, in the rhizosphere and geocaulosphere of potato plants grown under controlled and field conditions. Results obtained from controlled experiments showed that soil populations of LBUM223 significantly declined over a 15-week period. However, at week 15, the presence of S. scabies in the geocaulosphere was associated with significantly higher populations of LBUM223 than when the pathogen was absent. It also led to the detection of significantly higher phzC gene transcript numbers. Under field conditions, soil populations of LBUM223 followed a similar decline in time when a single inoculation was applied in spring but remained stable when reinoculated biweekly, which also led to greater phzC gene transcripts accumulation. Taken together, our findings suggest that LBUM223 must colonize the potato geocaulosphere at high levels (10(7) bacteria/g of soil) in order to achieve biocontrol of common scab through increased PCA production. PMID:27088392

  19. Synthesis and characterization of lanthanum phosphate nanoparticles as carriers for 223Ra and 225Ra for targeted alpha therapy

    Introduction: Targeted alpha therapy (TAT) has the potential for killing micro-metastases with minimum collateral damage to surrounding healthy tissue. In-vivo generator radionuclides, such as223Ra, 225Ra, and 225Ac, are of special interest for radiotherapeutic applications as they emit multiple α-particles during their decay. Utilizing appropriate carriers capable of retaining both the parent radioisotope as well as daughter products is important for the effective delivery of the radioisotope to the tumor site while mitigating global in vivo radiotoxicity. In this work, LaPO4 core and core + 2 shells nanoparticles (NPs) (NPs with 2 layers of cold LaPO4 deposited on the core surfaces) were synthesized containing either 223Ra or225Ra/225Ac, and the retention of the parents and daughters within the NPs in vitro was investigated. Methods: Core LaPO4 NPs were synthesized in aqueous solution by reacting 1 equivalent of La(NO3)3, along with few microcuries of either 223Ra or 225Ra/225Ac, with 1 equivalent of sodium tripolyphosphate (TPP) under moderate heating and purified by membrane dialysis. Core-shell NPs were also synthesized with one (core + 1 shell) and two (core + 2 shells) cold LaPO4 layers deposited onto the radioactive cores. The NPs were then characterized by transmission electron microscopy (TEM) and powder x-ray diffraction (XRD). Identification and quantification of radioactive parents and daughters released from the NPs in vitro were investigated using gamma-ray spectroscopy. Results: XRD and TEM analysis revealed that the NPs crystallized in the rhabdophane phase with mean diameters of 3.4 and 6.3 nm for core and core + 2 shells, respectively. The core LaPO4 NPs retained up to 88% of 223Ra over 35 days. However, in the core + 2 shells NPs, the retention of 223Ra and its daughter, 211Pb, was improved to > 99.9% over 27 days. Additionally, the retention of 225Ra/225Ac parents was > 99.98% and ~ 80% for the 221Fr and 213Bi daughters over 35 days for the

  20. Dosimetry of bone metastases in targeted radionuclide therapy with alpha-emitting {sup 223}Ra-dichloride

    Pacilio, Massimiliano [Azienda Ospealiera San Camillo Forlianini, Rome (Italy). Dept. of Medical Physics; Ventroni, Guido; Mango, Lucio [Azienda Ospealiera San Camillo Forlianini, Rome (Italy). Dept. of Nuclear Medicin; De Vincentis, Giuseppe; Di Castro, Elisabetta; Frantellizzi, Viviana; Follacchio, Giulia Anna; Garkavaya, Tatiana [Rome Univ. (Italy). Dept. of Radiological, Oncological and Anatomo Pathological Sciences; Cassano, Bartolomeo; Lorenzon, Leda [Rome Univ. (Italy). Postgraduate School of Medical Physics; Pellegrini, Rosanna; Pani, Roberto [Rome Univ. (Italy). Dept. of Molecular Medicine; Ialongo, Pasquale [Azienda Ospealiera San Camillo Forlianini, Rome (Italy). Dept. of Radiology

    2016-01-15

    Ra-dichloride is an alpha-emitting radiopharmaceutical used in the treatment of bone metastases from castration-resistant prostate cancer. Image-based dosimetric studies remain challenging because the emitted photons are few. The aim of this study was to implement a methodology for in-vivo quantitative planar imaging, and to assess the absorbed dose to lesions using the MIRD approach. The study included nine Caucasian patients with 24 lesions (6 humeral head lesions, 4 iliac wing lesions, 2 scapular lesions, 5 trochanter lesions, 3 vertebral lesions, 3 glenoid lesions, 1 coxofemoral lesion). The treatment consisted of six injections (one every 4 weeks) of 50 kBq per kg body weight. Gamma-camera calibrations for {sup 223}Ra included measurements of sensitivity and transmission curves. Patients were statically imaged for 30 min, using an MEGP collimator, double-peak acquisition, and filtering to improve the image quality. Lesions were delineated on {sup 99m}Tc-MDP whole-body images, and the ROIs superimposed on the {sup 223}Ra images after image coregistration. The activity was quantified with background, attenuation, and scatter correction. Absorbed doses were assessed deriving the S values from the S factors for soft-tissue spheres of OLINDA/EXM, evaluating the lesion volumes by delineation on the CT images. In 12 lesions with a wash-in phase the biokinetics were assumed to be biexponential, and to be monoexponential in the remainder. The optimal timing for serial acquisitions was between 1 and 5 h, between 18 and 24 h, between 48 and 60 h, and between 7 and 15 days. The error in cumulated activity neglecting the wash-in phase was between 2 % and 12 %. The mean effective half-life (T{sub 1/2eff}) of {sup 223}Ra was 8.2 days (range 5.5-11.4 days). The absorbed dose (D) after the first injection was 0.7 Gy (range 0.2-1.9 Gy). Considering the relative biological effectiveness (RBE) of alpha particles (RBE = 5), D{sub RBE} = 899 mGy/MBq (range 340-2,450 mGy/MBq). The

  1. miR-223 reverses the resistance of EGFR-TKIs through IGF1R/PI3K/Akt signaling pathway.

