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Sample records for astatine 223

  1. Radiochemistry of astatine

    Energy Technology Data Exchange (ETDEWEB)

    Ruth, T J; Dombsky, M; D' Auria, J M; Ward, T E

    1988-01-01

    This monograph is a review of the literature through 1987 and covers the methods of producing the radioisotopes of astatine and the inorganic, nuclear, and organic chemistry of astatine. The discussion is limited to chemical and physical chemical properties of astatine. The monograph, after the introduction, is divided into chapters titled: production methods, nuclear spectroscopy, chemistry of astatine, separation and isolation (dry and wet), and selected procedures. 209 refs., 15 figs., 7 tabs. (DLC)

  2. Discovery of the astatine, radon, francium, and radium isotopes

    Energy Technology Data Exchange (ETDEWEB)

    Fry, C.; Thoennessen, M., E-mail: thoennessen@nscl.msu.edu

    2013-09-15

    Thirty-nine astatine, thirty-nine radon, thirty-five francium, and thirty-four radium isotopes have so far been observed; the discovery of these isotopes is described. For each isotope a brief summary of the first refereed publication, including the production and identification method, is presented.

  3. Discovery of the astatine, radon, francium, and radium isotopes

    CERN Document Server

    Fry, C

    2012-01-01

    Currently, thirty-nine astatine, thirty-nine radon, thirty-five francium, and thirty-four radium 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.

  4. Discovery of the astatine, radon, francium, and radium isotopes

    Science.gov (United States)

    Fry, C.; Thoennessen, M.

    2013-09-01

    Thirty-nine astatine, thirty-nine radon, thirty-five francium, and thirty-four radium isotopes have so far been observed; the discovery of these isotopes is described. For each isotope a brief summary of the first refereed publication, including the production and identification method, is presented.

  5. Delayed and In-beam Spectroscopy on Francium and Astatine Nuclei at the Proton Drip Line

    Energy Technology Data Exchange (ETDEWEB)

    Uusitalo, J.; Jakobsson, U. [Department of Physics, University of Jyvaeskylae (Finland); Collaboration: RITU-Gamma Gollaboration

    2011-11-30

    Delayed and in-beam spectroscopy on francium and astatine nuclei at and beyond the proton drip line has been performed. In neutron deficient astatine nuclei a shift to deformed shapes as a function of decreasing neutron has been obtained. In neutron deficient francium isotope the same shift is evident.

  6. Delayed and In-beam Spectroscopy on Francium and Astatine Nuclei at the Proton Drip Line

    Science.gov (United States)

    Uusitalo, J.; Jakobsson, U.

    2011-11-01

    Delayed and in-beam spectroscopy on francium and astatine nuclei at and beyond the proton drip line has been performed. In neutron deficient astatine nuclei a shift to deformed shapes as a function of decreasing neutron has been obtained. In neutron deficient francium isotope the same shift is evident.

  7. Measurement of the first ionization potential of astatine by laser ionization spectroscopy

    CERN Document Server

    Rothe, S; Antalic, S; Borschevsky, A; Capponi, L; Cocolios, T E; De Witte, H; Eliav, E; Fedorov, D V; Fedosseev, V N; Fink, D A; Fritzsche, S; Ghys, L; Huyse, M; Imai, N; Kaldor, U; Kudryavtsev, Yu; Köster, U; Lane, J; Lassen, J; Liberati, V; Lynch, K M; Marsh, B A; Nishio, K; Pauwels, D; Pershina, V; Popescu, L; Procter, T J; Radulov, D; Raeder, S; Rajabali, M M; Rapisarda, E; Rossel, R E; Sandhu, K; Seliverstov, M D; Sjödin, A M; Van den Bergh, P; Van Duppen, P; Venhart, M; Wakabayashi, Y; Wendt K D A

    2013-01-01

    The radioactive element astatine exists only in trace amounts in nature. Its properties can therefore only be explored by study of smallest quantities of artificially produced isotopes or by performing theoretical calculations. One of the most important properties influencing the chemical behaviour is the energy required to remove one electron from the valence shell, referred to as the ionization potential. Here we use laser spectroscopy to probe the optical spectrum of astatine near the ionization threshold. The observed series of Rydberg states enabled the first determination of the ionization potential of the astatine atom, 9.317510(8) eV. New ab initio calculations were performed to support the experimental result. The measured value serves as a benchmark for quantum chemistry calculations of the properties of astatine as well as for the theoretical prediction of the ionization potential of super-heavy element 117, the heaviest homologue of astatine.

  8. Measurement of the first ionization potential of astatine by laser ionization spectroscopy.

    Science.gov (United States)

    Rothe, S; Andreyev, A N; Antalic, S; Borschevsky, A; Capponi, L; Cocolios, T E; De Witte, H; Eliav, E; Fedorov, D V; Fedosseev, V N; Fink, D A; Fritzsche, S; Ghys, L; Huyse, M; Imai, N; Kaldor, U; Kudryavtsev, Yuri; Köster, U; Lane, J F W; Lassen, J; Liberati, V; Lynch, K M; Marsh, B A; Nishio, K; Pauwels, D; Pershina, V; Popescu, L; Procter, T J; Radulov, D; Raeder, S; Rajabali, M M; Rapisarda, E; Rossel, R E; Sandhu, K; Seliverstov, M D; Sjödin, A M; Van den Bergh, P; Van Duppen, P; Venhart, M; Wakabayashi, Y; Wendt, K D A

    2013-01-01

    The radioactive element astatine exists only in trace amounts in nature. Its properties can therefore only be explored by study of the minute quantities of artificially produced isotopes or by performing theoretical calculations. One of the most important properties influencing the chemical behaviour is the energy required to remove one electron from the valence shell, referred to as the ionization potential. Here we use laser spectroscopy to probe the optical spectrum of astatine near the ionization threshold. The observed series of Rydberg states enabled the first determination of the ionization potential of the astatine atom, 9.31751(8) eV. New ab initio calculations are performed to support the experimental result. The measured value serves as a benchmark for quantum chemistry calculations of the properties of astatine as well as for the theoretical prediction of the ionization potential of superheavy element 117, the heaviest homologue of astatine.

  9. Spectroscopy of low-lying states in neutron-deficient astatine and francium nuclei

    Energy Technology Data Exchange (ETDEWEB)

    Jakobsson, U., E-mail: ulrjak@kth.se; Cederwall, B. [KTH, The Division of Nuclear Physics, AlbaNova University Center, SE-10691 Stockholm (Sweden); Uusitalo, J.; Auranen, K.; Badran, H.; Cox, D. M.; Grahn, T.; Greenlees, P. T.; Julin, R.; Juutinen, S.; Herzáň, A.; Konki, J.; Leino, M.; Mallaburn, M.; Pakarinen, J.; Papadakis, P.; Partanen, J.; Rahkila, P.; Sandzelius, M.; Sarén, J. [University of Jyvaskyla, Department of Physics, P.O. Box 35, FI-40014 University of Jyvaskyla (Finland); and others

    2015-10-15

    Low-lying states in neutron-deficient astatine and francium nuclei have been studied by means of in-beam and delayed spectroscopy. The 13/2{sup +} state has been observed in francium nuclei with a similar down-sloping trend as in neighbouring astatine and bismuth isotopes, as a function of decreasing neutron number. A systematic trend can also now be seen for the 1/2{sup +} state both in astatine and francium nuclei, where the level energy decreases steeply as a function of neutron number when moving further away from the neutron shell closure. This trend is very similar between astatine nuclei and their francium isotones. Moreover, shape coexistence has been observed between the 13/2{sup +} state and the spherical 9/2{sup −} ground state in {sup 203}Fr and {sup 205}Fr.

  10. Spectroscopy of low-lying states in neutron-deficient astatine and francium nuclei

    Science.gov (United States)

    Jakobsson, U.; Uusitalo, J.; Auranen, K.; Badran, H.; Cederwall, B.; Cox, D. M.; Grahn, T.; Greenlees, P. T.; Julin, R.; Juutinen, S.; HerzáÅ, A.; Konki, J.; Leino, M.; Mallaburn, M.; Pakarinen, J.; Papadakis, P.; Partanen, J.; Rahkila, P.; Sandzelius, M.; Sarén, J.; Scholey, C.; Sorri, J.; Stolze, S.

    2015-10-01

    Low-lying states in neutron-deficient astatine and francium nuclei have been studied by means of in-beam and delayed spectroscopy. The 13/2+ state has been observed in francium nuclei with a similar down-sloping trend as in neighbouring astatine and bismuth isotopes, as a function of decreasing neutron number. A systematic trend can also now be seen for the 1/2+ state both in astatine and francium nuclei, where the level energy decreases steeply as a function of neutron number when moving further away from the neutron shell closure. This trend is very similar between astatine nuclei and their francium isotones. Moreover, shape coexistence has been observed between the 13/2+ state and the spherical 9/2- ground state in 203Fr and 205Fr.

  11. Automated astatination of biomolecules - a stepping stone towards multicenter clinical trials

    DEFF Research Database (Denmark)

    Aneheim, Emma; Albertsson, Per; Bäck, Tom

    2015-01-01

    To facilitate multicentre clinical studies on targeted alpha therapy, it is necessary to develop an automated, on-site procedure for conjugating rare, short-lived, alpha-emitting radionuclides to biomolecules. Astatine-211 is one of the few alpha-emitting nuclides with appropriate chemical...

  12. Measurement of the first ionization potential of astatine by laser ionization spectroscopy

    NARCIS (Netherlands)

    Rothe, S.; Andreyev, A. N.; Antalic, S.; Borschevsky, A.; Capponi, L.; Cocolios, T. E.; De Witte, H.; Eliav, E.; Fedorov, D. V.; Fedosseev, V. N.; Fink, D. A.; Fritzsche, S.; Ghys, L.; Huyse, M.; Imai, N.; Kaldor, U.; Kudryavtsev, Yuri; Koester, U.; Lane, J. F. W.; Lassen, J.; Liberati, V.; Lynch, K. M.; Marsh, B. A.; Nishio, K.; Pauwels, D.; Pershina, V.; Popescu, L.; Procter, T. J.; Radulov, D.; Raeder, S.; Rajabali, M. M.; Rapisarda, E.; Rossel, R. E.; Sandhu, K.; Seliverstov, M. D.; Sjoedin, A. M.; Van den Bergh, P.; Van Duppen, P.; Venhart, M.; Wakabayashi, Y.; Wendt, K. D. A.

    The radioactive element astatine exists only in trace amounts in nature. Its properties can therefore only be explored by study of the minute quantities of artificially produced isotopes or by performing theoretical calculations. One of the most important properties influencing the chemical

  13. An attempt to explore the production routes of Astatine radionuclides: Theoretical approach

    OpenAIRE

    Maiti, Moumita; Lahiri, Susanta

    2008-01-01

    In order to fulfil the recent thrust of Astatine radionuclides in the field of nuclear medicine various production routes have been explored in the present work. The possible production routes of $^{209-211}$At comprise both light and heavy ion induced reactions at the bombarding energy range starting from threshold to maximum 100 MeV energy. For this purpose, we have used the nuclear reaction model codes TALYS, ALICE91 and PACE-II. Excitation functions of those radionuclides, produced throug...

  14. Synthesis and Evaluation of Astatinated N-[2-(Maleimido)ethyl]-3-(trimethylstannyl)benzamide Immunoconjugates

    DEFF Research Database (Denmark)

    Aneheim, Emma; Gustafsson, Anna; Albertsson, Per

    2016-01-01

    Effective treatment of metastasis is a great challenge in the treatment of different types of cancers. Targeted alpha therapy utilizes the short tissue range (50-100 μm) of α particles, making the method suitable for treatment of disseminated occult cancers in the form of microtumors or even sing...... of the in vivo distribution of the new immunoconjugate with other tin-based immunoconjugates in tumor-bearing mice, the MSB conjugation method was found to be a viable option for successful astatine labeling of different monoclonal antibodies....

  15. Laser photodetachment of radioactive ions: towards the determination of the electronegativity of astatine

    CERN Multimedia

    Rothe, Sebastian; Welander, Jakob Emanuel; Chrysalidis, Katerina; Day Goodacre, Thomas; Fedosseev, Valentine; Fiotakis, Spyridon; Forstner, Oliver; Heinke, Reinhard Matthias; Johnston, Karl; Kron, Tobias; Koester, Ulli; Liu, Yuan; Marsh, Bruce; Ringvall Moberg, Annie; Rossel, Ralf Erik; Seiffert, Christoph; Studer, Dominik; Wendt, Klaus; Hanstorp, Dag

    2017-01-01

    Negatively charged ions are mainly stabilized through the electron correlation effect. A measure of the stability of a negative ion is the electron affinity, which the energy gain by attaching an electron to a neutral atom. This fundamental quantity is, due to the almost general lack of bound excited states, the only atomic property that can be determined with high accuracy for negative ions. We will present the results of the first laser photodetachment studies of radioactive negative ions at CERN-ISOLDE. The photodetachment threshold for the radiogenic iodine isotope 128I was measured successfully, demonstrating the performance of the upgraded GANDALPH experimental beam line. The first detection of photo-detached astatine atoms marks a milestone towards the determination of the EA of this radioactive element.

  16. Complexation study on no-carrier-added astatine with insulin: A candidate radiopharmaceutical

    Energy Technology Data Exchange (ETDEWEB)

    Lahiri, Susanta [Chemical Sciences Division, Saha Institute of Nuclear Physics, 1/AF Bidhannagar, Kolkata 700 064 (India)], E-mail: susanta.lahiri@saha.ac.in; Roy, Kamalika [Chemical Sciences Division, Saha Institute of Nuclear Physics, 1/AF Bidhannagar, Kolkata 700 064 (India); Sen, Souvik [Berhampur Sadar Hospital, Berhampur, Murshidabad 742 101 (India)

    2008-12-15

    No-carrier-added astatine radionuclides produced in the {sup 7}Li-irradiated lead matrix were separated from bulk lead nitrate target by complexing At with insulin, followed by dialysis. The method offers simultaneous separation of At from lead as well as its complexation with insulin. The At-insulin complex might be a potential radiopharmaceutical in the treatment of hepatocellular carcinoma. The stability of At-insulin complex was checked by dialysis against deionized water and Ringer lactate (RL) solution. It has been found that the half-life of At-insulin complex is about {approx}12 h, when dialyzed against deionized water and is only 6 h, when dialyzed against RL solution having the same composition as blood serum. The 6 h half-life of this Insulin-At complex is perfect for killing cancer cells from external cell surfaces as the half-life of internalization of insulin molecule inside the cell is 7-12 h.

  17. Determination of the electron affinity of astatine and polonium by laser photodetachment

    CERN Multimedia

    We propose to conduct the first electron affinity (EA) measurements of the two elements astatine (At) and polonium (Po). Collinear photo-detachment spectroscopy will allow us to measure these quantities with an uncertainty limited only by the spectral line width of the laser. We plan to use negative ion beams of the two radioactive elements At and Po, which are only accessible on-line and at ISOLDE. The feasibility of our proposed method and the functionality of the experimental setup have been demonstrated at ISOLDE in off-line tests by the clear observation of the photo-detachment threshold for stable iodine. This proposal is based on our Letter of Intent I-148.

  18. Adsorption of the astatine species on a gold surface: A relativistic density functional theory study

    Science.gov (United States)

    Demidov, Yuriy; Zaitsevskii, Andréi

    2018-01-01

    We report first-principle based studies of the adsorption interaction of astatine species on a gold surface. These studies are aimed primarily at the support and interpretation of gas chromatographic experiments with superheavy elements, tennessine (Ts, Z = 117), a heavier homologue of At, and possibly its pseudo-homologue nihonium (Nh, Z = 113). We use gold clusters with up to 69 atoms to simulate the adsorption sites and estimate the desorption energies of At & AtOH from a stable gold (1 1 1) surface. To describe the electronic structure of At -Aun and AtOH -Aun complexes, we combine accurate shape-consistent relativistic pseudopotentials and non-collinear two-component relativistic density functional theory. The predicted desorption energies of At and AtOH on gold are 130 ± 10 kJ/mol and 90 ± 10 kJ/mol, respectively. These results confirm the validity of the estimates derived from chromatographic data (147 ± 15 kJ/mol for At, and 100-10+20 kJ/mol for AtOH).

  19. Comment: 223 [Taxonomy Icon

    Lifescience Database Archive (English)

    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 ...

  20. ASTATINE-211 RADIOCHEMISTRY: THE DEVELOPMENT OF METHODOLOGIES FOR HIGH ACTIVITY LEVEL RADIOSYNTHESIS

    Energy Technology Data Exchange (ETDEWEB)

    MICHAEL R. ZALUTSKY

    2012-08-08

    Targeted radionuclide therapy is emerging as a viable approach for cancer treatment because of its potential for delivering curative doses of radiation to malignant cell populations while sparing normal tissues. Alpha particles such as those emitted by 211At are particularly attractive for this purpose because of their short path length in tissue and high energy, making them highly effective in killing cancer cells. The current impact of targeted radiotherapy in the clinical domain remains limited despite the fact that in many cases, potentially useful molecular targets and labeled compounds have already been identified. Unfortunately, putting these concepts into practice has been impeded by limitations in radiochemistry methodologies. A critical problem is that the synthesis of therapeutic radiopharmaceuticals provides additional challenges in comparison to diagnostic reagents because of the need to perform radio-synthesis at high levels of radioactivity. This is particularly important for {alpha}-particle emitters such as 211At because they deposit large amounts of energy in a highly focal manner. The overall objective of this project is to develop convenient and reproducible radiochemical methodologies for the radiohalogenation of molecules with the {alpha}-particle emitter 211At at the radioactivity levels needed for clinical studies. Our goal is to address two problems in astatine radiochemistry: First, a well known characteristic of 211At chemistry is that yields for electrophilic astatination reactions decline as the time interval after radionuclide isolation from the cyclotron target increases. This is a critical problem that must be addressed if cyclotrons are to be able to efficiently supply 211At to remote users. And second, when the preparation of high levels of 211At-labeled compounds is attempted, the radiochemical yields can be considerably lower than those encountered at tracer dose. For these reasons, clinical evaluation of promising 211At

  1. An all-solid state laser system for the laser ion sources RILIS and in-source laser spectroscopy of astatine at ISOLDE/CERN

    Energy Technology Data Exchange (ETDEWEB)

    Rothe, Sebastian

    2012-09-24

    This doctoral thesis describes the extension of the resonance ionization laser ion source RILIS at CERN/ISOLDE by the addition of an all-solid state tunable titanium:sapphire (Ti:Sa) laser system to complement the well-established system of dye lasers. Synchronous operation of the so called Dual RILIS system of Ti:Sa and dye lasers was investigated and the potential for increased ion beam intensity, reliability, and reduced setup time has been demonstrated. In-source resonance ionization spectroscopy was performed at ISOLDE/CERN and at ISAC/TRIUMF radioactive ion beam facilities to develop an efficient and selective three-colour ionization scheme for the purely radioactive element astatine. A LabVIEW based monitoring, control and measurement system was conceived which enabled, in conjunction with Dual RILIS operation, the spectroscopy of high lying Rydberg states, from which the ionization potential of the astatine atom was determined for the first time experimentally.

  2. An all-solid state laser system for the laser ion source RILIS and in-source laser spectroscopy of astatine at ISOLDE, CERN

    CERN Document Server

    Rothe, Sebastian; Nörtershäuser, W

    This doctoral thesis describes the extension of the resonance ionization laser ion source RILIS at ISOLDE, CERN, by the addition of an all-solid state tuneable titanium: sapphire (Ti:Sa) laser system to complement the well-established system of dye lasers. Synchronous operation of the so called Dual RILIS system of Ti:Sa and dye lasers was investigated and the potential for increased ion beam intensity, reliability, and reduced setup time has been demonstrated. In-source resonance ionization spectroscopy was performed at ISOLDE, CERN, and at ISAC, TRIUMF, radioactive ion beam facilities to develop an efficient and selective three-colour ionization scheme for the purely radioactive element astatine. A LabVIEW based monitoring, control and measurement system was conceived which enabled, in conjunction with Dual RILIS operation, the spectroscopy of high lying Rydberg states, from which the ionization potential of the astatine atom was determined for the first time experimentally.

  3. 50 CFR 223.205 - Sea turtles.

    Science.gov (United States)

    2010-10-01

    ... 50 Wildlife and Fisheries 7 2010-10-01 2010-10-01 false Sea turtles. 223.205 Section 223.205... Threatened Marine and Anadromous Species § 223.205 Sea turtles. (a) The prohibitions of section 9 of the Act (16 U.S.C. 1538) relating to endangered species apply to threatened species of sea turtle, except as...

  4. 40 CFR 265.223 - Containment system.

    Science.gov (United States)

    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 cover...

  5. 7 CFR 1280.223 - Reports.

    Science.gov (United States)

    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 § 1280...

  6. 8 CFR 223.2 - Processing.

    Science.gov (United States)

    2010-01-01

    ... 8 Aliens and Nationality 1 2010-01-01 2010-01-01 false Processing. 223.2 Section 223.2 Aliens and..., AND ADVANCE PAROLE DOCUMENTS § 223.2 Processing. (a) General. An application for a reentry permit... travel document shall not affect the application. (e) Processing. Approval of an application is solely at...

  7. 31 CFR 223.5 - Business.

    Science.gov (United States)

    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 making...

  8. 49 CFR 234.223 - Gate arm.

    Science.gov (United States)

    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 than...

  9. 32 CFR 223.5 - Responsibilities.

    Science.gov (United States)

    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. (a...

  10. Final Report for research grant "Development of Methods for High Specific Activity Labeling of Biomolecules Using Astatine-211 in Different Oxidation States"

    Energy Technology Data Exchange (ETDEWEB)

    Wilbur, D. Scott [Univ. of Washington, Seattle, WA (United States)

    2011-12-14

    The overall objective of this research effort was to develop methods for labeling biomolecules with higher oxidation state species of At-211. This was to be done in an effort to develop reagents that had higher in vivo stability than the present carbon-bonded At-211-labeled compounds. We were unsuccessful in that effort, as none of the approaches studied provided reagents that were stable to in vivo deastatination. However, we gained a lot of information about At-211 in higher oxidation states. The studies proved to be very difficult as small changes in pH and other conditions appeared to change the nature of the species that obtained (by HPLC retention time analyses), with many of the species being unidentifiable. The fact that there are no stable isotopes of astatine, and the chemistry of the nearest halogen iodine is quite different, made it very difficult to interpret results of some experiments. With that said, we believe that a lot of valuable information was obtained from the studies. The research effort evaluated: (1) methods for chemical oxidation of At-211, (2) approaches to chelation of oxidized At-211, and (3) approaches to oxidation of astatophenyl compounds. A major hurdle that had to be surmounted to conduct the research was the development of HPLC conditions to separate and identify the various oxidized species formed. Attempts to develop conditions for separation of iodine and astatine species by normal and reversed-phase TLC and ITLC were not successful. However, we were successful in developing conditions (from a large number of attempts) to separate oxidized forms of iodine ([I-125]iodide, [I-125]iodate and [I-125]periodate) and astatine ([At-211]astatide, [At-211]astatate, [At-211]perastatate, and several unidentified At-211 species). Information on the basic oxidation and characterization of At-211 species is provided under Objective 1. Conditions were developed to obtain new At-211 labeling method where At-211 is chelated with the DOTA and

  11. Dicty_cDB: CFD223 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available CF (Link to library) CFD223 (Link to dictyBase) - - - Contig-U16452-1 CFD223P (Link to Original site) CFD...223F 595 CFD223Z 416 CFD223P 1011 - - Show CFD223 Library CF (Link to library) Clone ID CFD...e URL http://dictycdb.biol.tsukuba.ac.jp/CSM/CF/CFD2-A/CFD223Q.Seq.d/ Representative seq. ID CFD...223P (Link to Original site) Representative DNA sequence >CFD223 (CFD223Q) /CSM/CF/CFD2-A/CFD...DNA Score E Sequences producing significant alignments: (bits) Value CFD223 (CFD223Q) /CSM/CF/CFD2-A/CFD223Q

  12. 36 CFR 223.279 - Personal use.

    Science.gov (United States)

    2010-07-01

    ... 36 Parks, Forests, and Public Property 2 2010-07-01 2010-07-01 false Personal use. 223.279 Section... DISPOSAL OF NATIONAL FOREST SYSTEM TIMBER Forest Botanical Products § 223.279 Personal use. (a) Personal use. A person may harvest forest botanical products from National Forest Systems lands free of charge...

  13. 27 CFR 46.223 - Tax credit.

    Science.gov (United States)

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 2 2010-04-01 2010-04-01 false Tax credit. 46.223 Section... for Sale on April 1, 2009 Tax Liability Calculation § 46.223 Tax credit. The dealer is allowed a credit of up to $500 against the total floor stocks tax. However, controlled groups are eligible for only...

  14. 36 CFR 223.35 - Performance bond.

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    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 for...

  15. 36 CFR 223.13 - Compliance.

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    2010-07-01

    ... 36 Parks, Forests, and Public Property 2 2010-07-01 2010-07-01 false Compliance. 223.13 Section... OF NATIONAL FOREST SYSTEM TIMBER General Provisions § 223.13 Compliance. Forest officers authorizing free use shall ensure that such use is in compliance with applicable land management plans and is...

  16. 36 CFR 223.141 - Suspension.

    Science.gov (United States)

    2010-07-01

    ... 36 Parks, Forests, and Public Property 2 2010-07-01 2010-07-01 false Suspension. 223.141 Section... DISPOSAL OF NATIONAL FOREST SYSTEM TIMBER Suspension and Debarment of Timber Purchasers § 223.141 Suspension. (a) The suspending official may, in the public interest, suspend a purchaser on the basis of...

  17. 31 CFR 223.4 - Deposits.

    Science.gov (United States)

    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 STATES...

  18. 36 CFR 2.23 - Recreation fees.

    Science.gov (United States)

    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, or...

  19. 36 CFR 223.63 - Advertised rates.

    Science.gov (United States)

    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 to...

  20. Dicty_cDB: CFC223 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available CF (Link to library) CFC223 (Link to dictyBase) - G00185 DDB0190493 Contig-U14174-1 CFC...223E (Link to Original site) CFC223F 622 CFC223Z 722 CFC223P 1344 CFC223E 1190 Show CFC223 Library CF (L...ink to library) Clone ID CFC223 (Link to dictyBase) Atlas ID - NBRP ID G00185 dictyBase ID DDB0190493 Link t...o Contig Contig-U14174-1 Original site URL http://dictycdb.biol.tsukuba.ac.jp/CSM/CF/CFC2-A/CFC...223Q.Seq.d/ Representative seq. ID CFC223E (Link to Original site) Representative DNA sequence >CFC223 (CFC

  1. 32 CFR 223.4 - Policy.

    Science.gov (United States)

    2010-07-01

    ... increasing significantly the likelihood of the illegal production of nuclear weapons or the theft, diversion... DEFENSE UNCLASSIFIED CONTROLLED NUCLEAR INFORMATION (DOD UCNI) § 223.4 Policy. It is DoD policy: (a) To...

  2. Dosimetry of radium-223 and progeny

    Energy Technology Data Exchange (ETDEWEB)

    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.

  3. 50 CFR 223.204 - Tribal plans.

    Science.gov (United States)

    2010-10-01

    ... Threatened Marine and Anadromous Species § 223.204 Tribal plans. (a) Limits on the prohibitions. The... impact on the biological requirements of the species, and will assess the effect of the Tribal Plan on... or not implementation of a Tribal Plan will appreciably reduce the likelihood of survival and...

  4. 49 CFR 223.3 - Application.

    Science.gov (United States)

    2010-10-01

    ... connected with the general railroad system of transportation. (3) Locomotives, passenger cars and cabooses... TRANSPORTATION SAFETY GLAZING STANDARDS-LOCOMOTIVES, PASSENGER CARS AND CABOOSES General § 223.3 Application. (a..., cabooses, and passenger cars that operate only on track inside an installation that is not part of the...

  5. 32 CFR 223.3 - Definitions.

    Science.gov (United States)

    2010-07-01

    ..., modification, assembly, utilization, transportation, or retirement of nuclear weapons or nuclear weapon...) of this section, including the protection of nuclear weapons, nuclear weapon components, or DoD SNM... DEPARTMENT OF DEFENSE UNCLASSIFIED CONTROLLED NUCLEAR INFORMATION (DOD UCNI) § 223.3 Definitions. (a) Atomic...

  6. 36 CFR 223.227 - Sale advertisement.

    Science.gov (United States)

    2010-07-01

    ... advertisement. (a) The Forest Service shall advertise any special forest products sales with an appraised value... products without advertisement, or advertise a special forest products sale for a period less than 30 days... 36 Parks, Forests, and Public Property 2 2010-07-01 2010-07-01 false Sale advertisement. 223.227...

  7. 14 CFR 223.3 - Mandatory free transportation.

    Science.gov (United States)

    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 Mandatory...

  8. 50 CFR 223.201 - Guadalupe fur seal.

    Science.gov (United States)

    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 Assistant...

  9. 48 CFR 223.570 - Drug-free work force.

    Science.gov (United States)

    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. ...

  10. 31 CFR 223.6 - Requirements applicable to surety companies.

    Science.gov (United States)

    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 or...

  11. 17 CFR 256.223 - Advances from associate companies.

    Science.gov (United States)

    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. This...

  12. 31 CFR 223.14 - Schedules of single risks.

    Science.gov (United States)

    2010-07-01

    ... 31 Money and Finance: Treasury 2 2010-07-01 2010-07-01 false Schedules of single risks. 223.14 Section 223.14 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) FISCAL... UNITED STATES § 223.14 Schedules of single risks. During the months of January, April, July, and October...

  13. 14 CFR 13.223 - Standard of proof.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Standard of proof. 13.223 Section 13.223... INVESTIGATIVE AND ENFORCEMENT PROCEDURES Rules of Practice in FAA Civil Penalty Actions § 13.223 Standard of proof. The administrative law judge shall issue an initial decision or shall rule in a party's favor...

  14. 36 CFR 223.200 - Determinations of surplus species.

    Science.gov (United States)

    2010-07-01

    ... species. 223.200 Section 223.200 Parks, Forests, and Public Property FOREST SERVICE, DEPARTMENT OF... Relief Act of 1990 Program § 223.200 Determinations of surplus species. (a) Determinations that specific quantities of grades and species are surplus to domestic manufacturing needs and withdrawals of such...

  15. An automated flow system incorporating in-line acid dissolution of bismuth metal from a cyclotron irradiated target assembly for use in the isolation of astatine-211

    Energy Technology Data Exchange (ETDEWEB)

    O’Hara, Matthew J.; Krzysko, Anthony J.; Niver, Cynthia M.; Morrison, Samuel S.; Owsley, Stanley L.; Hamlin, Donald K.; Dorman, Eric F.; Scott Wilbur, D.

    2017-04-01

    Astatine-211 (211At) is a promising cyclotron-produced radionuclide being investigated for use in targeted alpha therapy of blood borne and metastatic cancers, as well as treatment of tumor remnants after surgical resections. The isolation of trace quantities of 211At, produced within several grams of a Bi metal cyclotron target, involves a complex, multi-step procedure: (1) Bi metal dissolution in strong HNO3, (2) distillation of the HNO3 to yield Bi salts containing 211At, (3) dissolution of the salts in strong HCl, (4) solvent extraction of 211At from bismuth salts with diisopropyl ether (DIPE), and (5) back-extraction of 211At from DIPE into NaOH, leading to a purified 211At product. Step (1) has been addressed first to begin the process of automating the onerous 211At isolation process. A computer-controlled Bi target dissolution system has been designed. The system performs in-line dissolution of Bi metal from the target assembly using an enclosed target dissolution block, routing the resulting solubilized 211At/Bi mixture to the subsequent process step. The primary parameters involved in Bi metal solubilization (HNO3 concentration and influent flow rate) were optimized prior to evaluation of the system performance on replicate cyclotron irradiated targets. The results indicate that the system performs reproducibly, having nearly quantitative release of 211At from irradiated targets, with cumulative 211At recoveries that follow a sigmoidal function. The predictable nature of the 211At release profile allows the user to tune the system to meet target processing requirements.

  16. Reagents for astatination of biomolecules. 2. Conjugation of anionic boron cage pendant groups to a protein provides a method for direct labeling that is stable to in vivo deastatination.

    Science.gov (United States)

    Wilbur, D Scott; Chyan, Ming-Kuan; Hamlin, Donald K; Vessella, Robert L; Wedge, Timothy J; Hawthorne, M Frederick

    2007-01-01

    Cancer-targeting biomolecules labeled with 211At must be stable to in vivo deastatination, as control of the 211At distribution is critical due to the highly toxic nature of alpha-particle emission. Unfortunately, no astatinated aryl conjugates have shown in vivo stability toward deastatination when (relatively) rapidly metabolized proteins, such as monoclonal antibody Fab' fragments, are labeled. As a means of increasing the in vivo stability of 211At-labeled proteins, we have been investigating antibody conjugates of boron cage moieties. In this investigation, protein-reactive derivatives containing a nido-carborane (2), a bis-nido-carborane derivative (Venus Flytrap Complex, 3), and four 2-nonahydro-closo-decaborate(2-) derivatives (4-7) were prepared and conjugated with an antibody Fab' fragment such that subsequent astatination and in vivo tissue distributions could be obtained. To aid in determination of stability toward in vivo deastatination, the Fab'-borane conjugates were also labeled with 125I, and that material was coinjected with the 211At-labeled Fab'. For comparison, direct labeling of the Fab' with 125I and 211At was conducted. Direct labeling with Na[125I]I and Chloramine-T gave an 89% radiochemical yield. However, direct labeling of the Fab' with Na[211At]At and Chloramine-T resulted in a yield of Studies to optimize the closo-decaborate(2-) conjugates for protein labeling are underway.

  17. Dicty_cDB: AHA223 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available ces producing significant alignments: (bits) Value AHA223 (AHA223Q) /CSM/AH/AHA2-A/AHA223Q.Seq.d/ 198 3e-50 ... Score E Sequences producing significant alignments: (bits) Value N AC115584 |AC115584.2 Dictyostelium disco...oducing significant alignments: (bits) Value S68963( S68963 ;S74306) phosphoprotein phosphatase (EC 3.1.3.16

  18. 31 CFR 223.1 - Certificate of authority.

    Science.gov (United States)

    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 THE...

  19. 31 CFR 223.2 - Application for certificate of authority.

    Science.gov (United States)

    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 (Continued) FISCAL SERVICE, DEPARTMENT OF THE TREASURY FINANCIAL MANAGEMENT SERVICE SURETY COMPANIES DOING...

  20. 31 CFR 223.3 - Issuance of certificates of authority.

    Science.gov (United States)

    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) FISCAL SERVICE, DEPARTMENT OF THE TREASURY FINANCIAL MANAGEMENT SERVICE SURETY COMPANIES DOING BUSINESS...

  1. 24 CFR 248.223 - Alternative State strategy.

    Science.gov (United States)

    2010-04-01

    ... 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 income... 24 Housing and Urban Development 2 2010-04-01 2010-04-01 false Alternative State strategy. 248.223...

  2. 31 CFR 223.9 - Valuation of assets and liabilities.

    Science.gov (United States)

    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..., the Secretary of the Treasury may value the assets and liabilities of such companies in his discretion...

  3. 36 CFR 223.53 - Urgent removal contract extensions.

    Science.gov (United States)

    2010-07-01

    ... 36 Parks, Forests, and Public Property 2 2010-07-01 2010-07-01 false Urgent removal contract extensions. 223.53 Section 223.53 Parks, Forests, and Public Property FOREST SERVICE, DEPARTMENT OF.... Catastrophic events include, but are not limited to, severe wildfire, wind, floods, insects and disease...

  4. Radium Ra 223 dichloride in castration-resistant prostate cancer.

    Science.gov (United States)

    Joung, J Y; Ha, Y S; Kim, I Y

    2013-08-01

    Radium Ra 223 dichloride (Xofigo®, formerly Alpharadin) is one of the representative α-particle-emitting isotopes that delivers radiation with a higher biological effect to a more localized area. Preclinical studies in mouse, rat and canine models have demonstrated that radium Ra 223 dichloride has a definite skeletal affinity and antitumor effect with a relatively low toxicity on bone marrow. More recently, in a large randomized phase III trial (ALSYMPCA), patients with bone metastasis and castration-resistant prostate cancer (CRPC) received six cycles of 50 kBq/kg of radium Ra 223 dichloride in 4-week intervals. In these men, radium Ra 223 dichloride improved the median overall survival by 3.6 months when compared to the placebo group. Collectively, these results suggest that radium Ra 223 dichloride is a promising candidate for managing bone metastases in patients with CRPC. Copyright 2013 Prous Science, S.A.U. or its licensors. All rights reserved.

  5. Alpha emitter radium-223 and survival in metastatic prostate cancer.

    Science.gov (United States)

    Parker, C; Nilsson, S; Heinrich, D; Helle, S I; O'Sullivan, J M; Fosså, S D; Chodacki, A; Wiechno, P; Logue, J; Seke, M; Widmark, A; Johannessen, D C; Hoskin, P; Bottomley, D; James, N D; Solberg, A; Syndikus, I; Kliment, J; Wedel, S; Boehmer, S; Dall'Oglio, M; Franzén, L; Coleman, R; Vogelzang, N J; O'Bryan-Tear, C G; Staudacher, K; Garcia-Vargas, J; Shan, M; Bruland, Ø S; Sartor, O

    2013-07-18

    Radium-223 dichloride (radium-223), an alpha emitter, selectively targets bone metastases with alpha particles. We assessed the efficacy and safety of radium-223 as compared with placebo, in addition to the best standard of care, in men with castration-resistant prostate cancer and bone metastases. In our phase 3, randomized, double-blind, placebo-controlled study, we randomly assigned 921 patients who had received, were not eligible to receive, or declined docetaxel, in a 2:1 ratio, to receive six injections of radium-223 (at a dose of 50 kBq per kilogram of body weight intravenously) or matching placebo; one injection was administered every 4 weeks. In addition, all patients received the best standard of care. The primary end point was overall survival. The main secondary efficacy end points included time to the first symptomatic skeletal event and various biochemical end points. A prespecified interim analysis, conducted when 314 deaths had occurred, assessed the effect of radium-223 versus placebo on survival. An updated analysis, when 528 deaths had occurred, was performed before crossover from placebo to radium-223. At the interim analysis, which involved 809 patients, radium-223, as compared with placebo, significantly improved overall survival (median, 14.0 months vs. 11.2 months; hazard ratio, 0.70; 95% confidence interval [CI], 0.55 to 0.88; two-sided P=0.002). The updated analysis involving 921 patients confirmed the radium-223 survival benefit (median, 14.9 months vs. 11.3 months; hazard ratio, 0.70; 95% CI, 0.58 to 0.83; Pradium-233 as compared with placebo. Radium-223 was associated with low myelosuppression rates and fewer adverse events. In this study, which was terminated for efficacy at the prespecified interim analysis, radium-223 improved overall survival. (Funded by Algeta and Bayer HealthCare Pharmaceuticals; ALSYMPCA ClinicalTrials.gov number, NCT00699751.).

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  7. Genetics Home Reference: 9q22.3 microdeletion

    Science.gov (United States)

    ... people with a 9q22.3 microdeletion experience overgrowth (macrosomia), which results in increased height and weight compared to unaffected peers. The macrosomia often begins before birth and continues into childhood. ...

  8. Practical guide to the use of radium 223 dichloride.

    Science.gov (United States)

    Den, Robert B; Doyle, Laura A; Knudsen, Karen E

    2014-04-01

    Bone seeking radiopharmaceuticals have been used for decades in the palliation of pain from bone metastases emerging from prostate cancer. Recent clinical evidence has demonstrated an improved survival in men with metastatic castration resistant prostate cancer (CRPC) with radium 223. A review of the literature was performed to identify the role of radiopharmaceuticals in the management of prostate cancer. We focused on prospective trials in order to identify the highest level of evidence describing this therapy. Further, we focused on providing a clinical guide for the use of radium 223. The phase III ALSYMPCA trial which compared radium 223 to placebo in men with symptomatic CRPC demonstrated a statistically significant improvement in median overall survival of 3.6 months and an improvement in time to first skeletal related event. There were higher rates of myelosuppression and diarrhea with radium 223, however, no clinically meaningful differences in the frequency of grade 3 or 4 adverse events were observed between the study groups. Radium 223 is a safe and effective therapy in men with symptomatic CRPC providing a survival advantage on par with novel antiandrogens, CYP-17 inhibitors, and chemotherapy. Radium 223 has huge potential in combination strategies as well as for use earlier in the natural history of metastatic prostate cancer.

  9. Guidance for Classifying Studies Conducted Using the OECD Test Guideline 223 (TG223) (Acute Avian Oral Sequential Dose Study)

    Science.gov (United States)

    Guidance based on comparison of results from the TG223 validation studies to results from avian acute oral studies previously submitted to EPA for two test chemicals following EPA's 850.2100 (public draft) guidelines.

  10. Recovery of Ra-223 from natural thorium irradiated by protons

    Energy Technology Data Exchange (ETDEWEB)

    Vasiliev, Aleksandr N.; Ostapenko, Valentina S. [Lomonosov Moscow State Univ. (Russian Federation); Russian Academy of Sciences, Moscow-Troitsk (Russian Federation). Inst. for Nuclear Research; Lapshina, Elena V.; Ermolaev, Stanislav V.; Zhuikov, Boris L. [Russian Academy of Sciences, Moscow-Troitsk (Russian Federation). Inst. for Nuclear Research; Danilov, Sergey S. [Lomonosov Moscow State Univ. (Russian Federation); Kalmykov, Stepan N. [Lomonosov Moscow State Univ. (Russian Federation); National Research Center ' Kurchatov Institute' (NRC ' Kurchatov Institute' ), Moscow (Russian Federation)

    2016-11-01

    Irradiation of natural thorium with medium-energy protons is considered to be a prospective approach to large-scale production of {sup 225}Ac and {sup 223}Ra. In addition to the earlier-developed method of {sup 225}Ac isolation, the present work focuses on the simultaneous recovery of {sup 223}Ra from the same thorium target. Radiochemical procedure is based on liquid-liquid extraction, cation exchange and extraction chromatography. The procedure provides separation of radium from spallation and fission products generated in the thorium target. High chemical yield (85-90%) and radionuclide purity of {sup 223}Ra (> 99.8% except {sup 224}Ra and {sup 225}Ra isotopes) have been achieved.

  11. Radium-223 Therapy of Bone Metastases in Prostate Cancer.

    Science.gov (United States)

    Nilsson, Sten

    2016-11-01

    Metastatic castration-resistant prostate cancer frequently metastasizes to the bone, often resulting in painful skeletal events, reduced quality of life, and reduced survival. Radium-223 is a first-in-class alpha-emitting radiopharmaceutical that has proven to prolong overall survival, delay time to symptomatic skeletal events, and improve quality of life in patients with castration-resistant prostate cancer and symptomatic bone metastases and no visceral metastases. Radium-223 provides survival benefit to patients with castration-resistant prostate cancer and symptomatic bone metastases, regardless of prior docetaxel use. This article gives an overview of the development of radium-223 from the first-in-human trial to current status. Copyright © 2016. Published by Elsevier Inc.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  13. 31 CFR 223.16 - List of certificate holding companies.

    Science.gov (United States)

    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 is...

  14. Concurrent psu dic(21)(q22.3)

    Indian Academy of Sciences (India)

    Velásquez A. I. 2014 Concurrent psu dic(21)(q22.3) and t(13;17)(q14.1;p12) in a mosaic Down's syndrome patient: review of thirty-one similar dicentrics. J. Genet. 93, 189–192]. Introduction. Pseudodicentric 'mirror-image' chromosomes 21 with break-.

  15. 48 CFR 552.223-71 - Nonconforming Hazardous Materials.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 4 2010-10-01 2010-10-01 false Nonconforming Hazardous....223-71 Nonconforming Hazardous Materials. As prescribed in 523.303(b), insert the following clause: Nonconforming Hazardous Materials (SEP 1999) (a) Nonconforming supplies that contain hazardous material or that...

  16. Radium-223 in metastatic castration resistant prostate cancer.

    Science.gov (United States)

    Vuong, Winston; Sartor, Oliver; Pal, Sumanta K

    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 benefit 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 influencing clinical implementation.

  17. Radium-223 for the treatment of prostate cancer.

    Science.gov (United States)

    Hafeez, Shaista; Parker, Christopher

    2013-03-01

    Bone metastases cause significant morbidity and mortality in castration-resistant prostate cancer (CRPC). Until recently, treatment options have been limited, but now six drugs are known to extend life expectancy, with docetaxel the current standard first-line cytotoxic therapy. Phase III studies have also shown a survival advantage for sipuleucel-T, cabazitaxel, abiraterone, enzalutamide and radium-223 . Radium-223 is unique among these agents, as the only bone-directed therapy shown to prolong survival in CRPC. This review covers the current standard of care for CRPC and recent drug developments that have demonstrated a survival benefit. It focuses on bone-directed therapies, in particular radium-223, the first-in-class alpha-emitting radionuclide and discusses the pivotal studies to date. A PubMed search using the keywords below was performed. Radium-223 is set to become a new standard of care for the treatment of bony metastatic CRPC. It improves both survival and quality of life, delays skeletal events and is well tolerated. Its optimal use in the evolving treatment strategies for men with CRPC and bone metastases is yet to be determined.

  18. Radium-223 dichloride for the treatment of metastatic prostate cancer.

    Science.gov (United States)

    Turner, Philip Geoffrey; O'Sullivan, Joe

    2014-10-01

    Bone metastases are a frequent complication of many malignancies and are particularly common in metastatic prostate cancer, where they are associated with a high degree of morbidity. Until recently, treatments relied on palliative bone targeting measures with no proven survival-prolonging action or on systemic agents with general anti-prostate cancer activity but significant toxicities. Radium-223 dichloride is a bone-seeking, α-emitting, radionuclide that has recently been licensed in the US and Europe for the treatment of men with castration-resistant prostate cancer, bone metastases and no known visceral metastases. Radium-223 is the first bone-seeking radionuclide therapy proven to result in increased overall survival versus placebo. The existing market of bone-targeted agents is reviewed before considering what radium-223 adds by examining its pharmacology, pharmacokinetics and clinical efficacy and safety data. Initial relevant papers were identified by searching PubMed using combinations of the terms, 'Radium', 'Prostatic neoplasms', 'Bone', 'Neoplasm metastasis'. Consideration is given to further preclinical work needed into the mechanism of action of radium-223 and future clinical directions of the drug including combinations with other agents.

  19. 40 CFR 60.223 - Monitoring of operations.

    Science.gov (United States)

    2010-07-01

    ... Fertilizer Industry: Diammonium Phosphate Plants § 60.223 Monitoring of operations. (a) The owner or operator of any granular diammonium phosphate plant subject to the provisions of this subpart shall install... percent over its operating range. (b) The owner or operator of any granular diammonium phosphate plant...

  20. 36 CFR 223.82 - Contents of advertisement.

    Science.gov (United States)

    2010-07-01

    ... 36 Parks, Forests, and Public Property 2 2010-07-01 2010-07-01 false Contents of advertisement... SALE AND DISPOSAL OF NATIONAL FOREST SYSTEM TIMBER Timber Sale Contracts Advertisement and Bids § 223.82 Contents of advertisement. (a) A timber sale advertisement shall include the following information...

  1. 36 CFR 223.228 - Contents of advertisement.

    Science.gov (United States)

    2010-07-01

    ... 36 Parks, Forests, and Public Property 2 2010-07-01 2010-07-01 false Contents of advertisement... SALE AND DISPOSAL OF NATIONAL FOREST SYSTEM TIMBER Special Forest Products Advertisement and Bids § 223.228 Contents of advertisement. The Forest Service shall include the following information in an...

  2. 36 CFR 223.80 - When advertisement is required.

    Science.gov (United States)

    2010-07-01

    ... 36 Parks, Forests, and Public Property 2 2010-07-01 2010-07-01 false When advertisement is... AGRICULTURE SALE AND DISPOSAL OF NATIONAL FOREST SYSTEM TIMBER Timber Sale Contracts Advertisement and Bids § 223.80 When advertisement is required. Except as otherwise provided in this part each sale in which...

  3. 36 CFR 223.81 - Shorter advertising periods in emergencies.

    Science.gov (United States)

    2010-07-01

    ... 36 Parks, Forests, and Public Property 2 2010-07-01 2010-07-01 false Shorter advertising periods... OF AGRICULTURE SALE AND DISPOSAL OF NATIONAL FOREST SYSTEM TIMBER Timber Sale Contracts Advertisement and Bids § 223.81 Shorter advertising periods in emergencies. In emergency situations where prompt...

  4. Radium-223 in metastatic castration resistant prostate cancer

    Directory of Open Access Journals (Sweden)

    Winston Vuong

    2014-06-01

    Full Text Available 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 benefit 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 influencing clinical implementation.

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

    Energy Technology Data Exchange (ETDEWEB)

    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. 36 CFR 223.218 - Consistency with plans, environmental standards, and other management requirements.

    Science.gov (United States)

    2010-07-01

    ..., environmental standards, and other management requirements. 223.218 Section 223.218 Parks, Forests, and Public... Special Forest Products § 223.218 Consistency with plans, environmental standards, and other management... with applicable land management plans. Each contract, permit, or other authorizing instrument shall...

  7. 25 CFR 162.223 - Must the rent be adjusted under an agricultural lease?

    Science.gov (United States)

    2010-04-01

    ... 25 Indians 1 2010-04-01 2010-04-01 false Must the rent be adjusted under an agricultural lease? 162.223 Section 162.223 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR LAND AND WATER LEASES AND PERMITS Agricultural Leases Lease Requirements § 162.223 Must the rent be adjusted under an...

  8. 36 CFR 223.117 - Administration of cooperative or Federal sustained yield units.

    Science.gov (United States)

    2010-07-01

    ... or Federal sustained yield units. 223.117 Section 223.117 Parks, Forests, and Public Property FOREST... Contracts Contract Administration § 223.117 Administration of cooperative or Federal sustained yield units. With respect to sustained yield units established pursuant to the provisions of the Act of March 29...

  9. 48 CFR 952.223-72 - Radiation protection and nuclear criticality.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Radiation protection and nuclear criticality. 952.223-72 Section 952.223-72 Federal Acquisition Regulations System DEPARTMENT OF ENERGY CLAUSES AND FORMS SOLICITATION PROVISIONS AND CONTRACT CLAUSES Text of Provisions and Clauses 952.223-72 Radiation protection and nuclear...

  10. 36 CFR 223.40 - Cancellation for environmental protection or inconsistency with plans.

    Science.gov (United States)

    2010-07-01

    ... Renewable Resources Planning Act of 1974, as amended. Such provision shall provide for reasonable... environmental protection or inconsistency with plans. 223.40 Section 223.40 Parks, Forests, and Public Property... Contracts Contract Conditions and Provisions § 223.40 Cancellation for environmental protection or...

  11. 36 CFR 223.4 - Exchange of trees or portions of trees.

    Science.gov (United States)

    2010-07-01

    ... 36 Parks, Forests, and Public Property 2 2010-07-01 2010-07-01 false Exchange of trees or portions of trees. 223.4 Section 223.4 Parks, Forests, and Public Property FOREST SERVICE, DEPARTMENT OF AGRICULTURE SALE AND DISPOSAL OF NATIONAL FOREST SYSTEM TIMBER General Provisions § 223.4 Exchange of trees or...

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

    Science.gov (United States)

    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 OF...

  13. 36 CFR 223.12 - Permission to cut, damage, or destroy trees without advertisement.

    Science.gov (United States)

    2010-07-01

    ... destroy trees without advertisement. 223.12 Section 223.12 Parks, Forests, and Public Property FOREST... § 223.12 Permission to cut, damage, or destroy trees without advertisement. Permission may be granted to... lands without advertisement when necessary for the occupancy of a right-of-way or other authorized use...

  14. 40 CFR 86.223-94 - Oxides of nitrogen analyzer calibration.

    Science.gov (United States)

    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... Trucks and New Medium-Duty Passenger Vehicles; Cold Temperature Test Procedures § 86.223-94 Oxides of...

  15. 36 CFR 223.44 - Collection rights on contracts involved in transfer of purchase credit.

    Science.gov (United States)

    2010-07-01

    ... 36 Parks, Forests, and Public Property 2 2010-07-01 2010-07-01 false Collection rights on contracts involved in transfer of purchase credit. 223.44 Section 223.44 Parks, Forests, and Public Property... Contracts Contract Conditions and Provisions § 223.44 Collection rights on contracts involved in transfer of...

  16. The miR-223 host non-coding transcript linc-223 induces IRF4 expression in acute myeloid leukemia by acting as a competing endogenous RNA

    KAUST Repository

    Mangiavacchi, Arianna

    2016-08-10

    Alterations in genetic programs required for terminal myeloid differentiation and aberrant proliferation characterize acute myeloid leukemia (AML) cells. Here, we identify the host transcript of miR-223, linc-223, as a novel functional long non-coding RNA (lncRNA) in AML. We show that from the primary nuclear transcript, the alternative production of miR-223 and linc-223 is finely regulated during monocytic differentiation. Moreover, linc-223 expression inhibits cell cycle progression and promotes monocytic differentiation of AML cells. We also demonstrate that endogenous linc-223 localizes in the cytoplasm and acts as a competing endogenous RNA for miR-125-5p, an oncogenic microRNA in leukemia. In particular, we show that linc-223 directly binds to miR-125-5p and that its knockdown increases the repressing activity of miR-125-5p resulting in the downregulation of its target interferon regulatory factor 4 (IRF4), which it was previously shown to inhibit the oncogenic activity of miR-125-5p in vivo. Furthermore, data from primary AML samples show significant downregulation of linc-223 in different AML subtypes. Therein, these findings indicate that the newly identified lncRNA linc-223 may have an important role in myeloid differentiation and leukemogenesis, at least in part, by cross-talking with IRF4 mRNA.

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

    Science.gov (United States)

    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.

  18. Real-Time Scintigraphic Assessment of Intravenous Radium-223 Administration for Quality Control

    Science.gov (United States)

    Wright, Chadwick L.; Monk, J. Paul; Murrey, Douglas A.; Hall, Nathan C.

    2015-01-01

    Radium-223 (223Ra) dichloride is an approved intravenous radiotherapy for patients with osseous metastases from castration-resistant prostate cancer (CRPC). In addition to the therapeutic alpha radiation, there is additional 223Ra radiation generated which produces photons that can be imaged with conventional gamma cameras. No studies have evaluated real-time and quality imaging during intravenous 223Ra administration to verify systemic circulation and exclude 223Ra extravasation at the injection site. A retrospective review was performed for fifteen 223Ra administrations for CRPC patients which were imaged using a large field of view portable gamma camera (LFOVPGC) for the purposes of quality control and patient safety. Dynamic imaging of the chest was performed before, during, and after the 223Ra administration to verify systemic circulation, per institutional clinical protocol. Before and after 223Ra administration, a static image was obtained of the intravenous access site. Dynamic imaging of the chest confirmed systemic administration early during the 1-minute injection period for all patients. There were no cases of focal 223Ra extravasation at the site of intravenous access. These results verify that systemic 223Ra administrations can be quantified with real-time imaging using an LFOVPGC. This simple approach can confirm and quantify systemic circulation of 223Ra early during injection and exclude focal extravasation for the purposes of quality control. PMID:25789312

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  20. Practical recommendations for radium-223 treatment of metastatic castration-resistant prostate cancer

    Energy Technology Data Exchange (ETDEWEB)

    Du, Yong [The Royal Marsden NHS Foundation Trust, Department of Nuclear Medicine and PET/CT, London (United Kingdom); Carrio, Ignasi [Hospital Sant Pau, Barcelona (Spain); De Vincentis, Giuseppe [Policlinico Umberto I University Hospital Rome, Rome (Italy); Fanti, Stefano [University Hospital Bologna, Bologna (Italy); Ilhan, Harun [Ludwig-Maximilians-University Hospital, Munich (Germany); Mommsen, Caroline [Praxis fuer diagnostische und therapeutische Nuklearmedizin Berlin, Berlin (Germany); Nitzsche, Egbert [Canton Hospital Aarau, Aarau (Switzerland); Sundram, Francis [University Hospital Southampton NHS Foundation Trust, Southampton (United Kingdom); Vogel, Wouter [The Netherlands Cancer Institute, Amsterdam (Netherlands); Oyen, Wim [The Royal Marsden NHS Foundation Trust, Department of Nuclear Medicine and PET/CT, London (United Kingdom); The Institute of Cancer Research, London (United Kingdom); Lewington, Val [Guy' s and St Thomas' NHS Foundation Trust, London (United Kingdom)

    2017-09-15

    Radium Ra 223 dichloride (radium-223, Xofigo registered) is the first targeted alpha therapy for patients with castration-resistant prostate cancer and symptomatic bone metastases. Radium-223 provides a new treatment option for this setting, but also necessitates a new treatment management approach. We provide straightforward and practical recommendations for European nuclear medicine centres to optimize radium-223 service provision. An independent research consultancy agency observed radium-223 procedures and conducted interviews with all key staff members involved in radium-223 treatment delivery in 11 nuclear medicine centres across six countries (Germany, Italy, the Netherlands, Spain, Switzerland and the UK) experienced in administering radium-223. The findings were collated and discussed at a meeting of experts from these centres, during which key consensus recommendations were defined. The recommendations cover centre organization and preparation; patient referral; radium-223 ordering, preparation and disposal; radium-223 treatment delivery/administration; and patient experience. Guidance includes structured coordination and communication within centres and multidisciplinary teams, focusing on sharing best practice to provide high-quality, patient-centred care throughout the treatment pathway. These expert recommendations are intended to complement existing management guidelines. Sharing best practice and experience will help nuclear medicine centres to optimize radium-223 service provision and improve patient care. (orig.)