    Han, Jing; Zhao, Fengyi; Zhang, Jing; Zhu, Haizhen; Ma, Hu; Li, Xuetao; Peng, Lina; Sun, Jianguo; Chen, Zhengtang

    2016-05-01

    Acquired resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), such as gefitinib and erlotinib, is a critical issue for the treatment of EGFR mutant-positive non-small cell lung cancer (NSCLC). Recent evidence supports the role of microRNA-223 (miR‑223) in modulating chemotherapeutic drug sensitivity, but its role in the resistance to EGFR-TKIs in NSCLC remains unclear. To this end, we investigated the involvement of miR‑223 in erlotinib resistance, using two pairs of TKI-sensitive or resistant cell lines, PC9 vs PC9/ER, and HCC827 vs HCC827/ER, as well as PC9/CD133+, which are lung cancer stem-like cells derived from PC9 cells. Downregulation of miR‑223 expression in PC9/ER and PC9/CD133+ cells was detected, and the reverse correlation of miR-233 and insulin-like growth factor 1 receptor (IGF1R) in these cells was also revealed. Next, levels of IGF1R mRNA and p-Akt were significantly reduced in miR‑223 stably transfected PC9/ER and PC9/CD133+ cells. However, the sensitivity of PC9/ER and PC9/CD133+ cells to erlotinib was partially restored, after overexpression of miR‑223 in those cells. Similar results were also observed in vivo. Furthermore, miR‑223-mediated inhibition of the IGF1R/PI3K/Akt signaling pathway may have been reversed by the agonist of IGF1R in miR‑223 transfected cells. Our findings indicated that downregulation of miR‑223, which can induce activation of the IGF1R/phosphatidylinositol 3-kinase (PI3K)/Akt pathway in PC9/ER and PC9/CD133+ cells, may be responsible for the resistance of PC9/ER and PC9/CD133+ cells to erlotinib, suggesting that miR‑223 is a potential therapeutic target for overcoming EGFR-TKIs resistance. PMID:26936292

  2. Radium-223 in the Treatment of Osteoblastic Metastases: A Critical Clinical Review

    The element radium (Ra) was discovered by the Curies in 1898 and within a decade was in broad scientific testing for the management of several forms of cancer. The compound was known to give rise to a series of both high-energy particulate and penetrating γ-emissions. The latter found an important role in early 20th century brachytherapy applications, but the short-range α-particles seemed much less useful. Although highly cytotoxic when released within a few cell diameters of critical cell nuclei, the dense double-strand break damage was poorly repaired, and concerns regarding treatment-related toxicities and secondary malignancies halted clinical development. Moreover, the most common isotope of Ra has an exceptionally long half-life (>1600 years for 226Ra) that proved daunting when aiming for a systemic cancer therapy. Fortunately, other radium isotopes have more convenient half-lives while still producing cytotoxic α particles. Radium-223 dichloride has a half-life of 11.4 days, and this isotope was identified as an excellent candidate for radionuclide therapy of cancers metastatic to bone. The calcium-mimetic chemical properties of the radium allowed intravenous infusion with rapid uptake to sites of new bone formation. The highly efficient bone localization suggested a potential therapeutic role for osteoblastic bone metastases, and a series of phase 1, 2, and 3 clinical trials was undertaken to explore this possibility. This series of clinical explorations culminated in the ALSYMPCA trial, an international, placebo-controlled, phase 3 study that accrued 921 symptomatic men with bone-metastatic, castrate-resistant prostate cancer. Results of this trial demonstrated a prolongation of overall survival, and regulatory agencies around the world have now approved this product as a treatment for advanced prostate cancer

  3. Radium-223 in the Treatment of Osteoblastic Metastases: A Critical Clinical Review

    Humm, John L. [Department of Medical Physics, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Sartor, Oliver [Departments of Medicine and Urology, Tulane Cancer Center, Tulane University School of Medicine, New Orleans, Louisiana (United States); Parker, Chris [Department of Clinical Oncology, Institute of Cancer Research, Sutton (United Kingdom); Bruland, Oyvind S. [Department of Oncology, Norwegian Radium Hospital and Institute for Clinical Medicine, University of Oslo, Oslo (Norway); Macklis, Roger, E-mail: rmmacklis@gmail.com [Department of Radiation Oncology, University Hospitals of Cleveland and Case Western Reserve University, Cleveland, Ohio (United States)

    2015-04-01

    The element radium (Ra) was discovered by the Curies in 1898 and within a decade was in broad scientific testing for the management of several forms of cancer. The compound was known to give rise to a series of both high-energy particulate and penetrating γ-emissions. The latter found an important role in early 20th century brachytherapy applications, but the short-range α-particles seemed much less useful. Although highly cytotoxic when released within a few cell diameters of critical cell nuclei, the dense double-strand break damage was poorly repaired, and concerns regarding treatment-related toxicities and secondary malignancies halted clinical development. Moreover, the most common isotope of Ra has an exceptionally long half-life (>1600 years for {sup 226}Ra) that proved daunting when aiming for a systemic cancer therapy. Fortunately, other radium isotopes have more convenient half-lives while still producing cytotoxic α particles. Radium-223 dichloride has a half-life of 11.4 days, and this isotope was identified as an excellent candidate for radionuclide therapy of cancers metastatic to bone. The calcium-mimetic chemical properties of the radium allowed intravenous infusion with rapid uptake to sites of new bone formation. The highly efficient bone localization suggested a potential therapeutic role for osteoblastic bone metastases, and a series of phase 1, 2, and 3 clinical trials was undertaken to explore this possibility. This series of clinical explorations culminated in the ALSYMPCA trial, an international, placebo-controlled, phase 3 study that accrued 921 symptomatic men with bone-metastatic, castrate-resistant prostate cancer. Results of this trial demonstrated a prolongation of overall survival, and regulatory agencies around the world have now approved this product as a treatment for advanced prostate cancer.

  4. Mid-IR Photometry and Near-IR Spectroscopy of the FU Ori Protostar V2775 Ori (HOPS 223)

    Fischer, William J.; Safron, Emily J.; Megeath, S. Thomas; Terebey, Susan; Soto, Edith; Wilson, Thomas L.; Adams, Joseph D.

    2016-02-01

    On 2015 November 20.39, we obtained mid-IR photometry of V2775 Ori (HOPS 223) with the FORCAST instrument aboard SOFIA. This is a low-mass embedded young stellar object that was reported to have undergone a luminosity outburst by Caratti o Garatti et al. (2011, A & A, 526, L1). Fischer et al. (2012, ApJ, 756, 99) dated the beginning of the outburst to between 2005 April and 2007 March and discussed the similarity of its near-IR spectrum to that of FU Orionis.

  5. Superconductivity in 2-2-3 Y2Ba2Cu3O(sub 8+ delta)

    Joshi, H. H.; Baldha, G. J.; Jotania, R. B.; Joshi, S. M.; Mohan, H.; Pandya, P. B.; Pandya, H. N.; Kulkarni, R. G.

    1990-01-01

    Researchers synthesized a new high T(sub c) 2-2-3 superconductor (Y2Ba2Cu3O8+delta) by a special preparation technique and characterized it by ac-susceptibility measurements. Diamagnetism and Meissner effect sets in at low fields and superconducting transition onsets at 90 K. The systematic investigation of the real and imaginary components of ac-susceptibility as a function of temperature and applied ac magnetic field reveals that the magnetic behavior is that of a granular type superconductor.

  6. A late jet rebrightening revealed from multi-wavelength monitoring of the black hole candidate XTE J1752-223

    Russell, D.M.; Curran, P.A.; Muñoz-Darias, T.; Lewis, F.; Motta, S.; Stiele, H.; Belloni, T.; Miller-Jones, J. C. A.; Jonker, P.G.; O'Brien, K; Homan, J.; P. Casella; P Gandhi; Soleri, P.; Markoff, S.

    2011-01-01

    We present optical monitoring of the black hole candidate XTE J1752-223 during its 2009 - 2010 outburst and decay to quiescence. The optical light curve can be described by an exponential decay followed by a plateau, then a more rapid fade towards quiescence. The plateau appears to be due to an extra component of optical emission that brightens and then fades over ~ 40 days. We show evidence for the origin of this optical 'flare' to be the synchrotron jet during the decaying hard state, and w...

  7. Nance-Horan syndrome: localization within the region Xp21.1-Xp22.3 by linkage analysis.

    Stambolian, D; Lewis, R. A.; Buetow, K; Bond, A; Nussbaum, R.

    1990-01-01

    Nance-Horan Syndrome (NHS) or X-linked cataract-dental syndrome (MIM 302350) is a disease of unknown pathogenesis characterized by congenital cataracts and dental anomalies. We performed linkage analysis in three kindreds with NHS by using six RFLP markers between Xp11.3 and Xp22.3. Close linkage was found between NHS and polymorphic loci DXS43 (theta = 0 with lod score 2.89), DXS41 (theta = 0 with lod score 3.44), and DXS67 (theta = 0 with lod score 2.74), defined by probes pD2, p99-6, and p...

  8. Leptin receptor polymorphism Gln223Arg (rs1137101) in oral squamous cell carcinoma and potentially malignant oral lesions

    Domingos, Patrícia Luciana Batista; Farias, Lucyana Conceição; Pereira, Camila Santos; das Graças Pena, Geórgia; Reis, Tatiana Carvalho; Silva, Rosângela Ramos Veloso; Fraga, Carlos Alberto de Carvalho; de Souza, Marcela Gonçalves; Soares, Mariana Batista; Jones, Kimberly Marie; Menezes, Elytania Veiga; Nobre, Sérgio Avelino Mota; Rodrigues Neto, João Felício; de Paula, Alfredo Maurício Batista; Velásquez-Meléndez, Jorge Gustavo

    2014-01-01

    The purpose of this study was to assess the LEPR gene Gln223Arg polymorphism (rs1137101) in oral squamous cell carcinoma (OSCC) and in potentially malignant oral lesions (PMOL) in comparison to normal oral mucosa in a Brazilian population. Smokers (n = 89) were selected from a representative sample of 471 individuals from the general population of Montes Claros, Brazil. Participants were age and gender matched to patients with OSCC (n = 25) and oral epithelial dysplasia (n = 25). We investiga...

  9. Pain, PSA flare, and bone scan response in a patient with metastatic castration-resistant prostate cancer treated with radium-223, a case report

    Radium-223 has been shown to improve overall survival in men with metastatic castration-resistant prostate cancer with symptomatic bone metastases. The bone scan response to radium-223 has only been described in one single center trial of 14 patients, none of whom achieved the outstanding bone scan response presented in the current case. In this case report, we describe a 75 year-old white man with extensively pre-treated metastatic castration-resistant prostate cancer and symptomatic bone metastases who experienced a flare in pain and prostate-specific antigen, followed by dramatic clinical (pain), biochemical (prostate-specific antigen), and imaging (bone scan) response. The flare phenomena and bone scan response we observed have not previously been described with radium-223. This case suggests that the degree and duration of bone scan response may be predictive of overall survival benefit

  10. Development of separation technology for the removal of radium-223 from decayed thorium-227 in drug formulations. Material screening and method development.