  1. Hematologic Safety of Radium-223 Dichloride: Baseline Prognostic Factors Associated With Myelosuppression in the ALSYMPCA Trial.

    Science.gov (United States)

    Vogelzang, Nicholas J; Coleman, Robert E; Michalski, Jeff M; Nilsson, Sten; O'Sullivan, Joe M; Parker, Christopher; Widmark, Anders; Thuresson, Marcus; Xu, Lei; Germino, Joseph; Sartor, Oliver

    2017-02-01

    Myelosuppression is common in patients with progressive castration-resistant prostate cancer and bone metastases. Radium-223 prolongs overall survival in these patients but may cause myelosuppression; understanding risk factors will improve clinical decision making. We describe hematologic safety of radium-223 in ALSYMPCA and post hoc analyses identifying patients at increased risk for hematologic toxicity. Hematologic parameters and adverse events were analyzed. Multivariate analyses assessing baseline risk factors for hematologic toxicities were performed separately for radium-223 and placebo patients. Nine hundred one patients received radium-223 (n = 600) or placebo (n = 301); 65% of radium-223 and 48% of placebo patients had the full 6 cycles. Grade 3/4 thrombocytopenia was more common in radium-223 versus placebo patients (6% vs. 2%). Logistic regression analyses identified significant baseline predictors for grade 2-4 hematologic toxicities related to radium-223 treatment: extent of disease (6-20 vs. radium-223 injections received (4-6 vs. 1-3). Radium-223 has a favorable safety profile with a low myelosuppression incidence. Understanding baseline factors associated with myelosuppression may assist clinicians in avoiding severe myelosuppression events with radium-223. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  2. Impact of treatment delay in Radium-223 therapy of metastatic castration-resistant prostate cancer patients

    DEFF Research Database (Denmark)

    Fosbøl, Marie Øbro; Petersen, Peter Meidahl; Daugaard, Gedske

    2018-01-01

    BACKGROUND: Radium-223-dichloride (Ra-223) is an alpha-emitting, bone seeking radionuclide therapy approved for patients with metastatic castration-resistant prostate cancer (mCRPC). In the fall of 2014, a global temporary shortage of Ra-223 occurred for 2 months due to production irregularities...... to non-disease related reasons on OS, rPFS or number of completed treatment cycles....

  3. Metabolism and pharmacokinetics of radium-223 in prostate cancer.

    Science.gov (United States)

    Yeku, Oladapo; Slovin, Susan F

    2015-05-01

    Prostate cancer metastatic to bone is a cause of significant morbidity and mortality. Bone pain and other skeletal events negatively impact the quality of life in patients who might otherwise be functioning well. As such, there has been intense interest in the development of strategies and pharmaceuticals to address this problem. The authors reviewed the current literature for articles relevant to metastatic prostate cancer, clinical radiopharmaceuticals, castrate-resistant prostate cancer and development of Radium-223 . The authors have referenced primary literature, clinical trials and relevant review articles that summarize the history, development and current utilization of radiopharmaceuticals for management of bone metastases from prostate cancer. Radium-223 is the first radiopharmaceutical with an overall survival benefit approved for the treatment of patients with castration-resistant prostate cancer, symptomatic bone metastasis and no known visceral metastatic disease. The additional benefit of clinically significant improved overall survival should lead to exploration of whether this agent can be used earlier in the treatment algorithm or combined with chemotherapy or androgen deprivation therapy. An individualized approach needs to be tailored to each patient based on their overall symptoms, disease burden, hematologic profile and goals of care.

  4. Radium-223 dichloride therapy in breast cancer with osseous metastases.

    Science.gov (United States)

    Takalkar, Amol; Paryani, Bhavna; Adams, Scott; Subbiah, Vivek

    2015-11-18

    Osseous metastases occur frequently in patients with breast cancer. Few options exist for bone targeted therapy for hormone refractory patients with breast cancer with progressive bone metastases. We present a case of breast cancer with osseous metastases but no visceral metastases. The patient had been treated with surgery, chemotherapy, radiation and hormonal therapy, but still had extensive symptomatic osseous metastases. She received radium-223 dichloride, a therapeutic radiopharmaceutical Food and Drug Administration (FDA) approved for castration resistant prostate cancer with bone metastases. She tolerated the therapy well with no significant adverse effects. She had an excellent response with significant pain relief obviating need for regular analgaesics. Her tumour markers also dropped significantly. Osseous metastases assessed with F-18 fluorodeoxy glucose (FDG) positron emission tomography/CT (PET/CT) and F-18 sodium fluoride (NaF) bone PET/CT) scans at baseline, after two and six cycles, also showed interval improvement in the lesions. Radium-223 dichloride could potentially be a safe and useful therapeutic option in this setting. 2015 BMJ Publishing Group Ltd.

  5. Nursing management of patients with castration-resistant prostate cancer undergoing radium-223 dichloride treatment.

    Science.gov (United States)

    Delacruz, Anthony; Arauz, Gabrielle; Curley, Tracy; Lindo, Amabella; Jensen, Trine

    2015-04-01

    Radium-223 dichloride, or radium-223, is a first-in-class alpha emitter that selectively targets bone metastases with high-energy, short-range alpha particles and is approved for the treatment of patients with castration-resistant prostate cancer (CRPC), symptomatic bone metastases, and no known visceral metastatic disease. Nurses are essential in educating patients about radium-223. This article provides oncology nurses with information from the randomized phase III Alpharadin in Symptomatic Prostate Cancer (ALSYMPCA) trial, as well as important handling, administration, and safety details unique to radium-223. Data from the ALSYMPCA trial and related published information on radium-223 were reviewed. Radium-223 is the only alpha-emitting radiopharmaceutical that has been shown to improve overall survival in patients with CRPC, as demonstrated in the ALSYMPCA trial. In addition, radium-223 delays time to first symptomatic skeletal event, and it is well tolerated with a low incidence of myelosuppression and gastrointestinal adverse events. Delivered on an outpatient basis, radium-223 requires universal precautions for handling and administration. Because of the potential for additive myelosuppression, the concomitant use of radium-223 with chemotherapy, other systemic radioisotopes, or hemibody external radiation therapy is not recommended.

  6. Glut4 Palmitoylation at Cys223 Plays a Critical Role in Glut4 Membrane Trafficking

    OpenAIRE

    Ren, Wenying; Sun, Yingmin; Du, Keyong

    2015-01-01

    Recently, we identified Glut4 as a palmitoylated protein in adipocytes. To understand the role of Glut4 palmitoylation in Glut4 membrane trafficking, a process that is essential for maintenance of whole body glucose homeostasis, we have characterized Glut4 palmitoylation. We found that Glut4 is palmitoylated at Cys223 and Glut4 palmitoylation at Cys223 is essential for insulin dependent Glut4 membrane translocation as substitution of Cys223 with a serine residue in Glut4 (C223S Glut4) diminis...

  7. Cluster emission in the radioactive decay of 223Ac

    CERN Document Server

    Steyn, G F; Faccio, D; Bonetti, R; Tretyakova, S P; Shishkin, S V; Ogloblin, A A; Pik-Pichak, G A; Vermeulen, C; van der Meulen, N P; van der Walt, T N; McGee, D

    2010-01-01

    The branching ratio of 223Ac decay by spontaneous 14C emission was measured and a search for 15N clusters was performed. After exposure of a hemispherical array of solid-state nuclear track detectors, 347 14C events were identified and no 15N events. B(14C) = λ(14C)/λ(α) = (3.2 ± 1.0) x 10-11 is consistent with a favoured ground state to ground state transition. As no nitrogen tracks were found, only an upper limit could be inferred for 15N emission, B(15N) = λ(15N)/λ(α) ≤ 2.2 x 10-13 (confidence limit 90%), consistent with an unfavoured transition. Intense 227Pa sources were produced for this study, using the reaction 232Th(p,6n)227Pa. This offered an opportunity to compare the measured source strength with predictions based on published excitation function data.

  8. Optical emission of 223 Radium: in vitro and in vivo preclinical applications.

    Science.gov (United States)

    Boschi, Federico; De Sanctis, Francesco; Spinelli, Antonello E

    2017-10-20

    223 Radium (223 Ra) is widely used in Nuclear medicine to treat patients with osseous metastatic prostate cancer. In clinical practice 223 Ra cannot be imaged directly, however gamma photons produced by its short-lived daughter nuclides can be captured by conventional gamma cameras. In this work we show that 223 Ra and its short-lived daughter nuclides can be detected with optical imaging techniques. The light emission of 223 Ra was investigated in vitro using different setups in order to clarify the mechanism of light production. The results demonstrate that the luminescence of the 223 Ra chloride solution, usually employed in clinical treatments, is compatible with Cerenkov luminescence having an emission spectrum that is almost indistinguishable from Cerenkov radiation one. This study proves that luminescence imaging can be successfully employed to detect 223 Ra in vivo in mice by imaging whole body 223 Ra biodistribution and more precisely its uptake in bones. This article is protected by copyright. All rights reserved.

  9. 36 CFR 223.11 - Free use to other Federal agencies.

    Science.gov (United States)

    2010-07-01

    ... Federal agencies. (a) National Forest timber will be granted free of charge to other branches of the... 36 Parks, Forests, and Public Property 2 2010-07-01 2010-07-01 false Free use to other Federal agencies. 223.11 Section 223.11 Parks, Forests, and Public Property FOREST SERVICE, DEPARTMENT OF...

  10. 48 CFR 952.223 - Clauses related to environment, energy and water efficiency, renewable energy technologies...

    Science.gov (United States)

    2010-10-01

    ... 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... related to environment, energy and water efficiency, renewable energy technologies, occupational safety...

  11. 14 CFR 120.223 - Alcohol misuse information, training, and substance abuse professionals.

    Science.gov (United States)

    2010-01-01

    ... substance abuse professionals. 120.223 Section 120.223 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION... misuse information, training, and substance abuse professionals. (a) Employer obligation to promulgate a... authority independent of this subpart. Any such additional policies or consequences must be clearly and...

  12. 37 CFR 2.23 - Additional requirements for TEAS Plus application.

    Science.gov (United States)

    2010-07-01

    ... 37 Patents, Trademarks, and Copyrights 1 2010-07-01 2010-07-01 false Additional requirements for TEAS Plus application. 2.23 Section 2.23 Patents, Trademarks, and Copyrights UNITED STATES PATENT AND TRADEMARK OFFICE, DEPARTMENT OF COMMERCE RULES OF PRACTICE IN TRADEMARK CASES Application for Registration...

  13. Radium-223 behandling af knoglemetastaser ved kastrationsrefraktær prostatacancer

    DEFF Research Database (Denmark)

    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...

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

    DEFF Research Database (Denmark)

    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...

  15. 36 CFR 223.201 - Limitations on unprocessed timber harvested in Alaska.

    Science.gov (United States)

    2010-07-01

    ... 36 Parks, Forests, and Public Property 2 2010-07-01 2010-07-01 false Limitations on unprocessed timber harvested in Alaska. 223.201 Section 223.201 Parks, Forests, and Public Property FOREST SERVICE...) Permit the salvage of timber damaged by wind, insects, fire or other catastrophe, (d) Bring into use a...

  16. 77 FR 37732 - Fourteenth Meeting: RTCA Special Committee 223, Airport Surface Wireless Communications

    Science.gov (United States)

    2012-06-22

    ...: Meeting Notice of RTCA Special Committee 223, Airport Surface Wireless Communications. SUMMARY: The FAA is... Wireless Communications. DATES: The meeting will be held July 24-25, 2012, from 9 a.m.-5 p.m. ADDRESSES... Federal Aviation Administration Fourteenth Meeting: RTCA Special Committee 223, Airport Surface Wireless...

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

    Science.gov (United States)

    2010-09-07

    ... 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 p.m... Federal Aviation Administration Sixth Meeting: RTCA Special Committee 223: Airport Surface Wireless...

  18. 78 FR 13395 - Meeting: RTCA Special Committee 223, Airport Surface Wireless Communications

    Science.gov (United States)

    2013-02-27

    ...: 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. daily... Federal Aviation Administration Meeting: RTCA Special Committee 223, Airport Surface Wireless...

  19. 76 FR 6179 - Eighth Meeting: RTCA Special Committee 223: Airport Surface Wireless Communications

    Science.gov (United States)

    2011-02-03

    ...: RTCA Special Committee 223: Airport Surface Wireless Communications AGENCY: Federal Aviation... 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: The meeting will be...

  20. 75 FR 14483 - Third Meeting: RTCA Special Committee 223: Airport Surface Wireless Communications

    Science.gov (United States)

    2010-03-25

    ...: 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: The... Committee 223: Airport Surface Wireless Communications meeting. The agenda will include: Tuesday, April 13...

  1. 75 FR 30899 - Fourth Meeting: RTCA Special Committee 223: Airport Surface Wireless Communications

    Science.gov (United States)

    2010-06-02

    ...: 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: The... Committee 223: Airport Surface Wireless Communications meeting. The agenda will include: Tuesday, June 15...

  2. 78 FR 33145 - Meeting: RTCA Special Committee 223, Airport Surface Wireless Communications

    Science.gov (United States)

    2013-06-03

    ...: 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. daily... Federal Aviation Administration Meeting: RTCA Special Committee 223, Airport Surface Wireless...

  3. 76 FR 20436 - Ninth Meeting: RTCA Special Committee 223: Airport Surface Wireless Communications

    Science.gov (United States)

    2011-04-12

    ... of RTCA Special Committee 223: Airport Surface Wireless Communications meeting. SUMMARY: The FAA is... Wireless Communications. DATES: The meeting will be held May 3-5, 2011 from 9 a.m. to 5 p.m. ADDRESSES: The... hereby given for a RTCA Special Committee 223: Airport Surface Wireless Communications meeting. Agenda...

  4. 77 FR 55894 - Thirteenth Meeting: RTCA Special Committee 223, Airport Surface Wireless Communications

    Science.gov (United States)

    2012-09-11

    ...: 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 a.m.-5... Federal Aviation Administration Thirteenth Meeting: RTCA Special Committee 223, Airport Surface Wireless...

  5. 75 FR 66423 - Seventh Meeting: RTCA Special Committee 223: Airport Surface Wireless Communications

    Science.gov (United States)

    2010-10-28

    ... 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. ADDRESSES...), notice is hereby given for a RTCA Special Committee 223: Airport Surface Wireless Communications meeting...

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

    Directory of Open Access Journals (Sweden)

    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.

  7. Radium-223 dichloride for metastatic castration-resistant prostate cancer: the urologist's perspective.

    Science.gov (United States)

    Shore, Neal D

    2015-04-01

    Radium-223 dichloride (radium-223) is an important therapeutic option for the treatment of patients with castration-resistant prostate cancer, symptomatic bone metastases, and no visceral disease. The unique mechanism of action of this first-in-class alpha-emitting radiopharmaceutical underlies its favorable safety profile and low incidence of myelosuppression. In the pivotal phase 3 ALpharadin in SYMptomatic Prostate CAncer Patients study, radium-223 reduced the risk of death by 30% and prolonged time to first symptomatic skeletal event by 5.8 months. This article summarizes current guidelines and clinical studies that led to the approval of radium-223 as an overall survival therapy, and discusses the urologist's perspective on using radium-223 in clinical practice. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  8. Survival benefit with radium-223 dichloride in a mouse model of breast cancer bone metastasis.

    Science.gov (United States)

    Suominen, Mari I; Rissanen, Jukka P; Käkönen, Rami; Fagerlund, Katja M; Alhoniemi, Esa; Mumberg, Dominik; Ziegelbauer, Karl; Halleen, Jussi M; Käkönen, Sanna-Maria; Scholz, Arne

    2013-06-19

    Bone metastases are associated with increased morbidity and poor prognosis in breast cancer patients. Radium-223 dichloride is a calcium mimetic that localizes to bone, providing targeted therapy for skeletal metastasis. We investigated the mode of action of radium-223 dichloride using breast cancer cell, osteoclast, and osteoblast cultures as well as a mouse model of breast cancer bone metastasis. A single dose of radium-223 dichloride was used in three different settings mimicking the prevention or treatment of bone metastasis. Disease progression was monitored using fluorescence and radiographic imaging and histological analyses. The effect of radium-223 dichloride alone and in combination with doxorubicin or zoledronic acid on survival of mice was analyzed by Kaplan-Meier methods. All statistical tests used were two-sided. Radium-223 dichloride incorporated into bone matrix and inhibited proliferation of breast cancer cells and differentiation of osteoblasts and osteoclasts (all P values radium-223 dichloride prevented tumor-induced cachexia (0/14 vs 7/14 control mice) and decreased osteolysis by 56% and tumor growth by 43% (all P values Radium-223 dichloride induced double-strand DNA breaks in cancer cells in vivo. Finally, radium-223 dichloride extended survival as a monotherapy (29.2 days, 95% confidence interval [CI] = 26.6 to 31.8 days, P = .039) and in combination with zoledronic acid (31.4 days, 95% CI = 28.8 to 34.0 days, P = .004) or doxorubicin (31.5 days, 95% CI = 29.5 to 33.5 days, P radium-223 dichloride was administered in a preventive or micrometastatic setting. Our findings strongly support the development of radium-223 dichloride for the treatment of breast cancer patients with or at high risk of developing bone metastases.

  9. Effect of radium-223 dichloride (Ra-223) on hospitalisation: An analysis from the phase 3 randomised Alpharadin in Symptomatic Prostate Cancer Patients (ALSYMPCA) trial.

    Science.gov (United States)

    Parker, Christopher; Zhan, Lin; Cislo, Paul; Reuning-Scherer, Jonathan; Vogelzang, Nicholas J; Nilsson, Sten; Sartor, Oliver; O'Sullivan, Joe M; Coleman, Robert E

    2017-01-01

    Symptomatic skeletal events (SSEs) commonly occur in patients with bone metastases, often leading to hospitalisations and decreased quality-of-life. In the ALSYMPCA trial, radium-223 significantly improved overall survival (hazard ratio 0.70, 95% confidence interval [CI] 0.58-0.83, P radium-223 (218/589; 37.0%) versus placebo patients (133/292; 45.5%) had at least one hospitalisation event (P = 0.016). However, mean number of hospitalisation events per patient was similar (radium-223 0.69 versus placebo 0.79, P = 0.226), likely due to the significantly longer follow-up time for radium-223 (7.82 months versus 6.92 months for placebo; P radium-223 (4.44 versus 6.68, respectively, P = 0.004). The reduction in hospitalisation days with radium-223 was observed both before first SSE (2.35 days versus 3.36 days, respectively) and after SSE (7.74 days versus 9.19 days, respectively). Our data suggest that this reduced hospital days along with the survival benefit and reduction in time to SSEs with radium-223 treatment may contribute to improvements in health-related quality-of-life in patients with castration-resistant prostate cancer with symptomatic bone metastases (ALSYMPCA ClinicalTrials.gov number, NCT00699751.). Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  10. MicroRNA-223 dose levels fine tune proliferation and differentiation in human cord blood progenitors and acute myeloid leukemia

    NARCIS (Netherlands)

    B. Gentner (Bernhard); N. Pochert (Nicole); A. Rouhi (Arefeh); F. Boccalatte (Francesco); T. Plati (Tiziana); T. Berg (Tobias); S.M. Sun; S.M. Mah (Sarah M.); M. Mirkovic-Hösle (Milijana); J. Ruschmann (Jens); A. Muranyi (Andrew); S. Leierseder (Simon); B. Argiropoulos (Bob); D.T. Starczynowski (Daniel T.); A. Karsan (Aly); M. Heuser (Michael); D. Hogge (Donna); F.D. Camargo (Fernando D.); S. Engelhardt (Stefan); H. Döhner (Hartmut); C. Buske (Christian); M. Jongen-Lavrencic (Mojca); L. Naldini (Luigi); R.K. Humphries (R. Keith); F. Kuchenbauer (Florian)

    2015-01-01

    textabstractA precise understanding of the role of miR-223 in human hematopoiesis and in the pathogenesis of acute myeloid leukemia (AML) is still lacking. By measuring miR-223 expression in blasts from 115 AML patients, we found significantly higher miR-223 levels in patients with favorable

  11. 48 CFR 952.223-71 - Integration of environment, safety, and health into work planning and execution.

    Science.gov (United States)

    2010-10-01

    ..., safety, and health into work planning and execution. 952.223-71 Section 952.223-71 Federal Acquisition... Provisions and Clauses 952.223-71 Integration of environment, safety, and health into work planning and... safety and health standards applicable to the work conditions of contractor and subcontractor employees...

  12. [Radium-223 treatment of bone metastases from castration-resistant prostate cancer].

    Science.gov (United States)

    Mortensen, Jann; Højgaard, Liselotte

    2014-07-21

    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 symptoms. Intravenously administered (22)3Ra-Cl2 (half-life 11.4 days) will likely be given every four weeks for six treatments to out-patients.

  13. 31 CFR 223.13 - Full penalty of the obligation regarded as the liability; exceptions.

    Science.gov (United States)

    2010-07-01

    ... the contract will be regarded as the liability. (e) Bonds for banks or trust companies as principals... SERVICE SURETY COMPANIES DOING BUSINESS WITH THE UNITED STATES § 223.13 Full penalty of the obligation...

  14. 36 CFR 223.193 - Procedures for reporting acquisition and disposition of unprocessed Federal timber.

    Science.gov (United States)

    2010-07-01

    ... Forest Resources Conservation and Shortage Relief Act of 1990 Program § 223.193 Procedures for reporting...; (iii) An agreement to maintain and/or replace all brands and paint identifying the Federal origin of...

  15. Imaging and dosimetry for radium-223: the potential for personalized treatment.

    Science.gov (United States)

    Flux, Glenn D

    2017-08-01

    Radium-223 ((223)Ra) offers a new option for the treatment of bone metastases from prostate cancer. As cancer treatment progresses towards personalization, the potential for an individualized approach is exemplified in treatments with radiotherapeutics due to the unique ability to image in vivo the uptake and retention of the therapeutic agent. This is unmatched in any other field of medicine. Currently, (223)Ra is administered according to standard fixed administrations, modified according to patient weight. Although gamma emissions comprise only 1% of the total emitted energy, there are increasing reports that quantitative imaging is feasible and can facilitate patient-specific dosimetry. The aim of this article is to review the application of imaging and dosimetry for (223)Ra and to consider the potential for treatment optimization accordingly, in order to ensure clinical and cost effectiveness of this promising agent.

  16. Alpha-emitter radium-223 in the management of solid tumors: current status and future directions.

    Science.gov (United States)

    Nilsson, Sten

    2014-01-01

    Bone metastases, which are commonly seen in patients with advanced cancers, are a major cause of skeletal events, disability, and death. Radium-223 dichloride (radium-223; Xofigo, formerly Alpharadin), a first-in-class, alpha-emitting radiopharmaceutical that selectively targets bone metastases with high-energy short-range alpha-particles, has been approved for the treatment of patients with castration-resistant prostate cancer (CRPC) with symptomatic bone metastases and no known visceral metastases. Approval is based on results of the randomized phase III trial Alpharadin in Symptomatic Prostate Cancer (ALSYMPCA), in which radium-223 prolonged overall survival and time to first symptomatic skeletal event versus placebo among patients with CRPC with symptomatic bone metastases and was generally well tolerated, with low myelosuppression rates and manageable gastrointestinal adverse events. Long-term follow-up of the ALSYMPCA safety population showed that the incidence of myelosuppression remained low among patients treated with radium-223, with no additional safety issues of acute myelogenous leukemia, myelodysplastic syndrome, aplastic anemia, or primary bone cancer within approximately 1.5 years after treatment. The radium-223 overall survival benefit and low toxicity make it an effective, well-tolerated, and novel treatment option for CRPC and symptomatic bone metastases and opens the possibility of exploring radium-223 in the treatment of bone metastases from other cancers. A phase I clinical trial of patients with breast and prostate cancer with skeletal metastases demonstrated that radium-223 was safe and well tolerated at all therapeutically relevant dosages. Moreover, a phase IIa trial of patients with advanced breast cancer and progressive bone-dominant disease demonstrated that radium-223 targeted areas of increased bone metabolism and showed biologic activity.

  17. MicroRNA-223 is a novel negative regulator of HSP90B1 in CLL.

    Science.gov (United States)

    Rodríguez-Vicente, Ana E; Quwaider, Dalia; Benito, Rocío; Misiewicz-Krzeminska, Irena; Hernández-Sánchez, María; de Coca, Alfonso García; Fisac, Rosa; Alonso, José-María; Zato, Carolina; de Paz, Juan Francisco; García, Juan Luis; Sarasquete, Ma Eugenia; Hernández, José Ángel; Corchado, Juan M; González, Marcos; Gutiérrez, Norma C; Hernández-Rivas, Jesús-María

    2015-04-08

    MicroRNAs are known to inhibit gene expression by binding to the 3'UTR of the target transcript. Downregulation of miR-223 has been recently reported to have prognostic significance in CLL. However, there is no evidence of the pathogenetic mechanism of this miRNA in CLL patients. By applying next-generation sequencing techniques we have detected a common polymorphism (rs2307842), in 24% of CLL patients, which disrupts the binding site for miR-223 in HSP90B1 3'UTR. We investigated whether miR-223 directly targets HSP90B1 through luciferase assays and ectopic expression of miR-223. Quantitative real-time polymerase chain reaction and western blot were used to determine HSP90B1 expression in CLL patients. The relationship between rs2307842 status, HSP90B1 expression and clinico-biological data were assessed. HSP90B1 is a direct target for miR-223 by interaction with the putative miR-223 binding site. The analysis in paired samples (CD19+ fraction cell and non-CD19+ fraction cell) showed that the presence of rs2307842 and IGHV unmutated genes determined HSP90B1 overexpression in B lymphocytes from CLL patients. These results were confirmed at the protein level by western blot. Of note, HSP90B1 overexpression was independently predictive of shorter time to the first therapy in CLL patients. By contrast, the presence of rs2307842 was not related to the outcome. HSP90B1 is a direct target gene of miR-223. Our results provide a plausible explanation of why CLL patients harboring miR-223 downregulation are associated with a poor outcome, pointing out HSP90B1 as a new pathogenic mechanism in CLL and a promising therapeutic target.

  18. MicroRNA-223 Expression Is Upregulated in Insulin Resistant Human Adipose Tissue

    Directory of Open Access Journals (Sweden)

    Tung-Yueh Chuang

    2015-01-01

    Full Text Available MicroRNAs (miRNAs are short noncoding RNAs involved in posttranscriptional regulation of gene expression and influence many cellular functions including glucose and lipid metabolism. We previously reported that adipose tissue (AT from women with polycystic ovary syndrome (PCOS or controls with insulin resistance (IR revealed a differentially expressed microRNA (miRNA profile, including upregulated miR-93 in PCOS patients and in non-PCOS women with IR. Overexpressed miR-93 directly inhibited glucose transporter isoform 4 (GLUT4 expression, thereby influencing glucose metabolism. We have now studied the role of miR-223, which is also abnormally expressed in the AT of IR subjects. Our data indicates that miR-223 is significantly overexpressed in the AT of IR women, regardless of whether they had PCOS or not. miR-223 expression in AT was positively correlated with HOMA-IR. Unlike what is reported in cardiomyocytes, overexpression of miR-223 in human differentiated adipocytes was associated with a reduction in GLUT4 protein content and insulin-stimulated glucose uptake. In addition, our data suggests miR-223 regulates GLUT4 expression by direct binding to its 3′ untranslated region (3′UTR. In conclusion, in AT miR-223 is an IR-related miRNA that may serve as a potential therapeutic target for the treatment of IR-related disorders.

  19. Radium-223 in treatment of castration-resistant prostate cancer with skeletal metastases

    Directory of Open Access Journals (Sweden)

    V. B. Matveev

    2017-01-01

    Full Text Available More than 90 % of patients with metastatic castration-resistant prostate cancer (CRPC have radiologically confirmed skeletal metastases. Traditional treatment methods such as administration of painkillers, external beam therapy, bisphosphonates or denosumab, as well as injections of strontium-89 or samarium-153 radionuclides, have only palliative effect and in some cases can postpone development of skeletal complications. Alpha-emitter radium-223 dichloride (Ra-223; alpharadin previously is currently one of the known drugs with proven effectiveness in relation to increasing overall survival of patients with CRPC. Ra-223 was developed specifically for patients with CRPC and symptomatic skeletal metastases. The drug targets the areas of skeletal tissue remodeling. Ra-223 is the therapy of choice in patients with CRPC and skeletal metastases and without confirmed visceral metastases before and after docetaxel chemotherapy. Chemotherapy after treatment with Ra-223 is a possible and satisfactory tolerable treatment option. Combination of Ra-223 with abiraterone, enzalutamide, or denosumab is, apparently, effective and safe, but further studies are necessary.

  20. Radium-223 chloride: Extending life in prostate cancer patients by treating bone metastases.

    Science.gov (United States)

    Wissing, Michel D; van Leeuwen, Fijs W B; van der Pluijm, Gabri; Gelderblom, Hans

    2013-11-01

    The treatment scope for patients with metastatic castrate-resistant prostate cancer (mCRPC) is rapidly expanding. On May 15, 2013, the U.S. Food and Drug Administration (FDA) approved radium-223 chloride ((223)RaCl2) for the treatment of mCRPC patients whose metastases are limited to the bones. Radium-223 is an α-emitting alkaline earth metal ion, which, similar to calcium ions, accumulates in the bone. In a phase III study (ALSYMPCA), mCRPC patients with bone metastases received best standard-of-care treatment with placebo or (223)RaCl2. At a prespecified interim analysis, the primary endpoint of median overall survival was significantly extended by 3.6 months in patients treated with radium-223 compared with placebo (P < 0.001). The radioisotope was well tolerated and gave limited bone marrow suppression. (223)RaCl2 is the first bone-targeting antitumor therapy that received FDA approval based on a significant extended median overall survival. Further studies are required to optimize its dosing and to confirm its efficacy and safety in cancer patients.

  1. Clinical Correlates of Benefit From Radium-223 Therapy in Metastatic Castration Resistant Prostate Cancer.

    Science.gov (United States)

    Alva, Ajjai; Nordquist, Luke; Daignault, Stephanie; George, Saby; Ramos, Jorge; Albany, Costantine; Isharwal, Sudhir; McDonald, Matthew; Campbell, Gregory; Danchaivijitr, Pongwut; Yentz, Sarah; Anand, Aseem; Yu, Evan Y

    2017-04-01

    We sought to identify potential clinical variables associated with outcomes after radium-223 therapy in routine practice. Consecutive non-trial mCRPC patients who received ≥1 dose of radium dichloride-223 at four academic and one community urology-specific cancer centers from May 2013 to June 2014 were retrospectively identified. Association of baseline and on-therapy clinical variables with number of radium doses received and clinical outcomes including overall survival were analyzed using chi-square statistics, cox proportional hazards, and Kaplan-Meier methods. Bone Scan Index (BSI) was derived from available bone scans using EXINI software. One hundred and forty-five patients were included. Radium-223 was administered for six cycles in 74 patients (51%). One-year survival in this heavily pre-treated population was 64% (95%CI: 54-73%). In univariate and multivariate analysis, survival was highly associated with receiving all six doses of Radium-223. Receipt of six doses was associated with ECOG PS of 0-1, lower baseline PSA & pain level, no prior abiraterone/enzalutamide, radium-223. Radium-223 therapy is well tolerated with most patients reporting declines in pain scores and BSI. Prostate 77:479-488, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  2. Bone-seeking radiopharmaceuticals as targeted agents of osteosarcoma: samarium-153-EDTMP and radium-223.

    Science.gov (United States)

    Anderson, Peter M; Subbiah, Vivek; Rohren, Eric

    2014-01-01

    Osteosarcoma is a cancer characterized by formation of bone by malignant cells. Routine bone scan imaging with Tc-99m-MDP is done at diagnosis to evaluate primary tumor uptake and check for bone metastases. At time of relapse the Tc-99m-MDP bone scan also provides a specific means to assess formation of bone by malignant osteosarcoma cells and the potential for bone-seeking radiopharmaceuticals to deliver radioactivity directly into osteoblastic osteosarcoma lesions. This chapter will review and compare a bone-seeking radiopharmaceutical that emits beta-particles, samarium-153-EDTMP, with an alpha-particle emitter, radium-223. The charged alpha particles from radium-223 have far more mass and energy than beta particles (electrons) from Sm-153-EDTMP. Because radium-223 has less marrow toxicity and more radiobiological effectiveness, especially if inside the bone forming cancer cell than samarium-153-EDTMP, radium-223 may have greater potential to become widely used against osteosarcoma as a targeted therapy. Radium-223 also has more potential to be used with chemotherapy against osteosarcoma and bone metastases. Because osteosarcoma makes bone and radium-223 acts like calcium, this radiopharmaceutical could possibly become a new targeted means to achieve safe and effective reduction of tumor burden as well as facilitate better surgery and/or radiotherapy for difficult to resect large, or metastatic tumors.

  3. Radium-223 dichloride for the treatment of castration-resistant prostate cancer with symptomatic bone metastases.

    Science.gov (United States)

    Vogelzang, Nicholas J

    2017-08-01

    Castration-resistant prostate cancer (CRPC) is associated with the development of bone metastases, increased mortality, and a reduction in the patient's quality of life (QOL). The management of metastatic CRPC (mCRPC) has rapidly evolved over the past decade, with a number of available therapeutic agents improving overall survival. Radium-223 dichloride (radium-223), the first targeted alpha therapy, improves survival accompanied by QOL benefits with a favorable safety profile. It is approved in over 40 countries for the treatment of patients with CRPC with symptomatic bone metastases and no known visceral metastatic disease. Areas covered: The current management of CRPC in men with bone metastases, and in particular the role of radium-223 in this setting, is reviewed and discussed. A search of bibliographic databases for peer-reviewed literature and major meetings was conducted. Expert commentary: In treating patients with mCRPC, the best sequencing and/or combination of radium-223 with other agents has yet to be fully elucidated. The role of radium-223 in treating patients with hormone-sensitive metastatic prostate cancer who are candidates for chemotherapy should also be investigated in well-designed trials. The ability to tailor radium-223 therapy to both the clinical and genetic profiles of CRPC patients would be a promising development.

  4. Radium-223 Use in Clinical Practice and Variables Associated With Completion of Therapy.

    Science.gov (United States)

    McKay, Rana R; Jacobus, Susanna; Fiorillo, Matthew; Ledet, Elisa M; Cotogna, Patrick M; Steinberger, Allie E; Jacene, Heather A; Sartor, Oliver; Taplin, Mary-Ellen

    2017-04-01

    Radium-223 has shown clinical efficacy in metastatic castration-resistant prostate cancer. Despite improvement in quality of life and survival, practice patterns and utility of this agent outside the context of clinical trials have not been fully characterized. The primary objective in this study was to evaluate variables associated with completion of 5 to 6 radium-223 doses. We conducted retrospective analyses of patients who received radium-223 (n = 135). Patients were classified into 3 cohorts: 1 to 2, 3 to 4, or 5 to 6 radium-223 doses. We evaluated the association of clinical and laboratory variables with the number of cycles administered (5-6 vs. 1-4 doses). Twenty-five patients (18.5%) received 1 to 2 radium-223 doses, 27 (20.0%) received 3 to 4, and 83 (61.5%) received 5 to 6. The most common reasons for treatment discontinuation included disease progression (61.5%, n = 40), patient preference (15.4%, n = 10), and toxicity (10.8%, n = 7). Factors associated with therapy completion in univariate analysis included previous sipuleucel-T treatment (P = .068), no previous abiraterone or enzalutamide treatment (P = .007), hemoglobin ≥ lower limit of normal (LLN; P = .006), white blood cell count ≥ LLN (P = .045), absolute neutrophil count (ANC) ≥ LLN (P = .049), lower alkaline phosphatase (P = .029), and lower lactate dehydrogenase levels (P = .014). Factors associated with therapy completion in multivariable analysis included previous sipuleucel-T treatment (P = .009), hemoglobin ≥ LLN (P = .037), and ANC ≥ LLN (P = .029). Several clinical parameters are associated with radium-223 therapy completion. In general, these parameters reflect earlier disease stage. These data are hypothesis-generating and prospective testing of the optimal number of radium-223 doses is warranted. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. MicroRNA-223 Displays a Protective Role Against Cardiomyocyte Hypertrophy by Targeting Cardiac Troponin I-Interacting Kinase

    Directory of Open Access Journals (Sweden)

    Yao-Sheng Wang

    2015-03-01

    Full Text Available Background/Aims: MicroRNAs play regulatory role in cardiovascular disease. MicroRNA-223 (miR-223 was found to be expressed abundantly in myocardium. TNNI3K, a novel cardiac troponin I (cTnI-interacting and cardiac hypertrophy related kinase, is computationally predicted as a potential target of miR-223. This study was designed to investigate the cellular and molecular effects of miR-223 on cardiomyoctye hypertrophy, focusing on the role of TNNI3K. Methods: Neonatal rat cardiomyocytes (CMs were cultured, and CMs hypertrophy was induced by endothelin-1 (ET-1. In vivo cardiac hypertrophy was induced by transverse aorta constriction (TAC in rats. Expression of miR-223 in CMs and myocardium was detected by real-time PCR (RT-PCR. MiR-223 and TNNI3K were overexpressed in CMs via chemically modifed sense RNA (miR-223 mimic transfection or recombinant adenovirus infection, respectively. Cell size was measured by surface area calculation using fluorescence microscopy after anti-α-actinin staining. Expression of hypertrophy-related genes was detected by RT-PCR. The protein expression of TNNI3K and cTnI was determined by Western blots. Luciferase assay was employed to confirm the direct binding of miR-223 to the 3'UTR of TNNI3K mRNA. Intracellular calcium was measured by sensitive fluorescent indicator (Furo-2. Video-based edge detection system was employed to measure cardiomyocyte contractility. Results: MiR-223 was downregulated in ET-1 induced hypertrophic CMs and in hypertrophic myocardium compared with respective controls. MiR-223 overexpression in CMs alleviated ET-1 induced hypertrophy, evidenced by smaller cell surface area and downregulated ANP, α-actinin, Myh6 and Myh7 expression. Luciferase reporter gene assay showed that TNNI3K serves as a direct target gene of miR-223. In miR-223-overexpressed CMs, the protein expression of TNNI3K was significantly downregulated. MiR-223 overexpression also rescued the upregulated TNNI3K expression in

  6. Lymphocyte function following radium-223 therapy in patients with metastasized, castration-resistant prostate cancer

    Energy Technology Data Exchange (ETDEWEB)

    Barsegian, Vahe; Moeckel, Daniel [Helios Kliniken, Institute of Nuclear Medicine, Schwerin (Germany); Mueller, Stefan P.; Bockisch, Andreas [University Hospital Essen, Department of Nuclear Medicine, Essen (Germany); Horn, Peter A.; Lindemann, Monika [University Hospital Essen, Institute for Transfusion Medicine, Essen (Germany)

    2017-02-15

    Therapy with the alpha-emitter radium-223 chloride ({sup 223}Ra) is an innovative therapeutic option in patients with metastasized, castration-resistant prostate cancer. However, radiotherapy can lead to hematopoietic toxicity. The aim of this study was to determine if {sup 223}Ra therapy induces an impairment of cellular antimicrobial immune responses. In 11 patients receiving {sup 223}Ra treatment, lymphocyte proliferation and the production of pro- and anti-inflammatory cytokines (interferon-γ and interleukin-10) were determined, using lymphocyte transformation testing and ELISpot, respectively. Lymphocyte function after stimulation with mitogens and microbial antigens was assessed prior to therapy and at day 1, 7 and 28 after therapy. Lymphocyte proliferation and the production of interferon-γ and interleukin-10 towards mitogens and antigens remained unchanged after therapy. Consistent with these in vitro data, we did not observe infectious complications after treatment. The results argue against an impairment of lymphocyte function after {sup 223}Ra therapy. Thus, immune responses against pathogens should remain unaffected. (orig.)

  7. Lymphocyte function following radium-223 therapy in patients with metastasized, castration-resistant prostate cancer.

    Science.gov (United States)

    Barsegian, Vahé; Müller, Stefan P; Möckel, Daniel; Horn, Peter A; Bockisch, Andreas; Lindemann, Monika

    2017-02-01

    Therapy with the alpha-emitter radium-223 chloride ((223)Ra) is an innovative therapeutic option in patients with metastasized, castration-resistant prostate cancer. However, radiotherapy can lead to hematopoietic toxicity. The aim of this study was to determine if (223)Ra therapy induces an impairment of cellular antimicrobial immune responses. In 11 patients receiving (223)Ra treatment, lymphocyte proliferation and the production of pro- and anti-inflammatory cytokines (interferon-γ and interleukin-10) were determined, using lymphocyte transformation testing and ELISpot, respectively. Lymphocyte function after stimulation with mitogens and microbial antigens was assessed prior to therapy and at day 1, 7 and 28 after therapy. Lymphocyte proliferation and the production of interferon-γ and interleukin-10 towards mitogens and antigens remained unchanged after therapy. Consistent with these in vitro data, we did not observe infectious complications after treatment. The results argue against an impairment of lymphocyte function after (223)Ra therapy. Thus, immune responses against pathogens should remain unaffected.

  8. [Alpha emitter radium-223 dichloride: new therapy in castration-resistant prostate cancer with symptomatic bone metastases].

    Science.gov (United States)

    Heinzer, H; König, F; Klutmann, S

    2014-04-01

    Radium-223 dichloride (Ra-223) is an alpha emitter with low toxicity for the treatment of patients with castrations-resistant prostate cancer (CRPC) and symptomatic bone metastases showing a 30% reduction in the risk of death, as compared to placebo. Because of the favorable physical and chemical characteristics, Ra-223 can be handled easily in daily practice based on interdisciplinary co-operation between urology and nuclear medicine. Ra-223 has been approved under the product name Xofigo® by the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA).

  9. [Role of microRNA-223 and its target gene oncogene c-myc in hepatocellular carcinoma pathogenesis].

    Science.gov (United States)

    Zhao, Wen-Yue; Wang, Dong-Dong; Song, Meng-Qi; Yang, Ling; Ye, Jin; Chen, Li-Bo

    2011-02-01

    To investigate the regulatory role of microRNA-223 (miR-223) on c-myc and its role in hepatocarcinogenesis. miR-223 and c-myc mRNA expressions in normal tissue, paraneoplastic tissue, liver cancer tissue and liver cancer cells were tested with microRNA microarray and quantitative real-time PCR (qRT-PCR). C-myc protein expression was detected by Western blot. MiR-223 mimic was transfected into HepG2 cells and the expression changes of c-myc mRNA and protein were tested with qRT-PCR and Western blot respectively. MiR-223 was down-regulated by 61.53% and 30.77% respectively in hepatocellular carcinoma and adjacent tissues as compared to normal liver tissues and the expression of miR-223 was also decreased in HepG2 cell as compared to fetal liver cells L02, whereas the expressions of c-myc mRNA and protein increased in paraneoplastic and HCC tissues compared with normal liver tissues. It prompts that the expressions of miR-223 and c-myc are negatively correlated. No obvious difference found among c-myc mRNA expressions after miR-223 mimics transfection. The c-myc abnormal high-expression may play a dynamic role in hepatocarcinogenesis due to the miR-223 down-regulation.

  10. Radium-223 therapy of advanced metastatic castration-resistant prostate cancer

    DEFF Research Database (Denmark)

    Fosbøl, Marie Øbro; Petersen, Peter Meidahl; Kjaer, Andreas

    2018-01-01

    ratio 2.65 [95% CI: 1.5-4.71];P= 0.001). Likewise, baseline BSI was prognostic for occurrence of hematological toxicity and patients with BSI > 5 had an odds ratio of 3.02 (95% CI: 1.2-7.8;P= 0.02) for toxicity. BSI declined during therapy in 44% of patients who completed three cycles of223RaCl2(n= 52......Aim: To investigate the prognostic value of quantitative assessment of skeletal tumor burden on bone scintigraphy (Bone Scan Index) in patients with advanced metastatic castration-resistant prostate cancer (mCRPC) receiving Radium-223-dichloride (223RaCl2). We hypothesize that Bone Scan Index (BSI...

  11. Radium-223 in Heavily Pretreated Metastatic Castrate-Resistant Prostate Cancer.

    Science.gov (United States)

    Modi, Dipenkumar; Hwang, Clara; Mamdani, Hirva; Kim, Seongho; Gayar, Hesham; Vaishampayan, Ulka; Joyrich, Richard; Heath, Elisabeth I

    2016-10-01

    Radium-223 is a bone-targeting radiopharmaceutical that extends survival in mCRPC. Postapproval data are limited, and the value of biochemical and radiologic monitoring during radium therapy is unknown. We conducted a retrospective study of 29 patients with mCRPC who received radium-223 at 1 of 3 participating institutions between August 2013 and December 2014. Trend of PSA, radiographic changes, and association of biochemical and clinical variables with PSA trend were measured. The median age of patients was 70 years, 79% of patients (N = 23) were European Americans, and 17% of patients (N = 5) were African Americans. Twenty patients (69%) had received at least 3 lines of prior therapies. Some 38% of patients (N = 11) received all 6 cycles of radium-223. Twenty patients (69%) had an increase in PSA during radium therapy, and 4 patients (14%) had a decline in PSA levels. Five patients had visceral metastases on computed tomography imaging performed during the course of radium-223. Radium therapy in mCRPC was associated with an increase in PSA in the majority of these heavily pretreated patients. The development of visceral disease was not uncommon, suggesting a need for follow-up computed tomography monitoring during radium-223 therapy. The significance of early increases in PSA and pain with radium-223 is still uncertain. Although pain and PSA flare have been reported in patients who subsequently have a dramatic response to therapy, we observed that a PSA increase or pain flare correlates to an improvement in bone scans only in a minority of patients. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. 2-(2,3-Dihydro-1H-indol-3-yl)ethanol

    DEFF Research Database (Denmark)

    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....

  13. Radium 223: how can we optimize this new tool for metastatic castration-resistant prostate cancer?

    Science.gov (United States)

    Dorff, Tanya Barauskas; Gross, Mitchell E

    2015-01-01

    Radium 223 is an alpha-emitting intravenous radiotherapy approved for the treatment of men with metastatic castration-resistant prostate cancer (mCRPC). The approved indication covers men with pain from bony metastatic disease and no visceral involvement; however, questions remain as to optimal patient selection and timing of this treatment relative to other life-extending therapies for mCRPC. Limited data exist to guide clinicians on how to position radium 223 in the therapeutic sequence, however, some theoretical considerations and data derived from the ALSYMPCA trial populations pre- and postdocetaxel will be outlined. Subgroup analyses may provide some insight into patient selection.

  14. Radium-223 dichloride: a novel treatment option for castration-resistant prostate cancer patients with symptomatic bone metastases.

    Science.gov (United States)

    McGann, Shane; Horton, Evan R

    2015-04-01

    To review and evaluate the clinical trial efficacy and safety of radium 223 ((223)Ra) along with its place in therapy in men with castration-resistant prostate cancer (CRPC). A literature search in PubMed/MEDLINE (up to October 2014) was performed using various combinations of the terms radium, hormone-refractory prostate cancer, and castration-resistant prostate cancer. The New Drug Application Medical, Pharmacology, and Clinical Pharmacology and Biopharmaceutics Reviews for radium (223)Ra dichloride were also utilized. The bibliographies of articles were reviewed to identify additional references. Phase 1, 2, and 3 studies that assessed the safety and/or efficacy of (223)Ra in patients with CRPC were reviewed. Peer-reviewed articles with clinically relevant information were reviewed for background information. In May 2013, the Food and Drug Administration approved intravenous use of (223)Ra for the treatment of patients with CRPC, symptomatic bone metastases, and no known visceral metastatic disease. In a phase 3 study comparing (223)Ra and the best standard of care (SOC) versus the best SOC plus placebo, (223)Ra was shown to increase survival. The most commonly seen adverse drug reactions and hematological laboratory abnormalities with (223)Ra include nausea, diarrhea, vomiting, peripheral edema, anemia, lymphocytopenia, leukopenia, thrombocytopenia, and neutropenia. (223)Ra is a first-in-class α-particle-emitting radioactive agent that is first-line therapy, providing an extra option for men suffering from CRPC with symptomatic bone metastases and no known visceral metastases. (223)Ra has also been shown to be relatively well tolerated when up to 6 injections are given. Further studies are needed to evaluate whether (223)Ra is safe and effective for more than 6 doses and if it can be used concomitantly with chemotherapy. © The Author(s) 2015.

  15. 36 CFR 223.113 - Modification of contracts to prevent environmental damage or to conform to forest plans.

    Science.gov (United States)

    2010-07-01

    ... 36 Parks, Forests, and Public Property 2 2010-07-01 2010-07-01 false Modification of contracts to prevent environmental damage or to conform to forest plans. 223.113 Section 223.113 Parks, Forests, and Public Property FOREST SERVICE, DEPARTMENT OF AGRICULTURE SALE AND DISPOSAL OF NATIONAL FOREST SYSTEM...

  16. A model-specific role of microRNA-223 as a mediator of kidney injury during experimental sepsis.

    Science.gov (United States)

    Colbert, James F; Ford, Joshay A; Haeger, Sarah M; Yang, Yimu; Dailey, Kyrie L; Allison, Kristen C; Neudecker, Viola; Evans, Christopher M; Richardson, Vanessa L; Brodsky, Kelley S; Faubel, Sarah; Eltzschig, Holger K; Schmidt, Eric P; Ginde, Adit A

    2017-08-01

    Sepsis outcomes are heavily dependent on the development of septic organ injury, but no interventions exist to interrupt or reverse this process. microRNA-223 (miR-223) is known to be involved in both inflammatory gene regulation and host-pathogen interactions key to the pathogenesis of sepsis. The goal of this study was to determine the role of miR-223 as a mediator of septic kidney injury. Using miR-223 knockout mice and multiple models of experimental sepsis, we found that miR-223 differentially influences acute kidney injury (AKI) based on the model used. In the absence of miR-223, mice demonstrated exaggerated AKI in sterile models of sepsis (LPS injection) and attenuated AKI in a live-infection model of sepsis (cecal ligation and puncture). We demonstrated that miR-223 expression is induced in kidney homogenate after cecal ligation and puncture, but not after LPS or fecal slurry injection. We investigated additional potential mechanistic explanations including differences in peritoneal bacterial clearance and host stool virulence. Our findings highlight the complex role of miR-223 in the pathogenesis of septic kidney injury, as well as the importance of differences in experimental sepsis models and their consequent translational applicability. Copyright © 2017 the American Physiological Society.

  17. 36 CFR 223.118 - Appeal process for small business timber sale set-aside program share recomputation decisions.

    Science.gov (United States)

    2010-07-01

    ... business timber sale set-aside program share recomputation decisions. 223.118 Section 223.118 Parks... business timber sale set-aside program share recomputation decisions. (a) Decisions subject to appeal. The... predecisional review and comment on any draft decision to reallocate shares, including the data used in making...

  18. 36 CFR 223.203 - Indirect substitution exception for National Forest System timber from within Washington State.

    Science.gov (United States)

    2010-07-01

    ... exception for National Forest System timber from within Washington State. 223.203 Section 223.203 Parks... Indirect substitution exception for National Forest System timber from within Washington State. (a... Washington State could have been acquired by a person otherwise covered by the prohibition against indirect...

  19. 12 CFR 223.23 - What valuation and timing principles apply to purchases of and investments in securities issued...

    Science.gov (United States)

    2010-01-01

    ....23 What valuation and timing principles apply to purchases of and investments in securities issued by... 12 Banks and Banking 3 2010-01-01 2010-01-01 false What valuation and timing principles apply to purchases of and investments in securities issued by an affiliate? 223.23 Section 223.23 Banks and Banking...

  20. Circulating MicroRNA-223 Serum Levels Do Not Predict Sepsis or Survival in Patients with Critical Illness

    Directory of Open Access Journals (Sweden)

    Fabian Benz

    2015-01-01

    Full Text Available Background and Aims. Dysregulation of miR-223 was recently linked to various diseases associated with systemic inflammatory responses such as type 2 diabetes, cancer, and bacterial infections. However, contradictory results are available on potential alterations of miR-223 serum levels during sepsis. We thus aimed to evaluate the diagnostic and prognostic value of miR-223 serum concentrations in patients with critical illness and sepsis. Methods. We used i.v. injection of lipopolysaccharide (LPS as well as cecal pole ligation and puncture (CLP for induction of polymicrobial sepsis in mice and measured alterations in serum levels of miR-223. These results from mice were translated into a large and well-characterized cohort of critically ill patients admitted to the medical intensive care unit (ICU. Finally, results from analysis in patients were correlated with clinical data and extensive sets of routine and experimental biomarkers. Results. Although LPS injection induced moderately elevated serum miR-223 levels in mice, no significant alterations in miR-223 serum levels were found in mice after CLP-induced sepsis. In accordance with these results from animal models, serum miR-223 levels did not differ between critically ill patients and healthy controls. However, ICU patients with more severe disease (APACHE-II score showed moderately reduced circulating miR-223. Strikingly, no differences in miR-223 levels were found in critically ill patients with or without sepsis, and serum levels of miR-223 did not correlate with classical markers of inflammation or bacterial infection. Finally, low miR-223 serum levels were moderately associated with an unfavorable prognosis of patients during the ICU treatment but did not predict long-term mortality. Conclusion. Recent reports on alterations in miR-223 serum levels during sepsis revealed contradictory results, preventing a potential use of this miRNA in clinical routine. We clearly show that miR-223 serum

  1. Circulating microRNA-223 serum levels do not predict sepsis or survival in patients with critical illness.

    Science.gov (United States)

    Benz, Fabian; Tacke, Frank; Luedde, Mark; Trautwein, Christian; Luedde, Tom; Koch, Alexander; Roderburg, Christoph

    2015-01-01

    Dysregulation of miR-223 was recently linked to various diseases associated with systemic inflammatory responses such as type 2 diabetes, cancer, and bacterial infections. However, contradictory results are available on potential alterations of miR-223 serum levels during sepsis. We thus aimed to evaluate the diagnostic and prognostic value of miR-223 serum concentrations in patients with critical illness and sepsis. We used i.v. injection of lipopolysaccharide (LPS) as well as cecal pole ligation and puncture (CLP) for induction of polymicrobial sepsis in mice and measured alterations in serum levels of miR-223. These results from mice were translated into a large and well-characterized cohort of critically ill patients admitted to the medical intensive care unit (ICU). Finally, results from analysis in patients were correlated with clinical data and extensive sets of routine and experimental biomarkers. Although LPS injection induced moderately elevated serum miR-223 levels in mice, no significant alterations in miR-223 serum levels were found in mice after CLP-induced sepsis. In accordance with these results from animal models, serum miR-223 levels did not differ between critically ill patients and healthy controls. However, ICU patients with more severe disease (APACHE-II score) showed moderately reduced circulating miR-223. Strikingly, no differences in miR-223 levels were found in critically ill patients with or without sepsis, and serum levels of miR-223 did not correlate with classical markers of inflammation or bacterial infection. Finally, low miR-223 serum levels were moderately associated with an unfavorable prognosis of patients during the ICU treatment but did not predict long-term mortality. Recent reports on alterations in miR-223 serum levels during sepsis revealed contradictory results, preventing a potential use of this miRNA in clinical routine. We clearly show that miR-223 serum levels do not reflect the presence of sepsis neither in mouse

  2. 36 CFR 223.195 - Procedures for identifying and marking unprocessed timber.

    Science.gov (United States)

    2010-07-01

    ... Conservation and Shortage Relief Act of 1990 Program § 223.195 Procedures for identifying and marking unprocessed timber. (a) Highway yellow paint. The use of highway yellow paint on unprocessed logs west of the... or placed in storage must be marked on both ends with yellow paint. (c) National Forest System logs...

  3. 36 CFR 223.194 - Procedures for reporting the acquisition and disposition of unprocessed private timber.

    Science.gov (United States)

    2010-07-01

    ... Forest Resources Conservation and Shortage Relief Act of 1990 Program § 223.194 Procedures for reporting... domestic manufacturing by a spot of highway yellow paint on each log end that must be retained on the... to maintain yellow paint markings on each log end until the timber is domestically processed or...

  4. XTE J1752-223 has faded to quiescence: optical and infrared magnitudes

    NARCIS (Netherlands)

    Russell, D. M.; Muñoz-Darias, T.; Lewis, F.; Soleri, P.

    We have been regularly monitoring the outburst decay of the black hole candidate X-ray binary XTE J1752-223 (discovered by RXTE; ATel #2258) with the 2-m Faulkes Telescopes North and South (located at Haleakala on Maui and Siding Spring, Australia, respectively). Exposures in B, V, R and i'-bands

  5. Yeast Interacting Proteins Database: YLR223C, YOR247W [Yeast Interacting Proteins Database

    Lifescience Database Archive (English)

    Full Text Available YLR223C IFH1 Essential protein with a highly acidic N-terminal domain; IFH1 exhibits genetic interactions...ion Essential protein with a highly acidic N-terminal domain; IFH1 exhibits genetic interactions with FHL1,

  6. 20 CFR 702.223 - Claims; time limitations; time to object.