    Frenvik, Janne Olsen; Kristensen, Solveig; Ryan, Olav B

    2016-08-01

    Targeted thorium conjugates are currently being investigated as a new class of alpha-radiopharmaceuticals. The natural decay of thorium-227 ((227)Th) results in the ingrowth of radium-223 ((223)Ra). Consideration must, therefore, be given to define acceptable limits of (223)Ra in the drug product at the time of dose administration. By effective sequestration of (223)Ra, we aim to improve the radiochemical purity and extend the effective user window of drug products containing (227)Th. (223)Ra is the first progeny of (227)Th and the only one with a long half-life (days). We have, therefore, focused on the removal of this specific species since the progenies of (223)Ra will have a very limited lifetime in the formulation once (223)Ra is removed. In this study, we investigated a multitude of materials for their ability to reduce the (223)Ra level by: (1) passive diffusion or (2) by cartridge filtration on gravity columns. In addition, we probe the compatibility of these materials in the presence of antibody trastuzumab to assess the level of protein binding and estimate the quenching of radiolysis by binding of radionuclides. A screening matrix of organic and inorganic materials was established, i.e. strontium and calcium alginate gel beads, distearoyl phosphatidylglycerol (DSPG) liposomes, ceramic hydroxyapatite, Zeolite UOP type 4A and cation exchange resins AG50W-X8 and SOURCE 30S. First, passive diffusional uptake of (223)Ra by suspended materials present in the formulation was measured as a decrease in sample radioactivity after separation. Second, selected materials were packed on gravity columns in order to evaluate the efficiency of column separation versus diffusional adsorption. The retention of (223)Ra and (227)Th were characterized by measuring the radioactivity in the eluate and on the columns. Finally, the compatibility between trastuzumab, as a selected model antibody, and suspensions of the binding materials was analyzed during storage of the drug

  11. Reflection Spectroscopy of the Black Hole Binary XTE J1752-223 in the Bright Hard State

    Garcia, Javier; Steiner, James F.; Grinberg, Victoria; McClintock, Jeffrey E.; Dauser, Thomas; Remillard, Ronald A.

    2016-04-01

    During its rise to maximum in 2009, XTE J1752-223 stalled for a full month in the bright hard state at about 30% of its peak (Eddington) luminosity. Along this extended period, 60 RXTE pointed observations showed the luminosity and hardness ratio of the source to be extraordinarily stable, resulting in a unique data set of exceptional quality. We combined all these 300 ks of RXTE data into a single PCA (3-45 keV) spectrum with 82 million counts and a single HEXTE spectrum (20-250 keV) with 10.4 million counts. Using our calibration tools PCACORR and HEXBCORR, we greatly enhanced the sensitivity of the detectors to faint spectral features, such as the Fe line and edge. Fitting the PCA+HEXTE spectrum using an advanced version of our reflection code, which includes a physical model of Comptonization, we constrained: the spin of the black hole (or alternatively the inner radius of the accretion disk); the inclination of the system; the ionization state and Fe abundance of the disk's atmosphere; and the temperature and optical depth of the corona. We compare these results with similar ones we reported earlier for GX 339-4 in the bright hard state. XTE J1752-223 and GX 339-4 are the first two of 29 black hole binaries we propose to study using recalibrated RXTE archival data and our reflection models.

  12. The Gln223Arg polymorphism of the leptin receptor in Pima Indians: influence on energy expenditure, physical activity and lipid metabolism

    Stefan, N; Vozarova, B; Del Parigi, A;

    2002-01-01

    Leptin regulates body weight by its receptor-mediated anorectic, thermogenic and antisteatotic effects. Recently, lower leptin binding to the soluble form of the leptin receptor (LEPR) was shown in carriers of the Arg223-encoding allele of the Gln223Arg polymorphism of the LEPR. To investigate wh...... who had undergone percutaneous fat biopsies from the periumbilical region (n=184). Genotype was not associated with percent body fat (P>0.39), but was associated with 24 h EE, PAL and mean subcutaneous abdominal adipocyte size (SAAS all P...

  13. MiR-223-3p as a Novel MicroRNA Regulator of Expression of Voltage-Gated K+ Channel Kv4.2 in Acute Myocardial Infarction

    Xue Liu

    2016-06-01

    Full Text Available Background/Aims: Acute myocardial infarction (AMI is a devastating cardiovascular disease with a high rate of morbidity and mortality, partly due to enhanced arrhythmogenicity. MicroRNAs (miRNAs have been shown to participate in the regulation of cardiac ion channels and the associated arrhythmias. The purpose of this study was to test our hypothesis that miR-223-3p contributes to the electrical disorders in AMI via modulating KCND2, the gene encoding voltage-gated channel Kv4.2 that carries transient outward K+ current Ito. Methods: AMI model was established in male Sprague-Dawley (SD rats by left anterior descending artery (LAD ligation. Evans blue and TTC staining was used to measure infarct area. Ito was recorded in isolated ventricular cardiomyocytes or cultured neonatal rat ventricular cells (NRVCs by whole-cell patch-clamp techniques. Western blot analysis was employed to detect the protein level of Kv4.2 and real-time RT-PCR to determine the transcript level of miR-223-3p. Luciferase assay was used to examine the interaction between miR-223-3p and KCND2 in cultured NRVCs. Results: Expression of miR-223-3p was remarkably upregulated in AMI relative to sham control rats. On the contrary, the protein level of Kv4.2 and Ito density were significantly decreased in AMI. Consistently, transfection of miR-223-3p mimic markedly reduced Kv4.2 protein level and Ito current in cultured NRVCs. Co-transfection of AMO-223-3p (an antisense inhibitor of miR-223-3p reversed the repressive effect of miR-223-3p. Luciferase assay showed that miR-223-3p, but not the negative control, substantially suppressed the luciferase activity, confirming the direct binding of miR-223-3p to the seed site within the KCND2 sequence. Finally, direct intramuscular injection of AMO-223-3p into the ischemic myocardium to knockdown endogenous miR-223-3p decreased the propensity of ischemic arrhythmias. Conclusions: Upregulation of miR-223-3p in AMI repressed the expression of

  14. Radium-223-Dichloride in Castration Resistant Metastatic Prostate Cancer—Preliminary Results of the Response Evaluation Using F-18-Fluoride PET/CT

    Kalevi Kairemo

    2015-10-01

    Full Text Available The purpose of this study was to evaluate the outcome after Radium-223-dichloride (223RaCl2 treatment of patients with skeletal metastases of castration resistant prostate cancer using whole-body 18F-Fluoride PET/CT. Sodium 18F-fluoride [18F]-NaF PET/CT was performed prior the treatment of 223RaCl2, after the first cycle and after the sixth cycle. The skeletal metastases were analyzed quantitatively using modified PET response evaluation PERCIST criteria. The patients were also analyzed for S-PSA. All ten patients responded in [18F]-NaF scans after 6 cycles, but interim analysis after the 1st cycle did not give additional information about the outcome. The S-PSA decrease correlated with [18F]-NaF response, only 1 patient demonstrated progressive disease, i.e., >25% increase in S-PSA values during 223RaCl2. Our results (although preliminary suggest that 18F-Fluoride PET/CT is useful in the follow-up of castration resistant prostate cancer with skeletal metastases.