    Science.gov (United States)

    2010-04-01

    ... such right unless objection to such failure is made at the first hearing of such claim in which all... 20 Employees' Benefits 3 2010-04-01 2010-04-01 false Claims; time limitations; time to object. 702... Procedures Claims § 702.223 Claims; time limitations; time to object. Notwithstanding the requirements of...

  7. 29 CFR 22.3 - Basis for civil penalties and assessments.

    Science.gov (United States)

    2010-07-01

    ... Labor Office of the Secretary of Labor PROGRAM FRAUD CIVIL REMEDIES ACT OF 1986 § 22.3 Basis for civil... made to the authority, recipient, or party when such claim is actually made to an agent, fiscal... an agent, fiscal intermediary, or other entity, including any State or political subdivision thereof...

  8. 48 CFR 1852.223-76 - Federal Automotive Statistical Tool Reporting.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 6 2010-10-01 2010-10-01 true Federal Automotive... Provisions and Clauses 1852.223-76 Federal Automotive Statistical Tool Reporting. As prescribed at 1823.271 and 1851.205, insert the following clause: Federal Automotive Statistical Tool Reporting (JUL 2003) If...

  9. 27 CFR 25.223 - Destruction of beer off brewery premises.

    Science.gov (United States)

    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 without...

  10. 12 CFR 223.54 - What advertisements and statements are prohibited by section 23B?

    Science.gov (United States)

    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 enter...

  11. 36 CFR 223.226 - Term adjustments for force majeure delay.

    Science.gov (United States)

    2010-07-01

    ... 36 Parks, Forests, and Public Property 2 2010-07-01 2010-07-01 false Term adjustments for force... AGRICULTURE SALE AND DISPOSAL OF NATIONAL FOREST SYSTEM TIMBER Special Forest Products Contract and Permit Conditions and Provisions § 223.226 Term adjustments for force majeure delay. Contracts or other authorizing...

  12. Dosimetry of {sup 223}Ra-chloride: dose to normal organs and tissues

    Energy Technology Data Exchange (ETDEWEB)

    Lassmann, Michael [University of Wuerzburg, Department of Nuclear Medicine, Wuerzburg (Germany); Nosske, Dietmar [Federal Office for Radiation Protection (BfS), Department of Radiation and Health, Oberschleissheim (Germany)

    2013-02-15

    {sup 223}Ra-Chloride (also called Alpharadin {sup 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 {sup 223}Ra-chloride. The purpose of this work was to provide a comprehensive dosimetric calculation of organ doses after intravenous administration of {sup 223}Ra-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 {sup 223}Ra-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.)

  13. 48 CFR 1252.223-73 - Seat belt use policies and programs.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Seat belt use policies and....223-73 Seat belt use policies and programs. As prescribed in (TAR) 48 CFR 1223.7000(c), insert the following clause: Seat Belt Use Policies and Programs (APR 2005) In accordance with Executive Order 13043...

  14. 12 CFR 223.33 - What rules apply to derivative transactions?

    Science.gov (United States)

    2010-01-01

    ... 12 Banks and Banking 3 2010-01-01 2010-01-01 false What rules apply to derivative transactions... 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...

  15. 36 CFR 223.6 - Cutting and removal of timber in free-use areas.

    Science.gov (United States)

    2010-07-01

    ... 36 Parks, Forests, and Public Property 2 2010-07-01 2010-07-01 false Cutting and removal of timber... OF AGRICULTURE SALE AND DISPOSAL OF NATIONAL FOREST SYSTEM TIMBER General Provisions § 223.6 Cutting... or designated by forest officers may be cut and removed for personal use for domestic purposes...

  16. Meeting Report From the Prostate Cancer Foundation Scientific Working Group on Radium-223.

    Science.gov (United States)

    Miyahira, Andrea K; Morris, Michael; Soule, Howard R

    2017-02-01

    The Prostate Cancer Foundation (PCF) convened a Scientific Working Group Meeting on Radium-223 on September 8, 2016, at The Sidney Kimmel Center for Prostate and Urologic Cancers, Memorial Sloan Kettering Cancer Center. The meeting was attended by 18 investigators with expertise in radium-223, bone biology, molecular imaging, biomarkers, and prostate cancer clinical trials. The goal of this meeting was to discuss the known and unknown surroundings the therapeutic effects of the bone targeting agent radium-223, in bone metastatic prostate cancer therapy, and to outline the most critical studies needed to improve the clinical use of this agent. Three major topic areas were discussed: (1) the basic science of radium; (2) immuno-adjuvant properties of radium therapy; and (3) high impact clinical trials and correlative science. This article reviews the major topics discussed at the meeting for the purpose of accelerating studies that will improve the use of radium-223 in the treatment of prostate cancer patients. Prostate 77:245-254, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  17. 31 CFR 800.223 - Solely for the purpose of passive investment.

    Science.gov (United States)

    2010-07-01

    ... (Continued) OFFICE OF INVESTMENT SECURITY, DEPARTMENT OF THE TREASURY REGULATIONS PERTAINING TO MERGERS, ACQUISITIONS, AND TAKEOVERS BY FOREIGN PERSONS Definitions § 800.223 Solely for the purpose of passive... Board of Directors. The acquisition by Corporation A of a voting interest in Corporation B is not solely...

  18. Hematologic Toxicity of Concurrent Administration of Radium-223 and Next-generation Antiandrogen Therapies.

    Science.gov (United States)

    Dan, Tu D; Eldredge-Hindy, Harriet B; Hoffman-Censits, Jean; Lin, Jianqing; Kelly, William K; Gomella, Leonard G; Lallas, Costas D; Trabulsi, Edouard J; Hurwitz, Mark D; Dicker, Adam P; Den, Robert B

    2017-08-01

    Radium-223 is a first-in-class radiopharmaceutical recently approved for the treatment of castration-resistant prostate cancer in patients with symptomatic bone metastases. Initial studies investigating Radium-223 primarily used nonsteroidal first-generation antiandrogens. Since that time, newer antiandrogen therapies have demonstrated improved survival in patients with castration-resistant prostate cancer. It has been suggested that the rational combination of these newly approved agents with Radium-223 may lead to improved response rates and clinical outcomes. Currently, there is lack of information regarding the safety of concurrent administration of these agents with radiopharmaceuticals. Here, we report on hematologic toxicity findings from our institution in patients receiving concurrent Radium-223 and next-generation antiandrogen therapies with either enzalutamide or abiraterone. In a retrospective study, we analyzed patients who received Radium-223 as part of an early-access trial, and following FDA approval in May 2013, patients receiving Radium-223 as part of standard care. Radium-223 was given at standard dosing of 50 kBq/kg each month for 6 total cycles. Complete blood counts were performed before treatment monthly and following each injection. Blood counts from patients receiving Radium alone and concurrently with next-generation antiandrogens were compared. To date, 25 total patients were analyzed, with a median of 5 monthly doses received per patient. Fourteen patients received concurrent therapy during monthly Radium-223 with either enzalutamide (n=8) or abiraterone (n=6). Six patients expired due to disease progression. Two patients discontinued treatment due to grade 3 myelosuppression. For patients receiving either Radium alone and with concurrent next-generation antiandrogen therapy, there did not appear to be any statistically significant differences between initial and nadir blood counts. Mean change from initial neutrophil count to nadir was

  19. SU-F-J-08: Quantitative SPECT Imaging of Ra-223 in a Phantom

    Energy Technology Data Exchange (ETDEWEB)

    Yue, J; Hobbs, R; Sgouros, G; Frey, E [Johns Hopkins University Baltimore, MD (United States)

    2016-06-15

    Purpose: Ra-223 therapy of prostate cancer bone metastases is being used to treat patients routinely. However, the absorbed dose distribution at the macroscopic and microscopic scales remains elusive, due to the inability to image the small activities injected. Accurate activity quantification through imaging is essential to calculate the absorbed dose in organs and sub-units in radiopharmaceutical therapy, enabling personalized absorbed dose-based treatment planning methodologies and more effective and optimal treatments. Methods: A 22 cm diameter by 20 cm long cylindrical phantom, containing a 3.52 cm diameter sphere, was used. A total of 2.01 MBq of Ra-223 was placed in the phantom with 177.6 kBq in the sphere. Images were acquired on a dual-head Siemens Symbia T16 gamma camera using three 20% full-width energy windows and centered at 84, 154, and 269 keV (120 projections, 360° rotation, 45 s per view). We have implemented reconstruction of Ra-223 SPECT projections using OS-EM (up to 20 iterations of 10 subsets) with compensation for attenuation using CT-based attenuation maps, collimator-detector response (CDR) (including septal penetration, scatter and Pb x-ray modeling), and scatter in the patient using the effective source scatter estimation (ESSE) method. The CDR functions and scatter kernels required for ESSE were computed using the SIMIND MC simulation code. All Ra-223 photon emissions as well as gamma rays from the daughters Rn-219 and Bi-211 were modeled. Results: The sensitivity of the camera in the three combined windows was 107.3 cps/MBq. The visual quality of the SPECT images was reasonably good and the activity in the sphere was 27% smaller than the true activity. This underestimation is likely due to partial volume effect. Conclusion: Absolute quantitative Ra-223 SPECT imaging is achievable with careful attention to compensate for image degrading factors and system calibration.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  1. Radium-223 dichloride: a review of its use in patients with castration-resistant prostate cancer with symptomatic bone metastases.

    Science.gov (United States)

    Shirley, Matt; McCormack, Paul L

    2014-04-01

    Radium-223 dichloride (Xofigo®; formerly Alpharadin™) [hereafter referred to as radium-223] is a first-in-class alpha particle-emitting radiopharmaceutical that has recently been approved for the treatment of patients with castration-resistant prostate cancer (CRPC) with symptomatic bone metastases and no known visceral metastatic disease. Radium-223 is a calcium mimetic, which targets bone, delivering cytotoxic radiation to the sites of bone metastases. In the recently reported Alpharadin™ in Symptomatic Prostate Cancer (ALSYMPCA) phase III study, radium-223 was associated with significantly improved overall survival compared with placebo, making it the first bone-targeted CRPC therapy for which an overall survival benefit has been demonstrated. The ALSYMPCA study also demonstrated the beneficial effects of radium-223 on disease-related symptomatic skeletal events, pain and health-related quality of life. Radium-223 was generally well tolerated, being associated with low rates of myelosuppression and generally mild gastrointestinal adverse events. Thus, radium-223 is a valuable addition to the treatment options for this poor-prognosis population.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.)

  3. The Impact of MicroRNA-223-3p on IL-17 Receptor D Expression in Synovial Cells.

    Directory of Open Access Journals (Sweden)

    Nozomu Moriya

    Full Text Available Rheumatoid arthritis (RA is an autoimmune inflammatory disease affecting joints. Elevated plasma levels of microRNA-223-3p (miR-223-3p in patients with RA are implicated in the pathogenesis of the disease. This study aimed to analyze the functional role of miR-223-3p in the pathogenesis of RA by overexpressing miR-223-3p in synovial cell lines.Arthritis was induced in the RA model of SKG mice by injection of ß-glucan. The histopathologic features of joints were examined using hematoxylin and eosin and immunohistochemical staining. Plasma levels of miRNA were determined by panel real-time PCR analysis. Target genes of the differentially expressed miRNAs in SKG mice were analyzed using miRNA target prediction algorithms. The dual-luciferase reporter system was used to evaluate the relationship between miR-223-3p and IL-17 receptor D (IL-17RD. The activity of miR-223-3p was analyzed by transfection of plasmid vectors overexpressing miR-223-3p into IL-17RD-expressing NIH3T3 and MH7A cell lines. Il6 and Il17rd mRNA expression was analyzed by quantitative real-time PCR. IL-17RD protein expression was analyzed by western blot analysis.We identified 17 upregulated miRNAs (fold change > 2.0 in plasma of SKG mice injected with ß-glucan relative to untreated SKG mice. Il17rd was identified as the candidate target gene of miR-223-3p using five miRNA target prediction algorithms. The transfection of plasmid vectors overexpressing miR-223-3p into NIH3T3 and MH7A cells resulted in the downregulation of Il17rd expression and upregulation of Il6 expression. Expression of miR-223-3p and Il6 mRNA in MH7A cells was upregulated; however, that of Il17rd mRNA was downregulated following TNF-α stimulation. IL-17RD expression in synovial tissues from SKG mice and RA patients was inversely correlated with the severity of arthritis.This study is the first to demonstrate that miR-223-3p downregulates IL-17RD in both mouse and human cells; miR-223-3p may contribute to

  4. Kepler-223: A Resonant Chain of Four Sub-Neptune Planets

    Science.gov (United States)

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

    2015-12-01

    The Kepler mission has revealed an abundance of pairs of planets in the same system which often lie near, but not exactly on, resonance. Understanding how and when they entered a resonance and were removed from it has implications for their birthplaces and planetary structure. Here we characterize Kepler-223 (KOI-730), an outstanding example of a system of small planets in resonance. We perform TTV, photodynamic, stability, and migration analyses to determine the system's most likely current parameters and resonant state. Its four sub-Neptune planets form a chain linked by 4:3, 3:2, and 2:1 resonances that cause measurable dynamical effects and imply a disk-migration origin. Tidal dissipation in the planets or wide-scale instability may eventually transform resonant chains of planets like Kepler-223 into the more common type of architecture.

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

    CERN Multimedia

    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.

  6. Radium-223 dichloride: a new paradigm in the treatment of prostate cancer.

    Science.gov (United States)

    Anido Herranz, Urbano; Fernández Calvo, Ovidio; Afonso Afonso, Francisco Javier; Rodríguez Martínez de Llano, Sofía; Lázaro Quintela, Martín; León Mateos, Luis; Vázquez Estévez, Sergio; Antón Aparicio, Luis Miguel

    2015-03-01

    Radionuclides have been widely used for cancer treatment. Recently, new research about radium-223 dichloride has been conducted in prostate cancer, which reveals that it is the first radiopharmaceutical to demonstrate an improvement in overall survival and time to first symptomatic skeletal event in patients with castration resistant prostate cancer with symptomatic bone metastases. This fact has created a new paradigm in the treatment of prostate cancer landscape, where only chemotherapy and hormone therapy had a role, while β-emitters had been confined exclusively to the role of pain relief with no impact on survival. The aim of this review is to outline current treatment approaches for advanced prostate cancer with a focus on the role of radium-223 dichloride, reviewing patients' profile that make them suitable to therapy and chances for further studies.

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

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    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.

  8. Leptin receptor Q223R polymorphism in Egyptian female patients with breast cancer

    Directory of Open Access Journals (Sweden)

    Mona Abo-Bakr El-Hussiny

    2017-03-01

    Full Text Available Aim of the study: Breast cancer is the most common cause of death in women. Obesity has been associated with increased risk of breast cancer in post-menopausal women. It induces chronic inflammation, which increases local and systemic levels of cytokines and adipokines such as leptin. Leptin (LEP and leptin receptor (LEPR genes have several polymorphisms in humans. This study aims to assess the association between blood levels of leptin and LEPR Q223R gene polymorphism in patients of cancer breast. Material and methods : The current study was carried on 48 female breast cancer patients and 48 heathy female subjects. Carcinoembryonic antigen (CEA, cancer antibody CA15-3, and leptin hormone were determined. Single nucleotide polymorphism of LEPR Q223R was assessed by PCR/RFLP. Statistical analysis used: The statistical analysis of data was done by using SPSS version 20. Results : There were significant increases in the concentrations of CEA (p = 0.004, CA15-3 (p < 0.001, and leptin hormone (p < 0.001 in BC patients in relation to the respective concentrations in control subjects. CEA and CA 15-3 showed significant differences between various BC stages. As regard to LEPR Q223R gene polymorphism, AA genotype showed significantly higher frequency in BC patients when compared to their respective controls, with higher risk to develop BC. Conclusions : Leptin hormone shows significantly higher concentrations in BC patients. As regard to LEPR Q223R gene polymorphism, AA genotype showed significantly higher frequency in BC patients.

  9. Extraction of (223)Radium by haemodialysis after treatment of metastatic castration-resistant prostate cancer.

    Science.gov (United States)

    Großer, Oliver Stephan; Wissel, Heiko; Wallbaum, Thekla; Genseke, Philipp; Kupitz, Dennis; Ricke, Jens; Ruf, Juri; Amthauer, Holger

    2017-06-13

    (223)Radium-dichloride ((223)Ra) administration is an upcoming therapeutic option in patients with castration-resistant metastatic prostate cancer (mCRPC), whose renal and faecal excretion of (223)Ra has been primarily estimated from data of a phase-I clinical trial in patients with normal renal function. In the rare case of concomitant renal insufficiency requiring haemodialysis (HD), an estimation of the contamination of dialysate would be beneficial. The excretion of (223)Ra and its concentration in the dialysate in a patient with mCRPC and end-stage renal disease was examined for six consecutive treatment cycles. Dialysate samples were measured using a commercial system with NaI-scintillation detector. HD showed a residual activity level in the remaining dialysate. The excreted activity was a median of 46.1 kBq (range = 42.0- 83.4 kBq) and 11.2 kBq (range = 8.4- 19.9 kBq) for the first (24 h post injection p.i.) and second HD (96 h p.i.), respectively. The activity concentration decreased significantly from a median of 4.18 kBq/l (range = 2.98-5.14 kBq/l) to 0.85 kBq/l (range = 0.69- 1.31 kBq/l, p handling has to be followed to fulfil the radiation protection regulations.

  10. Comparing Clinical Outcomes for Radium-223: Do Older Patients Do Worse?

    Science.gov (United States)

    Song, Yee Pei; Ellis, Tracey; Walshaw, Richard; Mbanu, Peter; Parikh, Omi; Logue, John; Choudhury, Ananya

    2017-07-15

    To examine the clinical benefits and toxicities of (223)Ra in 2 different age groups of patients with castrate-resistant prostate cancer. This was a retrospective study of patients treated with (223)Ra in 2 tertiary centers. Patients were divided into 2 different groups based on their age (≥72 years old and <72 years old). Treatment toxicities were graded according to Common Terminology Criteria for Adverse Events version 4.0. Comparison of characteristics and outcome was carried out with the Mann-Whitney test and analysis of overall survival with the log-rank test. In all, 129 patients were treated during the study period. Clinical benefit was similar in both groups. However, a statistically significant higher proportion of patients in the younger group had previously been treated with docetaxel. There was a higher rate of grade 3 anemia in younger patients. In line with other studies, (223)Ra was well tolerated with minimum toxicities. The significantly higher rate of grade 3 anemia in younger patients may be due to more cautious patient selection in the elderly population. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Dysregulation of miR-223 constitutes a promising biomarker that informs about clinical outcomes of acute liver failure.

    Science.gov (United States)

    Lauschke, Volker M

    2017-08-01

    In this issue of Clinical Science, Schueller et al. [Clin. Sci. (2017) 131, 1971-1987] evaluated the role of miR-223 across multiple etiologies of acute and chronic liver insults in murine models and clinical samples. The authors find that while miR-223 is not mechanistically involved in liver injury, its intracellular levels in hepatocytes are increased upon hepatic damage in a broad panel of mechanistically distinct injury models. Furthermore, the authors provide evidence that circulating miR-223 levels provide a promising minimally invasive biomarker for acute liver failure (ALF) that defines a distinct subset of ALF cases and correlates with clinical outcomes. Combined, the highlighted study suggests that miR-223 constitutes a promising biomarker whose clinical validity and utility warrant further investigations. © 2017 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

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

    Directory of Open Access Journals (Sweden)

    Harrison MR

    2013-01-01

    Full Text Available Michael R Harrison, Terence Z Wong, Andrew J Armstrong, Daniel J GeorgeDuke Cancer Institute, Durham, NC, USABackground: 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.Objective: This review describes the mechanism, radiobiology, and preclinical development of 223Ra and discusses the clinical data currently available regarding its safety and efficacy profile.Methods: 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.Conclusion: 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

  13. (223)Ra-dichloride spectrometric characterization: Searching for the presence of long-lived isotopes with radiological protection implications.

    Science.gov (United States)

    Sánchez-Jiménez, J; López-Montes, A; Núñez-Martínez, L; Villa-Abaunza, A; Fraile, L M; Sánchez-Tembleque, V; Udías, J M

    2017-03-01

    (223)Ra-dichloride was approved with the commercial name of Xofigo in 2014 for treatment of metastatic castration-resistant prostate cancer. (223)Ra is obtained by neutron irradiation of (226)Ra yielding (227)Ac, which decays to (227)Th and (223)Fr, both decaying to (223)Ra. Since (223)Ra is predominantly (95.3%) an alpha emitter with a 11.42days long half-life, the radiopharmaceutical, its remnants, the patient, and waste material can be managed and disposed with low radiation protection requirements. (227)Ac is a long-lived (T1/2=21.77years) beta emitter that demands strong radiation protection measures. In particular waste disposal has to follow the International Atomic Energy Agency (IAEA) and European Commission (EC) regulations. Since (227)Ac is involved in the production of (223)Ra, an impurity analysis of each batch is required after production. Due to time restrictions, the manufacturer's detection limit (<0.001%) exceeds the one required to assure that (227)Ac concentrations are below direct disposal levels. To improve the detection limit, long-term accurate spectroscopy is required. Alpha and gamma spectroscopy measurements were carried out at the Complutense University Nuclear Physics Laboratory. After twelve months follow up of a sample, (227)Ac concentration was found to be smaller than 10(-9). This allows for direct waste disposal and no additional radiation protection restrictions than those required for (223)Ra. The presence of contamination by other radioisotopes was also ruled out by this experiment. Specifically (226)Ra, involved in (223)Ra production as the original parent and with a very long-lived (T1/2=1577years) alpha emitter, was also below the experimental detection limit. Copyright © 2017 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

  14. A phase IIa, nonrandomized study of radium-223 dichloride in advanced breast cancer patients with bone-dominant disease.

    Science.gov (United States)

    Coleman, Robert; Aksnes, Anne-Kirsti; Naume, Bjørn; Garcia, Camilo; Jerusalem, Guy; Piccart, Martine; Vobecky, Nancy; Thuresson, Marcus; Flamen, Patrick

    2014-06-01

    Radium-223 dichloride (radium-223) mimics calcium and emits high-energy, short-range alpha-particles resulting in an antitumor effect on bone metastases. This open-label, phase IIa nonrandomized study investigated safety and short-term efficacy of radium-223 in breast cancer patients with bone-dominant disease. Twenty-three advanced breast cancer patients with progressive bone-dominant disease, and no longer candidates for further endocrine therapy, were to receive radium-223 (50 kBq/kg IV) every 4 weeks for 4 cycles. The coprimary end points were change in urinary N-telopeptide of type 1 (uNTX-1) and serum bone alkaline phosphatase (bALP) after 16 weeks of treatment. Exploratory end points included sequential (18)F-fluorodeoxyglucose positron emission tomography and computed tomography (FDG PET/CT) to assess metabolic changes in osteoblastic bone metastases. Safety data were collected for all patients. Radium-223 significantly reduced uNTX-1 and bALP from baseline to end of treatment. Median uNTX-1 change was -10.1 nmol bone collagen equivalents/mmol creatinine (-32.8 %; P = 0.0124); median bALP change was -16.7 ng/mL (-42.0 %; P = 0.0045). Twenty of twenty-three patients had FDG PET/CT identifying 155 hypermetabolic osteoblastic bone lesions at baseline: 50 lesions showed metabolic decrease (≥25 % reduction of maximum standardized uptake value from baseline) after 2 radium-223 injections [32.3 % metabolic response rate (mRR) at week 9], persisting after the treatment period (41.5 % mRR at week 17). Radium-223 was safe and well tolerated. Radium-223 targets areas of increased bone metabolism and shows biological activity in advanced breast cancer patients with bone-dominant disease.

  15. New short-lived isotope 223Np and the absence of the Z = 92 subshell closure near N = 126

    Science.gov (United States)

    Sun, M. D.; Liu, Z.; Huang, T. H.; Zhang, W. Q.; Wang, J. G.; Liu, X. Y.; Ding, B.; Gan, Z. G.; Ma, L.; Yang, H. B.; Zhang, Z. Y.; Yu, L.; Jiang, J.; Wang, K. L.; Wang, Y. S.; Liu, M. L.; Li, Z. H.; Li, J.; Wang, X.; Lu, H. Y.; Lin, C. J.; Sun, L. J.; Ma, N. R.; Yuan, C. X.; Zuo, W.; Xu, H. S.; Zhou, X. H.; Xiao, G. Q.; Qi, C.; Zhang, F. S.

    2017-08-01

    The N = 130 short-lived isotope 223Np was produced as evaporation residue (ER) in the fusion reaction 40Ar + 187Re at the gas-filled recoil separator Spectrometer for Heavy Atom and Nuclear Structure (SHANS). It was identified through temporal and spatial correlations with α decays of 215Ac and/or 211Fr, the third and fourth members of the α-decay chain starting from 223Np. The pileup signals of ER(223Np)-α(223Np)-α(219Pa) were resolved by using the digital pulse processing technique. An α decay with half-life of T1/2 = 2.15 (10052) μs and energy of Eα = 9477 (44) keV was attributed to 223Np. Spin and parity of 9 /2- were tentatively proposed for the ground state of 223Np by combining the reduced α-decay width and large-scale shell-model calculations. This assignment together with the proton separation energy disprove the existence of a Z = 92 subshell closure.

  16. Ginkgolide B Inhibits Human Bladder Cancer Cell Migration and Invasion Through MicroRNA-223-3p

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    Yi Zhi

    2016-10-01

    Full Text Available Background/Aims: Ginkgolide B (GB is currently used as an anticancer drug for treatment of some malignant cancers. However, whether it may have therapeutic effects on bladder cancer remains unknown. Here, we studied the effects of GB on bladder cancer cells. Methods: Bladder cells were treated with different doses of GB, and the effects on ZEB1 and microRNA-223-3p (miR-223-3p were analyzed by RT-qPCR and/or Western blot. Prediction of a regulatory relationship between miR-93 and 3'-UTR of Beclin-1 mRNA was performed by a bioinformatics algorithm and confirmed by a dual luciferase reporter assay. Results: We found that GB dose-dependently decreased ZEB1 protein, but not mRNA, in bladder cancer cells, resulting in suppression of cell invasion. Moreover, in bladder cancer cells, GB dose-dependently decreased the levels of miR-223-3p, which suppressed the protein translation of ZEB1 through binding to 3'-UTR of ZEB1 mRNA. Overexpression of miR-223-3p decreased ZEB1 protein, while depletion of miR-223-3p increased ZEB1 protein in bladder cancer cells. Conclusion: GB inhibits bladder cancer cell invasiveness through suppressing ZEB1 protein translation via upregulating miR-223-3p.

  17. MicroRNA-22-3p as a novel regulator and therapeutic target for autoimmune diseases.

    Science.gov (United States)

    Wang, Bin; Yao, Qiuming; Xu, Donghua; Zhang, Jin-An

    2017-05-04

    MicroRNAs (miRNAs) are a class of noncoding RNAs and have emerged as critical regulators of gene expression. Some miRNAs play important roles in regulating the function of the immune system and are involved in the pathogenesis of autoimmune diseases. Recent studies suggested that microRNA-22-3p (miR-22-3p) was able to regulate the function of several types of immune cells and may be involved in the development of autoimmune diseases. We systematically reviewed relevant literatures to provide a comprehensive review of the possible roles of miR-22-3p in autoimmune diseases. Published studies suggest that miR-22-3p can act as a novel regulator of autoimmune diseases via several pathways. More studies are needed to further elucidate the exact roles of miR-22-3p in autoimmune diseases. Treatment strategy targeting miR-22-3p is also a promising therapy for autoimmune diseases.

  18. Radium-223 dichloride for the treatment of bone metastatic castration-resistant prostate cancer: an evaluation of its safety.

    Science.gov (United States)

    Nilsson, Sten

    2015-07-01

    Approximately 10 - 20% of prostate cancer cases ultimately progress to castration-resistant prostate cancer (CRPC), for which there is a poor prognosis and a therapeutic need. Radium-223 dichloride (radium-223 [Xofigo]) is a first-in-class α-emitting radiopharmaceutical shown to significantly prolong overall survival in patients with CRPC with symptomatic bone metastases and no visceral metastases. Current treatment guidelines recommended it in both pre- and post-docetaxel settings. Radium-223 mechanism of action, pharmacokinetics and key efficacy and safety data are reviewed. The evaluation of adverse events reported in the Phase III ALSYMPCA trial is summarized for the overall population and patient subpopulations (prior docetaxel, concomitant external beam radiation therapy and baseline opioid use). An evaluation of how radium-223 is being incorporated into the CRPC treatment paradigm and the implications of its safety profile for future use are provided. The pronounced efficacy and safety profile of radium-223 positions it as a valuable new therapeutic tool in the CRPC armamentarium. Its novel mechanism of action underlies low rates of hematologic adverse events. Radium-223 treatment will become common in the majority of pre-docetaxel symptomatic CRPC cases, as it has proved to be highly efficient with few safety concerns earlier in the course of disease.

  19. The potential of {sup 223}Ra and {sup 18}F-fluoride imaging to predict bone lesion response to treatment with {sup 223}Ra-dichloride in castration-resistant prostate cancer

    Energy Technology Data Exchange (ETDEWEB)

    Murray, Iain; Chittenden, Sarah J.; Denis-Bacelar, Ana M.; Flux, Glenn D. [Royal Marsden NHS Foundation Trust, Joint Department of Physics, Sutton, Surrey (United Kingdom); The Institute of Cancer Research, London (United Kingdom); Hindorf, Cecilia [Royal Marsden NHS Foundation Trust, Joint Department of Physics, Sutton, Surrey (United Kingdom); The Institute of Cancer Research, London (United Kingdom); Skaane University Hospital, Department of Radiation Physics, Lund (Sweden); Parker, Christopher C. [Royal Marsden NHS Foundation Trust, Department of Urology, Sutton (United Kingdom); Chua, Sue [Royal Marsden NHS Foundation Trust, Department of Nuclear Medicine, Sutton (United Kingdom)

    2017-10-15

    The aims of this study were to calculate bone lesion absorbed doses resulting from a weight-based administration of {sup 223}Ra-dichloride, to assess the relationship between those doses and corresponding {sup 18}F-fluoride uptake and to assess the potential of quantitative {sup 18}F-fluoride imaging to predict response to treatment. Five patients received two intravenous injections of {sup 223}Ra-dichloride, 6 weeks apart, at 110 kBq/kg whole-body weight. The biodistribution of {sup 223}Ra in metastatic lesions as a function of time after administration as well as associated lesion dosimetry were determined from serial {sup 223}Ra scans. PET/CT imaging using {sup 18}F-fluoride was performed prior to the first treatment (baseline), and at week 6 immediately before the second treatment and at week 12 after baseline. Absorbed doses to metastatic bone lesions ranged from 0.6 Gy to 44.1 Gy. For individual patients, there was an average factor difference of 5.3 (range 2.5-11.0) between the maximum and minimum lesion dose. A relationship between lesion-absorbed doses and serial changes in {sup 18}F-fluoride uptake was demonstrated (r{sup 2} = 0.52). A log-linear relationship was demonstrated (r{sup 2} = 0.77) between baseline measurements of {sup 18}F-fluoride uptake prior to {sup 223}Ra-dichloride therapy and changes in uptake 12 weeks after the first cycle of therapy. Correlations were also observed between both {sup 223}Ra and {sup 18}F-fluoride uptake in lesions (r = 0.75) as well as between {sup 223}Ra absorbed dose and {sup 18}F-fluoride uptake (r = 0.96). There is both inter-patient and intra-patient heterogeneity of absorbed dose estimates to metastatic lesions. A relationship between {sup 223}Ra lesion absorbed dose and subsequent lesion response was observed. Analysis of this small group of patients suggests that baseline uptake of {sup 18}F-fluoride in bone metastases is significantly correlated with corresponding uptake of {sup 223}Ra, the associated {sup 223

  20. Inorganic Phosphate Accelerates the Migration of Vascular Smooth Muscle Cells: Evidence for the Involvement of miR-223

    Science.gov (United States)

    Metzinger-Le Meuth, Valérie; Hénaut, Lucie; Djelouat, Mohamed Seif el Islam; Benchitrit, Joyce; Massy, Ziad A.; Metzinger, Laurent

    2012-01-01

    Backgound An elevated serum inorganic phosphate (Pi) level is a major risk factor for kidney disease and downstream vascular complications. We focused on the effect of Pi levels on human aortic vascular smooth muscle cells (VSMCs), with an emphasis on the role of microRNAs (miRNAs). Methodology/Principal Findings Exposure of human primary VSMCs in vitro to pathological levels of Pi increased calcification, migration rate and concomitantly reduced cell proliferation and the amount of the actin cytoskeleton. These changes were evidenced by significant downregulation of miRNA-143 (miR-143) and miR-145 and concomitant upregulation of their targets and key markers in synthetic VSMCs, such as Krüppel-like factors−4 and −5 and versican. Interestingly, we also found that miR-223 (a marker of muscle damage and a key factor in osteoclast differentiation) is expressed in VSMCs and is significantly upregulated in Pi-treated cells. Over-expressing miR-223 in VSMCs increased proliferation and markedly enhanced VSMC migration. Additionally, we found that the expression of two of the known miR-223 targets, Mef2c and RhoB, was highly reduced in Pi treated as well as miR-223 over-expressing VSMCs. To complement these in vitro findings, we also observed significant downregulation of miR-143 and miR-145 and upregulation of miR-223 in aorta samples collected from ApoE knock-out mice, which display vascular calcification. Conclusions/Significance Our results suggest that (i) high levels of Pi increase VSMC migration and calcification, (ii) altered expression levels of miR-223 could play a part in this process and (iii) miR-223 is a potential new biomarker of VSMC damage. PMID:23094093

  1. Inorganic phosphate accelerates the migration of vascular smooth muscle cells: evidence for the involvement of miR-223.

    Directory of Open Access Journals (Sweden)

    Ashraf Yusuf Rangrez

    Full Text Available BACKGROUND: An elevated serum inorganic phosphate (Pi level is a major risk factor for kidney disease and downstream vascular complications. We focused on the effect of Pi levels on human aortic vascular smooth muscle cells (VSMCs, with an emphasis on the role of microRNAs (miRNAs. METHODOLOGY/PRINCIPAL FINDINGS: Exposure of human primary VSMCs in vitro to pathological levels of Pi increased calcification, migration rate and concomitantly reduced cell proliferation and the amount of the actin cytoskeleton. These changes were evidenced by significant downregulation of miRNA-143 (miR-143 and miR-145 and concomitant upregulation of their targets and key markers in synthetic VSMCs, such as Krüppel-like factors-4 and -5 and versican. Interestingly, we also found that miR-223 (a marker of muscle damage and a key factor in osteoclast differentiation is expressed in VSMCs and is significantly upregulated in Pi-treated cells. Over-expressing miR-223 in VSMCs increased proliferation and markedly enhanced VSMC migration. Additionally, we found that the expression of two of the known miR-223 targets, Mef2c and RhoB, was highly reduced in Pi treated as well as miR-223 over-expressing VSMCs. To complement these in vitro findings, we also observed significant downregulation of miR-143 and miR-145 and upregulation of miR-223 in aorta samples collected from ApoE knock-out mice, which display vascular calcification. CONCLUSIONS/SIGNIFICANCE: Our results suggest that (i high levels of Pi increase VSMC migration and calcification, (ii altered expression levels of miR-223 could play a part in this process and (iii miR-223 is a potential new biomarker of VSMC damage.

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

    Science.gov (United States)

    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.

  3. Treatment landscape of metastatic prostate cancer: the role of radium-223.

    Science.gov (United States)

    Dermine, Alexandre; Machiels, Jean-Pascal

    2017-02-01

    The landscape of metastatic prostate cancer has changed recently with the availability of six new molecules showing an overall survival benefit. The development of compounds able to decrease the rate of complications from bone metastasis has also led to improvements in overall morbidity associated with this disease. In this paper, we briefly review the currently available drugs indicated in the treatment of metastatic prostate cancer, focusing on the place of the radiopharmaceutical agent radium-223 and its very unique mechanism of action and safety profile.

  4. Leptin receptor gene Gln223Arg polymorphism is not associated with obesity and metabolic syndrome in Turkish children.

    Science.gov (United States)

    Komşu-Ornek, Zuhal; Demirel, Fatma; Dursun, Ahmet; Ermiş, Bahri; Pişkin, Etem; Bideci, Aysun

    2012-01-01

    The aim of the study was to investigate the relationship between leptin receptor gene (LEPR) Gln223Arg polymorphism and obesity in Turkish children. Ninety-two obese and 99 lean children (between 5-15 years) were included in the study. Twenty-three of the obese children were diagnosed with metabolic syndrome. Blood samples were collected for morning fasting blood glucose, insulin, leptin, and lipid level measurements. LEPR Gln223Arg polymorphism was analyzed by restriction fragment length polymorphism. Significant differences were observed in anthropometric measurements, fasting blood glucose, insulin, leptin, and lipid levels between obese and lean children. Serum leptin levels were markedly higher in obese children. No significant association was noted between Gln223Arg polymorphism and serum leptin, insulin and lipid levels. There were no differences in the genotype frequencies or allele distribution for Gln223Arg polymorphism among obese, obese with metabolic syndrome and lean children. Our findings suggest that there is no association between Gln223Arg polymorphism and obesity in Turkish children.

  5. Radium-223 Therapy for Patients with Metastatic Castrate-Resistant Prostate Cancer: An Update on Literature with Case Presentation

    Science.gov (United States)

    Appleman, Leonard J.; Mountz, James M.

    2016-01-01

    Background and Purpose. Radium-223 dichloride (Xofigo®, Bayer HealthCare Pharmaceuticals Inc.) is the first α-particle emitter therapeutic agent approved by the FDA, with benefits in overall survival and delay in symptomatic skeletal event for patients with metastatic castrate-resistant prostate cancer (CRPC). Recent post hoc analyses of the phase III ALSYMPCA trial support the previously established safety profile as well as therapeutic effect and clinical outcome of Radium-223. Currently, Radium-223 is approved as a single agent therapy for metastatic CRPC. Clinical trials are currently investigating Radium-223 in additional clinical settings such as earlier asymptomatic disease and in combination with other agents including hormonal therapeutic agents and immunotherapeutic as well as chemotherapeutic agents. Trials are also ongoing in patients with other primary cancers such as breast cancer, thyroid cancer, and renal cancer metastatic to bone. In this article, the physics and radiobiology, as well as a literature update on the use of Radium-223, are provided along with case presentations, aiming at a better appreciation of research data as well as the assimilation of research data into clinical practice. PMID:27774318

  6. Evolving treatment approaches for the management of metastatic castration-resistant prostate cancer – role of radium-223

    Directory of Open Access Journals (Sweden)

    Mukherji D

    2014-05-01

    Full Text Available Deborah Mukherji,1 Imane El Dika,1 Sally Temraz,1 Mohammed Haidar,2 Ali Shamseddine11Department of Hematology/Oncology, 2Department of Nuclear Medicine, American University of Beirut Medical Center, Beirut, LebanonAbstract: Radium-223 is a first-in-class alpha particle-emitting radiopharmaceutical approved for the treatment of bone metastatic castration-resistant prostate cancer. Radium-223 is administered intravenously with no requirement for complex shielding and specifically targets areas of bone metastasis. In a randomized placebo-controlled Phase III study, treatment with radium-223 was shown to improve overall survival, time to skeletal-related events, and health-related quality of life. Apart from radium-223, the cytotoxic chemotherapy agents docetaxel and cabazitaxel, androgen biosynthesis inhibitor abiraterone acetate, novel anti-androgen enzalutamide, and immunotherapy sipuleucel-T have also been shown to improve survival of men with advanced prostate cancer in Phase III trials. This review will outline current treatment approaches for advanced prostate cancer with a focus on the role of radium-223 in changing treatment paradigms.Keywords: Alpharadin, alpha-emitting radionuclide, bone metastasis

  7. 3D kinematics of the near-IR HH 223 outflow in L723

    Science.gov (United States)

    López, R.; Acosta-Pulido, J. A.; Estalella, R.; Gómez, G.; García-Lorenzo, B.

    2015-03-01

    In this work, we derive the full 3D kinematics of the near-infrared outflow HH 223, located in the dark cloud Lynds 723 (L723), where a well-defined quadrupolar CO outflow is found. HH 223 appears projected on to the two lobes of the east-west CO outflow. The radio continuum source VLA 2, towards the centre of the CO outflow, harbours a multiple system of low-mass young stellar objects. One of the components has been proposed to be the exciting source of the east-west CO outflow. From the analysis of the kinematics, we get further evidence on the relationship between the near-infrared and CO outflows and on the location of their exciting source. The proper motions were derived using multi-epoch, narrow-band H2 (2.122 μm line) images. Radial velocities were derived from the 2.122 μm line of the spectra. Because of the extended (˜5 arcmin), S-shaped morphology of the target, the spectra were obtained with the multi-object-spectroscopy (MOS) observing mode using the instrument Long-Slit Intermediate Resolution Infrared Spectrograph (LIRIS) at the 4.2 m William Herschel Telescope. To our knowledge, this work is the first time that MOS observing mode has been successfully used in the near-infrared range for an extended target.

  8. Therapy assessment of bone metastatic disease in the era of {sup 223}radium

    Energy Technology Data Exchange (ETDEWEB)

    Etchebehere, Elba; Brito, Ana Emilia [The University of Campinas, Division of Nuclear Medicine, Campinas (Brazil); Rezaee, Alireza; Langsteger, Werner [St. Vincent' s Hospital, Department of Nuclear Medicine and Endocrinology, PET - CT Center LINZ, Ordensklinikum, Linz (Austria); Beheshti, Mohsen [St. Vincent' s Hospital, Department of Nuclear Medicine and Endocrinology, PET - CT Center LINZ, Ordensklinikum, Linz (Austria); Paracelsus Medical University, Department of Nuclear Medicine and Endocrinology, Salzburg (Austria)

    2017-08-15

    Defining an optimal imaging modality for assessment of therapy and the best time of evaluation are pivotal for ideal patient's management. {sup 223}Ra (Xofigo registered, formerly Alpharadin) has been approved by the FDA and European Medicines Agency for treatment of metastatic castration-resistant prostate cancer with painful osseous involvement. PET/CT imaging using various radiotracers such as {sup 18}F-FDG, {sup 18}F-FCH, {sup 68}Ga-PSMA and {sup 18}F-NaF have been investigated to mitigate the limitations of conventional imaging modalities. Diagnostic radiotracers that have properties similar to a therapeutic radiotracer will precisely assess of the possibility and efficacy of a treatment; this is the theranostic concept. An example of a diagnostic test employed for selecting targeted therapy is the combined use of {sup 18}F-fluoride PET/CT for evaluation of possible therapy with {sup 223}Ra. This review examines the most recent publications related to this topic. (orig.)

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

    Science.gov (United States)

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

    2015-08-07

    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.

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

    Energy Technology Data Exchange (ETDEWEB)

    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

  11. Changes in prostate-specific antigen, markers of bone metabolism and bone scans after treatment with radium-223.

    Science.gov (United States)

    Nome, Ragnhild; Hernes, Eivor; Bogsrud, Trond Velde; Bjøro, Trine; Fosså, Sophie D

    2015-06-01

    The aim of this study was to assess treatment-related changes in prostate-specific antigen (PSA), total and bone alkaline phosphatase (total ALP, bone ALP), and changes on conventional bone scans in patients with metastatic castration-resistant prostate cancer (mCRPC) with bone metastases who received six cycles of radium-223 (Ra-223). Changes in PSA, total ALP and bone ALP (≥30% increase or decrease), and changes on bone scans were assessed before and after six monthly cycles of Ra-223 therapy (50 kBq/kg body weight) in 14 patients with mCRPC with bone metastases and four patients on placebo. Post-treatment PSA increased by at least 30% in 11 out of 14 patients and remained stable in three. Total ALP and bone ALP decreased in six and nine patients, respectively. In 10 out of 12 evaluable patients the uptake on post-treatment bone scan was reduced in lesions with high pretreatment uptake, in 11 patients accompanied by the development of new or expanded bone lesions. FACBC position emission tomography/computed tomography scans confirmed the growth of new or expanded bone metastases in two patients. These observations support the notion that Ra-223 kills tumour cells in metastases surrounded by highly proliferating osteoblasts, consistent with the reported survival benefit. The radiation effect in small tumour deposits not surrounded by increased osteoblast activity seems, however, insufficient, thus allowing continuous tumour growth. Long-lasting PSA reductions are the exception rather than the rule during Ra-223 treatment, whereas alkaline phosphatases decrease more frequently. To improve the overall anticancer effect, Ra-223 might be a valuable component of combination treatment.

  12. Radium 223 dichloride: a multidisciplinary approach to metastatic castration-resistant prostate cancer.

    Science.gov (United States)

    Borsò, Elisa; Boni, Giuseppe; Galli, Luca; Ricci, Sergio; Farnesi, Azzurra; Mazzarri, Sara; Cianci, Claudia; Mariani, Giuliano; Falcone, Alfredo

    2015-01-01

    The role of nuclear medicine physicians in the multidisciplinary team for the management of patients with prostate cancer has been restricted because of a lack of available tools. The only drugs approved to relieve pain related to bone metastases were β-emitting radiopharmaceuticals. These drugs did not prove to prolong survival when used as single agent and resulted associated with important adverse events. This situation has changed with the introduction of radium 223 because of evidence of improved survival in patients, the good safety profile and the opportunity to avoid clonal selection of tumor cells. Cooperation among physicians involved in cancer management will lead to improvements in the treatment of bone metastases due to prostate cancer and is thought to extend to other tumor types.

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

    Directory of Open Access Journals (Sweden)

    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

  14. 12 CFR 223.16 - What transactions by a member bank with any person are treated as transactions with an affiliate?

    Science.gov (United States)

    2010-01-01

    ... extent that the proceeds of the transaction are used for the benefit of, or transferred to, an affiliate... 12 Banks and Banking 3 2010-01-01 2010-01-01 false What transactions by a member bank with any person are treated as transactions with an affiliate? 223.16 Section 223.16 Banks and Banking FEDERAL...

  15. 40 CFR 421.223 - Effluent limitations guidelines representing the degree of effluent reduction attainable by the...

    Science.gov (United States)

    2010-07-01

    ...) Molybdenum filtrate solvent extraction raffinate. BAT Limitations for the Secondary Molybdenum and Vanadium... Molybdenum and Vanadium Subcategory § 421.223 Effluent limitations guidelines representing the degree of.... BAT Limitations for the Secondary Molybdenum and Vanadium Subcategory Pollutant or pollutant property...

  16. 78 FR 59624 - Guidance for Industry #223: Small Entity Compliance Guide-Declaring Color Additives in Animal...

    Science.gov (United States)

    2013-09-27

    ... HUMAN SERVICES Food and Drug Administration 21 CFR Part 501 Guidance for Industry 223: Small Entity Compliance Guide--Declaring Color Additives in Animal Foods; Availability AGENCY: Food and Drug... Color Additives in Animal Foods.'' This small entity compliance guide (SECG) aids industry in complying...

  17. 48 CFR 52.223-16 - IEEE 1680 Standard for the Environmental Assessment of Personal Computer Products.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 2 2010-10-01 2010-10-01 false IEEE 1680 Standard for the... CONTRACT CLAUSES Text of Provisions and Clauses 52.223-16 IEEE 1680 Standard for the Environmental Assessment of Personal Computer Products. As prescribed in 23.706(b)(1), insert the following clause: IEEE...

  18. Multistate observations of the Galactic black hole XTE J1752-223: evidence for an intermediate black hole spin

    NARCIS (Netherlands)

    Reis, R.C.; Miller, J.M.; Fabian, A.C.; Cackett, E.M.; Maitra, D.; Reynolds, C.S.; Rupen, M.; Steeghs, D.T.H.; Wijnands, R.

    2011-01-01

    The Galactic black hole candidate XTE J1752−223 was observed during the decay of its 2009 outburst with the Suzaku and XMM-Newton observatories. The observed spectra are consistent with the source being in the ‘intermediate’ and ‘low-hard’ states, respectively. The presence of a strong, relativistic

  19. 40 CFR 415.223 - Effluent limitations guidelines representing the degree of effluent reduction attainable by the...

    Science.gov (United States)

    2010-07-01

    ... to this subpart and producing titanium dioxide by the sulfate process must achieve the following... CATEGORY Titanium Dioxide Production Subcategory § 415.223 Effluent limitations guidelines representing the..., any existing point source subject to this subpart and producing titanium dioxide by the chloride...

  20. 5 CFR 838.223 - OPM action on receipt of a court order not acceptable for processing.

    Science.gov (United States)

    2010-01-01

    ... Procedures for Processing Court Orders Affecting Employee Annuities Application and Processing Procedures § 838.223 OPM action on receipt of a court order not acceptable for processing. If OPM receives an application from a former spouse not based on a court order acceptable for processing, OPM will inform the...

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

    NARCIS (Netherlands)

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

  2. Measuring the radium quartet (228Ra, 226Ra, 224Ra, 223Ra) in seawater samples using gamma spectrometry.

    Science.gov (United States)

    van Beek, P; Souhaut, M; Reyss, J-L

    2010-07-01

    Radium isotopes are widely used in marine studies (eg. to trace water masses, to quantify mixing processes or to study submarine groundwater discharge). While 228Ra and 226Ra are usually measured using gamma spectrometry, short-lived Ra isotopes (224Ra and 223Ra) are usually measured using a Radium Delayed Coincidence Counter (RaDeCC). Here we show that the four radium isotopes can be analyzed using gamma spectrometry. We report 226Ra, 228Ra, 224Ra, 223Ra activities measured using low-background gamma spectrometry in standard samples, in water samples collected in the vicinity of our laboratory (La Palme and Vaccarès lagoons, France) but also in seawater samples collected in the plume of the Amazon river, off French Guyana (AMANDES project). The 223Ra and 224Ra activities determined in these samples using gamma spectrometry were compared to the activities determined using RaDeCC. Activities determined using the two techniques are in good agreement. Uncertainties associated with the 224Ra activities are similar for the two techniques. RaDeCC is more sensitive for the detection of low 223Ra activities. Gamma spectrometry thus constitutes an alternate method for the determination of short-lived Ra isotopes. 2009 Elsevier Ltd. All rights reserved.

  3. Human miR223 promoter as a novel myelo-specific promoter for chronic granulomatous disease gene therapy.

    Science.gov (United States)

    Brendel, Christian; Hänseler, Walther; Wohlgensinger, Vital; Bianchi, Matteo; Tokmak, Serap; Chen-Wichmann, Linping; Kuzmenko, Elena; Cesarovic, Nikola; Nicholls, Flora; Reichenbach, Janine; Seger, Reinhard; Grez, Manuel; Siler, Ulrich

    2013-06-01

    Targeting transgene expression to specific hematopoietic cell lineages could contribute to the safety of retroviral vectors in gene therapeutic applications. Chronic granulomatous disease (CGD), a defect of phagocytic cells, can be managed by gene therapy, using retroviral vectors with targeted expression to myeloid cells. In this context, we analyzed the myelospecificity of the human miR223 promoter, which is known to be strongly upregulated during myeloid differentiation, to drive myeloid-restricted expression of p47(phox) and gp91(phox) in mouse models of CGD and in primary patient-derived cells. The miR223 promoter restricted the expression of p47(phox), gp91(phox), and green fluorescent protein (GFP) within self-inactivating (SIN) gamma- and lentiviral vectors to granulocytes and macrophages, with only marginal expression in lymphocytes or hematopoietic stem and progenitor cells. Furthermore, gene transfer into primary CD34+ cells derived from a p47(phox) patient followed by ex vivo differentiation to neutrophils resulted in restoration of Escherichia coli killing activity by miR223 promoter-mediated p47(phox) expression. These results indicate that the miR223 promoter as an internal promoter within SIN gene therapy vectors is able to efficiently correct the CGD phenotype with negligible activity in hematopoietic progenitors, thereby limiting the risk of insertional oncogenesis and development of clonal dominance.

  4. Myeloid-derived miR-223 regulates intestinal inflammation via repression of the NLRP3 inflammasome

    NARCIS (Netherlands)

    Neudecker, V.; Haneklaus, M.; Jensen, O.; Khailova, L.; Masterson, J.C.; Tye, H.; Biette, K.; Jedlicka, P.; Brodsky, K.S.; Gerich, M.E.; Mack, M.; Robertson, A.A.B.; Cooper, M.A.; Furuta, G.T.; Dinarello, C.A.; O'Neill, L.A.; Eltzschig, H.K.; Masters, S.L.; McNamee, E.N.

    2017-01-01

    MicroRNA (miRNA)-mediated RNA interference regulates many immune processes, but how miRNA circuits orchestrate aberrant intestinal inflammation during inflammatory bowel disease (IBD) is poorly defined. Here, we report that miR-223 limits intestinal inflammation by constraining the nlrp3

  5. Imaging response during therapy with radium-223 for castration-resistant prostate cancer with bone metastases-analysis of an international multicenter database

    DEFF Research Database (Denmark)

    Keizman, D; Fosboel, M O; Reichegger, H

    2017-01-01

    BACKGROUND: The imaging response to radium-223 therapy is at present poorly described. We aimed to describe the imaging response to radium-223 treatment. METHODS: We retrospectively evaluated the computed tomography (CT) and bone scintigraphy response of metastatic castration-resistant prostate...... of 54% (n=70) patients completed the planned six injections of radium-223. In patients with available data, a transient increase in bone metastases-related pain was observed in 27% (n=33/124) and an improvement of bone metastases-related pain on treatment with radium-223 was noted in 49% of patients (n......=61/124). At 3 and 6 months of treatment with radium-223, bone imaging showed stable disease in 74% (n=84/113) and 94% of patients (n=93/99) with available data, respectively. An increase in the number of bone lesions was documented at 3 months compared with baseline in 26% (n=29/113) and at 6 months...

  6. More for less: Analysis of the performance of avian acute oral guideline OECD 223 from empirical data.

    Science.gov (United States)

    Edwards, Peter J; Leopold, Annegaaike; Beavers, Joann B; Springer, Timothy A; Chapman, Peter; Maynard, Samuel K; Hubbard, Patrick

    2017-09-01

    Since the publication of the Organisation for Economic Co-operation and Development (OECD) avian acute oral guideline, OECD 223, empirical data have become available to compare the performance of OECD 223 with statistical simulations used to validate this guideline and with empirical data for US Environmental Protection Agency Office of Chemical Safety and Pollution Prevention (USEPA OCSPP) guideline OCSPP 850.2100. Empirical studies comprised 244 for Northern bobwhite, of which 73 were dose-response tests and 171 were limit tests. Of the dose-response tests, 26 were conducted to OECD 223 (using 3-4 stages) and 33 to OCSPP 850.2100 (using the single 50-bird design). Data were collected from 5 avian testing laboratories from studies performed between 2006 and 2013. The success with which the LD50 and slope could be determined was 100% and 96% for OECD 223 (mean 26 birds per test) and 100% and 51% for OCSPP 850.2100 (mean 50 birds per test). This was consistent with the statistical simulations. Control mortality across all species and designs amounted to 0.26% (n = 2655) with only single mortalities occurring in any 1 study and OECD 223 design showed that control mortality up to 1% will have no observable impact on the performance. The distribution of time to death for Northern bobwhite, zebra finch, and canary were obtained from 90, 29, and 17 studies, and mortalities appeared within 3 d for 71%, 95%, and 91% of birds tested, respectively. Integr Environ Assess Manag 2017;13:906-914. © 2017 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals, Inc. on behalf of Society of Environmental Toxicology & Chemistry (SETAC). © 2017 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals, Inc. on behalf of Society of Environmental Toxicology & Chemistry (SETAC).

  7. miRNA-223-3p regulates NLRP3 to promote apoptosis and inhibit proliferation of hep3B cells.

    Science.gov (United States)

    Wan, Lingfeng; Yuan, Xin; Liu, Mantian; Xue, Boyu

    2018-03-01

    Hepatocellular carcinoma (HCC) is a major malignant tumor type with a high incidence and mortality. Infection with hepatitis virus is a high-risk factor. Previous studies have demonstrated that microRNA (miR)-223 was downregulated in HCC tissues. NOD-like receptor family, pyrin domain containing 3 (NLRP3)-is a potential target of miR-223 and has a vital role in hepatitis infection. The present study was performed to investigate the role of miR-223 in the proliferation and apoptosis of HCC cells through regulating NLRP3. A dual luciferase reporter assay was performed to confirm the direct interaction between miR-223-3p and the 3' untranslated region of NLRP3 mRNA. Hep3B cells were then transfected with miR-223 mimics and the proliferation and apoptosis were determined by an MTT and a flow cytometric assay, respectively. The expression of NLRP3 and caspase-1 was analyzed at the mRNA as well as at the protein level by reverse transcription-quantitative polymerase chain reaction and western blot analysis, respectively. The secretion of interleukin (IL)-1β and IL-18 in the culture supernatants was measured by ELISA. The dual luciferase assay confirmed NLRP3 as a direct target of miR-223. Overexpression of miR-223 in hep3B cells significantly suppressed cell proliferation and promoted apoptosis. Furthermore, the expression of NLRP3 was downregulated by miR-223 transfection. Certain downstream factors of the NLRP3 pathway were also downregulated following overexpression of miR-223. Caspase-1 was decreased at the transcriptional level and the cleaved caspase-1 was decreased at the protein level. Secretion of IL-1β and IL-18 into the culture medium by cells transfected with miR-223 was lower than that by the control cells. In conclusion, the tumor suppressor role of miR-223 was associated with the regulation of NLRP3 inflammasome components. miR-223 inhibited HCC cell proliferation and promoted apoptosis by directly targeting NLRP3. Downstream production of caspase-1, IL

  8. Derivation of Soil Screening Guidelines for Gross Alpha/Beta Radioactivity for United States Air Force Deployment Sites

    Science.gov (United States)

    2007-04-19

    the emission of 7 alpha particles and 4 beta particles. Three radionuclides ( francium -223, astatine-215, and polonium-211) are not listed below...no no Uranium-233 159,200 y alpha yes no Thorium-229 7,300 y alpha yes no Radium-225 14.9 d beta no no Actinium-225 10.0 d alpha no no Francium

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

    Science.gov (United States)

    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.

  10. Management of metastatic castration-resistant prostate cancer: A focus on radium-223: Opinions and suggestions from an expert multidisciplinary panel.

    Science.gov (United States)

    Baldari, Sergio; Boni, Giuseppe; Bortolus, Roberto; Caffo, Orazio; Conti, Giario; De Vincentis, Giuseppe; Monari, Fabio; Procopio, Giuseppe; Santini, Daniele; Seregni, Ettore; Valdagni, Riccardo

    2017-05-01

    Radium-223, a calcium mimetic bone-seeking radionuclide that selectively targets bone metastases with alpha particles, is approved for the treatment of men with metastatic castration-resistant prostate cancer (mCRPC) and symptomatic bone metastases. In patients with mCRPC, treatment with radium-223 has been associated with survival benefit, regardless of prior docetaxel use, and also has a positive impact on symptomatic skeletal events and quality of life. Radium-223 is best suited for patients with symptomatic mCRPC and bone-predominant disease and no visceral metastases, and may lead to better outcomes when given early in the course of the disease. An expert multidisciplinary panel convened in Milan, Italy to review the current best-evidence literature on radium-223 and to convey their personal expertise with the use of radium-223 and identify possible strategies for best practice. This article summarizes the best available evidence for the use of radium-223, discusses the essential role of the multidisciplinary team in delivering effective treatment for mCRPC, clarifies pre- and post-treatment evaluation and monitoring, and outlines future scenarios for radium-223 in the treatment of men with MCRPC. Copyright © 2017. Published by Elsevier B.V.

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

    Directory of Open Access Journals (Sweden)

    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.

  12. Ly6G+ neutrophil-derived miR-223 inhibits the NLRP3 inflammasome in mitochondrial DAMP-induced acute lung injury.

    Science.gov (United States)

    Feng, Zunyong; Qi, Shimei; Zhang, Yue; Qi, Zhilin; Yan, Liang; Zhou, Jing; He, Fang; Li, Qianqian; Yang, Yanyan; Chen, Qun; Xiao, Shi; Li, Qiang; Chen, Yang; Zhang, Yao

    2017-11-16

    MicroRNA (miRNA) mediates RNA interference to regulate a variety of innate immune processes, but how miRNAs coordinate the mechanisms underlying acute lung injury/acute respiratory distress syndrome (ALI/ARDS) in patients with pulmonary inflammatory injury is still unknown. In this study, we demonstrated that miR-223 limits the number of Ly6G+ neutrophils and inhibits the activity of the NLRP3 inflammasome to alleviate ALI induced by mitochondrial damage-associated molecular patterns (DAMPs) (MTDs). miR-223 expression is increased in the lungs of MTD-induced mice or ARDS patients following trauma/transfusion or following the physiological remission of ALI/ARDS. miR-223-/+ mice exhibited more severe ALI and cytokine dysregulation. Other studies have shown that MTD-induced increases in miR-223 expression are mainly contributed by Ly6G+ neutrophils from the haematopoietic system. miR-223 blocks bone marrow-derived Ly6G+ neutrophil differentiation and inhibits peripheral cytokine release. In addition, MTD-induced miR-223 expression activates a negative feedback pathway that targets the inhibition of NLRP3 expression and IL-1β release; therefore, miR-223 deficiency can lead to the sustained activation of NLRP3-IL-1β. Finally, elimination of peripheral Ly6G+ neutrophils and pharmacological blockade of the miR-223-NLRP3-IL-1β signalling axis could alleviate MTD-induced ALI. In summary, miR-223 is essential for regulating the pathogenesis of DAMP-induced ALI.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  15. Haematopoietic toxicity of radium-223 in patients with high skeletal tumour burden.

    Science.gov (United States)

    Miederer, M; Thomas, C; Beck, J; Hampel, C; Krieger, C; Baqué, P E; Helisch, A; Schreckenberger, M

    2015-01-01

    In patients with metastasized, castration resistant prostate cancer (mCRPC) treatment with radium-223 (Xofigo) is an attractive therapeutic option. In particular, patients with high tumour load seem to profit from this treatment in regard of survival and quality of live. Aim of this study was to stratify mCRPC patients according to a quantitative imaging marker derived from routine bone scans (EXINI bone) and analyze haematopoietic toxicity of Xofigo in these patients. Toxicity and oncologic outcome were investigated in a cohort of 14 patients with high tumour load. Additionally, based on a web survey, experience of toxicity in 41 high tumour load patients in Germany in 2014 was collected. In patients with a bone scan index (BSI) greater than 5, significant toxicity occurred in more patients than expected from the ALSYMPCA trial. This was associated with application of fewer cycles. Similar experiences have been made in other centers in Germany. Approximately 7% of these patients will need very long time or will not recover from grade ≥ 3 toxicity. Close follow-up of haematopoietic indices and, in case of toxicity, early termination of therapy is in particular necessary in late stage disease where limited bone marrow reserve is likely.

  16. Radium-223: Insight and Perspectives in Bone-metastatic Castration-resistant Prostate Cancer.

    Science.gov (United States)

    Buroni, Federica Eleonora; Persico, Marco Giovanni; Pasi, Francesca; Lodola, Lorenzo; Nano, Rosanna; Aprile, Carlo

    2016-11-01

    (223)Ra prolongs overall survival in symptomatic patients affected by multiple bone-metastatic castration-resistant prostatic cancer, without visceral or nodal involvement. However, many questions remain about its mechanisms of action, and its use in clinical practice is still unresolved. First of all, what is the main target of alpha-particle emission, that is, in what way does it influences the tumor microenvironment? When is the best timing in the course of the disease, extending its use to asymptomatic low-volume or even to the micrometastatic phase? What are suitable biomarkers to be employed as prognostic factors and response indicators? Which associations with other drugs and their sequence can offer the best results, and is their effect additive or synergistic? Ultimately, in the current climate of spending review, what is the optimal cost and benefit ratio regarding available treatments? In this review, we tried to answer these questions by analyzing the available scientific literature. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  17. 2,2,3-trimethylbutane and differently-branched hydrocarbons through hydrogenation of trialkyl acetic acid

    Energy Technology Data Exchange (ETDEWEB)

    Bueren, H.

    1944-02-15

    This report described a method of producing Triptan (2,2,3-trimethylbutane). The starting material was diisopropyl ketone (Isobutyron). It was transformed into dimethylisopropyl acetic acid by first chlorinating the starting material and then treating it with a water-free alkali (sodium hydroxide) in a benzene solution containing a small amount of sodium metal to tie up any remaining water. The acid crystallized out as a sodium salt and then was redissolved with dilute hydrochloric acid. The dimethylisopropyl acetic acid had the same carbon skeleton as Triptan. Studies were underway on finding the best catalyst to accomplish the hydrogenation of the acid group to give Triptan. The best catalyst tried so far was catalyst 6718, a non-splitting catalyst containing nickel sulfide and tungsten sulfide in the ratio 1:1. That catalyst gave yields of 40% Triptan, 40% unchanged acid, 10% higher-boiling-point compounds, and 10% lower-boiling-point liquids and gases. It was supposed that a catalyst with nickel:tungsten ratio of 2:1 instead of 1:1 would have even better effects. Other catalysts were also being investigated. The starting material isobutyron was obtained as a byproduct of butyl alcohol production. The chlorination of Isobutyron was done by introducing chlorine gas into the material while the material was being held at 0/sup 0/ to 5/sup 0/C. Care had to be taken to stop the chlorination at the right time so that only the monochlorinated product was obtained.

  18. Mir-22-3p Inhibits Arterial Smooth Muscle Cell Proliferation and Migration and Neointimal Hyperplasia by Targeting HMGB1 in Arteriosclerosis Obliterans

    Directory of Open Access Journals (Sweden)

    Shui-chuan Huang

    2017-08-01

    Full Text Available Background: Aberrant vascular smooth muscle cell (VSMC proliferation and migration contribute to the development of vascular pathologies, such as atherosclerosis and post-angioplasty restenosis. The aim of this study was to determine whether miR-22-3p plays a role in regulating human artery vascular smooth muscle cell (HASMC function and neointima formation. Methods: Quantitative real-time PCR (qRT-PCR and fluorescence in situ hybridization (FISH were used to detect miR-22-3p expression in human arteries. Cell Counting Kit-8 (CCK-8 and EdU assays were performed to assess cell proliferation, and transwell and wound closure assays were performed to assess cell migration. Moreover, luciferase reporter assays were performed to identify the target genes of miR-22-3p. Finally, a rat carotid artery balloon-injury model was used to determine the role of miR-22-3p in neointima formation. Results: MiR-22-3p expression was downregulated in arteriosclerosis obliterans (ASO arteries compared with normal arteries, as well as in platelet-derived growth factor-BB (PDGF-BB-stimulated HASMCs compared with control cells. MiR-22-3p overexpression had anti-proliferative and anti-migratory effects and dual-luciferase assay showed that high mobility group box-1 (HMGB1 is a direct target of miR-22-3p in HASMCs. Furthermore, miR-22-3p expression was negatively correlated with HMGB1 expression in ASO tissue specimens. Finally, LV-miR-22-3p-mediated miR-22-3p upregulation significantly suppressed neointimal hyperplasia specifically by reducing HMGB1 expression in vivo. Conclusions: Our results indicate that miR-22-3p is a key molecule in regulating HASMC proliferation and migration by targeting HMGB1 and that miR-22-3p and HMGB1 may be therapeutic targets in the treatment of human ASO.

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

    DEFF Research Database (Denmark)

    Løvendorf, Marianne B; Zibert, John R; Gyldenløve, Mette

    2014-01-01

    BACKGROUND: Psoriasis is a systemic inflammatory skin disease. MicroRNAs (miRNAs) are a class of small non-coding RNA molecules that recently have been found in the blood to be relevant as disease biomarkers. OBJECTIVE: We aimed to explore miRNAs potential as blood biomarkers for psoriasis. METHODS......: Using microarray and quantitative real-time PCR we measured the global miRNA expression in whole blood, plasma and peripheral blood mononuclear cells (PBMCs) from patients with psoriasis and healthy controls. RESULTS: We identified several deregulated miRNAs in the blood from patients with psoriasis......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...

  20. Is Omentectomy Mandatory Among Early Stage (I, II) Malignant Ovarian Germ Cell Tumor Patients? A Retrospective Study of 223 Cases.

    Science.gov (United States)

    Xu, Wenyan; Li, Yanfang

    2017-09-01

    The aim of the study was to investigate whether omentectomy (OMT) is necessary in the operation for apparently early stage malignant ovarian germ cell tumors (MOGCTs). Searching medical records database of Sun Yat-sen University Cancer Center from January 1, 1966, to November 30, 2015, patients with MOGCTs were identified and their age, year of diagnosis, tumor grade, histologic subtype, International Federation of Gynecology and Obstetrics stage, nodal findings, gross observation of omentum, and performance of OMT were assessed. Overall survivals of patients with or without OMT were compared using Kaplan-Meier survival curves. A total of 223 MOGCT cases with clinically early stage (stage I and II) disease and with the 3 common histological subtypes of MOGCT were obtained, which include yolk sac tumor (YST), dysgerminoma (DSG), and immature teratoma (IMT). There were 192 stage I cases and 31 stage II cases. Fifty-four patients were diagnosed with YST, 61 with DSG, and 108 with IMT. Omentectomy was performed as part of the initial surgery in 74.0% patients (165/223) and was omitted in 26.0% patients (58/223). Chemotherapy was administered in 88.3% (197/223) of all patients. The median follow-up was 82.0 months. The 10-year overall survival rates of the patients with and without OMT were 90.5% and 98.1%, respectively (P = 0.156). Regarding different stages or histological subtypes, the 10-year survival rates of the 2 groups were 92.0% versus 97.9% (P = 0.324, stage I), 83.2% versus 100% (P = 0.351, stage II), 89.2% versus 100% (P = 0.303, YST), 94.1% versus 100% (P = 0.470, DSG), and 89.4% versus 96.0% (P = 0.405, IMT), respectively. In conclusion, OMT in patients with clinically early stage MOGCT may not improve patient survival and may be omitted.

  1. Does Q223R Polymorphism of Leptin Receptor Influence on Anthropometric Parameters and Bone Density in Childhood Cancer Survivors?

    Directory of Open Access Journals (Sweden)

    Malgorzata Sawicka-Żukowska

    2013-01-01

    Full Text Available Childhood cancer survivors are in augmented risk for developing obesity. For many factors leptin and leptin receptor gene polymorphism play an important role in the development and metabolism not only of fat, but also, bone tissue. The aim of the analysis was to find the relationships between Q223R, leptin levels, and anthropometric parameters. Patients and Methods. In the study 74 cancer survivors participated (ALL n=64, lymphomas n=10, and the control group consisted of 51 healthy peers. Leptin blood concentration was determined by ELISA method. To estimate leptin receptor gene polymorphism, RFLP method was used. Bone mineral density (BMD and content (BMC, fat, and lean tissue measurements were obtained by DXA. Results. We found no correlations between serum leptin concentrations and anthropometric parameters nor BMD. Serum leptin concentrations were significantly lower in the group of cancer survivors compared to controls; however, in those overweight from examined group we found leptin levels higher than those in nonoverweight. Genotype Q223R was not associated with higher leptin levels, BMI, BMD, body fat or lean tissue. Conclusion. To our knowledge, this is the first report describing the relationship between BMD and Q223R polymorphism in childhood cancer survivors. Further analysis, based on a larger group of patients, is needed to confirm these findings.

  2. Emerging role of Radium-223 in the growing therapeutic armamentarium of metastatic castration-resistant prostate cancer.

    Science.gov (United States)

    Picciotto, Maria; Franchina, Tindara; Russo, Alessandro; Ricciardi, Giuseppina Rosaria Rita; Provazza, Giusy; Sava, Serena; Baldari, Sergio; Caffo, Orazio; Adamo, Vincenzo

    2017-06-01

    During the last few years, the therapeutic armamentarium of castration resistant prostate cancer (mCRPC) has been enriched with the introduction of new effective therapies with proved survival benefit and quality of life gain, including cabazitaxel, abiraterone, enzalutamide, and Radium-223. Areas covered: Bone metastases represent a substantial cause of morbidity in mCRPC with a high rate of related skeletal events (SREs). In case of multifocal pain due to diffuse osteoblastic metastases, treatment with bone-targeting radiopharmaceutical agents can provide palliation from pain. Radium-223, a calcium-mimetic, is the first α-particle emitting radiopharmaceutical that prolonged overall survival, delayed symptomatic skeletal events and improved quality of life in mCRPC. Expert opinion: In this therapeutic scenario, no clear evidences support the best way to sequence these available agents and there is an urgent need for prospective studies to define it. 223Ra is a firmly established therapeutic option in CRPC with symptomatic bone metastases and no visceral/bulky nodal involvement, with an undeniable advantage over new hormonal agents, given its peculiar mechanism of action. Current ongoing randomized clinical trials will clarify the optimal use of this effective therapy in the therapeutic armamentarium of CRPC either alone or combined with other new approved agents and whether there is a role in patients with asymptomatic disease.

  3. Radium isotope ((223)Ra, (224)Ra, (226)Ra and (228)Ra) distribution near Brazil's largest port, Paranaguá Bay, Brazil.

    Science.gov (United States)

    Dias, Thais H; de Oliveira, Joselene; Sanders, Christian J; Carvalho, Franciane; Sanders, Luciana M; Machado, Eunice C; Sá, Fabian

    2016-10-15

    This work investigates the (223)Ra, (224)Ra, (226)Ra and (228)Ra isotope distribution in river, estuarine waters and sediments of the Paranaguá Estuarine Complex (PEC). The stratification of the Ra isotopes along water columns indicate differing natural sources. In sediments, the radium isotope activities was inversely proportional to the particle size. The highest concentrations of (223)Ra, (224)Ra, (226)Ra and (228)Ra in the water column were found in the bottom more saline waters and towards the inner of the estuary. These relatively high concentrations towards the bottom of the estuary may be attributed to the influence of tidally driven groundwater source and desorption from particles at the maximum turbidity zone. The apparent river water ages from the radium isotope ratios, (223)Ra/(224)Ra and (223)Ra/(228)Ra, indicate that the principal rivers that flow into the estuary have residence times from between 6 and 11days. Copyright © 2016 Elsevier Ltd. All rights reserved.

  4. Development of separation technology for the removal of radium-223 from targeted thorium conjugate formulations. Part II: purification of targeted thorium conjugates on cation exchange columns.

    Science.gov (United States)

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

    2017-09-01

    Tumor targeting pharmaceuticals will play a crucial role in future pharma pipelines. The targeted thorium conjugate (TTC) therapeutic platform could provide real benefit to patients, whereby targeting moieties like monoclonal antibodies are radiolabelled with the alpha-emitting radionuclide thorium-227 ((227)Th, t1/2 = 18.7 days). A potential problem could be the accumulation of the long-lived daughter nuclide radium-223 ((223)Ra, t1/2 = 11.4 days) in the drug product during manufacturing and distribution. Therefore, the level of (223)Ra must be standardized before administration to the patient. The focus in this study has been the removal of (223)Ra, as the other progenies will have a very limited stay in the formulation. In this study, the purification of TTCs labeled with decayed (227)Th has been explored. Columns packed with a strong cation exchange resin have been used to sequester (223)Ra. The separation of TTC from (223)Ra has been evaluated as influenced by both formulation and process parameters with a design of experiments (DOE) study; including citrate or acetate buffer, pH, buffer concentration, presence or absence of pABA + EDTA, resin amount and sodium chloride concentration. The aim was to achieve a separation with high sorption of (223)Ra and accompanying low TTC sorption. The results were analyzed by multivariate analysis. Four regression models of TTC and (223)Ra sorption from citrate and acetate buffered formulations were developed. The predictive accuracy of sorption in the four statistical models was given by standard deviations and confidence intervals. The TTC sorption in citrate and acetate buffered formulations was affected by the identical variables and the variation in TTC sorption was comparable for the two models. However, the DOE variables had a significantly stronger impact on the (223)Ra sorption in citrate buffered formulations than the (223)Ra sorption in acetate buffer. An optimal separation with a TTC sorption

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  6. Radium-223 in the treatment of osteoblastic metastases: a critical clinical review.

    Science.gov (United States)

    Humm, John L; Sartor, Oliver; Parker, Chris; Bruland, Oyvind S; Macklis, Roger

    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 (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. Copyright © 2015 Elsevier Inc. All rights reserved.

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

    Energy Technology Data Exchange (ETDEWEB)

    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

  8. Study of {sup 223}Ra uptake mechanism by Fe{sub 3}O{sub 4} nanoparticles: towards new prospective theranostic SPIONs

    Energy Technology Data Exchange (ETDEWEB)

    Mokhodoeva, Olga [Russian Academy of Sciences, Vernadsky Institute of Geochemistry and Analytical Chemistry (Russian Federation); Vlk, Martin; Málková, Eva; Kukleva, Ekaterina; Mičolová, Petra; Štamberg, Karel [Czech Technical University in Prague, Department of Nuclear Chemistry, Faculty of Nuclear Sciences and Physical Engineering (Czech Republic); Šlouf, Miroslav [Academy of Sciences of the Czech Republic, Institute of Macromolecular Chemistry (Czech Republic); Dzhenloda, Rustam [Russian Academy of Sciences, Vernadsky Institute of Geochemistry and Analytical Chemistry (Russian Federation); Kozempel, Ján, E-mail: jan.kozempel@fjfi.cvut.cz [Czech Technical University in Prague, Department of Nuclear Chemistry, Faculty of Nuclear Sciences and Physical Engineering (Czech Republic)

    2016-10-15

    The use of superparamagnetic iron oxide nanoparticles (SPIONs) and radiolabelled nanoparticles (NPs) has grown considerably over the recent years, and the SPIONs labelled with medicinal radionuclides offer new opportunities in multimodal diagnostics and in the drug-delivery systems for targeted alpha-particle therapy (TAT) driven by magnetic field gradient or by biologically active moieties bound on NPs shell. However, the mechanisms of NPs radiolabelling are not studied substantially and still remain unclear, even though the way of label attachment directly implies the stability of the label-nanoparticle construct. Since the {sup 223}Ra was the first clinically approved alpha-emitter, it is a promising nuclide for further development of its targeted carriers. We report here on the study of {sup 223}Ra uptake by the Fe{sub 3}O{sub 4}SPIONs, together with an attempt to propose the {sup 223}Ra uptake mechanism by the Fe{sub 3}O{sub 4}NPs in the presence of a phosphate buffer a typical formulation medium, under the pseudo-equilibrium conditions. Further, the in vitro stability tests of the prepared [{sup 223}Ra]Fe{sub 3}O{sub 4}NPs were performed to estimate the {sup 223}Ra label stability. The potential use of {sup 223}Ra-labelled SPIONs in theranostic applications is also discussed.Graphical abstract.

  9. High-Linear Energy Transfer Irradiation Targeted to Skeletal Metastases by the Alpha Emitter Ra-223: Adjuvant or Alternative to Conventional Modalities?

    Energy Technology Data Exchange (ETDEWEB)

    Bruland, Oyvind S.; Nilsson, Sten; Fisher, Darrell R.; Larsen, Roy H.

    2006-10-15

    The bone-seeking, alpha-particle emitting radiopharmaceutical Alpharadin, 223RaCl2 (t1/2 = 11.4 days) is under clinical development as a novel treatment for skeletal metastases from breast and prostate cancer. This paper summarizes the current status of preclinical and clinical research on 223RaCl2. Potential advantages of 223Ra to that of external beam irradiation or registered beta-emitting bone-seekers are discussed. Published data of 223Ra dosimetry in mice and a therapeutic study in a skeletal metastases model in nude rats have indicated significant therapeutic potential of bone-seeking alpha-emitters. This paper provides short-term and long-term results from the first clinical single dosage trial. We present data from a repeated dosage study of five consecutive injections of 50 kBq/kg bodyweight, once every third week, or two injections of 125 kBq/kg bodyweight, six weeks apart. Furthermore, preliminary results are given for a randomized phase II trial involving 64 patients with hormone-refractory prostate cancer and painful skeletal metastases who received four monthly injections of 223Ra or saline as an adjuvant to external beam radiotherapy. Also presented are preliminary dose estimates for 223Ra in humans. Results indicate that repeated dosing is feasible and that opportunities are available for combined treatment strategies.

  10. A case series of 223 patients with depersonalization-derealization syndrome.

    Science.gov (United States)

    Michal, Matthias; Adler, Julia; Wiltink, Jörg; Reiner, Iris; Tschan, Regine; Wölfling, Klaus; Weimert, Sabine; Tuin, Inka; Subic-Wrana, Claudia; Beutel, Manfred E; Zwerenz, Rüdiger

    2016-06-27

    Depersonalization-derealization syndrome (DDS) is an underdiagnosed and underresearched clinical phenomenon. In Germany, its administrative prevalence is far below the threshold for orphan diseases, although according to epidemiological surveys the diagnosis should be comparable frequent as anorexia nervosa for instance. Against this background, we carried out a large comprehensive survey of a DDS series in a tertiary mental health center with a specialized depersonalization-derealization clinic. To reveal differential characteristics, we compared the DDS patients, who consulted the specialized depersonalization-derealization clinic, with a group of patients with depressive disorders without comorbid DDS from the regular outpatient clinic of the mental health center. The sample comprised 223 patients with a diagnosis of depersonalization-derealization-syndrome and 1129 patients with a depressive disorder but without a comorbid diagnosis of DDS. DDS patients were described and compared with depressive outpatients in terms of sociodemographic characteristics, treatment history, treatment wishes, clinical symptomatology, prevailing psychosocial stressors, family history of common mental disorders and history of childhood trauma. Despite the high comorbidity of DDS patients with depressive disorders and comparable burden with symptoms of depression and anxiety, the clinical picture and course of both patient groups differed strongly. DDS patients were younger, had a significant preponderance of male sex, longer disease duration and an earlier age of onset, a higher education but were more often unemployed. They tended to show more severe functional impairment. They had higher rates of previous or current mental health care utilization. Nearly all DDS patients endorsed the wish for a symptom specific counseling and 70.7 % were interested in the internet-based treatment of their problems. DDS patients had lower levels of self-rated traumatic childhood experiences and

  11. MicroRNA-223 ameliorates alcoholic liver injury by inhibiting the IL-6–p47phox–oxidative stress pathway in neutrophils

    Science.gov (United States)

    Li, Man; He, Yong; Zhou, Zhou; Ramirez, Teresa; Gao, Yueqiu; Gao, Yanhang; Ross, Ruth A; Cao, Haixia; Cai, Yan; Xu, Mingjiang; Feng, Dechun; Zhang, Ping; Liangpunsakul, Suthat; Gao, Bin

    2017-01-01

    Objectives Chronic-plus-binge ethanol feeding activates neutrophils and exacerbates liver injury in mice. This study investigates how recent excessive drinking affects peripheral neutrophils and liver injury in alcoholics, and how miR-223, one of the most abundant microRNAs (miRNAs) in neutrophils, modulates neutrophil function and liver injury in ethanol-fed mice. Designs Three hundred alcoholics with (n=140) or without (n=160) recent excessive drinking and 45 healthy controls were enrolled. Mice were fed an ethanol diet for 10 days followed by a single binge of ethanol. Results Compared with healthy controls or alcoholics without recent drinking, alcoholics with recent excessive drinking had higher levels of circulating neutrophils, which correlated with serum levels of alanine transaminase (ALT) and aspartate transaminase (AST). miRNA array analysis revealed that alcoholics had elevated serum miR-223 levels compared with healthy controls. In chronic-plus-binge ethanol feeding mouse model, the levels of miR-223 were increased in both serum and neutrophils. Genetic deletion of the miR-223 gene exacerbated ethanol-induced hepatic injury, neutrophil infiltration, reactive oxygen species (ROS) and upregulated hepatic expression of interleukin (IL)-6 and phagocytic oxidase (phox) p47phox. Mechanistic studies revealed that miR-223 directly inhibited IL-6 expression and subsequently inhibited p47phox expression in neutrophils. Deletion of the p47phox gene ameliorated ethanol-induced liver injury and ROS production by neutrophils. Finally, miR-223 expression was downregulated, while IL-6 and p47phox expression were upregulated in peripheral blood neutrophils from alcoholics compared with healthy controls. Conclusions miR-223 is an important regulator to block neutrophil infiltration in alcoholic liver disease and could be a novel therapeutic target for the treatment of this malady. PMID:27679493

  12. Increased miR-223 expression in T cells from patients with rheumatoid arthritis leads to decreased insulin-like growth factor-1-mediated interleukin-10 production.

    Science.gov (United States)

    Lu, M-C; Yu, C-L; Chen, H-C; Yu, H-C; Huang, H-B; Lai, N-S

    2014-09-01

    We hypothesized that the aberrant expression of microRNAs (miRNAs) in rheumatoid arthritis (RA) T cells was involved in the pathogenesis of RA. The expression profile of 270 human miRNAs in T cells from the first five RA patients and five controls were analysed by real-time polymerase chain reaction. Twelve miRNAs exhibited potentially aberrant expression in RA T cells compared to normal T cells. After validation with another 22 RA patients and 19 controls, miR-223 and miR-34b were over-expressed in RA T cells. The expression levels of miR-223 were correlated positively with the titre of rheumatoid factor (RF) in RA patients. Transfection of Jurkat cells with miR-223 mimic suppressed insulin-like growth factor-1 receptor (IGF-1R) and transfection with miR-34b mimic suppressed cAMP response element binding protein (CREB) protein expression by Western blotting. The protein expression of IGF-1R but not CREB was decreased in RA T cells. The addition of recombinant IGF-1-stimulated interleukin (IL)-10 production by activated normal T cells, but not RA T cells. The transfection of miR-223 mimic impaired IGF-1-mediated IL-10 production in activated normal T cells. The expression levels of SCD5, targeted by miR-34b, were decreased in RA T cells after microarray analysis. In conclusion, both miR-223 and miR-34b were over-expressed in RA T cells, but only the miR-223 expression levels were correlated positively with RF titre in RA patients. Functionally, the increased miR-223 expression could impair the IGF-1-mediated IL-10 production in activated RA T cells in vivo, which might contribute to the imbalance between proinflammatory and anti-inflammatory cytokines. © 2014 British Society for Immunology.

  13. Interstitial deletion in Xp22.3 is associated with X linked ichthyosis, mental retardation, and epilepsy.

    Science.gov (United States)

    Gohlke, B C; Haug, K; Fukami, M; Friedl, W; Noeker, M; Rappold, G A; Haverkamp, F

    2000-08-01

    We describe monozygotic male twins with an interstitial deletion of Xp22.3 including the steroid sulphatase gene (STS). The twins had X linked ichthyosis, X linked mental retardation, and epilepsy. A locus for X linked mental retardation has been assigned to a region between STS and DXS31 spanning approximately 3 Mb. Recently the locus was further refined to an approximately 1 Mb region between DXS1060 and GS1. By PCR analysis of flanking STS gene markers in our patients we succeeded in narrowing down the locus to between DXS6837 and GS1.

  14. Interstitial deletion in Xp22.3 is associated with X linked ichthyosis, mental retardation, and epilepsy

    OpenAIRE

    Gohlke, B; Haug, K; Fukami, M; Friedl, W; Noeker, M; Rappold, G; Haverkamp, F.

    2000-01-01

    We describe monozygotic male twins with an interstitial deletion of Xp22.3 including the steroid sulphatase gene (STS). The twins had X linked ichthyosis, X linked mental retardation, and epilepsy. A locus for X linked mental retardation has been assigned to a region between STS and DXS31 spanning approximately 3 Mb. Recently the locus was further refined to an approximately 1 Mb region between DXS1060 and GS1. By PCR analysis of flanking STS gene markers in our patients we succeeded in narro...

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

    Science.gov (United States)

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

    1990-04-01

    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.

  16. [Bone-specific therapy with radium-223 dichloride : Castration-resistant prostate cancer with symptomatic bone metastases].

    Science.gov (United States)

    Tauber, R; Gschwend, J; Scheidhauer, K; Eiber, M; Krönke, M

    2017-01-01

    Radium-223 dichloride (Xofigo®, Alpharadin) is approved for the treatment of metastatic castration-resistant prostate cancer with symptomatic bone metastases and no known visceral metastases. As a calcium mimetic, it is integrated into osteoplastic bone lesions and emits alpha particles with high energy which leads to local destruction of tumor cells. In the 2013 published ALSYMPCA trial, a significant advantage for overall survival and quality of life in comparison to placebo was found. Recent data suggest an increased potential in combination with next generation hormonal treatment.

  17. An exploratory analysis of alkaline phosphatase, lactate dehydrogenase, and prostate-specific antigen dynamics in the phase 3 ALSYMPCA trial with radium-223

    Science.gov (United States)

    Coleman, R. E.; Nilsson, S.; Heinrich, D.; Helle, S. I.; O’Sullivan, J. M.; Vogelzang, N. J.; Bruland, Ø.; Kobina, S.; Wilhelm, S.; Xu, L.; Shan, M.; Kattan, M. W.; Parker, C.

    2017-01-01

    Background Baseline clinical variables are prognostic for overall survival (OS) in patients with castration-resistant prostate cancer (CRPC). Their prognostic and predictive value with agents targeting bone metastases, such as radium-223, is not established. Patients and methods The radium-223 ALSYMPCA trial enrolled patients with CRPC and symptomatic bone metastases. Prognostic potential of baseline variables was assessed using Cox models. Percentage changes in biomarker levels from baseline were evaluated during the trial period; changes from baseline to week 12 were evaluated for association with OS and surrogacy. Results Eastern Cooperative Oncology Group performance status, total alkaline phosphatase (tALP), lactate dehydrogenase (LDH), and prostate-specific antigen (PSA) at baseline were associated with OS (P ≤ 0.0003) in the intent-to-treat population (radium-223, N = 614; placebo, N = 307). tALP declined from baseline within 4 weeks after beginning radium-223, by week 12 declining in 87% of radium-223 and 23% of placebo patients (P radium-223 and 37.2% increase with placebo. Radium-223 patients with tALP decline from baseline to week 12 (confirmed ≥3 weeks from week 12) had 55% lower risk of death (hazard ratio = 0.45; 95% CI 0.34–0.61) versus those with no confirmed tALP decline. Proportional treatment effect (PTE) values for tALP, LDH, and PSA changes from baseline at week 12 as OS surrogate markers were 0.34 (95% CI: 0–0.746), 0.07 (95% CI: 0–0.211), and 0 (95% CI: 0–0.082), respectively. Conclusions Significant tALP declines (versus placebo) occurred as early as 4 weeks after beginning radium-223 therapy. tALP or LDH declines at 12 weeks correlated with longer OS, but did not meet statistical surrogacy requirements. Dynamic changes in tALP and LDH during radium-223 treatments may be useful to monitor, but do not serve as surrogates for survival. PMID:28453701

  18. Autosomal dominant hereditary spastic paraplegia with axonal sensory motor polyneuropathy maps to chromosome 21q 22.3.

    Science.gov (United States)

    Peddareddygari, Leema Reddy; Hanna, Philip A; Igo, Robert P; Luo, Yuqun A; Won, Sungho; Hirano, Michio; Grewal, Raji P

    2016-01-01

    Hereditary spastic paraplegia (HSP) are a genetically and clinically heterogeneous group of disorders. At present, 19 autosomal dominant loci for HSP have been mapped. We ascertained an American family of European descent segregating an autosomal dominant HSP associated with peripheral neuropathy. A genome wide scan was performed with 410 microsatellite repeat marker (Weber lab screening set 16) and following linkage and haplotype analysis, fine mapping was performed. Established genes or loci for HSP were excluded by direct sequencing or haplotype analysis. All established loci for HSP were excluded. Fine mapping suggested a locus on chromosome 21q22.3 flanked by markers D21S1411 and D21S1446 with a maximum logarithm of odds score of 2.05 and was supported by haplotype analysis. A number of candidate genes in this region were analyzed and no disease-producing mutations were detected. We present the clinical and genetic analysis of an American family with autosomal dominant HSP with axonal sensory motor polyneuropathy mapping to a novel locus on chromosome 21q22.3 designated SPG56.

  19. New X-linked mental retardation syndrome with the gene mapped tentatively in Xp22.3

    Energy Technology Data Exchange (ETDEWEB)

    Wittwer, B. [Institut fuer Humangenetik der Universitaet, Muenster (Germany); Kircheisen, R. [Institut fuer Humangenetik der Universitaet, Heidelberg (Germany); Leutelt, J.; Gal, A. [Institut fuer Humangenetik der Medizinischen Universitaet, Luebeck (Germany); Orth, U.; Gal, A. [Institut fuer Humangenetik, Universitaets-Krankenhaus Eppendorf, Hamburg (Germany)

    1996-07-12

    X-linked mental retardation (XLMR) is genetically heterogeneous and clinically variable. We describe a new XLMR syndrome of severe mental retardation and multiple congenital anomalies. Two sisters have (with 3 different partners) 3 severely handicapped sons. In 2 cases, oligohydramnios and intrauterine growth retardation were noted. Common anomalies included a square-shaped face, high and broad forehead, frontal bossing, downward slant of palpebral fissures, hypertelorism, epicanthic folds, long philtrum, thin upper lip, and apparently low-set ears. One boy has bilateral microphthalmos and sclerocornea, and his cousin has atrophy of the optic nerve. All 3 patients are blind and have profound statomotor and mental retardation, seizures, and a grossly abnormal electroencephalographic pattern. Additional findings are short stature, delayed bone matuation, hydronephrosis, vesicorenal reflux, cryptorchidism, clinodactyly of the 5th fingers, and transverse palmar creases. The karyotype is normal (46,XY). Segregation analysis showed perfect coinheritance between the clinical phenotype and alleles at several loci in Xp22.3, whereas recombinants were identified with marker loci from Xp22.2-qter. Analysis of multiple informative meioses suggests that the disease locus maps in Xp22.3 distal to DXS16. 9 refs., 5 figs., 2 tabs.

  20. One-Year Postapproval Clinical Experience with Radium-223 Dichloride in Patients with Metastatic Castrate-Resistant Prostate Cancer.

    Science.gov (United States)

    Jadvar, Hossein; Challa, Sudha; Quinn, David I; Conti, Peter S

    2015-06-01

    We report our 1-year postapproval clinical experience with Radium-223 dichloride for treatment of castrate-resistant prostate cancer with bone metastases. The clinical courses of the first 25 patients treated were reviewed retrospectively. Incidence of hematologic, gastrointestinal, and other adverse events were identified, including those events that led to cessation or delay in treatment. Alterations in bone pain and serum alkaline phosphatase and prostate-specific antigen (PSA) levels were evaluated. Six patients received all 6 scheduled doses of Radium-223 dichloride, 2 completed 5 doses, 6 received 4 doses, 2 completed 3 doses, 6 patients had 2 doses, and 3 patients received one dose, for a total of 91 doses administered. Nine patients discontinued treatment after receiving at least one dose due to progressive disease, 5 required blood transfusions, 5 developed gastrointestinal symptoms, 4 reported worsening bone pain, and 1 developed dermatitis. Downward trends in serum alkaline phosphatase and PSA were seen in 11 and 5 patients, respectively. About one-quarter of cohort completed the entire six-dose treatment. Advancing soft tissue disease was the primary reason for cessation of therapy. The adverse events were mild and manageable. A decline in serum alkaline phosphatase was more common than a decline in PSA.

  1. From palliative therapy to prolongation of survival: (223)RaCl2 in the treatment of bone metastases.

    Science.gov (United States)

    Liepe, Knut; Shinto, Ajit

    2016-07-01

    Patients with hormone-refractory prostate cancer often have multiple bone metastases. The resulting bone pain is associated with reduced life quality, increased cost of therapy and impairment of overall survival. Trials with bone-targeting β-emitters have mostly showed an effect on alleviation of bone pain along with prolongation in survival, documented in only a limited number of patients. A randomized phase III trial (ALSYMPCA) using the α-emitter (223)RaCl2 (Xofigo®) showed for the first time, a longer overall survival of 3.6 months in treated patients as a sign of an antitumor effect. The time to first skeletal-related events was also significantly longer in the therapy group compared with placebo. Because of the short range of α-emitter, the bone marrow toxicity of radium therapy is low, and so this radionuclide could also be a candidate for combination with chemotherapy. The elimination of (223)RaCl2 is mainly through the gastrointestinal tract and side effects are mainly in this area. The procedure is similar to treatment with other bone-seeking agents and consists of six administrations of 50 kBq/kg bodyweight Xofigo®, repeated every 4 weeks. At present Xofigo® is only approved for hormone-refractory prostate cancer.

  2. Submicroscopic interstitial deletion of chromosome 11q22.3 in a girl with mild mental retardation and facial dysmorphism: Case report

    Directory of Open Access Journals (Sweden)

    Zagorac Andreja

    2011-08-01

    Full Text Available Abstract Background Except for terminal deletions that lead to Jacobsen syndrome, interstitial deletions involving the long arm of chromosome 11 are not frequently reported. A clinically distinct phenotype is usually observed in these cases, and no clear genotype-phenotype correlation is proposed. Results Here we present a case study of a 5-year-old girl with de novo submicroscopic deletion of chromosome 11q22.3 with mild mental retardation and facial dysmorphism. A standard cytogenetic analysis did not reveal any structural aberrations. In contrary, array-CGH analysis indicated a small deletion of 11q22.3. Discussion To our knowledge, this is the smallest 11q22.3 deletion reported in literature, containing nine RefSeq genes. Although none of the deleted genes are obvious candidates for the features observed in our patient, genes CUL5 and SLN could play a key role in the features described.

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

    Science.gov (United States)

    McNamara, Megan A; George, Daniel J

    2015-05-07

    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.

  4. Development of separation technology for the removal of radium-223 from targeted thorium conjugate formulations. Part I: purification of decayed thorium-227 on cation exchange columns.

    Science.gov (United States)

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

    2017-02-01

    Targeted thorium conjugates (TTCs) are being explored as a potential future platform for specific tumor targeting pharmaceuticals. In TTCs, the alpha emitting radionuclide thorium-227 ((227)Th) with a half-life of 18.697 d is labeled to targeting moieties, such as monoclonal antibodies (mAbs). The amount of daughter nuclide radium-223 ((223)Ra, t1/2 = 11.435 d) will increase during manufacture and distribution, and so a technology for purification is required to assure an acceptable level of (223)Ra is administrated to the patient. Since (223)Ra is the only progeny of (227)Th with a long half-life (days), the progenies of (223)Ra will have a very limited stay in the formulation once (223)Ra is removed. The focus in this study has, therefore, been on the removal of (223)Ra. In this study, the sorption and separation of (223)Ra (radium(II)) and (227)Th (thorium(IV)) on cation exchange columns has been evaluated as a purification method of decayed (227)Th (i.e. prior to radiolabelling of a mAb and formation of TTC). The goal is to minimize the sorption of (227)Th and maximize the sorption of (223)Ra. Statistical experimental design with formulation and process parameters, including buffered formulations comprising citrate and acetate, at various concentrations and pH, presence of free radical scavenger and chelator, and resin amount have been evaluated for impact on the purification process. The studies have been interpreted by the aid of multivariate data analysis. The correlations between design of experimental variables and sorption are summarized by regression models. The predictive accuracy of radionuclide sorption was given by standard deviation and 95% confidence intervals originating from statistical cross validation. Experimental results and statistical models for citrate-buffered formulations verified reproducible and acceptable sorption levels of (223)Ra and (227)Th under selected conditions. For acetate-buffered formulations, prediction of (227)Th

  5. Mental retardation in a boy with an interstitial deletion at Xp22.3 involving STS, KAL1, and OA1: Implication for the MRX locus

    Energy Technology Data Exchange (ETDEWEB)

    Muroya, Koji; Ogata, Tsutomu; Natsuo, Nobutake [Keio Univ. School of Medicine, Tokyo (Japan)] [and others

    1996-09-06

    Although genotype-phenotype correlations in male patients with various types of nullisomy for Xp22.3 have assigned a locus for X-linked mental retardation (MRX) to an approximately 3-Mb region between DXS31 and STS, the precise location has not been determined. In this paper, we describe a 14 7/12 year old Japanese boy with mental retardation and an interstitial deletion at Xp22.3 involving STS, KAL1, and OA1, and compare the deletion map with that of previously reported three familial male patients with low-normal intelligence and a similar interstitial deletion at Xp22.3. The results suggest that the MRX gene is further localized to the roughly 1.5-Mb region between DXS1060 and DXS1139. 31 refs., 4 figs.

  6. SU-F-T-57: Delivered Activity Accuracy of Radium 223 Dichloride Injections, When Being Administrated for Castration Resistant Prostate Cancer, Symptomatic Bone Metastases. The Impact of Residual Activity in the Spent Syringe and Dispensing Accuracy of Ra 223

    Energy Technology Data Exchange (ETDEWEB)

    Jennings, G [Marsden Medical Physics Associates, Denville, NJ (United States)

    2016-06-15

    Purpose: To quantify the delivered activity accuracy of Radium 223 dichloride injections, when being administrated for castration – resistant prostate cancer, symptomatic bone metastases. The impact of residual activity in the spent syringe and dispensing accuracy of Ra 223. Methods: The administration is by slow intravenous injection over 1 minute followed by double flushing of the 10 mL syringe and IV with saline. Eighty (80) procedures was used to investigate variations in the activity from the amount prescribed (µCi) = 1.35 × Patient weight Kg. The Activity dispensed into a 10mL syringe using a NIST traceable Capintec CRC-25R Chamber and a cross calibrated capintec CRC-15R to measure activity in the syringe immediately before and after administration Results: The patients weight range from 121Ib to 235lb and doses ranging 74.25 µCi to 144.2 µCi. The deviation of dispensed dose vs Prescribed dose average +2.1% with a range of −1.1% to +5.7%. The Dose measured before administration ranges 79.3 µCi to 154.9 µCi. Deviation from the dispensed dose was show to average +2.9% with a range of −0.8% to +7.3%. The average residual dose post injection was 2.5 µCi or 2.2% of the pre injection activity. Ranging from 0.9 µCi to 6.2 µCi, 0.7% to 5.4% respectively. Subtracting the residual activity from that measured activity before injection and comparing it to prescription dose was shown to have an average variation of +2.7% with a range of −0.8% to 7.4%. Conclusion: The case resulted in the 6.2 µCi maximum residual dose had two syringes. A small, 82.8 µCi activity, case resulted in the 7.4% maximum variation in measures less residual verses prescription dose. The average +2.1 % dispenses activity of Ra 223 over the prescription dosage was seen to counteract the average 2.2% residual dosage found to remain in the syringe.

  7. Pathway of proton transfer in bacterial reaction centers: replacement of serine-L223 by alanine inhibits electron and proton transfers associated with reduction of quinone to dihydroquinone.

    Science.gov (United States)

    Paddock, M L; McPherson, P H; Feher, G; Okamura, M Y

    1990-01-01

    The pathway of proton transfer in the reaction center (RC) from Rhodobacter sphaeroides was investigated by site-directed mutagenesis. Ser-L223, a putative proton donor that forms a hydrogen bond with the secondary quinone acceptor QB, was replaced with Ala and Thr. RCs with Ala-L223 displayed reduced electron transfer and proton uptake rates in the reaction QA-QB- + 2H+----QAQBH2. The rate constant for this reaction, k(2)AB, was found to be reduced approximately 350-fold to 4.0 +/- 0.2 s-1. Proton uptake measurements using a pH indicator dye showed a rapid uptake of 1 H+ per RC followed by a slower uptake of 1 H+ per RC at a rate of 4.1 +/- 0.1 s-1; native RCs showed a rapid uptake of 2H+ per RC. Evidence is provided that these changes were not due to gross structural changes in the binding site of QB. RCs with Thr-L223 showed little reduction in the rates of electron and proton transfer. These results indicate that proton transfer from the hydroxyl group of Ser-L223 or Thr-L223 is required for fast electron and proton transfer associated with the formation of the dihydroquinone QH2. In contrast, previous work showed that replacing Glu-L212, another putative proton donor to QB, with Gln slowed proton uptake from solution without significantly altering electron transfer. We propose a model that involves two distinct proton transfer steps. The first step occurs prior to transfer of the second electron to QB and involves proton transfer from Ser-L223. The second step occurs after this electron transfer through a pathway involving Glu-L212. PMID:2168561

  8. Radium-223 outcomes after multiple lines of metastatic castration-resistant prostate cancer therapy in clinical practice: implication of pre-treatment spinal epidural disease.

    Science.gov (United States)

    Spratt, D E; Osborne, J R; Zumsteg, Z S; Rebeiz, K; Leeman, J; Rivera, A; Morris, M J; Zelefsky, M J

    2016-09-01

    Magnetic resonance imaging (MRI) is not routinely performed before initiating radium-223 to document spinal epidural disease. However, radium-223 decays to form α-particles with very short path lengths that may not reach the epidural space. Herein, we investigate the impact of baseline spinal epidural disease on metastatic castration-resistant prostate cancer (mCRPC) patients treated with radium-223. Between October 2013 to December 2014, 41 consecutive mCRPC patients at a large tertiary cancer center were prescribed radium-223 as part of standard of care. 29% of patients had pre-treatment epidural disease (posMRI), 27% had no epidural disease (negMRI), and 44% did not have a baseline MRI (noMRI). All patients had post-treatment spinal imaging. Actuarial survival times were calculated for overall survival (OS), spinal axis radiographic progression-free survival (spinePFS) and epidural progression-free survival (epiPFS) from time of first radium-223 treatment. For patients with posMRI (n=12), noMRI (n=18) and negMRI (n=11) cumulative rates of development or worsening of epidural disease and/or high-grade cord compression at time of last follow-up were 83%, 44% and 9%, respectively (P=0.001). For the posMRI, noMRI and negMRI groups the median OS was 6.3 months, 12.6 months and not reached (P=0.01), the median spinePFS was 3.2 months, 4.8 months and not reached (P=0.01), and the median epiPFS was 3.2 months, 10.4 months and not reached (P=0.001). Completing less than six cycles of radium-223 was significantly associated with worse OS (Pradium-223 therapy. Studies are needed to determine the optimal timing of radium-223 with other mCRPC therapies given the predilection for epidural disease and treatment failure after multiple prior lines of mCRPC therapy.

  9. A unique drug distribution process for radium Ra 223 dichloride injection and its implication for product quality, patient privacy, and delineation of professional responsibilities.

    Science.gov (United States)

    Dansereau, Raymond N

    2014-11-01

    On May 15, 2013, Bayer Healthcare Pharmaceuticals announced that it had received marketing approval for the therapeutic radioactive medication radium Ra 223 dichloride injection (Xofigo; Ra 223). The product acquisition and distribution process for hospital-based nuclear pharmacies and nuclear medicine services is unlike any other. The product is distributed as a low-risk compounded sterile preparation through a single compounding nuclear pharmacy located in Denver, Colorado, pursuant to a prescription. This model for drug distribution and delivery to the user institution has implications for product quality, patient privacy, and delineation of professional responsibilities. © The Author(s) 2014.

  10. Potential role of microRNA‑223‑3p in the tumorigenesis of hepatocellular carcinoma: A comprehensive study based on data mining and bioinformatics.

    Science.gov (United States)

    Zhang, Rui; Zhang, Li-Jie; Yang, Mei-Ling; Huang, Lan-Shan; Chen, Gang; Feng, Zhen-Bo

    2018-02-01

    The aims of the present study were to examine the potential role of microRNA‑233‑3p (miR)‑223‑3p in the tumorigenesis of hepatocellular carcinoma (HCC), and to investigate its diagnostic accuracy and potential molecular mechanisms. The expression data of miR‑223‑3p in HCC were obtained from the Gene Expression Omnibus (GEO). Data for the precursor miR‑223 were obtained from The Cancer Genome Atlas (TCGA). The diagnostic role of miR‑223‑3p was identified by the receiver operating curve (ROC), and the diagnostic value of miR‑223‑3p in HCC was calculated from qualified reports in the literature. In addition, associated data from the GEO, TCGA and qualified experiments were pooled for comprehensive meta‑analysis. Genes, which intersected between online prediction databases, natural language processing and differentially expressed genes from TCGA were regarded as potential targets of miR‑223‑3p in HCC. The Gene Ontology enrichment analysis and the Kyoto Encyclopedia of Genes and Genomes pathways of potential targets were performed using the Database for Annotation, Visualization and Integrated Discovery. The protein‑protein interactions were mapped using the Search Tool for the Retrieval of Interacting Genes. Among 15 qualified microarray data sets from GEO, seven showed that a significantly lower level of miR‑223‑3p was present in the HCC tissues, compared with that in non‑cancerous tissues (P0.80 (P<0.05). The diagnostic accuracy of the precursor miR‑223 in TCGA was also calculated (AUC=0.78, P<0.05). Similarly, the precursor miR‑223 showed a higher level of downregulation in HCC tissues, compared with that in healthy controls in TCGA (P<0.001). A summary ROC was also calculated as 0.89 (95% CI, 0.85‑0.91) in the meta‑analysis. A total of 72 potential targets were extracted, mainly involved in the terms 'microRNAs in cancer', 'ATP binding' and 'prostate cancer'. Five potential target genes were considered the hub genes of

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

    Directory of Open Access Journals (Sweden)

    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.

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

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    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

  13. 76 FR 24832 - Airworthiness Directives; Airbus Model A330-201, -202, -203, -223, and -243 Airplanes, A330-300...

    Science.gov (United States)

    2011-05-03

    ...-201, -202, -203, - 223, and -243 Airplanes, A330-300 Series Airplanes, A340-200 Series Airplanes, and A340-300 Series Airplanes AGENCY: Federal Aviation Administration (FAA), DOT. ACTION: Notice of... some rudders fitted on A330 and A340-200/-300 aeroplanes. An extended de-bonding, if not detected and...

  14. Dysbindin (DTNBP1, 6p22.3) is Associated with Childhood-Onset Psychosis and Endophenotypes Measured by the Premorbid Adjustment Scale (PAS)

    Science.gov (United States)

    Gornick, M. C.; Addington, A. M.; Sporn, A.; Gogtay, N.; Greenstein, D.; Lenane, M.; Gochman, P.; Ordonez, A.; Balkissoon, R.; Vakkalanka, R.; Weinberger, D. R.; Rapoport, J. L.; Straub, R. E.

    2005-01-01

    Straub "et al." ("2002") recently identified the 6p22.3 gene dysbindin (DTNBP1) through positional cloning as a schizophrenia susceptibility gene. We studied a rare cohort of 102 children with onset of psychosis before age 13. Standardized ratings of early development, medication response, neuropsychological and cognitive performance, premorbid…

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

    Directory of Open Access Journals (Sweden)

    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.

  16. Evaluation of bone metastases by 18F-choline PET/CT in a patient with castration-resistant prostate cancer treated with radium-223.

    Science.gov (United States)

    Scalzi, Piera; Baiocco, Cinzia; Genovese, Sabrina; Trevisan, Antonella; Sirotova, Zuzana; Poti, Carlo

    2017-02-03

    To date, bone metastases remain the main cause of morbidity and mortality in patients with metastatic castration-resistant prostate cancer (mCRPC). Therefore, the combination of accurate early detection of bony disease and effective treatment of these lesions is crucial in the management of mCRPC patients, but clinical trials specifically designed to test novel approaches are currently lacking. This report describes the case of a 74-year-old male with bone mCRPC and symptomatic and biochemical progression, who underwent radium-223 therapy, following previous treatment failure. 18F-choline positron emission tomography (PET)/computed tomography (CT) was used to assess changes in skeletal tumor activity before and after radium-223. Changes in prostate-specific antigen and alkaline phosphatase were also determined. 18F-choline PET/CT showed that treatment with radium-223 was able to effectively reduce bone metastatic disease, and this was accompanied by an excellent metabolic response. In clinical practice, metabolic assessment of lesions by 18F-choline PET/CT following radium-223 seems a valid approach to monitor treatment response. Until results from clinical trials become available, reporting of single cases relating to data on the use of this technique remains paramount.

  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

    Energy Technology Data Exchange (ETDEWEB)

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    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

  20. A Retrospective Analysis of the First 41 mCRPC Patients with Bone Pain Treated with Radium-223 at the National Institute of Oncology in Hungary.

    Science.gov (United States)

    Küronya, Zs; Sinkovics, I; Ágoston, P; Bíró, K; Bodrogi, I; Böde, I; Dank, M; Gyergyay, F; Vajdics, T; Kolonics, Zs; Nagyiványi, K; Rúzsa, Á; Géczi, L

    2017-10-01

    Radium-223 dichloride is an alpha-emitting radiopharmaceutical which significantly prolongs overall survival in patients with castration-resistant prostate cancer (CRPC) and symptomatic bone metastases. This was a retrospective analysis of the efficacy and safety of Radium-223 in the first 41 patients treated at a single center in Hungary. Radium-223 was given at a dose of 50 kBq/kg intravenously every 4 weeks for up to 6 cycles. Between 23rd July 2014 and 23rd February 2016, 41 patients were treated. Patient demographics, laboratory values, treatment outcomes and adverse events were collected from medical records. The mean age was 72.2 years (SD: 7.1). 24 patients received Radium-223 as first-line treatment (58%), 7 patients as second (17%), 3 as third (7.3%), 6 as (14.6%), and 1 as fifth-line therapy (2.4%). The mean number of cycles administered was 5.5 (SD: 1.1). The most common side effects were anemia (32% grade 1-3), nausea (28%, grade 1), diarrhea (4%, grade 2), thrombocytopenia (4%, grade 3). The mean baseline PSA level was 307.2 ng/ml (SD: 525.7), which increased to a mean value of 728.5 ng/ml (SD: 1277) by the end of treatment. The baseline mean ALP of 521.1 U/L (SD: 728) decreased to 245.1 U/L (SD: 283.5). The majority of patients experienced a decrease (37%) or complete cessation (43%) of bone pain intensity. In our symptomatic prostate cancer patient population, Radium-223 proved to be efficient in terms of pain relief, with moderate side effects. No PSA response was detected, while alkaline phosphatase levels significantly decreased.

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

    Energy Technology Data Exchange (ETDEWEB)

    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. Whole-Body and Microenvironmental Localization of Radium-223 in Naïve and Mouse Models of Prostate Cancer Metastasis.