  15. Perspectives of using the 223-nm wavelength of the KrCl excimer laser for refractive surgery and for the treatment of some eye diseases

    Bagayev, Sergei N.; Chernikh, Valery V.; Razhev, Alexander M.; Zhupikov, Andrey A.

    2000-06-01

    The new surgical UV ophthalmic laser system Medilex based on the KrCl (223 nm) excimer laser for refractive surgery was created. The comparative analysis of using the UV ophthalmic laser systems Medilex based on the ArF (193 nm) and the KrCl (223 nm) excimer lasers for the correction of refractive errors was performed. The system with the radiation wavelength of 223 nanometer of the KrCl excimer laser for refractive surgery was shown to have several medical and technical advantages over the system with the traditionally used radiation wavelength of 193 nanometer of the ArF excimer laser. In addition the use of the wavelength of 223 nanometer extends functional features of the system, allowing to make not only standard for this type systems surgical and therapeutic procedures but also to treat such ocular diseases as the glaucoma and herpetic keratities. For the UV ophthalmic laser systems Medilex three variations of the beam delivery system including special rotating masks and different beam homogenize systems were developed. All created beam delivery systems are able to make the correction of myopia, hyperopia, astigmatism and myopic or hyperopic astigmatism and may be used for therapeutic procedures. The results of the initial treatments of refractive error corrections using the UV ophthalmic laser systems Medilex for both photorefractive keratectomy (PRK) and LASIK procedures are presented.

  16. Efficient program for decoding the /255, 223/ Reed-Solomon code over GF/2 to the 8th/ with both errors and erasures, using transform decoding

    Miller, R. L.; Truong, T. K.; Reed, I. S.

    1980-07-01

    The paper deals with a method developed for decoding a (255, 223) Reed-Solomon code over GF(2 to the 8th) with both errors and erasures. The matrix of decoding times for correcting errors and erasures of the code using a simplified decoder is presented. It is shown that the algorithm proposed is faster by a factor of from three to seven.

  17. Changes in skeletal tumor activity on {sup 18}F-choline PET/CT in patients receiving {sup 223}radium radionuclide therapy for metastatic prostate cancer

    Miyazaki, Kyle S. [Oncology Research Dept. and Hamamatsu/Queen' s PET Imaging Center, The Queen' s Medical Center, Honolulu (United States); Kang, Yu; Kwee, Sandi A. [Dept. of Medical Physics, School of Allied Health Sciences, University of Nevada Las Vegas, Las Vegas (United States)

    2015-06-15

    Radium-223 dichloride is an alpha-emitting radiopharmaceutical shown to prolong survival in patients with castrate-resistant prostate cancer (CRPC) and symptomatic skeletal metastases. This report describes in two patients the acute changes in bone metastatic activity detected by F-18 choline PET/CT imaging midway during treatment with radium-223 dichloride. In addition to visual and standardized uptake value analysis, changes in the whole-body tumor burden were quantified by measuring the difference in net metabolically active tumor volume (MATV) and total lesion activity (TLA) between pre- and mid-treatment PET scans. After the third dose of radium-223 dichloride, near-total disappearance of abnormal skeletal activity was observed in one case (net MATV change from 260.7 to 0.8 cc; net TLA change from 510.7 to 2.1), while a heterogeneous tumor response was observed in the other (net MATV change from 272.2 to 241.3 cc; net TLA change from 987.1 to 779.4). Corresponding normalization and persistent elevation in serum alkaline phosphatase levels were observed in these cases, respectively. Further research is needed to determine the predictive value of serial F-18 choline PET/CT imaging in patients receiving radium-223 dichloride for CRPC.

  18. miRNA-197 and miRNA-223 Predict Cardiovascular Death in a Cohort of Patients with Symptomatic Coronary Artery Disease.

    Christian Schulte

    Full Text Available Circulating microRNAs (miRNAs have been described as potential diagnostic biomarkers in cardiovascular disease and in particular, coronary artery disease (CAD. Few studies were undertaken to perform analyses with regard to risk stratification of future cardiovascular events. miR-126, miR-197 and miR-223 are involved in endovascular inflammation and platelet activation and have been described as biomarkers in the diagnosis of CAD. They were identified in a prospective study in relation to future myocardial infarction.The aim of our study was to further evaluate the prognostic value of these miRNAs in a large prospective cohort of patients with documented CAD.Levels of miR-126, miR-197 and miR-223 were evaluated in serum samples of 873 CAD patients with respect to the endpoint cardiovascular death. miRNA quantification was performed using real time polymerase chain reaction (RT-qPCR.The median follow-up period was 4 years (IQR 2.78-5.04. The median age of all patients was 64 years (IQR 57-69 with 80.2% males. 38.9% of the patients presented with acute coronary syndrome (ACS, 61.1% were diagnosed with stable angina pectoris (SAP. Elevated levels of miRNA-197 and miRNA-223 reliably predicted future cardiovascular death in the overall group (miRNA-197: hazard ratio (HR 1.77 per one standard deviation (SD increase (95% confidence interval (CI 1.20; 2.60, p = 0.004, C-index 0.78; miRNA-223: HR 2.23 per one SD increase (1.20; 4.14, p = 0.011, C-index 0.80. In ACS patients the prognostic power of both miRNAs was even higher (miRNA-197: HR 2.24 per one SD increase (1.25; 4.01, p = 0.006, C-index 0.89; miRA-223: HR 4.94 per one SD increase (1.42; 17.20, p = 0.012, C-index 0.89.Serum-derived circulating miRNA-197 and miRNA-223 were identified as predictors for cardiovascular death in a large patient cohort with CAD. These results reinforce the assumption that circulating miRNAs are promising biomarkers with prognostic value with respect to future