    Science.gov (United States)

    Abou, Diane S; Ulmert, David; Doucet, Michele; Hobbs, Robert F; Riddle, Ryan C; Thorek, Daniel L J

    2016-05-01

    Bone-metastatic, castration-resistant prostate cancer (bmCRPC) represents a lethal stage of the most common noncutaneous cancer in men. The recent introduction of Radium-223 dichloride, a bone-seeking alpha particle (α)-emitting radiopharmaceutical, demonstrates statistically significant survival benefit and palliative effect for bmCRPC patients. Clinical results have established safety and efficacy, yet questions remain regarding pharmacodynamics and dosing for optimized patient benefit. We elucidated the biodistribution of (223)Ra as well as interaction with the bone and tumor compartments in skeletally mature mice (C57Bl/6 and CD-1, n = 3-6) and metastasis models (LNCaP and PC3, n = 4). Differences in uptake were evaluated by µCT and histological investigation. Novel techniques were leveraged on whole-mount undecalcified cryosections to determine microdistribution of Radium-223. All statistical tests were two-sided. (223)Ra uptake in the bones (>30% injected activity per gram) at 24 hours was also accompanied by non-negligible remnant activity in the kidney (2.33% ± 0.36%), intestines (5.73% ± 2.04%), and spleen (10.5% ± 5.9%) Skeletal accumulation across strains did not correspond with bone volume or surface area but instead to local blood vessel density (P = .04). Microdistribution analysis by autoradiography and α camera revealed targeting of the ossifying surfaces adjacent to the epiphyseal growth plate. In models of PCa metastasis, radioactivity does not localize directly within tumors but instead at the apposite bone surface. Osteoblastic and lytic lesions display similar intensity, which is comparable with uptake at sites of normal bone remodeling. Profiling the macro- and microdistribution of (223)Ra in healthy and diseased models has important implications to guide precision application of this emerging α-therapy approach for bmCRPC and other bone metastastic diseases. © The Author 2015. Published by Oxford University Press.

  3. High-Density Lipoprotein-Associated miR-223 Is Altered after Diet-Induced Weight Loss in Overweight and Obese Males.

    Directory of Open Access Journals (Sweden)

    Fatiha Tabet

    Full Text Available microRNAs (miRNAs are small, endogenous non-coding RNAs that regulate metabolic processes, including obesity. The levels of circulating miRNAs are affected by metabolic changes in obesity, as well as in diet-induced weight loss. Circulating miRNAs are transported by high-density lipoproteins (HDL but the regulation of HDL-associated miRNAs after diet-induced weight loss has not been studied. We aim to determine if HDL-associated miR-16, miR-17, miR-126, miR-222 and miR-223 levels are altered by diet-induced weight loss in overweight and obese males.HDL were isolated from 47 subjects following 12 weeks weight loss comparing a high protein diet (HP, 30% of energy with a normal protein diet (NP, 20% of energy. HDL-associated miRNAs (miR-16, miR-17, miR-126, miR-222 and miR-223 at baseline and after 12 weeks of weight loss were quantified by TaqMan miRNA assays. HDL particle sizes were determined by non-denaturing polyacrylamide gradient gel electrophoresis. Serum concentrations of human HDL constituents were measured immunoturbidometrically or enzymatically.miR-16, miR-17, miR-126, miR-222 and miR-223 were present on HDL from overweight and obese subjects at baseline and after 12 weeks of the HP and NP weight loss diets. The HP diet induced a significant decrease in HDL-associated miR-223 levels (p = 0.015, which positively correlated with changes in body weight (r = 0.488, p = 0.032. Changes in miR-223 levels were not associated to changes in HDL composition or size.HDL-associated miR-223 levels are significantly decreased after HP diet-induced weight loss in overweight and obese males. This is the first study reporting changes in HDL-associated miRNA levels with diet-induced weight loss.

  4. Metal ion mediated transition from random coil to β-sheet and aggregation of Bri2-23, a natural inhibitor of Aβ aggregation.

    Science.gov (United States)

    Luczkowski, Marek; De Ricco, Riccardo; Stachura, Monika; Potocki, Slawomir; Hemmingsen, Lars; Valensin, Daniela

    2015-03-01

    Furin-dependent maturation of the BRI2 protein generates the Bri2-23 fragment that is able to arrest the aggregation of amyloidβ, the peptide implicated in Alzheimer's disease (AD). Bri2-23 contains cysteines at positions 5 and 22, which are likely to bind to metal ions such as Cu(i). Metal ions may play a role in the etiology of neurodegenerative disorders such as AD, and in this work we explore the metal ion induced folding and aggregation of Bri2-23 using Hg(ii) and Ag(i) as spectroscopic probes with structural and ligand preferences similar to those of Cu(i), while not displaying redox activity under the experimental conditions. In general, interaction of Bri2-23 with soft metal ions changes the structural properties and solution behavior of the peptide that tune to increasing metal to peptide stoichiometry. Potentiometric, (199m)Hg PAC and ESI-MS data indicate that addition of up to 0.5 equivalents of Hg(ii) to Bri2-23 yields a two-coordinated HgS2 structure at the metal site. While the free peptide is inherently unstructured, the presence of Ag(i) and Hg(ii) gives rise to β-sheet formation. NMR spectroscopy supports the formation of β-sheet structure in the presence of 0.5 equivalents of Hg(ii), and displays an interesting and marked change in the TOCSY spectra when increasing the Hg(ii) to peptide stoichiometry from 0.5 to 0.7 equivalents, indicating the equilibrium between two structural analogues of the complex. Addition of more than 0.7 equivalents of Hg(ii) gives rise to line broadening, presumably reflecting aggregation. This is further supported by ThT fluorescence studies showing that the Bri2-23 peptide does not aggregate over 24 hours, while addition of over 0.7 equivalents of Ag(i) or Hg(ii) leads to increase of fluorescence, indicating that these metal ions induce aggregation. Thus, a model integrating all data into a coherent picture is that the metal ion binding to the two thiolates gives rise to folding of the peptide into a structure that

  5. Development and physical analysis of YAC contigs covering 7 Mb of Xp22.3-p22.2

    Energy Technology Data Exchange (ETDEWEB)

    Herrell, S.; Novo, F.J.; Charlton, R. [Univ. of Cambridge (United Kingdom)] [and others

    1995-01-20

    A total of YAC clones have been isolated from the region of Xp22.2-p22.3 extending from the amelogenin gene locus to DXS31. Restriction analysis of these clones in association with STS contenting and end clone analysis has facilitated the construction of 6 contigs covering a total of 7 Mb in which 20 potential CpG islands have been located. Thirty new STSs have been developed from probe and YAC end clone sequences, and these have been used in the analysis of patients suffering from different combinations of chondrodysplasia punctata, mental retardation, X-linked ichthyosis, and Kallmann syndrome. The results suggest that (1) the gene for chondrodysplasia punctata must lie between the X chromosome pseudoautosomal boundary (PABX) and DXS1145; (2) a gene for mental retardation lies between DXS1145 and the sequence tagged site GS1; and (3) the gene for ocular albinism type 1 lies proximal to the STS G13. The CpG islands within the YAC contigs constitute valuable markers for the potential positions of genes. Genes found associated with any of these potential CpG islands would be possible candidates for the disease genes mentioned above. 47 refs., 3 figs., 5 tabs.

  6. Effects of LEP G2548A and LEPR Q223R Polymorphisms on Serum Lipids and Response to Simvastatin Treatment in Chinese Patients With Primary Hyperlipidemia.

    Science.gov (United States)

    Li, Kang; Liu, Yanhong; Venners, Scott A; Hsu, Yi-Hsiang; Jiang, Shanqun; Weinstock, Justin; Sun, Yiyang; Wang, Binyan; Xu, Xiping

    2017-05-01

    To investigate whether LEP G2548A and LEPR Q223R polymorphisms influence serum lipid levels and whether the 2 polymorphisms affect the efficacy of simvastatin treatment in Chinese patients with primary hyperlipidemia. We used an extreme sampling approach by selecting 212 individuals from the top and bottom 15% of adjusted lipid-lowering response residuals to simvastatin (n = 106 in each group of good or bad response) from a total of 734 samples with primary hyperlipidemia. They were treated with simvastatin orally 20 mg/d. Fasting serum lipids were measured at baseline and after 4 and 8 weeks of treatment. Genotyping was carried out using polymerase chain reaction-restriction fragment length polymorphism. More patients in the good response group (27%) had LEPR Q223R than in the bad response group (16%, P = .046). Secondary stratified analyses showed that patients carrying the RR genotype of the LEPR Q223R gene had significantly higher high-density lipoprotein cholesterol levels than those with the QR genotype at baseline ( P = .034) among good responders. After 29 consecutive days of treatment with simvastatin, patients carrying the RR genotype had a significantly larger decrease in triglycerides (change: -0.74 ± 0.92, P = .036) and total cholesterol levels (change: -1.77 ± 0.68, P = .023) compared with those carrying QR genotype among bad responders. After Bonferroni correction, the results were not statistically significant. LEPR Q223R polymorphism, but not LEP G2548A, could modulate the efficacy of simvastatin in Chinese patients with primary hyperlipidemia.

  7. Qi-Shen-Yi-Qi Dripping Pills Promote Angiogenesis of Ischemic Cardiac Microvascular Endothelial Cells by Regulating MicroRNA-223-3p Expression

    Directory of Open Access Journals (Sweden)

    Guo-Hua Dai

    2016-01-01

    Full Text Available Traditional Chinese medicine (TCM research shows that Qi-Shen-Yi-Qi Dripping Pills (QSYQ can promote ischemic cardiac angiogenesis. Studies have shown that microRNAs (miRNAs are the key component of gene regulation networks, which play a vital role in angiogenesis and cardiovascular disease. Mechanisms involving miRNA by which TCM promotes ischemic cardiac angiogenesis have not been reported. We found that microRNA-223-3p (mir-223-3p was the core miRNA of angiogenesis of rats ischemic cardiac microvascular endothelial cells (CMECs and inhibited angiogenesis by affecting RPS6KB1/HIF-1α signal pathway in previous study. Based on the results, we observed biological characteristics and optimal dosage for QSYQ intervening in rats ischemic CMECs angiogenesis and concluded that QSYQ low-dose group had the strongest ability to promote angiogenesis of ischemic myocardium. Using miRNA chip and real-time PCR techniques in this study, we identified mir-223-3p as the pivotal miRNA in QSYQ that regulated angiogenesis of ischemic CMECs. From real-time PCR and western blot analysis, research showed that gene and protein expression of factors located RPS6KB1/HIF-1α signaling pathway, including HIF-1α, VEGF, MAPK, PI3K, and AKT, were significantly upregulated by QSYQ to regulate angiogenesis of ischemic CMECs. This study showed that QSYQ promote ischemic cardiac angiogenesis by downregulating mir-223-3p expression in rats ischemic CMECs.

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

    Science.gov (United States)

    Romão-Dumaresq, Aline S.; de Araújo, Welington Luiz; Talbot, Nicholas J.; 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 the fungus, and to determine their roles in the biocontrol of soil-borne plant pathogens. The loss of N-acetyl-ß-D-glucosaminidase activities was dispensable for biocontrol of the plurivorous damping-off pathogens Rhizoctonia solani and Sclerotinia sclerotiorum, and of the sugarcane pathogen Ceratocystis paradoxa, the causal agent of pineapple disease. Similarly, suppression of endochitinase activities had no effect on R. solani and S. sclerotiorum disease control, but had a pronounced effect on the ability of T. virens 223 to control pineapple disease. Our work demonstrates a critical requirement for T. virens 223 endochitinase activity in the biocontrol of C. paradoxa sugarcane disease, but not for general antagonism of other soil pathogens. This may reflect its lifestyle as a sugarcane root endophyte. PMID:23110120

  9. RNA interference of endochitinases in the sugarcane endophyte Trichoderma virens 223 reduces its fitness as a biocontrol agent of pineapple disease.

    Directory of Open Access Journals (Sweden)

    Aline S Romão-Dumaresq

    Full Text Available 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 the fungus, and to determine their roles in the biocontrol of soil-borne plant pathogens. The loss of N-acetyl-ß-D-glucosaminidase activities was dispensable for biocontrol of the plurivorous damping-off pathogens Rhizoctonia solani and Sclerotinia sclerotiorum, and of the sugarcane pathogen Ceratocystis paradoxa, the causal agent of pineapple disease. Similarly, suppression of endochitinase activities had no effect on R. solani and S. sclerotiorum disease control, but had a pronounced effect on the ability of T. virens 223 to control pineapple disease. Our work demonstrates a critical requirement for T. virens 223 endochitinase activity in the biocontrol of C. paradoxa sugarcane disease, but not for general antagonism of other soil pathogens. This may reflect its lifestyle as a sugarcane root endophyte.

  10. Severe intellectual disability, omphalocele, hypospadia and high blood pressure associated to a deletion at 2q22.1q22.3: case report

    Directory of Open Access Journals (Sweden)

    Mulatinho Milene

    2012-06-01

    Full Text Available Abstract Background Recently, array-comparative genomic hybridization (aCGH platforms have significantly improved the resolution of chromosomal analysis allowing the identification of genomic copy number gains and losses smaller than 5 Mb. Here we report on a young man with unexplained severe mental retardation, autism spectrum disorder, congenital malformations comprising hypospadia and omphalocele, and episodes of high blood pressure. An ~ 6 Mb interstitial deletion that includes the causative genes is identified by oligonucleotide-based aCGH. Results Our index case exhibited a de novo chromosomal abnormality at 2q22 [del(2(q22.1q22.3dn] which was not visible at the 550 haploid band level. The deleted region includes eight genes: HNMT, SPOPL, NXPH2, LOC64702, LRP1B, KYNU, ARHGAP15 and GTDC1. Discussion aCGH revealed an ~ 6 Mb deletion in 2q22.1 to 2q22.3 in an as-yet unique clinical case associated with intellectual disability, congenital malformations and autism spectrum disorder. Interestingly, the deletion is co-localized with a fragile site (FRA2K, which could be involved in the formation of this chromosomal aberration. Further studies are needed to determine if deletions of 2q22.1 to 2q22.3 define a new microdeletion syndrome.

  11. HiZELS: a high-redshift survey of Hα emitters - I. The cosmic star formation rate and clustering at z = 2.23

    Science.gov (United States)

    Geach, J. E.; Smail, Ian; Best, P. N.; Kurk, J.; Casali, M.; Ivison, R. J.; Coppin, K.

    2008-08-01

    We present results from a near-infrared narrow-band survey of emission-line galaxies at z = 2.23, using the Wide Field Camera on the United Kingdom Infrared Telescope. The H2S1 narrow-band filter (λc = 2.121μm) we employ selects the Hα emission-line redshifted to z = 2.23, and is thus suitable for selecting `typical' star-forming galaxies and active galactic nuclei at this epoch. The pilot study was undertaken in the well-studied Cosmological Evolution Survey field (COSMOS) and is already the largest near-infrared narrow-band survey at this depth, with a line flux limit of FHα ~ 10-16ergs-1cm-2 over 0.60deg2, probing ~220 × 103Mpc3 (comoving) down to a limiting star formation rate of ~30Msolaryr-1 (3σ). In this paper, we present the results from our pilot survey and evaluate the Hα luminosity function and estimate the clustering properties of Hα emitters at z = 2.23 from 55 detected galaxies. The integrated luminosity function is used to estimate the volume-averaged star formation rate at z = 2.23: ρSFR = 0.17+0.16-0.09Msolaryr-1Mpc-3 for LHα > 1042ergs-1. For the first time, we use the Hα star formation tracer to reliably constrain ρSFR out to z = 2.23 demonstrating the rapid increase in ρSFR out to this redshift as well as confirming the flattening in ρSFR between z ~ 1 and 2. In addition to the luminosity distribution, we analyse the clustering properties of these galaxies. Using the two-point angular correlation function, ω(θ), we estimate a real-space correlation length of r0 = 4.2+0.4-0.2h-1Mpc. In comparison to models of clustering which take into account bias evolution, we estimate that these galaxies are hosted by dark matter haloes of mass Mhalo ~ 1012Msolar consistent with the progenitors of the Milky Way. Based on observations obtained with the Wide Field CAMera (WFCAM) on the United Kingdom Infrared Telescope (UKIRT). E-mail: j.e.geach@durham.ac.uk

  12. MO-AB-201-01: Regulatory Compliance and Safety with New Radiotherapies: Spheres and Ra-223

    Energy Technology Data Exchange (ETDEWEB)

    Phillips, L. [Stanford University (United States)

    2015-06-15

    The role of the Radiation Safety Officer at a medical facility can be complicated. The complexity of the position is based on the breadth of services provided at the institution and the nature of the radioactive materials license. Medical practices are constantly changing and the use of ionizing radiation continues to rise in this area. Some of the newer medical applications involving radiation have unique regulatory and safety issues that must be addressed. Oversight of the uses of radiation start at the local level (radiation safety officer, radiation safety committee) and are heavily impacted by outside agencies (i.e. Nuclear Regulatory Commission, State Radiologic Health, The Joint Commission (TJC), etc). This session will provide both an overview of regulatory oversight and essential compliance practices as well as practical ways to assess and introduce some of the new applications utilizing radioactive materials into your medical facility. Learning Objectives: Regulatory Compliance and Safety with New Radiotherapies: Spheres and Ra-223 (Lance Phillips) Understand the radioactive materials license amendment process to add new radiotherapies (i.e., SIR-Spheres, Therasphere, Xofigo). Understand the AU approval process for microspheres and Xofigo. Examine the training and handling requirements for new procedures. Understand the process involved with protocol development, SOP in order to define roles and responsibilities. The RSO and The RSC: Challenges and Opportunities (Colin Dimock) Understand how to form an effective Committee. Examine what the Committee does for the Program and the RSO. Understand the importance of Committee engagement. Discuss the balance of the complimentary roles of the RSO and the Committee. The Alphabet Soup of Regulatory Compliance: Being Prepared for Inspections (Linda Kroger) Recognize the various regulatory bodies and organizations with oversight or impact in Nuclear Medicine, Radiology and Radiation Oncology. Examine 10CFR35

  13. Do clinicians and patients agree regarding symptoms? A comparison after definitive radiochemotherapy in 223 uterine cervical cancer patients

    Energy Technology Data Exchange (ETDEWEB)

    Kirchheiner, K.; Poetter, R. [Medical Univ. Vienna (Austria). Dept. of Radiotherapy; Nout, R. [University Medical Center Leiden (Netherlands). Dept. of Clinical Oncology; Lindegaard, J. [University Hospital Aarhus (Denmark). Dept. of Oncology; Petric, P. [Institute of Oncology Ljubljana (Slovenia). Dept. of Radiotherapy; Limbergen, E.V. [University Hospital Leuven (Belgium). Dept. of Radiotherapy; Juergenliemk-Schulz, I.M. [University Medical Center Utrecht (Netherlands). Dept. of Radiation Oncology; Haie-Meder, C. [Institut Gustave-Roussy, Villejuif (France). Dept. of Radiotherapy; Doerr, W. [Technische Univ. Dresden (Germany). Dept. of Radiotherapy and Radiooncology

    2012-10-15

    Background: In clinical cancer research of morbidity, low associations between clinician-assessed toxicity/morbidity and patient-reported symptoms are consistently described in the literature. While morbidity grading systems are supposed to follow more or less objective criteria, patient reported symptoms inherently are based on a subjective self-evaluation of the impact on quality of life. The aim of this study was to focus on major discrepancies with high clinical relevance and to evaluate its impact with regard to underreporting of morbidity. Material and methods: Early morbidity assessed by clinicians with CTCAEv.3 and patient reported quality of life (EORTC-QLQ-C30/CX24) were compared regarding 12 overlapping symptoms in 223 patients with uterine cervical cancer 3 months after definitive radio(chemo)therapy in the ongoing EMBRACE study. Mismatches showing discrepancies between both grading systems were classified, if patients reported substantial symptoms (quite a bit/very much) and CTCAE grading was rated G0. Results: In total, 360 substantial symptoms were reported by patients by EORTC-QLQ; 159 (44%) of those were not recognized by CTCAE. Symptoms with the highest occurrence of mismatches overall are urinary frequency, fatigue, and insomnia. Large institutional differences were found, showing two centers with 4 vs. 71% of patients with at least one mismatch. Conclusion: Analysis of mismatches indicated a high risk of underestimation of early morbidity. Thus, nearly half of the patient-reported substantial symptoms were not recognized by CTCAE scoring (G0) 3 months after treatment. Prospective assessment of morbidity in clinical studies should, therefore, integrate patient reported symptoms to receive a complete and comprehensive picture. (orig.)

  14. ORIGINAL ARTICLE 223

    African Journals Online (AJOL)

    boaz

    Basaca-Sevilla V., Cross J. H., Alquiza L.,. Lacap T. Prevalence of Trichomonasvaginalisin some Filipino women, Southeast. Asian J. Trop. Med. Public Health. 1986;. 17(2): 194–196. 6. Jamali R., Zareikar R., Kazemi A., Yousefee. S. Diagnosis of Trichomonasvaginalisinfection using PCR method compared to culture and.

  15. Radium-223 and concomitant therapies in patients with metastatic castration-resistant prostate cancer: an international, early access, open-label, single-arm phase 3b trial.

    Science.gov (United States)

    Saad, Fred; Carles, Joan; Gillessen, Silke; Heidenreich, Axel; Heinrich, Daniel; Gratt, Jeremy; Lévy, Jérémy; Miller, Kurt; Nilsson, Sten; Petrenciuc, Oana; Tucci, Marcello; Wirth, Manfred; Federhofer, Judith; O'Sullivan, Joe M

    2016-09-01

    In the previously reported ALSYMPCA trial in patients with castration-resistant prostate cancer and symptomatic bone metastases, overall survival was significantly longer in patients treated with radium-223 dichloride (radium-223) than in patients treated with placebo. In this study, we investigated safety and overall survival in radium-223 treated patients in an early access programme done after the ALSYMPCA study and before regulatory approval of radium-223. We did an international, prospective, interventional, open-label, single-arm, phase 3b study. Enrolled patients were aged 18 years or older with histologically or cytologically confirmed progressive bone-predominant metastatic castration-resistant prostate cancer with two or more skeletal metastases on imaging (with no restriction as to whether they were symptomatic or asymptomatic; without visceral disease but lymph node metastases were allowed). Patients received intravenous injections of radium-223, 50 kBq/kg (current recommendation 55 kBq/kg after implementation of National Institute of Standards and Technology update on April 18, 2016) every 4 weeks for up to six injections. Other concomitant anticancer therapies were allowed. Primary endpoints were safety and overall survival. The safety and efficacy analyses were done on all patients who received at least one dose of the study drug. The study has been completed, and we report the final analysis here. This study is registered with ClinicalTrials.gov, number NCT01618370, and the European Union Clinical Trials Register, EudraCT number 2012-000075-16. Between July 22, 2012, and Dec 19, 2013, 839 patients were enrolled from 113 sites in 14 countries. 696 patients received one or more doses of radium-223; 403 (58%) of these patients had all six planned injections. Any-grade treatment-emergent adverse events occurred in 523 (75%) of 696 patients; any-grade treatment-emergent adverse events deemed to be related to treatment were reported in 281 (40%) patients

  16. Post-traumatic stress symptoms and post-traumatic growth in 223 childhood cancer survivors: predictive risk factors

    Directory of Open Access Journals (Sweden)

    Marta eTremolada

    2016-02-01

    Full Text Available With modern therapies and supportive care, survival rates of childhood cancer have increased considerably. However, there are long-term psychological sequelae of these treatments that may not manifest until pediatric survivors are into adulthood. The prevalence of post-traumatic stress disorder (PTSD in young adult survivors of childhood cancer ranges from 6.2% to 22%; associated risk factors are young age at the assessment, female gender, low education level and some disease-related factors. The aim of this study was to investigate, in adolescent and young adult (AYA survivors of childhood cancer, the incidence and severity of post-traumatic stress symptoms (PTSS, and to identify the risk factors and the associated post-traumatic growth (PTG index.Participants were 223 AYA cancer survivors recruited during follow-up visits in the Oncohematology Clinic of the Department of Child and Woman’s Health, University of Padua. Data were collected from self-report questionnaires on PTSS incidence, PTG mean score, perceived social support, and medical and socio-demographic factors. Ex-patients’ mean age at the assessment was 19.33 years (SD = 3.01, 15-25, 123 males and 100 females, with a mean of years off-therapy of 9.64 (SD=4.17. Most (52.5% had survived an hematological disorder and 47.5% a solid tumor when they were aged, on average, 8.02 years (SD=4.40.The main results indicated a moderate presence of clinical (≥9 symptoms: 9.4% and sub-clinical PTSS (6-8 symptoms: 11.2%, with the avoidance criterion most often encountered. Re-experience symptoms and PTG mean score were significantly associated (r=0.24 p=0.0001. A hierarchical regression model (R2 = 0.08; F = 1.46; p = 0.05 identified female gender (β = 0.16; p = 0.05 and less perceived social support (β = -0.43; p = 0.05 as risk factors to developing PTSS. Another hierarchical regression model assessed the possible predictors of the PTG total score (R2 = 0.36; F = 9.1; p = 0.0001, with

  17. Post-traumatic Stress Symptoms and Post-traumatic Growth in 223 Childhood Cancer Survivors: Predictive Risk Factors.

    Science.gov (United States)

    Tremolada, Marta; Bonichini, Sabrina; Basso, Giuseppe; Pillon, Marta

    2016-01-01

    With modern therapies and supportive care, survival rates of childhood cancer have increased considerably. However, there are long-term psychological sequelae of these treatments that may not manifest until pediatric survivors are into adulthood. The prevalence of post-traumatic stress disorder in young adult survivors of childhood cancer ranges from 6.2 to 22%; associated risk factors are young age at the assessment, female gender, low education level, and some disease-related factors. The aim of this study was to investigate, in adolescent and young adult (AYA) survivors of childhood cancer, the incidence and severity of post-traumatic stress symptoms (PTSSs), and to identify the risk factors and the associated post-traumatic growth (PTG) index. Participants were 223 AYA cancer survivors recruited during follow-up visits in the Oncohematology Clinic of the Department of Child and Woman's Health, University of Padua. Data were collected from self-report questionnaires on PTSS incidence, PTG mean score, perceived social support, and medical and socio-demographic factors. Ex-patients' mean age at the assessment was 19.33 years (SD = 3.01, 15-25), 123 males and 100 females, with a mean of years off-therapy of 9.64 (SD = 4.17). Most (52.5%) had survived an hematological disorder and 47.5% a solid tumor when they were aged, on average, 8.02 years (SD = 4.40). The main results indicated a moderate presence of clinical (≥9 symptoms: 9.4%) and sub-clinical PTSS (6-8 symptoms: 11.2%), with the avoidance criterion most often encountered. Re-experience symptoms and PTG mean score were significantly associated (r = 0.24; p = 0.0001). A hierarchical regression model (R (2) = 0.08; F = 1.46; p = 0.05) identified female gender (β = 0.16; p = 0.05) and less perceived social support (β = -0.43; p = 0.05) as risk factors to developing PTSS. Another hierarchical regression model assessed the possible predictors of the PTG total score (R (2) = 0.36; F = 9.1; p = 0.0001), with

  18. Restrictions in Quality of Life after Intramedullary Nailing of Tibial Shaft Fracture. A retrospective follow-up study of 223 cases

    DEFF Research Database (Denmark)

    Larsen, Peter; Lund, Hans; Læssøe, Uffe

    2014-01-01

    OBJECTIVE: To evaluate the long term outcome after intramedullary nailing of tibial shaft fracture. DESIGN: Retrospective, Cross sectional study. SETTING: Level I, Trauma Center. METHODS: Retrospective review of 294 patients treated with intramedullary nailing after tibial shaft fracture from 1998......-2008. The participants completed Knee Injury and Osteoarthritis Outcome Score (KOOS) and these data were compared with published reference population. INTERVENTION: Intramedullary nailing of tibial shaft fracture. MAIN OUTCOME MEASURES: KOOS RESULTS:A total of 223 patients agreed to participate (76%). Mean time...

  19. catena-Poly[[bis-[2-(2,3-dimethyl-anilino)benzoato-κO]cadmium(II)]-di-μ-3-pyridylmethanol-κN:O;κO:N].

    Science.gov (United States)

    Moncol, Jan; Mikloš, Dušan; Segľa, Peter; Koman, Marian; Lis, Tadeusz

    2008-02-06

    In the crystal structure of the title compound, [Cd(C(15)H(14)NO(2))(2)(C(6)H(7)NO)(2)](n), the Cd atom displays a distorted octa-hedral geometry, including two pyridine N atoms and two hydroxyl O from four symmetry-related 3-pyridylmethanol (3-pyme) ligands and two carboxylate O atoms from mefenamate [2-(2,3-dimethyl-anilino)benzoate] anions. The Cd atoms are connected via the bridging 3-pyme ligands into chains, that extend in the a-axis direction. The Cd atom is located on a center of inversion, whereas the 3-pyme ligands and the mefenamate anions occupy general positions.

  20. Bone Metabolism and the c.-223C > T Polymorphism in the 5'UTR Region of the Osteoprotegerin Gene in Patients with Inflammatory Bowel Disease.

    Science.gov (United States)

    Krela-Kaźmierczak, Iwona; Kaczmarek-Ryś, Marta; Szymczak, Aleksandra; Michalak, Michał; Skrzypczak-Zielińska, Marzena; Drwęska-Matelska, Natalia; Marcinkowska, Michalina; Eder, Piotr; Łykowska-Szuber, Lilianna; Wysocka, Ewa; Linke, Krzysztof; Słomski, Ryszard

    2016-12-01

    Osteoporosis is more frequent in inflammatory bowel disease (IBD) patients. A reduction in bone mineral mass in these individuals is caused not only by inflammatory processes in the bowel, because osteoporosis occurs already in very young IBD patients and in newly diagnosed individuals who have not yet undergone any pharmacological treatment. One of individual determinants of the bone turnover parameters is osteoprotegerin (OPG) encoded by the TNFRSF11B gene. The c.-223C > T polymorphism in this gene has been extensively studied in post-menopausal osteoporosis patients. However, no such studies exist for osteoporosis related to IBD. The aim of our study was to determine whether the c.-223C > T (rs2073617) polymorphism in the 5'UTR region of the gene encoding osteoprotegerin is a functional polymorphism which may change the gene expression and resulting OPG levels, and so be associated with osteopenia and osteoporosis, and impaired bone metabolism in Crohn's disease and ulcerative colitis patients. Our study included 198 IBD patients and 41 healthy controls. Lumbar spine and femoral neck bone mineral density, T-score, Z-score as well as OPG, RANKL, vitamin D, calcium and interleukin 4 and 10 concentrations were determined for all study subjects. Genotyping of the TNFRSF11B polymorphic site was performed by restriction fragment length polymorphism technique. Statistical analyses were conducted using Statistica software. Odds ratios, 95 % confidence intervals, and P values were calculated using the HWE calculator. Our results did not allow determining an unequivocal association between the polymorphic variants of the TNFRSF11B 5'UTR region and a susceptibility to osteoporosis in IBD patients. We have shown, however, that the c.-223T allele was twice as more frequent in Crohn's disease (CD) patients than among controls (OR = 1.99, P value = 0.009). Interestingly, average osteoprotegerin levels in CD patients did not significantly differ from those in

  1. New high- Tc 2-2-3 type superconductor Y 2Ba 1.5Ca 0.5Cu 3O 8+δ

    Science.gov (United States)

    Kulkarni, R. G.; Baldha, G. J.; Mohan, H.; Jotania, R. B.; Joshi, H. H.; Skumryev, V.; Rao, K. V.

    1990-02-01

    We have prepared and identified as a single-phase the new high- Tc 2-2-3 type superconductor Y 2Ba 1.5Ca 0.5Cu 3O 8+δ by resistance and a.c.-susceptibility measurements. The resistive superconducting onset occurs at 82 K and "zero resistance" at 78 K. Diamagnetism and Meissner effect sets in at low fields and magnetic superconducting onset starts at 82 K. The systematic investigation of the real and imaginary components of a.c.-susceptibility reveals that the magnetic behavior is that of a granular type superconductor.

  2. Reflections on the therapeutic use of {sup 223}RaCl{sub 2} for bone metastases resulting from prostate cancer resistant to castration; Reflexiones sobre el uso terapeutico de {sup 223}RaCl{sub 2} para metastasis osea derivada de cancer de prostata resistente a la castracion

    Energy Technology Data Exchange (ETDEWEB)

    Astudillo V, A. J.; Paredes G, L., E-mail: armando.astudillo@inin.gob.mx [ININ, Carretera Mexico-Toluca s/n, 52750 Ocoyoacac, Estado de Mexico (Mexico)

    2015-10-15

    In January 2014 the Comision Federal para la Proteccion contra Riesgos Sanitarios of the Ministry of Health in Mexico, authorize the use of {sup 223}RaCl{sub 2} 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 {sup 223}RaCl{sub 2} 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)

  3. Efficacy and safety of radium-223 dichloride in patients with castration-resistant prostate cancer and symptomatic bone metastases, with or without previous docetaxel use: a prespecified subgroup analysis from the randomised, double-blind, phase 3 ALSYMPCA trial.

    Science.gov (United States)

    Hoskin, Peter; Sartor, Oliver; O'Sullivan, Joe M; Johannessen, Dag Clement; Helle, Svein I; Logue, John; Bottomley, David; Nilsson, Sten; Vogelzang, Nicholas J; Fang, Fang; Wahba, Mona; Aksnes, Anne-Kirsti; Parker, Christopher

    2014-11-01

    Primary results from the phase 3 ALSYMPCA trial showed that radium-223 dichloride (radium-223), a targeted α-emitter, improved overall survival compared with placebo and was well tolerated in patients with castration-resistant prostate cancer and symptomatic bone metastases. We did a prespecified subgroup analysis from ALSYMPCA to assess the effect of previous docetaxel use on the efficacy and safety of radium-223. In the phase 3, randomised, double-blind ALSYMPCA trial, patients with symptomatic castration-resistant prostate cancer, at least two symptomatic bone metastases, no known visceral metastases, and who were receiving best standard of care were randomly assigned (2:1) via an interactive voice response system to receive six injections of radium-223 (50 kBq/kg intravenously) or matching placebo, with one injection given every 4 weeks. Patients had either received previous docetaxel treatment or were unsuitable for or declined docetaxel; previous docetaxel use (yes or no) was a trial stratification factor. We investigated the effect of previous docetaxel use on radium-223 treatment for the primary endpoint of overall survival, the main secondary efficacy endpoints, and safety. Efficacy analyses were done for the intention-to-treat population; safety analyses were done for the safety population. The trial has been completed and is registered with ClinicalTrials.gov, number NCT00699751. Randomisation took place between June 12, 2008, and Feb 1, 2011. 526 (57%) of 921 randomly assigned patients had received previous docetaxel treatment (352 in the radium-223 group and 174 in the placebo group) and 395 (43%) had not (262 in the radium-223 group and 133 in the placebo group). Radium-223 prolonged median overall survival compared with placebo, irrespective of previous docetaxel use (previous docetaxel use, hazard ratio [HR] 0·70, 95% CI 0·56-0·88; p=0·002; no previous docetaxel use, HR 0·69, 0·52-0·92; p=0·01). The benefit of radium-223 compared with

  4. Failure to confirm allelic and haplotypic association between markers at the chromosome 6p22.3 dystrobrevin-binding protein 1 (DTNBP1 locus and schizophrenia

    Directory of Open Access Journals (Sweden)

    Kirwin Simon

    2007-09-01

    Full Text Available Abstract Background Previous linkage and association studies may have implicated the Dystrobrevin-binding protein 1 (DTNBP1 gene locus or a gene in linkage disequilibrium with DTNBP1 on chromosome 6p22.3 in genetic susceptibility to schizophrenia. Methods We used the case control design to test for of allelic and haplotypic association with schizophrenia in a sample of four hundred and fifty research subjects with schizophrenia and four hundred and fifty ancestrally matched supernormal controls. We genotyped the SNP markers previously found to be significantly associated with schizophrenia in the original study and also other markers found to be positive in subsequent studies. Results We could find no evidence of allelic, genotypic or haplotypic association with schizophrenia in our UK sample. Conclusion The results suggest that the DTNBP1 gene contribution to schizophrenia must be rare or absent in our sample. The discrepant allelic association results in previous studies of association between DTNBP1 and schizophrenia could be due population admixture. However, even positive studies of European populations do not show any consistent DTNBP1 alleles or haplotypes associated with schizophrenia. Further research is needed to resolve these issues. The possible confounding of linkage with association in family samples already showing linkage at 6p22.3 might be revealed by testing genes closely linked to DTNBP1 for allelic association and by restricting family based tests of association to only one case per family.

  5. Concurrent Supermassive Black Hole and Galazy Growth: Linking Environment and Nuclear Activity in Zeta Equals 2.23 H Alpha Emitters

    Science.gov (United States)

    Lehmer, B. D.; Lucy, A. B.; Alexander, D. M.; Best, P. N.; Geach, J. E.; Harrison, C. M.; Hornschemeier, A. E.; Matsuda, Y.; Mullaney, J. R.; Smail, Ian; hide

    2013-01-01

    We present results from an approximately equal 100 ks Chandra observation of the 2QZ Cluster 1004+00 structure at z = 2.23 (hereafter 2QZ Clus). 2QZ Clus was originally identified as an overdensity of four optically-selected QSOs at z = 2.23 within a 15 × 15 arcmin square region. Narrow-band imaging in the near-IR (within the K band) revealed that the structure contains an additional overdensity of 22 z = 2.23 H alpha-emitting galaxies (HAEs), resulting in 23 unique z = 2.23 HAEs/QSOs (22 within the Chandra field of view). Our Chandra observations reveal that three HAEs in addition to the four QSOs harbor powerfully accreting supermassive black holes (SMBHs), with 2-10 keV luminosities of approximately equal (8-60) × 10(exp 43) erg s(exp-1) and X-ray spectral slopes consistent with unobscured active galactic nucleus (AGN). Using a large comparison sample of 210 z = 2.23 HAEs in the Chandra-COSMOS field (C-COSMOS), we find suggestive evidence that the AGN fraction increases with local HAE galaxy density. The 2QZ Clus HAEs reside in a moderately overdense environment (a factor of approximately equal 2 times over the field), and after excluding optically-selected QSOs, we find that the AGN fraction is a factor of approximately equal 3.5(+3.8/ -2.2) times higher than C-COSMOS HAEs in similar environments. Using stacking analyses of the Chandra data and Herschel SPIRE observations at 250micrometers, we respectively estimate mean SMBH accretion rates ( M(BH)) and star formation rates (SFRs) for the 2QZ Clus and C-COSMOS samples. We find that the mean 2QZ Clus HAE stacked X-ray luminosity is QSO-like (L(2-10 keV) approximately equal [6-10] × 10(exp 43) erg s(exp -1)), and the implied M(BH)/SFR approximately equal (1.6-3.2) × 10(exp -3) is broadly consistent with the local M(BH)/Stellar Mass relation and z approximately equal 2 X-ray selected AGN. In contrast, the C-COSMOS HAEs are on average an order of magnitude less X-ray luminous and have M(BH)/SFR approximately

  6. Mild phenotypic effects of a de novo deletion Xpter {yields} Xp22.3 and duplication 3pter {yields} 3p23

    Energy Technology Data Exchange (ETDEWEB)

    Kulharya, A.S.; Roop, H.; Kukolich, M.K. [Texas Dept. of Health, Denton, TX (United States)] [and others

    1995-03-13

    We report on a girl with a de novo monosomy Xpter {yields} Xp22.3 and trisomy 3pter {yields} 3p23, normal development and stature, mildly affected phenotype, and learning disabilities with a low normal level of intelligence. Late replication studies using BudR demonstrated that the entire der(X) was inactive in 30% of cells. In 62% of cells the inactivation did not spread to the autosomal segment in the der(X). The normal X was inactivated in 8% of cells. Quantitative X-inactivation studies using the human androgen receptor locus assay (HAR) on peripheral leukocytes and buccal epithelial cells showed extreme skewing of methylation (90.4% of the paternal allele). The correlation of cytogenetic and molecular data suggest that the mild phenotype of the proposita is most likely due to preferential inactivation of the entire der(X), which seems to be of paternal origin. 11 refs., 5 figs., 3 tabs.

  7. Thermodynamic and Spectroscopic Investigation of Interactions between Reactive Red 223 and Reactive Orange 122 Anionic Dyes and Cetyltrimethyl Ammonium Bromide (CTAB Cationic Surfactant in Aqueous Solution

    Directory of Open Access Journals (Sweden)

    Muhammad Irfan

    2014-01-01

    Full Text Available The present study describes the conductometric and spectroscopic study of the interaction of reactive anionic dyes, namely, reactive red 223 and reactive orange 122 with the cationic surfactant cetyltrimethyl ammonium bromide (CTAB. In a systematic investigation, the electrical conductivity data was used to calculate various thermodynamic parameters such as free energy (ΔG, enthalpy (ΔH, and the entropy (ΔS of solubilization. The trend of change in these thermodynamic quantities indicates toward the entropy driven solubilization process. Moreover, the results from spectroscopic data reveal high degree of solubilization, with strong interactions observed in the cases of both dyes and the CTAB. The spontaneous nature of solubilization and binding was evident from the observed negative values of free energies (ΔGp and ΔGb.

  8. Xp22.3 interstitial deletion: a recognizable chromosomal abnormality encompassing VCX3A and STS genes in a patient with X-linked ichthyosis and mental retardation.

    Science.gov (United States)

    Ben Khelifa, Hela; Soyah, Najla; Ben-Abdallah-Bouhjar, Inesse; Gritly, Ryma; Sanlaville, Damien; Elghezal, Hatem; Saad, Ali; Mougou-Zerelli, Soumaya

    2013-09-25

    X-linked ichthyosis is a genetic disorder affecting the skin and caused by a deficit in the steroid sulfatase enzyme (STS), often associated with a recurrent microdeletion at Xp22.31. Most of the STS deleted patients have X-linked ichthyosis as the only clinical feature and it is believed that patients with more complex disorders including mental retardation could be present as a result of contiguous gene deletion. In fact, VCX3A gene, a member of the VCX (variable charge, X chromosome) gene family, was previously proposed as the candidate gene for X-linked non-specific mental retardation in patients with X-linked ichthyosis. We report on a boy with familial ichthyosis, dysmorphic features and moderate mental retardation with approximately 2 Mb interstitial deletion on Xp22.3 involving VCX3A and STS genes. Copyright © 2013 Elsevier B.V. All rights reserved.

  9. The Trend in Distribution of Q223R Mutation of Leptin Receptor Gene in Amoebic Liver Abscess Patients from North India: A Prospective Study

    Directory of Open Access Journals (Sweden)

    Anil Kumar Verma

    2014-01-01

    Full Text Available Host genetic susceptibility is an important risk factor in infectious diseases. We explored the distribution of Q223R mutation in leptin receptor gene of amoebic liver abscess (ALA patients of North India. A total of 55 ALA samples along with 102 controls were subjected to PCR-RFLP analysis. The frequency of allele “G” (coding for arginine was in general high in Indian population irrespective of the disease. Our results of Fisher exact test shows that heterozygous mutant (QQ versus QR, P=0.049 and homozygous mutant (QQ versus RR, P=0.004 were significantly associated with amoebic liver abscess when compared with homozygous wild (QQ.

  10. De Novo 3q22.3q24 Microdeletion in a Patient With Blepharophimosis–Ptosis–Epicanthus Inversus Syndrome, Dandy-Walker Malformation, and Wisconsin Syndrome

    Science.gov (United States)

    Ramineni, Anand

    2016-01-01

    Interstitial deletions affecting the long arm of chromosome 3 have been associated with a broad phenotype. This has included the features of blepharophimosis–ptosis–epicanthus inversus syndrome, Dandy-Walker malformation, and the rare Wisconsin syndrome. The authors report a young female patient presenting with features consistent with all 3 of these syndromes. This has occurred in the context of a de novo 3q22.3q24 microdeletion including FOXL2, ZIC1, and ZIC4. This patient provides further evidence for the role of ZIC1 and ZIC4 in Dandy-Walker malformation and is the third reported case of Dandy-Walker malformation to have associated corpus callosum thinning. This patient is also only the seventh to be reported with the rare Wisconsin syndrome phenotype. PMID:28503614

  11. De Novo 3q22.3q24 Microdeletion in a Patient With Blepharophimosis-Ptosis-Epicanthus Inversus Syndrome, Dandy-Walker Malformation, and Wisconsin Syndrome.

    Science.gov (United States)

    Ramineni, Anand; Coman, David

    2016-01-01

    Interstitial deletions affecting the long arm of chromosome 3 have been associated with a broad phenotype. This has included the features of blepharophimosis-ptosis-epicanthus inversus syndrome, Dandy-Walker malformation, and the rare Wisconsin syndrome. The authors report a young female patient presenting with features consistent with all 3 of these syndromes. This has occurred in the context of a de novo 3q22.3q24 microdeletion including FOXL2 , ZIC1 , and ZIC4 . This patient provides further evidence for the role of ZIC1 and ZIC4 in Dandy-Walker malformation and is the third reported case of Dandy-Walker malformation to have associated corpus callosum thinning. This patient is also only the seventh to be reported with the rare Wisconsin syndrome phenotype.

  12. De Novo 3q22.3q24 Microdeletion in a Patient With Blepharophimosis–Ptosis–Epicanthus Inversus Syndrome, Dandy-Walker Malformation, and Wisconsin Syndrome

    Directory of Open Access Journals (Sweden)

    Anand Ramineni BSc, MBBS, GSCpMed

    2016-08-01

    Full Text Available Interstitial deletions affecting the long arm of chromosome 3 have been associated with a broad phenotype. This has included the features of blepharophimosis–ptosis–epicanthus inversus syndrome, Dandy-Walker malformation, and the rare Wisconsin syndrome. The authors report a young female patient presenting with features consistent with all 3 of these syndromes. This has occurred in the context of a de novo 3q22.3q24 microdeletion including FOXL2 , ZIC1 , and ZIC4 . This patient provides further evidence for the role of ZIC1 and ZIC4 in Dandy-Walker malformation and is the third reported case of Dandy-Walker malformation to have associated corpus callosum thinning. This patient is also only the seventh to be reported with the rare Wisconsin syndrome phenotype.

  13. Discovery and Monitoring of a New Black Hole Candidate XTE J1752-223 with RXTE: RMS Spectrum Evolution, BH Mass and the Source Distance

    Science.gov (United States)

    Shaposhinikov, Nikolai; Markwardt, Craig; Swank, Jean; Krimm, Hans

    2010-01-01

    We report on the discovery and monitoring observations of a new galactic black hole candidate XTE J1752-223 by Rossi X-ray Timing Explorer (RXTE). The new source appeared on the X-ray sky on October 21 2009 and was active for almost 8 months. Phenomenologically, the source exhibited the low-hard/highsoft spectral state bi-modality and the variability evolution during the state transition that matches standard behavior expected from a stellar mass black hole binary. We model the energy spectrum throughout the outburst using a generic Comptonization model assuming that part of the input soft radiation in the form of a black body spectrum gets reprocessed in the Comptonizing medium. We follow the evolution of fractional root-mean-square (RMS) variability in the RXTE/PCA energy band with the source spectral state and conclude that broad band variability is strongly correlated with the source hardness (or Comptonized fraction). We follow changes in the energy distribution of rms variability during the low-hard state and the state transition and find further evidence that variable emission is strongly concentrated in the power-law spectral component. We discuss the implication of our results to the Comptonization regimes during different spectral states. Correlations of spectral and variability properties provide measurements of the BH mass and distance to the source. The spectral-timing correlation scaling technique applied to the RXTE observations during the hardto- soft state transition indicates a mass of the BH in XTE J1752-223 between 8 and 11 solar masses and a distance to the source about 3.5 kiloparsec.

  14. Final Report for grant entitled "Production of Astatine-211 for U.S. Investigators"

    Energy Technology Data Exchange (ETDEWEB)

    Wilbur, Daniel Scott

    2012-12-12

    Alpha-particle emitting radionuclides hold great promise in the therapy of cancer, but few alpha-emitters are available to investigators to evaluate. Of the alpha-emitters that have properties amenable for use in humans, 211At is of particular interest as it does not have alpha-emitting daughter radionuclides. Thus, there is a high interest in having a source of 211At for sale to investigators in the US. Production of 211At is accomplished on a cyclotron using an alpha-particle beam irradiation of bismuth metal. Unfortunately, there are few cyclotrons available that can produce an alpha particle beam for that production. The University of Washington has a cyclotron, one of three in the U.S., that is currently producing 211At. In the proposed studies, the things necessary for production and shipment of 211At to other investigators will be put into place at UW. Of major importance is the efficient production and isolation of 211At in a form that can be readily used by other investigators. In the studies, production of 211At on the UW cyclotron will be optimized by determining the best beam energy and the highest beam current to maximize 211At production. As it would be very difficult for most investigators to isolate the 211At from the irradiated target, the 211At-isolation process will be optimized and automated to more safely and efficiently obtain the 211At for shipment. Additional tasks to make the 211At available for distribution include obtaining appropriate shipping vials and containers, putting into place the requisite standard operating procedures for Radiation Safety compliance at the levels of 211At activity to be produced / shipped, and working with the Department of Energy, Isotope Development and Production for Research and Applications Program, to take orders, make shipments and be reimbursed for costs of production and shipment.

  15. Production of Astatine-211 at the Duke University Medical Center for its regional distribution

    Energy Technology Data Exchange (ETDEWEB)

    Zalutsky, Michael [Duke University Medical Center, Durham, NC (United States)

    2016-01-01

    Systemic targeted radiation therapy and radioimmunotherapy continue to be important tools in the treatment of certain cancers. Because of their high energy and short path length, alpha particle emitters such as 211At are more effective than either external beam x- ray or in vivo beta radiation in delivering potentially curative doses of radiation. The limited clinical trials that have been conducted to date have yielded encouraging responses in some patients, e.g., malignant brain tumors. In order to escalate the additional necessary research and development in radiochemistry, radiobiology and efficacy evaluation of alpha particle radiotherapeutics, it is universally agreed that access to an affordable, reliable supply of 211At is warranted. In conjunction with the Department of Energy's intent to enhance stable and radioactive isotope availability for research applications, it is the primary objective of this project to improve 211At production and purification capabilities at Duke so that this radionuclide can be supplied to researchers at other institutions throughout the US.The most widely used 211At production method involves the α,2n reaction on Bismuth using a cyclotron with beams ≤ 28 MeV. Yields can be enhanced with use of an internal target that allows for a higher alpha fluence plus efficient heat dissipation in the target. Both of these items are in place at Duke; however, in order to support production for multi-institutional use, irradiation campaigns in excess of 50 µAp and four hours duration will be needed. Further, post-irradiation processing equipment is lacking that will enable the distribution process. Financial support is sought for i) a shielded, ventilated processing/containment hood; ii) development of a post-irradiation target retrieval system; iii) fabrication of a 211At distillation and recovery module and iv) a performance review and, where needed, an enhancement of seven major subsystems that comprise the CS-30 Cyclotron. With these modifications in place, routine production of ≥200 mCi of At-211 should be readily achievable, given our methodological development of At-211 target preparation, internal target irradiation and dry distillation to recover the radionuclide.

  16. 228Ra, 226Ra, 224Ra and 223Ra in potential sources and sinks of land-derived material in the German Bight of the North Sea: implications for the use of radium as a tracer

    NARCIS (Netherlands)

    Schmidt, C.; Hanfland, C.; Regnier, P.; Van Cappellen, P.; Schlüter, M.; Knauthe, U.; Stimac, I.; Geibert, W.

    2011-01-01

    Activities of the naturally occurring radium nuclides 228Ra, 226Ra, 224Ra and 223Ra were determined in waters of the open German Bight and adjacent nearshore areas in the North Sea, in order to explore the potential use of radium isotopes as natural tracers of land–ocean interaction in an

  17. Evaluation of Alpha-Therapy with Radium-223-Dichloride in Castration Resistant Metastatic Prostate Cancer—the Role of Gamma Scintigraphy in Dosimetry and Pharmacokinetics

    Directory of Open Access Journals (Sweden)

    Kalevi Kairemo

    2015-07-01

    Full Text Available Radium-223-dichloride (223RaCl2 is a new bone-seeking calcium analogue alpha-emitter, which has obtained marketing authorization for the treatment skeletal metastases of hormone-refractory prostate cancer. The current treatment regimen is based on six consecutive doses of 223RaCl2 at 4 week intervals and the administered activity dose, 50 kBq/kg per cycle is based on patient weight. We analyzed two patients using quantitative serial gamma imaging to estimate dosimetry in tumors and see possible pharmacokinetic differences in the treatment cycles. The lesions were rather well visualized in gamma scintigraphy in spite of low gamma activity (<1.1% gamma radiation at 0, 7 and 28 days using 30–60 min acquisition times. Both our patients analyzed in serial gamma imagings, had two lesions in the gamma imaging field, the mean counts of the relative intensity varied from 27.8 to 36.5 (patient 1, and from 37.4 to 82.2 (patient 2. The half-lives varied from 1.8 days to 4.5 days during the six cycles (patient 1, and from 1.5 days to 3.6 days (patient 2, respectively. In the lesion half-lives calculated from the imaging the maximum difference between the treatment cycles in the same lesion was 2.0-fold (1.8 vs. 3.6. Of these patients, patient 1 demonstrated a serum PSA response, whereas there was no PSA response in patient 2. From our data, there were maximally up to 4.0-fold differences (62.1 vs. 246.6 between the relative absorbed radiation doses between patients as calculated from the quantitative standardized imaging to be delivered in only two lesions, and in the same lesion the maximum difference in the cycles was up to 2.3-fold (107.4 vs. 246.6. Our recommendation based on statistical simulation analysis, is serial measurement at days 0–8 at least 3 times, this improve the accuracy significantly to study the lesion activities, half-lives or calculated relative absorbed radiation doses as calculated from the imaging. Both our patients had

  18. Effect of radium-223 dichloride on symptomatic skeletal events in patients with castration-resistant prostate cancer and bone metastases: results from a phase 3, double-blind, randomised trial.

    Science.gov (United States)

    Sartor, Oliver; Coleman, Robert; Nilsson, Sten; Heinrich, Daniel; Helle, Svein I; O'Sullivan, Joe M; Fosså, Sophie D; Chodacki, Aleš; Wiechno, Paweł; Logue, John; Widmark, Anders; Johannessen, Dag Clement; Hoskin, Peter; James, Nicholas D; Solberg, Arne; Syndikus, Isabel; Vogelzang, Nicholas J; O'Bryan-Tear, C Gillies; Shan, Minghua; Bruland, Øyvind S; Parker, Christopher

    2014-06-01

    Bone metastases frequently cause skeletal events in patients with metastatic castration-resistant prostate cancer. Radium-223 dichloride (radium-223) selectively targets bone metastases with high-energy, short-range α-particles. We assessed the effect of radium-223 compared with placebo in patients with castration-resistant prostate cancer and bone metastases. In this phase 3, double-blind, randomised ALSYMPCA trial, we enrolled patients who had symptomatic castration-resistant prostate cancer with two or more bone metastases and no known visceral metastases, who were receiving best standard of care, and had previously either received or were unsuitable for docetaxel. Patients were stratified by previous docetaxel use, baseline total alkaline phosphatase level, and current bisphosphonate use, then randomly assigned (2:1) to receive either six intravenous injections of radium-223 (50 kBq/kg) or matching placebo; one injection was given every 4 weeks. Randomisation was done with an interactive voice response system, taking into account trial stratification factors. Participants and investigators were masked to treatment assignment. The primary endpoint was overall survival, which has been reported previously. Here we report on time to first symptomatic skeletal event, defined as the use of external beam radiation to relieve bone pain, or occurrence of a new symptomatic pathological fracture (vertebral or non-verterbal), or occurence of spinal cord compression, or tumour-related orthopeadic surgical intervention. All events were required to be clinically apparent and were not assessed by periodic radiological review. Statistical analyses of symptomatic skeletal events were based on the intention-to-treat population. The study has been completed and is registered with ClinicalTrials.gov, number NCT00699751. Between June 12, 2008, and Feb 1, 2011, 921 patients were enrolled, of whom 614 (67%) were randomly assigned to receive radium-223 and 307 (33%) placebo

  19. The Impact of LEP G-2548A and LEPR Gln223Arg Polymorphisms on Adiposity, Leptin, and Leptin-Receptor Serum Levels in a Mexican Mestizo Population

    Science.gov (United States)

    Chavarria-Avila, Efraín; Gomez-Bañuelos, Eduardo; Ruiz-Quezada, Sandra-Luz; Castro-Albarran, Jorge; Sánchez-López, Lizeth; Martín-Marquez, Beatriz Teresita; Navarro-Hernández, Rosa-Elena

    2015-01-01

    The polymorphisms in leptin (LEP G-2548A) and leptin-receptor (LEPR Gln223Arg) seem to influence obesity and lipid metabolism among others. The aim of this study was to investigate the effect of these polymorphisms on adiposity, leptin (sLeptin), and leptin-receptor (sLeptin-receptor) serum concentrations as well as inflammation markers. We included 382 adults originally from Western Mexico. They were genotyped by PCR-RFLP. Obese individuals showed higher sLeptin (58.2 ± 31.35 ng/mL) but lower sLeptin-receptor (12.6 ± 3.74 ng/mL) levels than normal weight ones (17.6 ± 14.62 ng/mL, 17.4 ± 4.62 ng/mL, resp.), P < 0.001. Obese subjects carriers of Arg/Arg genotype had more (P = 0.016) sLeptin-receptor (14.7 ± 4.96 ng/mL) and less (P = 0.004) sLeptin (44.0 ± 28.12 ng/mL) levels than Gln/Gln genotype (11.0 ± 2.92 ng/mL, 80.3 ± 33.24 ng/mL, resp.). Body fat mass was lower (P from 0.003 to 0.045) for A/A (36.5% ± 6.80) or Arg/Arg (36.8% ± 6.82) genotypes with respect to G/G (41.3% ± 5.52) and G/A (41.6% ± 5.61) or Gln/Gln (43.7% ± 4.74) and Gln/Arg (41.0% ± 5.52) genotypes carriers. Our results suggest that LEP -2548A and LEPR 223Arg could be genetic markers of less body fat mass accumulation in obese subjects from Western Mexico. PMID:26064921

  20. Holoprosencephaly: Characterization of the deletion of 21q22.3 and isolation of cDNAs by a direct selection technique

    Energy Technology Data Exchange (ETDEWEB)

    Yamakawa, K.; Colbern, S.; Brusilovsky, A. [Univ. of California, Los Angeles, CA (United States)] [and others

    1994-09-01

    Holoprosencephaly (HP) is characterized by impaired cleavage of the embryonic forebrain and incomplete mid-facial development. The etiology is heterogeneous and may include aneuploidies for chromosomes 2, 3, 7, 13, 18 and 21. We have narrowed the chromosome 21 candidate region by analyzing 2 cases of HP with deletion 21q22 using FISH and Southern blot techniques. For the smaller deletion, the regions for D21S25, D21S154, D21S171 and D21S44 were deleted and for D21S42 was not. Combining these data with previous reports of deletion of 21q22.3 (ColVIA2-ter) without the holoprosencephaly phenotype indicate that the region responsible for holoprosencephaly spans the 2-3 Mb region including PFKL and ITGB2 (CD18) that has also been linked to progressive myoclonus epilepsy (EPM1). In order to isolate genes responsible for these diseases, we constructed a cDNA library from a 14-week trisomy 21 fetal brain using Uni-Zap XR (Stratagene). More than 95% clones have inserts ranging from 1-4 kb (ave. 2 kb). In addition we applied a direct cDNA selection method to BACs (Bacterial Artificial Chromosomes) in the 21q22.3 region. Using cDNA synthesized from trisomy 21 fetal brain, we attached Sau3AI linkers, digested with Sau3AI, attached second linkers and hybridized to biotinylated BAC DNAs which cover the candidate region. cDNA/BAC DNA hybrid molecules were captured on streptavidin-coated magnetic beads, non-specific cDNA were washed out, and specifically hybridized cDNA were eluted and amplified by PCR. Twice-selected PCR products were subcloned and analyzed. Southern blot analyses revealed that 21 out of 30 (70%) of fragments yielded unique bands on the original BACs. Eight clones contained repetitive sequences. We are now isolating cDNAs expressed in the Down syndrome fetal brain using these cDNA fragments. These genes now provide candidates for EPM1 and holoprosencephaly.