  19. An N-terminally truncated envelope protein encoded by a human endogenous retrovirus W locus on chromosome Xq22.3

    Roebke Christina

    2010-08-01

    Full Text Available Abstract Background We previously showed that the envelope (env sequence of a human endogenous retrovirus (HERV-W locus on chromosome Xq22.3 is transcribed in human peripheral blood mononuclear cells. The env open reading frame (ORF of this locus is interrupted by a premature stop at codon 39, but otherwise harbors a long ORF for an N-terminally truncated 475 amino acid Env protein, starting at an in-frame ATG at codon 68. We set out to characterize the protein encoded by that ORF. Results Transient expression of the 475 amino acid Xq22.3 HERV-W env ORF produced an N-terminally truncated HERV-W Env protein, as detected by the monoclonal anti-HERV-W Env antibodies 6A2B2 and 13H5A5. Remarkably, reversion of the stop at codon 39 in Xq22.3 HERV-W env reconstituted a full-length HERV-W Xq22.3 Env protein. Similar to the full-length HERV-W Env protein Syncytin-1, reconstituted full-length Xq22.3 HERV-W Env is glycosylated, forms oligomers, and is expressed at the cell surface. In contrast, Xq22.3 HERV-W Env is unglycosylated, does not form oligomers, and is located intracellularly, probably due to lack of a signal peptide. Finally, we reconfirm by immunohistochemistry that monoclonal antibody 6A2B2 detects an antigen expressed in placenta and multiple sclerosis brain lesions. Conclusions A partially defective HERV-W env gene located on chromosome Xq22.3, which we propose to designate ERVWE2, has retained coding capacity and can produce ex vivo an N-terminally truncated Env protein, named N-Trenv. Detection of an antigen by 6A2B2 in placenta and multiple sclerosis lesions opens the possibility that N-Trenv could be expressed in vivo. More generally, our findings are compatible with the idea that defective HERV elements may be capable of producing incomplete HERV proteins that, speculatively, may exert functions in human physiology or pathology.

  20. Stathmin1 plays oncogenic role and is a target of microRNA-223 in gastric cancer.

    Wei Kang

    Full Text Available Stathmin1 (STMN1 is a candidate oncoprotein and prognosis marker in several kinds of cancers. This study was aimed to analyze its expression and biological functions in gastric cancer. The expression of STMN1 was evaluated by qRT-PCR, western blot and immunohistochemistry. The biological function of STMN1 was determined by MTT proliferation assays, monolayer colony formation and cell invasion assays using small interference RNA technique in gastric cancer cell lines. We also explored the regulation of STMN1 expression by microRNA-223. STMN1 was upregulated in gastric cancer cell lines and primary gastric adenocarcinomas. STMN1-positive tumors were more likely to be found in old age group and associated with p53 nuclear expression. In diffuse type gastric adenocarcinomas, STMN1 expression was correlated with age (p = 0.043, T stage (p = 0.004 and lymph node metastasis (p = 0.046. Expression of STMN1 in diffuse type gastric adenocarcinoma was associated with poor disease specific survival by univariate analysis (p = 0.01. STMN1 knockdown in AGS and MKN7 cell lines suppressed proliferation (p<0.001, reduced monolayer colony formation (p<0.001, inhibited cell invasion and migration ability (p<0.001 and induced G1 phase arrest. siSTMN1 could also suppress cell growth in vivo (p<0. 01. We finally confirmed that STMN1 is a putative downstream target of miR-223 in gastric cancer. Our findings supported an oncogenic role of STMN1 in gastric cancer. STMN1 might serve as a prognostic marker and a potential therapeutic target for gastric cancer.

  1. SU-E-T-588: Optimization of Imaging Following 223Ra Administration in Targeted Alpha-Emitting Radionuclide Therapy of Bone Metastases

    Benabdallah, N; Bernardini, M [Hopital Europeen George Pompidou, Paris, Ile de France (France); Desbree, A [Institut de Radioprotection et de Surete Nucleaire, Fontenay-aux-roses, Ile-de-France (France); Labriolle-Vaylet, C de [Hopital Trousseau, Paris, Ile de France (France); Franck, D [Institut de Radioprotection et de Suretu Nucleaire, Fontenay Aux Roses, Ile de France (France)

    2015-06-15

    Purpose: With a growing demand of alpha-emitting radiopharmaceuticals, especially Xofigo ({sup 223}RaCl{sub 2}) which is used in the treatment of metastatic bone disease, the optimization of dosimetry becomes necessary. Indeed, in Europe, as stated on the council directive 2013/59/euratom, exposures of target volumes for radiotherapeutic purposes shall be individually planned taking into account that doses to non-target volumes and tissues shall be as low as reasonably achievable. To that aim, the possibility of imaging {sup 223}Ra was first investigated. Methods: The experiments were conducted at the Hopital Europeen Georges Pompidou with an Infinia Hawkeye 4 gamma camera, equipped with a medium-energy collimator. Imaging parameters, such as sensibility, spatial resolution and energy spectrum, were determined using several physical phantoms with a source of 6 MBq of {sup 223}Ra. Bone metastases were modeled with a NEMA Body Phantom to investigate image degradation based on the concentration of {sup 223}Ra. Results: The acquired energy spectrum allowed to visualize several photon peaks: at 85, 154 and 270 keV. Camera sensitivity measured from the phantom study was 102.3 cps/MBq for the 85 keV ± 20 %, 89.9 cps/MBq for the 154 ± 20 % window and 65.4 cps/MBq for the 270 ± 10 % window. The spatial resolution (full-width at half-maximum) was respectively 1.7, 1.9 and 1.8 cm for the three energy windows. SPECT/CT images of NEMA Body Phantom without and with attenuation have permitted to determine the best reconstruction parameters. Conclusion: This study has demonstrated that it is possible to obtain clinically relevant information from images of {sup 223}Ra. All these results will be valuable to analyze biodistribution imaging of the radiopharmaceutical in the patient body and go further in the reconstruction of patient images in order to personalize the dosimetry.

  2. SU-E-T-588: Optimization of Imaging Following 223Ra Administration in Targeted Alpha-Emitting Radionuclide Therapy of Bone Metastases

    Purpose: With a growing demand of alpha-emitting radiopharmaceuticals, especially Xofigo (223RaCl2) which is used in the treatment of metastatic bone disease, the optimization of dosimetry becomes necessary. Indeed, in Europe, as stated on the council directive 2013/59/euratom, exposures of target volumes for radiotherapeutic purposes shall be individually planned taking into account that doses to non-target volumes and tissues shall be as low as reasonably achievable. To that aim, the possibility of imaging 223Ra was first investigated. Methods: The experiments were conducted at the Hopital Europeen Georges Pompidou with an Infinia Hawkeye 4 gamma camera, equipped with a medium-energy collimator. Imaging parameters, such as sensibility, spatial resolution and energy spectrum, were determined using several physical phantoms with a source of 6 MBq of 223Ra. Bone metastases were modeled with a NEMA Body Phantom to investigate image degradation based on the concentration of 223Ra. Results: The acquired energy spectrum allowed to visualize several photon peaks: at 85, 154 and 270 keV. Camera sensitivity measured from the phantom study was 102.3 cps/MBq for the 85 keV ± 20 %, 89.9 cps/MBq for the 154 ± 20 % window and 65.4 cps/MBq for the 270 ± 10 % window. The spatial resolution (full-width at half-maximum) was respectively 1.7, 1.9 and 1.8 cm for the three energy windows. SPECT/CT images of NEMA Body Phantom without and with attenuation have permitted to determine the best reconstruction parameters. Conclusion: This study has demonstrated that it is possible to obtain clinically relevant information from images of 223Ra. All these results will be valuable to analyze biodistribution imaging of the radiopharmaceutical in the patient body and go further in the reconstruction of patient images in order to personalize the dosimetry

  3. RADIATION SAFETY CONSIDERATIONS FOR THE USE OF 223RaCl2 DE IN MEN WITH CASTRATION-RESISTANT PROSTATE CANCER

    Dauer, Lawrence T.; Williamson, Matthew J.; Humm, John; O’Donoghue, Joseph; Ghani, Rashid; Awadallah, Robert; Carrasquillo, Jorge; Pandit-Taskar, Neeta; Aksnes, Anne-Kirsti; Biggin, Colin; Reinton, Vigdis; Morris, Michael; St Germain, Jean

    2016-01-01

    The majority of patients with late stage castration-resistant prostate cancer (CRPC) develop bone metastases that often result in significant bone pain. Therapeutic palliation strategies can delay or prevent skeletal complications and may prolong survival. An alpha-particle based therapy, radium-223 dichloride (223RaCl2), has been developed that delivers highly localized effects in target areas and likely reduces toxicity to adjacent healthy tissue, particularly bone marrow. Radiation safety aspects were evaluated for a single comprehensive cancer center clinical phase 1, open-label, single ascending-dose study for three cohorts at 50, 100, or 200 kBq kg−1 body weight. Ten patients received administrations, and six patients completed the study with 1 y follow-up. Dose rates from patients administered 223Ra dichloride were typically less than 2 μSv h−1 MBq−1 on contact and averaged 0.02 μSv h−1 MBq−1 at 1 m immediately following administration. Removal was primarily by fecal excretion, and whole body effective half-lives were highly dependent upon fecal compartment transfer, ranging from 2.5–11.4 d. Radium-223 is safe and straightforward to administer using conventional nuclear medicine equipment. For this clinical study, few radiation protection limitations were recommended post-therapy based on facility evaluations. Specific precautions are dependent on local regulatory authority guidance. Subsequent studies have demonstrated significantly improved overall survival and very low toxicity, suggesting that 223Ra may provide a new standard of care for patients with CRPC and bone metastases. PMID:24562070

  4. A polymorphism in the leptin receptor gene at position 223 is associated with growth hormone replacement therapy responsiveness in idiopathic short stature and growth hormone deficiency patients.

    Su, Pen-Hua; Yang, Shun-Fa; Yu, Ju-Shan; Chen, Suh-Jen; Chen, Jia-Yuh

    2012-12-01

    We hypothesized that responses to growth hormone (GH) therapy by idiopathic short stature (ISS) and growth hormone deficiency (GHD) patients were associated with single nucleotide polymorphisms (SNPs) in the leptin (LEP) and leptin receptor (LEPR) genes. We retrospectively enrolled ISS (n = 32) and GHD (n = 38) patients and forty healthy age-and gender-matched children. They were genotyped for the LEP promoter at nt.-2548, and LEPR K109R and LEPR Q223R polymorphisms. Clinical and laboratory variables were determined before and after 2 years of GH treatment. ISS patients with G/A or A/A genotypes of the LEPR Q223R SNP had a significantly higher height velocity (cm/y) than ISS patients with the G/G genotype at 2 years after GH treatment. For GHD patients, G/A or A/A genotype of the LEPR K109R SNP was associated with higher body weight, higher BMI, and higher weight velocity than patients with the G/G genotype before GH treatment, but not after GH treatment. G/A or A/A genotype of the LEPR Q223R SNP was associated with a significantly higher body weight, higher height velocity before treatment, but not after GH treatment. G/A or A/A genotype of the LEPR Q223R SNP was associated with a significantly higher weight velocity before treatment, but a significantly lower weight velocity was found at 2 years after GH treatment. These results suggest LEPR Q223R SNP (rs1137101) is associated with outcomes of GH replacement therapy in ISS and GHD patients. PMID:23009903