  1. The CALYMHA survey: Lyα luminosity function and global escape fraction of Lyα photons at z = 2.23

    Science.gov (United States)

    Sobral, David; Matthee, Jorryt; Best, Philip; Stroe, Andra; Röttgering, Huub; Oteo, Iván; Smail, Ian; Morabito, Leah; Paulino-Afonso, Ana

    2017-04-01

    We present the CAlibrating LYMan-α with Hα (CALYMHA) pilot survey and new results on Lyman α (Lyα) selected galaxies at z ˜ 2. We use a custom-built Lyα narrow-band filter at the Isaac Newton Telescope, designed to provide a matched volume coverage to the z = 2.23 Hα HiZELS survey. Here, we present the first results for the COSMOS and UDS fields. Our survey currently reaches a 3σ line flux limit of ˜4 × 10-17 erg s-1 cm-2, and a Lyα luminosity limit of ˜1042.3 erg s-1. We find 188 Lyα emitters over 7.3 × 105 Mpc3, but also find significant numbers of other line-emitting sources corresponding to He II, C III] and C IV emission lines. These sources are important contaminants, and we carefully remove them, unlike most previous studies. We find that the Lyα luminosity function at z = 2.23 is very well described by a Schechter function up to LLy α ≈ 1043 erg s-1 with L^{ast }=10^{42.59^{+0.16}_{-0.08}} erg s-1, φ ^{ast }=10^{-3.09^{+0.14}_{-0.34}} Mpc-3 and α = -1.75 ± 0.25. Above LLy α ≈ 1043 erg s-1, the Lyα luminosity function becomes power-law like, driven by X-ray AGN. We find that Lyα-selected emitters have a high escape fraction of 37 ± 7 per cent, anticorrelated with Lyα luminosity and correlated with Lyα equivalent width. Lyα emitters have ubiquitous large (≈40 kpc) Lyα haloes, ˜2 times larger than their Hα extents. By directly comparing our Lyα and Hα luminosity functions, we find that the global/overall escape fraction of Lyα photons (within a 13 kpc radius) from the full population of star-forming galaxies is 5.1 ± 0.2 per cent at the peak of the star formation history. An extra 3.3 ± 0.3 per cent of Lyα photons likely still escape, but at larger radii.

  2. Preparation of Silicon Rubber/2,2'-(3-methyl-4-dihydro-1,3,2-benzoxazinePropane Ablative-resistant Composites and Its Ablative Structure

    Directory of Open Access Journals (Sweden)

    DONG Yimin

    2017-10-01

    Full Text Available Benzoxazine resin is a new generation of anti-ablation resin with high char yield and high-temperature oxidation resistance. Using high temperature vulcanized silicon rubber as ablation resistance matrix and 2,2'-(3-methyl-4-dihydro-1,3,2-benzoxazinepropane as anti-ablation resin, silicon rubber/polybenzoxazine anti-ablation composite was prepared by blending method. The mechanical properties were tested,and the ablation structure and the composition of the composite were investigated by DSC,SEM,FT-IR and Raman.Experimental results show that the polybenzoxazine resin can improve the ablation resistance property of silicone rubber composite. The composite has good ablation resistance and mechanical property when the addition of polybenzoxazine resin reaches 20 phr. After ablated by oxygen acetylene flame,the ablation layer is divided into three obvious layers as surface ceramic layer,pyrolysis carbonization layer and base layer. The surface ceramic layer formed in the progress of ablation plays a positive role in the ablation property of the composite material.

  3. Cloning of the cDNA for a human homologue of the Drosophila white gene and mapping to chromosome 21q22.3

    Energy Technology Data Exchange (ETDEWEB)

    Haiming Chen; Lalioti, M.D.; Perrin, G.; Antonarakis, S.E. [Univ. of Geneva Medical School (Switzerland)] [and others

    1996-07-01

    In an effort to contribute to the transcript map of human chromosome 21 and the understanding of the pathophysiology of trisomy 21, we have used exon trapping to identify fragments of chromosome 21 genes. Two trapped exons, from pools of chromosome 21-specific cosmids, showed homology to the Drosophila white (w) gene. We subsequently cloned the corresponding cDNA for a human homologue of the Drosophila w gene (hW) from human retina and fetal brain cDNA libraries. The gene belongs to the ATP-binding cassette transporter gene family and is homologous to Drosophila w (and to 2 genes from other species) and to a lesser extent to Drosophila brown (bw) and scarlet (st) genes that are all involved in the transport of eye pigment precursor molecules. A DNA polymorphism with 62% heterozygosity due to variation of a poly (T) region in the 3{prime} UTR of the hW has been identified and used for the incorporation of this gene to the genetic map of chromosome 21. The hW is located at 21q22.3 between DNA markers D21S212 and D21S49 in a P1 clone that also contains marker BCEI. The gene is expressed at various levels in many human tissues. The contributions of this gene to the Down syndrome phenotypes, to human eye color, and to the resulting phenotypes of null or missense mutations are presently unknown. 56 refs., 8 figs., 1 tab.

  4. Psychiatric disorder in a familial 15;18 translocation and sublocalization of myelin basic protein to 18q22.3

    Energy Technology Data Exchange (ETDEWEB)

    Calzolari, E.; Aiello, V.; Palazzi, P.; Sensi, A. [Universita Ferrara (Italy)] [and others

    1996-04-09

    Two related patients with similar clinical features consisting of a few dysmorphic signs and psychiatric disturbance were reported to have a partial trisomy of chromosomes 15(pter-q13.3) and 18(q23-qter) deriving from a familial translocation t(15;18). One patient is affected by bipolar disorder and the other by schizoaffective disorder. Both cases have a predominantly affective course; nevertheless, a clear diagnosis is difficult in the first patient, who is 15 years of age, and only a longitudinal course will allow us to establish a definite diagnosis. The possibility that these two pathologies belong to a single category is discussed, and the presence of a susceptibility locus on chromosome 18 is hypothesized. Cytogenetic data, FISH, and DNA studies indicate that the myelin basic protein (MPB) gene is not involved in the translocation, and localize it centromeric to the breakpoint on chromosome 18(q22.3). Thus, it is unlikely to be involved in the disease. 58 refs., 8 figs.

  5. Health Economics and Radium-223 (Xofigo®) in the Treatment of Metastatic Castration-Resistant Prostate Cancer (mCRPC): A Case History and a Systematic Review of the Literature.

    Science.gov (United States)

    Norum, Jan; Traasdahl, Erik R; Totth, Arpad; Nieder, Carsten; Olsen, Jan Abel

    2015-07-30

    Prostate cancer (PC) is the most common cancer in Western countries. Recent advances in the treatment of metastatic castration resistant prostate cancer (mCRPC) have caused significant pressure on health care budgets. We aimed to exemplify this dilemma presenting an example, radium-223 (Xofigo®), and review the literature. A 74-year-old man diagnosed with mCRPC was referred to our department in October 2014 for radium-223 therapy. We faced the following dilemma: is radium-223 standard therapy? Is it cost-effective? Medline was searched employing the following search criteria: "radium-223", "alpharadin", "Xofigo" and "prostate". Exclusion and inclusion criteria were applied. Guidelines and cost-effectiveness analyses were focused. We also searched the websites of ASCO, ESMO and ISPOR. The web was searched, using Yahoo and Google search engines, for Health Technology Assessments (HTAs). 181 publications were identified in the Medline database. Only four studies included the word "cost", three "economics" and none "budget" in heading or abstract. None of the publications were thorough of cost analysis (cost-effectiveness, cost-utility, cost-minimizing or cost-of-illness analysis). Six HTAs and eight national guidelines were identified. The cost per quality adjusted life years was indicated €80.000-94,000. HTAs concluded reimbursement being not recommendable or no ultimate statement could be made. One pointed towards a limited use with caution. Guidelines were based on data from randomized clinical trials (RCTs). Health economics was not considered when guidelines were made. Most HTAs concluded this therapy not cost-effective or there was insufficient data for final conclusions. Licensing and reimbursement processes should be run simultaneously.

  6. Uptake of Radium-223 Dichloride and Early [18F]NaF PET Response Are Driven by Baseline [18F]NaF Parameters: a Pilot Study in Castration-Resistant Prostate Cancer Patients.

    Science.gov (United States)

    Letellier, Arthur; Johnson, Alison C; Kit, Nicolas How; Savigny, Jean-François; Batalla, Alain; Parienti, Jean-Jacques; Aide, Nicolas

    2017-10-12

    The purpose of this study is to identify predictive factors on baseline [ 18 F]NaF positron emission tomography (PET)/computed tomography (CT) of early response to radium-223 dichloride after 3 cycles of treatment in metastatic castration-resistant prostate cancer patients. Analysis of 152 metastases was performed in six consecutive patients who underwent [ 18 F]NaF PET/CT at baseline and for early monitoring after 3 cycles of radium-223 dichloride. All metastases depicted on whole-body [ 18 F]NaF PET/CT were contoured and CT (density in Hounsfield units, sclerotic, mixed, or lytic appearance) as well as [ 18 F]NaF [maximum standardized uptake value (SUV max ), SUV mean , and lesion volume (V 18F-NaF )] patterns were recorded. Tumor response was defined as percentage change in SUV max and SUV mean between baseline and post-treatment PET. Bone lesions were defined as stable, responsive, or progressive, according to thresholds derived from a recent multicentre test-retest study in [ 18 F]NaF PET/CT. Total [ 18 F]NaF uptake in metastases, defined as MATV × SUV mean , was correlated to uptake of radium-223 on biodistribution scintigraphy performed 7 days after the first cycle of treatment. Among metastases, 116 involved the axial skeleton and 36 the appendicular skeleton. Lesions were sclerotic in 126 cases and mixed in 26 cases. No lytic lesion was depicted. ROC analysis showed that SUV max and SUV mean were better predictors of lesion response than V 18F-NaF and density on CT (P < 0.0001 and P = 0.001, respectively). SUV max and SUV mean were predictors of individual tumor response in separate multivariate models (P = 0.01 and P = 0.02, respectively). CT pattern (mixed versus sclerotic) and lesion density were independent predictors only when assessing response with delta SUV max (P = 0.002 and 0.007, respectively). A good correlation between total [ 18 F]NaF uptake within metastases and their relative radium-223 uptake assessed by two observers 7

  7. Molecular characterization of human neogenin, a DCC-related protein, and the mapping of its gene (NEO1) to chromosomal position 15q22.3-q23

    Energy Technology Data Exchange (ETDEWEB)

    Vielmetter, J.; Miskevich, F.; Lane, R.P. [California Institute of Technology, Pasadena, CA (United States)] [and others

    1997-05-01

    Neogenin was first identified in the chick embryo, and like a number of cell surface proteins of the immunoglobulin (Ig) superfamily, including N-CAM and L{sub 1} (generally called cell adhesion molecules or CAMs), it is expressed on growing nerve cells in the developing nervous system of vertebrate embryos. Neogenin is also expressed in other embryonic tissues, suggesting a more general role in developmental processes such as tissue growth regulation, cell-cell recognition, and cell migration. Neogenin, unlike the CAMs, is closely related to a unique tumor suppressor candidate molecule, deleted in colorectal carcinoma (DCC). Like DCC, the neogenin protein consists of four immunoglobulin-like (Ig-like) domains followed by six fibronectin type III domains, a transmembrane domain, and an intracellular domain. We now report the cloning and sequencing of cDNA clones coding for the human neogenin protein. Human neogenin shares 87% identity with its chicken homolog, and like its chicken counterpart it is expressed in at least two different isoforms derived from alternative splicing in the intracellular domain. Northern blot analysis revealed two mRNA species of about 5 and 7 kb. The chromosomal location of the human neogenin gene (HGMW-approved symbol NEO1) was determined as 15q22.3-q23, using fluorescence in situ hybridization. The gene therefore maps in the vicinity of a locus associated with Bardet-Biedl syndrome. The identification of human neogenin and its chromosomal location provides a basis for studying its involvement in genetic disorders or diseases. 26 refs., 4 figs.

  8. 223 - 226_Modibbo et al.,

    African Journals Online (AJOL)

    pc

    1Department of Agricultural Education Federal College of Education (Tech) Gombe, Gombe State. 2Department of Plant Sciences Modibbo Adama University of Technology, Yola, .... The morphological, and cultural characteristics observed under the microscope was compared with structures in Alexopoulus and Mims.

  9. Serially measured circulating miR-22-3p is a biomarker for adverse clinical outcome in patients with chronic heart failure: The Bio-SHiFT study.

    Science.gov (United States)

    van Boven, Nick; Akkerhuis, K Martijn; Anroedh, Sharda S; Rizopoulos, Dimitris; Pinto, Yigal; Battes, Linda C; Hillege, Hans L; Caliskan, Kadir C; Germans, Tjeerd; Manintveld, Olivier C; Cornel, Jan-Hein; Constantinescu, Alina A; Boersma, Eric; Umans, Victor A; Kardys, Isabella

    2017-05-15

    Several studies have suggested circulating microRNAs (miRs) are associated with heart failure, but these studies were small, and limited to single miR measurements. We examined 7 miRs which were previously linked to heart failure, and tested whether their temporal expression level predicts prognosis in a prospective cohort of chronic heart failure (CHF) patients. In 2011-2013, 263 CHF patients were included. At inclusion and subsequently every 3months, we measured 7miRs. The primary endpoint (PE) comprised heart failure hospitalization, cardiovascular mortality, cardiac transplantation and LVAD implantation. Associations between temporal miR patterns and the PE were investigated by joint modelling, which combines mixed models with Cox regression. Mean age was 67±13years, 72% were men and 27% NYHA classes III-IV. We obtained 873 blood samples (median 3 [IQR 2-5] per patient). The PE was reached in 41 patients (16%) during a median follow-up of 0.9 [0.6-1.4] years. The temporal pattern of miR-22-3p was independently associated with the PE (HR [95% CI] per doubling of level: 0.64 [0.47-0.77]). The instantaneous change in level (slope of the temporal miR pattern) of miR-22-3p was also independently associated with the PE (HR [95% CI] per doubling of slope: 0.33 [0.20-0.51]). These associations remained statistically significant after adjustment for temporal patterns of NT-proBNP, Troponin T and CRP. The temporal pattern of circulating miR-22-3p contains important prognostic and independent information in CHF patients. This concept warrants further investigation in larger series with extended follow-up. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  10. Association of breast cancer risk in BRCA1 and BRCA2 mutation carriers with genetic variants showing differential allelic expression: identification of a modifier of breast cancer risk at locus 11q22.3.

    Science.gov (United States)

    Hamdi, Yosr; Soucy, Penny; Kuchenbaeker, Karoline B; Pastinen, Tomi; Droit, Arnaud; Lemaçon, Audrey; Adlard, Julian; Aittomäki, Kristiina; Andrulis, Irene L; Arason, Adalgeir; Arnold, Norbert; Arun, Banu K; Azzollini, Jacopo; Bane, Anita; Barjhoux, Laure; Barrowdale, Daniel; Benitez, Javier; Berthet, Pascaline; Blok, Marinus J; Bobolis, Kristie; Bonadona, Valérie; Bonanni, Bernardo; Bradbury, Angela R; Brewer, Carole; Buecher, Bruno; Buys, Saundra S; Caligo, Maria A; Chiquette, Jocelyne; Chung, Wendy K; Claes, Kathleen B M; Daly, Mary B; Damiola, Francesca; Davidson, Rosemarie; De la Hoya, Miguel; De Leeneer, Kim; Diez, Orland; Ding, Yuan Chun; Dolcetti, Riccardo; Domchek, Susan M; Dorfling, Cecilia M; Eccles, Diana; Eeles, Ros; Einbeigi, Zakaria; Ejlertsen, Bent; Engel, Christoph; Gareth Evans, D; Feliubadalo, Lidia; Foretova, Lenka; Fostira, Florentia; Foulkes, William D; Fountzilas, George; Friedman, Eitan; Frost, Debra; Ganschow, Pamela; Ganz, Patricia A; Garber, Judy; Gayther, Simon A; Gerdes, Anne-Marie; Glendon, Gord; Godwin, Andrew K; Goldgar, David E; Greene, Mark H; Gronwald, Jacek; Hahnen, Eric; Hamann, Ute; Hansen, Thomas V O; Hart, Steven; Hays, John L; Hogervorst, Frans B L; Hulick, Peter J; Imyanitov, Evgeny N; Isaacs, Claudine; Izatt, Louise; Jakubowska, Anna; James, Paul; Janavicius, Ramunas; Jensen, Uffe Birk; John, Esther M; Joseph, Vijai; Just, Walter; Kaczmarek, Katarzyna; Karlan, Beth Y; Kets, Carolien M; Kirk, Judy; Kriege, Mieke; Laitman, Yael; Laurent, Maïté; Lazaro, Conxi; Leslie, Goska; Lester, Jenny; Lesueur, Fabienne; Liljegren, Annelie; Loman, Niklas; Loud, Jennifer T; Manoukian, Siranoush; Mariani, Milena; Mazoyer, Sylvie; McGuffog, Lesley; Meijers-Heijboer, Hanne E J; Meindl, Alfons; Miller, Austin; Montagna, Marco; Mulligan, Anna Marie; Nathanson, Katherine L; Neuhausen, Susan L; Nevanlinna, Heli; Nussbaum, Robert L; Olah, Edith; Olopade, Olufunmilayo I; Ong, Kai-Ren; Oosterwijk, Jan C; Osorio, Ana; Papi, Laura; Park, Sue Kyung; Pedersen, Inge Sokilde; Peissel, Bernard; Segura, Pedro Perez; Peterlongo, Paolo; Phelan, Catherine M; Radice, Paolo; Rantala, Johanna; Rappaport-Fuerhauser, Christine; Rennert, Gad; Richardson, Andrea; Robson, Mark; Rodriguez, Gustavo C; Rookus, Matti A; Schmutzler, Rita Katharina; Sevenet, Nicolas; Shah, Payal D; Singer, Christian F; Slavin, Thomas P; Snape, Katie; Sokolowska, Johanna; Sønderstrup, Ida Marie Heeholm; Southey, Melissa; Spurdle, Amanda B; Stadler, Zsofia; Stoppa-Lyonnet, Dominique; Sukiennicki, Grzegorz; Sutter, Christian; Tan, Yen; Tea, Muy-Kheng; Teixeira, Manuel R; Teulé, Alex; Teo, Soo-Hwang; Terry, Mary Beth; Thomassen, Mads; Tihomirova, Laima; Tischkowitz, Marc; Tognazzo, Silvia; Toland, Amanda Ewart; Tung, Nadine; van den Ouweland, Ans M W; van der Luijt, Rob B; van Engelen, Klaartje; van Rensburg, Elizabeth J; Varon-Mateeva, Raymonda; Wappenschmidt, Barbara; Wijnen, Juul T; Rebbeck, Timothy; Chenevix-Trench, Georgia; Offit, Kenneth; Couch, Fergus J; Nord, Silje; Easton, Douglas F; Antoniou, Antonis C; Simard, Jacques

    2017-01-01

    Cis-acting regulatory SNPs resulting in differential allelic expression (DAE) may, in part, explain the underlying phenotypic variation associated with many complex diseases. To investigate whether common variants associated with DAE were involved in breast cancer susceptibility among BRCA1 and BRCA2 mutation carriers, a list of 175 genes was developed based of their involvement in cancer-related pathways. Using data from a genome-wide map of SNPs associated with allelic expression, we assessed the association of ~320 SNPs located in the vicinity of these genes with breast and ovarian cancer risks in 15,252 BRCA1 and 8211 BRCA2 mutation carriers ascertained from 54 studies participating in the Consortium of Investigators of Modifiers of BRCA1/2. We identified a region on 11q22.3 that is significantly associated with breast cancer risk in BRCA1 mutation carriers (most significant SNP rs228595 p = 7 × 10-6). This association was absent in BRCA2 carriers (p = 0.57). The 11q22.3 region notably encompasses genes such as ACAT1, NPAT, and ATM. Expression quantitative trait loci associations were observed in both normal breast and tumors across this region, namely for ACAT1, ATM, and other genes. In silico analysis revealed some overlap between top risk-associated SNPs and relevant biological features in mammary cell data, which suggests potential functional significance. We identified 11q22.3 as a new modifier locus in BRCA1 carriers. Replication in larger studies using estrogen receptor (ER)-negative or triple-negative (i.e., ER-, progesterone receptor-, and HER2-negative) cases could therefore be helpful to confirm the association of this locus with breast cancer risk.

  11. catena-Poly[[bis[2-(2,3-dimethylanilinobenzoato-κO]cadmium(II]-di-μ-3-pyridylmethanol-κ2N:O;κ2O:N

    Directory of Open Access Journals (Sweden)

    Tadeusz Lis

    2008-03-01

    Full Text Available In the crystal structure of the title compound, [Cd(C15H14NO22(C6H7NO2]n, the Cd atom displays a distorted octahedral geometry, including two pyridine N atoms and two hydroxyl O from four symmetry-related 3-pyridylmethanol (3-pyme ligands and two carboxylate O atoms from mefenamate [2-(2,3-dimethylanilinobenzoate] anions. The Cd atoms are connected via the bridging 3-pyme ligands into chains, that extend in the a-axis direction. The Cd atom is located on a center of inversion, whereas the 3-pyme ligands and the mefenamate anions occupy general positions.

  12. Use of benzodiazepines and benzodiazepine-related drugs among 223 patients with an acute hip fracture in Finland: Comparison of benzodiazepine findings in medical records and laboratory assays.

    Science.gov (United States)

    Nurmi-Lüthje, Ilona; Kaukonen, Juha-Pekka; Lüthje, Peter; Naboulsi, Helena; Tanninen, Salla; Kataja, Matti; Kallio, Maija-Leena; Leppilampi, Marjatta

    2006-01-01

    CNS drugs are a risk factor for falls and fractures among older people. Our aim was to describe the use of benzodiazepines and benzodiazepine-related drugs among patients admitted to two Finnish hospitals as a result of an acute hip fracture, and to analyse the concordance of benzodiazepine findings from different data sources. We studied the use of benzodiazepines and benzodiazepine-related drugs by (i) asking the patient or his/her relatives about his/her use of hypnotics; (ii) checking the patient's medical records; and (iii) analysing for the presence of benzodiazepines in serum and urine. Blood and urine samples were taken at admission. Detection of benzodiazepines in serum and urine was achieved by the fluorescence polarisation method. Concordance in benzodiazepine findings between medical records and laboratory results was estimated by calculating the degree of agreement (kappa) and described graphically using a Venn diagram. A total of 223 patients were enrolled in the study. Of these, 71% were women. The mean age of women was 80.5 years (SD: 10) and of men, 73 years (SD: 12) [p Benzodiazepine in serum or urine was detected in 83 (37%) patients. Over half of the patients coming from residential homes (53%) and institutions (54%) were benzodiazepine-positive. For home dwellers the proportion of patients that were benzodiazepine-positive was 29%. In 48% (40/83) of the benzodiazepine-positive patients, the type of benzodiazepine could not be identified because of a lack of drug records regarding benzodiazepines. A total of 113 (51%) patients used benzodiazepines or benzodiazepine-related drugs when both laboratory results and medical drug records were taken into account. Thirty-nine percent of these patients were home dwellers, 69% came from residential care and 76% from institutional care. The concordance between medical records and laboratory results expressed as overlap area was 32% in men and 59% in women, 38% in community-dwelling patients, 63% in

  13. The gene for human U2 snRNP auxiliary factor small 35-kDa subunit (U2AF1) maps to the progressive myoclonus epilepsy (EPM1) critical region on chromosome 21q22.3

    Energy Technology Data Exchange (ETDEWEB)

    Lalioti, M.D.; Rossier, C.; Antonarakis, S.E. [Univ. of Geneva Medical School (Switzerland)] [and others

    1996-04-15

    We used targeted exon trapping to clone portions of genes from human chromosome 21q22.3. One trapped sequence showed complete homology with the cDNA of human U2AF{sup 35} (M96982; HGM-approved nomenclature U2AF1), which encodes for the small 35-kDa subunit of the U2 snRNP auxiliary factor. Using the U2AF1 cDNA as a probe, we mapped this gene to cosmid Q15D2, a P1, and YAC 350F7 of the Chumakov et al. contig, close to the cystathionine-{beta}-synthase gene (CBS) on 21q22.3. This localization was confirmed by PCR using oligonucleotides from the 3{prime} UTR and by FISH. As U2AF1 associated with a number of different factors during mRNA splicing, overexpression in trisomy 21 individuals could contribute to some Down syndrome phenotypes by interfering with the splicing process. Furthermore, because this gene maps in the critical region for the progressive myoclonus epilepsy I locus (EPM1), mutation analysis will be carried out in patients to evaluate the potential role of U2AF1 as a candidate for EPM1. 24 refs., 1 fig.

  14. Dosimetric characterization of a 2-D array of 223 solid state detectors for daily morning checks in Tomo Therapy equipment; Caracterizacion dosimetrica de un arreglo 2D de 223 detectores de estado solido para verificaciones matutinas diarias en un equipo de Tomo Terapia

    Energy Technology Data Exchange (ETDEWEB)

    Reyes S, U.; Sosa A, M. [Universidad de Guanajuato, Division de Ciencias e Ingenieria, Lomas del Bosque No. 103, Col. Lomas del Campestre, 37150 Leon, Guanajuato (Mexico); Vega C, H. R., E-mail: uvaldoreyes@hotmail.com [Universidad Autonoma de Zacatecas, Unidad Academica de Estudios Nucleares, Cipres No. 10, Fracc. La Penuela, 98068 Zacatecas, Zac. (Mexico)

    2015-10-15

    Tomo Therapy is a new technique for the cancer treatment; however, the equipment must meet nearly all mechanical and dosimetric characteristics of a conventional linear accelerator for medical use. Daily quality controls are vital to the good operation of the equipment and thus guarantee excellent quality in the daily delivery of treatments. This paper presents the procedure of the dosimetric characterization of a two-dimensional array of 223 solid state detectors, called TomoDose of the Sun Nuclear Company. Dosimetric important criteria are established to perform these checks quickly and accurately. Dosimetric tests proposed are: repeatability, linearity, dependence of Sad and SSD. Some results are compared with readings of the ionization chamber Exradim A1SL. Finally the results of 30 consecutive days are presented to establish criteria for evidence of dose, field size, symmetry and flattening of the radiation beam on Tomo Therapy equipment. Expected values for daily verification are: Dose constancy of 194.89 c Gy, σ= 1.31 c Gy, symmetry in the X axis of -0.19 %, σ=0.08 %, symmetry in the Y axis of 1.66 %, σ= 0.05 %, flattened in the X axis of 25.71 %, σ= 0.05 % and flattened in the Y axis of 6.41 %, σ= 10.23 %. Field sizes obtained were 40.45 cm in the X axis and 5.10 on the Y axis, with standard deviations of 0.02 cm and 0.01 cm, respectively. TomoDose dosimetric values, compared to the values obtained with ionization chamber, presented differences smaller than 2%. (Author)

  15. Variations in HDL-carried miR-223 and miR-135a concentrations after consumption of dietary trans fat are associated with changes in blood lipid and inflammatory markers in healthy men - an exploratory study.

    Science.gov (United States)

    Desgagné, Véronique; Guay, Simon-Pierre; Guérin, Renée; Corbin, François; Couture, Patrick; Lamarche, Benoit; Bouchard, Luigi

    2016-06-02

    A high consumption of trans fatty acids (TFAs) is associated with an increased risk of cardiovascular diseases (CVDs). High-density lipoproteins (HDLs) have many cardioprotective properties and transport functional microRNAs (miRNAs) to recipient cells. We hypothesized that dietary TFAs modify the HDL-carried miRNA profile, therefore modulating its cardioprotective properties. We assessed whether consumption of dietary TFAs modifies HDL-carried miR-223-3p and miR-135a-3p concentration and the inter-relationship between diet-induced changes in HDL-carried miRNA concentration and CVD risk markers. In a double blind, randomized, crossover, controlled study, 9 men were fed each of 3 experimental isoenergetic diets: 1) High in industrial TFA (iTFA; 3.7% energy); 2) High in TFA from ruminants (rTFA; 3.7% energy); 3) Low in TFA (control; 0.8% energy) for 4 weeks each. HDLs were isolated by ultracentrifugation and miRNAs were quantified by RT-qPCR. Variations in HDL-miR-223-3p concentration were negatively correlated with variations in HDL-cholesterol after the iTFA diet (rs = 0.82; P = 0.007), and positively correlated with variations in C-reactive protein concentration after the rTFA diet (rs = 0.75; P = 0.020). Variations in HDL-miR-135a-3p concentration were positively correlated with variations in total triglyceride (TG) concentration following the iTFA diet (rs = -0.82; P = 0.007), and with variations in low-density lipoprotein (LDL)-TG concentration following the rTFA diet (rs = 0.83; P = 0.005), compared to the control diet. However, the consumption of dietary TFAs has no significant unidirectional impact on HDL-carried miR-223-3p and miR-135a-3p concentrations. Our results suggest that the variability in the HDL-carried miRNAs response to TFA intake, by being associated with variations in CVD risk factors, might reflect physiological changes in HDL functions.

  16. Evaluation of Novel Wet Chemistry Separation and Purification Methods to Facilitate Automation of Astatine-­211 Isolation

    Energy Technology Data Exchange (ETDEWEB)

    Wilbur, Daniel Scott [Univ. of Washington, Seattle, WA (United States)

    2016-07-19

    This research is a collaborative effort between the research groups of the PIs, Dr. D. Scott Wilbur in the Department of Radiation Oncology at the University of Washington (UW) and Matthew O’Hara at the Pacific Northwest National Laboratory (PNNL). In this report only those studies conducted at UW and the budget information from UW will be reported. A separate progress and financial report will be provided by PNNL. This final report outlines the experiments (Tasks) conducted and results obtained at UW from July 1, 2013 thru June 30, 2016 (2-­year project with 1 year no-­cost extension). The report divides the information on the experiments and results obtained into the 5 specific objectives of the research efforts and the Tasks within those objectives. This format is used so that it is easy to see what has been accomplished in each area. A brief summary of the major findings from the studies is provided below. Summary of Major Findings from Research/Training Activities at UW: Anion and cation exchange columns did not provide adequate 211At capture and/or extraction results under conditions studied to warrant further evaluation; PEG-­Merrifield resins containing mPEG350, mPEG750, mPEG2000 and mPEG5000 were synthesized and evaluated; All of the mPEG resins with different sized mPEG moieties conjugated gave similar 211At capture (>95%) from 8M HCl solutions and release with conc. NH4OH (~50-­80%), but very low quantities were released when NaOH was used as an eluent; Capture and release of 211At when loading [211At]astatate appeared to be similar to that of [211At]astatide on PEG columns, but further studies need to be conducted to confirm that; Capture of 211At on PEG columns was lower (e.g. 80-­90%) from solutions of 8M HNO3, but higher capture rates (e.g. 99%) can be obtained when 10M HNO3 is mixed with an equal quantity of 8M HCl; Addition of reductants to the 211At solutions did not appear to change the percent capture, but may have an effect on the % extracted; There was some indication that the PEG-­Merrifield resins could be saturated (perhaps with Bi) resulting in lower capture percentages, but more studies need to be done to confirm that; A target dissolution chamber, designed and built at PNNL, works well with syringe pumps so it can be used in an automated system; Preliminary semi-­automated 211At isolation studies have been conducted with full-scale target dissolution and 211At isolation using a PEG column on the Hamilton automated system gave low overall recoveries, but HNO3 was used (rather than HCl) for loading the 211At and flow rates were not optimized; Results obtained using PEG columns are high enough to warrant further development on a fully automated system; Results obtained also indicate that additional studies are warranted to evaluate other types of columns for 211At separation from bismuth, which allow use of HNO3/HCl mixtures for loading and NaOH for eluting 211At. Such a column could greatly simplify the overall isolation process and make it easier to automate.

  17. catena-Poly[[bis­[2-(2,3-dimethyl­anilino)benzoato-κO]cadmium(II)]-di-μ-3-pyridylmethanol-κ2 N:O;κ2 O:N

    Science.gov (United States)

    Moncol, Jan; Mikloš, Dušan; Segľa, Peter; Koman, Marian; Lis, Tadeusz

    2008-01-01

    In the crystal structure of the title compound, [Cd(C15H14NO2)2(C6H7NO)2]n, the Cd atom displays a distorted octa­hedral geometry, including two pyridine N atoms and two hydroxyl O from four symmetry-related 3-pyridylmethanol (3-pyme) ligands and two carboxylate O atoms from mefenamate [2-(2,3-dimethyl­anilino)benzoate] anions. The Cd atoms are connected via the bridging 3-pyme ligands into chains, that extend in the a-axis direction. The Cd atom is located on a center of inversion, whereas the 3-pyme ligands and the mefenamate anions occupy general positions. PMID:21201841

  18. Plasma miR-145, miR-20a, miR-21 and miR-223 as novel biomarkers for screening early-stage non-small cell lung cancer.

    Science.gov (United States)

    Zhang, Hui; Mao, Feng; Shen, Tuyang; Luo, Qingquan; Ding, Zhengping; Qian, Liqiang; Huang, Jia

    2017-02-01

    Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related mortality in the world. Late diagnosis is one of the most significant reasons for the high mortality rate of lung cancer. The identification of microRNAs (miRNAs) has opened a new field for molecular diagnosis of cancer. The purpose of the present study was to investigate whether plasma miRNAs may be used as biomarkers for early-stage NSCLC. A total of 232 participants, including 149 NSCLC patients and 83 healthy controls, were recruited between July 2012 and May 2014. We measured the levels of 10 miRNAs (miR-30d, miR-383, miR-20a, miR-145, miR-221, miR-25, miR-223, miR-21, miR-126 and miR-210) in plasma samples of 40 individuals (20 patients and 20 matched healthy controls) at the point of identification of disease, and 129 NSCLC patients and 83 healthy controls at the validation stage using reverse transcription-quantitative polymerase chain reaction. Receiver operating characteristics (ROC) curves were generated for each possible combination of the miRNAs. We observed that the expression of plasma miR-145, miR-20a, miR-21 and miR-223 was significantly increased in the early-stage NSCLC samples compared with controls. miRNAs have significant diagnostic value for early-stage NSCLC. Combined ROC analyses using these four miRNAs revealed an elevated area under the ROC curve (AUC) of 0.897, with a sensitivity and specificity of 81.8 and 90.1%, respectively. This AUC helped in distinguishing early-stage NSCLC. Furthermore, the levels of the four plasma miRNAs were significantly decreased following surgery (Pearly-stage NSCLC.

  19. A Monte Carlo approach to small-scale dosimetry of solid tumour microvasculature for nuclear medicine therapies with (223)Ra-, (131)I-, (177)Lu- and (111)In-labelled radiopharmaceuticals.

    Science.gov (United States)

    Amato, Ernesto; Leotta, Salvatore; Italiano, Antonio; Baldari, Sergio

    2015-07-01

    The small-scale dosimetry of radionuclides in solid-tumours is directly related to the intra-tumoral distribution of the administered radiopharmaceutical, which is affected by its egress from the vasculature and dispersion within the tumour. The aim of the present study was to evaluate the combined dosimetric effects of radiopharmaceutical distribution and range of the emitted radiation in a model of tumour microvasculature. We developed a computational model of solid-tumour microenvironment around a blood capillary vessel, and we simulated the transport of radiation emitted by (223)Ra, (111)In, (131)I and (177)Lu using the GEANT4 Monte Carlo. For each nuclide, several models of radiopharmaceutical dispersion throughout the capillary vessel were considered. Radial dose profiles around the capillary vessel, the Initial Radioactivity (IR) necessary to deposit 100 Gy of dose at the edge of the viable tumour-cell region, the Endothelial Cell Mean Dose (ECMD) and the Tumour Edge Mean Dose (TEMD), i.e. the mean dose imparted at the 250-μm layer of tissue, were computed. The results for beta and Auger emitters demonstrate that the photon dose is about three to four orders of magnitude lower than that deposited by electrons. For (223)Ra, the beta emissions of its progeny deliver a dose about three orders of magnitude lower than that delivered by the alpha emissions. Such results may help to characterize the dose inhomogeneities in solid tumour therapies with radiopharmaceuticals, taking into account the interplay between drug distribution from vasculature and range of ionizing radiations. Copyright © 2015 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

  20. Anna Camps and Teresa Ribas (coords.), «El verbo y su enseñanza. Hacia un modelo de enseñanza de la gramática basada en la actividad reflexiva», Barcelona, Octaedro, 2017, 223 pp.

    OpenAIRE

    Cuenca, Maria Josep

    2017-01-01

    Ressenya sobre el llibre d'Anna Camps and Teresa Ribas (coords.), «El verbo y su enseñanza. Hacia un modelo de enseñanza de la gramática basada en la actividad reflexiva», Barcelona, Octaedro, 2017, 223 pp., ISBN 978-84-9921-895-3.

  1. Plasma levels of leptin and soluble leptin receptor and polymorphisms of leptin gene -18G > A and leptin receptor genes K109R and Q223R, in survivors of childhood acute lymphoblastic leukemia

    Directory of Open Access Journals (Sweden)

    Gozdzik Jolanta

    2011-06-01

    Full Text Available Abstract Background Approximately 20% of children and adolescents in Europe are overweight. Survivors of pediatric acute lymphoblastic leukemia (ALL are at increased risk of overweight and obesity. The purpose of this study was to assess leptin and leptin soluble receptor levels, as well as polymorphisms of selected genes in survivors of pediatric ALL, and the influence of chemo- and radiotherapy on development of overweight in the context of leptin regulation. Methods Eighty two patients (55% males, of median age 13.2 years (m: 4.8 years; M: 26.2 years were included in the study. The ALL therapy was conducted according to modified Berlin-Frankfurt-Munster (BFM; n = 69 regimen or New York (n = 13 regimen. In 38% of patients cranial radiotherapy (CRT was used in median dose of 18.2Gy (m: 14Gy; M: 24Gy. Median age at diagnosis was 4.5 (m: 1 year; M: 16.9 years and median time from completion of ALL treatment was 3.2 years (m: 0.5 year; M: 4.3 years. Patients with BMI ≥85 percentile were classified as overweight. Correlation of plasma levels of leptin and leptin soluble receptor, and polymorphisms of leptin gene -18G > A, leptin receptor genes K109R and Q223R, and the overweight status were analyzed in relation to gender, intensity of chemotherapy (high intensity vs. standard intensity regimens and to the use of CRT. Results Significant differences of leptin levels in patients treated with and without CRT, both in the entire study group (22.2+/- 3.13 ng/ml vs. 14.9+/-1.6 ng/ml; p Conclusions The prevalence of overweight in our cohort was higher than in general European population (31% vs 20% and increased regardless of the use of CRT. Leptin and leptin receptor levels may be used as useful markers of high risk of becoming overweight in ALL survivors, particularly in females treated with CRT. Polymorphisms of leptin gene -18G > A and leptin receptor genes K109R and Q223R were not associated with overweight status in ALL survivors.

  2. Analysis of 133 meioses places the genes for nevoid basal cell carcinoma (gorlin) syndrome and fanconi anemia group C in a 2.6-cM interval and contributes to the fine map of 9q22.3

    Energy Technology Data Exchange (ETDEWEB)

    Farndon, P.A.; Hardy, C.; Kilpatrick, M.W. [Birmingham Maternity Hospital, Edgbaston (United Kingdom)] [and others

    1994-09-15

    Four disease genes (NBCCS, ESS1, XPAC, FACC) map to 9q22.3-q31. A fine map of this region was produced by linkage and haplotype analysis using 12 DNA markers. The gene for nevoid basal cell carcinoma syndrome (NBCCS, Gorlin) has an important role in congenital malformations and carcinogenesis. Phase-known recombinants in a study of 133 meioses place NBCCS between (D9S12/D9S151) and D9S176. Haplotype analysis in a two-generation family suggests that NBCCS lies in a smaller interval of 2.6 cM centromeric to D9S287. These flanking markers will be useful clinically for gene tracking. Recombinants also map FACC (Fanconi anemia, group C) to the same region, between (D9S12/D9S151) and D9S287. The recombination rate between (D9S12/D9S151) and D9S53 in males is 8.3% and 13.2% in females, giving a sex-specific male:female ratio of 1:1.6 and a sex-averaged map distance of 10.4 cM. No double recombinants were detected, in agreement with the apparently complete level of interference predicted from the male chiasmata map. 19 refs., 2 figs., 1 tab.

  3. Localization of cDNAs to a region poorly represented in the CEPH chromosome 21 YAC contig: Candidate genes for genetic diseases mapped to 21q22.3

    Energy Technology Data Exchange (ETDEWEB)

    Gardiner, K.; Patterson, D. [Eleanor Roosevelt Inst., Denver, CO (United States); Ichikawa, H.; Ohki, Misao [National Cancer Center, Tokyo (Japan); Cheng, Jan-Fang [Lawerence Berkeley National Lab., CA (United States)

    1995-11-20

    Fifty-three cDNA fragments previously obtained by hybridization selection from random clones in the chromosome 21 cosmid library LL21CNO2 failed to identify clones in the chromosome 21 YAC contig described. Using an expanded panel of somatic cell hybrids, we have verified that the majority of these cDNAs map to chromosome 21 and that in particular a very high proportion, {approximately}85%, localize to a 5-Mb region of distal 21q22.3. Pulsed-field analysis coupled with information from the NotI restriction map of the region further indicate that 17 cDNA fragments map within 650 kb of the PFKL gene and thus may be candidates for genetic diseases linked to this gene. This work helps to characterize a region poorly represented in the CEPH YAC contig and adds to the number of cDNAs useful in analysis of chromosome 21-associated diseases. 4 refs., 3 figs., 1 tab.

  4. Localization of cDNAs to a region poorly represented in the CEPH chromosome 21 YAC contig: candidate genes for genetic diseases mapped to 21q22.3.

    Science.gov (United States)

    Gardiner, K; Ichikawa, H; Ohki, M; Patterson, D; Cheng, J F

    1995-11-20

    Fifty-three cDNA fragments previously obtained by hybridization selection from random clones in the chromosome 21 cosmid library LL21CNO2 failed to identify clones in the chromosome 21 YAC contig described by Chumakov et al. (1992, Nature 359: 380-387). Using an expanded panel of somatic cell hybrids, we have verified that the majority of these cDNAs map to chromosome 21 and that in particular a very high proportion, approximately 85%, localize to a 5-Mb region of distal 21q22.3. Pulsed-field analysis coupled with information from the NotI restriction map of the region further indicate that 17 cDNA fragments map within 650 kb of the PFKL gene and thus may be candidates for genetic diseases linked to this gene. This work helps to characterize a region poorly represented in the CEPH YAC contig and adds to the number of cDNAs useful in analysis of chromosome 21-associated diseases.

  5. Syntheses, crystal structures and properties of one sodium(I) directed three-dimensional coordination polymer and one propeller-like dinuclear copper(II) complex with (1 S,3 R)-3-carbamoyl-2,2,3-trimethylcyclopentane-1-carboxylate

    Science.gov (United States)

    Huang, Wei; Qian, Huifen; Gou, Shaohua; Yao, Cheng

    2005-05-01

    A sodium(I) complex and a propeller-like dinuclear copper(II) complex formulated as [Na 3(L)(OH) 2(H 2O) 2] n ( 1) and [Cu 2(L) 4(H 2O) 2] ( 2) [LH=(1 S,3 R)-3-carbamoyl-2,2,3-trimethylcyclopentane-1-carboxylic acid which is also known as (1 R,3 S)-1-monoamidocamphoric acid and (1 R,3 S)- β-camphoramic acid] have been synthesized and characterized, respectively. X-ray single crystal determinations of 1 and 2 reveal that three types of sodium(I) centers are present in 1 and a 3D framework is constituted with the help of the weak coordinative bonds as well as the hydrogen bonding interactions, while 2 forms a tetrakis( μ2-carboxylic)-bridged dinuclear diaqua copper(II) complex with the Cu-Cu separation 2.601(4) Å. In 2, half of the ligands undergo the configuration inversion. It is deduced that the formation of the robust five-membered coordination ring (Cu 2CO 2) and the α-hydrogen atom of carboxylic group contribute this racemization. In addition, magnetic properties of 2 are also discussed.

  6. Association of the intermediate filament nestin with cancer stage: a meta-analysis based on 223 positive/high nestin cases and 460 negative/low case-free controls.

    Science.gov (United States)

    Zhong, Beilong; Wang, Tao; Zou, Jianyong; Zheng, Fangfang; Huang, Rijiao; Zheng, Xiaobin; Yang, Weilin; Chen, Zhenguang

    2015-09-08

    Nestin, a member of the intermediate filament protein family, has been reported to be associated with several types of neoplastic transformation. However, questions remain, with studies reporting sometimes inconclusive or conflicting data. Thus, the aim of this study was to evaluate literature reports on the relationship between nestin and cancer stage. Relevant articles published as of June 2014 were retrieved from multiple databases. After applying specific inclusion criteria, we chose seven articles relating to nestin expression and cancer stage, which included a total of 223 positive/high nestin cases and 460 negative/low case-free controls. Overall, positive/high nestin was significantly associated with median or advanced stages of several types of cancer (nestin and cancer stage: OR = 1.90, 95% CI = 1.30-2.78; nestin and lymph node: OR = 2.17, 95% CI = 1.26-3.72). Notably, studies relating to lung cancer (three qualifying articles) showed a significant association between nestin and lung cancer stage (OR = 2.00, 95% CI = 1.16-3.44). These findings indicate that positive/high nestin may be more strongly linked to median or advanced cancer stage and correlated with malignant characteristics that lead to poor prognosis in different cancers, especially lung cancer.

  7. Supramolecular Hydrogen-Bond Motifs in Chiral and Racemic Molecular Salts: A Comparison of (S-2-Methyl Piperizinium Hydrogen Phosphite Monohydrate, C5H14N2·HPO3·H2O and (R,S-2-Methyl Piperizinium Hydrogen Phosphite 2.23 Hydrate, C5H14N2·HPO3·2.23H2O

    Directory of Open Access Journals (Sweden)

    William T. A. Harrison

    2011-11-01

    Full Text Available The crystal structures of C5H14N2·HPO3·H2O (1 and C5H14N2·HPO3·2.23H2O (2 are described and compared. Compound 1 contains homochiral (S-2-methyl piperizinium cations, hydrogen phosphite ions and water molecules. The components are linked by N–H⋯O and O–H⋯O hydrogen bonds into a three-dimensional network. In compound 2, racemic (R,S-2-methyl piperizinium cations combine with the same anions and water molecules to generate a far more complex, high symmetry “supramolecular” structure, which features distinctive R66(12 loops and helical C(2 chain hydrogen-bonding motifs involving the water molecules. Crystal data: 1 (C5H17N2O4P, Mr = 200.18, orthorhombic, P212121 (No. 19, Z = 4, a = 8.564 (5 Å, b = 9.593 (6 Å, c = 11.607 (6 Å, V = 953.6 (9 Å3, R(F = 0.066, wR(F2 = 0.081. 2 (C5H19.47N2O5.24P, Mr = 222.49, trigonal, (No. 148, Z = 18, a = 31.075 (2 Å, c = 6.1875 (4 Å, V = 5174.5 (6 Å3, R(F = 0.044, wR(F2 = 0.107.

  8. Human fructose-1,6-bisphosphatase gene (FBP1): Exon-intron organization, localization to chromosome bands 9q22.2-q22.3, and mutation screening in subjects with fructose-1,6-bisphosphatase deficiency

    Energy Technology Data Exchange (ETDEWEB)

    El-Maghrabi, M.R.; Jiang, W. [State Univ. of New York, Stony Brook, NY (United States)] [and others

    1995-06-10

    Fructose-1,6-bisphosphatase (EC 3.1.3.11) is a key regulatory enzyme of gluconeogenesis that catalyzes the hydrolysis of fructose-1,6-bisphosphate to generate fructose-6-phosphate and inorganic phosphate. Deficiency of fructose-1,6-bisphosphatase is associated with fasting hypoglycemia and metabolic acidosis because of impaired gluconeogenesis. We have cloned and characterized the human liver fructose-1,6-bisphosphatase gene (FBP1). FBP1, localized to chromosome bands 9q22.2-q22.3 by fluorescence in situ hybridization, consists of seven exons that span > 31 kb, and the six introns are in the same position as in the rat gene. FBP1 was screened for mutations in two subjects with fructose-1,6-bisphosphatase deficiency. Four nucleotide substitutions were identified, two of which were silent mutations in the codons for Ala-216 (GCT {yields} GCC) and Gly-319 (GGG {yields} GGA). The other substitutions were in intron 3, a C {yields} T substitution 7 nucleotides downstream from the splice donor site, and in the promoter region, an A {yields} T substitution 188 nucleotides upstream from the start of transcription. These nucleotide substitutions were also found in normal unaffected subjects and thus are not the cause of fructose-1,6-bisphosphatase deficiency in the two subjects studied. The molecular basis of hepatic fructose-1,6-bisphosphatase deficiency in these subjects remains undetermined but could result from unidentified mutations in the promoter that decrease expression or from mutations in another gene that indirectly lead to decreased fructose-1,6-bisphosphatase activity. 18 refs., 3 figs., 3 tabs.

  9. Clinical safety of a polyvalent F(ab')2 equine antivenom in 223 African snake envenomations: a field trial in Cameroon. VAO (Venin Afrique de l'Ouest) Investigators.

    Science.gov (United States)

    Chippaux, J P; Lang, J; Eddine, S A; Fagot, P; Rage, V; Peyrieux, J C; Le Mener, V

    1998-01-01

    A large-scale clinical trials was conducted, according to World Health Organization Good Clinical Practice guidelines, in 7 centres in north Cameroon to determine the safety and efficacy of a polyvalent antivenom composed of purified F(ab')2. This study included 223 patients presenting clinically with obvious snake bite, predominantly due to Echis ocellatus (viper), the most abundant species in this savannah region. Clinical surveillance was maintained for 5 d in all patients and until the twenty-sixth day in 74% of cases. Two 10 mL ampoules of polyvalent F(ab')2 equine antivenom (Ipser Africa) were administered to each patient by intravenous infusion. If necessary, treatment was repeated 1 h after the end of the first infusion, and then with a frequency determined by the patient's clinical condition. Before initiation of antivenom treatment, the main clinical disorders observed on admission were oedema (93.7%) and haemorrhage (48.9%), with a clotting time longer than 30 min in 65.4% of patients. Clinical cure was obtained in 213 patients (96.8%). No amputation was necessary, and the case fatality rate was only 1.3%. On average, 4.6 (+/- 3.7) ampoules were administered per patient; 43% of subjects recovered after only a single infusion of 2 ampoules. Early adverse reactions, of varying degrees of severity, were observed in 6.3% of patients. A severe early reaction, anaphylactic shock, was observed in only one patient (0.4%). Serum sickness was observed in another patient. Polyvalent F(ab')2 equine antivenom given by repeated 20 mL intravenous infusions is a safe and effective treatment for envenomation caused by African vipers.

  10. A familial pericentric inversion of chromosome 11 associated with a microdeletion of 163 kb and microduplication of 288 kb at 11p13 and 11q22.3 without aniridia or eye anomalies.

    Science.gov (United States)

    Balay, Lara; Totten, Ellen; Okada, Luna; Zell, Sidney; Ticho, Benjamin; Israel, Jeannette; Kogan, Jillene

    2016-01-01

    Interstitial deletions of 11p13 involving MPPED2, DCDC5, DCDC1, DNAJC24, IMMP1L, and ELP4 are previously reported to have downstream transcriptional effects on the expression of PAX6, due to a downstream regulatory region (DRR). Currently, no clear genotype-phenotype correlations have been established allowing for conclusive information regarding the exact location of the PAX6 DRR, though its location has been approximated in mouse models to be within the Elp4 gene. Of the clinical reports currently published examining patients with intact PAX6 genes but harboring deletions identified in genes downstream of PAX6, 100% indicate phenotypes which include aniridia, whereas approximately half report additional eye deformities, autism, or intellectual disability. In this clinical report, we present a 12-year-old male patient, his brother, and mother with pericentric inversions of chromosome 11 associated with submicroscopic interstitial deletions of 11p13 and duplications of 11q22.3. The inversions were identified by standard cytogenetic analysis; microarray and FISH detected the chromosomal imbalance. The patient's phenotype includes intellectual disability, speech abnormalities, and autistic behaviors, but interestingly neither the patient, his brother, nor mother have aniridia or other eye anomalies. To the best of our knowledge, these findings in three family members represent the only reported cases with 11p13 deletions downstream of PAX6 not demonstrating phenotypic characteristics of aniridia or abnormal eye development. Although none of the deleted genes are obvious candidates for the patient's phenotype, the absence of aniridia in the presence of this deletion in all three family members further delineates the location of the DRR for PAX6. © 2015 Wiley Periodicals, Inc.

  11. X-linked ichthyosis and Crigler-Najjar syndrome I: Coexistence in a male patient with two copy number variable regions of 2q37.1 and Xp22.3.

    Science.gov (United States)

    Bai, Jinli; Qu, Yujin; Cao, Yanyan; Li, Yan; Zhang, Wenhui; Jin, Yuwei; Wang, Hong; Song, Fang

    2016-02-01

    X-linked ichthyosis (XLI) is an X-linked recessive skin disorder generally restricted to males, which arises from mutations in the steroid sulfatase (STS) gene located on Xp22.3. Crigler-Najjar syndrome (CN-I) is a rare autosomal recessive disease caused by the homozygous or compound heterozygous mutations in the UPD‑glucuronosyltransferase 1 family, polypeptide A1 (UGT1A1) gene on chromosome 2q37. A male patient was referred to the Department of Medical Genetics with of severe icterus and ichthyosis. The patient and his family members underwent genetic tests related to XLI and CN-I. Quantitative polymerase chain reaction on genomic DNA was performed to determine the gene copy number, while single nucleotide polymorphism array analysis was conducted to identify deletion mutations. Family pedigree analysis showed that the patient and his two cousins were all affected by ichthyosis, which was in accordance with the inheritance pattern of an X-linked recessive disease. In addition, the patient's serum bilirubin concentration (>340 mmol/l) was markedly greater than the normal level. The patient presented with kernicterus and phenobarbital treatment was ineffective. The clinical diagnosis of XLI was confirmed molecularly by laboratory evidence of a maternal 1.61 M deletion (including the STS gene) on ChrXp22.31. Coincidentally, the male patient was also confirmed to carry a rare maternal inherited microdeletion (374 Kb) comprising the entire UGT1A1 gene combined with a paternal UGT1A1 mutation (c.1253delT), a causative event of CN-I. To the best of our knowledge, this study reported for the first time the comorbidity of XLI and CN-I in a male patient. The results suggested that co-occurrence of these two recessive diseases in a patient may be incidental.

  12. Publications | Page 223 | IDRC - International Development ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    IDRC works with developing-country researchers and institutions to build local capacity through funding, knowledge sharing, and training. ... Audio slideshow: Overview and lessons from the Canadian Learning Forum 2012 on Virtual Platforms, Knowledge Management and International Development (open access).

  13. 50 CFR 223.208 - Corals.

    Science.gov (United States)

    2010-10-01

    ... Removal; Liability for Damage to Natural ResourcesFL Statute § 376.121 FDEP Land and Water Management... Natural and Environmental Resources, or the U.S. Virgin Islands Department of Planning and Natural Resources. The exportation or take must be in compliance with the applicable terms and conditions of the...

  14. 50 CFR 223.203 - Anadromous fish.

    Science.gov (United States)

    2010-10-01

    ... government in Oregon and pursuant to ordinances that Metro has found comply with its Urban Growth Management... of stormwater management and other conservation measures; and a summary of any flood damage... steelhead harvest. If NMFS does not receive a fishery management plan for Puget Sound steelhead by November...

  15. 48 CFR 223.7101 - Procedures.

    Science.gov (United States)

    2010-10-01

    ... OF DEFENSE SOCIOECONOMIC PROGRAMS ENVIRONMENT, ENERGY AND WATER EFFICIENCY, RENEWABLE ENERGY... authorization should specify the types, conditions, and quantities of toxic or hazardous materials that may be... commercial use of a DoD industrial-type facility. ...

  16. 36 CFR 223.186 - Definitions.

    Science.gov (United States)

    2010-07-01

    ... are removed. Hammer brand refers to an identifying mark or brand composed of numbers, letters... similar striking tool. The hammer brand must make a legible imprint of the brand in the end of a log when... factors, including but not limited to common ownership, common management, common facilities, and...

  17. Grievance Arbitration in Education. Fastback 223.

    Science.gov (United States)

    Lovell, Ned B.

    This pamphlet provides information necessary to analyze existing grievance procedures and sets forth principles to guide the formulation of a more effective grievance process. The introduction defines the grievance procedure in a contractual contest, describes its benefits to management, union members, and private citizens; and briefly reviews key…

  18. 48 CFR 223.370-1 - Scope.

    Science.gov (United States)

    2010-10-01

    ...) Oxidizers; (5) Powdered metals; or (6) Other materials having fire or explosive characteristics. ...-1 Scope. (a) This section applies to all acquisitions involving the use of ammunition and explosives... initiation, propulsion, or detonation as an integral or component part of an explosive, an ammunition, or...

  19. Voegborlo et al.2.2.3

    African Journals Online (AJOL)

    PUBLICATIONS1

    tions of Lead, Zinc, Copper and Cadmium all decreased with increasing distance from the road and with decreasing vehicular traffic ... distance from the roadside was found in the order Lead>Zinc>Copper>Cadmium. INTRODUCTION. Heavy metals ... clean plastic containers, labeled and transported to the laboratory where ...

  20. Publications | Page 223 | IDRC - International Development ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Kebijakan kawasan tanpa rokok : peluang dan hambatan (restricted access). Background: Currently, there are 1.2 billion smokers in the world, 80 percent of whom live in low-income countries and medium. Without prevention efforts in reducing cigarette consumption, the WHO predicts in 2025 the number of smokers will ...

  1. 49 CFR 223.5 - Definitions.

    Science.gov (United States)

    2010-10-01

    ... a manner that it will perform its intended function. Designated service means exclusive operation of... within a single yard area. [63 FR 24675, May 4, 1998; 63 FR 36376, July 6, 1998, as amended at 73 FR 6399...

  2. Reference: 223 [Arabidopsis Phenome Database[Archive

    Lifescience Database Archive (English)

    Full Text Available ion of NEDD8 from the cullin subunit of E3 ubiquitin ligases (deneddylation). Here, we report on Arabidopsis... mutants deficient in CSN5 function. We show that these mutants are phenotypically indistinguishable from the pre...o show that these mutants retain the CSN complex (lacking CSN5), and this finding is in contrast with the pre...viously described CSN subunit mutants, which lack the CSN complex. We therefore conclude that loss of CSN5 ...as part of CSN is sufficient to cause the cop/det/fus mutant phenotype. Furthermore

  3. 50 CFR 223.207 - Approved TEDs.

    Science.gov (United States)

    2010-10-01

    ... to this part). (4) Space between bars. The space between deflector bars and the deflector bars and... water, expressed in grams or kilograms, and must include the metric unit of measure. The marking may..., expressed in grams or kilograms, and must include the metric unit of measure. The marking may additionally...

  4. 40 CFR 52.223 - Approval status.

    Science.gov (United States)

    2010-07-01

    ... the resolution of the Lake Tahoe Regional Planning Agency banning new source construction pending the... during which the Tahoe Regional Planning Agency may remove its construction ban prior to EPA approval of..., 1980, for sources covered by Control Technique Guidelines (CTGs) issued between January 1978 and...

  5. 36 CFR 223.222 - Appraisal.

    Science.gov (United States)

    2010-07-01

    .... The Chief of the Forest Service shall determine the appraised value of special forest products. Valid methods to determine appraised value include, but are not limited to, transaction evidence appraisals... forest products must be sold at minimum rates or appraised value, whichever is higher. Contract and...

  6. 50 CFR 22.3 - Definitions.

    Science.gov (United States)

    2010-10-01

    ... the magnitude of the impacts to eagles, the following three things: the cost of remedy compared to... incremental environmental impact or effect of the proposed action, together with impacts of past, present, and... breeding, feeding, or sheltering behavior. Eagle nest means any readily identifiable structure built...

  7. 40 CFR 22.3 - Definitions.

    Science.gov (United States)

    2010-07-01

    ... CFR 2.201(h). Clerk of the Board means the Clerk of the Environmental Appeals Board, Mail Code 1103B... assessment of a penalty pursuant to sections 309(g)(4) and 311(b)(6)(C) of the Clean Water Act or section... Consolidated Rules of Practice. Hearing Clerk means the Hearing Clerk, Mail Code 1900, U.S. Environmental...

  8. 40 CFR 745.223 - Definitions.

    Science.gov (United States)

    2010-07-01

    ... preparation, cleanup, disposal, and post-abatement clearance testing activities associated with such measures..., newel posts, railing caps, balustrades, windows and trim (including sashes, window heads, jambs, sills..., such as pavement or concrete. Grass, mulch, and other landscaping materials are not considered...

  9. Flow measurements in ONKALO at Olkiluoto probe holes, ONK-PVA3, -PVA6, -PP187, -PP190, -PP194, -PP196, -PP223, -PP226 and -PP227

    Energy Technology Data Exchange (ETDEWEB)

    Pekkanen, J. (PRG-Tec Oy, Espoo (Finland))

    2010-06-15

    The Posiva Flow Log, Difference Flow Method (PFL DIFF) uses a flowmeter that incorporates a flow guide and can be used for relatively quick determinations of hydraulic conductivity and hydraulic head in fractures/fractured zones in cored drillholes. This report presents the principles of the method and the results of measurements carried out during the excavation of the underground access tunnel ONKALO at Olkiluoto. Phase 1, phase 2 and phase 3 of the probe hole measurements in the access tunnel started when the tunnel was 15 m long and finished at the tunnel length of 3288 m. The results of phases 1, 2 and 3 are presented in reports 2006-65 (Phase 1) /Reiman, M., Vaeisaesvaara, J and Poellaenen, J. 2006/, 2008-37 (Phase 2) /Pekkanen, J., 2008/ and 2010- 02 /Pekkanen, J and Vaeisaesvaara, J., 2010/. Probe hole measurements were continued normally in phase 4. The phase 4 results are presented in this report. Flow measurements started on April 15, 2009 when tunnel length was 3528 m and ended on November 25, 2009, tunnel length 3976 m. Probe hole measurements will continue normally below 3976 m. In addition to probe holes, shallow core-drilled drillholes were also measured in ONKALO. The drillholes discussed in this report are ONK-PVA3, ONK-PVA6, ONKPP187, ONK-PP190, ONK-PP194, ONK-PP196, ONK-PP223, ONK-PP226 and ONKPP227. The PFL DIFF probe was used to detect flow within single fractures in the drillhole or probe hole. The method utilizes rubber disks to isolate the flow in a test section from that in the rest of the probe hole or to measure the flow along the probe hole. The flow along the probe hole was measured in probe holes from ONK-TR3528 to ONK-TR3976 using 0.1 m and 0.2 m point interval. Core-drilled drillholes were measured using a 0.5 m section length (the distance isolated with the rubber disks) with a 0.1 m point interval. The device used includes a sensor for single point resistance (SPR). SPR was measured in connection with flow measurements. The flow

  10. Treatment-Induced Viral Cure of Hepatitis C Virus-Infected Patients Involves a Dynamic Interplay among three Important Molecular Players in Lipid Homeostasis: Circulating microRNA (miR-24, miR-223, and Proprotein Convertase Subtilisin/Kexin Type 9

    Directory of Open Access Journals (Sweden)

    Anastasia Hyrina

    2017-09-01

    Full Text Available In patients with chronic hepatitis C virus (HCV infection, viral hijacking of the host-cell biosynthetic pathways is associated with altered lipid metabolism, which contributes to disease progression and may influence antiviral response. We investigated the molecular interplay among four key regulators of lipid homeostasis [microRNA (miR-122, miR-24, miR-223, and proprotein convertase subtilisin/kexin type 9 (PCSK9] in HCV-infected patients (n = 72 who achieved a treatment-based viral cure after interferon-based therapy with first-generation direct-acting antivirals. Real-time PCR was used to quantify microRNA plasma levels, and ELISA assays were used to determine plasma concentrations of PCSK9. We report that levels of miR-24 and miR-223 significantly increased in patients achieving sustained virologic response (SVR, whereas the levels of miR-122, a liver-specific cofactor for HCV infection, decreased in these patients. PCSK9 concentrations were significantly increased in SVRs, suggesting that PCSK9 may help impede viral infection. The modulatory effect of PCSK9 on HCV infection was also demonstrated in the context of HCV-infected Huh-7.5.1 cells employing recombinant human PCSK9 mutants. Together, these results provide insights into a novel coordinated interplay among three important molecular players in lipid homeostasis — circulating miR-24, miR-223 and PCSK9 — whose regulation is affected by HCV infection and treatment-based viral cure.

  11. Molecular cytogenetic characterization of Xp22.32→pter deletion and Xq26.3→qter duplication in a male fetus associated with 46,Y,rec(X)dup(Xq) inv(X)(p22.3q26.3), a hypoplastic left heart, short stature, and maternal X chromosome pericentric inversion.

    Science.gov (United States)

    Chen, Chih-Ping; Chen, Chen-Yu; Chern, Schu-Rern; Wu, Peih-Shan; Chen, Yen-Ni; Chen, Shin-Wen; Lee, Chen-Chi; Town, Dai-Dyi; Lee, Meng-Shan; Yang, Chien-Wen; Wang, Wayseen

    2016-10-01

    We present molecular cytogenetic characterization of an Xp22.32→pter deletion and an Xq26.3→qter duplication in a male fetus with congenital malformations and maternal X chromosome pericentric inversion. A 22-year-old woman underwent amniocentesis at 17 weeks of gestation because of an abnormal maternal serum screening result. Prenatal ultrasound revealed a hypoplastic left heart and short limbs. Amniocentesis revealed a karyotype of 46,Y,der(X) t(X;?)(p22.31;?). The pregnancy was subsequently terminated, and a malformed fetus was delivered with short stature and facial dysmorphism. Repeat amniocentesis was performed before termination of the pregnancy. Array comparative genomic hybridization was performed on uncultured amniocytes and maternal blood. Conventional cytogenetic analysis was performed on cultured amniocytes, cord blood, and blood from both parents. Fluorescence in situ hybridization was performed on cultured amniocytes. The maternal karyotype was 46,X,inv(X)(p22.3q26.3). The fetal karyotype was 46,Y, rec(X)dup(Xq)inv(X)(p22.3q26.3) or 46,Y, rec(X)(qter→q26.3::p22.3→qter). Array comparative genomic hybridization on uncultured amniocytes revealed a 4.56-Mb deletion of Xp22.33-p22.32 encompassing SHOX, CSF2RA, and ARSE, and a 19.22-Mb duplication of Xq26.3-q28 encompassing SOX3, FMR1, MECP2, RAB39B, and CLIC2 in the fetus. The mother did not have X chromosome imbalance. Detection of X chromosome aberration in a male fetus should give suspicion of a recombinant X chromosome derived from maternal X chromosome pericentric inversion. Copyright © 2016. Published by Elsevier B.V.

  12. 49 CFR 571.223 - Standard No. 223; Rear impact guards.

    Science.gov (United States)

    2010-10-01

    ...) of this section. S5.2.2 Guard Energy Absorption. A guard, other than a hydraulic guard, shall absorb... the guard manufacturer's installation instructions. Hydraulic guard means a guard designed to use... must be met no matter how small an amount of energy is absorbed by the rigid test fixture. S5...

  13. Astatine-211 conjugated to an anti-CD20 monoclonal antibody eradicates disseminated B-cell lymphoma in a mouse model

    Energy Technology Data Exchange (ETDEWEB)

    Green, Damian J.; Shadman, Mazyar; Jones, Jon C.; Frayo, Shani; Kenoyer, Aimee L.; Hylarides, Mark; Hamlin, Donald K.; Wilbur, D. Scott; Balkan, Ethan R.; Lin, Yukang; Miller, Brian W.; Frost, Sophia; Gopal, Ajay K.; Orozco, Johnnie J.; Gooley, Ted; Laird, Kelley L.; Till, B. G.; Back, Tom; Sandmaier, B. M.; Pagel, John M.; Press, Oliver W.

    2015-03-26

    Alpha emitting radionuclides release a large amount of energy within a few cell diameters and may be particularly effective for radioimmunotherapy targeting minimal residual disease (MRD) conditions in which micrometastatic disease satellites are broadly distributed. To evaluate this hypothesis, 211At conjugated 1F5 mAb (anti-CD20) was studied in both bulky lymphoma tumor xenograft and MRD animal models. Superior treatment responses to 211At conjugated 1F5 mAb were evident in the MRD setting. Lymphoma xenograft tumor bearing animals treated with doses of up to 48µCi of anti-CD20 211At-decaborate [211At-B10-1F5] experienced modest responses (0% cures but 2-3-fold prolongation of survival compared to negative controls). In contrast, 70% of animals in the MRD lymphoma model demonstrated complete eradication of disease when treated with 211At-B10-1F5 at a radiation dose that was less than one-third (15 µCi) of the highest dose given to xenograft animals. Tumor progression among untreated control animals in both models was uniformly lethal. After 130 days, no significant renal or hepatic toxicity is observed in the cured animals receiving 15 µCi of 211At-B10-1F5. These findings suggest that in a MRD lymphoma model, where isolated cells and tumor microclusters prevail, α-emitters may be uniquely efficacious.

  14. Alpha particle emitters in medicine

    Energy Technology Data Exchange (ETDEWEB)

    Fisher, D.R.

    1989-09-01

    Radiation-induced cancer of bone, liver and lung has been a prominent harmful side-effect of medical applications of alpha emitters. In recent years, however, the potential use of antibodies labeled with alpha emitting radionuclides against cancer has seemed promising because alpha particles are highly effective in cell killing. High dose rates at high LET, effectiveness under hypoxic conditions, and minimal expectancy of repair are additional advantages of alpha emitters over antibodies labeled with beta emitting radionuclides for cancer therapy. Cyclotron-produced astatine-211 ({sup 211}At) and natural bismuth-212 ({sup 212}Bi) have been proposed and are under extensive study in the United States and Europe. Radium-223 ({sup 223}Ra) also has favorable properties as a potential alpha emitting label, including a short-lived daughter chain with four alpha emissions. The radiation dosimetry of internal alpha emitters is complex due to nonuniformly distributed sources, short particle tracks, and high relative specific ionization. The variations in dose at the cellular level may be extreme. Alpha-particle radiation dosimetry, therefore, must involve analysis of statistical energy deposition probabilities for cellular level targets. It must also account fully for nonuniform distributions of sources in tissues, source-target geometries, and particle-track physics. 18 refs., 4 figs.

  15. Publications | Page 223 | CRDI - Centre de recherches pour le ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Le CRDI collabore avec les chercheurs et les établissements des pays en développement au renforcement des capacités locales par le truchement du financement, de la mise en commun des connaissances et de la formation. Avec nos livres, nos articles, nos publications de recherche et nos études, nous visons à ...

  16. 48 CFR 252.223-7001 - Hazard warning labels.

    Science.gov (United States)

    2010-10-01

    ... and Rodenticide Act; (2) Federal Food, Drug and Cosmetics Act; (3) Consumer Product Safety Act; (4... accordance with the Hazard Communication Standard (29 CFR 1910.1200 et seq). The Standard requires that the hazard warning label conform to the requirements of the standard unless the material is otherwise subject...

  17. LEGO Turing machine : Vimeo.com [2:23

    NARCIS (Netherlands)

    J. van den Bos (Jeroen); D. Landman (Davy)

    2012-01-01

    htmlabstractThis is a short documentary about the LEGO Turing Machine built by Jeroen van den Bos and Davy Landman at Centrum Wiskunde & Informatica (CWI), Amsterdam (Netherlands). They built it for CWI's exposition "Turings Erfenis" in honor of the centenary of Alan Turing's birth on 23 June 1912.

  18. 36 CFR 223.83 - Contents of prospectus.

    Science.gov (United States)

    2010-07-01

    ... specified roads to be constructed. (16) The estimated road construction cost and the estimated public works construction cost. (17) For deficit sales: (i) An estimate of the difference between fair market value and..., the prospectus shall also include: (1) The road standards applicable to construction of permanent...

  19. 36 CFR 223.137 - Causes for debarment.

    Science.gov (United States)

    2010-07-01

    ... unsatisfactory performance of contract terms. (e) Among actions the Forest Service regards as so serious as to... sales; (6) Providing access to the Forest Service upon its request to purchaser's books and accounts; (7... relating to failure to cut designated timber by the contract termination date; (8) Performance of contract...

  20. 48 CFR 1552.223-72 - Care of laboratory animals.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 6 2010-10-01 2010-10-01 true Care of laboratory animals... Care of laboratory animals. As prescribed in 1523.303-72, insert the following clause: Care of Laboratory Animals (OCT 2000) (a) Before undertaking performance of any contract involving the use of...

  1. 223.pdf | 25jan2011 | currsci | Indian Academy of Sciences

    Indian Academy of Sciences (India)

    2011-01-25

    Jan 25, 2011 ... Joint Statement by the Three Science Academies of India on the teaching of the theory of evolution more... Introducing: Summer Schools. Posted on 21 December 2017. ASTROPHYSICS: An Observational View of the Universe. Math Art and Design: MAD about Math, Math Education and Outreach.

  2. Dicty_cDB: SHA223 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available Patent WO0168911. 40 0.098 4 BD460245 |BD460245.1 Diagnosis of Diseases Associated with Cell Cycle. 40 0.09...8 4 BD452167 |BD452167.1 Diagnosis of Diseases Associated with Cell Cycle. 40 0.098 4 AJ297856 |AJ297856.1 L

  3. Page 1 y=- An overview of fullerene chemistry 223 characterization ...

    Indian Academy of Sciences (India)

    Balch A L, Lee J. W. Nail B C and Olmstead M M 1992 J. Am. Chein, Soc. 114 10984. Balch A L, Lee JW, Nall B C and Olmstead M M 1993 J. Chem. Soc., Chem. Commun, 56. Balch A L, Cullison B, Fawcett W R, Ginwalla AS, Olmstead M M and Winkler K 1995 J. Chem. Soc.,. Chem. Commun, 2287. Balch A L, Ginwalla A S ...

  4. Dicty_cDB: CHJ223 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available query: 148 length of database: 80,480,566 effective HSP length: 17 effective length of query: 131 effective ...length of database: 78,821,179 effective search space: 10325574449 effective sear...s better than 10.0: 0 length of query: 148 length of database: ,471,893,557 effective HSP length: 21 effective... length of query: 127 effective length of database: [,621,228,308 effective search space: 5539895995116 effective

  5. 36 CFR 223.60 - Determining fair market value.

    Science.gov (United States)

    2010-07-01

    ... considered include, but are not limited to, prices paid and valuations established for comparable timber, selling value of products produced, estimated operating costs, operating difficulties, and quality of... influences. ...

  6. Dicty_cDB: SFH223 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available r**iin*ikn*kkiiik*scyrc*sidtifskwtlcvygwicryrl skgstncigrpcgkkwitg*ikneficwsiswtrdrrslgnvgydr*eisspkwtshs*w yk*r*nsfcrstfidick...kwtlcvygwicryrl skgstncigrpcgkkwitg*ikneficwsiswtrdrrslgnvgydr*eisspkwtshs*w yk*r*nsfcrstfidick*FIGWILYIDKPH

  7. Dicty_cDB: SSA223 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available id:none) Bacillus weihenstephanensis KBA... 143 2e-33 CP001283_2747( CP001283 |pid:none) Bacillus cereus AH8...4 AE017194_2836( AE017194 |pid:none) Bacillus cereus ATCC 10987, com... 144 9e-34 CP000903_2567( CP000903 |p

  8. 50 CFR 223.210 - North American green sturgeon.

    Science.gov (United States)

    2010-10-01

    ... that the likelihood of survival or recovery of the listed species is not reduced; a plan for minimizing... survival or recovery of the Southern DPS; include effective monitoring and evaluation plans; provide for... determine the Tribal Plan's impact on the biological requirements of the species, and will assess the effect...

  9. 48 CFR 952.223-78 - Sustainable acquisition program.

    Science.gov (United States)

    2010-10-01

    ... Transportation Management, and Executive Order 13514, Federal Leadership in Environmental, Energy, and Economic... Leadership in High Performance and Sustainable Buildings (Guiding Principles) shall be achieved through... Environmental, Energy and Transportation Management, (http://www.epa.gov/greeningepa/practices/eo13423.htm) and...

  10. Dicty_cDB: VFA223 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available dehydrogenase; EC=1.1.1.3... 221 1e-56 (Q0ABE6) RecName: Full=Malate dehydrogenase; EC=1.1.1.3... 221 1e-56...dehydrogenase; EC=1.1.1.3... 221 2e-56 (Q9K3J3) RecName: Full=Malate dehydrogenase; EC=1.1.1.3... 219 4e-56...dehydrogenase; EC=1.1.1.3... 218 9e-56 (A3M928) RecName: Full=Malate dehydrogenase; EC=1.1.1.3... 218 9e-56...dehydrogenase; EC=1.1.1.3... 218 1e-55 (Q0BAF9) RecName: Full=Malate dehydrogenase; EC=1.1.1.3... 218 1e-55...(Q393V1) RecName: Full=Malate dehydrogenase; EC=1.1.1.3... 218 2e-55 protein update 2009. 6.16 PSORT psg:

  11. Laser-driven ICF experiments: Laboratory Report No. 223

    Energy Technology Data Exchange (ETDEWEB)

    McCrory, R.L.

    1991-04-01

    Laser irradiation uniformity is a key issue and is treated in some detail. The basic irradiation uniformity requirements and practical ways of achieving these requirements are both discussed, along with two beam-smoothing techniques: induced spatial incoherence (ISI), and smoothing by spectral dispersion (SSD). Experiments to measure and control the irradiation uniformity are also highlighted. Following the discussion of irradiation uniformity, a brief review of coronal physics is given, including the basic physical processes and their experimental signatures, together with a summary of pertinent diagnostics and results from experiments. Methods of determining ablation rates and thermal transport are also described. The hydrodynamics of laser-driven targets must be fully understood on the basis of experiments. Results from implosion experiments, including a brief description of the diagnostics, are presented. Future experiments aimed at determining ignition scaling and demonstrating hydrodynamically equivalent physics applicable to high-gain designs.

  12. 48 CFR 352.223-70 - Safety and health.

    Science.gov (United States)

    2010-10-01

    .../biosfty/bmbl4/bmbl4toc.htm. (ii) Prudent Practices for Safety in Laboratories (1995), National Research... health and safety operating procedures and practices for both personnel and facilities involving the use... laboratories; and other applicable occupational health and safety standards issued by OSHA and included in 29...

  13. 50 CFR 223.202 - Steller sea lion.

    Science.gov (United States)

    2010-10-01

    ... 16460 SW Point, Lake Point. 22. Gramp rock 51°29.0 N 178°20.5 W 16460 Whole island. 23. Tag I. 51°33.5 N... EC01JY91.042 EC01JY91.043 EC01JY91.044 (4) Commercial Fishing Operations. The incidental mortality and serious injury of endangered and threatened Steller sea lions in commercial fisheries can be authorized in...

  14. 10 CFR 431.223 - Materials incorporated by reference.

    Science.gov (United States)

    2010-01-01

    ... (ITE), “Vehicle Traffic Control Signal Heads: Light Emitting Diode (LED) Circular Signal Supplement.... Department of Energy, Forrestal Building, Room 1J-018 (Resource Room of the Building Technologies Program... Environmental Protection Agency, Ariel Rios Building, 1200 Pennsylvania Avenue, NW., Washington, DC 20460, (202...

  15. Dicty_cDB: SHG223 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available vswv*t vvrqvsftlllsivcviva*fstrgtvmpdhwsvglfdkivtcryhpldng*tplsqnpf *krkpnalececcr*h*vvgggplstlnhminrcytavsf...*sfdvgssyhceaeftkcwivhpltrnvswv*t vvrqvsftlllsivcviva*fstrgtvmpdhwsvglfdkivtcryhpldng*tplsqnpf *krkpnalece

  16. Dicty_cDB: SHC223 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available sequence. 62 3e-05 1 CK808839 |CK808839.1 Rasgsc1686 Salivary Gland 4th instar 3rd period (spinning cocoon)...sequence. 34 4e-05 3 CK808739 |CK808739.1 Rasgsc1529 Salivary Gland 4th instar 3rd period (spinning cocoon)...sequence. 58 5e-04 1 CK808037 |CK808037.1 Rasgsc0316 Salivary Gland 4th instar 3rd period (spinning cocoon)

  17. All projects related to | Page 223 | IDRC - International Development ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Topic: BIOTECHNOLOGY, AGRICULTURAL ENGINEERING, NATIONAL INCOME, AGRICULTURAL PRODUCTIVITY, FOOD SECURITY, RURAL ECONOMY. Region: South Africa, South of Sahara, Canada. Program: Agriculture and Food Security. Total Funding: CA$ 3,146,230.00. Vaccines to Combat Livestock Diseases ...

  18. 14 CFR 417.223 - Flight hazard area analysis.

    Science.gov (United States)

    2010-01-01

    ... § 417.205(a) apply. The analysis must account for, at a minimum: (1) All trajectory times from liftoff to the planned safe flight state of § 417.219(c), including each planned impact, for an orbital... trajectory dispersion effects in the surface impact domain. (b) Public notices. A flight hazard areas...

  19. 1935 15' Quad #223 Aerial Photo Mosaic Index

    Data.gov (United States)

    Earth Data Analysis Center, University of New Mexico — Aerial Photo Reference Mosaics contain aerial photographs that are retrievable on a frame by frame basis. The inventory contains imagery from various sources that...

  20. 50 CFR 300.223 - Purse seine fishing restrictions.

    Science.gov (United States)

    2010-10-01

    ... one nautical mile of a FAD. (2) Set a purse seine in a manner intended to capture fish that have... (78.74 cm) inside diameter and a bag depth of at least 38 inches (96.52 cm). The bag mesh openings may... active, it must be returned to the sea in the manner described in paragraph (f)(2)(vii) of this section...

  1. Radium-223 Improves Survival in Patients with Advanced Prostate Cancer

    Science.gov (United States)

    ... on this post. All comments must follow our comment policy . National Cancer Institute at the National Institutes of Health FOLLOW US Facebook Twitter Instagram YouTube Google+ LinkedIn GovDelivery RSS CONTACT INFORMATION Contact Us LiveHelp Online Chat MORE INFORMATION About This Website Cancer.gov ...

  2. 48 CFR 1852.223-70 - Safety and health.

    Science.gov (United States)

    2010-10-01

    ..., occupational illness, damage to or loss of equipment or property, or damage to the environment. NASA's safety... cause any type mishap, or any injury, damage, or negative mission impact) that may be of immediate... report any necessary corrective action. (2) If the Contractor fails or refuses to institute prompt...

  3. 36 CFR 223.14 - Where timber may be cut.

    Science.gov (United States)

    2010-07-01

    ...) The cutting of trees, portions of trees or other forest products may be authorized on any National... claimant has failed to file a verified statement or has failed to establish the validity and effectiveness...) Timber on an unpatented claim may be cut by the claimant only for the actual development of the claim or...

  4. 19 CFR 10.223 - Articles eligible for preferential treatment.

    Science.gov (United States)

    2010-04-01

    ... 19 Customs Duties 1 2010-04-01 2010-04-01 false Articles eligible for preferential treatment. 10...; DEPARTMENT OF THE TREASURY ARTICLES CONDITIONALLY FREE, SUBJECT TO A REDUCED RATE, ETC. United States-Caribbean Basin Trade Partnership Act Textile and Apparel Articles Under the United States-Caribbean Basin...

  5. 31 CFR 223.12 - Recognition as reinsurer.

    Science.gov (United States)

    2010-07-01

    ... SERVICE, DEPARTMENT OF THE TREASURY FINANCIAL MANAGEMENT SERVICE SURETY COMPANIES DOING BUSINESS WITH THE... admitted reinsurer (except on excess risks running to the United States) of surety companies doing business... copy of its charter or articles of incorporation, and (2) A certified copy of a license from any State...

  6. 22 CFR 223.2 - Report of violations.

    Science.gov (United States)

    2010-04-01

    ... information to the Director of the Office of Government Ethics and to the Criminal Division, Department of Justice. Any investigation or administrative action shall be coordinated with the Department of Justice to avoid prejudicing possible criminal proceedings. If the Department of Justice informs the Agency that it...

  7. Dicty_cDB: VSF223 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available 196315 |pid:none) Auxenochlorella protothecoides rib... 271 2e-71 BC054263_1( BC054263 |pid:none) Xenopus la...F402813 |pid:none) Ictalurus punctatus 40S ribosomal ... 271 2e-71 FJ196315_1( FJ

  8. 75 FR 68698 - Airworthiness Directives; Airbus Model A330-201, -202, -203, -223, -223F, -243, and -243F...

    Science.gov (United States)

    2010-11-09

    ... aviation product. The MCAI describes the unsafe condition as: * * * * * Investigation conducted by Thales... conducted by Thales on the removed probes revealed oil residue between the stator and the rotor parts of the... inspection of the Thales Avionics AoA probe P/N [part number] C16291AA in order to identify the suspect parts...

  9. Reactions of M(CO)5X (M = Mn, Re; X = Cl, Br) with (Ph2PCH2)3CCH3 (P3) and (Ph2P(CH2)2)3P (P3P'): synthetic, spectroscopic, electrochemical, and electrospray mass spectrometric studies.

    Science.gov (United States)

    Bond, A M; Colton, R; van den Bergen, A; Walter, J N

    2000-10-16

    The reactions of M(CO)5X (M = Mn, Re; X = Cl, Br) with (Ph2PCH2)3CCH3 (P3) and (Ph2P(CH2)2)3P (P3P') are investigated, and the products are characterized by IR, NMR (31P and 13C), and electrospray mass spectrometric (ESMS) techniques. With P3, the major products are fac-M(CO)3(eta 2-P3)X (syn and anti isomers) and cis,fac-M(CO)2(eta 3-P3)X, and with P3P', the major product for each metal is cis,mer-M(CO)2(eta 3-P3P')X, but cis-[M(CO)2(eta 4-P3P')]X and fac-[Re(CO)3(eta 3-P3P')]X are also characterized. Addition of MeI to those complexes containing pendant phosphine groups produces the corresponding phosphonium cations without affecting the remainder of the molecule. On the voltammetric time scale, electrochemical oxidation of cis,fac-Mn(CO)2(eta 3-P3)X yields the corresponding 17e cation cis,fac-[Mn(CO)2(eta 3-P3)X]+, but on the longer time scale of exhaustive electrolysis or chemical oxidation, the product is fac-[Mn(CO)3(eta 3-P3)]+. In contrast, the rhenium cation cis,fac-[Re(CO)2(eta 3-P3)X]+ is stable on the synthetic time scale, but upon oxidation of cis,fac-Re(CO)2(eta 3-P3)X with NOBF4, the final product is the 18e [Re(CO)(NO)(eta 3-P3)X]+. cis,mer-Mn(CO)2(eta 3-P3P')X is reversibly oxidized to cis,mer-[Mn(CO)2(eta 3-P3P')X]+ on the voltammetric time scale, but on the longer synthetic time scale, the product isomerizes to trans-[Mn(CO)2(eta 3-P3P')X]+, which can be reduced to trans-Mn(CO)2(eta 3-P3P')X. Upon voltammetric oxidation, the corresponding rhenium complexes show an initial irreversible response associated with the pendant phosphine group prior to the reversible oxidation of the metal on the synthetic time scale; spectroscopic data indicate formation of cis,mer-Re(CO)2(eta 3-P3P'O)X. The complex cis,mer-[Re(CO)2(eta 3-P3P'Me)X]+ shows only the reversible metal oxidation response. ESMS data are obtained directly for the methylated cationic complexes, and neutral complexes are either oxidized or adducted with sodium ions to produce cationic species.

  10. Miscellaneous notes on Loranthaceae 9—15. (Nrs. 1—8 in Recueil Trav. Bot. Néerl. 31, p. 223223 and 751—760, 1937)

    NARCIS (Netherlands)

    Danser, B.H.

    1936-01-01

    Ramulus c. 2 mm crassus, apice paulum incrassatus, ad 5 mm dilatatus, 2 folia et 2 inflorescentias ferens, superficie tenuiter ferrugineo furfuraceus. Folia opposita; petiolus ut costae pars basalis ferrugineo furfuraceus, c. 8 mm longus, basi tereti c. 1.5 mm crassus, laminam versus supra

  11. 48 CFR 1552.223-71 - EPA Green Meetings and Conferences.

    Science.gov (United States)

    2010-10-01

    ... served? (7) Do you have an energy efficiency program? Please describe. (8) Do you have a water.../. Information about EPA voluntary partnerships may be found at http://www.epa.gov/partners/index.htm. (1) Do you...

  12. 32 CFR Appendix A to Part 223 - Procedures for Identifying and Controlling DoD UCNI

    Science.gov (United States)

    2010-07-01

    ... may only be discussed or transmitted over an unprotected telephone or telecommunications circuit (to... investigative and administrative actions to determine cause, assess impact, and fix responsibility. The DoD...

  13. Yeast Interacting Proteins Database: YGR223C, YOR089C [Yeast Interacting Proteins Database

    Lifescience Database Archive (English)

    Full Text Available micronucleophagy; predicted to fold as a seven-bladed beta-propeller; displays punctate cytoplasmic localiz...tion Phosphatidylinositol 3,5-bisphosphate-binding protein, plays a role in micronucleophagy; predicted to fold as a seven-blade

  14. 50 CFR 223.102 - Enumeration of threatened marine and anadromous species.

    Science.gov (United States)

    2010-10-01

    ... naturally spawned populations of fall-run Chinook salmon in the mainstem Snake River below Hells Canyon Dam... impassable barriers in streams in the Columbia River Basin upstream from the Yakima River, Washington, to the...

  15. 50 CFR 223.206 - Exceptions to prohibitions relating to sea turtles.

    Science.gov (United States)

    2010-10-01

    ... to prohibitions relating to sea turtles. (a) Permits—(1) Scientific research, education, zoological... zoological exhibition, or to enhance the propagation or survival of threatened species of sea turtles, in... of sea turtle is found injured, dead, or stranded, any agent or employee of the National Marine...

  16. 36 CFR 223.30 - Consistency with plans, environmental standards, and other management requirements.

    Science.gov (United States)

    2010-07-01

    ... Property FOREST SERVICE, DEPARTMENT OF AGRICULTURE SALE AND DISPOSAL OF NATIONAL FOREST SYSTEM TIMBER..., requirements for: (a) Fire protection and suppression; (b) Protection of residual timber; (c) Regeneration of...) Providing favorable conditions of water flow and quality; (f) Utilization of the timber resource to provide...

  17. 32 CFR Appendix B to Part 223 - Guidelines for the Determination of DoD UCNI

    Science.gov (United States)

    2010-07-01

    ... electrical systems, barriers, and back-up power systems not observable from a public area. b. Maps, plans... from a public area. c. Performance characteristics of installed systems. 5. Keys, Locks, Combinations, and Tamper-Indicating Devices a. Types and models of keys, locks, and combinations of locks used in Do...

  18. 48 CFR 52.223-5 - Pollution Prevention and Right-to-Know Information.

    Science.gov (United States)

    2010-10-01

    ...) Definitions. As used in this clause— Priority chemical means a chemical identified by the Interagency Environmental Leadership Workgroup or, alternatively, by an agency pursuant to section 503 of Executive Order 13148 of April 21, 2000, Greening the Government through Leadership in Environmental Management. Toxic...

  19. 18 CFR 367.2230 - Account 223, Advances from associate companies.

    Science.gov (United States)

    2010-04-01

    ... from associate companies. 367.2230 Section 367.2230 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY REGULATIONS UNDER THE PUBLIC UTILITY HOLDING COMPANY... COMPANIES SUBJECT TO THE PROVISIONS OF THE PUBLIC UTILITY HOLDING COMPANY ACT OF 2005, FEDERAL POWER ACT AND...

  20. 49 CFR Appendix A to Part 223 - Certification of Glazing Materials

    Science.gov (United States)

    2010-10-01

    ... full map of the Target Material. (6) The Witness Plate shall be an unbacked sheet of maximum 0.006 inch... following tests: (i) Ballistic Impact in which a standard 22 caliber long rifle lead bullet of 40 grains in... Impact in which a standard 22 caliber long rifle lead bullet of 40 grains in weight impacts at a minimum...

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

    Lifescience Database Archive (English)

    Full Text Available onds, involved in the repair of DNA lesions created by topoisomerase I and topoisomerase II; mutations in hu...-phosphotyrosyl bonds, involved in the repair of DNA lesions created by topoisomerase I and topoisomerase II

  2. 48 CFR 1852.223-74 - Drug- and alcohol-free workforce.

    Science.gov (United States)

    2010-10-01

    ... responsibility for safety-sensitive, security, or National security functions who are in need of assistance in resolving problems with the use of alcohol or controlled substances. (e) The requirements of this clause..., or orders that are inconsistent with the requirements of this clause. (f) For any collective...

  3. International Bathymetric Chart of the Arctic Ocean, Version 2.23

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The goal of this initiative is to develop a digital data base that contains all available bathymetric data north of 64 degrees North, for use by mapmakers,...

  4. : tous les projets | Page 223 | CRDI - Centre de recherches pour le ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Sujet: INTERNATIONAL FINANCE, INTERNATIONAL FINANCIAL MARKET, FINANCIAL POLICY, DEMOGRAPHY, DEMOGRAPHIC CHANGE, DEMOGRAPHIC TRANSITION. Région: Brazil, South America, China, Far East Asia, India, South Africa, North of Sahara, South of Sahara, North and Central America, Central Asia, ...

  5. Iu. Ushakov & A. Stukalov, Front voennykh prokurorov [The Military Procurators’ Front], Moskva, Viatka, 2000, 223 pages.

    Directory of Open Access Journals (Sweden)

    Vanessa Voisin

    2008-07-01

    Full Text Available Front voennykh prokurorov is a collection of essays written by two writers who are not known as specialists of military history, but obviously have access to archives, as proves the reprint, in the middle of the book, of several pages from the personal files of Afanas’ev, former Main Military Prosecutor of Soviet Armed Forces.The first part of the book is devoted to Nikolai Porfir’evich Afanas’ev’s memoirs, written, according to the editors, after his retirement in 1950. Afanas’ev, though les...

  6. 36 CFR 223.219 - Sustainable harvest of special forest products.

    Science.gov (United States)

    2010-07-01

    ... making their sustainability determination and establishing monitoring time frames consistent with... on International Trade in Endangered Species may be authorized. (c) Monitoring of established harvest... Forest Service shall monitor the effects of harvesting on the sustainability of special forest products...

  7. 24 CFR 884.223a - Preference for occupancy by elderly families.

    Science.gov (United States)

    2010-04-01

    ... 24 Housing and Urban Development 4 2010-04-01 2010-04-01 false Preference for occupancy by elderly... PROGRAM, SECTION 202 SUPPORTIVE HOUSING FOR THE ELDERLY PROGRAM AND SECTION 811 SUPPORTIVE HOUSING FOR... Preference for occupancy by elderly families. (a) Election of preference for occupancy by elderly families—(1...

  8. 4 CFR 22.3 - Appeals-How Taken [Rule 3].

    Science.gov (United States)

    2010-01-01

    ... original plus 3 copies of the appeal shall be filed with the Board by hand delivery, express or priority mail, approved commercial carrier (e.g., UPS or FedEx), facsimile, or e-mail, although e-mail is the...

  9. 36 CFR 223.5 - Scope of free use granted to individuals.

    Science.gov (United States)

    2010-07-01

    ... silvicultural improvement of the forests. Except in unusual cases, the material will be restricted to dead, insect-infested, or diseased timber, logging debris, and thinnings. Other material may be granted in... justify such action, the free use of green material may be refused. ...

  10. The Gln223Arg polymorphism in the leptin receptor is associated with familial combined hyperlipidemia.

    NARCIS (Netherlands)

    Vleuten, G.M. van der; Kluijtmans, L.A.J.; Hijmans, A.G.M.; Blom, H.J.; Stalenhoef, A.F.H.; Graaf, J. de

    2006-01-01

    OBJECTIVE: Familial combined hyperlipidemia (FCH) is characterized by elevated levels of total cholesterol (TC), triglycerides (TG) and apolipoprotein B (apo B) and is associated with premature cardiovascular disease (CVD). Other features of FCH are obesity and insulin resistance. Serum leptin

  11. 77 FR 71028 - Twelfth Meeting: RTCA Special Committee 223, Airport Surface Wireless Communications

    Science.gov (United States)

    2012-11-28

    ... Plenary Welcome, Introductions, Administrative Remarks by Special Committee Leadership Agenda Overview... November 8, 2012. Richard F. Gonzalez, Management Analyst, Business Operations Group, Federal Aviation...

  12. 75 FR 44306 - Fifth Meeting: RTCA Special Committee 223: Airport Surface Wireless Communications

    Science.gov (United States)

    2010-07-28

    ... Center Management: Dr. Gary Seng. Special Committee Leadership. Designated Federal Official (DFO): Mr..., 2010--Building 54 Room 101 0900 a.m.--Opening Plenary. Welcome, Introductions, Administrative Remarks...

  13. 76 FR 38740 - Tenth Meeting: RTCA Special Committee 223: Airport Surface Wireless Communications

    Science.gov (United States)

    2011-07-01

    ..., Administrative Remarks by Special Committee Leadership Designated Federal Officer (DFO): Mr. Brent Phillips Co... WMF Agreement Discussion of Chapters 5,6,8--EUROCAE Chap 5--Service Specific CS Draft Chap 8--Physical... Morning--MOPS WG Breakout Session Review Draft of Environmental (DO-160G)--Rockwell Collins Review Draft...

  14. 76 FR 72996 - Eleventh Meeting: RTCA Special Committee 223 Airport Surface Wireless Communications

    Science.gov (United States)

    2011-11-28

    ... Leadership Designated Federal Official (DFO): Mr. Brent Phillips Co-Chair: Mr. Aloke Roy, Honeywell... Control December 7, 2011 MOPS WG Breakout Session Discussion of Security Sub-layer--Honeywell Review draft of Environmental (DO-160G)--Rockwell Collins Review draft PICS--EUROCAE (Thales) Review draft CSRL...

  15. 48 CFR 52.223-13 - Certification of Toxic Chemical Release Reporting.

    Science.gov (United States)

    2010-10-01

    ...) Executive Order 13148, of April 21, 2000, Greening the Government through Leadership in Environmental Management, requires submission of this ertification as a prerequisite for contract award. (b) By signing... one of the following reasons: (Check each block that is applicable.) □ (i) The facility does not...

  16. 12 CFR 223.53 - What asset purchases are prohibited by section 23B?

    Science.gov (United States)

    2010-01-01

    ... fiduciary relationship; (2) By court order; or (3) By law of the jurisdiction governing the fiduciary relationship. (b) Purchase of a security underwritten by an affiliate. (1) A member bank, whether acting as...) Fiduciary purchases of assets from an affiliate. A member bank may not purchase as fiduciary any security or...

  17. 33 CFR 223.1 - Mississippi River Water Control Management Board.

    Science.gov (United States)

    2010-07-01

    ..., responsibilities and authority of the Mississippi River Water Control Management Board. (b) Applicability. This... control management within the Mississippi River Basin. (c) Objectives. The objectives of the Board are: (1...) Composition. The Mississippi River Water Control Management Board is a continuing board consisting of the...

  18. 75 FR 16696 - Airworthiness Directives; Airbus Model A330-223, -321, -322, and -323 Airplanes

    Science.gov (United States)

    2010-04-02

    ... Damage Tolerant--Airworthiness Limitation Item task 712106-01-01 from A330 ALS Part 2, an A330 operator..., contact Airbus SAS--Airworthiness Office--EAL, 1 Rond Point Maurice Bellonte, 31707 Blagnac Cedex, France...: During accomplishment of Damage Tolerant--Airworthiness Limitation Item task 712106-01-01 from A330 ALS...

  19. SU-F-T-223: Radiotherapy Incident Reporting and Analysis System (RIRAS):Early Experience

    Energy Technology Data Exchange (ETDEWEB)

    Kapoor, R; Palta, J; Hagan, M [National Radiation Oncology Program (10P4H), Dept. of Veterans Affairs, Richmond, VA (United States); Burkett, D; Leidholdt, E [National Health Physics Program (10P4X), Dept. of Veterans Affairs, Little Rock, AR (United States)

    2016-06-15

    Background & Purpose: RIRAS is a web-based information system deployed on the Veterans Health Administration intranet in early 2014 to collect adverse events and good catch data; analyze the causes and contributing factors; and find ways to prevent future occurrences. Material and Methods: Incident learning consists of a feedback loop which starts with reporting an event, followed by analysis of contributing factors, and culminates in the development of a patient safety work product (PSWP) to prevent recurrence. RIRAS permits both anonymous and non-anonymous reporting. Each report is analyzed by a team of medical physicists who are independent of the reporting facility. The analysts usually contact the reporting facilities for additional information. We analyzed all reports and held telephonic interviews (when necessary) with the reporters. We then generated PSWPs with corrective/preventive and learning actions. Anonymous reporting is handled in the same manner, except without the ability to further interview the reporter. Results: In a significant number of reports, the causes and recommended preventive actions were considerably altered by the independent analysis and additional information from the facility. 130 reports have been entered in RIRAS; 9 misadministrations, 83 good catches, 3 anonymous good catches, and 35 earlier reported incidents from FY2005-14. 45% of the reported incidents occurred in the treatment delivery stages, 19% in on-treatment management, and 16% in pre-treatment verification. 80% of the good catches were found in the treatment delivery workflow. Majority of these incidents were due to inconsistent patient setup instructions or documentation, nonadherence to policies and procedures, lax time-out policy, distracted RTTs, and inadequate RTT staffing. Conclusion: RIRAS has identified many areas for improvement and elevated the quality and safety of radiation treatments in the VHA. We found that the ability to learn is significantly diminished when the analysts do not have the ability to request additional information.

  20. Page 1 Hybrid rockets * 223 in a solid rocket and the perturbation ...

    Indian Academy of Sciences (India)

    including that needed for degradation) and #", the heat flux into the surface. Now, if by some mechanism r, increases by decrease of (Ah), this increase in rh causes an increase in boundary layer thickness, hence, reduction in gradients at the surface ...

  1. 48 CFR 1852.223-75 - Major breach of safety or security.

    Science.gov (United States)

    2010-10-01

    ..., equipment or property damage from vandalism greater than $250,000, or theft greater than $250,000. (c) In... from vandalism greater than $250,000, or theft greater than $250,000. (End of clause) ...

  2. Quantitative single-particle digital autoradiography with α-particle emitters for targeted radionuclide therapy using the iQID camera

    Energy Technology Data Exchange (ETDEWEB)

    Miller, Brian W., E-mail: brian.miller@pnnl.gov [Pacific Northwest National Laboratory, Richland, Washington 99354 and College of Optical Sciences, The University of Arizona, Tucson, Arizona 85719 (United States); Frost, Sofia H. L.; Frayo, Shani L.; Kenoyer, Aimee L.; Santos, Erlinda; Jones, Jon C.; Orozco, Johnnie J. [Fred Hutchinson Cancer Research Center, Seattle, Washington 98109 (United States); Green, Damian J.; Press, Oliver W.; Pagel, John M.; Sandmaier, Brenda M. [Fred Hutchinson Cancer Research Center, Seattle, Washington 98109 and Department of Medicine, University of Washington, Seattle, Washington 98195 (United States); Hamlin, Donald K.; Wilbur, D. Scott [Department of Radiation Oncology, University of Washington, Seattle, Washington 98195 (United States); Fisher, Darrell R. [Dade Moeller Health Group, Richland, Washington 99354 (United States)

    2015-07-15

    Purpose: Alpha-emitting radionuclides exhibit a potential advantage for cancer treatments because they release large amounts of ionizing energy over a few cell diameters (50–80 μm), causing localized, irreparable double-strand DNA breaks that lead to cell death. Radioimmunotherapy (RIT) approaches using monoclonal antibodies labeled with α emitters may thus inactivate targeted cells with minimal radiation damage to surrounding tissues. Tools are needed to visualize and quantify the radioactivity distribution and absorbed doses to targeted and nontargeted cells for accurate dosimetry of all treatment regimens utilizing α particles, including RIT and others (e.g., Ra-223), especially for organs and tumors with heterogeneous radionuclide distributions. The aim of this study was to evaluate and characterize a novel single-particle digital autoradiography imager, the ionizing-radiation quantum imaging detector (iQID) camera, for use in α-RIT experiments. Methods: The iQID camera is a scintillator-based radiation detection system that images and identifies charged-particle and gamma-ray/x-ray emissions spatially and temporally on an event-by-event basis. It employs CCD-CMOS cameras and high-performance computing hardware for real-time imaging and activity quantification of tissue sections, approaching cellular resolutions. In this work, the authors evaluated its characteristics for α-particle imaging, including measurements of intrinsic detector spatial resolutions and background count rates at various detector configurations and quantification of activity distributions. The technique was assessed for quantitative imaging of astatine-211 ({sup 211}At) activity distributions in cryosections of murine and canine tissue samples. Results: The highest spatial resolution was measured at ∼20 μm full width at half maximum and the α-particle background was measured at a rate as low as (2.6 ± 0.5) × 10{sup −4} cpm/cm{sup 2} (40 mm diameter detector area

  3. 78 FR 5445 - Federal Acquisition Regulation; Submission for OMB Review; Drug-Free Workplace (FAR 52.223-6)

    Science.gov (United States)

    2013-01-25

    ... Secretariat (MVCB), 1275 First Street NE., Washington, DC 20417. ATTN: Hada Flowers/IC 9000-0101, Drug-Free... clause is not applicable to commercial items, contracts at or below simplified acquisition threshold...

  4. 77 FR 52696 - Federal Acquisition Regulation; Information Collection; Drug-Free Workplace (FAR 52.223-6)

    Science.gov (United States)

    2012-08-30

    ... Secretariat (MVCB), 1275 First Street NE., Washington, DC 20417. ATTN: Hada Flowers/IC 9000-0101, Drug-Free... applicable to commercial items, contracts at or below simplified acquisition threshold (unless awarded to an...

  5. 75 FR 4477 - Airworthiness Directives; Airbus Model A330-201, -202, -203, -223, -243, -301, -302, -303, -321...

    Science.gov (United States)

    2010-01-28

    ... and, in case deformation or damage is detected, to apply the associated repair. The one-time...-time detailed inspections of both main landing gear bogie beams in the region of the bogie stop pad for...], the bogie stop pad was found deformed and cracked. Upon removal of the bogie stop pad for replacement...

  6. Jansen Metaphyseal Chondrodysplasia due to Heterozygous H223R-PTH1R Mutations With or Without Overt Hypercalcemia

    National Research Council Canada - National Science Library

    Nampoothiri, Sheela; Fernández-Rebollo, Eduardo; Yesodharan, Dhanya; Gardella, Thomas J; Rush, Eric T; Langman, Craig B; Jüppner, Harald

    2016-01-01

    Context: Jansen's metaphyseal chondrodysplasia (JMC) is a rare skeletal dysplasia characterized by abnormal endochondral bone formation and typically severe hypercalcemia despite normal/low levels of PTH...

  7. 75 FR 60655 - Airworthiness Directives; Airbus Model A330-201, -202, -203, -223, and -243 Airplanes; Airbus...

    Science.gov (United States)

    2010-10-01

    ... National Aviation Authorities (NAA) the application of a similar regulation. The aim of this regulation is to require * * * a definition review against explosion hazards. * * * * * Failure of the auxiliary... explosion and consequent loss of the airplane. The proposed AD would require actions that are intended to...

  8. 76 FR 432 - Airworthiness Directives; Airbus Model A330-201, -202, -203, -223, and -243 Airplanes; Airbus...

    Science.gov (United States)

    2011-01-05

    ... Authorities (NAA) the application of a similar regulation. The aim of this regulation is to require * * * a definition review against explosion hazards. * * * * * Failure of the auxiliary power unit (APU) bleed leak... of the fuel vapors in that tank, which could result in a fuel tank explosion and consequent loss of...

  9. 48 CFR 952.223-77 - Conditional payment of fee or profit-protection of worker safety and health.

    Science.gov (United States)

    2010-10-01

    ... “Contractor” as used in this clause to address failure to comply shall mean “Contractor or Contractor employee... allocation) and to support DOE corporate decision-making (e.g., policy, WS&H programs). (viii) Contractor... fee or profit to be allocated to each period shall be equal to the average monthly fee or profit that...

  10. Archeological Data Recovery of the Camino Site (16JE223), A Spanish Colonial Period Site Near New Orleans, Louisiana

    Science.gov (United States)

    1996-03-01

    left Havana for New Orleans on Sep - tember 1, 17,78. Uiririg ne voyage from the Canary islands, three children had been born and one had died. Another...Miguel Molina 1982 La Participacion Canaria en la Formacion y Reclutamiento del Batallon de Lu- isiana. In Coloquio de Historia Canario Americana...Gennrn HernAndez 1982 La Aportacion de La Isla de La Gomera al Poblamiento de La Luisiana 1777- 78. In ColoQuio de Historia Canario-Americana (1980

  11. Cruise report NOAA ship Miller Freeman R-223 during the period of October 11 through November 7, 1981

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — This was an opportunity to become more familiar with the wintering ecology of insular fauna of the Aleutian Islands as well as the pelagic fauna of the Bering Sea....

  12. 76 FR 42602 - Airworthiness Directives; Airbus Model A330-201, -202, -203, -223, -243, -301, -302, -303, -321...

    Science.gov (United States)

    2011-07-19

    ...: During A330 and A340 aeroplanes fatigue tests, cracks appeared on the right (RH) and left (LH) sides between the crossing area of the keel beam fitting and the front spar of the Centre Wing Box (CWB). This condition, if not corrected, could lead to keel beam rupture which would affect the area structural...

  13. 48 CFR 952.223-76 - Conditional payment of fee or profit-safeguarding restricted data and other classified...

    Science.gov (United States)

    2010-10-01

    ... level of information in a SAP, information identified as SCI, or high risk nuclear weapons-related data... SAP, information identified as SCI, or high risk nuclear weapons-related data. (iv) Failure to timely... information in a SAP, information identified as SCI, or high risk nuclear weapons-related data. (2) Second...

  14. 12 CFR 223.52 - What transactions with affiliates or others must comply with section 23B's market terms requirement?

    Science.gov (United States)

    2010-01-01

    ... deemed to be a transaction with an affiliate of the member bank if any of the proceeds of the transaction... 12 Banks and Banking 3 2010-01-01 2010-01-01 false What transactions with affiliates or others... FEDERAL RESERVE SYSTEM (CONTINUED) BOARD OF GOVERNORS OF THE FEDERAL RESERVE SYSTEM TRANSACTIONS BETWEEN...

  15. A novel variant on chromosome 7q22.3 associated with mean platelet volume, counts, and function

    OpenAIRE

    Soranzo, Nicole; Rendon, Augusto; Gieger, Christian; Jones, Chris I.; Watkins, Nicholas A.; Menzel, Stephan; Döring, Angela; Stephens, Jonathan; Prokisch, Holger; Erber, Wendy; Potter, Simon C.; Bray, Sarah L.; Burns, Philippa; Jolley, Jennifer; Falchi, Mario

    2009-01-01

    Mean platelet volume (MPV) and platelet count (PLT) are highly heritable and tightly regulated traits. We performed a genome-wide association study for MPV and identified one SNP, rs342293, as having highly significant and reproducible association with MPV (per-G allele effect 0.016 ± 0.001 log fL; P < 1.08 × 10−24) and PLT (per-G effect −4.55 ± 0.80 109/L; P < 7.19 × 10−8) in 8586 healthy subjects. Whole-genome expression analysis in the 1-MB region showed a significant association with plat...