  5. Reflections on the therapeutic use of 223RaCl2 for bone metastases resulting from prostate cancer resistant to castration

    In January 2014 the Comision Federal para la Proteccion contra Riesgos Sanitarios of the Ministry of Health in Mexico, authorize the use of 223RaCl2 as the first radiopharmaceutical emitter α for therapeutic purposes in cases of bone metastases resulting from prostate cancer resistant to castration. The paper analyzes the main variables that affect the metrological traceability using activity meters to evaluate the gamma activity of 223RaCl2 in hospitals, because it has a chain of complex decay with alpha, beta and gamma emitters, so was important to verify if a gamma activity measurement for a multiple emitter is reliable to determine the total alpha absorbed dose to bone in a patient. (Author)

  6. RNA Interference of Endochitinases in the Sugarcane Endophyte Trichoderma virens 223 Reduces Its Fitness as a Biocontrol Agent of Pineapple Disease

    Aline S Romão-Dumaresq; Welington Luiz Araújo; Nicholas J Talbot; Thornton, Christopher R.

    2012-01-01

    The sugarcane root endophyte Trichoderma virens 223 holds enormous potential as a sustainable alternative to chemical pesticides in the control of sugarcane diseases. Its efficacy as a biocontrol agent is thought to be associated with its production of chitinase enzymes, including N-acetyl-ß-D-glucosaminidases, chitobiosidases and endochitinases. We used targeted gene deletion and RNA-dependent gene silencing strategies to disrupt N-acetyl-ß-D-glucosaminidase and endochitinase activities of t...

  7. Autosomal dominant congenital cataract in a Libyan Jewish family: cosegregation with a reciprocal chromosomal translocation [t(3;5)(p22.3; p15.1)

    Zafer, Emre; Meck, Jeanne; Gerrad, Liora; Pras, Elon; Frydman, Moshe; Reish, Orit; Avni, Isaac; Pras, Eran

    2008-01-01

    Purpose To describe a Jewish family of Libyan ancestry in which autosomal dominant congenital cataract segregates with an apparently balanced reciprocal chromosomal translocation. Methods Detailed family history and clinical data were recorded. Cytogenetic studies were performed on 13 family members. Results Embryonal cataracts cosegregated through three generations with a balanced chromosomal translocation [t(3;5)(p22.3; p15.1)] while the unbalanced translocation product, 46,XY,-5,+der(5)t(3...

  8. Relationships between plasma leptin levels, leptin G2548A, leptin receptor Gln223Arg polymorphisms and gestational diabetes mellitus in Chinese population

    Mei Yang; Songxu Peng; Wei Li; Zhihua Wan; Linlin Fan; Yukai Du

    2016-01-01

    The purposes of this study were to examine concentrations of leptin and biochemical parameters in gestational diabetes mellitus (GDM) patients and normal glucose tolerance (NGT) individuals, and also to explore the links of leptin (LEP) G2548A and leptin receptor (LEPR) Gln223Arg polymorphisms with leptin levels and GDM risk among Chinese. Our study included 357 GDM and 355 NGT individuals who were at 24~30 gestational weeks. Plasma leptin and insulin levels were analyzed by ELISA. Gene polym...

  9. Plasmid stability in immobilized and free recombinant Escherichia coli JM105(pKK223-200): importance of oxygen diffusion, growth rate, and plasmid copy number.

    de Taxis du Poët, P; Arcand, Y; Bernier, R.; Barbotin, J N; Thomas, D.

    1987-01-01

    Stability of the plasmid pKK223-200 in Escherichia coli JM105 was studied for both free and immobilized cells during continuous culture. The relationship between plasmid copy number, xylanase activity, which was coded for by the plasmid, and growth rate and culture conditions involved complex interactions which determined the plasmid stability. Generally, the plasmid stability was enhanced in cultured immobilized cells compared with free-cell cultures. This stability was associated with modif...

  10. Association of LEP G2548A and LEPR Q223R polymorphisms with cancer susceptibility: evidence from a meta-analysis.

    Jing He

    Full Text Available BACKGROUND: Numerous epidemiological studies have examined associations of genetic variations in LEP (G2548A, -2548 nucleotide upstream of the ATG start site and LEPR (Q223R, nonsynonymous SNP in exon 6 with cancer susceptibility; however, the findings are inconsistent. Therefore, we performed a meta-analysis to comprehensively evaluate such associations. METHODS: We searched published literature from MEDLINE, EMBASE, Web of Science and CBM for eligible publications. We also assessed genotype-based mRNA expression data from HapMap for rs7799039 (G2548A and rs1137101 (Q223R in normal cell lines derived from 270 subjects with different ethnicities. RESULTS: The final analysis included 16 published studies of 6569 cases and 8405 controls for the LEP G2548A and 19 studies of 7504 cases and 9581 controls for the LEPR Q223R. Overall, LEP G2548A was statistically significantly associated with an increased risk of overall cancer (AA vs. GG: OR=1.27, 95% CI=1.05-1.54; recessive model: OR=1.19, 95% CI=1.00-1.41. Further stratifications by cancer type showed an increased risk for prostate cancer (recessive model: OR=1.26, 95% CI=1.05-1.51 but not for other cancers. For LEPR Q223R, no statistical evidence for an association with risk of cancer was found for all; however, further stratification by ethnicity showed an increased risk for Africans but not for other ethnicities. No significantly differences in LEP and LEPR mRNA expression were found among genotypes or by ethnicity. CONCLUSIONS: Despite some limitations, this meta-analysis found some statistical evidence for an association between the LEP 2548AA genotype and overall risk of cancer, particularly for prostate cancer, but given this variant did not have an effect on mRNA expression, this association warrants additional validation in large and well-designed studies.