  16. δ37Cl : the geochemistry of chlorine isotopes

    NARCIS (Netherlands)

    Eggenkamp, H.G.M.

    1994-01-01

    In this thesis the geochemistry of the stable isotopes of chlorine will be examined. Chlorine is one of the halogens, the seventh group in the periodic system of elements. This group consists of five elements, fluorine, chlorine, bromine, iodine, and astatine.

  17. δ³⁷Cl : the geochemistry of chlorine isotopes

    NARCIS (Netherlands)

    Eggenkamp, H.G.M.

    1994-01-01

    In this thesis the geochemistry of the stable isotopes of chlorine will be examined. Chlorine is one of the halogens, the seventh group in the periodic system of elements. This group consists of five elements, fluorine, chlorine, bromine, iodine, and astatine. This thesis presents the first chlorine

  18. SPECT assay of radiolabeled monoclonal antibodies. Final performance report, March 1992--November 1995

    Energy Technology Data Exchange (ETDEWEB)

    Jaszczak, R.J.

    1995-12-01

    Research is described in the following areas: development and evaluation quantitatively of reconstruction algorithms with improved compensations for attenuation, scatter, and geometric collimator response; evaluation of single photon emission computed tomography (SPECT) quantification of iodine 123 and astatine 211; and the development and evaluation of SPECT pinhole imaging for low and medium energy photons.

  19. $\\beta$-delayed fission, laser spectroscopy and shape-coexistence studies with radioactive At beams

    CERN Multimedia

    We propose to study the $\\beta$-delayed fission, laser spectroscopy and radioactive decay of the newly available pure beams of neutron-deficient and neutron-rich astatine (Z=85) isotopes. The fission probability and the fission fragment distribution of the even-even isotopes $^{194,196}$Po following the $\\beta$-decay of the isotopes $^{194,196}$At will be studied with the Windmill setup. In-source laser spectroscopy will be performed on the entire astatine isotopic chain, using a combination of the Windmill setup, ISOLTRAP MR-ToF and ISOLDE Faraday. Radioactive decay data will be acquired at the Windmill setup throughout those studies and contribute to the global understanding of the phenomenon of shape coexistence in the neutron-deficient lead region.

  20. Production cross section of At radionuclides from $^{7}$Li+$^{\\textrm{nat}}$Pb and $^{9}$Be+$^{\\textrm{nat}}$Tl reactions

    CERN Document Server

    Maiti, Moumita

    2011-01-01

    Earlier we reported theoretical studies on the probable production of astatine radionuclides from $^{6,7}$Li and $^{9}$Be-induced reactions on natural lead and thalliun targets, respectively. For the first time, in this report, production of astatine radionuclides has been investigated experimentally with two heavy ion induced reactions: $^{9}$Be+$^{\\textrm{nat}}$Tl and $^{7}$Li+$^{\\textrm{nat}}$Pb. Formation cross sections of the evaporation residues, $^{207,208,209,210}$At, produced in (HI, xn) channel, have been measured by the stacked-foil technique followed by the off-line $\\gamma$-spectrometry at the low incident energies ($<$50 MeV). Measured excitation functions have been explained in terms of compound nuclear reaction mechanism using Weisskopf-Ewing and Hauser-Feshbach model. Absolute cross section values are lower than the respective theoretical predictions.

  1. Production cross section of At radionuclides from 7Li+natPb and 9Be+natTl reactions

    Science.gov (United States)

    Maiti, Moumita; Lahiri, Susanta

    2011-12-01

    Earlier we reported theoretical studies on the probable production of astatine radionuclides from 6,7Li- and 9Be-induced reactions on natural lead and thallium targets, respectively. The production of astatine radionuclides were investigated experimentally with two heavy-ion-induced reactions: 9Be + natTl and 7Li + natPb. Formation cross sections of the evaporation residues, 207,208,209,210At, produced in the (HI,xn) channel, were measured by the stacked-foil technique followed by off-line γ spectrometry at low incident energies (<50 MeV). Measured excitation functions were interpreted in terms of a compound nuclear reaction mechanism using Weisskopf-Ewing and Hauser-Feshbach models. Measured cross-section values are lower than the respective theoretical predictions.

  2. A single nucleotide polymorphism of AIRE gene located in the 21q22.3 increases the risk of rheumatoid arthritis.

    Science.gov (United States)

    Xu, Yuan-Sheng; Jiang, Xi-Jia; Chen, Jian-Min

    2017-09-22

    Several studies addressed the association of autoimmune regulator (AIRE) gene polymorphism with the risk of rheumatoid arthritis (RA); however, their conclusions were inconsistent. For better investigating the effects of this polymorphism on the risk of RA, we conducted this study to evaluate the role of AIRE rs2075786 polymorphism in the risk of RA. Four eligible studies involving 6,755 cases and 7,970 controls were identified by searching the databases of PubMed, CNKI and EMBASE up to February 2017. Our study revealed that AIRE rs2075786 polymorphism was associated with an increased risk of RA under all genetic models. In the subgroup analysis, AIRE rs2075786 polymorphism contributed to RA susceptibility among Asians, but not among Caucasians. To summarize,, this meta-analysis confirms that AIRE rs2075786 polymorphism may play a significant role in increasing the risk of RA. Stratification analysis by ethnicity reveals that AIRE rs2075786 polymorphism is associated with an increased risk of RA among Asians, but not among Caucasians. These findings need further validation in the large multicenter case-control studies.

  3. {4,5-Dimethoxy-2-[(2,3-η-2-prop-2-en-1-yl]phenyl-κC1}(8-hydroxyquinolinato-κN,Oplatinum(II

    Directory of Open Access Journals (Sweden)

    Thi Yen Hang Bui

    2016-01-01

    Full Text Available The crystal structure of the organoplatinum(II title complex, [Pt(C9H6NO(C11H13O2] or [Pt(methyleugenol(8-hydroxyquinolinato], has been determined in order to verify the coordination environment of the PtII cation, which was found to be square-planar with the N and O atoms of the quinolinate ligand cis and trans, respectively, with respect to the ethylenic double bond. The least-squares planes through the two aromatic ring systems make an angle of 39.87 (10°. In the crystal, chains are formed parallel to [100] sustained by C—H...O hydrogen bonds. Parallel chains further interact via C—H...O and C—H...π contacts. The complex shows interesting activity on four human cancer cell lines with IC50 values between 1.92 and 4.86 µM.

  4. 12 CFR 223.2 - What is an “affiliate” for purposes of sections 23A and 23B and this part?

    Science.gov (United States)

    2010-01-01

    ... conducting a safe deposit business; (4) Government securities. Any company engaged solely in holding... this section, “affiliate” with respect to a member bank means: (1) Parent companies. Any company that controls the member bank; (2) Companies under common control by a parent company. Any company, including...

  5. H1N1 2009 Pandemic Influenza Virus: Resistance of the I223R Neuraminidase Mutant Explained by Kinetic and Structural Analysis

    NARCIS (Netherlands)

    E. van der Vries (Erhard); P.J. Collins (Patrick ); S.G. Vachieri (Sebastien); X. Xiong (Xiaoli); J. Liu (Jinhua); P.A. Walker (Philip); L.F. Haire (Lesley ); A.J. Hay (Alan); M. Schutten (Martin); A.D.M.E. Osterhaus (Albert); S.R. Martin (Steve ); C.A. Boucher (Charles); J.J. Skehel (John ); S.J. Gamblin (Steve )

    2012-01-01

    textabstractTwo 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

  6. Partial monosomy of 11q22.2q22.3 including the SDHD gene in individuals with developmental delay.

    Science.gov (United States)

    Yelavarthi, Krishna; Cabral, Huong; Wilson, Golder N; Rohena, Luis; Risheg, Hiba; Penton, Andrea; Schleede, Justin; Burnside, Rachel D

    2015-04-01

    Deletions in the middle portion of 11q are not as well described in the literature as terminal 11q deletions that result in Jacobsen syndrome. One confounding factor in the older literature is that the G-banding pattern of 11q13q21 is very similar to 11q21q23. The advent of fluorescence in situ hybridization and later microarray technologies have allowed for a better resolution of many of these deletions, but genotype-phenotype correlations are still difficult since these deletions are rare events. We present five individuals who presented with developmental delays with de novo 11q22.2q23.3 deletions. Deletions were observed by standard G-banded chromosome analysis with clarification of breakpoints and gene content by SNP microarray analysis. Of note, all individuals had identical distal breakpoints. All deletions include SDHD, which is implicated in hereditary paraganglioma/pheochromocytoma, for which the patients will need to be monitored in adulthood. In spite of the large deletions of 8.6 Mb (Patients 1 and 3), 13.98 Mb (Patient 2), and 12.6 Mb (Patients 4 and 5) all patients show somewhat mild intellectual disability and dysmorphism. © 2015 Wiley Periodicals, Inc.

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

    DEFF Research Database (Denmark)

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

    2002-01-01

    whether this variant influences energy metabolism and adiposity in Pima Indians, we genotyped non-diabetic Pima Indians in whom we had measured body composition and 24 h energy expenditure (24 h EE), physical activity level (PAL) and 24 h respiratory quotient (24 h RQ) in a respiratory chamber (n=268...

  8. Submarine groundwater discharge revealed by radium isotopes (Ra-223 and Ra-224 near a paleochannel on the Southern Brazilian continental shelf

    Directory of Open Access Journals (Sweden)

    Karina Kammer Attisano

    2013-09-01

    Full Text Available Submarine Groundwater Discharge (SGD has been recognized as an important component of the ocean-continent interface. The few previous studies in Brazil have focused on nearshore areas. This paper explores SGD on the Southern Brazilian Continental Shelf using multiple lines of evidence that include radium isotopes, dissolved nutrients, and water mass observations. The results indicated that SGD may be occurring on the Continental Shelf in the Albardão region, near a paleochannel located 50 km offshore. This paleochannel may thus be a preferential pathway for the delivery of nutrient- and metal-enriched groundwater and porewater into continental shelf waters.

  9. Tourette syndrome in a pedigree with a 7;18 translocation: Identification of a YAC spanning the translocation breakpoint at 18q22.3

    Energy Technology Data Exchange (ETDEWEB)

    Boghosian-Sell, L.; Overhauser, J. [Thomas Jefferson Univ., Philadelphia, PA (United States); Comings, D.E. [City of Hope Medical Center, Duarte, CA (United States)

    1996-11-01

    Tourette syndrome is a neuropsychiatric disorder characterized by the presence of multiple, involuntary motor and vocal tics. Associated pathologies include attention deficit disorder and obsessive-compulsive disorder (OCD). Extensive linkage analysis based on an autosomal dominant mode of transmission with reduced penetrance has failed to show linkage with polymorphic markers, suggesting either locus heterogeneity or a polygenic origin for Tourette syndrome. An individual diagnosed with Tourette syndrome has been described carrying a constitutional chromosome translocation. Other family members carrying the translocation exhibit features seen in Tourette syndrome including motor tics, vocal tics, and OCD. Since the disruption of specific genes by a chromosomal rearrangement can elicit a particular phenotype, we have undertaken the physical mapping of the 7;18 translocation such that genes mapping at the site of the breakpoint can be identified and evaluated for a possible involvement in Tourette syndrome. Using somatic cell hybrids retaining either the der(7) or the der(18), a more precise localization of the breakpoints on chromosomes 7 and 18 have been determined. Furthermore, physical mapping has identified two YAC clones that span the translocation breakpoint on chromosome 18 as determined by FISH. These YAC clones will be useful for the eventual identification of genes that map to chromosomes 7 and 18 at the site of the translocation. 41 refs., 3 figs., 1 tab.

  10. Renato Cristi, El Pensamiento Político de Jaime Guzmán. Autoridad y Libertad, Ediciones Lom, 2000, Santiago, 223 p.

    OpenAIRE

    Benítez, Hermes H.

    2012-01-01

    Puesto que es imposible hacer justicia, en unas cuantas páginas, a un libro tan bien investigado, organizado y escrito, no trataremos de resumir aquí el contenido de sus diferentes capítulos. Nos limitaremos, simplemente, a destacar lo que en éste nos ha parecido ser lo más significativo e importante; por lo menos en términos de su capacidad para interpretar el pensamiento y la acción política de Jaime Guzmán; pero, en especial, en cuanto a su capacidad para iluminar el significado y las proy...

  11. 12 CFR 223.31 - How does section 23A apply to a member bank's acquisition of an affiliate that becomes an...

    Science.gov (United States)

    2010-01-01

    ... GAAP; and (ii) Sales of the assets of the transferred company. (c) Valuation example. The parent... affiliate. A member bank's acquisition of a security issued by a company that was an affiliate of the member... of the transaction, the company becomes an operating subsidiary of the member bank; and (2) The...

  12. Discriminant effect of morphology and range of attack on the performance level of volleyball players. DOI: 10.5007/1980-0037.2011v13n3p223

    Directory of Open Access Journals (Sweden)

    Victor Machado Reis

    2011-04-01

    Full Text Available The aim of this study was to identify the discriminant effect of morphology and range of attack-related variables on the performance level of under-17 female volleyball players. The sample consisted of young volleyball players (n=40 divided into two groups: players of the Brazilian national team (n=21 aged 15.86 ± 0.36 years, body weight of 68.11 ± 8.73 kg, and height of 181.61 ± 6.11 cm, and players of the state team of Rio Grande do Norte (n=19 aged 15.16 ± 0.88 years, body weight of 60.54 ± 7.60 kg, and height of 170.52 ± 7.97 cm. The somatotype was assessed using the Heath & Carter method. A modified Sargent test was used to assess vertical jump height and maximum attack height. The measures were compared between the two groups using the Student t-test for independent samples. Discriminant function analysis was applied to predict group allocation using the measures obtained as independent variables. The two groups differed significantly in terms of body weight, fat mass, height, maximum attack height, range of attack, and somatotype. Discriminant function analysis identified the somato-type measures (endomorphy, ectomorphy, and mesomorphy with correlation coefficients below 0.30. The canonical correlation coefficient obtained with this function was 0.856. In conclusion, somatotype or vertical jump ability does not seem to distinguish elite athletes from non-elite athletes in under-17 female volleyball players, and height is the main morphological determinant to achieve elite level performance.

  13. Radiohalogenation of biomolecules. An experimental study on radiohalogen preparation, precursor synthesis, radiolabeling and biodistribution

    Energy Technology Data Exchange (ETDEWEB)

    Koziorowski, J

    1998-10-01

    Radiohalogens are widely used in nuclear medicine, both as tool for diagnostic in vivo imaging, and in radionuclide therapy. This study deals with the use of radiohalogens; separation, precursor synthesis, labeling and biological behavior. The focus is on {sup 211}At and {sup 124}I, the former being a candidate for nuclide therapy and the latter potentially useful for diagnostic imaging and Auger-electron based radiotherapy. For astatine the separation, labeling and some biological behavior is described, and for iodine the latter two. Astatine was separated from an irradiated bismuth target by dry distillation. A novel cryotrap was developed for the isolation of astatine and subsequent synthesis of radiolabeled compounds. 5-[{sup 211}At]astato-2`-deoxyuridine (AUdR) and N-succinimidyl-4-[{sup 211}At]astatobenzoate (SAB) were synthesized in 95% respectively 90% radiochemical yields. The former is incorporated into DNA of proliferating cells and can therefore be used as an endoradiotherapeutic agent. The latter is a conjugate for the astatination of proteins. Human epidermal growth factor (hEGF) was tagged with astatine using three approaches: a) direct labeling of native hEGF, b) conjugation with SAB, and c) direct labeling of an hEGF - 7-(3-aminopropyl)-7,8-dicarba-nido-undecaborate(1-) conjugate. The overall labeling yields were 3.5% for direct labeling, 44% for SAB and 70% for the hEGF-nido-carborane conjugate. A new route to N-succinimidyl 3- and 4- [{sup 124}I]iodobenzoate, two reagents for radioiodination of proteins is described affording 90% radiochemical yield. Three radioiodinated analogs of PK11195, 1-(2-chlorophenyl)-N-methyl-N-(1-methylpropyl)isoquinoline-3-carboxyam ide, a peripheral-type benzodiazepine receptor antagonist, were synthesized. All three analogs were obtained in >90% radiochemical yield. Synthesis and application of 5-[{sup 124}I]iodo-2`-deoxyuridine (IUdR) is presented. The closo-dodecaborate anion was evaluated as prosthetic group for

  14. Dicty_cDB: [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available VF (Link to library) VFC223 (Link to dictyBase) - - - Contig-U10989-1 VFC223P (Link... to Original site) VFC223F 476 VFC223Z 486 VFC223P 962 - - Show VFC223 Library VF (Link to library) Clone ID VFC223 (Link to dict...yBase) Atlas ID - NBRP ID - dictyBase ID - Link to Contig Contig-U10989-1 Original site URL http://dict...drial 4.0 %: endoplasmic reticulum >> prediction for VFC223 is cyt 5' end seq. ID

  15. Alpha particle induced DNA damage and repair in normal cultured thyrocytes of different proliferation status

    DEFF Research Database (Denmark)

    Lyckesvärd, Madeleine Nordén; Delle, Ulla; Kahu, Helena

    2014-01-01

    Childhood exposure to ionizing radiation increases the risk of developing thyroid cancer later in life and this is suggested to be due to higher proliferation of the young thyroid. The interest of using high-LET alpha particles from Astatine-211 ((211)At), concentrated in the thyroid by the same...... mechanism as (131)I [1], in cancer treatment has increased during recent years because of its high efficiency in inducing biological damage and beneficial dose distribution when compared to low-LET radiation. Most knowledge of the DNA damage response in thyroid is from studies using low-LET irradiation...

  16. Plasma levels of leptin and soluble leptin receptor and polymorphisms of leptin gene -18G > A and leptin receptor genes K109R and Q223R, in survivors of childhood acute lymphoblastic leukemia

    National Research Council Canada - National Science Library

    Skoczen, Szymon; Tomasik, Przemyslaw J; Bik-Multanowski, Miroslaw; Surmiak, Marcin; Balwierz, Walentyna; Pietrzyk, Jacek J; Sztefko, Krystyna; Gozdzik, Jolanta; Galicka-Latała, Danuta; Strojny, Wojciech

    2011-01-01

    ...) are at increased risk of overweight and obesity. The purpose of this study was to assess leptin and leptin soluble receptor levels, as well as polymorphisms of selected genes in survivors of pediatric ALL, and the influence of chemo- and radio...

  17. Association of breast cancer risk in BRCA1 and BRCA2 mutation carriers with genetic variants showing differential allelic expression : Identification of a modifier of breast cancer risk at locus 11q22.3

    NARCIS (Netherlands)

    Hamdi, Yosr; Soucy, Penny; Kuchenbaeker, Karoline B.; Pastinen, Tomi; Droit, Arnaud; Lemacon, Audrey; Adlard, Julian; Aittomaki, Kristiina; Andrulis, Irene L.; Arason, Adalgeir; Arnold, Norbert; Arun, Banu K.; Azzollini, Jacopo; Bane, Anita; Barjhoux, Laure; Barrowdale, Daniel; Benitez, Javier; Berthet, Pascaline; Blok, Marinus J.; Bobolis, Kristie; Bonadona, Valerie; Bonanni, Bernardo; Bradbury, Angela R.; Brewer, Carole; Buecher, Bruno; Buys, Saundra; Caligo, Maria A.; Chiquette, Jocelyne; Chung, Wendy K.; Claes, Kathleen B. M.; Daly, Mary B.; Damiola, Francesca; Davidson, Rosemarie; de la Hoya, Miguel; De Leeneer, Kim; Diez, Orland; Ding, Yuan Chun; Dolcetti, Riccardo; Domchek, Susan M.; Dorfling, Cecilia M.; Eccles, Diana; Eeles, Ros; Einbeigi, Zakaria; Ejlertsen, Bent; Engel, Christoph; Evans, D. Gareth; Feliubadalo, Lidia; Foretova, Lenka; Fostira, Florentia; Foulkes, William D.; Fountzilas, George; Friedman, Eitan; Frost, Debra; Ganschow, Pamela; Ganz, Patricia A.; Garber, Judy; Gayther, Simon A.; Gerdes, Anne-Marie; Glendon, Gord; Godwin, Andrew K.; Goldgar, David E.; Greene, Mark H.; Gronwald, Jacek; Hahnen, Eric; Hamann, Ute; Hansen, Thomas V. O.; Hart, Steven; Hays, John L.; Hogervorst, Frans B. L.; Hulick, Peter J.; Imyanitov, Evgeny N.; Isaacs, Claudine; Izatt, Louise; Jakubowska, Anna; James, Paul A.; Janavicius, Ramunas; Jensen, Uffe Birk; John, Esther M.; Joseph, Vijai; Just, Walter; Kaczmarek, Katarzyna; Karlan, Beth Y.; Kets, Carolien M.; Kirk, Judy; Kriege, Mieke; Laitman, Yael; Laurent, Maite; Lazaro, Conxi; Leslie, Goska; Lester, Jenny; Lesueur, Fabienne; Liljegren, Annelie; Loman, Niklas; Loud, Jennifer T.; Manoukian, Siranoush; Mariani, Milena; Mazoyer, Sylvie; McGuffog, Lesley; Meijers-Heijboer, Hanne E. J.; Meindl, Alfons; Miller, Austin; Montagna, Marco; Mulligan, Anna Marie; Nathanson, Katherine L.; Neuhausen, Susan L.; Nevanlinna, Heli; Nussbaum, Robert L.; Olah, Edith; Olopade, Olufunmilayo I.; Ong, Kai-Ren; Oosterwijk, Jan C.; Osorio, Ana; Papi, Laura; Park, Sue Kyung; Pedersen, Inge Sokilde; Peissel, Bernard; Segura, Pedro Perez; Peterlongo, Paolo; Phelan, Catherine M.; Radice, Paolo; Rantala, Johanna; Rappaport-Fuerhauser, Christine; Rennert, Gad; Richardson, Andrea L.; Robson, Mark; Rodriguez, Gustavo C.; Rookus, Matti A.; Schmutzler, Rita Katharina; Sevenet, Nicolas; Shah, Payal D.; Singer, Christian F.; Slavin, Thomas P.; Snape, Katie; Sokolowska, Johanna; Sonderstrup, Ida Marie Heeholm; Southey, Melissa; Spurdle, Amanda B.; Stadler, Zsofia; Stoppa-Lyonnet, Dominique; Sukiennicki, Grzegorz; Sutter, Christian; Tan, Thean-Yen; Tea, Muy-Kheng; Teixeira, Manuel R.; Teule, Alex; Teo, Soo-Hwang; Terry, Mary Beth; Thomassen, Mads; Tihomirova, Laima; Tischkowitz, Marc; Tognazzo, Silvia; Toland, Amanda Ewart; Tung, Nadine; van den Ouweland, Ans M. W.; van der Luijt, Rob B.; van Engelen, Klaartje; van Rensburg, Elizabeth J.; Varon-Mateeva, Raymonda; Wappenschmidt, Barbara; Wijnen, Juul T.; Rebbeck, Timothy; Chenevix-Trench, Georgia; Offit, Kenneth; Couch, Fergus J.; Nord, Silje; Easton, Douglas F.; Antoniou, Antonis C.; Simard, Jacques

    Cis-acting regulatory SNPs resulting in differential allelic expression (DAE) may, in part, explain the underlying phenotypic variation associated with many complex diseases. To investigate whether common variants associated with DAE were involved in breast cancer susceptibility among BRCA1 and

  18. Association of breast cancer risk in BRCA1 and BRCA2 mutation carriers with genetic variants showing differential allelic expression : identification of a modifier of breast cancer risk at locus 11q22.3

    NARCIS (Netherlands)

    Hamdi, Yosr; Soucy, Penny; Kuchenbaeker, Karoline B; Pastinen, Tomi; Droit, Arnaud; Lemaçon, Audrey; Adlard, Julian; Aittomäki, Kristiina; Andrulis, Irene L; Arason, Adalgeir; Arnold, Norbert; Arun, Banu K; Azzollini, Jacopo; Bane, Anita; Barjhoux, Laure; Barrowdale, Daniel; Benitez, Javier; Berthet, Pascaline; Blok, Marinus J; Bobolis, Kristie; Bonadona, Valérie; Bonanni, Bernardo; Bradbury, Angela R; Brewer, Carole; Buecher, Bruno; Buys, Saundra S; Caligo, Maria A; Chiquette, Jocelyne; Chung, Wendy K; Claes, Kathleen B M; Daly, Mary B; Damiola, Francesca; Davidson, Rosemarie; De la Hoya, Miguel; De Leeneer, Kim; Diez, Orland; Ding, Yuan Chun; Dolcetti, Riccardo; Domchek, Susan M; Dorfling, Cecilia M; Eccles, Diana; Eeles, Ros; Einbeigi, Zakaria; Ejlertsen, Bent; Engel, Christoph; Gareth Evans, D; Feliubadalo, Lidia; Foretova, Lenka; Fostira, Florentia; Foulkes, William D; Fountzilas, George; Friedman, Eitan; Frost, Debra; Ganschow, Pamela; Ganz, Patricia A; Garber, Judy; Gayther, Simon A; Gerdes, Anne-Marie; Glendon, Gord; Godwin, Andrew K; Goldgar, David E; Greene, Mark H; Gronwald, Jacek; Hahnen, Eric; Hamann, Ute; Hansen, Thomas V O; Hart, Steven; Hays, John L; Hogervorst, Frans B L; Hulick, Peter J; Imyanitov, Evgeny N; Isaacs, Claudine; Izatt, Louise; Jakubowska, Anna; James, Paul; Janavicius, Ramunas; Jensen, Uffe Birk; John, Esther M; Joseph, Vijai; Just, Walter; Kaczmarek, Katarzyna; Karlan, Beth Y; Kets, Carolien M; Kirk, Judy; Kriege, Mieke; Laitman, Yael; Laurent, Maïté; Lazaro, Conxi; Leslie, Goska; Lester, Jenny; Lesueur, Fabienne; Liljegren, Annelie; Loman, Niklas; Loud, Jennifer T; Manoukian, Siranoush; Mariani, Milena; Mazoyer, Sylvie; McGuffog, Lesley; Meijers-Heijboer, Hanne E J; Meindl, Alfons; Miller, Austin; Montagna, Marco; Mulligan, Anna Marie; Nathanson, Katherine L; Neuhausen, Susan L; Nevanlinna, Heli; Nussbaum, Robert L; Olah, Edith; Olopade, Olufunmilayo I; Ong, Kai-Ren; Oosterwijk, Jan C; Osorio, Ana; Papi, Laura; Park, Sue Kyung; Pedersen, Inge Sokilde; Peissel, Bernard; Segura, Pedro Perez; Peterlongo, Paolo; Phelan, Catherine M; Radice, Paolo; Rantala, Johanna; Rappaport-Fuerhauser, Christine; Rennert, Gad; Richardson, Andrea; Robson, Mark; Rodriguez, Gustavo C; Rookus, Matti A; Schmutzler, Rita Katharina; Sevenet, Nicolas; Shah, Payal D; Singer, Christian F; Slavin, Thomas P; Snape, Katie; Sokolowska, Johanna; Sønderstrup, Ida Marie Heeholm; Southey, Melissa; Spurdle, Amanda B; Stadler, Zsofia; Stoppa-Lyonnet, Dominique; Sukiennicki, Grzegorz; Sutter, Christian; Tan, Yen; Tea, Muy-Kheng; Teixeira, Manuel R; Teulé, Alex; Teo, Soo-Hwang; Terry, Mary Beth; Thomassen, Mads; Tihomirova, Laima; Tischkowitz, Marc; Tognazzo, Silvia; Toland, Amanda Ewart; Tung, Nadine; van den Ouweland, Ans M W; van der Luijt, Rob B; van Engelen, Klaartje; van Rensburg, Elizabeth J; Varon-Mateeva, Raymonda; Wappenschmidt, Barbara; Wijnen, Juul T; Rebbeck, Timothy; Chenevix-Trench, Georgia; Offit, Kenneth; Couch, Fergus J; Nord, Silje; Easton, Douglas F; Antoniou, Antonis C; Simard, Jacques

    PURPOSE: Cis-acting regulatory SNPs resulting in differential allelic expression (DAE) may, in part, explain the underlying phenotypic variation associated with many complex diseases. To investigate whether common variants associated with DAE were involved in breast cancer susceptibility among BRCA1

  19. Association of breast cancer risk in BRCA1 and BRCA2 mutation carriers with genetic variants showing differential allelic expression: identification of a modifier of breast cancer risk at locus 11q22.3

    NARCIS (Netherlands)

    Hamdi, Y.; Soucy, P.; Kuchenbaeker, K.B.; Pastinen, T.; Droit, A.; Lemacon, A.; Adlard, J.; Aittomaki, K.; Andrulis, I.L.; Arason, A.; Arnold, N.; Arun, B.K.; Azzollini, J.; Bane, A.; Barjhoux, L.; Barrowdale, D.; Benitez, J.; Berthet, P.; Blok, M.J.; Bobolis, K.; Bonadona, V.; Bonanni, B.; Bradbury, A.R.; Brewer, C.; Buecher, B.; Buys, S.S.; Caligo, M.A.; Chiquette, J.; Chung, W.K.; Claes, K.B.; Daly, M.B.; Damiola, F.; Davidson, R.; Hoya, M. de la; Leeneer, K. De; Diez, O.; Ding, Y.C.; Dolcetti, R.; Domchek, S.M.; Dorfling, C.M.; Eccles, D.; Eeles, R.; Einbeigi, Z.; Ejlertsen, B.; Engel, C.; Evans, D.; Feliubadalo, L.; Foretova, L.; Fostira, F.; Foulkes, W.D.; Fountzilas, G.; Friedman, E.; Frost, D.; Ganschow, P.; Ganz, P.A.; Garber, J.; Gayther, S.A.; Gerdes, A.M.; Glendon, G.; Godwin, A.K.; Goldgar, D.E.; Greene, M.H.; Gronwald, J.; Hahnen, E.; Hamann, U.; Hansen, T.V.; Hart, S.; Hays, J.L.; Hogervorst, F.B.; Hulick, P.J.; Imyanitov, E.N.; Isaacs, C.; Izatt, L.; Jakubowska, A.; James, P.; Janavicius, R.; Jensen, U.B.; John, E.M.; Joseph, V.; Just, W.; Kaczmarek, K.; Karlan, B.Y.; Kets, C.M.; Kirk, J.; Kriege, M.; Laitman, Y.; Laurent, M.; Lazaro, C.; Leslie, G.; Lester, J.; Lesueur, F.; Liljegren, A.; Loman, N.; Loud, J.T.; Manoukian, S.; Mariani, M.; Mazoyer, S.; McGuffog, L.; Meijers-Heijboer, H.E.; Meindl, A.; et al.,

    2017-01-01

    PURPOSE: Cis-acting regulatory SNPs resulting in differential allelic expression (DAE) may, in part, explain the underlying phenotypic variation associated with many complex diseases. To investigate whether common variants associated with DAE were involved in breast cancer susceptibility among BRCA1

  20. Association of breast cancer risk in BRCA1 and BRCA2 mutation carriers with genetic variants showing differential allelic expression: identification of a modifier of breast cancer risk at locus 11q22.3

    NARCIS (Netherlands)

    Y. Hamdi (Yosr); Soucy, P. (Penny); Kuchenbaeker, K.B. (Karoline B.); Pastinen, T. (Tomi); A. Droit (Arnaud); Lemaçon, A. (Audrey); J.W. Adlard (Julian); K. Aittomäki (Kristiina); I.L. Andrulis (Irene); A. Arason (Adalgeir); N. Arnold (Norbert); B.K. Arun (Banu); J. Azzollini; A.L. Bane (Anita L.); Barjhoux, L. (Laure); D. Barrowdale (Daniel); J. Benítez (Javier); P. Berthet (Pascaline); M.J. Blok (Marinus); K.A. Bobolis (Kristie A.); V. Bonadona (Valérie); B. Bonnani (Bernardo); Bradbury, A.R. (Angela R.); C. Brewer (Carole); B. Buecher (Bruno); Buys, S.S. (Saundra S.); M.A. Caligo (Maria); Chiquette, J. (Jocelyne); W. Chung (Wendy); K.B.M. Claes (Kathleen B.M.); Daly, M.B. (Mary B.); F. Damiola (Francesca); R. Davidson (Rosemarie); M. de La Hoya (Miguel); K. De Leeneer (Kim); O. Díez (Orland); Y.C. Ding (Yuan); R. Dolcetti (Riccardo); S.M. Domchek (Susan); C.M. Dorfling (Cecilia); D. Eccles (Diana); R. Eeles (Ros); Z. Einbeigi (Zakaria); B. Ejlertsen (Bent); EMBRACE; C.W. Engel (Christoph); Gareth Evans, D.; L. Feliubadaló (L.); L. Foretova (Lenka); F. Fostira (Florentia); Foulkes, W.D. (William D.); G. Fountzilas (George); E. Friedman (Eitan); D. Frost (Debra); P. Ganschow (Pamela); P.A. Ganz (Patricia A.); J. Garber (Judy); S.A. Gayther (Simon); GEMO Study Collaborators; A-M. Gerdes (Anne-Marie); G. Glendon (Gord); A.K. Godwin (Andrew K.); D. Goldgar (David); M.H. Greene (Mark H.); J. Gronwald (Jacek); E. Hahnen (Eric); U. Hamann (Ute); T.V.O. Hansen (Thomas); S. Hart (Stewart); J. Hays (John); HEBON; F.B.L. Hogervorst (Frans); P.J. Hulick (Peter); E.N. Imyanitov (Evgeny); C. Isaacs (Claudine); L. Izatt (Louise); A. Jakubowska (Anna); M. James (Margaret); R. Janavicius (Ramunas); U.B. Jensen; E.M. John (Esther); V. Joseph (Vijai); Just, W. (Walter); Kaczmarek, K. (Katarzyna); Karlan, B.Y. (Beth Y.); KConFab Investigators; C.M. Kets; J. Kirk (Judy); Kriege, M. (Mieke); Y. Laitman (Yael); Laurent, M. (Maïté); C. Lazaro (Conxi); Leslie, G. (Goska); K.J. Lester (Kathryn); F. Lesueur (Fabienne); A. Liljegren (Annelie); N. Loman (Niklas); J.T. Loud (Jennifer); S. Manoukian (Siranoush); Mariani, M. (Milena); S. Mazoyer (Sylvie); L. McGuffog (Lesley); E.J. Meijers-Heijboer (Hanne); A. Meindl (Alfons); A. Miller (Austin); M. Montagna (Marco); A.-M. Mulligan (Anna-Marie); K.L. Nathanson (Katherine); S.L. Neuhausen (Susan); H. Nevanlinna (Heli); R.L. Nussbaum (Robert L.); Olah, E. (Edith); O.I. Olopade (Olufunmilayo I.); K.-R. Ong (Kai-Ren); J.C. Oosterwijk (Jan); A. Osorio (Ana); L. Papi (Laura); S.K. Park (Sue K.); Pedersen, I.S. (Inge Sokilde); B. Peissel (Bernard); P.P. Segura (Pedro Perez); P. Peterlongo (Paolo); C. Phelan (Catherine); P. Radice (Paolo); J. Rantala (Johanna); Rappaport-Fuerhauser, C. (Christine); G. Rennert (Gad); A.L. Richardson (Andrea); M. Robson (Mark); G.C. Rodriguez (Gustavo); M.A. Rookus (Matti); R.K. Schmutzler (Rita); N. Sevenet (Nicolas); Shah, P.D. (Payal D.); C.F. Singer (Christian); Slavin, T.P. (Thomas P.); Snape, K. (Katie); J. Sokolowska (Johanna); Sønderstrup, I.M.H. (Ida Marie Heeholm); M.C. Southey (Melissa); A.B. Spurdle (Amanda); Stadler, Z. (Zsofia); D. Stoppa-Lyonnet (Dominique); G. Sukiennicki (Grzegorz); C. Sutter (Christian); Tan, Y. (Yen); M.-K. Tea; P.J. Teixeira; A. Teulé (A.); S.-H. Teo; M.B. Terry (Mary Beth); M. Thomassen (Mads); L. Tihomirova (Laima); M. Tischkowitz (Marc); S. Tognazzo (Silvia); A.E. Toland (Amanda); N. Tung (Nadine); A.M.W. van den Ouweland (Ans); R.B. van der Luijt (Rob); K. van Engelen (Klaartje); E.J. van Rensburg (Elizabeth); R. Varon-Mateeva (Raymonda); B. Wapenschmidt (Barbara); J.T. Wijnen (Juul); R. Rebbeck (Timothy); G. Chenevix-Trench (Georgia); K. Offit (Kenneth); Couch, F.J. (Fergus J.); S. Nord (Silje); D.F. Easton (Douglas F.); A.C. Antoniou (Antonis C.); Simard, J. (Jacques)

    2016-01-01

    textabstractPurpose: Cis-acting regulatory SNPs resulting in differential allelic expression (DAE) may, in part, explain the underlying phenotypic variation associated with many complex diseases. To investigate whether common variants associated with DAE were involved in breast cancer susceptibility

  1. CALABI, Francesca. Fílon de Alexandria (Filone di Alessandria. Tradução: José Bortolini. São Paulo: Paulus, 2014. 223 pp. ISBN: 978-85-349-3854-9. R$ 38,00.

    Directory of Open Access Journals (Sweden)

    Rodrigo Pinto de Brito

    2016-08-01

    Full Text Available Francesca Calabi é professora do Dipartamento di Studi Umanistici – Filosofia na Università degli Studi di Pavia, na Itália, onde leciona desde 2004 disciplinas de História da Filosofia Tardo-antiga. Seus cursos versam sobre temas como “O daimon de Sócrates” e “O asno de ouro” (ambas obras de Apuleio. Também lê, revisa e finaliza traduções suas em sala de aula, como a da “Carta de Aristeas a Filócrates”, um texto do séc. III a.C que descreve a tradução da Torá para o grego pelos 72 sábios e tradutores enviados a Alexandria a convite do então bibliotecário alexandrino, o peripatético Demétrio de Falero.

  2. Inhibition of very-long-chain fatty acid formation by indanofan, 2-[2-(3-chlorophenyl)oxiran-2-ylmethyl]-2-ethylindan-1,3-dione, and its relatives.

    Science.gov (United States)

    Takahashi, Hideomi; Schmalfuss, Jochen; Ohki, Aiko; Hosokawa, Akemi; Tanaka, Akira; Sato, Yukiharu; Matthes, Bernd; Böger, Peter; Wakabayashi, Ko

    2002-01-01

    Indanofan and its analogs inhibited the elongation of stearoyl- or arachidoyl-CoA by [2-14C]-malonyl-CoA in leek microsomes from Allium porrum. Although the precise mode of interaction of indanofan at the molecular level is not completely clarified by the present study, it is concluded that indanofan and analogs act as inhibitor of the elongase enzyme involved in de novo biosynthesis of fatty acids with an alkyl chain longer than C18, called very-long-chain fatty acids (VLCFAs). For a strong inhibition of VLCFA formation chloro substituents at the benzene ring and the oxirane group were necessary. Furthermore, the greenhouse test showed strong activity for indanofan and its analogs, and the scores coincided with cell-free elongation inhibition. The cell-free assay, however, failed to indicate any activity for an analog having a methylene instead of the oxirane group, while both Digitaria ciliaris and Echinochloa oryzicola were killed with 1 kg a.i./ha. This finding cannot be discussed because the applied use rate of 1 kg a.i./ha is too high to allow for a score differentiation. For high concentrations of this compound additional unknown inhibitory effects may be involved besides fatty acid elongation.

  3. Retraction notice to “A novel technique of multi-track percutaneous balloon mitral commissurotomy (PBMC” [Egypt. J. Chest Dis. Tuberc. 61/3 (2013 223–228

    Directory of Open Access Journals (Sweden)

    Sherif A. Sakr

    2015-01-01

    This paper has been retracted upon mutual agreement between the publisher and the Editor-in-Chief of EJCDT when it was discovered that this article had also been submitted and published in the International Heart Journal http://dx.doi.org/10.1536/ihj.54.196. The authors did not give clarification for the action; therefore the paper was retracted following international publishing practices.

  4. BARRETO, Vicente de Paulo; PEREIRA, Vitor Pimentel. !VIVA LA PEPA! A história não contada da Constitución Española de 1812 em terras brasileiras, p.201-223.

    OpenAIRE

    ,

    2012-01-01

    O texto refere-se à adoção da Constituição Espanhola de 1812, alcunhada “La Pepa”, no Brasil, na segunda década do século XIX, episódio pouco conhecido da história constitucional brasileira. Examina, por outro lado, a influência ideológica da Constituição Espanhola na evolução constitucional brasileira, especificamente, na primeira constituição brasileira, a Constituição do Império Brasileiro de 1824. O texto refere-se à adoção da Constituição Espanhola de 1812, alcunhada “La Pepa”, no Bra...

  5. Genome-wide association analysis of genetic generalized epilepsies implicates susceptibility loci at 1q43, 2p16.1, 2q22.3 and 17q21.32

    DEFF Research Database (Denmark)

    Steffens, M.; Leu, C.; Ruppert, A. K.

    2012-01-01

    Genetic generalized epilepsies (GGEs) have a lifetime prevalence of 0.3 and account for 2030 of all epilepsies. Despite their high heritability of 80, the genetic factors predisposing to GGEs remain elusive. To identify susceptibility variants shared across common GGE syndromes, we carried out a ...

  6. SU-F-J-223: Patterns of Failure for Laryngeal Cancer Patients Treated with Definitive IMRT: Comparing Two Different Methods for Determining the Origin of Recurrence From Follow-Up PET/CT Scans

    Energy Technology Data Exchange (ETDEWEB)

    Brodin, P; Guha, C; Tome, W [Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, New York (United States); Kabarriti, R; Kalnicki, S; Garg, M [Montefiore Medical Center, Bronx, New York (United States); Vogelius, I [Rigshospitalet, Copenhagen University Hospital, Copenhagen (Denmark)

    2016-06-15

    Purpose: To determine patterns of failure in laryngeal cancer treated with definitive IMRT by comparing two different methods for identifying the recurrence epicenter on follow-up PET/CT. Methods: We identified 20 patients treated for laryngeal squamous cell carcinoma with definitive IMRT who had loco-regional recurrence diagnosed on PET/CT. Recurrence PET/CT scans were co-registered with the original treatment planning CT using deformable image registration with the VoxAlign deformation engine in MIM Software. Recurrence volumes were delineated on co-registered follow-up scans using a semi-automatic PETedge tool and two separate methods were used to identify the recurrence point of origin: a) Finding the point within the recurrence volume for which the maximum distance to the surface of the surrounding recurrence volume is smaller than for any other point. b) Finding the point within the recurrence volume with the maximum standardized uptake value (SUVmax), without geometric restrictions.For each method the failure pattern was determined as whether the recurrence origin fell within the original high-dose target volumes GTV70, CTV70, PTV70 (receiving 70Gy), intermediate-risk PTV59 (receiving 59.4Gy) or low-risk PTV54 (receiving 54.1Gy), in the original treatment planning CT. Results: 23 primary/nodal recurrences from the 20 patients were analyzed. The three-dimensional distance between the two different origins was on average 10.5mm (std.dev. 10mm). Most recurrences originated in the high-dose target volumes for both methods with 13 (57%) and 11 (48%) in the GTV70 and 20 (87%) and 20 (87%) in the PTV70 for method a) and b), respectively. There was good agreement between the two methods in classifying the origin target volumes with 69% concordance for GTV70, 89% for CTV70 and 100% for PTV70. Conclusion: With strong agreement in patterns of failure between two separate methods for determining recurrence origin, we conclude that most recurrences occurred within the high-dose treatment region, which influences potential risk-adaptive treatment strategies.

  7. ORF Alignment: NC_004463 [GENIUS II[Archive

    Lifescience Database Archive (English)

    Full Text Available y: 164 ASYFTINVSSPNTPGLRNLQEGALLDDLLARVIDARERVRQKAGDTPVLLKIAPDLSLAQ 223 ... ASYFTINVSSPNTPGLRNLQEGALLDDLLARVIDARE...RVRQKAGDTPVLLKIAPDLSLAQ Sbjct: 121 ASYFTINVSSPNTPGLRNLQEGALLDDLLARVIDARE

  8. ORF Alignment: NC_005296 [GENIUS II[Archive

    Lifescience Database Archive (English)

    Full Text Available y: 164 ASYFTVNVSSPNTPGLRNXXXXXXXXXXXXRVIDARERVRAAAGDTPVLLKIAPDLSLGE 223 ... ASYFTVNVSSPNTPGLRN ... RVIDARE...RVRAAAGDTPVLLKIAPDLSLGE Sbjct: 121 ASYFTVNVSSPNTPGLRNLQQAAALDDLLARVIDARE

  9. ORF Alignment: NC_004463 [GENIUS II[Archive

    Lifescience Database Archive (English)

    Full Text Available INA 60 ... Query: 164 AEDHMLLLGRKTSLERVAAFLLEMDERLAHPAMMLLPMNRRDIADYLGITLETVSRAFSI 223 ... AEDHMLLLGRKTSLERVAAFLLEMDERLAHPAM...MLLPMNRRDIADYLGITLETVSRAFSI Sbjct: 121 AEDHMLLLGRKTSLERVAAFLLEMDERLAHPAMMLLPMNRRDIADYLGITLETVSRAFSI 180 ...

  10. Efeitos da restrição energética para suínos na fase final de terminação sobre o desempenho, característica de carcaça e poluição ambiental - DOI: 10.4025/actascianimsci.v29i2.223 Effect of energy restriction for late finishing pigs on performance, carcass traits and environmental pollution - DOI: 10.4025/actascianimsci.v29i2.223

    Directory of Open Access Journals (Sweden)

    Antonio Cláudio Furlan

    2007-11-01

    Full Text Available . Foram conduzidos dois experimentos com o objetivo de avaliar níveis de restrição energética (3.200, 2.960 e 2.720 kcal de EM kg-1, por meio da elevação da fibra dietéica (casca de arroz, para suínos abatidos com peso elevado. Experimento 1 - Foram utilizados 36 suínos (69,39 ± 5,38 kg. As variáveis estudadas (desempenho, carcaça e NUP foram agrupadas de acordo com o peso de abate (70 - 90 kg e 90 - 115 kg. Ao todo, foram abatidos 12 animais com peso de 87,55 ± 3,12 kg e 15 animais com peso de 115,41 ± 6,20 kg. Nenhuma das variáveis estudadas foi influenciada pelos diferentes níveis de EM. Experimento 2 - Foram utilizados 15 suínos machos (84,8 ± 4,5 kg, alojados em gaiolas de metabolismo. Houve aumento linear da produção total de fezes, matéria seca e matéria orgânica, com a redução do nível energético, contudo sem aumentar a excreção total de fósforo (P e nitrogênio (N. Houve redução do coeficiente de digestibilidade da MS e PB das raízes com a redução da energia (elevação da fibra, o que levou a redução do GDP e piora na CA. Os resultados sugerem que o abate de suínos com peso de até 115 kg é possível sem prejuízo do desempenho e das características da carcaça, independente do nível de EM das dietas, entretanto ocorre aumento na produção total de fezes com a redução da EM e aumento da fibra dietética sem, contudo, aumentar a excreção de N e P.Two trials were carried out to study the energy restriction (3200, 2960 and 2720 kcal of ME kg-1 for late finishing pigs, by means of adding dietary fiber (ground rice hull. Experiment I - 36 pigs were used (69.39 ア 5.38 kg. The variables studied (performance, carcass traits and PUN were separated according to the slaughter weight (70-90 kg and 90-115 kg. 12 pigs weighting 87.55 ア 3.12 kg and 15 pigs weighting 115.41 ア 6.20 kg were slaughtered. None of the variables studied were influenced by the different levels of ME. Experiment II -15 barrows were used (84.8 ア 4.5 kg and kept on metabolism crates. There was a linear increase of total feces, dry matter (DM and organic matter output, according to dietary energy reduction, without causing an increase in total phosphorous (P and nitrogen (N excretion. Digestibility coefficient of DM and crude protein decreased, which led to a decrease in daily weight gain and an increase in feed: gain ratio. Results suggest the possibility to slaughter high lean meat pigs, weighting up to 115 kg, without impairing performance and carcass traits, regardless dietary energy level. However, total feces output increased without causing an increase in N and P excretion, as ME decreased and crude fiber increased.

  11. Gclust Server: 9115 [Gclust Server

    Lifescience Database Archive (English)

    Full Text Available 9115 Atu_Atu5169=avhB8 Cluster Sequences - 223 agrobacterium virulence homologue vi...luster sequences Cluster Sequences Link to related sequences - Sequence length 223 Representative annotation agrobacterium

  12. Dicty_cDB: SLD494 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available 1999. 2.23 Translated Amino Acid sequence QYGAEGLKFFENGAFGEDAAYIAKLMGSLKLIACTGFLILLIAILFPIFIVVKTKGAVDW ...Amino Acid sequence (All Frames) Frame A: QYGAEGLKFFENGAFGEDAAYIAKLMGSLKLIACTGFLILLIAILFPIFIVVKTKGAVDW

  13. ORF Alignment: NC_002936 [GENIUS II[Archive

    Lifescience Database Archive (English)

    Full Text Available ... Length = 222 ... Query: 164 LGRHRLVCGDSTKAETFAVLLDDRKANLVITDPPYNVNYEGSAGKIKNDNMANDAFYNFL 223 ... ... ... LGRHRLVCGDSTKAETFAVLLDDRKANLVITDPPYNVNYEGSAGKIKNDNMANDAFYNFL Sbjct: 1 ... LGRHRL...VCGDSTKAETFAVLLDDRKANLVITDPPYNVNYEGSAGKIKNDNMANDAFYNFL 60 ... Query: 284 QHEPVLYGWKKSGKHQWYSGRKETTIWEFDKPKKNGDH

  14. ORF Alignment: NC_005125 [GENIUS II[Archive

    Lifescience Database Archive (English)

    Full Text Available 421] ... Length = 223 ... Query: 1 ... MMKTILMVTSSHDRFEGPDPRPTGVWLEEFAVPYMELLARKIGITVASPRGGAMPVDPRS 60 ... ... ... MMKTILMVTSSHDRFEGPDPRPTGVWLEEFAVPYMELLARKIGITVASPRGGAMPVDPRS Sbjct: 1 ... M...MKTILMVTSSHDRFEGPDPRPTGVWLEEFAVPYMELLARKIGITVASPRGGAMPVDPRS 60 ... Query: 121 KAGKIIAAICHGPAGLVGARRPDGAPLVAGVTL

  15. ORF Alignment: NT_037436 [GENIUS II[Archive

    Lifescience Database Archive (English)

    Full Text Available CIYRMKTIQAFHMKSFGW Sbjct: 1 ... HILDRSEWLGEPPSGKYPHLKLPVSNIIIHHTATEGCEQEDVCIYRMKTIQAFHMKSFGW 60 ... Query: 178 MDEGVRLHRLQPDYHIYAHRQLSPTES...PGQKLFELMQNWPRFTQDP 223 ... MDEGVRLHRLQPDYHIYAHRQLSPTESPGQKLFELMQNWPRFTQDP Sbjct: 121 MDEGVRLHRLQPDYHIYAHRQLSPTESPGQKLFELMQNWPRFTQDP 166

  16. ORF Alignment: NC_005823 [GENIUS II[Archive

    Lifescience Database Archive (English)

    Full Text Available KKFSSKNRVKFEYFHFPENLGYGVANNRSILKSNMEFHLVL 103 ... Query: 121 SFAPDILKKVFRKYLDQYDLRDKDWNQIQEDVSLISGCFIFA...RTKSLKQIRGFDERFFLY 180 ... SFAPDILKKVFRKYLDQYDLRDKDWNQIQEDVSLISGCFIFARTKSLKQI GFDE...RFFLY Sbjct: 164 SFAPDILKKVFRKYLDQYDLRDKDWNQIQEDVSLISGCFIFARTKSLKQIGGFDERFFLY 223 ...

  17. EFFECT OF MECHANICAL PROPERTIES OF MARTENSITE AND LOADING RATE ON DUAL PHASE STEELS

    Directory of Open Access Journals (Sweden)

    Ali BAYRAM

    1998-03-01

    Full Text Available In this study, steel sheet materials were used in order to obtain dual-phase steel. Specimens for this purpose have been annealed in ferrite + astatine regions at the temperatures of 740, 760, 800 and 820 °C. The specimens were annealed at the different temperatures with corresponding times 20, 40 and 60 minutes and quenched into water. As a result of this dual-phase steels at different ferrite + martensite ratio were produced. Sheet specimens were tested at the range of loading rates of 10, 50 and 259 mm/min. Strength properties of dual-phase steels were investigated depending on annealing temperature, ratio of martensite and loading rate.

  18. New developments of the in-source spectroscopy method at RILIS/ISOLDE

    CERN Document Server

    Marsh, B A; Imai, N; Seliverstov, M D; Rothe, S; Sels, S; Capponi, L; Rossel, R E; Franchoo, S; Wendt, K; Focker, G J; Kalaninova, Z; Sjoedin, A M; Popescu, L; Nicol, T; Huyse, M; Radulov, D; Atanasov, D; Kesteloot, N; Borgmann, Ch; Cocolios, T E; Lecesne, N; Ghys, L; Pauwels, D; Rapisarda, E; Kreim, S; Liberati, V; Wolf, R N; Andel, B; Schweikhard, L; Lane, J; Derkx, X; Kudryavtsev, Yu; Zemlyanoy, S G; Fedosseev, V N; Lynch, K M; Rosenbusch, M; Van Duppen, P; Lunney, D; Manea, V; Barzakh, A E; Andreyev, A N; Truesdale, V; Flanagan, K T; Molkanov, P L; Koester, U; Van Beveren, C; Wienholtz, F; Goodacre, T Day; Antalic, S; Bastin, B; De Witte, H; Fink, D A; Fedorov, D V

    2013-01-01

    At the CERN ISOLDE facility, long isotope chains of many elements are produced by proton-induced reactions in target materials such as uranium carbide. The Resonance Ionization Laser Ion Source (RILIS) is an efficient and selective means of ionizing the reaction products to produce an ion beam of a chosen isotope. Coupling the RILIS with modern ion detection techniques enables highly sensitive studies of nuclear properties (spins, electromagnetic moments and charge radii) along an isotope chain, provided that the isotope shifts and hyperfine structure splitting of the atomic transitions can be resolved. At ISOLDE the campaign to measure the systematics of isotopes in the lead region (Pb, Bi, Tl and Po) has been extended to include the gold and astatine isotope chains. Several developments were specifically required for the feasibility of the most recent measurements: new ionization schemes (Po, At); a remote controlled narrow line-width mode of operation for the RILIS Ti:sapphire laser (At, Au, Po); isobar fr...

  19. Nuclear and in-source laser spectroscopy with the ISAC yield station

    Energy Technology Data Exchange (ETDEWEB)

    Kunz, Peter, E-mail: pkunz@triumf.ca; Bricault, Pierre; Dombsky, Marik; Lassen, Jens; Teigelhöfer, Andrea; Heggen, Henning [TRIUMF, 4004 Wesbrook Mall, Vancouver, British Columbia V6T 2A3 (Canada); Andreoiu, Corina; Wong, Fiona [Department of Chemistry, Simon Fraser University, Burnaby, British Columbia V5A 1S6 (Canada)

    2014-05-15

    A new decay station has been built for the ISAC facility at TRIUMF for the rapid and reliable characterization of radioactive ion beam (RIB) compositions and intensities with the capability of simultaneously collecting α, β, and γ decay data from RIB with intensities between a few and ≈10{sup 11} ions per second. It features user-friendly control, data acquisition, and analysis software. The analysis of individual decay time structures allows the unambiguous assignment of α and γ lines even with substantial isobaric contamination present. The capability for accurate half-life measurements is demonstrated with the example of {sup 46}K. The coupling of the yield station to the laser ion source, TRILIS, allows the correlation of radiometric data with automated laser frequency scans. First results of in-source laser spectroscopy measurements on astatine are discussed.

  20. Nuclear and in-source laser spectroscopy with the ISAC yield station.

    Science.gov (United States)

    Kunz, Peter; Andreoiu, Corina; Bricault, Pierre; Dombsky, Marik; Lassen, Jens; Teigelhöfer, Andrea; Heggen, Henning; Wong, Fiona

    2014-05-01

    A new decay station has been built for the ISAC facility at TRIUMF for the rapid and reliable characterization of radioactive ion beam (RIB) compositions and intensities with the capability of simultaneously collecting α, β, and γ decay data from RIB with intensities between a few and ≈10(11) ions per second. It features user-friendly control, data acquisition, and analysis software. The analysis of individual decay time structures allows the unambiguous assignment of α and γ lines even with substantial isobaric contamination present. The capability for accurate half-life measurements is demonstrated with the example of (46)K. The coupling of the yield station to the laser ion source, TRILIS, allows the correlation of radiometric data with automated laser frequency scans. First results of in-source laser spectroscopy measurements on astatine are discussed.